AVAHO

The observation that women with lung cancer seem to live longer than men can be explained by known prognostic factors, a new study suggests.

“In this first Australian prospective study of lung cancer survival comparing men and women, we found that men had a 43% greater risk of dying from their lung cancer than women,” comments lead author Xue Qin Yu, PhD, the Daffodil Centre, the University of Sydney, and colleagues.

“[However], when all prognostic factors were considered together, most of the survival differential disappeared,” they add.

“These results suggest that sex differences in lung cancer survival can be largely explained by known prognostic factors,” Dr. Yu and colleagues emphasize.

The study was published in the May issue of the Journal of Thoracic Oncology.
 

The ‘45 and up’ study

The findings come from the Sax Institute’s 45 and Up Study, an ongoing trial involving over 267,000 participants aged 45 years and older living in New South Wales, Australia. Patients were recruited to the study between 2006 and 2009. At the time of recruitment, patients were cancer free.

A total of 1,130 participants were diagnosed with having lung cancer during follow-up – 488 women and 642 men. Compared with men, women were, on average, younger at the time of diagnosis, had fewer comorbidities, and were more likely to be never-smokers or to have been exposed to passive smoke.

Women were also more likely to be diagnosed with adenocarcinoma than men and to receive surgery within 6 months of their diagnosis.

“Lung cancer survival was significantly higher for women,” the authors report, at a median of 1.28 years versus 0.77 years for men (P < .0001).

Within each subgroup of major prognostic factors – histologic subtype, cancer stage, cancer treatment, and smoking status – women again survived significantly longer than men.

Interestingly, the authors note that “women with adenocarcinoma had significantly better survival than men with adenocarcinoma independent of smoking status,” (P = .0009). This suggests that sex differences in tumor biology may play a role in explaining the sex survival differential between men and women, they commented. That said, never-smokers had a 16% lower risk for lung cancer death than ever-smokers after adjusting for age, the authors point out.

The authors also note that approximately half of the disparity in survival between the sexes could be explained by differences in the receipt of anticancer therapy within 6 months of the diagnosis. “This could partly be due to a lower proportion of men having surgery within 6 months than women,” investigators speculate, at 17% versus 25%, respectively.

Men were also older than women at the time of diagnosis, were less likely to be never-smokers, and had more comorbidities, all of which might also have prevented them from having surgery. Women with lung cancer may also respond better to chemotherapy than men, although the sex disparity in survival persisted even among patients who did not receive any treatment for their cancer within 6 months of their diagnosis, investigators point out.

Furthermore, “smoking history at baseline was identified as a significant contributing factor to the sex survival disparity, explaining approximately 28% of the overall disparity,” Dr. Yu and colleagues observe.

Only 8% of men diagnosed with lung cancer were never-smokers, compared with 23% of women. The authors note that never-smokers are more likely to receive aggressive or complete treatment and respond well to treatment.

Similarly, tumor-related factors together explained about one-quarter of the overall sex disparity in survival.
 

Screening guidelines

Commenting on the findings in an accompanying editorial, Claudia Poleri, MD, Hospital María Ferrer, Buenos Aires, says that this Australian study provides “valuable information.”

“The risk of dying from lung cancer was significantly higher for men than for women,” she writes. “Differences in treatment-related factors explained 50% of the sex survival differential, followed by lifestyle and tumor-related factors (28% and 26%, respectively).

“Nevertheless, these differences alone do not explain the higher survival in women,” she comments.

“Does it matter to analyze the differences by sex in lung cancer?” Dr. Poleri asks in the editorial, and then answers herself: “It matters.”

“It is necessary to implement screening programs and build artificial intelligence diagnostic algorithms considering the role of sex and gender equity to ensure that innovative technologies do not induce disparities in clinical care,” she writes.

“It is crucial to conduct education and health public programs that consider these differences, optimizing the use of available resources, [and] it is essential to improve the accuracy of research design and clinical trials,” she adds.

Dr. Yu and Dr. Poleri declared no relevant financial interests.

A version of this article first appeared on Medscape.com.

The observation that women with lung cancer seem to live longer than men can be explained by known prognostic factors, a new study suggests.

“In this first Australian prospective study of lung cancer survival comparing men and women, we found that men had a 43% greater risk of dying from their lung cancer than women,” comments lead author Xue Qin Yu, PhD, the Daffodil Centre, the University of Sydney, and colleagues.

“[However], when all prognostic factors were considered together, most of the survival differential disappeared,” they add.

“These results suggest that sex differences in lung cancer survival can be largely explained by known prognostic factors,” Dr. Yu and colleagues emphasize.

The study was published in the May issue of the Journal of Thoracic Oncology.
 

The ‘45 and up’ study

The findings come from the Sax Institute’s 45 and Up Study, an ongoing trial involving over 267,000 participants aged 45 years and older living in New South Wales, Australia. Patients were recruited to the study between 2006 and 2009. At the time of recruitment, patients were cancer free.

A total of 1,130 participants were diagnosed with having lung cancer during follow-up – 488 women and 642 men. Compared with men, women were, on average, younger at the time of diagnosis, had fewer comorbidities, and were more likely to be never-smokers or to have been exposed to passive smoke.

Women were also more likely to be diagnosed with adenocarcinoma than men and to receive surgery within 6 months of their diagnosis.

“Lung cancer survival was significantly higher for women,” the authors report, at a median of 1.28 years versus 0.77 years for men (P < .0001).

Within each subgroup of major prognostic factors – histologic subtype, cancer stage, cancer treatment, and smoking status – women again survived significantly longer than men.

Interestingly, the authors note that “women with adenocarcinoma had significantly better survival than men with adenocarcinoma independent of smoking status,” (P = .0009). This suggests that sex differences in tumor biology may play a role in explaining the sex survival differential between men and women, they commented. That said, never-smokers had a 16% lower risk for lung cancer death than ever-smokers after adjusting for age, the authors point out.

The authors also note that approximately half of the disparity in survival between the sexes could be explained by differences in the receipt of anticancer therapy within 6 months of the diagnosis. “This could partly be due to a lower proportion of men having surgery within 6 months than women,” investigators speculate, at 17% versus 25%, respectively.

Men were also older than women at the time of diagnosis, were less likely to be never-smokers, and had more comorbidities, all of which might also have prevented them from having surgery. Women with lung cancer may also respond better to chemotherapy than men, although the sex disparity in survival persisted even among patients who did not receive any treatment for their cancer within 6 months of their diagnosis, investigators point out.

Furthermore, “smoking history at baseline was identified as a significant contributing factor to the sex survival disparity, explaining approximately 28% of the overall disparity,” Dr. Yu and colleagues observe.

Only 8% of men diagnosed with lung cancer were never-smokers, compared with 23% of women. The authors note that never-smokers are more likely to receive aggressive or complete treatment and respond well to treatment.

Similarly, tumor-related factors together explained about one-quarter of the overall sex disparity in survival.
 

Screening guidelines

Commenting on the findings in an accompanying editorial, Claudia Poleri, MD, Hospital María Ferrer, Buenos Aires, says that this Australian study provides “valuable information.”

“The risk of dying from lung cancer was significantly higher for men than for women,” she writes. “Differences in treatment-related factors explained 50% of the sex survival differential, followed by lifestyle and tumor-related factors (28% and 26%, respectively).

“Nevertheless, these differences alone do not explain the higher survival in women,” she comments.

“Does it matter to analyze the differences by sex in lung cancer?” Dr. Poleri asks in the editorial, and then answers herself: “It matters.”

“It is necessary to implement screening programs and build artificial intelligence diagnostic algorithms considering the role of sex and gender equity to ensure that innovative technologies do not induce disparities in clinical care,” she writes.

“It is crucial to conduct education and health public programs that consider these differences, optimizing the use of available resources, [and] it is essential to improve the accuracy of research design and clinical trials,” she adds.

Dr. Yu and Dr. Poleri declared no relevant financial interests.

A version of this article first appeared on Medscape.com.

The observation that women with lung cancer seem to live longer than men can be explained by known prognostic factors, a new study suggests.

“In this first Australian prospective study of lung cancer survival comparing men and women, we found that men had a 43% greater risk of dying from their lung cancer than women,” comments lead author Xue Qin Yu, PhD, the Daffodil Centre, the University of Sydney, and colleagues.

“[However], when all prognostic factors were considered together, most of the survival differential disappeared,” they add.

“These results suggest that sex differences in lung cancer survival can be largely explained by known prognostic factors,” Dr. Yu and colleagues emphasize.

The study was published in the May issue of the Journal of Thoracic Oncology.
 

The ‘45 and up’ study

The findings come from the Sax Institute’s 45 and Up Study, an ongoing trial involving over 267,000 participants aged 45 years and older living in New South Wales, Australia. Patients were recruited to the study between 2006 and 2009. At the time of recruitment, patients were cancer free.

A total of 1,130 participants were diagnosed with having lung cancer during follow-up – 488 women and 642 men. Compared with men, women were, on average, younger at the time of diagnosis, had fewer comorbidities, and were more likely to be never-smokers or to have been exposed to passive smoke.

Women were also more likely to be diagnosed with adenocarcinoma than men and to receive surgery within 6 months of their diagnosis.

“Lung cancer survival was significantly higher for women,” the authors report, at a median of 1.28 years versus 0.77 years for men (P < .0001).

Within each subgroup of major prognostic factors – histologic subtype, cancer stage, cancer treatment, and smoking status – women again survived significantly longer than men.

Interestingly, the authors note that “women with adenocarcinoma had significantly better survival than men with adenocarcinoma independent of smoking status,” (P = .0009). This suggests that sex differences in tumor biology may play a role in explaining the sex survival differential between men and women, they commented. That said, never-smokers had a 16% lower risk for lung cancer death than ever-smokers after adjusting for age, the authors point out.

The authors also note that approximately half of the disparity in survival between the sexes could be explained by differences in the receipt of anticancer therapy within 6 months of the diagnosis. “This could partly be due to a lower proportion of men having surgery within 6 months than women,” investigators speculate, at 17% versus 25%, respectively.

Men were also older than women at the time of diagnosis, were less likely to be never-smokers, and had more comorbidities, all of which might also have prevented them from having surgery. Women with lung cancer may also respond better to chemotherapy than men, although the sex disparity in survival persisted even among patients who did not receive any treatment for their cancer within 6 months of their diagnosis, investigators point out.

Furthermore, “smoking history at baseline was identified as a significant contributing factor to the sex survival disparity, explaining approximately 28% of the overall disparity,” Dr. Yu and colleagues observe.

Only 8% of men diagnosed with lung cancer were never-smokers, compared with 23% of women. The authors note that never-smokers are more likely to receive aggressive or complete treatment and respond well to treatment.

Similarly, tumor-related factors together explained about one-quarter of the overall sex disparity in survival.
 

Screening guidelines

Commenting on the findings in an accompanying editorial, Claudia Poleri, MD, Hospital María Ferrer, Buenos Aires, says that this Australian study provides “valuable information.”

“The risk of dying from lung cancer was significantly higher for men than for women,” she writes. “Differences in treatment-related factors explained 50% of the sex survival differential, followed by lifestyle and tumor-related factors (28% and 26%, respectively).

“Nevertheless, these differences alone do not explain the higher survival in women,” she comments.

“Does it matter to analyze the differences by sex in lung cancer?” Dr. Poleri asks in the editorial, and then answers herself: “It matters.”

“It is necessary to implement screening programs and build artificial intelligence diagnostic algorithms considering the role of sex and gender equity to ensure that innovative technologies do not induce disparities in clinical care,” she writes.

“It is crucial to conduct education and health public programs that consider these differences, optimizing the use of available resources, [and] it is essential to improve the accuracy of research design and clinical trials,” she adds.

Dr. Yu and Dr. Poleri declared no relevant financial interests.

A version of this article first appeared on Medscape.com.

A relationship between consumption of dairy products and risk of various cancers has been intensively investigated in the past but yielded inconclusive or conflicting results. Now a large new study comparing Chinese dairy consumption with that in the United Kingdom, shows that increased dairy consumption was linked to higher risks of liver cancer and female breast cancer.

The study, by researchers from Oxford University’s department of population health, and Peking University and the Chinese Academy of Medical Sciences in Beijing, used data from the China Kadoorie Biobank Study, a long-term prospective study involving more than over 510,000 participants recruited from 10 geographically diverse areas across China, including both rural and urban regions. They compared this to data from the UK biobank.

Subjects were 59% female, 41% male, aged 30-79 years, and had no history of cancer at recruitment between 2004 and 2008. Food questionnaires were completed at the outset and participants followed for an average of 11 years, using national cancer and death registries and health insurance records to identify new cancer diagnoses, including both fatal and nonfatal events.

Participants were categorized into three groups according to how often they consumed dairy products (primarily milk):

• Regular consumers (at least once a week): 20.4% of the cohort.
• Monthly consumers: 11.1%.
• Nonconsumers who never or rarely consumed dairy products: 68.5%.

Average dairy consumption was 37.9 g/day overall and 80.8 g/day among regular consumers. This compares with an average consumption of around 300 g/day in participants in the UK Biobank cohort.

Over the course of the study, 29,277 new cancer cases were recorded, including 6,282 lung, 2,582 female breast, 3,577 stomach, 3,350 colorectal, and 3,191 liver cancer cases.

Analyses correlating cases with consumption took into account a range of other factors potentially affecting cancer risk, including age, sex, region, family history of cancer, socioeconomic status (education and income), lifestyle factors (alcohol intake, smoking, physical activity, soy consumption, and fresh fruit intake), body mass index, chronic hepatitis B virus infection, and female reproductive factors.

Higher dairy intakes linked with risk of liver and breast cancers

Results revealed that higher regular dairy intake was associated with significantly higher risks of liver cancer and female breast cancer, both common types of cancer in China. Analyses indicated that for each 50-g/day intake, the risks increased by 12% and 17%, respectively.

There was also an increase in total cancer diagnoses, and an increased risk of lymphoma, though this was not statistically significant after correction for confounders. No association was found between dairy products and colorectal cancer, prostate cancer, or any other site-specific cancer.

The research, published in BMC Medicine, is the first major study to investigate dairy consumption and cancer risk in Chinese adults. The results conflict with previous studies on Western populations, which have suggested that dairy products may be associated with a lower risk of colorectal cancer and a higher risk of prostate cancer but have found no clear link for breast or other types of cancer.

Lead researchers Maria Kakkoura, PhD, MSc, and associate professor Huaidong Du, MD, PhD, told this news organization that, although they don’t know the reason for the difference, “there is clear evidence that colorectal cancer has a different incidence pattern in China, compared with Western countries. Other risk factors, like adiposity, may have a stronger effect on the risk of colorectal cancer in Western countries than in China.” Notably, the mean body mass index in the study population was around 23 kg/m², they said – by contrast in the United Kingdom it is 27.6 kg/m2.

Effects not necessarily causal

Ian Givens, PhD, professor of food chain nutrition at the University of Reading (England), said the study was “potentially very important for Chinese people, if it can be confirmed that dairy products affect the risk of breast and/or liver cancer differently in Chinese subjects to those in Western Societies, especially as dairy consumption in China is much lower than in most Western diets.”

He added: “As always it needs to be kept in mind that this type of study can only establish associations with disease risk, not cause.”

Dr. Kakkoura, nutritional epidemiologist at Oxford (England) University’s department of population health, said: “This was the first major study to investigate the link between dairy products and cancer risk in a Chinese population. Further studies are needed to validate these current findings, establish if these associations are causal, and investigate the potential underlying mechanisms involved.”

The researchers said that, while the results do not prove causation, “there are several plausible biological mechanisms that may explain these associations.” They pointed to higher dairy consumption potentially increasing levels of insulinlike growth factor-I, known to promote cell proliferation and associated with higher risks of several types of cancer.

In addition, estrogen and progesterone present in cows’ milk may play a role in increasing breast cancer risk, whilst saturated and trans-fatty acids from dairy products may increase the risk of liver cancer. As many Chinese people are lactase deficient, dairy products may also be broken down into products that affect cancer risk.

No justification for dietary change

Confounding factors may also have influenced the results, commented Duane Mellor, PhD, RD, RNutr, registered dietitian and senior teaching fellow at Aston University, Birmingham, England. “Those in the study who consumed dairy were more likely to live in cities and have other health conditions, including cardiovascular disease and diabetes – although some of these factors were considered in the analysis, not all of these covariates were, which could influence the findings.

“In my view this study alone does not provide strong evidence that reducing dairy intake would reduce cancer risk.”

He added: “Although the paper suggests a 12% increased relative risk for female breast cancer, this does not equate to 12 more cases per 100 individuals – in absolute terms this would be more like 1 or 2 cases per 1,000 people.”

Similarly, Kevin McConway, PhD, emeritus professor of applied statistics at the Open University, Milton Keynes, England, said: “An issue is that there were many differences between the people that consumed different amounts of dairy products, apart from their difference in dairy consumption. For instance, of those who never or rarely consumed dairy products, fewer than a third lived in urban areas, but of regular dairy consumers (at least once a week), 83% lived in urban areas. Regular consumers were considerably more likely to be well educated than those who never or rarely consumed dairy products, and there were other differences too. 

“So if, as the researchers found, a greater proportion of the regular consumers than of the never or rare consumers had a cancer diagnosis, that could have been because of their different dairy consumption, or it could have been (in part or entirely) because of the different places they lived, or their different education levels, or any of the other factors on which the groups differed.

“One can never be sure that all the relevant factors have been adjusted for. That’s why the researchers rightly say that these results can’t establish whether the associations between dairy consumption and the risks of some cancers, that they found, are there because the dairy consumption differences change the cancer risks in a cause-and-effect way. They might, or they might not.”

He cautioned: “I don’t think anyone should decide to change their individual diet solely because of the results of this new study.”

Commenting on the study, Fiona Osgun, senior health information manager at Cancer Research UK, London, told this news organization: “This early-stage study found an association between dairy consumption and the risks of certain cancers, but that doesn’t mean that they’re causing them or that people need to avoid dairy. Dairy products can be part of a healthy balanced diet and, in the U.K., the Food Standards Agency regulates them to make sure they’re safe. There’s good evidence that dairy reduces the risk of bowel cancer, but no clear evidence for other cancer types, and this is no different for people who are lactose intolerant.”

A version of this article first appeared on Medscape UK.

A relationship between consumption of dairy products and risk of various cancers has been intensively investigated in the past but yielded inconclusive or conflicting results. Now a large new study comparing Chinese dairy consumption with that in the United Kingdom, shows that increased dairy consumption was linked to higher risks of liver cancer and female breast cancer.

The study, by researchers from Oxford University’s department of population health, and Peking University and the Chinese Academy of Medical Sciences in Beijing, used data from the China Kadoorie Biobank Study, a long-term prospective study involving more than over 510,000 participants recruited from 10 geographically diverse areas across China, including both rural and urban regions. They compared this to data from the UK biobank.

Subjects were 59% female, 41% male, aged 30-79 years, and had no history of cancer at recruitment between 2004 and 2008. Food questionnaires were completed at the outset and participants followed for an average of 11 years, using national cancer and death registries and health insurance records to identify new cancer diagnoses, including both fatal and nonfatal events.

Participants were categorized into three groups according to how often they consumed dairy products (primarily milk):

• Regular consumers (at least once a week): 20.4% of the cohort.
• Monthly consumers: 11.1%.
• Nonconsumers who never or rarely consumed dairy products: 68.5%.

Average dairy consumption was 37.9 g/day overall and 80.8 g/day among regular consumers. This compares with an average consumption of around 300 g/day in participants in the UK Biobank cohort.

Over the course of the study, 29,277 new cancer cases were recorded, including 6,282 lung, 2,582 female breast, 3,577 stomach, 3,350 colorectal, and 3,191 liver cancer cases.

Analyses correlating cases with consumption took into account a range of other factors potentially affecting cancer risk, including age, sex, region, family history of cancer, socioeconomic status (education and income), lifestyle factors (alcohol intake, smoking, physical activity, soy consumption, and fresh fruit intake), body mass index, chronic hepatitis B virus infection, and female reproductive factors.

Higher dairy intakes linked with risk of liver and breast cancers

Results revealed that higher regular dairy intake was associated with significantly higher risks of liver cancer and female breast cancer, both common types of cancer in China. Analyses indicated that for each 50-g/day intake, the risks increased by 12% and 17%, respectively.

There was also an increase in total cancer diagnoses, and an increased risk of lymphoma, though this was not statistically significant after correction for confounders. No association was found between dairy products and colorectal cancer, prostate cancer, or any other site-specific cancer.

The research, published in BMC Medicine, is the first major study to investigate dairy consumption and cancer risk in Chinese adults. The results conflict with previous studies on Western populations, which have suggested that dairy products may be associated with a lower risk of colorectal cancer and a higher risk of prostate cancer but have found no clear link for breast or other types of cancer.

Lead researchers Maria Kakkoura, PhD, MSc, and associate professor Huaidong Du, MD, PhD, told this news organization that, although they don’t know the reason for the difference, “there is clear evidence that colorectal cancer has a different incidence pattern in China, compared with Western countries. Other risk factors, like adiposity, may have a stronger effect on the risk of colorectal cancer in Western countries than in China.” Notably, the mean body mass index in the study population was around 23 kg/m², they said – by contrast in the United Kingdom it is 27.6 kg/m2.

Effects not necessarily causal

Ian Givens, PhD, professor of food chain nutrition at the University of Reading (England), said the study was “potentially very important for Chinese people, if it can be confirmed that dairy products affect the risk of breast and/or liver cancer differently in Chinese subjects to those in Western Societies, especially as dairy consumption in China is much lower than in most Western diets.”

He added: “As always it needs to be kept in mind that this type of study can only establish associations with disease risk, not cause.”

Dr. Kakkoura, nutritional epidemiologist at Oxford (England) University’s department of population health, said: “This was the first major study to investigate the link between dairy products and cancer risk in a Chinese population. Further studies are needed to validate these current findings, establish if these associations are causal, and investigate the potential underlying mechanisms involved.”

The researchers said that, while the results do not prove causation, “there are several plausible biological mechanisms that may explain these associations.” They pointed to higher dairy consumption potentially increasing levels of insulinlike growth factor-I, known to promote cell proliferation and associated with higher risks of several types of cancer.

In addition, estrogen and progesterone present in cows’ milk may play a role in increasing breast cancer risk, whilst saturated and trans-fatty acids from dairy products may increase the risk of liver cancer. As many Chinese people are lactase deficient, dairy products may also be broken down into products that affect cancer risk.

No justification for dietary change

Confounding factors may also have influenced the results, commented Duane Mellor, PhD, RD, RNutr, registered dietitian and senior teaching fellow at Aston University, Birmingham, England. “Those in the study who consumed dairy were more likely to live in cities and have other health conditions, including cardiovascular disease and diabetes – although some of these factors were considered in the analysis, not all of these covariates were, which could influence the findings.

“In my view this study alone does not provide strong evidence that reducing dairy intake would reduce cancer risk.”

He added: “Although the paper suggests a 12% increased relative risk for female breast cancer, this does not equate to 12 more cases per 100 individuals – in absolute terms this would be more like 1 or 2 cases per 1,000 people.”

Similarly, Kevin McConway, PhD, emeritus professor of applied statistics at the Open University, Milton Keynes, England, said: “An issue is that there were many differences between the people that consumed different amounts of dairy products, apart from their difference in dairy consumption. For instance, of those who never or rarely consumed dairy products, fewer than a third lived in urban areas, but of regular dairy consumers (at least once a week), 83% lived in urban areas. Regular consumers were considerably more likely to be well educated than those who never or rarely consumed dairy products, and there were other differences too. 

“So if, as the researchers found, a greater proportion of the regular consumers than of the never or rare consumers had a cancer diagnosis, that could have been because of their different dairy consumption, or it could have been (in part or entirely) because of the different places they lived, or their different education levels, or any of the other factors on which the groups differed.

“One can never be sure that all the relevant factors have been adjusted for. That’s why the researchers rightly say that these results can’t establish whether the associations between dairy consumption and the risks of some cancers, that they found, are there because the dairy consumption differences change the cancer risks in a cause-and-effect way. They might, or they might not.”

He cautioned: “I don’t think anyone should decide to change their individual diet solely because of the results of this new study.”

Commenting on the study, Fiona Osgun, senior health information manager at Cancer Research UK, London, told this news organization: “This early-stage study found an association between dairy consumption and the risks of certain cancers, but that doesn’t mean that they’re causing them or that people need to avoid dairy. Dairy products can be part of a healthy balanced diet and, in the U.K., the Food Standards Agency regulates them to make sure they’re safe. There’s good evidence that dairy reduces the risk of bowel cancer, but no clear evidence for other cancer types, and this is no different for people who are lactose intolerant.”

A version of this article first appeared on Medscape UK.

A relationship between consumption of dairy products and risk of various cancers has been intensively investigated in the past but yielded inconclusive or conflicting results. Now a large new study comparing Chinese dairy consumption with that in the United Kingdom, shows that increased dairy consumption was linked to higher risks of liver cancer and female breast cancer.

The study, by researchers from Oxford University’s department of population health, and Peking University and the Chinese Academy of Medical Sciences in Beijing, used data from the China Kadoorie Biobank Study, a long-term prospective study involving more than over 510,000 participants recruited from 10 geographically diverse areas across China, including both rural and urban regions. They compared this to data from the UK biobank.

Subjects were 59% female, 41% male, aged 30-79 years, and had no history of cancer at recruitment between 2004 and 2008. Food questionnaires were completed at the outset and participants followed for an average of 11 years, using national cancer and death registries and health insurance records to identify new cancer diagnoses, including both fatal and nonfatal events.

Participants were categorized into three groups according to how often they consumed dairy products (primarily milk):

• Regular consumers (at least once a week): 20.4% of the cohort.
• Monthly consumers: 11.1%.
• Nonconsumers who never or rarely consumed dairy products: 68.5%.

Average dairy consumption was 37.9 g/day overall and 80.8 g/day among regular consumers. This compares with an average consumption of around 300 g/day in participants in the UK Biobank cohort.

Over the course of the study, 29,277 new cancer cases were recorded, including 6,282 lung, 2,582 female breast, 3,577 stomach, 3,350 colorectal, and 3,191 liver cancer cases.

Analyses correlating cases with consumption took into account a range of other factors potentially affecting cancer risk, including age, sex, region, family history of cancer, socioeconomic status (education and income), lifestyle factors (alcohol intake, smoking, physical activity, soy consumption, and fresh fruit intake), body mass index, chronic hepatitis B virus infection, and female reproductive factors.

Higher dairy intakes linked with risk of liver and breast cancers

Results revealed that higher regular dairy intake was associated with significantly higher risks of liver cancer and female breast cancer, both common types of cancer in China. Analyses indicated that for each 50-g/day intake, the risks increased by 12% and 17%, respectively.

There was also an increase in total cancer diagnoses, and an increased risk of lymphoma, though this was not statistically significant after correction for confounders. No association was found between dairy products and colorectal cancer, prostate cancer, or any other site-specific cancer.

The research, published in BMC Medicine, is the first major study to investigate dairy consumption and cancer risk in Chinese adults. The results conflict with previous studies on Western populations, which have suggested that dairy products may be associated with a lower risk of colorectal cancer and a higher risk of prostate cancer but have found no clear link for breast or other types of cancer.

Lead researchers Maria Kakkoura, PhD, MSc, and associate professor Huaidong Du, MD, PhD, told this news organization that, although they don’t know the reason for the difference, “there is clear evidence that colorectal cancer has a different incidence pattern in China, compared with Western countries. Other risk factors, like adiposity, may have a stronger effect on the risk of colorectal cancer in Western countries than in China.” Notably, the mean body mass index in the study population was around 23 kg/m², they said – by contrast in the United Kingdom it is 27.6 kg/m2.

Effects not necessarily causal

Ian Givens, PhD, professor of food chain nutrition at the University of Reading (England), said the study was “potentially very important for Chinese people, if it can be confirmed that dairy products affect the risk of breast and/or liver cancer differently in Chinese subjects to those in Western Societies, especially as dairy consumption in China is much lower than in most Western diets.”

He added: “As always it needs to be kept in mind that this type of study can only establish associations with disease risk, not cause.”

Dr. Kakkoura, nutritional epidemiologist at Oxford (England) University’s department of population health, said: “This was the first major study to investigate the link between dairy products and cancer risk in a Chinese population. Further studies are needed to validate these current findings, establish if these associations are causal, and investigate the potential underlying mechanisms involved.”

The researchers said that, while the results do not prove causation, “there are several plausible biological mechanisms that may explain these associations.” They pointed to higher dairy consumption potentially increasing levels of insulinlike growth factor-I, known to promote cell proliferation and associated with higher risks of several types of cancer.

In addition, estrogen and progesterone present in cows’ milk may play a role in increasing breast cancer risk, whilst saturated and trans-fatty acids from dairy products may increase the risk of liver cancer. As many Chinese people are lactase deficient, dairy products may also be broken down into products that affect cancer risk.

No justification for dietary change

Confounding factors may also have influenced the results, commented Duane Mellor, PhD, RD, RNutr, registered dietitian and senior teaching fellow at Aston University, Birmingham, England. “Those in the study who consumed dairy were more likely to live in cities and have other health conditions, including cardiovascular disease and diabetes – although some of these factors were considered in the analysis, not all of these covariates were, which could influence the findings.

“In my view this study alone does not provide strong evidence that reducing dairy intake would reduce cancer risk.”

He added: “Although the paper suggests a 12% increased relative risk for female breast cancer, this does not equate to 12 more cases per 100 individuals – in absolute terms this would be more like 1 or 2 cases per 1,000 people.”

Similarly, Kevin McConway, PhD, emeritus professor of applied statistics at the Open University, Milton Keynes, England, said: “An issue is that there were many differences between the people that consumed different amounts of dairy products, apart from their difference in dairy consumption. For instance, of those who never or rarely consumed dairy products, fewer than a third lived in urban areas, but of regular dairy consumers (at least once a week), 83% lived in urban areas. Regular consumers were considerably more likely to be well educated than those who never or rarely consumed dairy products, and there were other differences too. 

“So if, as the researchers found, a greater proportion of the regular consumers than of the never or rare consumers had a cancer diagnosis, that could have been because of their different dairy consumption, or it could have been (in part or entirely) because of the different places they lived, or their different education levels, or any of the other factors on which the groups differed.

“One can never be sure that all the relevant factors have been adjusted for. That’s why the researchers rightly say that these results can’t establish whether the associations between dairy consumption and the risks of some cancers, that they found, are there because the dairy consumption differences change the cancer risks in a cause-and-effect way. They might, or they might not.”

He cautioned: “I don’t think anyone should decide to change their individual diet solely because of the results of this new study.”

Commenting on the study, Fiona Osgun, senior health information manager at Cancer Research UK, London, told this news organization: “This early-stage study found an association between dairy consumption and the risks of certain cancers, but that doesn’t mean that they’re causing them or that people need to avoid dairy. Dairy products can be part of a healthy balanced diet and, in the U.K., the Food Standards Agency regulates them to make sure they’re safe. There’s good evidence that dairy reduces the risk of bowel cancer, but no clear evidence for other cancer types, and this is no different for people who are lactose intolerant.”

A version of this article first appeared on Medscape UK.

We have a half-forgotten Indian immigrant to thank – a hospital night porter turned biochemist –for revolutionizing treatment of leukemia, the once deadly childhood scourge that is still the most common pediatric cancer.

Dr. Yellapragada SubbaRow has been called the “father of chemotherapy” for developing methotrexate, a powerful, inexpensive therapy for leukemia and other diseases, and he is celebrated for additional scientific achievements. Yet Dr. SubbaRow’s life was marked more by struggle than glory.

1995 Indian stamp; photo in public domain

Born poor in southeastern India, he nearly succumbed to a tropical disease that killed two older brothers, and he didn’t focus on schoolwork until his father died. Later, prejudice dogged his years as an immigrant to the United States, and a blood clot took his life at the age of 53.

Scientifically, however, Dr. SubbaRow (pronounced sue-buh-rao) triumphed, despite mammoth challenges and a lack of recognition that persists to this day. National Cancer Research Month is a fitting time to look back on his extraordinary life and work and pay tribute to his accomplishments.
 

‘Yella,’ folic acid, and a paradigm shift

No one appreciates Dr. SubbaRow more than a cadre of Indian-born physicians who have kept his legacy alive in journal articles, presentations, and a Pulitzer Prize-winning book. Among them is author and oncologist Siddhartha Mukherjee, MD, who chronicled Dr. SubbaRow’s achievements in his New York Times No. 1 bestseller, “The Emperor of All Maladies: A Biography of Cancer.”

As Dr. Mukherjee wrote, Dr. SubbaRow was a “pioneer in many ways, a physician turned cellular physiologist, a chemist who had accidentally wandered into biology.” (Per Indian tradition, SubbaRow is the doctor’s first name, and Yellapragada is his surname, but medical literature uses SubbaRow as his cognomen, with some variations in spelling. Dr. Mukherjee wrote that his friends called him “Yella.”)

Dr. SubbaRow came to the United States in 1923, after enduring a difficult childhood and young adulthood. He’d survived bouts of religious fervor, childhood rebellion (including a bid to run away from home and become a banana trader), and a failed arranged marriage. His wife bore him a child who died in infancy. He left it all behind.

In Boston, medical officials rejected his degree. Broke, he worked for a time as a night porter at Brigham and Women’s Hospital in Boston, changing sheets and cleaning urinals. To a poor but proud high-caste Indian Brahmin, the culture shock of carrying out these tasks must have been especially jarring.

Dr. SubbaRow went on to earn a diploma from Harvard Medical School, also in Boston, and became a junior faculty member. As a foreigner, Dr. Mukherjee wrote, Dr. SubbaRow was a “reclusive, nocturnal, heavily accented vegetarian,” so different from his colleagues that advancement seemed impossible. Despite his pioneering biochemistry work, Harvard later declined to offer Dr. SubbaRow a tenured faculty position.

By the early 1940s, he took a job at an upstate New York pharmaceutical company called Lederle Labs (later purchased by Pfizer). At Lederle, Dr. SubbaRow strove to synthesize the vitamin known as folic acid. He ended up creating a kind of antivitamin, a lookalike that acted like folic acid but only succeeded in gumming up the works in receptors. But what good would it do to stop the body from absorbing folic acid? Plenty, it turned out.
 

Discoveries pile up, but credit and fame prove elusive

Dr. SubbaRow was no stranger to producing landmark biological work. He’d previously codiscovered phosphocreatine and ATP, which are crucial to muscular contractions. However, “in 1935, he had to disown the extent of his role in the discovery of the color test related to phosphorus, instead giving the credit to his co-author, who was being considered for promotion to a full professorship at Harvard,” wrote author Gerald Posner in his 2020 book, “Pharma: Greed, Lies and the Poisoning of America.”

Houston-area oncologist Kirtan Nautiyal, MD, who paid tribute to Dr. SubbaRow in a 2018 article, contended that “with his Indian instinct for self-effacement, he had irreparably sabotaged his own career.”

Dr. SubbaRow and his team also developed “the first effective treatment of filariasis, which causes elephantiasis of the lower limbs and genitals in millions of people, mainly in tropical countries,” Dr. Nautiyal wrote. “Later in the decade, his antibiotic program generated polymyxin, the first effective treatment against the class of bacteria called Gram negatives, and aureomycin, the first “broad-spectrum’ antibiotic.” (Aureomycin is also the first tetracycline antibiotic.)

Dr. SubbaRow’s discovery of a folic acid antagonist would again go largely unheralded. But first came the realization that folic acid made childhood leukemia worse, not better, and the prospect that this process could potentially be reversed.
 

Rise of methotrexate and fall of leukemia

In Boston, Sidney Farber, MD, a Boston pathologist, was desperate to help Robert Sandler, a 2-year-old leukemia patient. Dr. Farber contacted his ex-colleague Dr. SubbaRow to request a supply of aminopterin, an early version of methotrexate that Dr. SubbaRow and his team had developed. Dr. Farber injected Robert with the substance and within 3 days, the toddler’s white blood count started falling – fast. He stopped bleeding, resumed eating, and once again seemed almost identical to his twin brother, as Dr. Mukherjee wrote in his book.

Leukemia had never gone into remission before. Unfortunately, the treatment only worked temporarily. Robert, like other children treated with the drug, relapsed and died within months. But Dr. Farber “saw a door open” – a chemical, a kind of chemotherapy, that could turn back cancer. In the case of folic acid antagonists, they do so by stopping cancer cells from replicating.

Methotrexate, a related agent synthesized by Dr. SubbaRow, would become a mainstay of leukemia treatment and begin to produce long-term remission from acute lymphoblastic leukemia in 1970, when combination chemotherapy was developed.

Other cancers fell to methotrexate treatment. “Previous assumptions that cancer was nearly always fatal were revised, and the field of medical oncology (treatment of cancer with chemotherapy), which had not previously existed, was formally established in 1971,” according to the National Cancer Institute’s history of methotrexate. This account does not mention Dr. SubbaRow.
 

Death takes the doctor, but his legacy remains

In biographies, as well as his own words, Dr. SubbaRow comes across as a prickly, hard-driving workaholic who had little interest in intimate human connections. “It is not good to ask in every letter when I will be back,” he wrote to his wife back in India, before cutting off ties completely in the early 1930s. “I will come as early as possible. ... I do not want to write anything more.”

It seems, as his biographer S.P.K. Gupta noted, that “he was quite determined that the time allotted to him on Earth should be completely devoted to finding cures for ailments that plagued mankind.”

Still, Dr. SubbaRow’s research team was devoted to him, and he had plenty of reasons to be bitter, such as the prejudice and isolation he encountered in the United States and earlier, in British-run India. According to Mr. Posner’s book, even as a young medical student, Dr. SubbaRow heeded the call of Indian independence activist Mohandas Gandhi. He “refused the British surgical gown given him at school and instead donned a traditional and simple cotton Khadi. That act of defiance cost SubbaRow the college degree that was necessary for him to get into the State Medical College.”

During the last year of his life, Dr. SubbaRow faced yet another humiliation: In his landmark 1948 study about aminopterin as a treatment for leukemia, his colleague Dr. Farber failed to credit him, an “astonishing omission” as Yaddanapudi Ravindranath, MBBS, a pediatric hematologist/oncologist at Wayne State University, Detroit, put it. “From everything I know, Dr. Farber spent the rest of his career apologizing and trying to make amends for it,” Dr. Ravindranath said in an interview.
 

A career cut short, and a lasting legacy

In 1948, at the age of 53, Dr. SubbaRow suddenly died. “Many think Dr. SubbaRow would have won [the] Nobel Prize had he lived a few years longer,” said Dr. Ravindranath.

Like Dr. SubbaRow, Dr. Ravindranath was born in Andhra Pradesh state, near the city of Chennai formerly known as Madras. “Being a compatriot, in a way I continue his legacy, and I am obviously proud of him,” said Dr. Ravindranath, who has conducted his own landmark research regarding methotrexate and leukemia.

Nearly 75 years after Dr. SubbaRow’s death, Indian-born physicians like Dr. Ravindranath continue to honor him in print, trying to ensure that he’s not forgotten. Methotrexate remains a crucial treatment for leukemia, along with a long list of other ailments, including psoriasis.

Recognition for “Yella” may have come late and infrequently, but a Lederle Laboratories research library named after him offered Dr. SubbaRow a kind of immortality. A plaque there memorialized him in stone as a scientist, teacher, philosopher, and humanitarian, featuring the quote: “Science simply prolongs life. Religion deepens it.”

By all accounts, Dr. SubbaRow was a man of science and faith who had faith in science.

We have a half-forgotten Indian immigrant to thank – a hospital night porter turned biochemist –for revolutionizing treatment of leukemia, the once deadly childhood scourge that is still the most common pediatric cancer.

Dr. Yellapragada SubbaRow has been called the “father of chemotherapy” for developing methotrexate, a powerful, inexpensive therapy for leukemia and other diseases, and he is celebrated for additional scientific achievements. Yet Dr. SubbaRow’s life was marked more by struggle than glory.

1995 Indian stamp; photo in public domain

Born poor in southeastern India, he nearly succumbed to a tropical disease that killed two older brothers, and he didn’t focus on schoolwork until his father died. Later, prejudice dogged his years as an immigrant to the United States, and a blood clot took his life at the age of 53.

Scientifically, however, Dr. SubbaRow (pronounced sue-buh-rao) triumphed, despite mammoth challenges and a lack of recognition that persists to this day. National Cancer Research Month is a fitting time to look back on his extraordinary life and work and pay tribute to his accomplishments.
 

‘Yella,’ folic acid, and a paradigm shift

No one appreciates Dr. SubbaRow more than a cadre of Indian-born physicians who have kept his legacy alive in journal articles, presentations, and a Pulitzer Prize-winning book. Among them is author and oncologist Siddhartha Mukherjee, MD, who chronicled Dr. SubbaRow’s achievements in his New York Times No. 1 bestseller, “The Emperor of All Maladies: A Biography of Cancer.”

As Dr. Mukherjee wrote, Dr. SubbaRow was a “pioneer in many ways, a physician turned cellular physiologist, a chemist who had accidentally wandered into biology.” (Per Indian tradition, SubbaRow is the doctor’s first name, and Yellapragada is his surname, but medical literature uses SubbaRow as his cognomen, with some variations in spelling. Dr. Mukherjee wrote that his friends called him “Yella.”)

Dr. SubbaRow came to the United States in 1923, after enduring a difficult childhood and young adulthood. He’d survived bouts of religious fervor, childhood rebellion (including a bid to run away from home and become a banana trader), and a failed arranged marriage. His wife bore him a child who died in infancy. He left it all behind.

In Boston, medical officials rejected his degree. Broke, he worked for a time as a night porter at Brigham and Women’s Hospital in Boston, changing sheets and cleaning urinals. To a poor but proud high-caste Indian Brahmin, the culture shock of carrying out these tasks must have been especially jarring.

Dr. SubbaRow went on to earn a diploma from Harvard Medical School, also in Boston, and became a junior faculty member. As a foreigner, Dr. Mukherjee wrote, Dr. SubbaRow was a “reclusive, nocturnal, heavily accented vegetarian,” so different from his colleagues that advancement seemed impossible. Despite his pioneering biochemistry work, Harvard later declined to offer Dr. SubbaRow a tenured faculty position.

By the early 1940s, he took a job at an upstate New York pharmaceutical company called Lederle Labs (later purchased by Pfizer). At Lederle, Dr. SubbaRow strove to synthesize the vitamin known as folic acid. He ended up creating a kind of antivitamin, a lookalike that acted like folic acid but only succeeded in gumming up the works in receptors. But what good would it do to stop the body from absorbing folic acid? Plenty, it turned out.
 

Discoveries pile up, but credit and fame prove elusive

Dr. SubbaRow was no stranger to producing landmark biological work. He’d previously codiscovered phosphocreatine and ATP, which are crucial to muscular contractions. However, “in 1935, he had to disown the extent of his role in the discovery of the color test related to phosphorus, instead giving the credit to his co-author, who was being considered for promotion to a full professorship at Harvard,” wrote author Gerald Posner in his 2020 book, “Pharma: Greed, Lies and the Poisoning of America.”

Houston-area oncologist Kirtan Nautiyal, MD, who paid tribute to Dr. SubbaRow in a 2018 article, contended that “with his Indian instinct for self-effacement, he had irreparably sabotaged his own career.”

Dr. SubbaRow and his team also developed “the first effective treatment of filariasis, which causes elephantiasis of the lower limbs and genitals in millions of people, mainly in tropical countries,” Dr. Nautiyal wrote. “Later in the decade, his antibiotic program generated polymyxin, the first effective treatment against the class of bacteria called Gram negatives, and aureomycin, the first “broad-spectrum’ antibiotic.” (Aureomycin is also the first tetracycline antibiotic.)

Dr. SubbaRow’s discovery of a folic acid antagonist would again go largely unheralded. But first came the realization that folic acid made childhood leukemia worse, not better, and the prospect that this process could potentially be reversed.
 

Rise of methotrexate and fall of leukemia

In Boston, Sidney Farber, MD, a Boston pathologist, was desperate to help Robert Sandler, a 2-year-old leukemia patient. Dr. Farber contacted his ex-colleague Dr. SubbaRow to request a supply of aminopterin, an early version of methotrexate that Dr. SubbaRow and his team had developed. Dr. Farber injected Robert with the substance and within 3 days, the toddler’s white blood count started falling – fast. He stopped bleeding, resumed eating, and once again seemed almost identical to his twin brother, as Dr. Mukherjee wrote in his book.

Leukemia had never gone into remission before. Unfortunately, the treatment only worked temporarily. Robert, like other children treated with the drug, relapsed and died within months. But Dr. Farber “saw a door open” – a chemical, a kind of chemotherapy, that could turn back cancer. In the case of folic acid antagonists, they do so by stopping cancer cells from replicating.

Methotrexate, a related agent synthesized by Dr. SubbaRow, would become a mainstay of leukemia treatment and begin to produce long-term remission from acute lymphoblastic leukemia in 1970, when combination chemotherapy was developed.

Other cancers fell to methotrexate treatment. “Previous assumptions that cancer was nearly always fatal were revised, and the field of medical oncology (treatment of cancer with chemotherapy), which had not previously existed, was formally established in 1971,” according to the National Cancer Institute’s history of methotrexate. This account does not mention Dr. SubbaRow.
 

Death takes the doctor, but his legacy remains

In biographies, as well as his own words, Dr. SubbaRow comes across as a prickly, hard-driving workaholic who had little interest in intimate human connections. “It is not good to ask in every letter when I will be back,” he wrote to his wife back in India, before cutting off ties completely in the early 1930s. “I will come as early as possible. ... I do not want to write anything more.”

It seems, as his biographer S.P.K. Gupta noted, that “he was quite determined that the time allotted to him on Earth should be completely devoted to finding cures for ailments that plagued mankind.”

Still, Dr. SubbaRow’s research team was devoted to him, and he had plenty of reasons to be bitter, such as the prejudice and isolation he encountered in the United States and earlier, in British-run India. According to Mr. Posner’s book, even as a young medical student, Dr. SubbaRow heeded the call of Indian independence activist Mohandas Gandhi. He “refused the British surgical gown given him at school and instead donned a traditional and simple cotton Khadi. That act of defiance cost SubbaRow the college degree that was necessary for him to get into the State Medical College.”

During the last year of his life, Dr. SubbaRow faced yet another humiliation: In his landmark 1948 study about aminopterin as a treatment for leukemia, his colleague Dr. Farber failed to credit him, an “astonishing omission” as Yaddanapudi Ravindranath, MBBS, a pediatric hematologist/oncologist at Wayne State University, Detroit, put it. “From everything I know, Dr. Farber spent the rest of his career apologizing and trying to make amends for it,” Dr. Ravindranath said in an interview.
 

A career cut short, and a lasting legacy

In 1948, at the age of 53, Dr. SubbaRow suddenly died. “Many think Dr. SubbaRow would have won [the] Nobel Prize had he lived a few years longer,” said Dr. Ravindranath.

Like Dr. SubbaRow, Dr. Ravindranath was born in Andhra Pradesh state, near the city of Chennai formerly known as Madras. “Being a compatriot, in a way I continue his legacy, and I am obviously proud of him,” said Dr. Ravindranath, who has conducted his own landmark research regarding methotrexate and leukemia.

Nearly 75 years after Dr. SubbaRow’s death, Indian-born physicians like Dr. Ravindranath continue to honor him in print, trying to ensure that he’s not forgotten. Methotrexate remains a crucial treatment for leukemia, along with a long list of other ailments, including psoriasis.

Recognition for “Yella” may have come late and infrequently, but a Lederle Laboratories research library named after him offered Dr. SubbaRow a kind of immortality. A plaque there memorialized him in stone as a scientist, teacher, philosopher, and humanitarian, featuring the quote: “Science simply prolongs life. Religion deepens it.”

By all accounts, Dr. SubbaRow was a man of science and faith who had faith in science.

We have a half-forgotten Indian immigrant to thank – a hospital night porter turned biochemist –for revolutionizing treatment of leukemia, the once deadly childhood scourge that is still the most common pediatric cancer.

Dr. Yellapragada SubbaRow has been called the “father of chemotherapy” for developing methotrexate, a powerful, inexpensive therapy for leukemia and other diseases, and he is celebrated for additional scientific achievements. Yet Dr. SubbaRow’s life was marked more by struggle than glory.

1995 Indian stamp; photo in public domain

Born poor in southeastern India, he nearly succumbed to a tropical disease that killed two older brothers, and he didn’t focus on schoolwork until his father died. Later, prejudice dogged his years as an immigrant to the United States, and a blood clot took his life at the age of 53.

Scientifically, however, Dr. SubbaRow (pronounced sue-buh-rao) triumphed, despite mammoth challenges and a lack of recognition that persists to this day. National Cancer Research Month is a fitting time to look back on his extraordinary life and work and pay tribute to his accomplishments.
 

‘Yella,’ folic acid, and a paradigm shift

No one appreciates Dr. SubbaRow more than a cadre of Indian-born physicians who have kept his legacy alive in journal articles, presentations, and a Pulitzer Prize-winning book. Among them is author and oncologist Siddhartha Mukherjee, MD, who chronicled Dr. SubbaRow’s achievements in his New York Times No. 1 bestseller, “The Emperor of All Maladies: A Biography of Cancer.”

As Dr. Mukherjee wrote, Dr. SubbaRow was a “pioneer in many ways, a physician turned cellular physiologist, a chemist who had accidentally wandered into biology.” (Per Indian tradition, SubbaRow is the doctor’s first name, and Yellapragada is his surname, but medical literature uses SubbaRow as his cognomen, with some variations in spelling. Dr. Mukherjee wrote that his friends called him “Yella.”)

Dr. SubbaRow came to the United States in 1923, after enduring a difficult childhood and young adulthood. He’d survived bouts of religious fervor, childhood rebellion (including a bid to run away from home and become a banana trader), and a failed arranged marriage. His wife bore him a child who died in infancy. He left it all behind.

In Boston, medical officials rejected his degree. Broke, he worked for a time as a night porter at Brigham and Women’s Hospital in Boston, changing sheets and cleaning urinals. To a poor but proud high-caste Indian Brahmin, the culture shock of carrying out these tasks must have been especially jarring.

Dr. SubbaRow went on to earn a diploma from Harvard Medical School, also in Boston, and became a junior faculty member. As a foreigner, Dr. Mukherjee wrote, Dr. SubbaRow was a “reclusive, nocturnal, heavily accented vegetarian,” so different from his colleagues that advancement seemed impossible. Despite his pioneering biochemistry work, Harvard later declined to offer Dr. SubbaRow a tenured faculty position.

By the early 1940s, he took a job at an upstate New York pharmaceutical company called Lederle Labs (later purchased by Pfizer). At Lederle, Dr. SubbaRow strove to synthesize the vitamin known as folic acid. He ended up creating a kind of antivitamin, a lookalike that acted like folic acid but only succeeded in gumming up the works in receptors. But what good would it do to stop the body from absorbing folic acid? Plenty, it turned out.
 

Discoveries pile up, but credit and fame prove elusive

Dr. SubbaRow was no stranger to producing landmark biological work. He’d previously codiscovered phosphocreatine and ATP, which are crucial to muscular contractions. However, “in 1935, he had to disown the extent of his role in the discovery of the color test related to phosphorus, instead giving the credit to his co-author, who was being considered for promotion to a full professorship at Harvard,” wrote author Gerald Posner in his 2020 book, “Pharma: Greed, Lies and the Poisoning of America.”

Houston-area oncologist Kirtan Nautiyal, MD, who paid tribute to Dr. SubbaRow in a 2018 article, contended that “with his Indian instinct for self-effacement, he had irreparably sabotaged his own career.”

Dr. SubbaRow and his team also developed “the first effective treatment of filariasis, which causes elephantiasis of the lower limbs and genitals in millions of people, mainly in tropical countries,” Dr. Nautiyal wrote. “Later in the decade, his antibiotic program generated polymyxin, the first effective treatment against the class of bacteria called Gram negatives, and aureomycin, the first “broad-spectrum’ antibiotic.” (Aureomycin is also the first tetracycline antibiotic.)

Dr. SubbaRow’s discovery of a folic acid antagonist would again go largely unheralded. But first came the realization that folic acid made childhood leukemia worse, not better, and the prospect that this process could potentially be reversed.
 

Rise of methotrexate and fall of leukemia

In Boston, Sidney Farber, MD, a Boston pathologist, was desperate to help Robert Sandler, a 2-year-old leukemia patient. Dr. Farber contacted his ex-colleague Dr. SubbaRow to request a supply of aminopterin, an early version of methotrexate that Dr. SubbaRow and his team had developed. Dr. Farber injected Robert with the substance and within 3 days, the toddler’s white blood count started falling – fast. He stopped bleeding, resumed eating, and once again seemed almost identical to his twin brother, as Dr. Mukherjee wrote in his book.

Leukemia had never gone into remission before. Unfortunately, the treatment only worked temporarily. Robert, like other children treated with the drug, relapsed and died within months. But Dr. Farber “saw a door open” – a chemical, a kind of chemotherapy, that could turn back cancer. In the case of folic acid antagonists, they do so by stopping cancer cells from replicating.

Methotrexate, a related agent synthesized by Dr. SubbaRow, would become a mainstay of leukemia treatment and begin to produce long-term remission from acute lymphoblastic leukemia in 1970, when combination chemotherapy was developed.

Other cancers fell to methotrexate treatment. “Previous assumptions that cancer was nearly always fatal were revised, and the field of medical oncology (treatment of cancer with chemotherapy), which had not previously existed, was formally established in 1971,” according to the National Cancer Institute’s history of methotrexate. This account does not mention Dr. SubbaRow.
 

Death takes the doctor, but his legacy remains

In biographies, as well as his own words, Dr. SubbaRow comes across as a prickly, hard-driving workaholic who had little interest in intimate human connections. “It is not good to ask in every letter when I will be back,” he wrote to his wife back in India, before cutting off ties completely in the early 1930s. “I will come as early as possible. ... I do not want to write anything more.”

It seems, as his biographer S.P.K. Gupta noted, that “he was quite determined that the time allotted to him on Earth should be completely devoted to finding cures for ailments that plagued mankind.”

Still, Dr. SubbaRow’s research team was devoted to him, and he had plenty of reasons to be bitter, such as the prejudice and isolation he encountered in the United States and earlier, in British-run India. According to Mr. Posner’s book, even as a young medical student, Dr. SubbaRow heeded the call of Indian independence activist Mohandas Gandhi. He “refused the British surgical gown given him at school and instead donned a traditional and simple cotton Khadi. That act of defiance cost SubbaRow the college degree that was necessary for him to get into the State Medical College.”

During the last year of his life, Dr. SubbaRow faced yet another humiliation: In his landmark 1948 study about aminopterin as a treatment for leukemia, his colleague Dr. Farber failed to credit him, an “astonishing omission” as Yaddanapudi Ravindranath, MBBS, a pediatric hematologist/oncologist at Wayne State University, Detroit, put it. “From everything I know, Dr. Farber spent the rest of his career apologizing and trying to make amends for it,” Dr. Ravindranath said in an interview.
 

A career cut short, and a lasting legacy

In 1948, at the age of 53, Dr. SubbaRow suddenly died. “Many think Dr. SubbaRow would have won [the] Nobel Prize had he lived a few years longer,” said Dr. Ravindranath.

Like Dr. SubbaRow, Dr. Ravindranath was born in Andhra Pradesh state, near the city of Chennai formerly known as Madras. “Being a compatriot, in a way I continue his legacy, and I am obviously proud of him,” said Dr. Ravindranath, who has conducted his own landmark research regarding methotrexate and leukemia.

Nearly 75 years after Dr. SubbaRow’s death, Indian-born physicians like Dr. Ravindranath continue to honor him in print, trying to ensure that he’s not forgotten. Methotrexate remains a crucial treatment for leukemia, along with a long list of other ailments, including psoriasis.

Recognition for “Yella” may have come late and infrequently, but a Lederle Laboratories research library named after him offered Dr. SubbaRow a kind of immortality. A plaque there memorialized him in stone as a scientist, teacher, philosopher, and humanitarian, featuring the quote: “Science simply prolongs life. Religion deepens it.”

By all accounts, Dr. SubbaRow was a man of science and faith who had faith in science.

Women with ductal carcinoma in situ (DCIS) breast cancer are generally uninformed about their diagnosis and are making uninformed treatment decisions, according to results of a study presented this month at ESMO Breast Cancer 2022, an annual meeting of the European Society for Medical Oncology.

The standard of care for women diagnosed with DCIS includes surgery with or without radiotherapy – even low-risk patients who are increasingly being steered toward active surveillance with annual mammograms. But few patients understand their diagnosis well enough to make informed decisions about treatment, according to a study led by Ellen Engelhardt, PhD, a postdoctoral fellow at The Netherlands Cancer Institute, Amsterdam.

“You’re not able to really have an informed preference until you understand the choices,” she said.

Dr. Engelhardt and colleagues surveyed 200 patients (mean age 59 years) from the LORD study, which is currently underway at The Netherlands Cancer Institute. The women were asked to complete a survey before treatment decisions were made. Their objective was to determine how knowledgeable patients were about DCIS. They found that only 34% of women answered four out of seven questions correctly: 19% of patients believed that DCIS could metastasize to organs other than the breast; 31% did not realize DCIS could progress to invasive breast cancer if left untreated; 79% thought DCIS could always be seen on mammograms; and, 93% said that progression could always be detected before it becomes “too extensive.” Knowledge of DCIS was found not to be associated with patient education level.

Susie X. Sun, MD, FACS, a breast surgeon at the University of Texas MD Anderson Cancer Center, Houston, said the findings clearly highlight a disconnect in communication between doctor and patient.

“I was surprised, because this clearly demonstrates there is a disconnect between what patients are being told by their providers and what is being perceived. It really shows us that we need to do a better job of making sure that our patients understand the information they’re given,” she said.

Dr. Sun, who was not involved in the study, said that DCIS needs to be explained well to patients. When they receive a diagnosis, often all they hear is, “I have breast cancer. It is really important for us to stress to patients how DCIS is different from invasive breast cancer,” she said.

The “Management of Low-risk (grade I and II) DCIS (LORD)” study is one of three studies comparing active surveillance to surgery (with or without radiotherapy).

A limitation of the study presented at ESMO Breast Cancer is that it remains unclear why patients answered questions incorrectly. Was information never communicated to them? Or, did they mishear or misunderstand the doctor? In future studies, Dr. Engelhardt and her colleagues plan to record and analyze audio tapes of consultations to determine where the communication disconnect lies.

Dr. Engelhardt did not disclose any conflicts associated with this work.

Women with ductal carcinoma in situ (DCIS) breast cancer are generally uninformed about their diagnosis and are making uninformed treatment decisions, according to results of a study presented this month at ESMO Breast Cancer 2022, an annual meeting of the European Society for Medical Oncology.

The standard of care for women diagnosed with DCIS includes surgery with or without radiotherapy – even low-risk patients who are increasingly being steered toward active surveillance with annual mammograms. But few patients understand their diagnosis well enough to make informed decisions about treatment, according to a study led by Ellen Engelhardt, PhD, a postdoctoral fellow at The Netherlands Cancer Institute, Amsterdam.

“You’re not able to really have an informed preference until you understand the choices,” she said.

Dr. Engelhardt and colleagues surveyed 200 patients (mean age 59 years) from the LORD study, which is currently underway at The Netherlands Cancer Institute. The women were asked to complete a survey before treatment decisions were made. Their objective was to determine how knowledgeable patients were about DCIS. They found that only 34% of women answered four out of seven questions correctly: 19% of patients believed that DCIS could metastasize to organs other than the breast; 31% did not realize DCIS could progress to invasive breast cancer if left untreated; 79% thought DCIS could always be seen on mammograms; and, 93% said that progression could always be detected before it becomes “too extensive.” Knowledge of DCIS was found not to be associated with patient education level.

Susie X. Sun, MD, FACS, a breast surgeon at the University of Texas MD Anderson Cancer Center, Houston, said the findings clearly highlight a disconnect in communication between doctor and patient.

“I was surprised, because this clearly demonstrates there is a disconnect between what patients are being told by their providers and what is being perceived. It really shows us that we need to do a better job of making sure that our patients understand the information they’re given,” she said.

Dr. Sun, who was not involved in the study, said that DCIS needs to be explained well to patients. When they receive a diagnosis, often all they hear is, “I have breast cancer. It is really important for us to stress to patients how DCIS is different from invasive breast cancer,” she said.

The “Management of Low-risk (grade I and II) DCIS (LORD)” study is one of three studies comparing active surveillance to surgery (with or without radiotherapy).

A limitation of the study presented at ESMO Breast Cancer is that it remains unclear why patients answered questions incorrectly. Was information never communicated to them? Or, did they mishear or misunderstand the doctor? In future studies, Dr. Engelhardt and her colleagues plan to record and analyze audio tapes of consultations to determine where the communication disconnect lies.

Dr. Engelhardt did not disclose any conflicts associated with this work.

Women with ductal carcinoma in situ (DCIS) breast cancer are generally uninformed about their diagnosis and are making uninformed treatment decisions, according to results of a study presented this month at ESMO Breast Cancer 2022, an annual meeting of the European Society for Medical Oncology.

The standard of care for women diagnosed with DCIS includes surgery with or without radiotherapy – even low-risk patients who are increasingly being steered toward active surveillance with annual mammograms. But few patients understand their diagnosis well enough to make informed decisions about treatment, according to a study led by Ellen Engelhardt, PhD, a postdoctoral fellow at The Netherlands Cancer Institute, Amsterdam.

“You’re not able to really have an informed preference until you understand the choices,” she said.

Dr. Engelhardt and colleagues surveyed 200 patients (mean age 59 years) from the LORD study, which is currently underway at The Netherlands Cancer Institute. The women were asked to complete a survey before treatment decisions were made. Their objective was to determine how knowledgeable patients were about DCIS. They found that only 34% of women answered four out of seven questions correctly: 19% of patients believed that DCIS could metastasize to organs other than the breast; 31% did not realize DCIS could progress to invasive breast cancer if left untreated; 79% thought DCIS could always be seen on mammograms; and, 93% said that progression could always be detected before it becomes “too extensive.” Knowledge of DCIS was found not to be associated with patient education level.

Susie X. Sun, MD, FACS, a breast surgeon at the University of Texas MD Anderson Cancer Center, Houston, said the findings clearly highlight a disconnect in communication between doctor and patient.

“I was surprised, because this clearly demonstrates there is a disconnect between what patients are being told by their providers and what is being perceived. It really shows us that we need to do a better job of making sure that our patients understand the information they’re given,” she said.

Dr. Sun, who was not involved in the study, said that DCIS needs to be explained well to patients. When they receive a diagnosis, often all they hear is, “I have breast cancer. It is really important for us to stress to patients how DCIS is different from invasive breast cancer,” she said.

The “Management of Low-risk (grade I and II) DCIS (LORD)” study is one of three studies comparing active surveillance to surgery (with or without radiotherapy).

A limitation of the study presented at ESMO Breast Cancer is that it remains unclear why patients answered questions incorrectly. Was information never communicated to them? Or, did they mishear or misunderstand the doctor? In future studies, Dr. Engelhardt and her colleagues plan to record and analyze audio tapes of consultations to determine where the communication disconnect lies.

Dr. Engelhardt did not disclose any conflicts associated with this work.

Nasopharyngeal carcinoma (NPC) differs from other head and neck (H&N) cancers in its epidemiology and treatment. Unlike other H&N cancers, NPC has a distinct geographical distribution with a much higher incidence in endemic areas, such as southern China, than in areas where it is relatively uncommon, such as the United States.¹ The etiology of NPC varies based on the geographical distribution, with Epstein-Barr virus (EBV) thought to be the primary etiologic agent in endemic areas. On the other hand, in North America 2 additional subsets of NPC have been identified: human papillomavirus (HPV)–positive/EBV-negative and HPV-negative/EBV-negative.^2,3 NPC arises from the epithelial lining of the nasopharynx, often in the fossa of Rosenmuller, and is the most seen tumor in the nasopharynx.⁴ NPC is less surgically accessible than other H&N cancers, and surgery to the nasopharynx poses more risks given the proximity of critical surrounding structures. NPC is radiosensitive, and therefore radiotherapy (RT), in combination with chemotherapy for locally advanced tumors, has become the mainstay of treatment for nonmetastatic NPC.⁴

NPC often presents with an asymptomatic neck mass or with symptoms of epistaxis, nasal obstruction, and otitis media.⁵ Advanced cases of NPC can present with direct extension into the skull base, paranasal sinuses, and orbit, as well as involvement of cranial nerves. Radiation planning for tumors of the nasopharynx is complicated by the need to deliver an adequate dose to the tumor while limiting dose and toxicity to nearby critical structures such as the brainstem, optic chiasm, eyes, spinal cord (SC), temporal lobes, and cochleae. Achieving an adequate dose to nasopharyngeal primary tumors is especially complicated for T4 tumors invading the skull base with intracranial extension, in direct contact with these critical structures (Table 1).

Case Presentation

A 34-year-old male patient with no previous medical history presented to the emergency department with worsening diplopia, nasal obstruction, facial pain, and neck stiffness. The patient reported a 3 pack-year smoking history with recent smoking cessation. His physical examination was notable for a right abducens nerve palsy and an ulcerated nasopharyngeal mass on endoscopy.

Computed tomography (CT) scan revealed a 7-cm mass in the nasopharynx, eroding through the skull base with destruction and replacement of the clivus by tumor. Also noted was erosion of the petrous apices, carotid canals, sella turcica, dens, and the bilateral occipital condyles. There was intracranial extension with replacement of portions of the cavernous sinuses as well as mass effect on the prepontine cistern. Additional brain imaging studies, including magnetic resonance imaging (MRI) and positron emission tomography (PET) scans, were obtained for completion of the staging workup. The MRI correlated with the findings noted on CT and demonstrated involvement of Meckel cave, foramen ovale, foramen rotundum, Dorello canal, and the hypoglossal canals. No cervical lymphadenopathy or distant metastases were noted on imaging. Pathology from biopsy revealed poorly differentiated squamous cell carcinoma, EBV-negative, strongly p16-positive, HPV-16 positive, and P53-negative.

RT planning was complicated by the tumor’s contact with the brainstem and upper cervical SC, as well as proximity of the tumor to the optic apparatus. The patient underwent 2 replanning CT scans at 26 Gy and 44 Gy to evaluate for tumor shrinkage. These CT scans demonstrated shrinkage of the tumor away from critical neural structures, allowing the treatment volume to be reduced away from these structures in order to achieve required dose tolerances (brainstem < 54 Gy, optic nerves and chiasm < 50 Gy, SC < 45 Gy for this case). The replanning CT scan at 44 Gy, 5 weeks after treatment initiation, demonstrated that dramatic tumor shrinkage had occurred early in treatment, with separation of the remaining tumor from the area of the SC and brainstem with which it was initially in contact (Figure 1). This improvement allowed for shrinkage of the high-dose radiation field away from these critical neural structures.

Discussion

RT for NPC is complicated by the proximity of these tumors to critical surrounding neural structures. It is challenging to achieve the required dose constraints to surrounding neural tissues while delivering the usual 70-Gy dose to the gross tumor, especially when the tumor comes into direct contact with these structures.

This case provides an example of response-adapted RT using imaging during treatment to shrink the high-dose target as the tumor shrinks away from critical surrounding structures.⁷ This strategy permits delivery of the maximum dose to the tumor while minimizing radiation dose, and therefore risk of toxicity, to normal surrounding structures. While it is typical to deliver 70 Gy to the full extent of tumor involvement for H&N tumors, this was not possible in this case as the tumor was in contact with the brainstem and upper cervical SC. Delivering the full 70 Gy to these areas of tumor would have placed this patient at substantial risk of brainstem and/or SC toxicity. This report demonstrates that response-adapted RT with shrinking fields can allow for tumor control while avoiding toxicity to critical neural structures for cases of locally advanced NPC in which tumor is abutting these structures.

Bony regeneration of the skull base following RT has been reported in the literature, but in limited reviews. Early reports used plain radiography to follow changes. Unger and colleagues demonstrated the regeneration of bone using skull radiographs 4 to 6 months after completion of RT for NPC.⁸ More recent literature details the ability of bone to regenerate after RT based on CT findings. Fang and colleagues reported on 90 cases of NPC with skull base destruction, with 63% having bony regeneration on posttreatment CT.⁹ Most of the patients in Fang’s report had bony regeneration within 1 year of treatment, and in general, bony regeneration became more evident on imaging with longer follow-up. Of note, local control was significantly greater in patients with regeneration vs persistent destruction (77% vs 21%, P < .001). On multivariate analysis, complete tumor response was significantly associated with bony regeneration; other factors such as age, sex, radiation dose, and chemotherapy were not significantly associated with the likelihood of bony regeneration.

Our report details a nasopharyngeal tumor that destroyed the skull base with no intact bony barrier. In such cases, concern arises regarding craniospinal instability with tumor regression if there is not simultaneous bone regeneration. Tumor invasion of the skull base and C1-2 vertebral bodies and complications from treatment of such tumor extent can lead to symptoms of craniospinal instability, including pain, difficulty with neck range of motion, and loss of strength and sensation in the upper and lower extremities.¹⁰ A case report of a woman treated with chemoradiation for a plasmacytoma of the skull base detailed her posttreatment presentation with quadriparesis resulting from craniospinal instability after tumor regression.¹¹ Such instability is generally treated surgically, and during this woman’s surgery, there was an injury to the right vertebral artery, although this did not cause any additional neurologic deficits.

Conclusions

There is a paucity of literature on bony regeneration in patients with skull base destruction from advanced NPC, and in particular, the ability of skull base regeneration to occur during treatment simultaneous with tumor regression. Our patient had HPV-positive/EBV-negative NPC, but it is unclear how this subtype affected his prognosis. Factors such as tumor histology, radiosensitivity with rapid tumor regression, and young age may have all contributed to the rapidity of bone regeneration in our patient. This case report demonstrates that an impressive tumor response to chemoradiation with simultaneous bony regeneration is possible among patients presenting with tumor destruction of the skull base, precluding the need for neurosurgical intervention.

Nasopharyngeal carcinoma (NPC) differs from other head and neck (H&N) cancers in its epidemiology and treatment. Unlike other H&N cancers, NPC has a distinct geographical distribution with a much higher incidence in endemic areas, such as southern China, than in areas where it is relatively uncommon, such as the United States.¹ The etiology of NPC varies based on the geographical distribution, with Epstein-Barr virus (EBV) thought to be the primary etiologic agent in endemic areas. On the other hand, in North America 2 additional subsets of NPC have been identified: human papillomavirus (HPV)–positive/EBV-negative and HPV-negative/EBV-negative.^2,3 NPC arises from the epithelial lining of the nasopharynx, often in the fossa of Rosenmuller, and is the most seen tumor in the nasopharynx.⁴ NPC is less surgically accessible than other H&N cancers, and surgery to the nasopharynx poses more risks given the proximity of critical surrounding structures. NPC is radiosensitive, and therefore radiotherapy (RT), in combination with chemotherapy for locally advanced tumors, has become the mainstay of treatment for nonmetastatic NPC.⁴

NPC often presents with an asymptomatic neck mass or with symptoms of epistaxis, nasal obstruction, and otitis media.⁵ Advanced cases of NPC can present with direct extension into the skull base, paranasal sinuses, and orbit, as well as involvement of cranial nerves. Radiation planning for tumors of the nasopharynx is complicated by the need to deliver an adequate dose to the tumor while limiting dose and toxicity to nearby critical structures such as the brainstem, optic chiasm, eyes, spinal cord (SC), temporal lobes, and cochleae. Achieving an adequate dose to nasopharyngeal primary tumors is especially complicated for T4 tumors invading the skull base with intracranial extension, in direct contact with these critical structures (Table 1).

Case Presentation

A 34-year-old male patient with no previous medical history presented to the emergency department with worsening diplopia, nasal obstruction, facial pain, and neck stiffness. The patient reported a 3 pack-year smoking history with recent smoking cessation. His physical examination was notable for a right abducens nerve palsy and an ulcerated nasopharyngeal mass on endoscopy.

Computed tomography (CT) scan revealed a 7-cm mass in the nasopharynx, eroding through the skull base with destruction and replacement of the clivus by tumor. Also noted was erosion of the petrous apices, carotid canals, sella turcica, dens, and the bilateral occipital condyles. There was intracranial extension with replacement of portions of the cavernous sinuses as well as mass effect on the prepontine cistern. Additional brain imaging studies, including magnetic resonance imaging (MRI) and positron emission tomography (PET) scans, were obtained for completion of the staging workup. The MRI correlated with the findings noted on CT and demonstrated involvement of Meckel cave, foramen ovale, foramen rotundum, Dorello canal, and the hypoglossal canals. No cervical lymphadenopathy or distant metastases were noted on imaging. Pathology from biopsy revealed poorly differentiated squamous cell carcinoma, EBV-negative, strongly p16-positive, HPV-16 positive, and P53-negative.

RT planning was complicated by the tumor’s contact with the brainstem and upper cervical SC, as well as proximity of the tumor to the optic apparatus. The patient underwent 2 replanning CT scans at 26 Gy and 44 Gy to evaluate for tumor shrinkage. These CT scans demonstrated shrinkage of the tumor away from critical neural structures, allowing the treatment volume to be reduced away from these structures in order to achieve required dose tolerances (brainstem < 54 Gy, optic nerves and chiasm < 50 Gy, SC < 45 Gy for this case). The replanning CT scan at 44 Gy, 5 weeks after treatment initiation, demonstrated that dramatic tumor shrinkage had occurred early in treatment, with separation of the remaining tumor from the area of the SC and brainstem with which it was initially in contact (Figure 1). This improvement allowed for shrinkage of the high-dose radiation field away from these critical neural structures.

Discussion

RT for NPC is complicated by the proximity of these tumors to critical surrounding neural structures. It is challenging to achieve the required dose constraints to surrounding neural tissues while delivering the usual 70-Gy dose to the gross tumor, especially when the tumor comes into direct contact with these structures.

This case provides an example of response-adapted RT using imaging during treatment to shrink the high-dose target as the tumor shrinks away from critical surrounding structures.⁷ This strategy permits delivery of the maximum dose to the tumor while minimizing radiation dose, and therefore risk of toxicity, to normal surrounding structures. While it is typical to deliver 70 Gy to the full extent of tumor involvement for H&N tumors, this was not possible in this case as the tumor was in contact with the brainstem and upper cervical SC. Delivering the full 70 Gy to these areas of tumor would have placed this patient at substantial risk of brainstem and/or SC toxicity. This report demonstrates that response-adapted RT with shrinking fields can allow for tumor control while avoiding toxicity to critical neural structures for cases of locally advanced NPC in which tumor is abutting these structures.

Bony regeneration of the skull base following RT has been reported in the literature, but in limited reviews. Early reports used plain radiography to follow changes. Unger and colleagues demonstrated the regeneration of bone using skull radiographs 4 to 6 months after completion of RT for NPC.⁸ More recent literature details the ability of bone to regenerate after RT based on CT findings. Fang and colleagues reported on 90 cases of NPC with skull base destruction, with 63% having bony regeneration on posttreatment CT.⁹ Most of the patients in Fang’s report had bony regeneration within 1 year of treatment, and in general, bony regeneration became more evident on imaging with longer follow-up. Of note, local control was significantly greater in patients with regeneration vs persistent destruction (77% vs 21%, P < .001). On multivariate analysis, complete tumor response was significantly associated with bony regeneration; other factors such as age, sex, radiation dose, and chemotherapy were not significantly associated with the likelihood of bony regeneration.

Our report details a nasopharyngeal tumor that destroyed the skull base with no intact bony barrier. In such cases, concern arises regarding craniospinal instability with tumor regression if there is not simultaneous bone regeneration. Tumor invasion of the skull base and C1-2 vertebral bodies and complications from treatment of such tumor extent can lead to symptoms of craniospinal instability, including pain, difficulty with neck range of motion, and loss of strength and sensation in the upper and lower extremities.¹⁰ A case report of a woman treated with chemoradiation for a plasmacytoma of the skull base detailed her posttreatment presentation with quadriparesis resulting from craniospinal instability after tumor regression.¹¹ Such instability is generally treated surgically, and during this woman’s surgery, there was an injury to the right vertebral artery, although this did not cause any additional neurologic deficits.

Conclusions

There is a paucity of literature on bony regeneration in patients with skull base destruction from advanced NPC, and in particular, the ability of skull base regeneration to occur during treatment simultaneous with tumor regression. Our patient had HPV-positive/EBV-negative NPC, but it is unclear how this subtype affected his prognosis. Factors such as tumor histology, radiosensitivity with rapid tumor regression, and young age may have all contributed to the rapidity of bone regeneration in our patient. This case report demonstrates that an impressive tumor response to chemoradiation with simultaneous bony regeneration is possible among patients presenting with tumor destruction of the skull base, precluding the need for neurosurgical intervention.

Nasopharyngeal carcinoma (NPC) differs from other head and neck (H&N) cancers in its epidemiology and treatment. Unlike other H&N cancers, NPC has a distinct geographical distribution with a much higher incidence in endemic areas, such as southern China, than in areas where it is relatively uncommon, such as the United States.¹ The etiology of NPC varies based on the geographical distribution, with Epstein-Barr virus (EBV) thought to be the primary etiologic agent in endemic areas. On the other hand, in North America 2 additional subsets of NPC have been identified: human papillomavirus (HPV)–positive/EBV-negative and HPV-negative/EBV-negative.^2,3 NPC arises from the epithelial lining of the nasopharynx, often in the fossa of Rosenmuller, and is the most seen tumor in the nasopharynx.⁴ NPC is less surgically accessible than other H&N cancers, and surgery to the nasopharynx poses more risks given the proximity of critical surrounding structures. NPC is radiosensitive, and therefore radiotherapy (RT), in combination with chemotherapy for locally advanced tumors, has become the mainstay of treatment for nonmetastatic NPC.⁴

NPC often presents with an asymptomatic neck mass or with symptoms of epistaxis, nasal obstruction, and otitis media.⁵ Advanced cases of NPC can present with direct extension into the skull base, paranasal sinuses, and orbit, as well as involvement of cranial nerves. Radiation planning for tumors of the nasopharynx is complicated by the need to deliver an adequate dose to the tumor while limiting dose and toxicity to nearby critical structures such as the brainstem, optic chiasm, eyes, spinal cord (SC), temporal lobes, and cochleae. Achieving an adequate dose to nasopharyngeal primary tumors is especially complicated for T4 tumors invading the skull base with intracranial extension, in direct contact with these critical structures (Table 1).

Case Presentation

A 34-year-old male patient with no previous medical history presented to the emergency department with worsening diplopia, nasal obstruction, facial pain, and neck stiffness. The patient reported a 3 pack-year smoking history with recent smoking cessation. His physical examination was notable for a right abducens nerve palsy and an ulcerated nasopharyngeal mass on endoscopy.

Computed tomography (CT) scan revealed a 7-cm mass in the nasopharynx, eroding through the skull base with destruction and replacement of the clivus by tumor. Also noted was erosion of the petrous apices, carotid canals, sella turcica, dens, and the bilateral occipital condyles. There was intracranial extension with replacement of portions of the cavernous sinuses as well as mass effect on the prepontine cistern. Additional brain imaging studies, including magnetic resonance imaging (MRI) and positron emission tomography (PET) scans, were obtained for completion of the staging workup. The MRI correlated with the findings noted on CT and demonstrated involvement of Meckel cave, foramen ovale, foramen rotundum, Dorello canal, and the hypoglossal canals. No cervical lymphadenopathy or distant metastases were noted on imaging. Pathology from biopsy revealed poorly differentiated squamous cell carcinoma, EBV-negative, strongly p16-positive, HPV-16 positive, and P53-negative.

RT planning was complicated by the tumor’s contact with the brainstem and upper cervical SC, as well as proximity of the tumor to the optic apparatus. The patient underwent 2 replanning CT scans at 26 Gy and 44 Gy to evaluate for tumor shrinkage. These CT scans demonstrated shrinkage of the tumor away from critical neural structures, allowing the treatment volume to be reduced away from these structures in order to achieve required dose tolerances (brainstem < 54 Gy, optic nerves and chiasm < 50 Gy, SC < 45 Gy for this case). The replanning CT scan at 44 Gy, 5 weeks after treatment initiation, demonstrated that dramatic tumor shrinkage had occurred early in treatment, with separation of the remaining tumor from the area of the SC and brainstem with which it was initially in contact (Figure 1). This improvement allowed for shrinkage of the high-dose radiation field away from these critical neural structures.

Discussion

RT for NPC is complicated by the proximity of these tumors to critical surrounding neural structures. It is challenging to achieve the required dose constraints to surrounding neural tissues while delivering the usual 70-Gy dose to the gross tumor, especially when the tumor comes into direct contact with these structures.

This case provides an example of response-adapted RT using imaging during treatment to shrink the high-dose target as the tumor shrinks away from critical surrounding structures.⁷ This strategy permits delivery of the maximum dose to the tumor while minimizing radiation dose, and therefore risk of toxicity, to normal surrounding structures. While it is typical to deliver 70 Gy to the full extent of tumor involvement for H&N tumors, this was not possible in this case as the tumor was in contact with the brainstem and upper cervical SC. Delivering the full 70 Gy to these areas of tumor would have placed this patient at substantial risk of brainstem and/or SC toxicity. This report demonstrates that response-adapted RT with shrinking fields can allow for tumor control while avoiding toxicity to critical neural structures for cases of locally advanced NPC in which tumor is abutting these structures.

Bony regeneration of the skull base following RT has been reported in the literature, but in limited reviews. Early reports used plain radiography to follow changes. Unger and colleagues demonstrated the regeneration of bone using skull radiographs 4 to 6 months after completion of RT for NPC.⁸ More recent literature details the ability of bone to regenerate after RT based on CT findings. Fang and colleagues reported on 90 cases of NPC with skull base destruction, with 63% having bony regeneration on posttreatment CT.⁹ Most of the patients in Fang’s report had bony regeneration within 1 year of treatment, and in general, bony regeneration became more evident on imaging with longer follow-up. Of note, local control was significantly greater in patients with regeneration vs persistent destruction (77% vs 21%, P < .001). On multivariate analysis, complete tumor response was significantly associated with bony regeneration; other factors such as age, sex, radiation dose, and chemotherapy were not significantly associated with the likelihood of bony regeneration.

Our report details a nasopharyngeal tumor that destroyed the skull base with no intact bony barrier. In such cases, concern arises regarding craniospinal instability with tumor regression if there is not simultaneous bone regeneration. Tumor invasion of the skull base and C1-2 vertebral bodies and complications from treatment of such tumor extent can lead to symptoms of craniospinal instability, including pain, difficulty with neck range of motion, and loss of strength and sensation in the upper and lower extremities.¹⁰ A case report of a woman treated with chemoradiation for a plasmacytoma of the skull base detailed her posttreatment presentation with quadriparesis resulting from craniospinal instability after tumor regression.¹¹ Such instability is generally treated surgically, and during this woman’s surgery, there was an injury to the right vertebral artery, although this did not cause any additional neurologic deficits.

Conclusions

There is a paucity of literature on bony regeneration in patients with skull base destruction from advanced NPC, and in particular, the ability of skull base regeneration to occur during treatment simultaneous with tumor regression. Our patient had HPV-positive/EBV-negative NPC, but it is unclear how this subtype affected his prognosis. Factors such as tumor histology, radiosensitivity with rapid tumor regression, and young age may have all contributed to the rapidity of bone regeneration in our patient. This case report demonstrates that an impressive tumor response to chemoradiation with simultaneous bony regeneration is possible among patients presenting with tumor destruction of the skull base, precluding the need for neurosurgical intervention.

Early-onset colorectal cancer (CRC) affecting patients younger than 50 years has risen sharply since 1988 from 7.9 to 12.9 cases in 2015 per 100,000 people. The reason for the increase isn’t well understood.

The findings were highlighted in a recent review article published online in the New England Journal of Medicine. “It’s a national phenomenon and it’s also occurring in other parts of the developed world. We’re used to seeing mostly older people who have this diagnosis. Now we’re seeing a lot of younger people with this disease. It’s rather alarming,” said author Frank Sinicrope, MD, a medical oncologist with Mayo Clinic, Rochester, Minn.

The trend contrasts with a decline in later-onset CRC likely attributable to increases in screening. As a result of the two trends, but especially the increased number of early-onset cases, the median age of diagnosis dropped from 72 in the early 2000s to 66 today.

“Although patients with early-onset colorectal cancer are more likely to have a hereditary syndrome than those who have later-onset disease, most cases are sporadic, with no identifiable cause. Furthermore, somatic mutational profiling of early-onset colorectal cancers has not revealed previously unidentified or actionable alterations to inform our understanding of the pathogenesis of these cancers or to guide treatment,” he wrote in the review.

“Early-onset colorectal cancers are most commonly detected in the rectum, followed by the distal colon; more than 70% of early-onset colorectal cancers are in the left colon at presentation,” he wrote in the review. Younger patients tend to be unfamiliar with CRC symptoms, which are often mistaken for benign conditions.

“We’ve moved the screening age down to 45, but that still is not going to capture a lot of these patients,” Dr. Sinicrope said. He estimates that 25% of rectal cancers and 10%-12% of colon cancers diagnosed in the next 10 years will be early onset.

Although the direct cause of the increased incidence isn’t clear, Dr. Sinicrope suggested it may reflect changing dietary habits and rising obesity among adolescents. “The sugar-containing beverages, the processed sugar and a lot of red meat in the diet and refined grains … reflect changes in the diet over the last 50 years. We may now be seeing the end result of many of these dietary changes that have occurred,” he said, calling for a greater emphasis on plant-based diets, which promote a healthier gut microbiome that may reduce CRC risk. Western-style diets can change the gut microbiome leading to inflammation which increases the risk of CRC.

Most patients with early CRC present with advanced disease in the left colon. And, pathogenic germline variants are present in one in six patients – half of which are associated with Lynch syndrome which increases the risk for CRC.

Dr. Sinicrope highlighted the need for more risk-based intervention, which in turn requires a better knowledge of family history.

“We need to do better job to risk stratify, and that will help us figure out who’s best to target our screening efforts toward,” Dr. Sinicrope said. He pointed out guidelines from the U.S. Multi-Society Task Force on Colorectal Cancer and the American Cancer Society that can help physicians identify patients who might benefit from earlier screening. The American Cancer Society recommends that CRC screening be conducted at 45 years for average-risk individuals.

“The best screening test is the one that the patient will do,” Dr. Sinicrope said.

Early-onset colorectal cancer (CRC) affecting patients younger than 50 years has risen sharply since 1988 from 7.9 to 12.9 cases in 2015 per 100,000 people. The reason for the increase isn’t well understood.

The findings were highlighted in a recent review article published online in the New England Journal of Medicine. “It’s a national phenomenon and it’s also occurring in other parts of the developed world. We’re used to seeing mostly older people who have this diagnosis. Now we’re seeing a lot of younger people with this disease. It’s rather alarming,” said author Frank Sinicrope, MD, a medical oncologist with Mayo Clinic, Rochester, Minn.

The trend contrasts with a decline in later-onset CRC likely attributable to increases in screening. As a result of the two trends, but especially the increased number of early-onset cases, the median age of diagnosis dropped from 72 in the early 2000s to 66 today.

“Although patients with early-onset colorectal cancer are more likely to have a hereditary syndrome than those who have later-onset disease, most cases are sporadic, with no identifiable cause. Furthermore, somatic mutational profiling of early-onset colorectal cancers has not revealed previously unidentified or actionable alterations to inform our understanding of the pathogenesis of these cancers or to guide treatment,” he wrote in the review.

“Early-onset colorectal cancers are most commonly detected in the rectum, followed by the distal colon; more than 70% of early-onset colorectal cancers are in the left colon at presentation,” he wrote in the review. Younger patients tend to be unfamiliar with CRC symptoms, which are often mistaken for benign conditions.

“We’ve moved the screening age down to 45, but that still is not going to capture a lot of these patients,” Dr. Sinicrope said. He estimates that 25% of rectal cancers and 10%-12% of colon cancers diagnosed in the next 10 years will be early onset.

Although the direct cause of the increased incidence isn’t clear, Dr. Sinicrope suggested it may reflect changing dietary habits and rising obesity among adolescents. “The sugar-containing beverages, the processed sugar and a lot of red meat in the diet and refined grains … reflect changes in the diet over the last 50 years. We may now be seeing the end result of many of these dietary changes that have occurred,” he said, calling for a greater emphasis on plant-based diets, which promote a healthier gut microbiome that may reduce CRC risk. Western-style diets can change the gut microbiome leading to inflammation which increases the risk of CRC.

Most patients with early CRC present with advanced disease in the left colon. And, pathogenic germline variants are present in one in six patients – half of which are associated with Lynch syndrome which increases the risk for CRC.

Dr. Sinicrope highlighted the need for more risk-based intervention, which in turn requires a better knowledge of family history.

“We need to do better job to risk stratify, and that will help us figure out who’s best to target our screening efforts toward,” Dr. Sinicrope said. He pointed out guidelines from the U.S. Multi-Society Task Force on Colorectal Cancer and the American Cancer Society that can help physicians identify patients who might benefit from earlier screening. The American Cancer Society recommends that CRC screening be conducted at 45 years for average-risk individuals.

“The best screening test is the one that the patient will do,” Dr. Sinicrope said.

Early-onset colorectal cancer (CRC) affecting patients younger than 50 years has risen sharply since 1988 from 7.9 to 12.9 cases in 2015 per 100,000 people. The reason for the increase isn’t well understood.

The findings were highlighted in a recent review article published online in the New England Journal of Medicine. “It’s a national phenomenon and it’s also occurring in other parts of the developed world. We’re used to seeing mostly older people who have this diagnosis. Now we’re seeing a lot of younger people with this disease. It’s rather alarming,” said author Frank Sinicrope, MD, a medical oncologist with Mayo Clinic, Rochester, Minn.

The trend contrasts with a decline in later-onset CRC likely attributable to increases in screening. As a result of the two trends, but especially the increased number of early-onset cases, the median age of diagnosis dropped from 72 in the early 2000s to 66 today.

“Although patients with early-onset colorectal cancer are more likely to have a hereditary syndrome than those who have later-onset disease, most cases are sporadic, with no identifiable cause. Furthermore, somatic mutational profiling of early-onset colorectal cancers has not revealed previously unidentified or actionable alterations to inform our understanding of the pathogenesis of these cancers or to guide treatment,” he wrote in the review.

“Early-onset colorectal cancers are most commonly detected in the rectum, followed by the distal colon; more than 70% of early-onset colorectal cancers are in the left colon at presentation,” he wrote in the review. Younger patients tend to be unfamiliar with CRC symptoms, which are often mistaken for benign conditions.

“We’ve moved the screening age down to 45, but that still is not going to capture a lot of these patients,” Dr. Sinicrope said. He estimates that 25% of rectal cancers and 10%-12% of colon cancers diagnosed in the next 10 years will be early onset.

Although the direct cause of the increased incidence isn’t clear, Dr. Sinicrope suggested it may reflect changing dietary habits and rising obesity among adolescents. “The sugar-containing beverages, the processed sugar and a lot of red meat in the diet and refined grains … reflect changes in the diet over the last 50 years. We may now be seeing the end result of many of these dietary changes that have occurred,” he said, calling for a greater emphasis on plant-based diets, which promote a healthier gut microbiome that may reduce CRC risk. Western-style diets can change the gut microbiome leading to inflammation which increases the risk of CRC.

Most patients with early CRC present with advanced disease in the left colon. And, pathogenic germline variants are present in one in six patients – half of which are associated with Lynch syndrome which increases the risk for CRC.

Dr. Sinicrope highlighted the need for more risk-based intervention, which in turn requires a better knowledge of family history.

“We need to do better job to risk stratify, and that will help us figure out who’s best to target our screening efforts toward,” Dr. Sinicrope said. He pointed out guidelines from the U.S. Multi-Society Task Force on Colorectal Cancer and the American Cancer Society that can help physicians identify patients who might benefit from earlier screening. The American Cancer Society recommends that CRC screening be conducted at 45 years for average-risk individuals.

“The best screening test is the one that the patient will do,” Dr. Sinicrope said.

A qualitative analysis of 20 people with head and neck cancer (HNC) has led to recommendations for improvements in care.

HNC has a high burden of treatment-related adverse events, along with frequent trouble with speech, swallowing, facial disfigurement, and psychological distress.

Among cancer patients, “they have the highest rates of emergency department use and hospitalization during treatment. They also have the highest rates of psychological distress. We have some Ontario data that shows they’ve got the highest rates of suicide and self-harm. So I think this is a really special population that we need to support,” Christopher Noel, MD, PhD, said in an interview. Dr. Noel was the lead author of the study, which was published in JAMA Otolaryngology – Head & Neck Surgery.

These issues can strongly affect quality of life, and even patient outcomes. “Even a 1-day interruption in treatment has been shown to impact oncologic outcomes. This is a very big issue whether you’re a surgeon, a medical oncologist, or a radiation oncologist,” said Dr. Noel, who is a resident physician at the University of Toronto.

He advocates that physicians interview patients and review the results in a structured way and then act on it. “If we just rely on patient [provided] communication, we’re going to miss about 50% of patient symptoms,” he said.

The researchers aimed for the patient’s perspective on treatment. “What is the patient’s perception of going through head neck cancer and their treatment, and managing their symptoms at home? And where do they think that we could do better?” Dr. Noel asked.

The most pressing issue was that patients felt their emotional and informational needs often were not met. That challenge is even harder for patients who have trouble communicating, which in turn makes them more prone to isolation and loneliness. Many felt that they had to get the information on their own. “They wanted it to be a more effortless process,” said Dr. Noel.

He described one patient with oropharynx cancer who was able to talk to people about her grief over her diagnosis, but treatment led to her throat becoming swollen and she lost the ability to communicate. “She felt very isolated and lonely. She really highlighted the emotional and psychosocial barriers in cancer care. Her treatment inherently leaves her feeling very isolated and lonely, and she had such a hard time connecting with a psychotherapist,” Dr. Noel said.

Another common issue revolved around efforts to communicate about symptoms and adverse effects of treatment. Resources often aren’t available on evenings or weekends, and it can take time for a nurse to call them back. Patients wanted to see more modern approaches, such as use of email or apps.

The patients in the study recommended 11 health care improvements.

• 1. Nurse navigator teams should have hours extended to evenings and weekends.
• 2. Patient communication methods should be expanded, using methods like email or apps.
• 3. HNC resources should be more broadly disseminated.
• 4. Education and information approaches should be individualized to the patient.
• 5. All HNC patients should be offered psychological resources.
• 6. Mental health needs should be assessed repeatedly throughout treatment and extended care.
• 7. Physicians should recognize the added symptom burden often faced by patients who travel extensively for treatment.
• 8. Partners and caregivers should be included as part of the treatment team.
• 9. Share symptom data with patients, which can improve engagement.
• 10. Review symptom scores and act on them regularly.
• 11. A member of the care team should be identified to oversee symptom management.

Dr. Noel had no relevant financial disclosures.

A qualitative analysis of 20 people with head and neck cancer (HNC) has led to recommendations for improvements in care.

HNC has a high burden of treatment-related adverse events, along with frequent trouble with speech, swallowing, facial disfigurement, and psychological distress.

Among cancer patients, “they have the highest rates of emergency department use and hospitalization during treatment. They also have the highest rates of psychological distress. We have some Ontario data that shows they’ve got the highest rates of suicide and self-harm. So I think this is a really special population that we need to support,” Christopher Noel, MD, PhD, said in an interview. Dr. Noel was the lead author of the study, which was published in JAMA Otolaryngology – Head & Neck Surgery.

These issues can strongly affect quality of life, and even patient outcomes. “Even a 1-day interruption in treatment has been shown to impact oncologic outcomes. This is a very big issue whether you’re a surgeon, a medical oncologist, or a radiation oncologist,” said Dr. Noel, who is a resident physician at the University of Toronto.

He advocates that physicians interview patients and review the results in a structured way and then act on it. “If we just rely on patient [provided] communication, we’re going to miss about 50% of patient symptoms,” he said.

The researchers aimed for the patient’s perspective on treatment. “What is the patient’s perception of going through head neck cancer and their treatment, and managing their symptoms at home? And where do they think that we could do better?” Dr. Noel asked.

The most pressing issue was that patients felt their emotional and informational needs often were not met. That challenge is even harder for patients who have trouble communicating, which in turn makes them more prone to isolation and loneliness. Many felt that they had to get the information on their own. “They wanted it to be a more effortless process,” said Dr. Noel.

He described one patient with oropharynx cancer who was able to talk to people about her grief over her diagnosis, but treatment led to her throat becoming swollen and she lost the ability to communicate. “She felt very isolated and lonely. She really highlighted the emotional and psychosocial barriers in cancer care. Her treatment inherently leaves her feeling very isolated and lonely, and she had such a hard time connecting with a psychotherapist,” Dr. Noel said.

Another common issue revolved around efforts to communicate about symptoms and adverse effects of treatment. Resources often aren’t available on evenings or weekends, and it can take time for a nurse to call them back. Patients wanted to see more modern approaches, such as use of email or apps.

The patients in the study recommended 11 health care improvements.

• 1. Nurse navigator teams should have hours extended to evenings and weekends.
• 2. Patient communication methods should be expanded, using methods like email or apps.
• 3. HNC resources should be more broadly disseminated.
• 4. Education and information approaches should be individualized to the patient.
• 5. All HNC patients should be offered psychological resources.
• 6. Mental health needs should be assessed repeatedly throughout treatment and extended care.
• 7. Physicians should recognize the added symptom burden often faced by patients who travel extensively for treatment.
• 8. Partners and caregivers should be included as part of the treatment team.
• 9. Share symptom data with patients, which can improve engagement.
• 10. Review symptom scores and act on them regularly.
• 11. A member of the care team should be identified to oversee symptom management.

Dr. Noel had no relevant financial disclosures.

A qualitative analysis of 20 people with head and neck cancer (HNC) has led to recommendations for improvements in care.

HNC has a high burden of treatment-related adverse events, along with frequent trouble with speech, swallowing, facial disfigurement, and psychological distress.

Among cancer patients, “they have the highest rates of emergency department use and hospitalization during treatment. They also have the highest rates of psychological distress. We have some Ontario data that shows they’ve got the highest rates of suicide and self-harm. So I think this is a really special population that we need to support,” Christopher Noel, MD, PhD, said in an interview. Dr. Noel was the lead author of the study, which was published in JAMA Otolaryngology – Head & Neck Surgery.

These issues can strongly affect quality of life, and even patient outcomes. “Even a 1-day interruption in treatment has been shown to impact oncologic outcomes. This is a very big issue whether you’re a surgeon, a medical oncologist, or a radiation oncologist,” said Dr. Noel, who is a resident physician at the University of Toronto.

He advocates that physicians interview patients and review the results in a structured way and then act on it. “If we just rely on patient [provided] communication, we’re going to miss about 50% of patient symptoms,” he said.

The researchers aimed for the patient’s perspective on treatment. “What is the patient’s perception of going through head neck cancer and their treatment, and managing their symptoms at home? And where do they think that we could do better?” Dr. Noel asked.

The most pressing issue was that patients felt their emotional and informational needs often were not met. That challenge is even harder for patients who have trouble communicating, which in turn makes them more prone to isolation and loneliness. Many felt that they had to get the information on their own. “They wanted it to be a more effortless process,” said Dr. Noel.

He described one patient with oropharynx cancer who was able to talk to people about her grief over her diagnosis, but treatment led to her throat becoming swollen and she lost the ability to communicate. “She felt very isolated and lonely. She really highlighted the emotional and psychosocial barriers in cancer care. Her treatment inherently leaves her feeling very isolated and lonely, and she had such a hard time connecting with a psychotherapist,” Dr. Noel said.

Another common issue revolved around efforts to communicate about symptoms and adverse effects of treatment. Resources often aren’t available on evenings or weekends, and it can take time for a nurse to call them back. Patients wanted to see more modern approaches, such as use of email or apps.

The patients in the study recommended 11 health care improvements.

• 1. Nurse navigator teams should have hours extended to evenings and weekends.
• 2. Patient communication methods should be expanded, using methods like email or apps.
• 3. HNC resources should be more broadly disseminated.
• 4. Education and information approaches should be individualized to the patient.
• 5. All HNC patients should be offered psychological resources.
• 6. Mental health needs should be assessed repeatedly throughout treatment and extended care.
• 7. Physicians should recognize the added symptom burden often faced by patients who travel extensively for treatment.
• 8. Partners and caregivers should be included as part of the treatment team.
• 9. Share symptom data with patients, which can improve engagement.
• 10. Review symptom scores and act on them regularly.
• 11. A member of the care team should be identified to oversee symptom management.

Dr. Noel had no relevant financial disclosures.

I’m often in the position of caring for patients after they’ve stopped active cancer treatments, but before they’ve made the decision to enroll in hospice. They remain under my care until they feel emotionally ready, or until their care needs have escalated to the point in which hospice is unavoidable.

Jenny, a mom in her 50s with metastatic pancreatic cancer, stopped coming to the clinic. She lived about 40 minutes away from the clinic and was no longer receiving treatment. The car rides were painful and difficult for her. I held weekly video visits with her for 2 months before she eventually went to hospice and passed away. Before she died, she shared with me her sadness that her oncologist – who had taken care of her for 3 years – had “washed his hands of [me].” She rarely heard from him after their final conversation in the clinic when he informed her that she was no longer a candidate for further therapy. The sense of abandonment Jenny described was visceral and devastating. With her permission, I let her oncology team know how she felt and they reached out to her just 1 week before her death. After she died, her husband told me how meaningful it had been for the whole family to hear from Jenny’s oncologist who told them that she had done everything possible to fight her cancer and that “no stone was left unturned.” Her husband felt this final conversation provided Jenny with the closure she needed to pass away peacefully.

Transitioning from active therapy to symptom management

Switching gears from an all-out pursuit of active therapy to focusing on cancer symptoms is often a scary transition for patients and their families. The transition is often viewed as a movement away from hope and optimism to “giving up the fight.” Whether you agree with the warrior language or not, many patients still describe their journey in these terms and thus, experience enrollment in hospice as a sense of having failed.

The sense of failure can be compounded by feelings of abandonment by oncology providers when they are referred without much guidance or continuity through the hospice enrollment process. Unfortunately, the consequences of suboptimal hospice transitions can be damaging, especially for the mental health and well-being of the patient and their surviving loved ones. Hospice transitions seem to reside in an area of clinical practice that is overlooked or, in my experience they are considered an afterthought by many oncologists.

When managed poorly, hospice transitions can easily lead to patient and family harm, which is a claim supported by research. A qualitative study published in 2019 included 92 caregivers of patients with terminal cancer. The authors found three common pathways for end-of-life transitions – a frictionless transition in which the patient and family are well prepared in advance by their oncologist; a more turbulent transition in which patient and family had direct conversations with their oncologist about the incurability of the disease and the lack of efficacy of further treatments, but were given no guidance on prognosis; and a third type of transition marked by abrupt shifts toward end-of-life care occurring in extremis and typically in the hospital.

In the latter two groups, caregivers felt their loved ones died very quickly after stopping treatment, taking them by surprise and leaving them rushing to put end-of-life care plans in place without much support from their oncologists. In the last group, caregivers shared they received their first prognostic information from the hospital or ICU doctor caring for their actively dying loved one, leaving them with a sense of anger and betrayal toward their oncologist for allowing them to be so ill-prepared.

A Japanese survey published in 2018 in The Oncologist of families of cancer patients who had passed away under hospice care over a 2-year period (2012-2014), found that about one-quarter felt abandoned by oncologists. Several factors that were associated with feeling either more or less abandonment. Spouses of patients, patients aged less than 60 years, and patients whose oncologists informed them that there was “nothing more to do” felt more abandoned by oncologists; whereas families for whom the oncologist provided reassurance about the trajectory of care, recommended hospice, and engaged with a palliative care team felt less abandoned by oncologists. Families who felt more abandoned had higher levels of depression and grief when measured with standardized instruments.
 

‘Don’t just put in the hospice order and walk away’

Fortunately, there are a few low-resource interventions that can improve the quality of care-to-hospice transitions and prevent the sense of abandonment felt by many patients and families.

First, don’t just put in the hospice order and walk away. Designate a staffer in your office to contact hospice directly, ensure all medical records are faxed and received, and update the patient and family on this progress throughout the transition. Taking care of details like these ensures the patient enrolls in hospice in a timely manner and reduces the chance the patient, who is likely to be quite sick at this point, will end up in the hospital despite your best efforts to get hospice involved.

Make sure the patient and family understand that you are still their oncologist and still available to them. If they want to continue care with you, have them name you as the “non–hospice-attending physician” so that you can continue to bill for telemedicine and office visits using the terminal diagnosis (with a billing modifier). This does not mean that you will be expected to manage the patient’s hospice problem list or respond to hospice nurse calls at 2 a.m. – the hospice doctor will still do this. It just ensures that patients do not receive a bill if you continue to see them.

If ongoing office or video visits are too much for the patient and family, consider assigning a member of your team to call the patient and family on a weekly basis to check in and offer support. A small 2018 pilot study aimed at improving communication found that when caregivers of advanced cancer patients transitioning to hospice received weekly supportive phone calls by a member of their oncology team (typically a nurse or nurse practitioner), they felt emotionally supported, had good continuity of care throughout the hospice enrollment, and appreciated the ability to have closure with their oncology team. In other words, a sense of abandonment was prevented and the patient-provider relationship was actually deepened through the transition.

These suggestions are not rocket science – they are simple, obvious ways to try to restore patient-centeredness to a transition that for providers can seem routine, but for patients and families is often the first time they have confronted the reality that death is approaching. That reality is terrifying and overwhelming. Patients and caregivers need our support more during hospice transitions than at any other point during their cancer journey – except perhaps at diagnosis.

As with Jenny, my patient who felt abandoned, all it took was a single call by her oncology team to restore the trust and heal the sense of feeling forsaken by the people who cared for her for years. Sometimes, even just one more phone call can feel like a lot to a chronically overburdened provider – but what a difference a simple call can make.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

I’m often in the position of caring for patients after they’ve stopped active cancer treatments, but before they’ve made the decision to enroll in hospice. They remain under my care until they feel emotionally ready, or until their care needs have escalated to the point in which hospice is unavoidable.

Jenny, a mom in her 50s with metastatic pancreatic cancer, stopped coming to the clinic. She lived about 40 minutes away from the clinic and was no longer receiving treatment. The car rides were painful and difficult for her. I held weekly video visits with her for 2 months before she eventually went to hospice and passed away. Before she died, she shared with me her sadness that her oncologist – who had taken care of her for 3 years – had “washed his hands of [me].” She rarely heard from him after their final conversation in the clinic when he informed her that she was no longer a candidate for further therapy. The sense of abandonment Jenny described was visceral and devastating. With her permission, I let her oncology team know how she felt and they reached out to her just 1 week before her death. After she died, her husband told me how meaningful it had been for the whole family to hear from Jenny’s oncologist who told them that she had done everything possible to fight her cancer and that “no stone was left unturned.” Her husband felt this final conversation provided Jenny with the closure she needed to pass away peacefully.

Transitioning from active therapy to symptom management

Switching gears from an all-out pursuit of active therapy to focusing on cancer symptoms is often a scary transition for patients and their families. The transition is often viewed as a movement away from hope and optimism to “giving up the fight.” Whether you agree with the warrior language or not, many patients still describe their journey in these terms and thus, experience enrollment in hospice as a sense of having failed.

The sense of failure can be compounded by feelings of abandonment by oncology providers when they are referred without much guidance or continuity through the hospice enrollment process. Unfortunately, the consequences of suboptimal hospice transitions can be damaging, especially for the mental health and well-being of the patient and their surviving loved ones. Hospice transitions seem to reside in an area of clinical practice that is overlooked or, in my experience they are considered an afterthought by many oncologists.

When managed poorly, hospice transitions can easily lead to patient and family harm, which is a claim supported by research. A qualitative study published in 2019 included 92 caregivers of patients with terminal cancer. The authors found three common pathways for end-of-life transitions – a frictionless transition in which the patient and family are well prepared in advance by their oncologist; a more turbulent transition in which patient and family had direct conversations with their oncologist about the incurability of the disease and the lack of efficacy of further treatments, but were given no guidance on prognosis; and a third type of transition marked by abrupt shifts toward end-of-life care occurring in extremis and typically in the hospital.

In the latter two groups, caregivers felt their loved ones died very quickly after stopping treatment, taking them by surprise and leaving them rushing to put end-of-life care plans in place without much support from their oncologists. In the last group, caregivers shared they received their first prognostic information from the hospital or ICU doctor caring for their actively dying loved one, leaving them with a sense of anger and betrayal toward their oncologist for allowing them to be so ill-prepared.

A Japanese survey published in 2018 in The Oncologist of families of cancer patients who had passed away under hospice care over a 2-year period (2012-2014), found that about one-quarter felt abandoned by oncologists. Several factors that were associated with feeling either more or less abandonment. Spouses of patients, patients aged less than 60 years, and patients whose oncologists informed them that there was “nothing more to do” felt more abandoned by oncologists; whereas families for whom the oncologist provided reassurance about the trajectory of care, recommended hospice, and engaged with a palliative care team felt less abandoned by oncologists. Families who felt more abandoned had higher levels of depression and grief when measured with standardized instruments.
 

‘Don’t just put in the hospice order and walk away’

Fortunately, there are a few low-resource interventions that can improve the quality of care-to-hospice transitions and prevent the sense of abandonment felt by many patients and families.

First, don’t just put in the hospice order and walk away. Designate a staffer in your office to contact hospice directly, ensure all medical records are faxed and received, and update the patient and family on this progress throughout the transition. Taking care of details like these ensures the patient enrolls in hospice in a timely manner and reduces the chance the patient, who is likely to be quite sick at this point, will end up in the hospital despite your best efforts to get hospice involved.

Make sure the patient and family understand that you are still their oncologist and still available to them. If they want to continue care with you, have them name you as the “non–hospice-attending physician” so that you can continue to bill for telemedicine and office visits using the terminal diagnosis (with a billing modifier). This does not mean that you will be expected to manage the patient’s hospice problem list or respond to hospice nurse calls at 2 a.m. – the hospice doctor will still do this. It just ensures that patients do not receive a bill if you continue to see them.

If ongoing office or video visits are too much for the patient and family, consider assigning a member of your team to call the patient and family on a weekly basis to check in and offer support. A small 2018 pilot study aimed at improving communication found that when caregivers of advanced cancer patients transitioning to hospice received weekly supportive phone calls by a member of their oncology team (typically a nurse or nurse practitioner), they felt emotionally supported, had good continuity of care throughout the hospice enrollment, and appreciated the ability to have closure with their oncology team. In other words, a sense of abandonment was prevented and the patient-provider relationship was actually deepened through the transition.

These suggestions are not rocket science – they are simple, obvious ways to try to restore patient-centeredness to a transition that for providers can seem routine, but for patients and families is often the first time they have confronted the reality that death is approaching. That reality is terrifying and overwhelming. Patients and caregivers need our support more during hospice transitions than at any other point during their cancer journey – except perhaps at diagnosis.

As with Jenny, my patient who felt abandoned, all it took was a single call by her oncology team to restore the trust and heal the sense of feeling forsaken by the people who cared for her for years. Sometimes, even just one more phone call can feel like a lot to a chronically overburdened provider – but what a difference a simple call can make.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

I’m often in the position of caring for patients after they’ve stopped active cancer treatments, but before they’ve made the decision to enroll in hospice. They remain under my care until they feel emotionally ready, or until their care needs have escalated to the point in which hospice is unavoidable.

Jenny, a mom in her 50s with metastatic pancreatic cancer, stopped coming to the clinic. She lived about 40 minutes away from the clinic and was no longer receiving treatment. The car rides were painful and difficult for her. I held weekly video visits with her for 2 months before she eventually went to hospice and passed away. Before she died, she shared with me her sadness that her oncologist – who had taken care of her for 3 years – had “washed his hands of [me].” She rarely heard from him after their final conversation in the clinic when he informed her that she was no longer a candidate for further therapy. The sense of abandonment Jenny described was visceral and devastating. With her permission, I let her oncology team know how she felt and they reached out to her just 1 week before her death. After she died, her husband told me how meaningful it had been for the whole family to hear from Jenny’s oncologist who told them that she had done everything possible to fight her cancer and that “no stone was left unturned.” Her husband felt this final conversation provided Jenny with the closure she needed to pass away peacefully.

Transitioning from active therapy to symptom management

Switching gears from an all-out pursuit of active therapy to focusing on cancer symptoms is often a scary transition for patients and their families. The transition is often viewed as a movement away from hope and optimism to “giving up the fight.” Whether you agree with the warrior language or not, many patients still describe their journey in these terms and thus, experience enrollment in hospice as a sense of having failed.

The sense of failure can be compounded by feelings of abandonment by oncology providers when they are referred without much guidance or continuity through the hospice enrollment process. Unfortunately, the consequences of suboptimal hospice transitions can be damaging, especially for the mental health and well-being of the patient and their surviving loved ones. Hospice transitions seem to reside in an area of clinical practice that is overlooked or, in my experience they are considered an afterthought by many oncologists.

When managed poorly, hospice transitions can easily lead to patient and family harm, which is a claim supported by research. A qualitative study published in 2019 included 92 caregivers of patients with terminal cancer. The authors found three common pathways for end-of-life transitions – a frictionless transition in which the patient and family are well prepared in advance by their oncologist; a more turbulent transition in which patient and family had direct conversations with their oncologist about the incurability of the disease and the lack of efficacy of further treatments, but were given no guidance on prognosis; and a third type of transition marked by abrupt shifts toward end-of-life care occurring in extremis and typically in the hospital.

In the latter two groups, caregivers felt their loved ones died very quickly after stopping treatment, taking them by surprise and leaving them rushing to put end-of-life care plans in place without much support from their oncologists. In the last group, caregivers shared they received their first prognostic information from the hospital or ICU doctor caring for their actively dying loved one, leaving them with a sense of anger and betrayal toward their oncologist for allowing them to be so ill-prepared.

A Japanese survey published in 2018 in The Oncologist of families of cancer patients who had passed away under hospice care over a 2-year period (2012-2014), found that about one-quarter felt abandoned by oncologists. Several factors that were associated with feeling either more or less abandonment. Spouses of patients, patients aged less than 60 years, and patients whose oncologists informed them that there was “nothing more to do” felt more abandoned by oncologists; whereas families for whom the oncologist provided reassurance about the trajectory of care, recommended hospice, and engaged with a palliative care team felt less abandoned by oncologists. Families who felt more abandoned had higher levels of depression and grief when measured with standardized instruments.
 

‘Don’t just put in the hospice order and walk away’

Fortunately, there are a few low-resource interventions that can improve the quality of care-to-hospice transitions and prevent the sense of abandonment felt by many patients and families.

First, don’t just put in the hospice order and walk away. Designate a staffer in your office to contact hospice directly, ensure all medical records are faxed and received, and update the patient and family on this progress throughout the transition. Taking care of details like these ensures the patient enrolls in hospice in a timely manner and reduces the chance the patient, who is likely to be quite sick at this point, will end up in the hospital despite your best efforts to get hospice involved.

Make sure the patient and family understand that you are still their oncologist and still available to them. If they want to continue care with you, have them name you as the “non–hospice-attending physician” so that you can continue to bill for telemedicine and office visits using the terminal diagnosis (with a billing modifier). This does not mean that you will be expected to manage the patient’s hospice problem list or respond to hospice nurse calls at 2 a.m. – the hospice doctor will still do this. It just ensures that patients do not receive a bill if you continue to see them.

If ongoing office or video visits are too much for the patient and family, consider assigning a member of your team to call the patient and family on a weekly basis to check in and offer support. A small 2018 pilot study aimed at improving communication found that when caregivers of advanced cancer patients transitioning to hospice received weekly supportive phone calls by a member of their oncology team (typically a nurse or nurse practitioner), they felt emotionally supported, had good continuity of care throughout the hospice enrollment, and appreciated the ability to have closure with their oncology team. In other words, a sense of abandonment was prevented and the patient-provider relationship was actually deepened through the transition.

These suggestions are not rocket science – they are simple, obvious ways to try to restore patient-centeredness to a transition that for providers can seem routine, but for patients and families is often the first time they have confronted the reality that death is approaching. That reality is terrifying and overwhelming. Patients and caregivers need our support more during hospice transitions than at any other point during their cancer journey – except perhaps at diagnosis.

As with Jenny, my patient who felt abandoned, all it took was a single call by her oncology team to restore the trust and heal the sense of feeling forsaken by the people who cared for her for years. Sometimes, even just one more phone call can feel like a lot to a chronically overburdened provider – but what a difference a simple call can make.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

BERLIN – Some breast cancer specialists still have misconceptions about the appropriate use of multigene signatures in making prognostic and treatment decisions in early-stage disease, a European survey suggests.

The authors found, for instance, that while most specialists agreed that molecular intrinsic subtypes had clinical utility for understanding prognosis in early-stage hormone receptor (HR)–positive disease and for identifying patients for whom chemotherapy could be safely avoided, about 1 in 4 experts either disagreed or felt neutral about the use of signatures in these settings.

Similarly, almost 75% of respondents felt that these signatures were not useful in the triple-negative or metastatic setting, but a small percentage believed they were, and about 10% were neutral.

“Considering that breast cancer multigene signatures were developed in the post menopausal HR+/HER2- early breast cancer setting, the fact that some experts consider [them] useful in triple-negative, HER2+ breast cancer or in the metastatic setting corroborates a misunderstanding on how to interpret the results,” study author Giuseppe Curigliano, MD, PhD, associate professor of medical oncology at the University of Milan, and colleagues wrote.

Dr. Curigliano, who is also head of the Division of Early Drug Development at the European Institute of Oncology, presented the survey findings on May 4 at the European Society for Medical Oncology (ESMO BCC) Breast Cancer Congress.

Although several breast cancer multigene signatures are available to profile early breast cancer, little information exists on how these signatures should be used in clinical practice.

To investigate, Dr. Curigliano and colleagues convened a scientific committee of eight breast cancer experts to develop a Delphi questionnaire to examine respondents’ opinions and uses of these signatures.

The questionnaire asked about the clinical utility of multigene signatures in breast cancer and recommendations for their use in clinical practice.

In all, 133 breast cancer specialists from 11 European countries completed the questionnaire. Respondents were about 49 years old on average, and most (86.5%) worked in a teaching hospital. More than 72% were medical oncologists; 12% were pathologists.

Consensus was considered to be reached when 70% or more of the respondents were in agreement on a topic.

Participants had “extensive experience in the management of breast cancer patients and have been using breast cancer multigene signatures in clinical practice,” Dr. Curigliano said.

Almost all respondents (93.6%) reported using breast cancer multigene signatures routinely or in selected patients, and 73.4% had more than 5 years of experience with them.

Overall, more than 70% of respondents agreed that identifying tumor intrinsic subtype via gene expression profiling was important in making prognostic and treatment decisions; however, a consensus was not reached on the use of immunohistochemistry.

In addition, most respondents (76%) agreed that identifying breast cancer molecular intrinsic subtypes had clinical utility for prognosis in early-stage HR-positive disease and for identifying patients for whom chemotherapy can be safely avoided (75%). However, in both cases, about one-quarter of respondents either disagreed or felt neutral.

No consensus was reached on the clinical utility of these subtypes for selecting the most appropriate chemotherapy treatment – two-thirds disagreed, while 13% agreed and 17% felt neutral.

When deciding on the use of chemotherapy in the adjuvant setting in early node-negative breast cancer, 88% of respondents felt that breast cancer multigene signatures were important. Moreover, 75% considered such signatures important when deciding whether to use chemotherapy in the adjuvant setting for patients with one to three positive lymph nodes. However, no consensus was reached on the utility of signatures for deciding whether to extend endocrine therapy in either setting.

When examining the usefulness of signatures in more special settings, the authors found that the vast majority (90%) of respondents believed that multigene signatures had clinical utility for postmenopausal early breast cancer patients, and 82% did not consider signatures clinically useful in the early-stage HER2-overexpressed setting.

In addition, 74% thought that breast cancer multigene signatures were not useful in triple-negative disease or in the metastatic setting.

Respondents did not reach a consensus on the clinical utility of multigene signatures in the neoadjuvant setting – only 27% considered them useful, and almost half did not.

The “low percentage” of respondents using the signatures in the neoadjuvant setting and the “misconception regarding the predictive value of these tests on chemotherapy benefits suggest there is still room for training on results interpretation [for breast cancer multigene signatures],” the authors write.

The study was sponsored by Veracyte. Dr. Curigliano has relationships with Pfizer, Novartis, Lilly, Roche, Seattle Genetics, Celltrion, and Veracyte. No other relevant financial relationships were disclosed.

A version of this article first appeared on Medscape.com.

This article was updated 5/9/22.

BERLIN – Some breast cancer specialists still have misconceptions about the appropriate use of multigene signatures in making prognostic and treatment decisions in early-stage disease, a European survey suggests.

The authors found, for instance, that while most specialists agreed that molecular intrinsic subtypes had clinical utility for understanding prognosis in early-stage hormone receptor (HR)–positive disease and for identifying patients for whom chemotherapy could be safely avoided, about 1 in 4 experts either disagreed or felt neutral about the use of signatures in these settings.

Similarly, almost 75% of respondents felt that these signatures were not useful in the triple-negative or metastatic setting, but a small percentage believed they were, and about 10% were neutral.

“Considering that breast cancer multigene signatures were developed in the post menopausal HR+/HER2- early breast cancer setting, the fact that some experts consider [them] useful in triple-negative, HER2+ breast cancer or in the metastatic setting corroborates a misunderstanding on how to interpret the results,” study author Giuseppe Curigliano, MD, PhD, associate professor of medical oncology at the University of Milan, and colleagues wrote.

Dr. Curigliano, who is also head of the Division of Early Drug Development at the European Institute of Oncology, presented the survey findings on May 4 at the European Society for Medical Oncology (ESMO BCC) Breast Cancer Congress.

Although several breast cancer multigene signatures are available to profile early breast cancer, little information exists on how these signatures should be used in clinical practice.

To investigate, Dr. Curigliano and colleagues convened a scientific committee of eight breast cancer experts to develop a Delphi questionnaire to examine respondents’ opinions and uses of these signatures.

The questionnaire asked about the clinical utility of multigene signatures in breast cancer and recommendations for their use in clinical practice.

In all, 133 breast cancer specialists from 11 European countries completed the questionnaire. Respondents were about 49 years old on average, and most (86.5%) worked in a teaching hospital. More than 72% were medical oncologists; 12% were pathologists.

Consensus was considered to be reached when 70% or more of the respondents were in agreement on a topic.

Participants had “extensive experience in the management of breast cancer patients and have been using breast cancer multigene signatures in clinical practice,” Dr. Curigliano said.

Almost all respondents (93.6%) reported using breast cancer multigene signatures routinely or in selected patients, and 73.4% had more than 5 years of experience with them.

Overall, more than 70% of respondents agreed that identifying tumor intrinsic subtype via gene expression profiling was important in making prognostic and treatment decisions; however, a consensus was not reached on the use of immunohistochemistry.

In addition, most respondents (76%) agreed that identifying breast cancer molecular intrinsic subtypes had clinical utility for prognosis in early-stage HR-positive disease and for identifying patients for whom chemotherapy can be safely avoided (75%). However, in both cases, about one-quarter of respondents either disagreed or felt neutral.

No consensus was reached on the clinical utility of these subtypes for selecting the most appropriate chemotherapy treatment – two-thirds disagreed, while 13% agreed and 17% felt neutral.

When deciding on the use of chemotherapy in the adjuvant setting in early node-negative breast cancer, 88% of respondents felt that breast cancer multigene signatures were important. Moreover, 75% considered such signatures important when deciding whether to use chemotherapy in the adjuvant setting for patients with one to three positive lymph nodes. However, no consensus was reached on the utility of signatures for deciding whether to extend endocrine therapy in either setting.

When examining the usefulness of signatures in more special settings, the authors found that the vast majority (90%) of respondents believed that multigene signatures had clinical utility for postmenopausal early breast cancer patients, and 82% did not consider signatures clinically useful in the early-stage HER2-overexpressed setting.

In addition, 74% thought that breast cancer multigene signatures were not useful in triple-negative disease or in the metastatic setting.

Respondents did not reach a consensus on the clinical utility of multigene signatures in the neoadjuvant setting – only 27% considered them useful, and almost half did not.

The “low percentage” of respondents using the signatures in the neoadjuvant setting and the “misconception regarding the predictive value of these tests on chemotherapy benefits suggest there is still room for training on results interpretation [for breast cancer multigene signatures],” the authors write.

The study was sponsored by Veracyte. Dr. Curigliano has relationships with Pfizer, Novartis, Lilly, Roche, Seattle Genetics, Celltrion, and Veracyte. No other relevant financial relationships were disclosed.

A version of this article first appeared on Medscape.com.

This article was updated 5/9/22.

BERLIN – Some breast cancer specialists still have misconceptions about the appropriate use of multigene signatures in making prognostic and treatment decisions in early-stage disease, a European survey suggests.

The authors found, for instance, that while most specialists agreed that molecular intrinsic subtypes had clinical utility for understanding prognosis in early-stage hormone receptor (HR)–positive disease and for identifying patients for whom chemotherapy could be safely avoided, about 1 in 4 experts either disagreed or felt neutral about the use of signatures in these settings.

Similarly, almost 75% of respondents felt that these signatures were not useful in the triple-negative or metastatic setting, but a small percentage believed they were, and about 10% were neutral.

“Considering that breast cancer multigene signatures were developed in the post menopausal HR+/HER2- early breast cancer setting, the fact that some experts consider [them] useful in triple-negative, HER2+ breast cancer or in the metastatic setting corroborates a misunderstanding on how to interpret the results,” study author Giuseppe Curigliano, MD, PhD, associate professor of medical oncology at the University of Milan, and colleagues wrote.

Dr. Curigliano, who is also head of the Division of Early Drug Development at the European Institute of Oncology, presented the survey findings on May 4 at the European Society for Medical Oncology (ESMO BCC) Breast Cancer Congress.

Although several breast cancer multigene signatures are available to profile early breast cancer, little information exists on how these signatures should be used in clinical practice.

To investigate, Dr. Curigliano and colleagues convened a scientific committee of eight breast cancer experts to develop a Delphi questionnaire to examine respondents’ opinions and uses of these signatures.

The questionnaire asked about the clinical utility of multigene signatures in breast cancer and recommendations for their use in clinical practice.

In all, 133 breast cancer specialists from 11 European countries completed the questionnaire. Respondents were about 49 years old on average, and most (86.5%) worked in a teaching hospital. More than 72% were medical oncologists; 12% were pathologists.

Consensus was considered to be reached when 70% or more of the respondents were in agreement on a topic.

Participants had “extensive experience in the management of breast cancer patients and have been using breast cancer multigene signatures in clinical practice,” Dr. Curigliano said.

Almost all respondents (93.6%) reported using breast cancer multigene signatures routinely or in selected patients, and 73.4% had more than 5 years of experience with them.

Overall, more than 70% of respondents agreed that identifying tumor intrinsic subtype via gene expression profiling was important in making prognostic and treatment decisions; however, a consensus was not reached on the use of immunohistochemistry.

In addition, most respondents (76%) agreed that identifying breast cancer molecular intrinsic subtypes had clinical utility for prognosis in early-stage HR-positive disease and for identifying patients for whom chemotherapy can be safely avoided (75%). However, in both cases, about one-quarter of respondents either disagreed or felt neutral.

No consensus was reached on the clinical utility of these subtypes for selecting the most appropriate chemotherapy treatment – two-thirds disagreed, while 13% agreed and 17% felt neutral.

When deciding on the use of chemotherapy in the adjuvant setting in early node-negative breast cancer, 88% of respondents felt that breast cancer multigene signatures were important. Moreover, 75% considered such signatures important when deciding whether to use chemotherapy in the adjuvant setting for patients with one to three positive lymph nodes. However, no consensus was reached on the utility of signatures for deciding whether to extend endocrine therapy in either setting.

When examining the usefulness of signatures in more special settings, the authors found that the vast majority (90%) of respondents believed that multigene signatures had clinical utility for postmenopausal early breast cancer patients, and 82% did not consider signatures clinically useful in the early-stage HER2-overexpressed setting.

In addition, 74% thought that breast cancer multigene signatures were not useful in triple-negative disease or in the metastatic setting.

Respondents did not reach a consensus on the clinical utility of multigene signatures in the neoadjuvant setting – only 27% considered them useful, and almost half did not.

The “low percentage” of respondents using the signatures in the neoadjuvant setting and the “misconception regarding the predictive value of these tests on chemotherapy benefits suggest there is still room for training on results interpretation [for breast cancer multigene signatures],” the authors write.

The study was sponsored by Veracyte. Dr. Curigliano has relationships with Pfizer, Novartis, Lilly, Roche, Seattle Genetics, Celltrion, and Veracyte. No other relevant financial relationships were disclosed.

A version of this article first appeared on Medscape.com.

This article was updated 5/9/22.

A team of experts is recommending that doctors forgo describing early, low-grade prostate tumors as “cancers” as a way to ease anxiety among patients and their families and reduce unnecessary treatment.

Physicians often advise that men with low-risk prostate tumors wait to see if the disease worsens – an approach called “active surveillance” – rather than rushing to treat the condition. After all, low-grade tumors rarely cause harm, and therapies such as radiation and surgery can carry serious side effects, including impotence and urinary leakage.

Yet doctors still label these lesions “cancer,” and as a result, some experts say, many men in the United States opt for treatment they don’t need.

In a new paper likely to stoke debate, experts from a range of disciplines, as well as one patient, argue that overtreatment could be reduced by removing the word “cancer” from low-risk disease. Tumors that rate 6 on the Gleason score (GS) cannot invade other organs but nonetheless scare patients into undergoing risky treatments, they argue. Fewer than 1% of men with GS6 prostate tumors experience metastatic disease or die from cancer within 15 years of the initial diagnosis, they report.

“No matter how much time a physician may spend downplaying the significance of a GS6 diagnosis or emphasizing the phrase low-risk, the words ‘you have cancer’ have a potent psychological effect on most men and their families,” they wrote in a paper published in the Journal of Clinical Oncology.

Dropping the C word for low-risk tumors, which make up about half of 268,000 prostate cancer diagnoses annually in the United States, is not a new idea. An independent panel convened by the National Institutes of Health proposed just that in 2011.

However, clinician support for the shift appears to be growing, said Scott Eggener, MD, a urologic oncologist and professor of surgery at the University of Chicago, and a coauthor of the new article.

Dr. Eggener said active surveillance has been increasing dramatically in the United States, to about 60% of patients with GS6. “We feel like the landscape is right now to be talking about this issue,” Dr. Eggener told this news organization.

Reducing unnecessary treatment, he and his coauthors argue, could reduce the cost of health care — and boost the benefit of prostate-specific antigen testing for prostate cancer, which the U.S. Preventive Services Task Force at the moment deems small.

In addition, patients with prostate cancer diagnoses encounter increased risk of depression and suicide, disqualification or higher rates for life insurance, and questions from family and friends if they choose active surveillance over treatment – all of which might be ameliorated by a change in terminology.

The word “cancer” has been dropped from bladder, cervical, and thyroid conditions and prostate abnormalities that used to be classified as Gleason 2 through 5, they noted.
 

Keeping the status quo

But some physicians say GS6 doesn’t need a name change.

From a scientific standpoint, GS6 disease has molecular hallmarks of cancer, according to Jonathan Epstein, MD, professor of pathology, urology, and oncology at Johns Hopkins University, Baltimore. More important, Dr. Epstein told Medscape, the classification does not guarantee that more serious cancer is not present, only that it has not been found yet in tissue samples.

Dr. Eggener acknowledged that while GS6 does have molecular markers associated with cancer – a fact that’s “challenging to reconcile with” – giving it another name “would still require surveillance, and since the window of opportunity for curing localized [prostate cancer] is typically measured in years or decades, evidence of histologic progression to a higher-grade cancer would far precede the potential time of future metastasis in the majority of cases.”

Still, Dr. Epstein worries that dropping the cancer designation may lead some patients to forgo active surveillance, which involves repeated imaging and biopsies to check for worse disease. Without such monitoring, he said, “if they do have higher grade cancer that’s unsampled, it will pose a threat to their life.”

Gleason 6 tumors “may progress, some significantly, or be incompletely sampled at the time of diagnosis. Both clinicians and patients need to understand such risk,” Peter Carroll, MD, MPH, a urologist at the University of California, San Francisco, who is critical of the proposed name change, told this news organization.

Regardless of what it’s called, Gleason 6 disease warrants close monitoring, said Joe Gallo, a 77-year-old Pennsylvania man whose high-risk cancer was detected during active surveillance. “If I had taken a laid-back, or less, approach” to monitoring, Mr. Gallo said, “necessary treatment may have been delayed and my condition may have become more serious.”

Some advocates say patients and their families need to be educated that cancer exists on a spectrum of severity.

Mark Lichty, 73, chairman of a support group called Active Surveillance Patients International, received a Gleason 6 diagnosis 17 years ago. He resisted treatment against medical advice, and the cancer never progressed.

Mr. Lichty said active surveillance has been more widely adopted in Sweden, where physicians assure patients that treatment is unnecessary and support systems exist. “Yes, a diagnosis of cancer is frightening,” he said in an interview. But “we can do a lot better in how we communicate the diagnosis.”

Dr. Eggener reported consulting or advisory roles with Sophiris Bio, Francis Medical, Insightec, Profound Medical, and Candel Therapeutics; speakers bureau at Janssen; and fees for travel, accommodations, and expenses from Janssen Biotech and Insightec; as well as an uncompensated relationship with Steba Biotech. The remaining coauthors reported several financial relationships, which are listed in the paper. Dr. Epstein and Dr. Carroll have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A team of experts is recommending that doctors forgo describing early, low-grade prostate tumors as “cancers” as a way to ease anxiety among patients and their families and reduce unnecessary treatment.

Physicians often advise that men with low-risk prostate tumors wait to see if the disease worsens – an approach called “active surveillance” – rather than rushing to treat the condition. After all, low-grade tumors rarely cause harm, and therapies such as radiation and surgery can carry serious side effects, including impotence and urinary leakage.

Yet doctors still label these lesions “cancer,” and as a result, some experts say, many men in the United States opt for treatment they don’t need.

In a new paper likely to stoke debate, experts from a range of disciplines, as well as one patient, argue that overtreatment could be reduced by removing the word “cancer” from low-risk disease. Tumors that rate 6 on the Gleason score (GS) cannot invade other organs but nonetheless scare patients into undergoing risky treatments, they argue. Fewer than 1% of men with GS6 prostate tumors experience metastatic disease or die from cancer within 15 years of the initial diagnosis, they report.

“No matter how much time a physician may spend downplaying the significance of a GS6 diagnosis or emphasizing the phrase low-risk, the words ‘you have cancer’ have a potent psychological effect on most men and their families,” they wrote in a paper published in the Journal of Clinical Oncology.

Dropping the C word for low-risk tumors, which make up about half of 268,000 prostate cancer diagnoses annually in the United States, is not a new idea. An independent panel convened by the National Institutes of Health proposed just that in 2011.

However, clinician support for the shift appears to be growing, said Scott Eggener, MD, a urologic oncologist and professor of surgery at the University of Chicago, and a coauthor of the new article.

Dr. Eggener said active surveillance has been increasing dramatically in the United States, to about 60% of patients with GS6. “We feel like the landscape is right now to be talking about this issue,” Dr. Eggener told this news organization.

Reducing unnecessary treatment, he and his coauthors argue, could reduce the cost of health care — and boost the benefit of prostate-specific antigen testing for prostate cancer, which the U.S. Preventive Services Task Force at the moment deems small.

In addition, patients with prostate cancer diagnoses encounter increased risk of depression and suicide, disqualification or higher rates for life insurance, and questions from family and friends if they choose active surveillance over treatment – all of which might be ameliorated by a change in terminology.

The word “cancer” has been dropped from bladder, cervical, and thyroid conditions and prostate abnormalities that used to be classified as Gleason 2 through 5, they noted.
 

Keeping the status quo

But some physicians say GS6 doesn’t need a name change.

From a scientific standpoint, GS6 disease has molecular hallmarks of cancer, according to Jonathan Epstein, MD, professor of pathology, urology, and oncology at Johns Hopkins University, Baltimore. More important, Dr. Epstein told Medscape, the classification does not guarantee that more serious cancer is not present, only that it has not been found yet in tissue samples.

Dr. Eggener acknowledged that while GS6 does have molecular markers associated with cancer – a fact that’s “challenging to reconcile with” – giving it another name “would still require surveillance, and since the window of opportunity for curing localized [prostate cancer] is typically measured in years or decades, evidence of histologic progression to a higher-grade cancer would far precede the potential time of future metastasis in the majority of cases.”

Still, Dr. Epstein worries that dropping the cancer designation may lead some patients to forgo active surveillance, which involves repeated imaging and biopsies to check for worse disease. Without such monitoring, he said, “if they do have higher grade cancer that’s unsampled, it will pose a threat to their life.”

Gleason 6 tumors “may progress, some significantly, or be incompletely sampled at the time of diagnosis. Both clinicians and patients need to understand such risk,” Peter Carroll, MD, MPH, a urologist at the University of California, San Francisco, who is critical of the proposed name change, told this news organization.

Regardless of what it’s called, Gleason 6 disease warrants close monitoring, said Joe Gallo, a 77-year-old Pennsylvania man whose high-risk cancer was detected during active surveillance. “If I had taken a laid-back, or less, approach” to monitoring, Mr. Gallo said, “necessary treatment may have been delayed and my condition may have become more serious.”

Some advocates say patients and their families need to be educated that cancer exists on a spectrum of severity.

Mark Lichty, 73, chairman of a support group called Active Surveillance Patients International, received a Gleason 6 diagnosis 17 years ago. He resisted treatment against medical advice, and the cancer never progressed.

Mr. Lichty said active surveillance has been more widely adopted in Sweden, where physicians assure patients that treatment is unnecessary and support systems exist. “Yes, a diagnosis of cancer is frightening,” he said in an interview. But “we can do a lot better in how we communicate the diagnosis.”

Dr. Eggener reported consulting or advisory roles with Sophiris Bio, Francis Medical, Insightec, Profound Medical, and Candel Therapeutics; speakers bureau at Janssen; and fees for travel, accommodations, and expenses from Janssen Biotech and Insightec; as well as an uncompensated relationship with Steba Biotech. The remaining coauthors reported several financial relationships, which are listed in the paper. Dr. Epstein and Dr. Carroll have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A team of experts is recommending that doctors forgo describing early, low-grade prostate tumors as “cancers” as a way to ease anxiety among patients and their families and reduce unnecessary treatment.

Physicians often advise that men with low-risk prostate tumors wait to see if the disease worsens – an approach called “active surveillance” – rather than rushing to treat the condition. After all, low-grade tumors rarely cause harm, and therapies such as radiation and surgery can carry serious side effects, including impotence and urinary leakage.

Yet doctors still label these lesions “cancer,” and as a result, some experts say, many men in the United States opt for treatment they don’t need.

In a new paper likely to stoke debate, experts from a range of disciplines, as well as one patient, argue that overtreatment could be reduced by removing the word “cancer” from low-risk disease. Tumors that rate 6 on the Gleason score (GS) cannot invade other organs but nonetheless scare patients into undergoing risky treatments, they argue. Fewer than 1% of men with GS6 prostate tumors experience metastatic disease or die from cancer within 15 years of the initial diagnosis, they report.

“No matter how much time a physician may spend downplaying the significance of a GS6 diagnosis or emphasizing the phrase low-risk, the words ‘you have cancer’ have a potent psychological effect on most men and their families,” they wrote in a paper published in the Journal of Clinical Oncology.

Dropping the C word for low-risk tumors, which make up about half of 268,000 prostate cancer diagnoses annually in the United States, is not a new idea. An independent panel convened by the National Institutes of Health proposed just that in 2011.

However, clinician support for the shift appears to be growing, said Scott Eggener, MD, a urologic oncologist and professor of surgery at the University of Chicago, and a coauthor of the new article.

Dr. Eggener said active surveillance has been increasing dramatically in the United States, to about 60% of patients with GS6. “We feel like the landscape is right now to be talking about this issue,” Dr. Eggener told this news organization.

Reducing unnecessary treatment, he and his coauthors argue, could reduce the cost of health care — and boost the benefit of prostate-specific antigen testing for prostate cancer, which the U.S. Preventive Services Task Force at the moment deems small.

In addition, patients with prostate cancer diagnoses encounter increased risk of depression and suicide, disqualification or higher rates for life insurance, and questions from family and friends if they choose active surveillance over treatment – all of which might be ameliorated by a change in terminology.

The word “cancer” has been dropped from bladder, cervical, and thyroid conditions and prostate abnormalities that used to be classified as Gleason 2 through 5, they noted.
 

Keeping the status quo

But some physicians say GS6 doesn’t need a name change.

From a scientific standpoint, GS6 disease has molecular hallmarks of cancer, according to Jonathan Epstein, MD, professor of pathology, urology, and oncology at Johns Hopkins University, Baltimore. More important, Dr. Epstein told Medscape, the classification does not guarantee that more serious cancer is not present, only that it has not been found yet in tissue samples.

Dr. Eggener acknowledged that while GS6 does have molecular markers associated with cancer – a fact that’s “challenging to reconcile with” – giving it another name “would still require surveillance, and since the window of opportunity for curing localized [prostate cancer] is typically measured in years or decades, evidence of histologic progression to a higher-grade cancer would far precede the potential time of future metastasis in the majority of cases.”

Still, Dr. Epstein worries that dropping the cancer designation may lead some patients to forgo active surveillance, which involves repeated imaging and biopsies to check for worse disease. Without such monitoring, he said, “if they do have higher grade cancer that’s unsampled, it will pose a threat to their life.”

Gleason 6 tumors “may progress, some significantly, or be incompletely sampled at the time of diagnosis. Both clinicians and patients need to understand such risk,” Peter Carroll, MD, MPH, a urologist at the University of California, San Francisco, who is critical of the proposed name change, told this news organization.

Regardless of what it’s called, Gleason 6 disease warrants close monitoring, said Joe Gallo, a 77-year-old Pennsylvania man whose high-risk cancer was detected during active surveillance. “If I had taken a laid-back, or less, approach” to monitoring, Mr. Gallo said, “necessary treatment may have been delayed and my condition may have become more serious.”

Some advocates say patients and their families need to be educated that cancer exists on a spectrum of severity.

Mark Lichty, 73, chairman of a support group called Active Surveillance Patients International, received a Gleason 6 diagnosis 17 years ago. He resisted treatment against medical advice, and the cancer never progressed.

Mr. Lichty said active surveillance has been more widely adopted in Sweden, where physicians assure patients that treatment is unnecessary and support systems exist. “Yes, a diagnosis of cancer is frightening,” he said in an interview. But “we can do a lot better in how we communicate the diagnosis.”

Dr. Eggener reported consulting or advisory roles with Sophiris Bio, Francis Medical, Insightec, Profound Medical, and Candel Therapeutics; speakers bureau at Janssen; and fees for travel, accommodations, and expenses from Janssen Biotech and Insightec; as well as an uncompensated relationship with Steba Biotech. The remaining coauthors reported several financial relationships, which are listed in the paper. Dr. Epstein and Dr. Carroll have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.