Hematology Times

Extended follow-up of the PRAGUE-17 trial suggests left atrial appendage closure (LAAC) remains noninferior to direct-acting oral anticoagulants (DOACs) with regard to major cardiovascular and neurologic events in high-risk patients with atrial fibrillation.

At a median follow-up of 3.5 years, the annualized rate of the primary outcome – a composite of stroke, transient ischemic attack (TIA), systemic embolism, cardiovascular death, clinically relevant bleeding, or significant procedure- or device-related complications – was 8.6% in patients who underwent LAAC and 11.9% in those managed with DOACs (P value for noninferiority = .006).

The study was not powered to assess the individual components, but most were similar between the LAAC and DOAC groups, including cardiovascular death (20 vs. 30 events) and all stroke/TIA (16 vs. 18 events).

Nonprocedural clinically relevant bleeding was lower with LAAC (23 vs. 40 events; annualized rate, 3.4% vs. 5.9%; P = .039), said Pavel Osmancik, MD, PhD, Charles University and University Hospital Kralovske Vinohrady, both in Prague.

The data were presented at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando and sponsored by the Cardiovascular Research Foundation, and was published simultaneously in the Journal of the American College of Cardiology.

The results are generally in line with those reported in 2020 with an average follow-up of 20 months, when the annualized primary event rate was 11% with LAAC and 13% with DOACs, also known as novel OACs (NOACs).

The trial randomly assigned 415 patients to LAAC with the Amulet (Abbott Vascular) or Watchman/Watchman FLX devices (Boston Scientific) or to rivaroxaban, dabigatran, or preferably apixaban (96%). The modified intention-to-treat analysis included 201 patients in each group, with follow-up extending to 4.3 years in the LAAC group and 4.2 years in the DOAC group.

Dr. Osmancik said the trial enrolled a very-high-risk atrial fibrillation cohort, citing a CHA2DS2-VASc score of 4.7 in both groups and a HAS-BLED score of 3.0-3.1. More than half of the LAAC group (54.2%) and 47.3% of the DOAC group had a history of bleeding or bleeding predisposition.

During a discussion of the results, the panel questioned whether the continuing divergence of the primary event curves at 4 years was potentially related to the effect of noncompliance to the NOACs over time.

Dr. Osmancik replied: “We didn’t do any medication look among the patients, but I don’t think that the number of patients who stopped the NOAC treatment was too high because the rate of strokes was very similar to that in the NOAC trials.”

He reported that 26 patients in the DOAC group permanently stopped their DOAC during follow-up; 15 (58%) because of clinically relevant bleeding, and 13 crossed over to LAAC. Of the 13 patients, 12 cases were successful with dual antiplatelet therapy for 3 months.

In the LAAC group, 17 patients started a DOAC during follow-up. Of these, three (18%) initiated DOAC treatment because of device-related thrombus (DRT) on transesophageal echocardiography, three (18%) because of a peridevice leak (PDL), and five (29%) because of a stroke/TIA.

“Given the observed trend of significantly increased nonprocedural clinically relevant bleeding in the NOAC arm, it is likely that late bleeding events will increasingly favor LAAC over time,” Faisal Merchant, MD, Emory University, Atlanta, wrote in an accompanying editorial.

NOACs, he noted, have important indications beyond prevention of left atrial appendage thrombi, including prevention of non-LAA sources of stroke/systemic embolism (SSE) and treatment of venous thromboembolism. “If significant numbers of patients treated with LAAC end up on anticoagulation in the long run, the benefits of LAAC are likely to be attenuated.”

Although PRAGUE-17 provides some insights into the longer-term indications for resuming anticoagulation in patients previously treated with LAAC, Dr. Merchant said the trial is a “real missed opportunity” in terms of understanding late device-associated risks. Unfortunately, two-thirds of the follow-up transesophageal echocardiograms were canceled because of the COVID-19 pandemic.

“Although the incidence of late DRT and PDL isn’t known, the longer-term PRAGUE-17 data are helpful in demonstrating that rates of SSE remain similar in the LAAC and NOAC groups over time, without any obvious signal of late ischemic events in the LAAC group,” he wrote.

The editorialist also called attention to the “often overlooked” issue of aspirin adherence in long-term medical therapy. Although patients treated with LAAC typically remain on aspirin indefinitely, the percentage who discontinue long-term aspirin is not well described and is not reported in PRAGUE-17. In the AVERROES trial, comparing aspirin with apixaban in patients with atrial fibrillation, however, 20.5% of patients permanently discontinued aspirin at 2 years, compared with only 17.9% on apixaban.

“It is plausible that discontinuation of aspirin may contribute to late ischemic events in patients treated with LAAC, potentially by increasing the risk of late DRT or through other mechanisms,” Dr. Merchant wrote. “Adherence to, and the impact of, long-term antiplatelet therapy should be a focus of future LAAC studies.”

The study was funded by a research grant from the Ministry of Health, Czech Republic. Dr. Osmancik reported occasional speaking honoraria from Bayer and Abbott. Dr. Merchant disclosed no relevant financial relationships.

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

Extended follow-up of the PRAGUE-17 trial suggests left atrial appendage closure (LAAC) remains noninferior to direct-acting oral anticoagulants (DOACs) with regard to major cardiovascular and neurologic events in high-risk patients with atrial fibrillation.

At a median follow-up of 3.5 years, the annualized rate of the primary outcome – a composite of stroke, transient ischemic attack (TIA), systemic embolism, cardiovascular death, clinically relevant bleeding, or significant procedure- or device-related complications – was 8.6% in patients who underwent LAAC and 11.9% in those managed with DOACs (P value for noninferiority = .006).

The study was not powered to assess the individual components, but most were similar between the LAAC and DOAC groups, including cardiovascular death (20 vs. 30 events) and all stroke/TIA (16 vs. 18 events).

Nonprocedural clinically relevant bleeding was lower with LAAC (23 vs. 40 events; annualized rate, 3.4% vs. 5.9%; P = .039), said Pavel Osmancik, MD, PhD, Charles University and University Hospital Kralovske Vinohrady, both in Prague.

The data were presented at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando and sponsored by the Cardiovascular Research Foundation, and was published simultaneously in the Journal of the American College of Cardiology.

The results are generally in line with those reported in 2020 with an average follow-up of 20 months, when the annualized primary event rate was 11% with LAAC and 13% with DOACs, also known as novel OACs (NOACs).

The trial randomly assigned 415 patients to LAAC with the Amulet (Abbott Vascular) or Watchman/Watchman FLX devices (Boston Scientific) or to rivaroxaban, dabigatran, or preferably apixaban (96%). The modified intention-to-treat analysis included 201 patients in each group, with follow-up extending to 4.3 years in the LAAC group and 4.2 years in the DOAC group.

Dr. Osmancik said the trial enrolled a very-high-risk atrial fibrillation cohort, citing a CHA2DS2-VASc score of 4.7 in both groups and a HAS-BLED score of 3.0-3.1. More than half of the LAAC group (54.2%) and 47.3% of the DOAC group had a history of bleeding or bleeding predisposition.

During a discussion of the results, the panel questioned whether the continuing divergence of the primary event curves at 4 years was potentially related to the effect of noncompliance to the NOACs over time.

Dr. Osmancik replied: “We didn’t do any medication look among the patients, but I don’t think that the number of patients who stopped the NOAC treatment was too high because the rate of strokes was very similar to that in the NOAC trials.”

He reported that 26 patients in the DOAC group permanently stopped their DOAC during follow-up; 15 (58%) because of clinically relevant bleeding, and 13 crossed over to LAAC. Of the 13 patients, 12 cases were successful with dual antiplatelet therapy for 3 months.

In the LAAC group, 17 patients started a DOAC during follow-up. Of these, three (18%) initiated DOAC treatment because of device-related thrombus (DRT) on transesophageal echocardiography, three (18%) because of a peridevice leak (PDL), and five (29%) because of a stroke/TIA.

“Given the observed trend of significantly increased nonprocedural clinically relevant bleeding in the NOAC arm, it is likely that late bleeding events will increasingly favor LAAC over time,” Faisal Merchant, MD, Emory University, Atlanta, wrote in an accompanying editorial.

NOACs, he noted, have important indications beyond prevention of left atrial appendage thrombi, including prevention of non-LAA sources of stroke/systemic embolism (SSE) and treatment of venous thromboembolism. “If significant numbers of patients treated with LAAC end up on anticoagulation in the long run, the benefits of LAAC are likely to be attenuated.”

Although PRAGUE-17 provides some insights into the longer-term indications for resuming anticoagulation in patients previously treated with LAAC, Dr. Merchant said the trial is a “real missed opportunity” in terms of understanding late device-associated risks. Unfortunately, two-thirds of the follow-up transesophageal echocardiograms were canceled because of the COVID-19 pandemic.

“Although the incidence of late DRT and PDL isn’t known, the longer-term PRAGUE-17 data are helpful in demonstrating that rates of SSE remain similar in the LAAC and NOAC groups over time, without any obvious signal of late ischemic events in the LAAC group,” he wrote.

The editorialist also called attention to the “often overlooked” issue of aspirin adherence in long-term medical therapy. Although patients treated with LAAC typically remain on aspirin indefinitely, the percentage who discontinue long-term aspirin is not well described and is not reported in PRAGUE-17. In the AVERROES trial, comparing aspirin with apixaban in patients with atrial fibrillation, however, 20.5% of patients permanently discontinued aspirin at 2 years, compared with only 17.9% on apixaban.

“It is plausible that discontinuation of aspirin may contribute to late ischemic events in patients treated with LAAC, potentially by increasing the risk of late DRT or through other mechanisms,” Dr. Merchant wrote. “Adherence to, and the impact of, long-term antiplatelet therapy should be a focus of future LAAC studies.”

The study was funded by a research grant from the Ministry of Health, Czech Republic. Dr. Osmancik reported occasional speaking honoraria from Bayer and Abbott. Dr. Merchant disclosed no relevant financial relationships.

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

Extended follow-up of the PRAGUE-17 trial suggests left atrial appendage closure (LAAC) remains noninferior to direct-acting oral anticoagulants (DOACs) with regard to major cardiovascular and neurologic events in high-risk patients with atrial fibrillation.

At a median follow-up of 3.5 years, the annualized rate of the primary outcome – a composite of stroke, transient ischemic attack (TIA), systemic embolism, cardiovascular death, clinically relevant bleeding, or significant procedure- or device-related complications – was 8.6% in patients who underwent LAAC and 11.9% in those managed with DOACs (P value for noninferiority = .006).

The study was not powered to assess the individual components, but most were similar between the LAAC and DOAC groups, including cardiovascular death (20 vs. 30 events) and all stroke/TIA (16 vs. 18 events).

Nonprocedural clinically relevant bleeding was lower with LAAC (23 vs. 40 events; annualized rate, 3.4% vs. 5.9%; P = .039), said Pavel Osmancik, MD, PhD, Charles University and University Hospital Kralovske Vinohrady, both in Prague.

The data were presented at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando and sponsored by the Cardiovascular Research Foundation, and was published simultaneously in the Journal of the American College of Cardiology.

The results are generally in line with those reported in 2020 with an average follow-up of 20 months, when the annualized primary event rate was 11% with LAAC and 13% with DOACs, also known as novel OACs (NOACs).

The trial randomly assigned 415 patients to LAAC with the Amulet (Abbott Vascular) or Watchman/Watchman FLX devices (Boston Scientific) or to rivaroxaban, dabigatran, or preferably apixaban (96%). The modified intention-to-treat analysis included 201 patients in each group, with follow-up extending to 4.3 years in the LAAC group and 4.2 years in the DOAC group.

Dr. Osmancik said the trial enrolled a very-high-risk atrial fibrillation cohort, citing a CHA2DS2-VASc score of 4.7 in both groups and a HAS-BLED score of 3.0-3.1. More than half of the LAAC group (54.2%) and 47.3% of the DOAC group had a history of bleeding or bleeding predisposition.

During a discussion of the results, the panel questioned whether the continuing divergence of the primary event curves at 4 years was potentially related to the effect of noncompliance to the NOACs over time.

Dr. Osmancik replied: “We didn’t do any medication look among the patients, but I don’t think that the number of patients who stopped the NOAC treatment was too high because the rate of strokes was very similar to that in the NOAC trials.”

He reported that 26 patients in the DOAC group permanently stopped their DOAC during follow-up; 15 (58%) because of clinically relevant bleeding, and 13 crossed over to LAAC. Of the 13 patients, 12 cases were successful with dual antiplatelet therapy for 3 months.

In the LAAC group, 17 patients started a DOAC during follow-up. Of these, three (18%) initiated DOAC treatment because of device-related thrombus (DRT) on transesophageal echocardiography, three (18%) because of a peridevice leak (PDL), and five (29%) because of a stroke/TIA.

“Given the observed trend of significantly increased nonprocedural clinically relevant bleeding in the NOAC arm, it is likely that late bleeding events will increasingly favor LAAC over time,” Faisal Merchant, MD, Emory University, Atlanta, wrote in an accompanying editorial.

NOACs, he noted, have important indications beyond prevention of left atrial appendage thrombi, including prevention of non-LAA sources of stroke/systemic embolism (SSE) and treatment of venous thromboembolism. “If significant numbers of patients treated with LAAC end up on anticoagulation in the long run, the benefits of LAAC are likely to be attenuated.”

Although PRAGUE-17 provides some insights into the longer-term indications for resuming anticoagulation in patients previously treated with LAAC, Dr. Merchant said the trial is a “real missed opportunity” in terms of understanding late device-associated risks. Unfortunately, two-thirds of the follow-up transesophageal echocardiograms were canceled because of the COVID-19 pandemic.

“Although the incidence of late DRT and PDL isn’t known, the longer-term PRAGUE-17 data are helpful in demonstrating that rates of SSE remain similar in the LAAC and NOAC groups over time, without any obvious signal of late ischemic events in the LAAC group,” he wrote.

The editorialist also called attention to the “often overlooked” issue of aspirin adherence in long-term medical therapy. Although patients treated with LAAC typically remain on aspirin indefinitely, the percentage who discontinue long-term aspirin is not well described and is not reported in PRAGUE-17. In the AVERROES trial, comparing aspirin with apixaban in patients with atrial fibrillation, however, 20.5% of patients permanently discontinued aspirin at 2 years, compared with only 17.9% on apixaban.

“It is plausible that discontinuation of aspirin may contribute to late ischemic events in patients treated with LAAC, potentially by increasing the risk of late DRT or through other mechanisms,” Dr. Merchant wrote. “Adherence to, and the impact of, long-term antiplatelet therapy should be a focus of future LAAC studies.”

The study was funded by a research grant from the Ministry of Health, Czech Republic. Dr. Osmancik reported occasional speaking honoraria from Bayer and Abbott. Dr. Merchant disclosed no relevant financial relationships.

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

The obesity epidemic in the United States may be slowing improvements in cancer mortality, according to a new analysis of over 50 million cancer and heart disease deaths.

“By integrating 20 years of cancer mortality data, we demonstrated that trends in obesity-associated cancer mortality showed signs of recent deceleration, consistent with recent findings for heart disease mortality,” Christy L. Avery, PhD, and associates wrote in JAMA Network Open.

Improvements in mortality related to heart disease slowed after 2011, a phenomenon that has been associated with rising obesity rates. The age-adjusted mortality rate (AAMR) declined at an average of 3.8 deaths per 100,000 persons from 1999 to 2011 but only 0.7 deaths per 100,000 from 2011 to 2018, based on data from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research (WONDER).

To understand trends in cancer mortality and their possible connection with obesity, data for 1999-2018 from the WONDER database were divided into obesity-associated and non–obesity-associated categories and compared with heart disease mortality, they explained. The database included more than 50 million deaths that matched inclusion criteria.

The analysis showed there was difference between obesity-associated and non–obesity-associated cancers that was obscured when all cancer deaths were considered together. The average annual change in AAMR for obesity-associated cancers slowed from –1.19 deaths per 100,000 in 1999-2011 to –0.83 in 2011-2018, Dr. Avery and associates reported.

For non–obesity-associated cancers, the annual change in AAMR increased from –1.62 per 100,000 for 1999-2011 to –2.29 for 2011-2018, following the trend for all cancers: –1.48 per 100,000 during 1999-2011 and –1.77 in 2011-2018, they said.

“The largest mortality decreases were observed for melanoma of the skin and lung cancer, two cancers not associated with obesity. For obesity-associated cancers, stable or increasing mortality rates have been observed for liver and pancreatic cancer among both men and women as well as for uterine cancer among women,” the investigators wrote.

Demographically, however, the slowing improvement in mortality for obesity-associated cancers did not follow the trend for heart disease. The deceleration for cancer was more pronounced for women and for non-Hispanic Whites and not seen at all in non-Hispanic Asian/Pacific Islander individuals. “For heart disease, evidence of a deceleration was consistent across sex, race, and ethnicity,” they said.

There are “longstanding disparities in obesity” among various populations in the United States, and the recent trend of obesity occurring earlier in life may be having an effect. “Whether the findings of decelerating mortality rates potentially signal a changing profile of cancer and heart disease mortality as the consequences of the obesity epidemic are realized remains to be seen,” they concluded.

The investigators reported receiving grants from the National Institutes of Health during the conduct of the study, but no other disclosures were reported.

rfranki@mdedge.com

The obesity epidemic in the United States may be slowing improvements in cancer mortality, according to a new analysis of over 50 million cancer and heart disease deaths.

“By integrating 20 years of cancer mortality data, we demonstrated that trends in obesity-associated cancer mortality showed signs of recent deceleration, consistent with recent findings for heart disease mortality,” Christy L. Avery, PhD, and associates wrote in JAMA Network Open.

Improvements in mortality related to heart disease slowed after 2011, a phenomenon that has been associated with rising obesity rates. The age-adjusted mortality rate (AAMR) declined at an average of 3.8 deaths per 100,000 persons from 1999 to 2011 but only 0.7 deaths per 100,000 from 2011 to 2018, based on data from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research (WONDER).

To understand trends in cancer mortality and their possible connection with obesity, data for 1999-2018 from the WONDER database were divided into obesity-associated and non–obesity-associated categories and compared with heart disease mortality, they explained. The database included more than 50 million deaths that matched inclusion criteria.

The analysis showed there was difference between obesity-associated and non–obesity-associated cancers that was obscured when all cancer deaths were considered together. The average annual change in AAMR for obesity-associated cancers slowed from –1.19 deaths per 100,000 in 1999-2011 to –0.83 in 2011-2018, Dr. Avery and associates reported.

For non–obesity-associated cancers, the annual change in AAMR increased from –1.62 per 100,000 for 1999-2011 to –2.29 for 2011-2018, following the trend for all cancers: –1.48 per 100,000 during 1999-2011 and –1.77 in 2011-2018, they said.

“The largest mortality decreases were observed for melanoma of the skin and lung cancer, two cancers not associated with obesity. For obesity-associated cancers, stable or increasing mortality rates have been observed for liver and pancreatic cancer among both men and women as well as for uterine cancer among women,” the investigators wrote.

Demographically, however, the slowing improvement in mortality for obesity-associated cancers did not follow the trend for heart disease. The deceleration for cancer was more pronounced for women and for non-Hispanic Whites and not seen at all in non-Hispanic Asian/Pacific Islander individuals. “For heart disease, evidence of a deceleration was consistent across sex, race, and ethnicity,” they said.

There are “longstanding disparities in obesity” among various populations in the United States, and the recent trend of obesity occurring earlier in life may be having an effect. “Whether the findings of decelerating mortality rates potentially signal a changing profile of cancer and heart disease mortality as the consequences of the obesity epidemic are realized remains to be seen,” they concluded.

The investigators reported receiving grants from the National Institutes of Health during the conduct of the study, but no other disclosures were reported.

rfranki@mdedge.com

The obesity epidemic in the United States may be slowing improvements in cancer mortality, according to a new analysis of over 50 million cancer and heart disease deaths.

“By integrating 20 years of cancer mortality data, we demonstrated that trends in obesity-associated cancer mortality showed signs of recent deceleration, consistent with recent findings for heart disease mortality,” Christy L. Avery, PhD, and associates wrote in JAMA Network Open.

Improvements in mortality related to heart disease slowed after 2011, a phenomenon that has been associated with rising obesity rates. The age-adjusted mortality rate (AAMR) declined at an average of 3.8 deaths per 100,000 persons from 1999 to 2011 but only 0.7 deaths per 100,000 from 2011 to 2018, based on data from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research (WONDER).

To understand trends in cancer mortality and their possible connection with obesity, data for 1999-2018 from the WONDER database were divided into obesity-associated and non–obesity-associated categories and compared with heart disease mortality, they explained. The database included more than 50 million deaths that matched inclusion criteria.

The analysis showed there was difference between obesity-associated and non–obesity-associated cancers that was obscured when all cancer deaths were considered together. The average annual change in AAMR for obesity-associated cancers slowed from –1.19 deaths per 100,000 in 1999-2011 to –0.83 in 2011-2018, Dr. Avery and associates reported.

For non–obesity-associated cancers, the annual change in AAMR increased from –1.62 per 100,000 for 1999-2011 to –2.29 for 2011-2018, following the trend for all cancers: –1.48 per 100,000 during 1999-2011 and –1.77 in 2011-2018, they said.

“The largest mortality decreases were observed for melanoma of the skin and lung cancer, two cancers not associated with obesity. For obesity-associated cancers, stable or increasing mortality rates have been observed for liver and pancreatic cancer among both men and women as well as for uterine cancer among women,” the investigators wrote.

Demographically, however, the slowing improvement in mortality for obesity-associated cancers did not follow the trend for heart disease. The deceleration for cancer was more pronounced for women and for non-Hispanic Whites and not seen at all in non-Hispanic Asian/Pacific Islander individuals. “For heart disease, evidence of a deceleration was consistent across sex, race, and ethnicity,” they said.

There are “longstanding disparities in obesity” among various populations in the United States, and the recent trend of obesity occurring earlier in life may be having an effect. “Whether the findings of decelerating mortality rates potentially signal a changing profile of cancer and heart disease mortality as the consequences of the obesity epidemic are realized remains to be seen,” they concluded.

The investigators reported receiving grants from the National Institutes of Health during the conduct of the study, but no other disclosures were reported.

rfranki@mdedge.com

Excess mortality among people with endogenous Cushing’s syndrome (CS) has declined in the past 20 years yet remains three times higher than in the general population, new research finds.

Among more than 90,000 individuals with endogenous CS, the overall proportion of mortality – defined as the ratio of the number of deaths from CS divided by the total number of CS patients – was 0.05, and the standardized mortality rate was an “unacceptable” three times that of the general population, Padiporn Limumpornpetch, MD, reported on March 20 at ENDO 2021: The Endocrine Society Annual Meeting.

Excess deaths were higher among those with adrenal CS, compared with those with Cushing’s disease. The most common causes of death among those with CS were cardiovascular diseases, cerebrovascular accident, infection, and malignancy, noted Dr. Limumpornpetch, of Songkla University, Hat Yai, Thailand, who is also a PhD student at the University of Leeds, United Kingdom.

“While mortality has improved since 2000, it is still significantly compromised compared to the background population ... The causes of death highlight the need for aggressive management of cardiovascular risk, prevention of thromboembolism, infection control, and a normalized cortisol level,” she said.

Asked to comment, Maria Fleseriu, MD, told this news organization that the new data show “we are making improvements in the care of patients with CS and thus outcomes, but we are not there yet ... This meta-analysis highlights the whole spectrum of acute and life-threatening complications in CS and their high prevalence, even before disease diagnosis and after successful surgery.”

She noted that although she wasn’t surprised by the overall results, “the improvement over time was indeed lower than I expected. However, interestingly here, the risk of mortality in adrenal Cushing’s was unexpectedly high despite patients with adrenal cancer being excluded.”

Dr. Fleseriu, who is director of the Pituitary Center at Oregon Health and Science University, Portland, advised, “Management of hyperglycemia and diabetes, hypertension, hypokalemia, hyperlipidemia, and other cardiovascular risk factors is generally undertaken in accordance with standard of clinical care.”

“But we should focus more on optimizing more aggressively this care in addition to the specific Cushing’s treatment,” she stressed.

In addition, she noted, “Medical therapy for CS may be needed even prior to surgery in severe and/or prolonged hypercortisolism to decrease complications ... We definitely need a multidisciplinary approach to address complications and etiologic treatment as well as the reduced long-term quality of life in patients with CS.”

Largest study in scale and scope of Cushing’s syndrome mortality

Endogenous Cushing’s syndrome occurs when the body overproduces cortisol. The most common cause of the latter is a tumor of the pituitary gland (Cushing’s disease), but another cause is a usually benign tumor of the adrenal glands (adrenal Cushing’s syndrome). Surgery is the mainstay of initial treatment of Cushing’s syndrome. If an operation to remove the tumor fails to cause remission, medications are available.

Prior to this new meta-analysis, there had been limited data on mortality among patients with endogenous CS. Research has mostly been limited to single-cohort studies. A previous systematic review/meta-analysis comprised only seven articles with 780 patients. All the studies were conducted prior to 2012, and most were limited to Cushing’s disease.

“In 2021, we lacked a detailed understanding of patient outcomes and mortality because of the rarity of Cushing’s syndrome,” Dr. Limumpornpetch noted.

The current meta-analysis included 91 articles that reported mortality among patients with endogenous CS. There was a total of 19,181 patients from 92 study cohorts, including 49 studies on CD (n = 14,971), 24 studies on adrenal CS (n = 2304), and 19 studies that included both (n = 1906).

Among 21 studies that reported standardized mortality rate (SMR) data, including 13 CD studies (n = 2160) and seven on adrenal CS (n = 1531), the overall increase in mortality compared to the background population was a significant 3.00 (range, 1.15-7.84).

This SMR was higher among patients with adrenal Cushing’s syndrome (3.3) versus Cushing’s disease (2.8) (P = .003) and among patients who had active disease (5.7) versus those whose disease was in remission (2.3) (P < .001).

The SMR was also worse among patients with Cushing’s disease with larger tumors (macroadenomas), at 7.4, than among patients with very small tumors (microadenomas), at 1.9 (P = .004).

The proportion of death was 0.05 for CS overall, with 0.04 for CD and 0.02 for adrenal adenomas.

Compared to studies published prior to the year 2000, more recent studies seem to reflect advances in treatment and care. The overall proportion of death for all CS cohorts dropped from 0.10 to 0.03 (P < .001); for all CD cohorts, it dropped from 0.14 to 0.03; and for adrenal CS cohorts, it dropped from 0.09 to 0.03 (P = .04).

Causes of death were cardiovascular diseases (29.5% of cases), cerebrovascular accident (11.5%), infection (10.5%), and malignancy (10.1%). Less common causes of death were gastrointestinal bleeding and acute pancreatitis (3.7%), active CS (3.5%), adrenal insufficiency (2.5%), suicide (2.5%), and surgery (1.6%).

Overall, in the CS groups, the proportion of deaths within 30 days of surgery dropped from 0.04 prior to 2000 to 0.01 since (P = .07). For CD, the proportion dropped from 0.02 to 0.01 (P = .25).

Preventing perioperative mortality: Consider thromboprophylaxis

Dr. Fleseriu told this news organization that she believes hypercoagulability is “the least recognized complication with a big role in mortality.” Because most of the perioperative mortality is due to venous thromboembolism and infections, “thromboprophylaxis should be considered for CS patients with severe hypercortisolism and/or postoperatively, based on individual risk factors of thromboembolism and bleeding.”

Recently, Dr. Fleseriu’s group showed in a single retrospective study that the risk for arterial and venous thromboembolic events among patients with CS was approximately 20%. Many patients experienced more than one event. Risk was higher 30 to 60 days postoperatively.

The odds ratio of venous thromoboembolism among patients with CS was 18 times higher than in the normal population.

“Due to the additional thrombotic risk of surgery or any invasive procedure, anticoagulation prophylaxis should be at least considered in all patients with Cushing’s syndrome and balanced with individual bleeding risk,” Dr. Fleseriu advised.

A recent Pituitary Society workshop discussed the management of complications of CS at length; proceedings will be published soon, she noted.

Dr. Limumpornpetch commented, “We look forward to the day when our interdisciplinary approach to managing these challenging patients can deliver outcomes similar to the background population.”

Dr. Limumpornpetch has disclosed no relevant financial relationships. Dr. Fleseriu has been a scientific consultant to Recordati, Sparrow, and Strongbridge and has received grants (inst) from Novartis and Strongbridge.

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

Excess mortality among people with endogenous Cushing’s syndrome (CS) has declined in the past 20 years yet remains three times higher than in the general population, new research finds.

Among more than 90,000 individuals with endogenous CS, the overall proportion of mortality – defined as the ratio of the number of deaths from CS divided by the total number of CS patients – was 0.05, and the standardized mortality rate was an “unacceptable” three times that of the general population, Padiporn Limumpornpetch, MD, reported on March 20 at ENDO 2021: The Endocrine Society Annual Meeting.

Excess deaths were higher among those with adrenal CS, compared with those with Cushing’s disease. The most common causes of death among those with CS were cardiovascular diseases, cerebrovascular accident, infection, and malignancy, noted Dr. Limumpornpetch, of Songkla University, Hat Yai, Thailand, who is also a PhD student at the University of Leeds, United Kingdom.

“While mortality has improved since 2000, it is still significantly compromised compared to the background population ... The causes of death highlight the need for aggressive management of cardiovascular risk, prevention of thromboembolism, infection control, and a normalized cortisol level,” she said.

Asked to comment, Maria Fleseriu, MD, told this news organization that the new data show “we are making improvements in the care of patients with CS and thus outcomes, but we are not there yet ... This meta-analysis highlights the whole spectrum of acute and life-threatening complications in CS and their high prevalence, even before disease diagnosis and after successful surgery.”

She noted that although she wasn’t surprised by the overall results, “the improvement over time was indeed lower than I expected. However, interestingly here, the risk of mortality in adrenal Cushing’s was unexpectedly high despite patients with adrenal cancer being excluded.”

Dr. Fleseriu, who is director of the Pituitary Center at Oregon Health and Science University, Portland, advised, “Management of hyperglycemia and diabetes, hypertension, hypokalemia, hyperlipidemia, and other cardiovascular risk factors is generally undertaken in accordance with standard of clinical care.”

“But we should focus more on optimizing more aggressively this care in addition to the specific Cushing’s treatment,” she stressed.

In addition, she noted, “Medical therapy for CS may be needed even prior to surgery in severe and/or prolonged hypercortisolism to decrease complications ... We definitely need a multidisciplinary approach to address complications and etiologic treatment as well as the reduced long-term quality of life in patients with CS.”

Largest study in scale and scope of Cushing’s syndrome mortality

Endogenous Cushing’s syndrome occurs when the body overproduces cortisol. The most common cause of the latter is a tumor of the pituitary gland (Cushing’s disease), but another cause is a usually benign tumor of the adrenal glands (adrenal Cushing’s syndrome). Surgery is the mainstay of initial treatment of Cushing’s syndrome. If an operation to remove the tumor fails to cause remission, medications are available.

Prior to this new meta-analysis, there had been limited data on mortality among patients with endogenous CS. Research has mostly been limited to single-cohort studies. A previous systematic review/meta-analysis comprised only seven articles with 780 patients. All the studies were conducted prior to 2012, and most were limited to Cushing’s disease.

“In 2021, we lacked a detailed understanding of patient outcomes and mortality because of the rarity of Cushing’s syndrome,” Dr. Limumpornpetch noted.

The current meta-analysis included 91 articles that reported mortality among patients with endogenous CS. There was a total of 19,181 patients from 92 study cohorts, including 49 studies on CD (n = 14,971), 24 studies on adrenal CS (n = 2304), and 19 studies that included both (n = 1906).

Among 21 studies that reported standardized mortality rate (SMR) data, including 13 CD studies (n = 2160) and seven on adrenal CS (n = 1531), the overall increase in mortality compared to the background population was a significant 3.00 (range, 1.15-7.84).

This SMR was higher among patients with adrenal Cushing’s syndrome (3.3) versus Cushing’s disease (2.8) (P = .003) and among patients who had active disease (5.7) versus those whose disease was in remission (2.3) (P < .001).

The SMR was also worse among patients with Cushing’s disease with larger tumors (macroadenomas), at 7.4, than among patients with very small tumors (microadenomas), at 1.9 (P = .004).

The proportion of death was 0.05 for CS overall, with 0.04 for CD and 0.02 for adrenal adenomas.

Compared to studies published prior to the year 2000, more recent studies seem to reflect advances in treatment and care. The overall proportion of death for all CS cohorts dropped from 0.10 to 0.03 (P < .001); for all CD cohorts, it dropped from 0.14 to 0.03; and for adrenal CS cohorts, it dropped from 0.09 to 0.03 (P = .04).

Causes of death were cardiovascular diseases (29.5% of cases), cerebrovascular accident (11.5%), infection (10.5%), and malignancy (10.1%). Less common causes of death were gastrointestinal bleeding and acute pancreatitis (3.7%), active CS (3.5%), adrenal insufficiency (2.5%), suicide (2.5%), and surgery (1.6%).

Overall, in the CS groups, the proportion of deaths within 30 days of surgery dropped from 0.04 prior to 2000 to 0.01 since (P = .07). For CD, the proportion dropped from 0.02 to 0.01 (P = .25).

Preventing perioperative mortality: Consider thromboprophylaxis

Dr. Fleseriu told this news organization that she believes hypercoagulability is “the least recognized complication with a big role in mortality.” Because most of the perioperative mortality is due to venous thromboembolism and infections, “thromboprophylaxis should be considered for CS patients with severe hypercortisolism and/or postoperatively, based on individual risk factors of thromboembolism and bleeding.”

Recently, Dr. Fleseriu’s group showed in a single retrospective study that the risk for arterial and venous thromboembolic events among patients with CS was approximately 20%. Many patients experienced more than one event. Risk was higher 30 to 60 days postoperatively.

The odds ratio of venous thromoboembolism among patients with CS was 18 times higher than in the normal population.

“Due to the additional thrombotic risk of surgery or any invasive procedure, anticoagulation prophylaxis should be at least considered in all patients with Cushing’s syndrome and balanced with individual bleeding risk,” Dr. Fleseriu advised.

A recent Pituitary Society workshop discussed the management of complications of CS at length; proceedings will be published soon, she noted.

Dr. Limumpornpetch commented, “We look forward to the day when our interdisciplinary approach to managing these challenging patients can deliver outcomes similar to the background population.”

Dr. Limumpornpetch has disclosed no relevant financial relationships. Dr. Fleseriu has been a scientific consultant to Recordati, Sparrow, and Strongbridge and has received grants (inst) from Novartis and Strongbridge.

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

Excess mortality among people with endogenous Cushing’s syndrome (CS) has declined in the past 20 years yet remains three times higher than in the general population, new research finds.

Among more than 90,000 individuals with endogenous CS, the overall proportion of mortality – defined as the ratio of the number of deaths from CS divided by the total number of CS patients – was 0.05, and the standardized mortality rate was an “unacceptable” three times that of the general population, Padiporn Limumpornpetch, MD, reported on March 20 at ENDO 2021: The Endocrine Society Annual Meeting.

Excess deaths were higher among those with adrenal CS, compared with those with Cushing’s disease. The most common causes of death among those with CS were cardiovascular diseases, cerebrovascular accident, infection, and malignancy, noted Dr. Limumpornpetch, of Songkla University, Hat Yai, Thailand, who is also a PhD student at the University of Leeds, United Kingdom.

“While mortality has improved since 2000, it is still significantly compromised compared to the background population ... The causes of death highlight the need for aggressive management of cardiovascular risk, prevention of thromboembolism, infection control, and a normalized cortisol level,” she said.

Asked to comment, Maria Fleseriu, MD, told this news organization that the new data show “we are making improvements in the care of patients with CS and thus outcomes, but we are not there yet ... This meta-analysis highlights the whole spectrum of acute and life-threatening complications in CS and their high prevalence, even before disease diagnosis and after successful surgery.”

She noted that although she wasn’t surprised by the overall results, “the improvement over time was indeed lower than I expected. However, interestingly here, the risk of mortality in adrenal Cushing’s was unexpectedly high despite patients with adrenal cancer being excluded.”

Dr. Fleseriu, who is director of the Pituitary Center at Oregon Health and Science University, Portland, advised, “Management of hyperglycemia and diabetes, hypertension, hypokalemia, hyperlipidemia, and other cardiovascular risk factors is generally undertaken in accordance with standard of clinical care.”

“But we should focus more on optimizing more aggressively this care in addition to the specific Cushing’s treatment,” she stressed.

In addition, she noted, “Medical therapy for CS may be needed even prior to surgery in severe and/or prolonged hypercortisolism to decrease complications ... We definitely need a multidisciplinary approach to address complications and etiologic treatment as well as the reduced long-term quality of life in patients with CS.”

Largest study in scale and scope of Cushing’s syndrome mortality

Endogenous Cushing’s syndrome occurs when the body overproduces cortisol. The most common cause of the latter is a tumor of the pituitary gland (Cushing’s disease), but another cause is a usually benign tumor of the adrenal glands (adrenal Cushing’s syndrome). Surgery is the mainstay of initial treatment of Cushing’s syndrome. If an operation to remove the tumor fails to cause remission, medications are available.

Prior to this new meta-analysis, there had been limited data on mortality among patients with endogenous CS. Research has mostly been limited to single-cohort studies. A previous systematic review/meta-analysis comprised only seven articles with 780 patients. All the studies were conducted prior to 2012, and most were limited to Cushing’s disease.

“In 2021, we lacked a detailed understanding of patient outcomes and mortality because of the rarity of Cushing’s syndrome,” Dr. Limumpornpetch noted.

The current meta-analysis included 91 articles that reported mortality among patients with endogenous CS. There was a total of 19,181 patients from 92 study cohorts, including 49 studies on CD (n = 14,971), 24 studies on adrenal CS (n = 2304), and 19 studies that included both (n = 1906).

Among 21 studies that reported standardized mortality rate (SMR) data, including 13 CD studies (n = 2160) and seven on adrenal CS (n = 1531), the overall increase in mortality compared to the background population was a significant 3.00 (range, 1.15-7.84).

This SMR was higher among patients with adrenal Cushing’s syndrome (3.3) versus Cushing’s disease (2.8) (P = .003) and among patients who had active disease (5.7) versus those whose disease was in remission (2.3) (P < .001).

The SMR was also worse among patients with Cushing’s disease with larger tumors (macroadenomas), at 7.4, than among patients with very small tumors (microadenomas), at 1.9 (P = .004).

The proportion of death was 0.05 for CS overall, with 0.04 for CD and 0.02 for adrenal adenomas.

Compared to studies published prior to the year 2000, more recent studies seem to reflect advances in treatment and care. The overall proportion of death for all CS cohorts dropped from 0.10 to 0.03 (P < .001); for all CD cohorts, it dropped from 0.14 to 0.03; and for adrenal CS cohorts, it dropped from 0.09 to 0.03 (P = .04).

Causes of death were cardiovascular diseases (29.5% of cases), cerebrovascular accident (11.5%), infection (10.5%), and malignancy (10.1%). Less common causes of death were gastrointestinal bleeding and acute pancreatitis (3.7%), active CS (3.5%), adrenal insufficiency (2.5%), suicide (2.5%), and surgery (1.6%).

Overall, in the CS groups, the proportion of deaths within 30 days of surgery dropped from 0.04 prior to 2000 to 0.01 since (P = .07). For CD, the proportion dropped from 0.02 to 0.01 (P = .25).

Preventing perioperative mortality: Consider thromboprophylaxis

Dr. Fleseriu told this news organization that she believes hypercoagulability is “the least recognized complication with a big role in mortality.” Because most of the perioperative mortality is due to venous thromboembolism and infections, “thromboprophylaxis should be considered for CS patients with severe hypercortisolism and/or postoperatively, based on individual risk factors of thromboembolism and bleeding.”

Recently, Dr. Fleseriu’s group showed in a single retrospective study that the risk for arterial and venous thromboembolic events among patients with CS was approximately 20%. Many patients experienced more than one event. Risk was higher 30 to 60 days postoperatively.

The odds ratio of venous thromoboembolism among patients with CS was 18 times higher than in the normal population.

“Due to the additional thrombotic risk of surgery or any invasive procedure, anticoagulation prophylaxis should be at least considered in all patients with Cushing’s syndrome and balanced with individual bleeding risk,” Dr. Fleseriu advised.

A recent Pituitary Society workshop discussed the management of complications of CS at length; proceedings will be published soon, she noted.

Dr. Limumpornpetch commented, “We look forward to the day when our interdisciplinary approach to managing these challenging patients can deliver outcomes similar to the background population.”

Dr. Limumpornpetch has disclosed no relevant financial relationships. Dr. Fleseriu has been a scientific consultant to Recordati, Sparrow, and Strongbridge and has received grants (inst) from Novartis and Strongbridge.

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

A personalized genomic cancer vaccine proved feasible to manufacture and was well tolerated in a phase 1 trial, according to researchers.

The vaccine, PGV-001, was given to 13 patients with solid tumors or multiple myeloma who had a high risk of recurrence after surgery or autologous stem cell transplant.

At last follow-up, four patients were still alive without evidence of disease and had not received subsequent therapy, four were alive and receiving therapy, three had died, and two were lost to follow-up.

Thomas Marron, MD, PhD , of Mount Sinai in New York presented these results in a poster at the American Association for Cancer Research Annual Meeting 2021: Week 1 ( Abstract LB048 ). Data in the abstract differ from the data presented.

“While cancer immunotherapy has revolutionized the treatment of cancer, we know that the majority of patients fail to achieve significant clinical response,” Dr. Marron said during his presentation. “One reason for this may be due to lack of preexisting primed T-cell response needed for PD-1 blockade to have a significant effect. To address this, personalized neoantigen vaccines may help prime an improved immune response against tumor cells.”

With this in mind, Dr. Marron and colleagues developed PGV-001, a vaccine consisting of patient-specific synthetic neoantigen peptides given to patients in the adjuvant setting.
 

Creating a personalized vaccine

The researchers synthesized PGV-001 for 15 patients with advanced malignancies. The patients first underwent tumor and germline DNA sequencing as well as HLA typing. Bulk RNA sequencing was performed on patients’ tumors as well.

Then, the researchers used a computational pipeline called OpenVax to identify candidate neoantigens. This pipeline, developed at Mount Sinai, identified and prioritized candidate neoantigens using predicted MHC class I binding affinity and neoantigen abundance.

OpenVax identified an average of 71.5 neoantigens per patient (range, 7-193). The goal was to synthesize a maximum of 10 peptides per patient, but two patients did not have an adequate number of neoantigens.
 

Vaccine administration

The peptides were administered over the course of 27 weeks along with poly-ICLC and a tetanus helper peptide. Before receiving their vaccine doses, patients with solid tumors had undergone curative-intent surgery, and those with multiple myeloma had undergone autologous stem cell transplant.

“Most experimental personalized cancer vaccines are administered in the metastatic setting, but prior research indicates that immunotherapies tend to be more effective in patients who have less cancer spread,” principal investigator Nina Bhardwaj, MD, PhD , of Mount Sinai, explained in a press release .

“We have, therefore, developed a neoantigen vaccine that is administered after standard-of-care adjuvant therapy, such as surgery in solid tumors and bone marrow transplant in multiple myeloma, when patients have minimal, typically microscopic, residual disease.”
 

Feasibility, safety, and immunogenicity

PGV-001 was synthesized for 15 patients and administered to 13 of them. Six of the 13 patients had head and neck squamous cell carcinoma, three had multiple myeloma, two had non–small cell lung cancer, one had breast cancer, and one had urothelial carcinoma.

Eleven patients received all 10 intended doses, and two patients received at least 8 doses.

“The vaccine was well tolerated, with only half of patients experiencing mild, grade 1 adverse events,” Dr. Marron said.

Transient injection site reactions occurred in four patients, and grade 1 fever was reported in one patient.

Immune monitoring is ongoing, but an initial analysis in one patient showed “robust responses” in CD4 and CD8 T cells by intracellular cytokine staining for interferon-gamma, tumor necrosis factor–alpha, and interleukin-2 after in vitro expansion in the presence of vaccine antigens, according to the researchers.

Dr. Marron noted that robust T-cell reactivity was seen at the completion of all 10 doses but was not seen after the 6th dose, and this supports the need for a prolonged dosing schedule.
 

Survival and subsequent therapy

At a mean follow-up of 880 days, four patients had no evidence of disease and had not received subsequent therapy. This includes one patient with stage IIIA non–small cell lung cancer, one with stage IVA HER-2 positive breast cancer, one with stage II urothelial carcinoma, and one with multiple myeloma.

Four patients were alive and receiving subsequent lines of therapy. Two of these patients had significant responses to anti–PD-1 therapy.

Three patients have died, two of whom had documented recurrence of their malignancy. The last two patients were lost to follow-up without documented recurrence.

“Our results demonstrate that the OpenVax pipeline is a viable approach to generate a safe, personalized cancer vaccine, which could potentially be used to treat a range of tumor types,” Dr. Bhardwaj said.

Trials combining neoantigens identified with the OpenVax platform are ongoing in patients with urothelial carcinoma and glioblastoma multiforme, Dr. Marron said.

The current study ( NCT02721043 ) is sponsored by Dr. Bhardwaj. Dr. Marron and Dr. Bhardwaj reported having no disclosures. Their colleagues disclosed relationships with Bristol Myers Squibb, Sema4, and Related Sciences.

A personalized genomic cancer vaccine proved feasible to manufacture and was well tolerated in a phase 1 trial, according to researchers.

The vaccine, PGV-001, was given to 13 patients with solid tumors or multiple myeloma who had a high risk of recurrence after surgery or autologous stem cell transplant.

At last follow-up, four patients were still alive without evidence of disease and had not received subsequent therapy, four were alive and receiving therapy, three had died, and two were lost to follow-up.

Thomas Marron, MD, PhD , of Mount Sinai in New York presented these results in a poster at the American Association for Cancer Research Annual Meeting 2021: Week 1 ( Abstract LB048 ). Data in the abstract differ from the data presented.

“While cancer immunotherapy has revolutionized the treatment of cancer, we know that the majority of patients fail to achieve significant clinical response,” Dr. Marron said during his presentation. “One reason for this may be due to lack of preexisting primed T-cell response needed for PD-1 blockade to have a significant effect. To address this, personalized neoantigen vaccines may help prime an improved immune response against tumor cells.”

With this in mind, Dr. Marron and colleagues developed PGV-001, a vaccine consisting of patient-specific synthetic neoantigen peptides given to patients in the adjuvant setting.
 

Creating a personalized vaccine

The researchers synthesized PGV-001 for 15 patients with advanced malignancies. The patients first underwent tumor and germline DNA sequencing as well as HLA typing. Bulk RNA sequencing was performed on patients’ tumors as well.

Then, the researchers used a computational pipeline called OpenVax to identify candidate neoantigens. This pipeline, developed at Mount Sinai, identified and prioritized candidate neoantigens using predicted MHC class I binding affinity and neoantigen abundance.

OpenVax identified an average of 71.5 neoantigens per patient (range, 7-193). The goal was to synthesize a maximum of 10 peptides per patient, but two patients did not have an adequate number of neoantigens.
 

Vaccine administration

The peptides were administered over the course of 27 weeks along with poly-ICLC and a tetanus helper peptide. Before receiving their vaccine doses, patients with solid tumors had undergone curative-intent surgery, and those with multiple myeloma had undergone autologous stem cell transplant.

“Most experimental personalized cancer vaccines are administered in the metastatic setting, but prior research indicates that immunotherapies tend to be more effective in patients who have less cancer spread,” principal investigator Nina Bhardwaj, MD, PhD , of Mount Sinai, explained in a press release .

“We have, therefore, developed a neoantigen vaccine that is administered after standard-of-care adjuvant therapy, such as surgery in solid tumors and bone marrow transplant in multiple myeloma, when patients have minimal, typically microscopic, residual disease.”
 

Feasibility, safety, and immunogenicity

PGV-001 was synthesized for 15 patients and administered to 13 of them. Six of the 13 patients had head and neck squamous cell carcinoma, three had multiple myeloma, two had non–small cell lung cancer, one had breast cancer, and one had urothelial carcinoma.

Eleven patients received all 10 intended doses, and two patients received at least 8 doses.

“The vaccine was well tolerated, with only half of patients experiencing mild, grade 1 adverse events,” Dr. Marron said.

Transient injection site reactions occurred in four patients, and grade 1 fever was reported in one patient.

Immune monitoring is ongoing, but an initial analysis in one patient showed “robust responses” in CD4 and CD8 T cells by intracellular cytokine staining for interferon-gamma, tumor necrosis factor–alpha, and interleukin-2 after in vitro expansion in the presence of vaccine antigens, according to the researchers.

Dr. Marron noted that robust T-cell reactivity was seen at the completion of all 10 doses but was not seen after the 6th dose, and this supports the need for a prolonged dosing schedule.
 

Survival and subsequent therapy

At a mean follow-up of 880 days, four patients had no evidence of disease and had not received subsequent therapy. This includes one patient with stage IIIA non–small cell lung cancer, one with stage IVA HER-2 positive breast cancer, one with stage II urothelial carcinoma, and one with multiple myeloma.

Four patients were alive and receiving subsequent lines of therapy. Two of these patients had significant responses to anti–PD-1 therapy.

Three patients have died, two of whom had documented recurrence of their malignancy. The last two patients were lost to follow-up without documented recurrence.

“Our results demonstrate that the OpenVax pipeline is a viable approach to generate a safe, personalized cancer vaccine, which could potentially be used to treat a range of tumor types,” Dr. Bhardwaj said.

Trials combining neoantigens identified with the OpenVax platform are ongoing in patients with urothelial carcinoma and glioblastoma multiforme, Dr. Marron said.

The current study ( NCT02721043 ) is sponsored by Dr. Bhardwaj. Dr. Marron and Dr. Bhardwaj reported having no disclosures. Their colleagues disclosed relationships with Bristol Myers Squibb, Sema4, and Related Sciences.

A personalized genomic cancer vaccine proved feasible to manufacture and was well tolerated in a phase 1 trial, according to researchers.

The vaccine, PGV-001, was given to 13 patients with solid tumors or multiple myeloma who had a high risk of recurrence after surgery or autologous stem cell transplant.

At last follow-up, four patients were still alive without evidence of disease and had not received subsequent therapy, four were alive and receiving therapy, three had died, and two were lost to follow-up.

Thomas Marron, MD, PhD , of Mount Sinai in New York presented these results in a poster at the American Association for Cancer Research Annual Meeting 2021: Week 1 ( Abstract LB048 ). Data in the abstract differ from the data presented.

“While cancer immunotherapy has revolutionized the treatment of cancer, we know that the majority of patients fail to achieve significant clinical response,” Dr. Marron said during his presentation. “One reason for this may be due to lack of preexisting primed T-cell response needed for PD-1 blockade to have a significant effect. To address this, personalized neoantigen vaccines may help prime an improved immune response against tumor cells.”

With this in mind, Dr. Marron and colleagues developed PGV-001, a vaccine consisting of patient-specific synthetic neoantigen peptides given to patients in the adjuvant setting.
 

Creating a personalized vaccine

The researchers synthesized PGV-001 for 15 patients with advanced malignancies. The patients first underwent tumor and germline DNA sequencing as well as HLA typing. Bulk RNA sequencing was performed on patients’ tumors as well.

Then, the researchers used a computational pipeline called OpenVax to identify candidate neoantigens. This pipeline, developed at Mount Sinai, identified and prioritized candidate neoantigens using predicted MHC class I binding affinity and neoantigen abundance.

OpenVax identified an average of 71.5 neoantigens per patient (range, 7-193). The goal was to synthesize a maximum of 10 peptides per patient, but two patients did not have an adequate number of neoantigens.
 

Vaccine administration

The peptides were administered over the course of 27 weeks along with poly-ICLC and a tetanus helper peptide. Before receiving their vaccine doses, patients with solid tumors had undergone curative-intent surgery, and those with multiple myeloma had undergone autologous stem cell transplant.

“Most experimental personalized cancer vaccines are administered in the metastatic setting, but prior research indicates that immunotherapies tend to be more effective in patients who have less cancer spread,” principal investigator Nina Bhardwaj, MD, PhD , of Mount Sinai, explained in a press release .

“We have, therefore, developed a neoantigen vaccine that is administered after standard-of-care adjuvant therapy, such as surgery in solid tumors and bone marrow transplant in multiple myeloma, when patients have minimal, typically microscopic, residual disease.”
 

Feasibility, safety, and immunogenicity

PGV-001 was synthesized for 15 patients and administered to 13 of them. Six of the 13 patients had head and neck squamous cell carcinoma, three had multiple myeloma, two had non–small cell lung cancer, one had breast cancer, and one had urothelial carcinoma.

Eleven patients received all 10 intended doses, and two patients received at least 8 doses.

“The vaccine was well tolerated, with only half of patients experiencing mild, grade 1 adverse events,” Dr. Marron said.

Transient injection site reactions occurred in four patients, and grade 1 fever was reported in one patient.

Immune monitoring is ongoing, but an initial analysis in one patient showed “robust responses” in CD4 and CD8 T cells by intracellular cytokine staining for interferon-gamma, tumor necrosis factor–alpha, and interleukin-2 after in vitro expansion in the presence of vaccine antigens, according to the researchers.

Dr. Marron noted that robust T-cell reactivity was seen at the completion of all 10 doses but was not seen after the 6th dose, and this supports the need for a prolonged dosing schedule.
 

Survival and subsequent therapy

At a mean follow-up of 880 days, four patients had no evidence of disease and had not received subsequent therapy. This includes one patient with stage IIIA non–small cell lung cancer, one with stage IVA HER-2 positive breast cancer, one with stage II urothelial carcinoma, and one with multiple myeloma.

Four patients were alive and receiving subsequent lines of therapy. Two of these patients had significant responses to anti–PD-1 therapy.

Three patients have died, two of whom had documented recurrence of their malignancy. The last two patients were lost to follow-up without documented recurrence.

“Our results demonstrate that the OpenVax pipeline is a viable approach to generate a safe, personalized cancer vaccine, which could potentially be used to treat a range of tumor types,” Dr. Bhardwaj said.

Trials combining neoantigens identified with the OpenVax platform are ongoing in patients with urothelial carcinoma and glioblastoma multiforme, Dr. Marron said.

The current study ( NCT02721043 ) is sponsored by Dr. Bhardwaj. Dr. Marron and Dr. Bhardwaj reported having no disclosures. Their colleagues disclosed relationships with Bristol Myers Squibb, Sema4, and Related Sciences.

Patients who are profoundly immunosuppressed after extensive cancer treatment, and who fall ill with COVID-19, can shed viable SARS-CoV-2 virus for at least 2 months after symptom onset and may need extended periods of isolation.

Live-virus shedding was detected in 18 patients who had undergone hematopoietic stem cell transplants or chimeric antigen receptor (CAR) T-cell therapy and in 2 patients with lymphoma. 

The finding was reported Dec. 1 in a research letter in the New England Journal of Medicine. 

Individuals who are otherwise healthy when they get COVID-19 are “no longer infectious after the first week of illness,” said lead author Mini Kamboj, MD, chief medical epidemiologist, Memorial Sloan Kettering Cancer Center, New York. 

“We need to keep an open mind about how [much] longer immunocompromised patients could pose an infection risk to others,” she added.

Dr. Kamboj said in an interview that her team’s previous experience with stem cell transplant recipients had suggested that severely immunocompromised patients shed other viruses (such as respiratory syncytial virus, parainfluenza, and influenza) for longer periods of time than do healthy controls.

Based on their latest findings, the investigators suggest that current guidelines for COVID-19 isolation precautions may need to be revised for immunocompromised patients. Even if only a small proportion of patients with cancer who have COVID-19 remain contagious for prolonged periods of time, “it’s a residual risk that we need to address,” Dr. Kamboj said. 

Dr. Kamboj also suggested that physicians follow test-based criteria to determine when a patient undergoing transplant can be released from isolation.
 

Shedding of viable virus

For this study, the investigators used cell cultures to detect viable virus in serially collected nasopharyngeal and sputum samples from 20 immunocompromised patients who had COVID-19 (diagnosed with COVID-19 between March 10 and April 20).  

Patients had lymphoma (n = 8), multiple myeloma (n= 7), acute leukemia/myelodysplastic syndrome (n = 4), and chronic leukemia (n = 1). There were 16 patients who had undergone transplant, 2 who had received CAR T-cell therapy, and 2 who had received other therapy.

There were 15 patients receiving active treatment or chemotherapy, and 11 developed severe COVID-19 infection. 

In total, 78 respiratory samples were collected.

“Viral RNA was detected for up to 78 days after the onset of symptoms,” the researchers reported, “[and] viable virus was detected in 10 of 14 nasopharyngeal samples (71%) that were available from the first day of laboratory testing.”

Five patients were followed up, and from these patients, the team grew virus in culture for up to 61 days after symptom onset. Two among this small group of five patients had received allogenic hematopoietic stem cell transplantation and one patient had been treated with CAR T-cell therapy within the previous 6 months. This patient remained seronegative for antibodies to the coronavirus.

For 11 patients, the team obtained serial sample genomes and found that  “each patient was infected by a distinct virus and there were no major changes in the consensus sequences of the original serial specimens or cultured isolates.” These findings were consistent with persistent infection, they noted.

The authors have disclosed no relevant financial relationships.

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

Patients who are profoundly immunosuppressed after extensive cancer treatment, and who fall ill with COVID-19, can shed viable SARS-CoV-2 virus for at least 2 months after symptom onset and may need extended periods of isolation.

Live-virus shedding was detected in 18 patients who had undergone hematopoietic stem cell transplants or chimeric antigen receptor (CAR) T-cell therapy and in 2 patients with lymphoma. 

The finding was reported Dec. 1 in a research letter in the New England Journal of Medicine. 

Individuals who are otherwise healthy when they get COVID-19 are “no longer infectious after the first week of illness,” said lead author Mini Kamboj, MD, chief medical epidemiologist, Memorial Sloan Kettering Cancer Center, New York. 

“We need to keep an open mind about how [much] longer immunocompromised patients could pose an infection risk to others,” she added.

Dr. Kamboj said in an interview that her team’s previous experience with stem cell transplant recipients had suggested that severely immunocompromised patients shed other viruses (such as respiratory syncytial virus, parainfluenza, and influenza) for longer periods of time than do healthy controls.

Based on their latest findings, the investigators suggest that current guidelines for COVID-19 isolation precautions may need to be revised for immunocompromised patients. Even if only a small proportion of patients with cancer who have COVID-19 remain contagious for prolonged periods of time, “it’s a residual risk that we need to address,” Dr. Kamboj said. 

Dr. Kamboj also suggested that physicians follow test-based criteria to determine when a patient undergoing transplant can be released from isolation.
 

Shedding of viable virus

For this study, the investigators used cell cultures to detect viable virus in serially collected nasopharyngeal and sputum samples from 20 immunocompromised patients who had COVID-19 (diagnosed with COVID-19 between March 10 and April 20).  

Patients had lymphoma (n = 8), multiple myeloma (n= 7), acute leukemia/myelodysplastic syndrome (n = 4), and chronic leukemia (n = 1). There were 16 patients who had undergone transplant, 2 who had received CAR T-cell therapy, and 2 who had received other therapy.

There were 15 patients receiving active treatment or chemotherapy, and 11 developed severe COVID-19 infection. 

In total, 78 respiratory samples were collected.

“Viral RNA was detected for up to 78 days after the onset of symptoms,” the researchers reported, “[and] viable virus was detected in 10 of 14 nasopharyngeal samples (71%) that were available from the first day of laboratory testing.”

Five patients were followed up, and from these patients, the team grew virus in culture for up to 61 days after symptom onset. Two among this small group of five patients had received allogenic hematopoietic stem cell transplantation and one patient had been treated with CAR T-cell therapy within the previous 6 months. This patient remained seronegative for antibodies to the coronavirus.

For 11 patients, the team obtained serial sample genomes and found that  “each patient was infected by a distinct virus and there were no major changes in the consensus sequences of the original serial specimens or cultured isolates.” These findings were consistent with persistent infection, they noted.

The authors have disclosed no relevant financial relationships.

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

Patients who are profoundly immunosuppressed after extensive cancer treatment, and who fall ill with COVID-19, can shed viable SARS-CoV-2 virus for at least 2 months after symptom onset and may need extended periods of isolation.

Live-virus shedding was detected in 18 patients who had undergone hematopoietic stem cell transplants or chimeric antigen receptor (CAR) T-cell therapy and in 2 patients with lymphoma. 

The finding was reported Dec. 1 in a research letter in the New England Journal of Medicine. 

Individuals who are otherwise healthy when they get COVID-19 are “no longer infectious after the first week of illness,” said lead author Mini Kamboj, MD, chief medical epidemiologist, Memorial Sloan Kettering Cancer Center, New York. 

“We need to keep an open mind about how [much] longer immunocompromised patients could pose an infection risk to others,” she added.

Dr. Kamboj said in an interview that her team’s previous experience with stem cell transplant recipients had suggested that severely immunocompromised patients shed other viruses (such as respiratory syncytial virus, parainfluenza, and influenza) for longer periods of time than do healthy controls.

Based on their latest findings, the investigators suggest that current guidelines for COVID-19 isolation precautions may need to be revised for immunocompromised patients. Even if only a small proportion of patients with cancer who have COVID-19 remain contagious for prolonged periods of time, “it’s a residual risk that we need to address,” Dr. Kamboj said. 

Dr. Kamboj also suggested that physicians follow test-based criteria to determine when a patient undergoing transplant can be released from isolation.
 

Shedding of viable virus

For this study, the investigators used cell cultures to detect viable virus in serially collected nasopharyngeal and sputum samples from 20 immunocompromised patients who had COVID-19 (diagnosed with COVID-19 between March 10 and April 20).  

Patients had lymphoma (n = 8), multiple myeloma (n= 7), acute leukemia/myelodysplastic syndrome (n = 4), and chronic leukemia (n = 1). There were 16 patients who had undergone transplant, 2 who had received CAR T-cell therapy, and 2 who had received other therapy.

There were 15 patients receiving active treatment or chemotherapy, and 11 developed severe COVID-19 infection. 

In total, 78 respiratory samples were collected.

“Viral RNA was detected for up to 78 days after the onset of symptoms,” the researchers reported, “[and] viable virus was detected in 10 of 14 nasopharyngeal samples (71%) that were available from the first day of laboratory testing.”

Five patients were followed up, and from these patients, the team grew virus in culture for up to 61 days after symptom onset. Two among this small group of five patients had received allogenic hematopoietic stem cell transplantation and one patient had been treated with CAR T-cell therapy within the previous 6 months. This patient remained seronegative for antibodies to the coronavirus.

For 11 patients, the team obtained serial sample genomes and found that  “each patient was infected by a distinct virus and there were no major changes in the consensus sequences of the original serial specimens or cultured isolates.” These findings were consistent with persistent infection, they noted.

The authors have disclosed no relevant financial relationships.

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

Rates of cancer increased by 30% from 1973 to 2015 in adolescents and young adults (AYAs) aged 15–39 years in the United States, according to a review of almost a half million cases in the National Institutes of Health’s Surveillance, Epidemiology, and End Results database.

There was an annual increase of 0.537 new cases per 100,000 people, from 57.2 cases per 100,000 in 1973 to 74.2 in 2015.

Kidney carcinoma led with the highest rate increase. There were also marked increases in thyroid and colorectal carcinoma, germ cell and trophoblastic neoplasms, and melanoma, among others.

The report was published online December 1 in JAMA Network Open.

“Clinicians should be on the lookout for these cancers in their adolescent and young adult patients,” said senior investigator Nicholas Zaorsky, MD, an assistant professor of radiation oncology and public health sciences at the Penn State Cancer Institute, Hershey, Pennsylvania.

“Now that there is a better understanding of the types of cancer that are prevalent and rising in this age group, prevention, screening, diagnosis and treatment protocols specifically targeted to this population should be developed,” he said in a press release.

The reasons for the increases are unclear, but environmental and dietary factors, increasing obesity, and changing screening practices are likely in play, the authors comment. In addition, “cancer screening and overdiagnosis are thought to account for much of the increasing rates of thyroid and kidney carcinoma, among others,” they add.

The American Cancer Society (ACS) recently found similar increases in thyroid, kidney, and colorectal cancer among AYAs, as well as an increase in uterine cancer.

It’s important to note, however, that “this phenomenon is largely driven by trends for thyroid cancer, which is thought to be a result of overdiagnosis,” said ACS surveillance researcher Kimberly Miller, MPH, when asked to comment on the new study.

“As such, it is extremely important to also consider trends in cancer mortality rates among this age group, which are declining overall but are increasing for colorectal and uterine cancers. The fact that both incidence and mortality rates are increasing for these two cancers suggests a true increase in disease burden and certainly requires further attention and research,” she said.

Historically, management of cancer in AYAs has fallen somewhere between pediatric and adult oncology, neither of which capture the distinct biological, social, and economic needs of AYAs. Research has also focused on childhood and adult cancers, leaving cancer in AYAs inadequately studied.

The new findings are “valuable to guide more targeted research and interventions specifically to AYAs,” Zaorsky and colleagues say in their report.

Among female patients ― 59.1% of the study population ― incidence increased for 15 cancers, including kidney carcinoma (annual percent change [APC], 3.632), thyroid carcinoma (APC, 3.456), and myeloma, mast cell, and miscellaneous lymphoreticular neoplasms not otherwise specified (APC, 2.805). Rates of five cancers declined, led by astrocytoma not otherwise specified (APC, –3.369) and carcinoma of the gonads (APC, –1.743).

Among male patients, incidence increased for 14 cancers, including kidney carcinoma (APC, 3.572), unspecified soft tissue sarcoma (APC 2.543), and thyroid carcinoma (APC, 2.273). Incidence fell for seven, led by astrocytoma not otherwise specified (APC, –3.759) and carcinoma of the trachea, bronchus, and lung (APC, –2.635).

Increased testicular cancer rates (APC, 1.246) could be related to greater prenatal exposure to estrogen and progesterone or through dairy consumption; increasing survival of premature infants; and greater exposure to cannabis, among other possibilities, the investigators say.

Increases in colorectal cancer might be related to fewer vegetables and more fat and processed meat in the diet; lack of exercise; and increasing obesity. Human papillomavirus infection has also been implicated.

Higher rates of melanoma could be related to tanning bed use.

Declines in some cancers could be related to greater use of oral contraceptives; laws reducing exposure to benzene and other chemicals; and fewer people smoking.

Although kidney carcinoma has increased at the greatest rate, it’s uncommon. Colorectal and thyroid carcinoma, melanoma, non-Hodgkin lymphoma, and germ cell and trophoblastic neoplasms of the gonads contribute more to the overall increase in cancers among AYAs, the investigators note.

Almost 80% of the patients were White; 10.3% were Black.

The study was funded by the National Center for Advancing Translational Sciences. The investigators have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Rates of cancer increased by 30% from 1973 to 2015 in adolescents and young adults (AYAs) aged 15–39 years in the United States, according to a review of almost a half million cases in the National Institutes of Health’s Surveillance, Epidemiology, and End Results database.

There was an annual increase of 0.537 new cases per 100,000 people, from 57.2 cases per 100,000 in 1973 to 74.2 in 2015.

Kidney carcinoma led with the highest rate increase. There were also marked increases in thyroid and colorectal carcinoma, germ cell and trophoblastic neoplasms, and melanoma, among others.

The report was published online December 1 in JAMA Network Open.

“Clinicians should be on the lookout for these cancers in their adolescent and young adult patients,” said senior investigator Nicholas Zaorsky, MD, an assistant professor of radiation oncology and public health sciences at the Penn State Cancer Institute, Hershey, Pennsylvania.

“Now that there is a better understanding of the types of cancer that are prevalent and rising in this age group, prevention, screening, diagnosis and treatment protocols specifically targeted to this population should be developed,” he said in a press release.

The reasons for the increases are unclear, but environmental and dietary factors, increasing obesity, and changing screening practices are likely in play, the authors comment. In addition, “cancer screening and overdiagnosis are thought to account for much of the increasing rates of thyroid and kidney carcinoma, among others,” they add.

The American Cancer Society (ACS) recently found similar increases in thyroid, kidney, and colorectal cancer among AYAs, as well as an increase in uterine cancer.

It’s important to note, however, that “this phenomenon is largely driven by trends for thyroid cancer, which is thought to be a result of overdiagnosis,” said ACS surveillance researcher Kimberly Miller, MPH, when asked to comment on the new study.

“As such, it is extremely important to also consider trends in cancer mortality rates among this age group, which are declining overall but are increasing for colorectal and uterine cancers. The fact that both incidence and mortality rates are increasing for these two cancers suggests a true increase in disease burden and certainly requires further attention and research,” she said.

Historically, management of cancer in AYAs has fallen somewhere between pediatric and adult oncology, neither of which capture the distinct biological, social, and economic needs of AYAs. Research has also focused on childhood and adult cancers, leaving cancer in AYAs inadequately studied.

The new findings are “valuable to guide more targeted research and interventions specifically to AYAs,” Zaorsky and colleagues say in their report.

Among female patients ― 59.1% of the study population ― incidence increased for 15 cancers, including kidney carcinoma (annual percent change [APC], 3.632), thyroid carcinoma (APC, 3.456), and myeloma, mast cell, and miscellaneous lymphoreticular neoplasms not otherwise specified (APC, 2.805). Rates of five cancers declined, led by astrocytoma not otherwise specified (APC, –3.369) and carcinoma of the gonads (APC, –1.743).

Among male patients, incidence increased for 14 cancers, including kidney carcinoma (APC, 3.572), unspecified soft tissue sarcoma (APC 2.543), and thyroid carcinoma (APC, 2.273). Incidence fell for seven, led by astrocytoma not otherwise specified (APC, –3.759) and carcinoma of the trachea, bronchus, and lung (APC, –2.635).

Increased testicular cancer rates (APC, 1.246) could be related to greater prenatal exposure to estrogen and progesterone or through dairy consumption; increasing survival of premature infants; and greater exposure to cannabis, among other possibilities, the investigators say.

Increases in colorectal cancer might be related to fewer vegetables and more fat and processed meat in the diet; lack of exercise; and increasing obesity. Human papillomavirus infection has also been implicated.

Higher rates of melanoma could be related to tanning bed use.

Declines in some cancers could be related to greater use of oral contraceptives; laws reducing exposure to benzene and other chemicals; and fewer people smoking.

Although kidney carcinoma has increased at the greatest rate, it’s uncommon. Colorectal and thyroid carcinoma, melanoma, non-Hodgkin lymphoma, and germ cell and trophoblastic neoplasms of the gonads contribute more to the overall increase in cancers among AYAs, the investigators note.

Almost 80% of the patients were White; 10.3% were Black.

The study was funded by the National Center for Advancing Translational Sciences. The investigators have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Rates of cancer increased by 30% from 1973 to 2015 in adolescents and young adults (AYAs) aged 15–39 years in the United States, according to a review of almost a half million cases in the National Institutes of Health’s Surveillance, Epidemiology, and End Results database.

There was an annual increase of 0.537 new cases per 100,000 people, from 57.2 cases per 100,000 in 1973 to 74.2 in 2015.

Kidney carcinoma led with the highest rate increase. There were also marked increases in thyroid and colorectal carcinoma, germ cell and trophoblastic neoplasms, and melanoma, among others.

The report was published online December 1 in JAMA Network Open.

“Clinicians should be on the lookout for these cancers in their adolescent and young adult patients,” said senior investigator Nicholas Zaorsky, MD, an assistant professor of radiation oncology and public health sciences at the Penn State Cancer Institute, Hershey, Pennsylvania.

“Now that there is a better understanding of the types of cancer that are prevalent and rising in this age group, prevention, screening, diagnosis and treatment protocols specifically targeted to this population should be developed,” he said in a press release.

The reasons for the increases are unclear, but environmental and dietary factors, increasing obesity, and changing screening practices are likely in play, the authors comment. In addition, “cancer screening and overdiagnosis are thought to account for much of the increasing rates of thyroid and kidney carcinoma, among others,” they add.

The American Cancer Society (ACS) recently found similar increases in thyroid, kidney, and colorectal cancer among AYAs, as well as an increase in uterine cancer.

It’s important to note, however, that “this phenomenon is largely driven by trends for thyroid cancer, which is thought to be a result of overdiagnosis,” said ACS surveillance researcher Kimberly Miller, MPH, when asked to comment on the new study.

“As such, it is extremely important to also consider trends in cancer mortality rates among this age group, which are declining overall but are increasing for colorectal and uterine cancers. The fact that both incidence and mortality rates are increasing for these two cancers suggests a true increase in disease burden and certainly requires further attention and research,” she said.

Historically, management of cancer in AYAs has fallen somewhere between pediatric and adult oncology, neither of which capture the distinct biological, social, and economic needs of AYAs. Research has also focused on childhood and adult cancers, leaving cancer in AYAs inadequately studied.

The new findings are “valuable to guide more targeted research and interventions specifically to AYAs,” Zaorsky and colleagues say in their report.

Among female patients ― 59.1% of the study population ― incidence increased for 15 cancers, including kidney carcinoma (annual percent change [APC], 3.632), thyroid carcinoma (APC, 3.456), and myeloma, mast cell, and miscellaneous lymphoreticular neoplasms not otherwise specified (APC, 2.805). Rates of five cancers declined, led by astrocytoma not otherwise specified (APC, –3.369) and carcinoma of the gonads (APC, –1.743).

Among male patients, incidence increased for 14 cancers, including kidney carcinoma (APC, 3.572), unspecified soft tissue sarcoma (APC 2.543), and thyroid carcinoma (APC, 2.273). Incidence fell for seven, led by astrocytoma not otherwise specified (APC, –3.759) and carcinoma of the trachea, bronchus, and lung (APC, –2.635).

Increased testicular cancer rates (APC, 1.246) could be related to greater prenatal exposure to estrogen and progesterone or through dairy consumption; increasing survival of premature infants; and greater exposure to cannabis, among other possibilities, the investigators say.

Increases in colorectal cancer might be related to fewer vegetables and more fat and processed meat in the diet; lack of exercise; and increasing obesity. Human papillomavirus infection has also been implicated.

Higher rates of melanoma could be related to tanning bed use.

Declines in some cancers could be related to greater use of oral contraceptives; laws reducing exposure to benzene and other chemicals; and fewer people smoking.

Although kidney carcinoma has increased at the greatest rate, it’s uncommon. Colorectal and thyroid carcinoma, melanoma, non-Hodgkin lymphoma, and germ cell and trophoblastic neoplasms of the gonads contribute more to the overall increase in cancers among AYAs, the investigators note.

Almost 80% of the patients were White; 10.3% were Black.

The study was funded by the National Center for Advancing Translational Sciences. The investigators have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Men with genetic variants that cause hereditary hemochromatosis have an increased risk of liver cancer and death, according to a large cohort study.

Hereditary hemochromatosis is primarily caused by HFE gene variants. Past research suggested that 81% of patients with hereditary hemochromatosis carry the p.C282Y variant and 5% carry the p.C282Y/p.H63D compound heterozygote genotype.

In a new study, the presence of HFE p.C282Y and p.H63D genotypes was associated with a 10-fold greater risk of developing a hepatic malignancy among men of European ancestry aged 40-70 years. In addition, men with HFE variants were 1.2 times more likely to die of any cause, compared with men who had neither pathogenic variant.

Janice L. Atkins, PhD, of the University of Exeter (England), and colleagues reported these findings in JAMA.

For this study, Dr. Atkins and colleagues used follow-up data from a large genotyped community sample to estimate the incidence of primary hepatic carcinomas and deaths by HFE variant status in participants of European descent.

Data for the two linked coprimary endpoints, incident primary liver carcinoma and all-cause mortality, were derived from hospital and death certificate records. Where available, primary care data was also included.
 

Results: Increased risks for men, not women

The researchers analyzed data from 451,186 men and women, aged 40-70 years, from the UK Biobank. There were 2,890 (0.9%) patients who were p.C282Y homozygous, 1,294 of whom were men.

Among the 1,294 men with HFE p.C282Y homozygosity, 21 were diagnosed with a primary hepatic malignancy. Ten of these patients were not diagnosed with hemochromatosis at baseline.

At a median follow-up of 8.9 years, the risk of primary hepatic malignancy was significantly higher in men with HFE p.C282Y homozygosity, compared with men without HFE pathogenic variants (hazard ratio, 10.5; 95% confidence interval, 6.6-16.7; P < .001).

The risk of all-cause death was significantly higher in men with HFE p.C282Y homozygosity as well (HR, 1.2; 95% CI, 1.0-1.5; P  = .046).

In contrast, female HFE p.C282Y homozygotes had no significant increases in the risk of incident primary hepatic malignancy or all-cause mortality.

Life table projections estimated that 7.2% of men with HFE p.C282Y homozygosity will develop a primary hepatic malignancy by age 75, compared with 0.6% of men without p.C282Y or p.H63D variants.

The researchers acknowledged that a key limitation of this study was the ancestral homogeneity of the cohort. Thus, the findings may not be generalizable to all patient populations.
 

Implications: Earlier diagnosis and treatment

The results of this study underline the importance of early diagnosis and genetic testing, according to the researchers.

“Tragically, men with the hemochromatosis faulty genes have been dying of liver cancer for many years, but this was thought to be rare,” study author David Melzer, MBBCh, PhD, of University of Exeter, said in a press release.

“The large scale of the UK Biobank study allowed us to measure cancer risk accurately. We were shocked to find that more than 7% of men with two faulty genes are likely to develop liver cancer by age 75, particularly considering that the U.K. has the second-highest rate of these faulty genes in the world. Fortunately, most of these cancers could be prevented with early treatment,” Dr. Melzer added.

“Physicians and scientists have long acknowledged that iron overload is an important cofactor fueling the development of many serious diseases, including cancer,” said study author Jeremy Shearman, MBChB, DPhil, of Nuffield Health and South Warwickshire NHS Foundation Trust in the United Kingdom.

“This research is a vital step towards quantifying that risk and should raise awareness of the importance of iron in the minds of both clinicians and patients. Measurement of iron stores and recognition of the genetic risk of iron overload needs to become a routine part of health assessment and monitoring in the U.K.,” Dr. Shearman added.

“The UK Biobank project is a glimpse into the future of medicine where all known genes are tested and then treatable conditions are offered treatment before serious complications develop,” said study author Paul Adams, MD, of the University of Western Ontario in London.

This research was funded by the UK Medical Research Council. Dr. Melzer disclosed financial affiliations with the UK Medical Research Council during the conduct of the study.

SOURCE: Atkins JL et al. JAMA. 2020 Nov 24. doi: 10.1001/jama.2020.21566.

Men with genetic variants that cause hereditary hemochromatosis have an increased risk of liver cancer and death, according to a large cohort study.

Hereditary hemochromatosis is primarily caused by HFE gene variants. Past research suggested that 81% of patients with hereditary hemochromatosis carry the p.C282Y variant and 5% carry the p.C282Y/p.H63D compound heterozygote genotype.

In a new study, the presence of HFE p.C282Y and p.H63D genotypes was associated with a 10-fold greater risk of developing a hepatic malignancy among men of European ancestry aged 40-70 years. In addition, men with HFE variants were 1.2 times more likely to die of any cause, compared with men who had neither pathogenic variant.

Janice L. Atkins, PhD, of the University of Exeter (England), and colleagues reported these findings in JAMA.

For this study, Dr. Atkins and colleagues used follow-up data from a large genotyped community sample to estimate the incidence of primary hepatic carcinomas and deaths by HFE variant status in participants of European descent.

Data for the two linked coprimary endpoints, incident primary liver carcinoma and all-cause mortality, were derived from hospital and death certificate records. Where available, primary care data was also included.
 

Results: Increased risks for men, not women

The researchers analyzed data from 451,186 men and women, aged 40-70 years, from the UK Biobank. There were 2,890 (0.9%) patients who were p.C282Y homozygous, 1,294 of whom were men.

Among the 1,294 men with HFE p.C282Y homozygosity, 21 were diagnosed with a primary hepatic malignancy. Ten of these patients were not diagnosed with hemochromatosis at baseline.

At a median follow-up of 8.9 years, the risk of primary hepatic malignancy was significantly higher in men with HFE p.C282Y homozygosity, compared with men without HFE pathogenic variants (hazard ratio, 10.5; 95% confidence interval, 6.6-16.7; P < .001).

The risk of all-cause death was significantly higher in men with HFE p.C282Y homozygosity as well (HR, 1.2; 95% CI, 1.0-1.5; P  = .046).

In contrast, female HFE p.C282Y homozygotes had no significant increases in the risk of incident primary hepatic malignancy or all-cause mortality.

Life table projections estimated that 7.2% of men with HFE p.C282Y homozygosity will develop a primary hepatic malignancy by age 75, compared with 0.6% of men without p.C282Y or p.H63D variants.

The researchers acknowledged that a key limitation of this study was the ancestral homogeneity of the cohort. Thus, the findings may not be generalizable to all patient populations.
 

Implications: Earlier diagnosis and treatment

The results of this study underline the importance of early diagnosis and genetic testing, according to the researchers.

“Tragically, men with the hemochromatosis faulty genes have been dying of liver cancer for many years, but this was thought to be rare,” study author David Melzer, MBBCh, PhD, of University of Exeter, said in a press release.

“The large scale of the UK Biobank study allowed us to measure cancer risk accurately. We were shocked to find that more than 7% of men with two faulty genes are likely to develop liver cancer by age 75, particularly considering that the U.K. has the second-highest rate of these faulty genes in the world. Fortunately, most of these cancers could be prevented with early treatment,” Dr. Melzer added.

“Physicians and scientists have long acknowledged that iron overload is an important cofactor fueling the development of many serious diseases, including cancer,” said study author Jeremy Shearman, MBChB, DPhil, of Nuffield Health and South Warwickshire NHS Foundation Trust in the United Kingdom.

“This research is a vital step towards quantifying that risk and should raise awareness of the importance of iron in the minds of both clinicians and patients. Measurement of iron stores and recognition of the genetic risk of iron overload needs to become a routine part of health assessment and monitoring in the U.K.,” Dr. Shearman added.

“The UK Biobank project is a glimpse into the future of medicine where all known genes are tested and then treatable conditions are offered treatment before serious complications develop,” said study author Paul Adams, MD, of the University of Western Ontario in London.

This research was funded by the UK Medical Research Council. Dr. Melzer disclosed financial affiliations with the UK Medical Research Council during the conduct of the study.

SOURCE: Atkins JL et al. JAMA. 2020 Nov 24. doi: 10.1001/jama.2020.21566.

Men with genetic variants that cause hereditary hemochromatosis have an increased risk of liver cancer and death, according to a large cohort study.

Hereditary hemochromatosis is primarily caused by HFE gene variants. Past research suggested that 81% of patients with hereditary hemochromatosis carry the p.C282Y variant and 5% carry the p.C282Y/p.H63D compound heterozygote genotype.

In a new study, the presence of HFE p.C282Y and p.H63D genotypes was associated with a 10-fold greater risk of developing a hepatic malignancy among men of European ancestry aged 40-70 years. In addition, men with HFE variants were 1.2 times more likely to die of any cause, compared with men who had neither pathogenic variant.

Janice L. Atkins, PhD, of the University of Exeter (England), and colleagues reported these findings in JAMA.

For this study, Dr. Atkins and colleagues used follow-up data from a large genotyped community sample to estimate the incidence of primary hepatic carcinomas and deaths by HFE variant status in participants of European descent.

Data for the two linked coprimary endpoints, incident primary liver carcinoma and all-cause mortality, were derived from hospital and death certificate records. Where available, primary care data was also included.
 

Results: Increased risks for men, not women

The researchers analyzed data from 451,186 men and women, aged 40-70 years, from the UK Biobank. There were 2,890 (0.9%) patients who were p.C282Y homozygous, 1,294 of whom were men.

Among the 1,294 men with HFE p.C282Y homozygosity, 21 were diagnosed with a primary hepatic malignancy. Ten of these patients were not diagnosed with hemochromatosis at baseline.

At a median follow-up of 8.9 years, the risk of primary hepatic malignancy was significantly higher in men with HFE p.C282Y homozygosity, compared with men without HFE pathogenic variants (hazard ratio, 10.5; 95% confidence interval, 6.6-16.7; P < .001).

The risk of all-cause death was significantly higher in men with HFE p.C282Y homozygosity as well (HR, 1.2; 95% CI, 1.0-1.5; P  = .046).

In contrast, female HFE p.C282Y homozygotes had no significant increases in the risk of incident primary hepatic malignancy or all-cause mortality.

Life table projections estimated that 7.2% of men with HFE p.C282Y homozygosity will develop a primary hepatic malignancy by age 75, compared with 0.6% of men without p.C282Y or p.H63D variants.

The researchers acknowledged that a key limitation of this study was the ancestral homogeneity of the cohort. Thus, the findings may not be generalizable to all patient populations.
 

Implications: Earlier diagnosis and treatment

The results of this study underline the importance of early diagnosis and genetic testing, according to the researchers.

“Tragically, men with the hemochromatosis faulty genes have been dying of liver cancer for many years, but this was thought to be rare,” study author David Melzer, MBBCh, PhD, of University of Exeter, said in a press release.

“The large scale of the UK Biobank study allowed us to measure cancer risk accurately. We were shocked to find that more than 7% of men with two faulty genes are likely to develop liver cancer by age 75, particularly considering that the U.K. has the second-highest rate of these faulty genes in the world. Fortunately, most of these cancers could be prevented with early treatment,” Dr. Melzer added.

“Physicians and scientists have long acknowledged that iron overload is an important cofactor fueling the development of many serious diseases, including cancer,” said study author Jeremy Shearman, MBChB, DPhil, of Nuffield Health and South Warwickshire NHS Foundation Trust in the United Kingdom.

“This research is a vital step towards quantifying that risk and should raise awareness of the importance of iron in the minds of both clinicians and patients. Measurement of iron stores and recognition of the genetic risk of iron overload needs to become a routine part of health assessment and monitoring in the U.K.,” Dr. Shearman added.

“The UK Biobank project is a glimpse into the future of medicine where all known genes are tested and then treatable conditions are offered treatment before serious complications develop,” said study author Paul Adams, MD, of the University of Western Ontario in London.

This research was funded by the UK Medical Research Council. Dr. Melzer disclosed financial affiliations with the UK Medical Research Council during the conduct of the study.

SOURCE: Atkins JL et al. JAMA. 2020 Nov 24. doi: 10.1001/jama.2020.21566.

Two new protein biomarkers may serve as prognostic indicators for outcomes in chronic lymphocytic leukemia (CLL) patients, according to the results of a proteomic assessment of patients’ serum compared to their event-free survival (EFS).

The results were published in Experimental Hematology.

The study attempted to validate the prognostic ability of known proteomic markers measured pretreatment and to search for new proteomic markers that might be related to treatment response in CLL, according to Fatemeh Saberi Hosnijeh, MD, of Erasmus MC, University Medical Center, Rotterdam, The Netherlands, and colleagues.

Baseline serum samples were taken from 51 CLL patients who were then treated with chemoimmunotherapy. The samples were analyzed for 360 proteomic markers, and those results were compared with patient EFS.

Study subjects were selected from patients enrolled in the HOVON 109 clinical trial, a phase 1/2 trial designed to assess the efficacy and safety of first-line therapy involving chlorambucil, rituximab,and lenalidomide in elderly patients and young frail patients with advanced CLL.

The patients assessed comprised 30 men and 21 women, and the median EFS for all patients was 23 months (ranging from 1.25 to 60.9 months).
 

Promising biomarkers

The researchers found that patients who had high serum levels of the proteins sCD23 (P = .026), sCD27 (P = .04), the serine peptidase inhibitor SPINT1 (P = .001), and the surface antigen protein LY9 (P = .0003) had a shorter EFS than those with marker levels below the median.

“Taken together, our results validate the prognostic impact of sCD23 and highlight SPINT1 and LY9 as possible promising markers for treatment response in CLL patients,” the researchers stated.

“Despite the relatively small number of available cases, which had an impact on statistical power, our pilot study identified SPINT1 and LY9 as promising independent prognostic proteomic markers next to sCD23 and sCD27 in patients treated for CLL. Further studies with larger sample sizes are required to validate these results,” the researchers concluded.

This research was supported by a grant from Gilead Sciences and an EU TRANSCAN/Dutch Cancer Society grant. The authors declared that they had no conflicts of interest.

mlesney@mdedge.com

SOURCE: Hosnijeh FS et al. Exp Hematol. 2020;89:55-60.

Two new protein biomarkers may serve as prognostic indicators for outcomes in chronic lymphocytic leukemia (CLL) patients, according to the results of a proteomic assessment of patients’ serum compared to their event-free survival (EFS).

The results were published in Experimental Hematology.

The study attempted to validate the prognostic ability of known proteomic markers measured pretreatment and to search for new proteomic markers that might be related to treatment response in CLL, according to Fatemeh Saberi Hosnijeh, MD, of Erasmus MC, University Medical Center, Rotterdam, The Netherlands, and colleagues.

Baseline serum samples were taken from 51 CLL patients who were then treated with chemoimmunotherapy. The samples were analyzed for 360 proteomic markers, and those results were compared with patient EFS.

Study subjects were selected from patients enrolled in the HOVON 109 clinical trial, a phase 1/2 trial designed to assess the efficacy and safety of first-line therapy involving chlorambucil, rituximab,and lenalidomide in elderly patients and young frail patients with advanced CLL.

The patients assessed comprised 30 men and 21 women, and the median EFS for all patients was 23 months (ranging from 1.25 to 60.9 months).
 

Promising biomarkers

The researchers found that patients who had high serum levels of the proteins sCD23 (P = .026), sCD27 (P = .04), the serine peptidase inhibitor SPINT1 (P = .001), and the surface antigen protein LY9 (P = .0003) had a shorter EFS than those with marker levels below the median.

“Taken together, our results validate the prognostic impact of sCD23 and highlight SPINT1 and LY9 as possible promising markers for treatment response in CLL patients,” the researchers stated.

“Despite the relatively small number of available cases, which had an impact on statistical power, our pilot study identified SPINT1 and LY9 as promising independent prognostic proteomic markers next to sCD23 and sCD27 in patients treated for CLL. Further studies with larger sample sizes are required to validate these results,” the researchers concluded.

This research was supported by a grant from Gilead Sciences and an EU TRANSCAN/Dutch Cancer Society grant. The authors declared that they had no conflicts of interest.

mlesney@mdedge.com

SOURCE: Hosnijeh FS et al. Exp Hematol. 2020;89:55-60.

Two new protein biomarkers may serve as prognostic indicators for outcomes in chronic lymphocytic leukemia (CLL) patients, according to the results of a proteomic assessment of patients’ serum compared to their event-free survival (EFS).

The results were published in Experimental Hematology.

The study attempted to validate the prognostic ability of known proteomic markers measured pretreatment and to search for new proteomic markers that might be related to treatment response in CLL, according to Fatemeh Saberi Hosnijeh, MD, of Erasmus MC, University Medical Center, Rotterdam, The Netherlands, and colleagues.

Baseline serum samples were taken from 51 CLL patients who were then treated with chemoimmunotherapy. The samples were analyzed for 360 proteomic markers, and those results were compared with patient EFS.

Study subjects were selected from patients enrolled in the HOVON 109 clinical trial, a phase 1/2 trial designed to assess the efficacy and safety of first-line therapy involving chlorambucil, rituximab,and lenalidomide in elderly patients and young frail patients with advanced CLL.

The patients assessed comprised 30 men and 21 women, and the median EFS for all patients was 23 months (ranging from 1.25 to 60.9 months).
 

Promising biomarkers

The researchers found that patients who had high serum levels of the proteins sCD23 (P = .026), sCD27 (P = .04), the serine peptidase inhibitor SPINT1 (P = .001), and the surface antigen protein LY9 (P = .0003) had a shorter EFS than those with marker levels below the median.

“Taken together, our results validate the prognostic impact of sCD23 and highlight SPINT1 and LY9 as possible promising markers for treatment response in CLL patients,” the researchers stated.

“Despite the relatively small number of available cases, which had an impact on statistical power, our pilot study identified SPINT1 and LY9 as promising independent prognostic proteomic markers next to sCD23 and sCD27 in patients treated for CLL. Further studies with larger sample sizes are required to validate these results,” the researchers concluded.

This research was supported by a grant from Gilead Sciences and an EU TRANSCAN/Dutch Cancer Society grant. The authors declared that they had no conflicts of interest.

mlesney@mdedge.com

SOURCE: Hosnijeh FS et al. Exp Hematol. 2020;89:55-60.

In the wake of the COVID-19 pandemic, the virtual medical meeting is now the norm. And while it’s admirable that key data are being disseminated (often for free), there is no escaping the fact that it is a fundamentally different and lesser experience.

Watching from home, most of us split our attention between live streams of the meeting and work and family obligations. There is far less urgency when early live presentations are recorded and can be viewed later.

In terms of discussing the data, Twitter may offer broader participation than a live meeting, yet only a small number of attendees actively engage online.

And the exhibit halls for these online meetings? With neither free coffee nor company-branded tchotchkes, I expect that they have virtual tumbleweeds blowing through and crickets chirping.

Even still, the virtual meeting experience, while inferior to the live one, is a tremendous advance. It should never be banished as a historical footnote but rather should remain an option. It’s analogous to watching the Super Bowl at home: Obviously, it’s not the same as being there, but it’s a terrific alternative. Like telemedicine, this pandemic has provided a critical proof of concept that there is a better model.
 

Reshaping the medical meeting

Let’s consider five reasons why medical meetings should be permanently reshaped by this pandemic.

This pandemic isn’t going away in 2020. While nearly every country has done a far better job than the United States of containing COVID-19 thus far, outbreaks remain a problem wherever crowds assemble. You’d be hard-pressed to devise a setting more conducive to mass spread than a conference of 20,000 attendees from all over the world sitting alongside each other cheek to jowl for 5 days. Worse yet is the thought of them returning home and infecting their patients, families, and friends. What medical society wants to be remembered for creating a COVID-19 superspreader event? Professional medical societies will need to offer this option as the safest alternative moving forward.

Virtual learning still conveys the most important content. Despite the many social benefits of a live meeting, its core purpose is to disseminate new research and current and emerging treatment options. Virtual meetings have proven that this format can effectively deliver the content, and not as a secondary offering but as the sole platform in real time.

Virtual learning levels the playing field. Traveling to attend conferences typically costs thousands of dollars, accounting for the registration fees, inflated hotel rates, ground transportation, and meals out for days on end. Most meetings also demand several days away from our work and families, forcing many of us to work extra in the days before we leave and upon our return. Parents and those with commitments at home also face special challenges. For international participants, the financial and time costs are even greater. A virtual meeting helps overcome these hurdles and erases barriers that have long precluded many from attending a conference.

Virtual learning is efficient and comfortable. Virtual meetings over the past 6 months have given us a glimpse of an astonishingly more efficient form. If the content seems of a lower magnitude without the fanfare of a live conference, it is in part because so much of a live meeting is spent walking a mile between session rooms, waiting in concession or taxi lines, sitting in traffic between venues, or simply waiting for a session to begin. All of that has been replaced with time that you can use productively in between video sessions viewed either live or on demand. And with a virtual meeting, you can comfortably watch the sessions. There’s no need to stand along the back wall of an overcrowded room or step over 10 people to squeeze into an open middle seat. You can be focused, rather than having an end-of-day presentation wash over you as your eyes cross because you’ve been running around for the past 12 hours.

Virtual learning and social media will only improve. While virtual meetings unquestionably have limitations, it’s important to acknowledge that the successes thus far still represent only the earliest forays into this endeavor. In-person meetings evolved to their present form over centuries. In contrast, virtual meetings are being cobbled together within a few weeks or months. They can only be expected to improve as presenters adapt their skills to the online audience and new tools improve virtual discussions.

I am not implying that live meetings will or should be replaced by virtual ones. We still need that experience of trainees and experts presenting to a live audience and discussing the results together, all while sharing the energy of the moment. But there should be room for both a live conference and a virtual version.

Practically speaking, it is unclear whether professional societies could forgo the revenue they receive from registration fees, meeting sponsorships, and corporate exhibits. Yet, there are certainly ways to obtain sponsorship revenue for a virtual program. Even if the virtual version of a conference costs far less than attending in person, there is plenty of room between that number and free. It costs remarkably little for a professional society to share its content, and virtual offerings further the mission of distributing this content broadly.

We should not rush to return to the previous status quo. Despite their limitations, virtual meetings have brought a new, higher standard of access and efficiency for sharing important new data and treatment options in medicine.

H. Jack West, MD, associate clinical professor and executive director of employer services at City of Hope Comprehensive Cancer Center in Duarte, Calif., regularly comments on lung cancer for Medscape. West serves as web editor for JAMA Oncology, edits and writes several sections on lung cancer for UpToDate, and leads a wide range of continuing education programs and other educational programs, including hosting the audio podcast West Wind.

This article first appeared on Medscape.com.

In the wake of the COVID-19 pandemic, the virtual medical meeting is now the norm. And while it’s admirable that key data are being disseminated (often for free), there is no escaping the fact that it is a fundamentally different and lesser experience.

Watching from home, most of us split our attention between live streams of the meeting and work and family obligations. There is far less urgency when early live presentations are recorded and can be viewed later.

In terms of discussing the data, Twitter may offer broader participation than a live meeting, yet only a small number of attendees actively engage online.

And the exhibit halls for these online meetings? With neither free coffee nor company-branded tchotchkes, I expect that they have virtual tumbleweeds blowing through and crickets chirping.

Even still, the virtual meeting experience, while inferior to the live one, is a tremendous advance. It should never be banished as a historical footnote but rather should remain an option. It’s analogous to watching the Super Bowl at home: Obviously, it’s not the same as being there, but it’s a terrific alternative. Like telemedicine, this pandemic has provided a critical proof of concept that there is a better model.
 

Reshaping the medical meeting

Let’s consider five reasons why medical meetings should be permanently reshaped by this pandemic.

This pandemic isn’t going away in 2020. While nearly every country has done a far better job than the United States of containing COVID-19 thus far, outbreaks remain a problem wherever crowds assemble. You’d be hard-pressed to devise a setting more conducive to mass spread than a conference of 20,000 attendees from all over the world sitting alongside each other cheek to jowl for 5 days. Worse yet is the thought of them returning home and infecting their patients, families, and friends. What medical society wants to be remembered for creating a COVID-19 superspreader event? Professional medical societies will need to offer this option as the safest alternative moving forward.

Virtual learning still conveys the most important content. Despite the many social benefits of a live meeting, its core purpose is to disseminate new research and current and emerging treatment options. Virtual meetings have proven that this format can effectively deliver the content, and not as a secondary offering but as the sole platform in real time.

Virtual learning levels the playing field. Traveling to attend conferences typically costs thousands of dollars, accounting for the registration fees, inflated hotel rates, ground transportation, and meals out for days on end. Most meetings also demand several days away from our work and families, forcing many of us to work extra in the days before we leave and upon our return. Parents and those with commitments at home also face special challenges. For international participants, the financial and time costs are even greater. A virtual meeting helps overcome these hurdles and erases barriers that have long precluded many from attending a conference.

Virtual learning is efficient and comfortable. Virtual meetings over the past 6 months have given us a glimpse of an astonishingly more efficient form. If the content seems of a lower magnitude without the fanfare of a live conference, it is in part because so much of a live meeting is spent walking a mile between session rooms, waiting in concession or taxi lines, sitting in traffic between venues, or simply waiting for a session to begin. All of that has been replaced with time that you can use productively in between video sessions viewed either live or on demand. And with a virtual meeting, you can comfortably watch the sessions. There’s no need to stand along the back wall of an overcrowded room or step over 10 people to squeeze into an open middle seat. You can be focused, rather than having an end-of-day presentation wash over you as your eyes cross because you’ve been running around for the past 12 hours.

Virtual learning and social media will only improve. While virtual meetings unquestionably have limitations, it’s important to acknowledge that the successes thus far still represent only the earliest forays into this endeavor. In-person meetings evolved to their present form over centuries. In contrast, virtual meetings are being cobbled together within a few weeks or months. They can only be expected to improve as presenters adapt their skills to the online audience and new tools improve virtual discussions.

I am not implying that live meetings will or should be replaced by virtual ones. We still need that experience of trainees and experts presenting to a live audience and discussing the results together, all while sharing the energy of the moment. But there should be room for both a live conference and a virtual version.

Practically speaking, it is unclear whether professional societies could forgo the revenue they receive from registration fees, meeting sponsorships, and corporate exhibits. Yet, there are certainly ways to obtain sponsorship revenue for a virtual program. Even if the virtual version of a conference costs far less than attending in person, there is plenty of room between that number and free. It costs remarkably little for a professional society to share its content, and virtual offerings further the mission of distributing this content broadly.

We should not rush to return to the previous status quo. Despite their limitations, virtual meetings have brought a new, higher standard of access and efficiency for sharing important new data and treatment options in medicine.

H. Jack West, MD, associate clinical professor and executive director of employer services at City of Hope Comprehensive Cancer Center in Duarte, Calif., regularly comments on lung cancer for Medscape. West serves as web editor for JAMA Oncology, edits and writes several sections on lung cancer for UpToDate, and leads a wide range of continuing education programs and other educational programs, including hosting the audio podcast West Wind.

This article first appeared on Medscape.com.

In the wake of the COVID-19 pandemic, the virtual medical meeting is now the norm. And while it’s admirable that key data are being disseminated (often for free), there is no escaping the fact that it is a fundamentally different and lesser experience.

Watching from home, most of us split our attention between live streams of the meeting and work and family obligations. There is far less urgency when early live presentations are recorded and can be viewed later.

In terms of discussing the data, Twitter may offer broader participation than a live meeting, yet only a small number of attendees actively engage online.

And the exhibit halls for these online meetings? With neither free coffee nor company-branded tchotchkes, I expect that they have virtual tumbleweeds blowing through and crickets chirping.

Even still, the virtual meeting experience, while inferior to the live one, is a tremendous advance. It should never be banished as a historical footnote but rather should remain an option. It’s analogous to watching the Super Bowl at home: Obviously, it’s not the same as being there, but it’s a terrific alternative. Like telemedicine, this pandemic has provided a critical proof of concept that there is a better model.
 

Reshaping the medical meeting

Let’s consider five reasons why medical meetings should be permanently reshaped by this pandemic.

This pandemic isn’t going away in 2020. While nearly every country has done a far better job than the United States of containing COVID-19 thus far, outbreaks remain a problem wherever crowds assemble. You’d be hard-pressed to devise a setting more conducive to mass spread than a conference of 20,000 attendees from all over the world sitting alongside each other cheek to jowl for 5 days. Worse yet is the thought of them returning home and infecting their patients, families, and friends. What medical society wants to be remembered for creating a COVID-19 superspreader event? Professional medical societies will need to offer this option as the safest alternative moving forward.

Virtual learning still conveys the most important content. Despite the many social benefits of a live meeting, its core purpose is to disseminate new research and current and emerging treatment options. Virtual meetings have proven that this format can effectively deliver the content, and not as a secondary offering but as the sole platform in real time.

Virtual learning levels the playing field. Traveling to attend conferences typically costs thousands of dollars, accounting for the registration fees, inflated hotel rates, ground transportation, and meals out for days on end. Most meetings also demand several days away from our work and families, forcing many of us to work extra in the days before we leave and upon our return. Parents and those with commitments at home also face special challenges. For international participants, the financial and time costs are even greater. A virtual meeting helps overcome these hurdles and erases barriers that have long precluded many from attending a conference.

Virtual learning is efficient and comfortable. Virtual meetings over the past 6 months have given us a glimpse of an astonishingly more efficient form. If the content seems of a lower magnitude without the fanfare of a live conference, it is in part because so much of a live meeting is spent walking a mile between session rooms, waiting in concession or taxi lines, sitting in traffic between venues, or simply waiting for a session to begin. All of that has been replaced with time that you can use productively in between video sessions viewed either live or on demand. And with a virtual meeting, you can comfortably watch the sessions. There’s no need to stand along the back wall of an overcrowded room or step over 10 people to squeeze into an open middle seat. You can be focused, rather than having an end-of-day presentation wash over you as your eyes cross because you’ve been running around for the past 12 hours.

Virtual learning and social media will only improve. While virtual meetings unquestionably have limitations, it’s important to acknowledge that the successes thus far still represent only the earliest forays into this endeavor. In-person meetings evolved to their present form over centuries. In contrast, virtual meetings are being cobbled together within a few weeks or months. They can only be expected to improve as presenters adapt their skills to the online audience and new tools improve virtual discussions.

I am not implying that live meetings will or should be replaced by virtual ones. We still need that experience of trainees and experts presenting to a live audience and discussing the results together, all while sharing the energy of the moment. But there should be room for both a live conference and a virtual version.

Practically speaking, it is unclear whether professional societies could forgo the revenue they receive from registration fees, meeting sponsorships, and corporate exhibits. Yet, there are certainly ways to obtain sponsorship revenue for a virtual program. Even if the virtual version of a conference costs far less than attending in person, there is plenty of room between that number and free. It costs remarkably little for a professional society to share its content, and virtual offerings further the mission of distributing this content broadly.

We should not rush to return to the previous status quo. Despite their limitations, virtual meetings have brought a new, higher standard of access and efficiency for sharing important new data and treatment options in medicine.

H. Jack West, MD, associate clinical professor and executive director of employer services at City of Hope Comprehensive Cancer Center in Duarte, Calif., regularly comments on lung cancer for Medscape. West serves as web editor for JAMA Oncology, edits and writes several sections on lung cancer for UpToDate, and leads a wide range of continuing education programs and other educational programs, including hosting the audio podcast West Wind.

This article first appeared on Medscape.com.

The largest study of its kind has found no positive association between personal use of permanent hair dye and the risk for most cancers and cancer mortality.

The findings come from the Nurses’ Health Study, an ongoing prospective cohort study of more than 117,000 women who have been followed for 36 years and who did not have cancer at baseline.

The findings were published online on September 2 in the BMJ.

The results “offer some reassurance against concerns that personal use of permanent hair dyes might be associated with increased cancer risk or mortality,” write the investigators, with first author Yin Zhang, PhD, of Harvard Medical School, Boston.

The findings, which are limited to White women in the United States, indicate correlation, not causation, the authors emphasize.

Nevertheless, the researchers found an increased risk for some cancers among hair dye users, especially with greater cumulative dose (200 or more uses during the study period). The risk was increased for basal cell carcinoma, breast cancer (specifically, estrogen receptor negative [ER–], progesterone receptor negative [PR–], and hormone receptor negative [ER–, PR–]), and ovarian cancer.

A British expert not involved in the study dismissed these findings. “The reported associations are very weak, and, given the number of associations reported in this manuscript, they are very likely to be chance findings,” commented Paul Pharoah, PhD, professor of cancer epidemiology at the University of Cambridge (England).

“For the cancers where an increase in risk is reported, the results are not compelling. Even if they were real findings, the associations may not be cause-and-effect, and, even if they were causal associations, the magnitude of the effects are so small that any risk would be trivial.

“In short, none of the findings reported in this manuscript suggest that women who use hair dye are putting themselves at increased risk of cancer,” he stated.

A U.S. researcher who has previously coauthored a study suggesting an association between hair dye and breast cancer agreed that the increases in risk reported in this current study are “small.” But they are “of interest,” especially for breast and ovarian cancer, said Alexandra White, PhD, of the National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, N.C.

Hair dyes include compounds that “are not just potential carcinogens but also act as endocrine disruptors,” she said in an interview.

“In both breast and ovarian cancer, we know that hormones play an important part in the etiology ... so it’s biologically plausible that you would see [these associations in the current study],” added Dr. White, who was approached for comment.

However, she added that, even with the “modest” 20%-28% increase in the relative risk for certain breast cancers linked to a heavy cumulative dose of dyes in the current study, “there doesn’t seem to be any strong association with any cancer type.”

But she also pointed out that the most outstanding risk association was among ER–/PR– breast cancers, which are the “most aggressive and difficult to treat,” and thus the new findings are “important.”

Dr. White is the lead author of a 2019 study that received a lot of media attention because it rang an alarm bell about hair dyes and breast cancer risk.

That study concluded that ever using permanent hair dye or hair straighteners was associated with a higher risk for breast cancer than never using them and that this higher risk was especially associated with Black women. However, the study participants were from the prospective Sister Study. The participants in that study had no history of breast cancer, but they each had at least one sister who did. This family history of breast cancer may represent selection bias.
 

With changes in the 1980s, even safer now?

The study of hair dyes and cancer has “major public health implications” because the use of hair dye is widespread, Dr. Zhang and colleagues write in their article. They estimate that 50% to 80% of women and 10% of men aged 40 years and older in the United States and Europe use hair dye.

Permanent hair dyes “pose the greatest potential concern,” they stated, adding that these account for approximately 80% of hair dyes used in the United States and Europe and an even higher percentage in Asia.

The International Agency for Research on Cancer classifies occupational exposure to hair dyes as probably carcinogenic, but the carcinogenicity resulting from personal use of hair dyes is not classifiable – thus, there is no warning about at-home usage.

Notably, there was “a huge and very important” change in hair dye ingredients in the 1980s after the Food and Drug Administration warned about some chemicals in permanent hair dyes and the cosmetic industry altered their formulas, lead author Dr. Zhang said.

However, the researchers could not analyze use before and after the changes because not enough women reported first use of permanent hair dye after 1980 (only 1890 of 117,200 participants).

“We could expect that the current ingredients should make it safer,” Dr. Zhang said.
 

Study details

The researchers report that ever-users of permanent hair dyes had no significant increases in risk for solid cancers (n = 20,805; hazard ratio, 0.98, 95% confidence interval, 0.96-1.01) or hematopoietic cancers overall (n = 1,807; HR, 1.00; 95% CI, 0.91-1.10) compared with nonusers.

Additionally, ever-users did not have an increased risk for most specific cancers or cancer-related death (n = 4,860; HR, 0.96; 95% CI, 0.91-1.02).

As noted above, there were some exceptions.

Basal cell carcinoma risk was slightly increased for ever-users (n = 22,560; HR, 1.05; 95% CI, 1.02-1.08). Cumulative dose (a calculation of duration and frequency) was positively associated with risk for ER– breast cancer, PR– breast cancer, ER–/PR– breast cancer, and ovarian cancer, with risk rising in accordance with the total amount of dye.

Notably, at a cumulative dose of ≥200 uses, there was a 20% increase in the relative risk for ER- breast cancer (n = 1521; HR, 1.20; 95% CI, 1.02-1.41; P value for trend, .03). At the same cumulative dose, there was a 28% increase in the relative risk for ER-/PR- breast cancer (n = 1287; HR, 1.28, 95% CI, 1.08-1.52; P value for trend, .006).

In addition, an increased risk for Hodgkin lymphoma was observed, but only for women with naturally dark hair (the calculation was based on 70 women, 24 of whom had dark hair).

In a press statement, senior author Eva Schernhammer, PhD, of Harvard and the Medical University of Vienna, said the results “justify further prospective validation.”

She also explained that there are many variables to consider in this research, including different populations and countries, different susceptibility genotypes, different exposure settings (personal use vs. occupational exposure), and different colors of the permanent hair dyes used (dark dyes vs. light dyes).

Geographic location is a particularly important variable, suggested the study authors.

They pointed out that Europe, but not the United States, banned some individual hair dye ingredients that were considered carcinogenic during both the 1980s and 2000s. One country has even tighter oversight: “The most restrictive regulation of hair dyes exists in Japan, where cosmetic products are considered equivalent to drugs.”

The study was funded by the Centers for Disease Control and Prevention and the National Institute for Occupational Safety and Health. The study authors and Dr. White have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The largest study of its kind has found no positive association between personal use of permanent hair dye and the risk for most cancers and cancer mortality.

The findings come from the Nurses’ Health Study, an ongoing prospective cohort study of more than 117,000 women who have been followed for 36 years and who did not have cancer at baseline.

The findings were published online on September 2 in the BMJ.

The results “offer some reassurance against concerns that personal use of permanent hair dyes might be associated with increased cancer risk or mortality,” write the investigators, with first author Yin Zhang, PhD, of Harvard Medical School, Boston.

The findings, which are limited to White women in the United States, indicate correlation, not causation, the authors emphasize.

Nevertheless, the researchers found an increased risk for some cancers among hair dye users, especially with greater cumulative dose (200 or more uses during the study period). The risk was increased for basal cell carcinoma, breast cancer (specifically, estrogen receptor negative [ER–], progesterone receptor negative [PR–], and hormone receptor negative [ER–, PR–]), and ovarian cancer.

A British expert not involved in the study dismissed these findings. “The reported associations are very weak, and, given the number of associations reported in this manuscript, they are very likely to be chance findings,” commented Paul Pharoah, PhD, professor of cancer epidemiology at the University of Cambridge (England).

“For the cancers where an increase in risk is reported, the results are not compelling. Even if they were real findings, the associations may not be cause-and-effect, and, even if they were causal associations, the magnitude of the effects are so small that any risk would be trivial.

“In short, none of the findings reported in this manuscript suggest that women who use hair dye are putting themselves at increased risk of cancer,” he stated.

A U.S. researcher who has previously coauthored a study suggesting an association between hair dye and breast cancer agreed that the increases in risk reported in this current study are “small.” But they are “of interest,” especially for breast and ovarian cancer, said Alexandra White, PhD, of the National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, N.C.

Hair dyes include compounds that “are not just potential carcinogens but also act as endocrine disruptors,” she said in an interview.

“In both breast and ovarian cancer, we know that hormones play an important part in the etiology ... so it’s biologically plausible that you would see [these associations in the current study],” added Dr. White, who was approached for comment.

However, she added that, even with the “modest” 20%-28% increase in the relative risk for certain breast cancers linked to a heavy cumulative dose of dyes in the current study, “there doesn’t seem to be any strong association with any cancer type.”

But she also pointed out that the most outstanding risk association was among ER–/PR– breast cancers, which are the “most aggressive and difficult to treat,” and thus the new findings are “important.”

Dr. White is the lead author of a 2019 study that received a lot of media attention because it rang an alarm bell about hair dyes and breast cancer risk.

That study concluded that ever using permanent hair dye or hair straighteners was associated with a higher risk for breast cancer than never using them and that this higher risk was especially associated with Black women. However, the study participants were from the prospective Sister Study. The participants in that study had no history of breast cancer, but they each had at least one sister who did. This family history of breast cancer may represent selection bias.
 

With changes in the 1980s, even safer now?

The study of hair dyes and cancer has “major public health implications” because the use of hair dye is widespread, Dr. Zhang and colleagues write in their article. They estimate that 50% to 80% of women and 10% of men aged 40 years and older in the United States and Europe use hair dye.

Permanent hair dyes “pose the greatest potential concern,” they stated, adding that these account for approximately 80% of hair dyes used in the United States and Europe and an even higher percentage in Asia.

The International Agency for Research on Cancer classifies occupational exposure to hair dyes as probably carcinogenic, but the carcinogenicity resulting from personal use of hair dyes is not classifiable – thus, there is no warning about at-home usage.

Notably, there was “a huge and very important” change in hair dye ingredients in the 1980s after the Food and Drug Administration warned about some chemicals in permanent hair dyes and the cosmetic industry altered their formulas, lead author Dr. Zhang said.

However, the researchers could not analyze use before and after the changes because not enough women reported first use of permanent hair dye after 1980 (only 1890 of 117,200 participants).

“We could expect that the current ingredients should make it safer,” Dr. Zhang said.
 

Study details

The researchers report that ever-users of permanent hair dyes had no significant increases in risk for solid cancers (n = 20,805; hazard ratio, 0.98, 95% confidence interval, 0.96-1.01) or hematopoietic cancers overall (n = 1,807; HR, 1.00; 95% CI, 0.91-1.10) compared with nonusers.

Additionally, ever-users did not have an increased risk for most specific cancers or cancer-related death (n = 4,860; HR, 0.96; 95% CI, 0.91-1.02).

As noted above, there were some exceptions.

Basal cell carcinoma risk was slightly increased for ever-users (n = 22,560; HR, 1.05; 95% CI, 1.02-1.08). Cumulative dose (a calculation of duration and frequency) was positively associated with risk for ER– breast cancer, PR– breast cancer, ER–/PR– breast cancer, and ovarian cancer, with risk rising in accordance with the total amount of dye.

Notably, at a cumulative dose of ≥200 uses, there was a 20% increase in the relative risk for ER- breast cancer (n = 1521; HR, 1.20; 95% CI, 1.02-1.41; P value for trend, .03). At the same cumulative dose, there was a 28% increase in the relative risk for ER-/PR- breast cancer (n = 1287; HR, 1.28, 95% CI, 1.08-1.52; P value for trend, .006).

In addition, an increased risk for Hodgkin lymphoma was observed, but only for women with naturally dark hair (the calculation was based on 70 women, 24 of whom had dark hair).

In a press statement, senior author Eva Schernhammer, PhD, of Harvard and the Medical University of Vienna, said the results “justify further prospective validation.”

She also explained that there are many variables to consider in this research, including different populations and countries, different susceptibility genotypes, different exposure settings (personal use vs. occupational exposure), and different colors of the permanent hair dyes used (dark dyes vs. light dyes).

Geographic location is a particularly important variable, suggested the study authors.

They pointed out that Europe, but not the United States, banned some individual hair dye ingredients that were considered carcinogenic during both the 1980s and 2000s. One country has even tighter oversight: “The most restrictive regulation of hair dyes exists in Japan, where cosmetic products are considered equivalent to drugs.”

The study was funded by the Centers for Disease Control and Prevention and the National Institute for Occupational Safety and Health. The study authors and Dr. White have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The largest study of its kind has found no positive association between personal use of permanent hair dye and the risk for most cancers and cancer mortality.

The findings come from the Nurses’ Health Study, an ongoing prospective cohort study of more than 117,000 women who have been followed for 36 years and who did not have cancer at baseline.

The findings were published online on September 2 in the BMJ.

The results “offer some reassurance against concerns that personal use of permanent hair dyes might be associated with increased cancer risk or mortality,” write the investigators, with first author Yin Zhang, PhD, of Harvard Medical School, Boston.

The findings, which are limited to White women in the United States, indicate correlation, not causation, the authors emphasize.

Nevertheless, the researchers found an increased risk for some cancers among hair dye users, especially with greater cumulative dose (200 or more uses during the study period). The risk was increased for basal cell carcinoma, breast cancer (specifically, estrogen receptor negative [ER–], progesterone receptor negative [PR–], and hormone receptor negative [ER–, PR–]), and ovarian cancer.

A British expert not involved in the study dismissed these findings. “The reported associations are very weak, and, given the number of associations reported in this manuscript, they are very likely to be chance findings,” commented Paul Pharoah, PhD, professor of cancer epidemiology at the University of Cambridge (England).

“For the cancers where an increase in risk is reported, the results are not compelling. Even if they were real findings, the associations may not be cause-and-effect, and, even if they were causal associations, the magnitude of the effects are so small that any risk would be trivial.

“In short, none of the findings reported in this manuscript suggest that women who use hair dye are putting themselves at increased risk of cancer,” he stated.

A U.S. researcher who has previously coauthored a study suggesting an association between hair dye and breast cancer agreed that the increases in risk reported in this current study are “small.” But they are “of interest,” especially for breast and ovarian cancer, said Alexandra White, PhD, of the National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, N.C.

Hair dyes include compounds that “are not just potential carcinogens but also act as endocrine disruptors,” she said in an interview.

“In both breast and ovarian cancer, we know that hormones play an important part in the etiology ... so it’s biologically plausible that you would see [these associations in the current study],” added Dr. White, who was approached for comment.

However, she added that, even with the “modest” 20%-28% increase in the relative risk for certain breast cancers linked to a heavy cumulative dose of dyes in the current study, “there doesn’t seem to be any strong association with any cancer type.”

But she also pointed out that the most outstanding risk association was among ER–/PR– breast cancers, which are the “most aggressive and difficult to treat,” and thus the new findings are “important.”

Dr. White is the lead author of a 2019 study that received a lot of media attention because it rang an alarm bell about hair dyes and breast cancer risk.

That study concluded that ever using permanent hair dye or hair straighteners was associated with a higher risk for breast cancer than never using them and that this higher risk was especially associated with Black women. However, the study participants were from the prospective Sister Study. The participants in that study had no history of breast cancer, but they each had at least one sister who did. This family history of breast cancer may represent selection bias.
 

With changes in the 1980s, even safer now?

The study of hair dyes and cancer has “major public health implications” because the use of hair dye is widespread, Dr. Zhang and colleagues write in their article. They estimate that 50% to 80% of women and 10% of men aged 40 years and older in the United States and Europe use hair dye.

Permanent hair dyes “pose the greatest potential concern,” they stated, adding that these account for approximately 80% of hair dyes used in the United States and Europe and an even higher percentage in Asia.

The International Agency for Research on Cancer classifies occupational exposure to hair dyes as probably carcinogenic, but the carcinogenicity resulting from personal use of hair dyes is not classifiable – thus, there is no warning about at-home usage.

Notably, there was “a huge and very important” change in hair dye ingredients in the 1980s after the Food and Drug Administration warned about some chemicals in permanent hair dyes and the cosmetic industry altered their formulas, lead author Dr. Zhang said.

However, the researchers could not analyze use before and after the changes because not enough women reported first use of permanent hair dye after 1980 (only 1890 of 117,200 participants).

“We could expect that the current ingredients should make it safer,” Dr. Zhang said.
 

Study details

The researchers report that ever-users of permanent hair dyes had no significant increases in risk for solid cancers (n = 20,805; hazard ratio, 0.98, 95% confidence interval, 0.96-1.01) or hematopoietic cancers overall (n = 1,807; HR, 1.00; 95% CI, 0.91-1.10) compared with nonusers.

Additionally, ever-users did not have an increased risk for most specific cancers or cancer-related death (n = 4,860; HR, 0.96; 95% CI, 0.91-1.02).

As noted above, there were some exceptions.

Basal cell carcinoma risk was slightly increased for ever-users (n = 22,560; HR, 1.05; 95% CI, 1.02-1.08). Cumulative dose (a calculation of duration and frequency) was positively associated with risk for ER– breast cancer, PR– breast cancer, ER–/PR– breast cancer, and ovarian cancer, with risk rising in accordance with the total amount of dye.

Notably, at a cumulative dose of ≥200 uses, there was a 20% increase in the relative risk for ER- breast cancer (n = 1521; HR, 1.20; 95% CI, 1.02-1.41; P value for trend, .03). At the same cumulative dose, there was a 28% increase in the relative risk for ER-/PR- breast cancer (n = 1287; HR, 1.28, 95% CI, 1.08-1.52; P value for trend, .006).

In addition, an increased risk for Hodgkin lymphoma was observed, but only for women with naturally dark hair (the calculation was based on 70 women, 24 of whom had dark hair).

In a press statement, senior author Eva Schernhammer, PhD, of Harvard and the Medical University of Vienna, said the results “justify further prospective validation.”

She also explained that there are many variables to consider in this research, including different populations and countries, different susceptibility genotypes, different exposure settings (personal use vs. occupational exposure), and different colors of the permanent hair dyes used (dark dyes vs. light dyes).

Geographic location is a particularly important variable, suggested the study authors.

They pointed out that Europe, but not the United States, banned some individual hair dye ingredients that were considered carcinogenic during both the 1980s and 2000s. One country has even tighter oversight: “The most restrictive regulation of hair dyes exists in Japan, where cosmetic products are considered equivalent to drugs.”

The study was funded by the Centers for Disease Control and Prevention and the National Institute for Occupational Safety and Health. The study authors and Dr. White have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.