Lung Cancer

A new study links the COVID-19 pandemic to decreased lung cancer diagnoses, changes in disease severity, and worsened outcomes for patients with lung cancer.

The two-center study showed a 38% decrease in new lung cancer diagnoses during the pandemic. Patients diagnosed with non–small cell lung cancer (NSCLC) during the pandemic had more severe disease than patients diagnosed prepandemic, but cases of SCLC were not more severe during the pandemic. Still, the 30-day mortality rate nearly doubled for both NSCLC and SCLC patients during the pandemic.

“The prioritization of the health care system towards COVID-19 patients has led to drastic changes in cancer management that could interfere with the initial diagnosis of lung cancer, resulting in delayed treatment and worse outcomes,” said Roxana Reyes, MD, of Hospital Clínic de Barcelona. “Delay of cancer treatment is associated with increased mortality.”

Dr. Reyes and colleagues conducted a retrospective study of the impact of COVID-19 on the incidence of new lung cancer cases, disease severity, and clinical outcomes. Dr. Reyes reported the group’s findings at the 2020 World Conference on Lung Cancer (Abstract 3700), which was rescheduled for January 2021.
 

Study details

Dr. Reyes and colleagues compared data from two tertiary hospitals in Spain in the first 6 months of 2020 with data from the same period in 2019. Spain was one of the countries most affected by COVID-19 during the first wave of the pandemic.

The study’s primary endpoint was differences by period in the number of new lung cancer cases and disease severity. A secondary endpoint was 30-day mortality rate by period and histology.

The study included 162 patients newly diagnosed with lung cancer – 100 diagnosed before the pandemic began and 62 diagnosed during the pandemic. Overall, 68% of patients had NSCLC, and 32% had SCLC.

Baseline characteristics were similar between the prepandemic and pandemic groups, except for the proportion of nonsmokers. Twice as many patients diagnosed during the pandemic were nonsmokers (16% vs. 8%).
 

Differences by time period and subtype

During the pandemic, there was a 38% reduction in all lung cancer diagnoses, a 36% reduction in NSCLC diagnoses, and a 42% reduction in SCLC diagnoses.

Respiratory symptoms were more common during the pandemic for both NSCLC (30% vs. 23%) and SCLC (32% vs. 24%).

Cases of NSCLC diagnosed during the pandemic were more severe, but SCLC cases were not.

In the NSCLC cohort, symptomatic disease was more common during the pandemic (74% vs. 63%), as were advanced disease (58% vs. 46%), more than two metastatic sites (16% vs. 12%), oncologic emergencies (7% vs. 3%), hospitalization (21% vs. 18%), and death during hospitalization (44% vs. 17%).

For SCLC, symptomatic disease was less common during the pandemic (74% vs. 79%), as were advanced disease (52% vs. 67%), more than two metastatic sites (26% vs. 36%), oncologic emergencies (5% vs. 12%), hospitalization (21% vs. 33%), and death during hospitalization (0% vs. 18%).

Nevertheless, the 30-day mortality rate almost doubled during the pandemic for both NSCLC (49% vs. 25%) and SCLC (32% vs. 18%).

For both subtypes together, the median overall survival was 6.7 months during the pandemic and 7.9 months before the pandemic.
 

Implications and next steps

“In our descriptive study, lung cancer diagnosis is being affected during the COVID-19 pandemic,” Dr. Reyes said. “Fewer new lung cancer cases were diagnosed during COVID-19.”

Some patients with acute respiratory infections who tested negative for COVID-19 during the first 6 months of the pandemic may have had undiagnosed lung cancer, noted Matthew Peters, MD, of Concord Repatriation General Hospital and Macquarie University Hospital, both in Sydney, who was not involved in this study.

“They receive a negative result and think their problem is reduced but wonder why they still have a cough,” Dr. Peters said. “The various lockdowns and social distancing reduced the diagnosis of respiratory viral illnesses that often result in an accidental diagnosis of lung cancer. As time goes by, we will recapture harvesting of accidental diagnosis of lung cancer and provide curative treatments.”

Dr. Reyes emphasized that strategies for maintaining cancer diagnoses need to be implemented during the pandemic. She also noted that this study is ongoing, with the goal of assessing the long-term impact of COVID-19.

Dr. Reyes disclosed relationships with Roche, Bristol-Myers Squibb, and Merck Sharp & Dohme. She did not disclose funding for this study. Dr. Peters disclosed relationships with Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche, and Takeda.

A new study links the COVID-19 pandemic to decreased lung cancer diagnoses, changes in disease severity, and worsened outcomes for patients with lung cancer.

The two-center study showed a 38% decrease in new lung cancer diagnoses during the pandemic. Patients diagnosed with non–small cell lung cancer (NSCLC) during the pandemic had more severe disease than patients diagnosed prepandemic, but cases of SCLC were not more severe during the pandemic. Still, the 30-day mortality rate nearly doubled for both NSCLC and SCLC patients during the pandemic.

“The prioritization of the health care system towards COVID-19 patients has led to drastic changes in cancer management that could interfere with the initial diagnosis of lung cancer, resulting in delayed treatment and worse outcomes,” said Roxana Reyes, MD, of Hospital Clínic de Barcelona. “Delay of cancer treatment is associated with increased mortality.”

Dr. Reyes and colleagues conducted a retrospective study of the impact of COVID-19 on the incidence of new lung cancer cases, disease severity, and clinical outcomes. Dr. Reyes reported the group’s findings at the 2020 World Conference on Lung Cancer (Abstract 3700), which was rescheduled for January 2021.
 

Study details

Dr. Reyes and colleagues compared data from two tertiary hospitals in Spain in the first 6 months of 2020 with data from the same period in 2019. Spain was one of the countries most affected by COVID-19 during the first wave of the pandemic.

The study’s primary endpoint was differences by period in the number of new lung cancer cases and disease severity. A secondary endpoint was 30-day mortality rate by period and histology.

The study included 162 patients newly diagnosed with lung cancer – 100 diagnosed before the pandemic began and 62 diagnosed during the pandemic. Overall, 68% of patients had NSCLC, and 32% had SCLC.

Baseline characteristics were similar between the prepandemic and pandemic groups, except for the proportion of nonsmokers. Twice as many patients diagnosed during the pandemic were nonsmokers (16% vs. 8%).
 

Differences by time period and subtype

During the pandemic, there was a 38% reduction in all lung cancer diagnoses, a 36% reduction in NSCLC diagnoses, and a 42% reduction in SCLC diagnoses.

Respiratory symptoms were more common during the pandemic for both NSCLC (30% vs. 23%) and SCLC (32% vs. 24%).

Cases of NSCLC diagnosed during the pandemic were more severe, but SCLC cases were not.

In the NSCLC cohort, symptomatic disease was more common during the pandemic (74% vs. 63%), as were advanced disease (58% vs. 46%), more than two metastatic sites (16% vs. 12%), oncologic emergencies (7% vs. 3%), hospitalization (21% vs. 18%), and death during hospitalization (44% vs. 17%).

For SCLC, symptomatic disease was less common during the pandemic (74% vs. 79%), as were advanced disease (52% vs. 67%), more than two metastatic sites (26% vs. 36%), oncologic emergencies (5% vs. 12%), hospitalization (21% vs. 33%), and death during hospitalization (0% vs. 18%).

Nevertheless, the 30-day mortality rate almost doubled during the pandemic for both NSCLC (49% vs. 25%) and SCLC (32% vs. 18%).

For both subtypes together, the median overall survival was 6.7 months during the pandemic and 7.9 months before the pandemic.
 

Implications and next steps

“In our descriptive study, lung cancer diagnosis is being affected during the COVID-19 pandemic,” Dr. Reyes said. “Fewer new lung cancer cases were diagnosed during COVID-19.”

Some patients with acute respiratory infections who tested negative for COVID-19 during the first 6 months of the pandemic may have had undiagnosed lung cancer, noted Matthew Peters, MD, of Concord Repatriation General Hospital and Macquarie University Hospital, both in Sydney, who was not involved in this study.

“They receive a negative result and think their problem is reduced but wonder why they still have a cough,” Dr. Peters said. “The various lockdowns and social distancing reduced the diagnosis of respiratory viral illnesses that often result in an accidental diagnosis of lung cancer. As time goes by, we will recapture harvesting of accidental diagnosis of lung cancer and provide curative treatments.”

Dr. Reyes emphasized that strategies for maintaining cancer diagnoses need to be implemented during the pandemic. She also noted that this study is ongoing, with the goal of assessing the long-term impact of COVID-19.

Dr. Reyes disclosed relationships with Roche, Bristol-Myers Squibb, and Merck Sharp & Dohme. She did not disclose funding for this study. Dr. Peters disclosed relationships with Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche, and Takeda.

A new study links the COVID-19 pandemic to decreased lung cancer diagnoses, changes in disease severity, and worsened outcomes for patients with lung cancer.

The two-center study showed a 38% decrease in new lung cancer diagnoses during the pandemic. Patients diagnosed with non–small cell lung cancer (NSCLC) during the pandemic had more severe disease than patients diagnosed prepandemic, but cases of SCLC were not more severe during the pandemic. Still, the 30-day mortality rate nearly doubled for both NSCLC and SCLC patients during the pandemic.

“The prioritization of the health care system towards COVID-19 patients has led to drastic changes in cancer management that could interfere with the initial diagnosis of lung cancer, resulting in delayed treatment and worse outcomes,” said Roxana Reyes, MD, of Hospital Clínic de Barcelona. “Delay of cancer treatment is associated with increased mortality.”

Dr. Reyes and colleagues conducted a retrospective study of the impact of COVID-19 on the incidence of new lung cancer cases, disease severity, and clinical outcomes. Dr. Reyes reported the group’s findings at the 2020 World Conference on Lung Cancer (Abstract 3700), which was rescheduled for January 2021.
 

Study details

Dr. Reyes and colleagues compared data from two tertiary hospitals in Spain in the first 6 months of 2020 with data from the same period in 2019. Spain was one of the countries most affected by COVID-19 during the first wave of the pandemic.

The study’s primary endpoint was differences by period in the number of new lung cancer cases and disease severity. A secondary endpoint was 30-day mortality rate by period and histology.

The study included 162 patients newly diagnosed with lung cancer – 100 diagnosed before the pandemic began and 62 diagnosed during the pandemic. Overall, 68% of patients had NSCLC, and 32% had SCLC.

Baseline characteristics were similar between the prepandemic and pandemic groups, except for the proportion of nonsmokers. Twice as many patients diagnosed during the pandemic were nonsmokers (16% vs. 8%).
 

Differences by time period and subtype

During the pandemic, there was a 38% reduction in all lung cancer diagnoses, a 36% reduction in NSCLC diagnoses, and a 42% reduction in SCLC diagnoses.

Respiratory symptoms were more common during the pandemic for both NSCLC (30% vs. 23%) and SCLC (32% vs. 24%).

Cases of NSCLC diagnosed during the pandemic were more severe, but SCLC cases were not.

In the NSCLC cohort, symptomatic disease was more common during the pandemic (74% vs. 63%), as were advanced disease (58% vs. 46%), more than two metastatic sites (16% vs. 12%), oncologic emergencies (7% vs. 3%), hospitalization (21% vs. 18%), and death during hospitalization (44% vs. 17%).

For SCLC, symptomatic disease was less common during the pandemic (74% vs. 79%), as were advanced disease (52% vs. 67%), more than two metastatic sites (26% vs. 36%), oncologic emergencies (5% vs. 12%), hospitalization (21% vs. 33%), and death during hospitalization (0% vs. 18%).

Nevertheless, the 30-day mortality rate almost doubled during the pandemic for both NSCLC (49% vs. 25%) and SCLC (32% vs. 18%).

For both subtypes together, the median overall survival was 6.7 months during the pandemic and 7.9 months before the pandemic.
 

Implications and next steps

“In our descriptive study, lung cancer diagnosis is being affected during the COVID-19 pandemic,” Dr. Reyes said. “Fewer new lung cancer cases were diagnosed during COVID-19.”

Some patients with acute respiratory infections who tested negative for COVID-19 during the first 6 months of the pandemic may have had undiagnosed lung cancer, noted Matthew Peters, MD, of Concord Repatriation General Hospital and Macquarie University Hospital, both in Sydney, who was not involved in this study.

“They receive a negative result and think their problem is reduced but wonder why they still have a cough,” Dr. Peters said. “The various lockdowns and social distancing reduced the diagnosis of respiratory viral illnesses that often result in an accidental diagnosis of lung cancer. As time goes by, we will recapture harvesting of accidental diagnosis of lung cancer and provide curative treatments.”

Dr. Reyes emphasized that strategies for maintaining cancer diagnoses need to be implemented during the pandemic. She also noted that this study is ongoing, with the goal of assessing the long-term impact of COVID-19.

Dr. Reyes disclosed relationships with Roche, Bristol-Myers Squibb, and Merck Sharp & Dohme. She did not disclose funding for this study. Dr. Peters disclosed relationships with Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche, and Takeda.

All patients receiving active cancer treatment should receive a COVID-19 vaccine and should be prioritized for vaccination, according to preliminary recommendations from the National Comprehensive Cancer Network (NCCN).

Vaccination timing considerations vary based on factors such as cancer and treatment type, and reasons for delaying vaccination in the general public also apply to cancer patients (recent COVID-19 exposure, for example).

In general, however, patients with cancer should be assigned to Centers for Disease Control and Prevention priority group 1 b/c and immunized when vaccination is available to them, the guidelines state. Exceptions to this recommendation include:

• Patients undergoing hematopoietic stem cell transplant or receiving engineered cellular therapy such as chimeric antigen receptor T-cell therapy. Vaccination should be delayed for at least 3 months in these patients to maximize vaccine efficacy. Caregivers of these patients, however, should be immunized when possible.
• Patients with hematologic malignancies who are receiving intensive cytotoxic chemotherapy, such as cytarabine- or anthracycline-based regimens for acute myeloid leukemia. Vaccination in these patients should be delayed until absolute neutrophil count recovery.
• Patients undergoing major surgery. Vaccination should occur at least a few days before or after surgery.
• Patients who have experienced a severe or immediate adverse reaction to any of the ingredients in the mRNA COVID-19 vaccines.

Conversely, vaccination should occur when available in patients with hematologic malignancies and marrow failure who are expected to have limited or no recovery, patients with hematologic malignancies who are on long-term maintenance therapy, and patients with solid tumors who are receiving cytotoxic chemotherapy, targeted therapy, checkpoint inhibitors and other immunotherapy, or radiotherapy.

Caregivers, household contacts, and other close contacts who are 16 years of age and older should be vaccinated whenever they are eligible.
 

Unique concerns in patients with cancer

The NCCN recommendations were developed to address the unique issues and concerns with respect to patients with cancer, who have an increased risk of severe illness from SARS-CoV-2 infection. But the guidelines come with a caveat: “[t]here are limited safety and efficacy data in these patients,” the NCCN emphasized in a press statement.

“Right now, there is urgent need and limited data,” Steven Pergam, MD, co-leader of the NCCN COVID-19 Vaccination Committee, said in the statement.

“Our number one goal is helping to get the vaccine to as many people as we can,” Dr. Pergam said. “That means following existing national and regional directions for prioritizing people who are more likely to face death or severe illness from COVID-19.”

Dr. Pergam, associate professor at Fred Hutchinson Cancer Research Center in Seattle, further explained that “people receiving active cancer treatment are at greater risk for worse outcomes from COVID-19, particularly if they are older and have additional comorbidities, like immunosuppression.”

NCCN’s recommendations couldn’t have come at a better time for patients with cancer, according to Nora Disis, MD, a professor at the University of Washington in Seattle.

“The NCCN’s recommendations to prioritize COVID vaccinations for cancer patients on active treatment is an important step forward in protecting our patients from the infection,” Dr. Disis said in an interview.

“Cancer patients may be at higher risk for the complications seen with infection. In addition, cancer is a disease of older people, and a good number of our patients have the comorbidities that would predict a poorer outcome if they should become sick,” Dr. Disis added. “With the correct treatment, many patients with cancer will be long-term survivors. It is important that they be protected from infection with COVID to realize their best outcome.”
 

Additional vaccine considerations

The NCCN recommendations also address several other issues of importance for cancer patients, including:

• Deprioritizing other vaccines. COVID-19 vaccines should take precedence over other vaccines because data on dual vaccination are lacking. The NCCN recommends waiting 14 days after COVID-19 vaccination to deliver other vaccines.
• Vaccinating clinical trial participants. Trial leads should be consulted to prevent protocol violations or exclusions.
• Decision-making in the setting of limited vaccine availability. The NCCN noted that decisions on allocation must be made in accordance with state and local vaccine guidance but suggests prioritizing appropriate patients on active treatment, those planning to start treatment, and those who have just completed treatment. Additional risk factors for these patients, as well as other factors associated with risk for adverse COVID-19 outcomes, should also be considered. These include advanced age, comorbidities, and adverse social and demographic factors such as poverty and limited health care access.
• The need for ongoing prevention measures. Vaccines have been shown to decrease the incidence of COVID-19 and related complications, but it remains unclear whether vaccines prevent infection and subsequent transmission. This means everyone should continue following prevention recommendations, such as wearing masks and avoiding crowds.

The NCCN stressed that these recommendations are “intended to be a living document that is constantly evolving – it will be updated rapidly whenever new data comes out, as well as any potential new vaccines that may get approved in the future.” The NCCN also noted that the advisory committee will meet regularly to refine the recommendations as needed.

Dr. Pergam disclosed relationships with Chimerix Inc., Merck & Co., Global Life Technologies Inc., and Sanofi-Aventis. Dr. Disis disclosed grants from Pfizer, Bavarian Nordisk, Janssen, and Precigen. She is the founder of EpiThany and editor-in-chief of JAMA Oncology.

sworcester@mdedge.com

All patients receiving active cancer treatment should receive a COVID-19 vaccine and should be prioritized for vaccination, according to preliminary recommendations from the National Comprehensive Cancer Network (NCCN).

Vaccination timing considerations vary based on factors such as cancer and treatment type, and reasons for delaying vaccination in the general public also apply to cancer patients (recent COVID-19 exposure, for example).

In general, however, patients with cancer should be assigned to Centers for Disease Control and Prevention priority group 1 b/c and immunized when vaccination is available to them, the guidelines state. Exceptions to this recommendation include:

• Patients undergoing hematopoietic stem cell transplant or receiving engineered cellular therapy such as chimeric antigen receptor T-cell therapy. Vaccination should be delayed for at least 3 months in these patients to maximize vaccine efficacy. Caregivers of these patients, however, should be immunized when possible.
• Patients with hematologic malignancies who are receiving intensive cytotoxic chemotherapy, such as cytarabine- or anthracycline-based regimens for acute myeloid leukemia. Vaccination in these patients should be delayed until absolute neutrophil count recovery.
• Patients undergoing major surgery. Vaccination should occur at least a few days before or after surgery.
• Patients who have experienced a severe or immediate adverse reaction to any of the ingredients in the mRNA COVID-19 vaccines.

Conversely, vaccination should occur when available in patients with hematologic malignancies and marrow failure who are expected to have limited or no recovery, patients with hematologic malignancies who are on long-term maintenance therapy, and patients with solid tumors who are receiving cytotoxic chemotherapy, targeted therapy, checkpoint inhibitors and other immunotherapy, or radiotherapy.

Caregivers, household contacts, and other close contacts who are 16 years of age and older should be vaccinated whenever they are eligible.
 

Unique concerns in patients with cancer

The NCCN recommendations were developed to address the unique issues and concerns with respect to patients with cancer, who have an increased risk of severe illness from SARS-CoV-2 infection. But the guidelines come with a caveat: “[t]here are limited safety and efficacy data in these patients,” the NCCN emphasized in a press statement.

“Right now, there is urgent need and limited data,” Steven Pergam, MD, co-leader of the NCCN COVID-19 Vaccination Committee, said in the statement.

“Our number one goal is helping to get the vaccine to as many people as we can,” Dr. Pergam said. “That means following existing national and regional directions for prioritizing people who are more likely to face death or severe illness from COVID-19.”

Dr. Pergam, associate professor at Fred Hutchinson Cancer Research Center in Seattle, further explained that “people receiving active cancer treatment are at greater risk for worse outcomes from COVID-19, particularly if they are older and have additional comorbidities, like immunosuppression.”

NCCN’s recommendations couldn’t have come at a better time for patients with cancer, according to Nora Disis, MD, a professor at the University of Washington in Seattle.

“The NCCN’s recommendations to prioritize COVID vaccinations for cancer patients on active treatment is an important step forward in protecting our patients from the infection,” Dr. Disis said in an interview.

“Cancer patients may be at higher risk for the complications seen with infection. In addition, cancer is a disease of older people, and a good number of our patients have the comorbidities that would predict a poorer outcome if they should become sick,” Dr. Disis added. “With the correct treatment, many patients with cancer will be long-term survivors. It is important that they be protected from infection with COVID to realize their best outcome.”
 

Additional vaccine considerations

The NCCN recommendations also address several other issues of importance for cancer patients, including:

• Deprioritizing other vaccines. COVID-19 vaccines should take precedence over other vaccines because data on dual vaccination are lacking. The NCCN recommends waiting 14 days after COVID-19 vaccination to deliver other vaccines.
• Vaccinating clinical trial participants. Trial leads should be consulted to prevent protocol violations or exclusions.
• Decision-making in the setting of limited vaccine availability. The NCCN noted that decisions on allocation must be made in accordance with state and local vaccine guidance but suggests prioritizing appropriate patients on active treatment, those planning to start treatment, and those who have just completed treatment. Additional risk factors for these patients, as well as other factors associated with risk for adverse COVID-19 outcomes, should also be considered. These include advanced age, comorbidities, and adverse social and demographic factors such as poverty and limited health care access.
• The need for ongoing prevention measures. Vaccines have been shown to decrease the incidence of COVID-19 and related complications, but it remains unclear whether vaccines prevent infection and subsequent transmission. This means everyone should continue following prevention recommendations, such as wearing masks and avoiding crowds.

The NCCN stressed that these recommendations are “intended to be a living document that is constantly evolving – it will be updated rapidly whenever new data comes out, as well as any potential new vaccines that may get approved in the future.” The NCCN also noted that the advisory committee will meet regularly to refine the recommendations as needed.

Dr. Pergam disclosed relationships with Chimerix Inc., Merck & Co., Global Life Technologies Inc., and Sanofi-Aventis. Dr. Disis disclosed grants from Pfizer, Bavarian Nordisk, Janssen, and Precigen. She is the founder of EpiThany and editor-in-chief of JAMA Oncology.

sworcester@mdedge.com

All patients receiving active cancer treatment should receive a COVID-19 vaccine and should be prioritized for vaccination, according to preliminary recommendations from the National Comprehensive Cancer Network (NCCN).

Vaccination timing considerations vary based on factors such as cancer and treatment type, and reasons for delaying vaccination in the general public also apply to cancer patients (recent COVID-19 exposure, for example).

In general, however, patients with cancer should be assigned to Centers for Disease Control and Prevention priority group 1 b/c and immunized when vaccination is available to them, the guidelines state. Exceptions to this recommendation include:

• Patients undergoing hematopoietic stem cell transplant or receiving engineered cellular therapy such as chimeric antigen receptor T-cell therapy. Vaccination should be delayed for at least 3 months in these patients to maximize vaccine efficacy. Caregivers of these patients, however, should be immunized when possible.
• Patients with hematologic malignancies who are receiving intensive cytotoxic chemotherapy, such as cytarabine- or anthracycline-based regimens for acute myeloid leukemia. Vaccination in these patients should be delayed until absolute neutrophil count recovery.
• Patients undergoing major surgery. Vaccination should occur at least a few days before or after surgery.
• Patients who have experienced a severe or immediate adverse reaction to any of the ingredients in the mRNA COVID-19 vaccines.

Conversely, vaccination should occur when available in patients with hematologic malignancies and marrow failure who are expected to have limited or no recovery, patients with hematologic malignancies who are on long-term maintenance therapy, and patients with solid tumors who are receiving cytotoxic chemotherapy, targeted therapy, checkpoint inhibitors and other immunotherapy, or radiotherapy.

Caregivers, household contacts, and other close contacts who are 16 years of age and older should be vaccinated whenever they are eligible.
 

Unique concerns in patients with cancer

The NCCN recommendations were developed to address the unique issues and concerns with respect to patients with cancer, who have an increased risk of severe illness from SARS-CoV-2 infection. But the guidelines come with a caveat: “[t]here are limited safety and efficacy data in these patients,” the NCCN emphasized in a press statement.

“Right now, there is urgent need and limited data,” Steven Pergam, MD, co-leader of the NCCN COVID-19 Vaccination Committee, said in the statement.

“Our number one goal is helping to get the vaccine to as many people as we can,” Dr. Pergam said. “That means following existing national and regional directions for prioritizing people who are more likely to face death or severe illness from COVID-19.”

Dr. Pergam, associate professor at Fred Hutchinson Cancer Research Center in Seattle, further explained that “people receiving active cancer treatment are at greater risk for worse outcomes from COVID-19, particularly if they are older and have additional comorbidities, like immunosuppression.”

NCCN’s recommendations couldn’t have come at a better time for patients with cancer, according to Nora Disis, MD, a professor at the University of Washington in Seattle.

“The NCCN’s recommendations to prioritize COVID vaccinations for cancer patients on active treatment is an important step forward in protecting our patients from the infection,” Dr. Disis said in an interview.

“Cancer patients may be at higher risk for the complications seen with infection. In addition, cancer is a disease of older people, and a good number of our patients have the comorbidities that would predict a poorer outcome if they should become sick,” Dr. Disis added. “With the correct treatment, many patients with cancer will be long-term survivors. It is important that they be protected from infection with COVID to realize their best outcome.”
 

Additional vaccine considerations

The NCCN recommendations also address several other issues of importance for cancer patients, including:

• Deprioritizing other vaccines. COVID-19 vaccines should take precedence over other vaccines because data on dual vaccination are lacking. The NCCN recommends waiting 14 days after COVID-19 vaccination to deliver other vaccines.
• Vaccinating clinical trial participants. Trial leads should be consulted to prevent protocol violations or exclusions.
• Decision-making in the setting of limited vaccine availability. The NCCN noted that decisions on allocation must be made in accordance with state and local vaccine guidance but suggests prioritizing appropriate patients on active treatment, those planning to start treatment, and those who have just completed treatment. Additional risk factors for these patients, as well as other factors associated with risk for adverse COVID-19 outcomes, should also be considered. These include advanced age, comorbidities, and adverse social and demographic factors such as poverty and limited health care access.
• The need for ongoing prevention measures. Vaccines have been shown to decrease the incidence of COVID-19 and related complications, but it remains unclear whether vaccines prevent infection and subsequent transmission. This means everyone should continue following prevention recommendations, such as wearing masks and avoiding crowds.

The NCCN stressed that these recommendations are “intended to be a living document that is constantly evolving – it will be updated rapidly whenever new data comes out, as well as any potential new vaccines that may get approved in the future.” The NCCN also noted that the advisory committee will meet regularly to refine the recommendations as needed.

Dr. Pergam disclosed relationships with Chimerix Inc., Merck & Co., Global Life Technologies Inc., and Sanofi-Aventis. Dr. Disis disclosed grants from Pfizer, Bavarian Nordisk, Janssen, and Precigen. She is the founder of EpiThany and editor-in-chief of JAMA Oncology.

sworcester@mdedge.com

A model that crunches data from routine blood tests can accurately identify cancer patients who will develop acute kidney injury (AKI) up to a month before it happens, according to a cohort study.

The algorithm spotted nearly 74% of the patients who went on to develop AKI within 30 days, providing a window for intervention and possibly prevention, according to investigators.

These results were reported at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (abstract PR-11).

“Cancer patients are a high-risk population for AKI due to the nature of their treatment and illness,” said presenter Lauren A. Scanlon, PhD, a data scientist at The Christie NHS Foundation Trust in Huddersfield, England. “AKI causes a huge disruption in treatment and distress for the patient, so it would be amazing if we could, say, predict the AKI before it occurs and prevent it from even happening.”

U.K. health care providers are already using an algorithm to monitor patients’ creatinine levels, comparing new values against historic ones, Dr. Scanlon explained. When that algorithm detects AKI, it issues an alert that triggers implementation of an AKI care bundle, including measures such as fluid monitoring and medication review, within 24 hours.

Taking this concept further, Dr. Scanlon and colleagues developed a random forest model, a type of machine learning algorithm, that incorporates other markers from blood tests routinely obtained for all patients, with the aim of predicting AKI up to 30 days in advance.

“Using routinely collected blood test results will ensure that the model is applicable to all our patients and can be implemented in an automated manner,” Dr. Scanlon noted.

The investigators developed and trained the model using 597,403 blood test results from 48,865 patients undergoing cancer treatment between January 2017 and May 2020.

The model assigns patients to five categories of risk for AKI in the next 30 days: very low, low, medium, high, and very high.

“We wanted the model to output in this way so that it could be used by clinicians alongside their own insight and knowledge on a case-by-case basis,” Dr. Scanlon explained.

The investigators then prospectively validated the model and its risk categories in another 9,913 patients who underwent cancer treatment between June and August 2020.

Using a model threshold of medium risk or higher, the model correctly predicted AKI in 330 (73.8%) of the 447 patients in the validation cohort who ultimately developed AKI.

“This is pretty amazing and shows that this model really is working and can correctly detect these AKIs up to 30 days before they occur, giving a huge window to put in place preventive strategies,” Dr. Scanlon said.

Among the 154 patients in whom the model incorrectly predicted AKI, 9 patients had only a single follow-up blood test and 17 patients did not have any, leaving their actual outcomes unclear.

“Given that AKI detection uses blood tests, an AKI in these patients was never confirmed,” Dr. Scanlon noted. “So this could give a potential benefit of the model that we never intended: It could reduce undiagnosed AKI by flagging those who are at risk.”

“Our next steps are to test the model through a technology clinical trial to see if putting intervention strategies in place does prevent these AKIs from taking place,” Dr. Scanlon concluded. “We are also going to move to ongoing monitoring of the model performance.”

Dr. Scanlon disclosed no conflicts of interest. The study did not receive specific funding.

A model that crunches data from routine blood tests can accurately identify cancer patients who will develop acute kidney injury (AKI) up to a month before it happens, according to a cohort study.

The algorithm spotted nearly 74% of the patients who went on to develop AKI within 30 days, providing a window for intervention and possibly prevention, according to investigators.

These results were reported at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (abstract PR-11).

“Cancer patients are a high-risk population for AKI due to the nature of their treatment and illness,” said presenter Lauren A. Scanlon, PhD, a data scientist at The Christie NHS Foundation Trust in Huddersfield, England. “AKI causes a huge disruption in treatment and distress for the patient, so it would be amazing if we could, say, predict the AKI before it occurs and prevent it from even happening.”

U.K. health care providers are already using an algorithm to monitor patients’ creatinine levels, comparing new values against historic ones, Dr. Scanlon explained. When that algorithm detects AKI, it issues an alert that triggers implementation of an AKI care bundle, including measures such as fluid monitoring and medication review, within 24 hours.

Taking this concept further, Dr. Scanlon and colleagues developed a random forest model, a type of machine learning algorithm, that incorporates other markers from blood tests routinely obtained for all patients, with the aim of predicting AKI up to 30 days in advance.

“Using routinely collected blood test results will ensure that the model is applicable to all our patients and can be implemented in an automated manner,” Dr. Scanlon noted.

The investigators developed and trained the model using 597,403 blood test results from 48,865 patients undergoing cancer treatment between January 2017 and May 2020.

The model assigns patients to five categories of risk for AKI in the next 30 days: very low, low, medium, high, and very high.

“We wanted the model to output in this way so that it could be used by clinicians alongside their own insight and knowledge on a case-by-case basis,” Dr. Scanlon explained.

The investigators then prospectively validated the model and its risk categories in another 9,913 patients who underwent cancer treatment between June and August 2020.

Using a model threshold of medium risk or higher, the model correctly predicted AKI in 330 (73.8%) of the 447 patients in the validation cohort who ultimately developed AKI.

“This is pretty amazing and shows that this model really is working and can correctly detect these AKIs up to 30 days before they occur, giving a huge window to put in place preventive strategies,” Dr. Scanlon said.

Among the 154 patients in whom the model incorrectly predicted AKI, 9 patients had only a single follow-up blood test and 17 patients did not have any, leaving their actual outcomes unclear.

“Given that AKI detection uses blood tests, an AKI in these patients was never confirmed,” Dr. Scanlon noted. “So this could give a potential benefit of the model that we never intended: It could reduce undiagnosed AKI by flagging those who are at risk.”

“Our next steps are to test the model through a technology clinical trial to see if putting intervention strategies in place does prevent these AKIs from taking place,” Dr. Scanlon concluded. “We are also going to move to ongoing monitoring of the model performance.”

Dr. Scanlon disclosed no conflicts of interest. The study did not receive specific funding.

A model that crunches data from routine blood tests can accurately identify cancer patients who will develop acute kidney injury (AKI) up to a month before it happens, according to a cohort study.

The algorithm spotted nearly 74% of the patients who went on to develop AKI within 30 days, providing a window for intervention and possibly prevention, according to investigators.

These results were reported at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (abstract PR-11).

“Cancer patients are a high-risk population for AKI due to the nature of their treatment and illness,” said presenter Lauren A. Scanlon, PhD, a data scientist at The Christie NHS Foundation Trust in Huddersfield, England. “AKI causes a huge disruption in treatment and distress for the patient, so it would be amazing if we could, say, predict the AKI before it occurs and prevent it from even happening.”

U.K. health care providers are already using an algorithm to monitor patients’ creatinine levels, comparing new values against historic ones, Dr. Scanlon explained. When that algorithm detects AKI, it issues an alert that triggers implementation of an AKI care bundle, including measures such as fluid monitoring and medication review, within 24 hours.

Taking this concept further, Dr. Scanlon and colleagues developed a random forest model, a type of machine learning algorithm, that incorporates other markers from blood tests routinely obtained for all patients, with the aim of predicting AKI up to 30 days in advance.

“Using routinely collected blood test results will ensure that the model is applicable to all our patients and can be implemented in an automated manner,” Dr. Scanlon noted.

The investigators developed and trained the model using 597,403 blood test results from 48,865 patients undergoing cancer treatment between January 2017 and May 2020.

The model assigns patients to five categories of risk for AKI in the next 30 days: very low, low, medium, high, and very high.

“We wanted the model to output in this way so that it could be used by clinicians alongside their own insight and knowledge on a case-by-case basis,” Dr. Scanlon explained.

The investigators then prospectively validated the model and its risk categories in another 9,913 patients who underwent cancer treatment between June and August 2020.

Using a model threshold of medium risk or higher, the model correctly predicted AKI in 330 (73.8%) of the 447 patients in the validation cohort who ultimately developed AKI.

“This is pretty amazing and shows that this model really is working and can correctly detect these AKIs up to 30 days before they occur, giving a huge window to put in place preventive strategies,” Dr. Scanlon said.

Among the 154 patients in whom the model incorrectly predicted AKI, 9 patients had only a single follow-up blood test and 17 patients did not have any, leaving their actual outcomes unclear.

“Given that AKI detection uses blood tests, an AKI in these patients was never confirmed,” Dr. Scanlon noted. “So this could give a potential benefit of the model that we never intended: It could reduce undiagnosed AKI by flagging those who are at risk.”

“Our next steps are to test the model through a technology clinical trial to see if putting intervention strategies in place does prevent these AKIs from taking place,” Dr. Scanlon concluded. “We are also going to move to ongoing monitoring of the model performance.”

Dr. Scanlon disclosed no conflicts of interest. The study did not receive specific funding.

The molecular biomarkers of advanced non–small cell lung cancer (NSCLC) – and hence the best treatment option – may soon be identified in real time from scans, thanks to a new decision support tool that uses artificial intelligence (AI).

Researchers developed deep learning models that could accurately predict a patient’s PD-L1 and EGFR mutation status without the need for a biopsy. If these models are validated in prospective trials, they could guide treatment decisions in patients with NSCLC, according to the researchers.

Wei Mu, PhD, of Moffitt Cancer Center and Research Institute in Tampa, Fla., described this research at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (abstract PR-03).
 

Rationale

Guidelines from the National Comprehensive Cancer Network (NCCN) endorse tailored treatment for patients with NSCLC; namely, immune checkpoint inhibitors for those with PD-L1-positive tumors and EGFR tyrosine kinase inhibitors for patients with tumors harboring a mutation in EGFR.

However, the conventional approach to ascertaining tumor status for these biomarkers has disadvantages, Dr. Mu noted.

“Both require biopsy, which may fail due to insufficient quality of the tissue and, particularly for NSCLC, may increase the chance of morbidity,” Dr. Mu said.

In addition, there is room for improvement in the rigor of the biomarker assays, and there can be substantial wait times for results.

To address these issues, Dr. Mu and colleagues explored an AI radiomics approach using PET/CT scans.

“We know that EGFR mutation and positive PD-L1 expression may change the metabolism of the peritumor and intratumor microenvironment,” Dr. Mu explained. “Therefore, we had the hypothesis that they can be captured by the FDG-PET/CT images.”
 

Results

The investigators used FDG-PET/CT images from 837 patients with advanced NSCLC treated at four institutions. The team developed AI deep learning models that generated one score for PD-L1 positivity and another score for presence of an EGFR mutation, as well as an associated algorithm that would direct patients to the appropriate treatments depending on the scores.

Results for the PD-L1 deep learning score showed good accuracy in predicting positivity for this ligand, with an area under the curve of 0.89 in the training cohort, 0.84 in the validation cohort, and 0.82 in an external test cohort, Dr. Mu reported. All exceeded the corresponding areas under the curve for maximal standardized uptake values.

Moreover, the score was prognostic and statistically indistinguishable from PD-L1 status determined by immunohistochemistry in predicting progression-free survival.

Similarly, the EGFR deep learning score showed good accuracy in predicting mutational status, with an area under the curve of 0.86 in the training cohort, 0.83 in the validation cohort, and 0.81 in an external test cohort. It outperformed a clinical score based on sex, smoking status, tumor histology, and maximal standardized uptake value in each cohort.

The EGFR deep learning score was prognostic and statistically indistinguishable from EGFR mutational status determined by polymerase chain reaction in predicting progression-free survival.

The models showed good stability when size of the input region of interest was varied, and when different radiologists delineated the region of interest, with an intraclass correlation coefficient of 0.91.

“We developed deep learning models to predict PD-L1 status and EGFR mutation with high accuracy. Using the generated deep learning scores, we obtained a noninvasive treatment decision support tool, which may be useful as a clinical decision support tool pending validation of its clinical utility in a large prospective trial,” Dr. Mu summarized. “Using our tool, NSCLC patients could be directly offered a treatment decision without the need of biopsy.”

“In the future, we will perform a prospective observational trial to compare the results of our noninvasive treatment decision tool with molecular biomarker–based NCCN guidelines,” she said.

The investigators plan to add ALK rearrangement status and prediction of serious adverse events and cachexia to the decision support tool.

Dr. Mu disclosed no conflicts of interest. The study did not have specific funding.

The molecular biomarkers of advanced non–small cell lung cancer (NSCLC) – and hence the best treatment option – may soon be identified in real time from scans, thanks to a new decision support tool that uses artificial intelligence (AI).

Researchers developed deep learning models that could accurately predict a patient’s PD-L1 and EGFR mutation status without the need for a biopsy. If these models are validated in prospective trials, they could guide treatment decisions in patients with NSCLC, according to the researchers.

Wei Mu, PhD, of Moffitt Cancer Center and Research Institute in Tampa, Fla., described this research at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (abstract PR-03).
 

Rationale

Guidelines from the National Comprehensive Cancer Network (NCCN) endorse tailored treatment for patients with NSCLC; namely, immune checkpoint inhibitors for those with PD-L1-positive tumors and EGFR tyrosine kinase inhibitors for patients with tumors harboring a mutation in EGFR.

However, the conventional approach to ascertaining tumor status for these biomarkers has disadvantages, Dr. Mu noted.

“Both require biopsy, which may fail due to insufficient quality of the tissue and, particularly for NSCLC, may increase the chance of morbidity,” Dr. Mu said.

In addition, there is room for improvement in the rigor of the biomarker assays, and there can be substantial wait times for results.

To address these issues, Dr. Mu and colleagues explored an AI radiomics approach using PET/CT scans.

“We know that EGFR mutation and positive PD-L1 expression may change the metabolism of the peritumor and intratumor microenvironment,” Dr. Mu explained. “Therefore, we had the hypothesis that they can be captured by the FDG-PET/CT images.”
 

Results

The investigators used FDG-PET/CT images from 837 patients with advanced NSCLC treated at four institutions. The team developed AI deep learning models that generated one score for PD-L1 positivity and another score for presence of an EGFR mutation, as well as an associated algorithm that would direct patients to the appropriate treatments depending on the scores.

Results for the PD-L1 deep learning score showed good accuracy in predicting positivity for this ligand, with an area under the curve of 0.89 in the training cohort, 0.84 in the validation cohort, and 0.82 in an external test cohort, Dr. Mu reported. All exceeded the corresponding areas under the curve for maximal standardized uptake values.

Moreover, the score was prognostic and statistically indistinguishable from PD-L1 status determined by immunohistochemistry in predicting progression-free survival.

Similarly, the EGFR deep learning score showed good accuracy in predicting mutational status, with an area under the curve of 0.86 in the training cohort, 0.83 in the validation cohort, and 0.81 in an external test cohort. It outperformed a clinical score based on sex, smoking status, tumor histology, and maximal standardized uptake value in each cohort.

The EGFR deep learning score was prognostic and statistically indistinguishable from EGFR mutational status determined by polymerase chain reaction in predicting progression-free survival.

The models showed good stability when size of the input region of interest was varied, and when different radiologists delineated the region of interest, with an intraclass correlation coefficient of 0.91.

“We developed deep learning models to predict PD-L1 status and EGFR mutation with high accuracy. Using the generated deep learning scores, we obtained a noninvasive treatment decision support tool, which may be useful as a clinical decision support tool pending validation of its clinical utility in a large prospective trial,” Dr. Mu summarized. “Using our tool, NSCLC patients could be directly offered a treatment decision without the need of biopsy.”

“In the future, we will perform a prospective observational trial to compare the results of our noninvasive treatment decision tool with molecular biomarker–based NCCN guidelines,” she said.

The investigators plan to add ALK rearrangement status and prediction of serious adverse events and cachexia to the decision support tool.

Dr. Mu disclosed no conflicts of interest. The study did not have specific funding.

The molecular biomarkers of advanced non–small cell lung cancer (NSCLC) – and hence the best treatment option – may soon be identified in real time from scans, thanks to a new decision support tool that uses artificial intelligence (AI).

Researchers developed deep learning models that could accurately predict a patient’s PD-L1 and EGFR mutation status without the need for a biopsy. If these models are validated in prospective trials, they could guide treatment decisions in patients with NSCLC, according to the researchers.

Wei Mu, PhD, of Moffitt Cancer Center and Research Institute in Tampa, Fla., described this research at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (abstract PR-03).
 

Rationale

Guidelines from the National Comprehensive Cancer Network (NCCN) endorse tailored treatment for patients with NSCLC; namely, immune checkpoint inhibitors for those with PD-L1-positive tumors and EGFR tyrosine kinase inhibitors for patients with tumors harboring a mutation in EGFR.

However, the conventional approach to ascertaining tumor status for these biomarkers has disadvantages, Dr. Mu noted.

“Both require biopsy, which may fail due to insufficient quality of the tissue and, particularly for NSCLC, may increase the chance of morbidity,” Dr. Mu said.

In addition, there is room for improvement in the rigor of the biomarker assays, and there can be substantial wait times for results.

To address these issues, Dr. Mu and colleagues explored an AI radiomics approach using PET/CT scans.

“We know that EGFR mutation and positive PD-L1 expression may change the metabolism of the peritumor and intratumor microenvironment,” Dr. Mu explained. “Therefore, we had the hypothesis that they can be captured by the FDG-PET/CT images.”
 

Results

The investigators used FDG-PET/CT images from 837 patients with advanced NSCLC treated at four institutions. The team developed AI deep learning models that generated one score for PD-L1 positivity and another score for presence of an EGFR mutation, as well as an associated algorithm that would direct patients to the appropriate treatments depending on the scores.

Results for the PD-L1 deep learning score showed good accuracy in predicting positivity for this ligand, with an area under the curve of 0.89 in the training cohort, 0.84 in the validation cohort, and 0.82 in an external test cohort, Dr. Mu reported. All exceeded the corresponding areas under the curve for maximal standardized uptake values.

Moreover, the score was prognostic and statistically indistinguishable from PD-L1 status determined by immunohistochemistry in predicting progression-free survival.

Similarly, the EGFR deep learning score showed good accuracy in predicting mutational status, with an area under the curve of 0.86 in the training cohort, 0.83 in the validation cohort, and 0.81 in an external test cohort. It outperformed a clinical score based on sex, smoking status, tumor histology, and maximal standardized uptake value in each cohort.

The EGFR deep learning score was prognostic and statistically indistinguishable from EGFR mutational status determined by polymerase chain reaction in predicting progression-free survival.

The models showed good stability when size of the input region of interest was varied, and when different radiologists delineated the region of interest, with an intraclass correlation coefficient of 0.91.

“We developed deep learning models to predict PD-L1 status and EGFR mutation with high accuracy. Using the generated deep learning scores, we obtained a noninvasive treatment decision support tool, which may be useful as a clinical decision support tool pending validation of its clinical utility in a large prospective trial,” Dr. Mu summarized. “Using our tool, NSCLC patients could be directly offered a treatment decision without the need of biopsy.”

“In the future, we will perform a prospective observational trial to compare the results of our noninvasive treatment decision tool with molecular biomarker–based NCCN guidelines,” she said.

The investigators plan to add ALK rearrangement status and prediction of serious adverse events and cachexia to the decision support tool.

Dr. Mu disclosed no conflicts of interest. The study did not have specific funding.

Patients with rheumatoid arthritis–associated interstitial lung disease showed increases in overall mortality, respiratory mortality, and cancer mortality, compared with RA patients without interstitial lung disease, based on data from more than 500,000 patients in a nationwide cohort study.

RA-associated interstitial lung disease (RA-ILD) has been associated with worse survival rates as well as reduced quality of life, functional impairment, and increased health care use and costs, wrote Jeffrey A. Sparks, MD, of Brigham and Women’s Hospital, Boston, and colleagues. However, data on the incidence and prevalence of RA-ILD have been inconsistent and large studies are lacking.

In a study published online in Rheumatology, the researchers identified 509,787 RA patients aged 65 years and older from Medicare claims data. The average age of the patients was 72.6 years, and 76.2% were women.

At baseline, 10,306 (2%) of the study population had RA-ILD, and 13,372 (2.7%) developed RA-ILD over an average of 3.8 years’ follow-up per person (total of 1,873,127 person-years of follow-up). The overall incidence of RA-ILD was 7.14 per 1,000 person-years.

Overall mortality was significantly higher among RA-ILD patients than in those with RA alone in a multivariate analysis (38.7% vs. 20.7%; hazard ratio, 1.66).

In addition, RA-ILD was associated with an increased risk of respiratory mortality (HR, 4.39) and cancer mortality (HR, 1.56), compared with RA without ILD. For these hazard regression analyses, the researchers used Fine and Gray subdistribution HRs “to handle competing risks of alternative causes of mortality. For example, the risk of respiratory mortality for patients with RA-ILD, compared with RA without ILD also accounted for the competing risk of cardiovascular, cancer, infection and other types of mortality.”

Case courtesy A.Prof Frank Gaillard, Radiopaedia.org, rID: 12274

In another multivariate analysis, male gender, smoking, asthma, chronic obstructive pulmonary disorder, and medication use (specifically biologic disease-modifying antirheumatic drugs, targeted synthetic DMARDs, and glucocorticoids) were independently associated with increased incident RA-ILD at baseline. However, “the associations of RA-related medications with incident RA-ILD risk should be interpreted with caution since they may be explained by unmeasured factors, including RA disease activity, severity, comorbidities, and prior or concomitant medication use,” the researchers noted.

The study findings were limited by several factors, including the lack of data on disease activity, disease duration, disease severity, and RA-related autoantibodies, the researchers noted. However, the results support data from previous studies and were strengthened by the large sample size and data on demographics and health care use.

“Ours is the first to study the epidemiology and mortality outcomes of RA-ILD using a validated claims algorithm to identify RA and RA-ILD,” and “to quantify the mortality burden of RA-ILD and to identify a potentially novel association of RA-ILD with cancer mortality,” they noted.

The study was supported by an investigator-initiated grant from Bristol-Myers Squibb. Lead author Dr. Sparks disclosed support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Rheumatology Research Foundation, the Brigham Research Institute, and the R. Bruce and Joan M. Mickey Research Scholar Fund. Dr. Sparks also disclosed serving as a consultant to Bristol-Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer for work unrelated to the current study. Other authors reported research funding from Bristol-Myers Squibb, involvement in a clinical trial funded by Genentech and Bristol-Myers Squibb, and receiving research support to Brigham and Women’s Hospital for other studies from AbbVie, Bayer, Bristol-Myers Squibb, Novartis, Pfizer, Roche, and Vertex.

Patients with rheumatoid arthritis–associated interstitial lung disease showed increases in overall mortality, respiratory mortality, and cancer mortality, compared with RA patients without interstitial lung disease, based on data from more than 500,000 patients in a nationwide cohort study.

RA-associated interstitial lung disease (RA-ILD) has been associated with worse survival rates as well as reduced quality of life, functional impairment, and increased health care use and costs, wrote Jeffrey A. Sparks, MD, of Brigham and Women’s Hospital, Boston, and colleagues. However, data on the incidence and prevalence of RA-ILD have been inconsistent and large studies are lacking.

In a study published online in Rheumatology, the researchers identified 509,787 RA patients aged 65 years and older from Medicare claims data. The average age of the patients was 72.6 years, and 76.2% were women.

At baseline, 10,306 (2%) of the study population had RA-ILD, and 13,372 (2.7%) developed RA-ILD over an average of 3.8 years’ follow-up per person (total of 1,873,127 person-years of follow-up). The overall incidence of RA-ILD was 7.14 per 1,000 person-years.

Overall mortality was significantly higher among RA-ILD patients than in those with RA alone in a multivariate analysis (38.7% vs. 20.7%; hazard ratio, 1.66).

In addition, RA-ILD was associated with an increased risk of respiratory mortality (HR, 4.39) and cancer mortality (HR, 1.56), compared with RA without ILD. For these hazard regression analyses, the researchers used Fine and Gray subdistribution HRs “to handle competing risks of alternative causes of mortality. For example, the risk of respiratory mortality for patients with RA-ILD, compared with RA without ILD also accounted for the competing risk of cardiovascular, cancer, infection and other types of mortality.”

Case courtesy A.Prof Frank Gaillard, Radiopaedia.org, rID: 12274

In another multivariate analysis, male gender, smoking, asthma, chronic obstructive pulmonary disorder, and medication use (specifically biologic disease-modifying antirheumatic drugs, targeted synthetic DMARDs, and glucocorticoids) were independently associated with increased incident RA-ILD at baseline. However, “the associations of RA-related medications with incident RA-ILD risk should be interpreted with caution since they may be explained by unmeasured factors, including RA disease activity, severity, comorbidities, and prior or concomitant medication use,” the researchers noted.

The study findings were limited by several factors, including the lack of data on disease activity, disease duration, disease severity, and RA-related autoantibodies, the researchers noted. However, the results support data from previous studies and were strengthened by the large sample size and data on demographics and health care use.

“Ours is the first to study the epidemiology and mortality outcomes of RA-ILD using a validated claims algorithm to identify RA and RA-ILD,” and “to quantify the mortality burden of RA-ILD and to identify a potentially novel association of RA-ILD with cancer mortality,” they noted.

The study was supported by an investigator-initiated grant from Bristol-Myers Squibb. Lead author Dr. Sparks disclosed support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Rheumatology Research Foundation, the Brigham Research Institute, and the R. Bruce and Joan M. Mickey Research Scholar Fund. Dr. Sparks also disclosed serving as a consultant to Bristol-Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer for work unrelated to the current study. Other authors reported research funding from Bristol-Myers Squibb, involvement in a clinical trial funded by Genentech and Bristol-Myers Squibb, and receiving research support to Brigham and Women’s Hospital for other studies from AbbVie, Bayer, Bristol-Myers Squibb, Novartis, Pfizer, Roche, and Vertex.

Patients with rheumatoid arthritis–associated interstitial lung disease showed increases in overall mortality, respiratory mortality, and cancer mortality, compared with RA patients without interstitial lung disease, based on data from more than 500,000 patients in a nationwide cohort study.

RA-associated interstitial lung disease (RA-ILD) has been associated with worse survival rates as well as reduced quality of life, functional impairment, and increased health care use and costs, wrote Jeffrey A. Sparks, MD, of Brigham and Women’s Hospital, Boston, and colleagues. However, data on the incidence and prevalence of RA-ILD have been inconsistent and large studies are lacking.

In a study published online in Rheumatology, the researchers identified 509,787 RA patients aged 65 years and older from Medicare claims data. The average age of the patients was 72.6 years, and 76.2% were women.

At baseline, 10,306 (2%) of the study population had RA-ILD, and 13,372 (2.7%) developed RA-ILD over an average of 3.8 years’ follow-up per person (total of 1,873,127 person-years of follow-up). The overall incidence of RA-ILD was 7.14 per 1,000 person-years.

Overall mortality was significantly higher among RA-ILD patients than in those with RA alone in a multivariate analysis (38.7% vs. 20.7%; hazard ratio, 1.66).

In addition, RA-ILD was associated with an increased risk of respiratory mortality (HR, 4.39) and cancer mortality (HR, 1.56), compared with RA without ILD. For these hazard regression analyses, the researchers used Fine and Gray subdistribution HRs “to handle competing risks of alternative causes of mortality. For example, the risk of respiratory mortality for patients with RA-ILD, compared with RA without ILD also accounted for the competing risk of cardiovascular, cancer, infection and other types of mortality.”

Case courtesy A.Prof Frank Gaillard, Radiopaedia.org, rID: 12274

In another multivariate analysis, male gender, smoking, asthma, chronic obstructive pulmonary disorder, and medication use (specifically biologic disease-modifying antirheumatic drugs, targeted synthetic DMARDs, and glucocorticoids) were independently associated with increased incident RA-ILD at baseline. However, “the associations of RA-related medications with incident RA-ILD risk should be interpreted with caution since they may be explained by unmeasured factors, including RA disease activity, severity, comorbidities, and prior or concomitant medication use,” the researchers noted.

The study findings were limited by several factors, including the lack of data on disease activity, disease duration, disease severity, and RA-related autoantibodies, the researchers noted. However, the results support data from previous studies and were strengthened by the large sample size and data on demographics and health care use.

“Ours is the first to study the epidemiology and mortality outcomes of RA-ILD using a validated claims algorithm to identify RA and RA-ILD,” and “to quantify the mortality burden of RA-ILD and to identify a potentially novel association of RA-ILD with cancer mortality,” they noted.

The study was supported by an investigator-initiated grant from Bristol-Myers Squibb. Lead author Dr. Sparks disclosed support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Rheumatology Research Foundation, the Brigham Research Institute, and the R. Bruce and Joan M. Mickey Research Scholar Fund. Dr. Sparks also disclosed serving as a consultant to Bristol-Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer for work unrelated to the current study. Other authors reported research funding from Bristol-Myers Squibb, involvement in a clinical trial funded by Genentech and Bristol-Myers Squibb, and receiving research support to Brigham and Women’s Hospital for other studies from AbbVie, Bayer, Bristol-Myers Squibb, Novartis, Pfizer, Roche, and Vertex.

The COVID-19 pandemic led to a drastic reduction in lung cancer screening, but the rate of decline was similar between Whites and non-Whites and between rural and nonrural populations. All groups saw their rates of lung cancer screening (LCS) return to near prepandemic levels by June 2020, according to a new analysis of two academic and two community imaging sites in North Carolina.

The study was led by Louise Henderson, PhD, of the Lineberger Comprehensive Cancer Center, and M. Patricia Rivera, MD, FCCP, of the department of medicine, division of pulmonary disease and critical care medicine, both at the University of North Carolina at Chapel Hill. The findings appeared online in Chest.

“I am [not] surprised by the decline, but I am certainly reassured,” Abbie Begnaud, MD, FCCP, said in an interview. Dr. Begnaud is assistant professor of medicine at the University of Minnesota, Minneapolis. She was not involved in the study.

The COVID-19 pandemic led to a drastic reduction in lung cancer screening, but the rate of decline was similar between Whites and non-Whites and between rural and nonrural populations. All groups saw their rates of lung cancer screening (LCS) return to near prepandemic levels by June 2020, according to a new analysis of two academic and two community imaging sites in North Carolina.

The study was led by Louise Henderson, PhD, of the Lineberger Comprehensive Cancer Center, and M. Patricia Rivera, MD, FCCP, of the department of medicine, division of pulmonary disease and critical care medicine, both at the University of North Carolina at Chapel Hill. The findings appeared online in Chest.

“I am [not] surprised by the decline, but I am certainly reassured,” Abbie Begnaud, MD, FCCP, said in an interview. Dr. Begnaud is assistant professor of medicine at the University of Minnesota, Minneapolis. She was not involved in the study.

The COVID-19 pandemic led to a drastic reduction in lung cancer screening, but the rate of decline was similar between Whites and non-Whites and between rural and nonrural populations. All groups saw their rates of lung cancer screening (LCS) return to near prepandemic levels by June 2020, according to a new analysis of two academic and two community imaging sites in North Carolina.

The study was led by Louise Henderson, PhD, of the Lineberger Comprehensive Cancer Center, and M. Patricia Rivera, MD, FCCP, of the department of medicine, division of pulmonary disease and critical care medicine, both at the University of North Carolina at Chapel Hill. The findings appeared online in Chest.

“I am [not] surprised by the decline, but I am certainly reassured,” Abbie Begnaud, MD, FCCP, said in an interview. Dr. Begnaud is assistant professor of medicine at the University of Minnesota, Minneapolis. She was not involved in the study.

Nearly a quarter of ED visits were deemed preventable in a single-center study of patients with non–small cell lung cancer.

The leading cause of ED visits in the study was the cancer itself, although many visits were unrelated to non–small cell lung cancer (NSCLC) or cancer therapy.

Less than 10% of ED visits were related to cancer therapy, but visits were much more common among patients receiving chemotherapy than among those receiving immunotherapy or tyrosine kinase inhibitors (TKIs).

Manan P. Shah, MD, and Joel W. Neal, MD, PhD, both of Stanford (Calif. ) University, reported these results in JCO Oncology Practice.

The authors noted that, in the United States, care of patients with cancer, among all diseases, leads to the highest per-person cost. Unplanned hospital visits are among the largest drivers of increased spending in advanced cancer care, accounting for 48% of spending. However, that spending may not be indicative of better quality care, but rather of inefficiency, according to the authors.

One registry spanning 2009-2012 and including more than 400,000 newly diagnosed cancer patients found lung cancer to have the third-highest rate of unplanned hospitalizations (after hepatobiliary and pancreatic cancer). Those findings were published in JCO Oncology Practice in 2018.

While the reason for presentation to the ED is often the cancer or its therapy in this population, there is a paucity of research on the relative contribution of factors leading to unplanned hospital visits.

Common precipitants of medical emergencies in advanced stages of lung cancer include pulmonary embolism, obstructive pneumonia, spinal cord compression caused by metastasis, and tumor progression or pleural effusion leading to respiratory failure.

Lung cancer therapies, such as TKIs, immunotherapy, and cytotoxic chemotherapy, can also cause various medical emergencies arising out of skin reactions, gastrointestinal dysfunction, organ inflammatory processes, and bone marrow suppression.
 

Identifying drivers of unplanned ED visits

The primary goals of Dr. Shah and Dr. Neal’s study were to understand the drivers of unplanned ED visits and identify potential strategies to prevent them.

Drawing from the Stanford Medicine Research Data Repository, the authors identified 97 NSCLC patients with 173 ED visits at Stanford.

Patients were sorted according to which of the three therapies they had been receiving in the 3 months prior to the unplanned visit – TKIs (n = 47), immunotherapy (n = 24), or chemotherapy (n = 26). Patients receiving a combination of chemotherapy and immunotherapy were classified under the immunotherapy category.

ED visits were divided into four categories: cancer related, therapy related, unrelated to cancer or therapy, and rule-out (when an outpatient provider sent the patient to rule out medico-oncologic emergencies such as pulmonary embolism or cord compression).

If the patient’s main complaint(s) began 2 or more days before presentation, the diagnostics or therapeutics could have been provided in an outpatient setting (e.g., in clinic or urgent care), and the patient was discharged directly from the ED, the encounter was classified as potentially preventable. Among these preventable encounters, those made during business hours were also labeled unnecessary because they could have been managed through the Stanford sick call system for same-day urgent visits.
 

Leading cause is cancer

Overall, the leading cause of ED visits was NSCLC itself (54%). The patient’s cancer contributed to 61% of ED visits in the TKI group, 49% in the immunotherapy group, and 42% in the chemotherapy group.

Many ED visits were deemed unrelated to cancer or its therapies – 30% in the TKI group, 26% in the immunotherapy group, and 32% in the chemotherapy group.

Rule-out cases contributed to 7% of ED visits in the TKI group, 14% in the immunotherapy group, and 5% in the chemotherapy group.

Overall, 9% of ED visits were therapy related. The smallest proportion of these was observed in the TKI group (2%), which was significantly smaller than in the immunotherapy group (12%), a rate also significantly smaller than in the chemotherapy group (21%, P < .001).

Most unplanned ED visits did not lead to admissions (55%), were for complaints that began 2 or more days prior to presentation (53%), led to diagnostics or therapeutics that could have been administered in an outpatient setting (48%), and were during business hours (52%).

As a result, 24% of visits were classified as preventable, and 10% were deemed unnecessary.
 

Preventive strategies

“Our study suggests that TKIs lead to fewer emergency room visits than immunotherapy and chemotherapy,” Dr. Shah said in an interview.

“Overall, this may not necessarily change which therapy we prescribe,” he added, “as TKI therapy is often first line for patients with targeted mutations. However, recognizing that those on chemotherapy or immunotherapy are at higher risk for emergency room visits, we may target preventative strategies, for example, nursing phone calls, telemonitoring of symptoms, and frequent video visits toward this high-risk population.”

Dr. Shah and Dr. Neal said it’s “reassuring” that TKIs and immunotherapy are small drivers of unplanned hospital care. However, they also said efforts aimed at reducing chemotherapy-related ED visits are warranted.

The authors speculated that early intervention, extension of ambulatory care, and patient education about outpatient avenues of care could eliminate a significant proportion (at least 20%) of unplanned ED visits by NSCLC patients.

There was no specific funding for this study. Dr. Shah disclosed no conflicts of interest. Dr. Neal disclosed relationships with many companies, including this news organization.

Nearly a quarter of ED visits were deemed preventable in a single-center study of patients with non–small cell lung cancer.

The leading cause of ED visits in the study was the cancer itself, although many visits were unrelated to non–small cell lung cancer (NSCLC) or cancer therapy.

Less than 10% of ED visits were related to cancer therapy, but visits were much more common among patients receiving chemotherapy than among those receiving immunotherapy or tyrosine kinase inhibitors (TKIs).

Manan P. Shah, MD, and Joel W. Neal, MD, PhD, both of Stanford (Calif. ) University, reported these results in JCO Oncology Practice.

The authors noted that, in the United States, care of patients with cancer, among all diseases, leads to the highest per-person cost. Unplanned hospital visits are among the largest drivers of increased spending in advanced cancer care, accounting for 48% of spending. However, that spending may not be indicative of better quality care, but rather of inefficiency, according to the authors.

One registry spanning 2009-2012 and including more than 400,000 newly diagnosed cancer patients found lung cancer to have the third-highest rate of unplanned hospitalizations (after hepatobiliary and pancreatic cancer). Those findings were published in JCO Oncology Practice in 2018.

While the reason for presentation to the ED is often the cancer or its therapy in this population, there is a paucity of research on the relative contribution of factors leading to unplanned hospital visits.

Common precipitants of medical emergencies in advanced stages of lung cancer include pulmonary embolism, obstructive pneumonia, spinal cord compression caused by metastasis, and tumor progression or pleural effusion leading to respiratory failure.

Lung cancer therapies, such as TKIs, immunotherapy, and cytotoxic chemotherapy, can also cause various medical emergencies arising out of skin reactions, gastrointestinal dysfunction, organ inflammatory processes, and bone marrow suppression.
 

Identifying drivers of unplanned ED visits

The primary goals of Dr. Shah and Dr. Neal’s study were to understand the drivers of unplanned ED visits and identify potential strategies to prevent them.

Drawing from the Stanford Medicine Research Data Repository, the authors identified 97 NSCLC patients with 173 ED visits at Stanford.

Patients were sorted according to which of the three therapies they had been receiving in the 3 months prior to the unplanned visit – TKIs (n = 47), immunotherapy (n = 24), or chemotherapy (n = 26). Patients receiving a combination of chemotherapy and immunotherapy were classified under the immunotherapy category.

ED visits were divided into four categories: cancer related, therapy related, unrelated to cancer or therapy, and rule-out (when an outpatient provider sent the patient to rule out medico-oncologic emergencies such as pulmonary embolism or cord compression).

If the patient’s main complaint(s) began 2 or more days before presentation, the diagnostics or therapeutics could have been provided in an outpatient setting (e.g., in clinic or urgent care), and the patient was discharged directly from the ED, the encounter was classified as potentially preventable. Among these preventable encounters, those made during business hours were also labeled unnecessary because they could have been managed through the Stanford sick call system for same-day urgent visits.
 

Leading cause is cancer

Overall, the leading cause of ED visits was NSCLC itself (54%). The patient’s cancer contributed to 61% of ED visits in the TKI group, 49% in the immunotherapy group, and 42% in the chemotherapy group.

Many ED visits were deemed unrelated to cancer or its therapies – 30% in the TKI group, 26% in the immunotherapy group, and 32% in the chemotherapy group.

Rule-out cases contributed to 7% of ED visits in the TKI group, 14% in the immunotherapy group, and 5% in the chemotherapy group.

Overall, 9% of ED visits were therapy related. The smallest proportion of these was observed in the TKI group (2%), which was significantly smaller than in the immunotherapy group (12%), a rate also significantly smaller than in the chemotherapy group (21%, P < .001).

Most unplanned ED visits did not lead to admissions (55%), were for complaints that began 2 or more days prior to presentation (53%), led to diagnostics or therapeutics that could have been administered in an outpatient setting (48%), and were during business hours (52%).

As a result, 24% of visits were classified as preventable, and 10% were deemed unnecessary.
 

Preventive strategies

“Our study suggests that TKIs lead to fewer emergency room visits than immunotherapy and chemotherapy,” Dr. Shah said in an interview.

“Overall, this may not necessarily change which therapy we prescribe,” he added, “as TKI therapy is often first line for patients with targeted mutations. However, recognizing that those on chemotherapy or immunotherapy are at higher risk for emergency room visits, we may target preventative strategies, for example, nursing phone calls, telemonitoring of symptoms, and frequent video visits toward this high-risk population.”

Dr. Shah and Dr. Neal said it’s “reassuring” that TKIs and immunotherapy are small drivers of unplanned hospital care. However, they also said efforts aimed at reducing chemotherapy-related ED visits are warranted.

The authors speculated that early intervention, extension of ambulatory care, and patient education about outpatient avenues of care could eliminate a significant proportion (at least 20%) of unplanned ED visits by NSCLC patients.

There was no specific funding for this study. Dr. Shah disclosed no conflicts of interest. Dr. Neal disclosed relationships with many companies, including this news organization.

Nearly a quarter of ED visits were deemed preventable in a single-center study of patients with non–small cell lung cancer.

The leading cause of ED visits in the study was the cancer itself, although many visits were unrelated to non–small cell lung cancer (NSCLC) or cancer therapy.

Less than 10% of ED visits were related to cancer therapy, but visits were much more common among patients receiving chemotherapy than among those receiving immunotherapy or tyrosine kinase inhibitors (TKIs).

Manan P. Shah, MD, and Joel W. Neal, MD, PhD, both of Stanford (Calif. ) University, reported these results in JCO Oncology Practice.

The authors noted that, in the United States, care of patients with cancer, among all diseases, leads to the highest per-person cost. Unplanned hospital visits are among the largest drivers of increased spending in advanced cancer care, accounting for 48% of spending. However, that spending may not be indicative of better quality care, but rather of inefficiency, according to the authors.

One registry spanning 2009-2012 and including more than 400,000 newly diagnosed cancer patients found lung cancer to have the third-highest rate of unplanned hospitalizations (after hepatobiliary and pancreatic cancer). Those findings were published in JCO Oncology Practice in 2018.

While the reason for presentation to the ED is often the cancer or its therapy in this population, there is a paucity of research on the relative contribution of factors leading to unplanned hospital visits.

Common precipitants of medical emergencies in advanced stages of lung cancer include pulmonary embolism, obstructive pneumonia, spinal cord compression caused by metastasis, and tumor progression or pleural effusion leading to respiratory failure.

Lung cancer therapies, such as TKIs, immunotherapy, and cytotoxic chemotherapy, can also cause various medical emergencies arising out of skin reactions, gastrointestinal dysfunction, organ inflammatory processes, and bone marrow suppression.
 

Identifying drivers of unplanned ED visits

The primary goals of Dr. Shah and Dr. Neal’s study were to understand the drivers of unplanned ED visits and identify potential strategies to prevent them.

Drawing from the Stanford Medicine Research Data Repository, the authors identified 97 NSCLC patients with 173 ED visits at Stanford.

Patients were sorted according to which of the three therapies they had been receiving in the 3 months prior to the unplanned visit – TKIs (n = 47), immunotherapy (n = 24), or chemotherapy (n = 26). Patients receiving a combination of chemotherapy and immunotherapy were classified under the immunotherapy category.

ED visits were divided into four categories: cancer related, therapy related, unrelated to cancer or therapy, and rule-out (when an outpatient provider sent the patient to rule out medico-oncologic emergencies such as pulmonary embolism or cord compression).

If the patient’s main complaint(s) began 2 or more days before presentation, the diagnostics or therapeutics could have been provided in an outpatient setting (e.g., in clinic or urgent care), and the patient was discharged directly from the ED, the encounter was classified as potentially preventable. Among these preventable encounters, those made during business hours were also labeled unnecessary because they could have been managed through the Stanford sick call system for same-day urgent visits.
 

Leading cause is cancer

Overall, the leading cause of ED visits was NSCLC itself (54%). The patient’s cancer contributed to 61% of ED visits in the TKI group, 49% in the immunotherapy group, and 42% in the chemotherapy group.

Many ED visits were deemed unrelated to cancer or its therapies – 30% in the TKI group, 26% in the immunotherapy group, and 32% in the chemotherapy group.

Rule-out cases contributed to 7% of ED visits in the TKI group, 14% in the immunotherapy group, and 5% in the chemotherapy group.

Overall, 9% of ED visits were therapy related. The smallest proportion of these was observed in the TKI group (2%), which was significantly smaller than in the immunotherapy group (12%), a rate also significantly smaller than in the chemotherapy group (21%, P < .001).

Most unplanned ED visits did not lead to admissions (55%), were for complaints that began 2 or more days prior to presentation (53%), led to diagnostics or therapeutics that could have been administered in an outpatient setting (48%), and were during business hours (52%).

As a result, 24% of visits were classified as preventable, and 10% were deemed unnecessary.
 

Preventive strategies

“Our study suggests that TKIs lead to fewer emergency room visits than immunotherapy and chemotherapy,” Dr. Shah said in an interview.

“Overall, this may not necessarily change which therapy we prescribe,” he added, “as TKI therapy is often first line for patients with targeted mutations. However, recognizing that those on chemotherapy or immunotherapy are at higher risk for emergency room visits, we may target preventative strategies, for example, nursing phone calls, telemonitoring of symptoms, and frequent video visits toward this high-risk population.”

Dr. Shah and Dr. Neal said it’s “reassuring” that TKIs and immunotherapy are small drivers of unplanned hospital care. However, they also said efforts aimed at reducing chemotherapy-related ED visits are warranted.

The authors speculated that early intervention, extension of ambulatory care, and patient education about outpatient avenues of care could eliminate a significant proportion (at least 20%) of unplanned ED visits by NSCLC patients.

There was no specific funding for this study. Dr. Shah disclosed no conflicts of interest. Dr. Neal disclosed relationships with many companies, including this news organization.

Cancer can be transmitted from a mother with cervical cancer to a newborn when the baby passes through the birth canal.

That’s the conclusion of two ground-breaking cases from Japan in which investigators describe lung cancer in two boys that “probably developed” from their respective mothers via vaginal transmission during birth.

“Transmission of maternal cancer to offspring is extremely rare and is estimated to occur in approximately 1 infant per every 500,000 mothers with cancer,” wrote Ayumu Arakawa, MD, of the National Cancer Center Hospital in Japan, and colleagues, in a paper published Jan. 7 in The New England Journal of Medicine.

Previous cases, of which only 18 have been recorded, have been presumed to occur via transplacental transmission, they said.

In the two new cases, genetic analyses and other evidence suggest that both boys’ lung cancers developed after aspirating uterine cervical cancer tumor cells into their lungs during passage through the birth canal.

Tragically, both mothers, each of whom was diagnosed with cervical cancer after the births, died while their boys were still infants.

“Most of the maternal-to-infant cases reported have been leukemia or melanoma,” said Mel Greaves, PhD, of the Institute of Cancer Research, London, who was asked for comment. In 2009, Dr. Greaves and colleagues published a case study of maternal-to-infant cancer transmission (presumably via the placenta). “It attracted an enormous amount of publicity and no doubt some alarm,” he said in an interview. He emphasized that the phenomenon is “incredibly rare.”

Dr. Greaves explains why such transmission is so rare. “We suspect that cancer cells do transit from mum to unborn child more often, but the foreign (aka paternal) antigens (HLA) on the tumor cells prompt immunological rejection. The extremely rare cases of successful transmission probably do depend on the fortuitous loss of paternal HLA.”

Advances in genetic technology may allow such cases, which have been recorded since 1950, to be rapidly identified now, he said.

“Where there is an adult-type cancer in an infant or child whose mother carried cancer when pregnant, then whole-genome sequencing should quickly tell if the infant’s tumor was of maternal origin,” Dr. Greaves explained.

“I think we will be seeing more reports like this in the future, now that this phenomenon has been described and next-generation sequencing is more readily available,” added Mae Zakhour, MD, of the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, when asked for comment.

In the case of the Japanese boys, both cases were discovered incidentally during an analysis of the results of routine next-generation sequencing testing in a prospective gene-profiling trial in cancer patients, known as TOP-GEAR.

How do the investigators know that the spread happened vaginally and not via the placenta?

They explained that, in other cases of mother-to-fetus transmission, the offspring presented with multiple metastases in the brain, bones, liver, lungs, and soft tissues, which were “consistent with presumed hematogenous spread from the placenta.” However, in the two boys, tumors were observed only in the lungs and were localized along the bronchi.

That peribronchial pattern of tumor growth “suggested that the tumors arose from mother-to-infant vaginal transmission through aspiration of tumor-contaminated vaginal fluids during birth.”

In addition, the tumors in both boys lacked the Y chromosome and shared multiple somatic mutations, an HPV genome, and SNP alleles with tumors from the mothers.

“The identical molecular profiles of maternal and pediatric tumors demonstrated by next-generation sequencing, as well as the location of the tumors in the children, provides strong evidence for cancer transmission during delivery,” Dr. Zakhour summarized.
 

C-section question

The first of the cases reported by the Japanese team was a toddler (23 months) who presented to a local hospital with a 2-week history of a productive cough. Computed tomography revealed multiple masses scattered along the bronchi in both lungs, and a biopsy revealed neuroendocrine carcinoma of the lung.

Notably, the mother’s cervical cancer was not diagnosed during her pregnancy. A cervical cytologic test performed in the mother 7 months before the birth was negative. The infant was delivered transvaginally at 39 weeks of gestation.

It was only 3 months after the birth that the 35-year-old mother received a diagnosis of squamous cell carcinoma of the cervix. She then underwent radical hysterectomy with pelvic lymphadenectomy, followed by chemotherapy.

Had it been known that she had cervical cancer, she may have been advised to have a cesarean section.

The study authors propose, on the basis of their paper, that all women with cervical cancer should have a cesarean section.

But a U.S. expert questioned this, and said the situation is “a bit nuanced.”

William Grobman, MD, of Northwestern University in Chicago, said the current standard recommendation for many pregnant women known to have cervical cancer is to have a cesarean section and that “the strength of the recommendation is dependent on factors such as stage and size.”

However, in an interview, he added that “it may be premature to make a blanket recommendation for all people based on two reports without any idea of the frequency of this event, and with such uncertainty, it seems that disclosure of all information and shared decision-making would be a key approach.”

In this case report, the authors also noted that the cancer found in the toddler looked similar to the cancer in the mother.

“Histologic similarities between the tumor samples from the mother and child prompted us to compare the results of their next-generation sequencing tests,” they said.

The result? “The comparison of the gene profiles in the samples of tumor and normal tissue confirmed that transmission of maternal tumor to the child had occurred.”

The lung cancer in the toddler progressed despite two chemotherapy regimens, so he was enrolled in a clinical trial of nivolumab therapy. He had a response that continued for 7 months, with no appearance of new lesions. Lobectomy was performed to resect a single remaining nodule. The boy had no evidence of disease recurrence at 12 months after lobectomy.

His mother was also enrolled in a nivolumab trial, but her cervical cancer had spread, and she died 5 months after disease progression.
 

Second case

In the second reported case, a 6-year-old boy presented to a local hospital with chest pain on the left side. Computed tomography revealed a mass in the left lung, and mucinous adenocarcinoma was eventually diagnosed.

In this case, the mother had a cervical polypoid tumor detected during pregnancy. But, as in the other case, cervical cytologic analysis was negative. Because the tumor was stable without any intervention, the mother delivered the boy vaginally at 38 weeks of gestation.

However, after the delivery, biopsy of the cervical lesion revealed adenocarcinoma. The mother underwent radical hysterectomy and bilateral salpingo-oophorectomy 3 months after delivery. She died of the disease 2 years after the surgery.

The boy received chemotherapy and had a partial response, with a reduction in levels of the tumor marker CA19-9 to normal levels. But 3 months later, the disease recurred in the left lung. After more chemotherapy, he underwent total left pneumonectomy and was subsequently free of disease.

The study authors said that they did not suspect maternal transmission of the cancer when her child received a diagnosis at 6 years of age. They explained that metastatic cervical cancer is typically a fast-growing tumor and the slow growth in the child seemed inconsistent with the idea that the cancer had been transmitted to him.

However, the pathology exam showed that the boy had mucinous adenocarcinoma, “which is an unusual morphologic finding for a primary lung tumor, but it was similar to the uterine cervical tumor in the mother,” the authors reported.

Samples of the cervical tumor from the mother and from the lung tumor of the child were submitted for next-generation sequencing tests and, said the authors, indicated mother-to-infant transmission.

The study was supported by grants from the Japan Agency for Medical Research and Development; the National Cancer Center Research and Development Fund; and the Ministry of Education, Culture, Sports, Science and Technology; and funding from Ono Pharmaceutical.

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

Cancer can be transmitted from a mother with cervical cancer to a newborn when the baby passes through the birth canal.

That’s the conclusion of two ground-breaking cases from Japan in which investigators describe lung cancer in two boys that “probably developed” from their respective mothers via vaginal transmission during birth.

“Transmission of maternal cancer to offspring is extremely rare and is estimated to occur in approximately 1 infant per every 500,000 mothers with cancer,” wrote Ayumu Arakawa, MD, of the National Cancer Center Hospital in Japan, and colleagues, in a paper published Jan. 7 in The New England Journal of Medicine.

Previous cases, of which only 18 have been recorded, have been presumed to occur via transplacental transmission, they said.

In the two new cases, genetic analyses and other evidence suggest that both boys’ lung cancers developed after aspirating uterine cervical cancer tumor cells into their lungs during passage through the birth canal.

Tragically, both mothers, each of whom was diagnosed with cervical cancer after the births, died while their boys were still infants.

“Most of the maternal-to-infant cases reported have been leukemia or melanoma,” said Mel Greaves, PhD, of the Institute of Cancer Research, London, who was asked for comment. In 2009, Dr. Greaves and colleagues published a case study of maternal-to-infant cancer transmission (presumably via the placenta). “It attracted an enormous amount of publicity and no doubt some alarm,” he said in an interview. He emphasized that the phenomenon is “incredibly rare.”

Dr. Greaves explains why such transmission is so rare. “We suspect that cancer cells do transit from mum to unborn child more often, but the foreign (aka paternal) antigens (HLA) on the tumor cells prompt immunological rejection. The extremely rare cases of successful transmission probably do depend on the fortuitous loss of paternal HLA.”

Advances in genetic technology may allow such cases, which have been recorded since 1950, to be rapidly identified now, he said.

“Where there is an adult-type cancer in an infant or child whose mother carried cancer when pregnant, then whole-genome sequencing should quickly tell if the infant’s tumor was of maternal origin,” Dr. Greaves explained.

“I think we will be seeing more reports like this in the future, now that this phenomenon has been described and next-generation sequencing is more readily available,” added Mae Zakhour, MD, of the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, when asked for comment.

In the case of the Japanese boys, both cases were discovered incidentally during an analysis of the results of routine next-generation sequencing testing in a prospective gene-profiling trial in cancer patients, known as TOP-GEAR.

How do the investigators know that the spread happened vaginally and not via the placenta?

They explained that, in other cases of mother-to-fetus transmission, the offspring presented with multiple metastases in the brain, bones, liver, lungs, and soft tissues, which were “consistent with presumed hematogenous spread from the placenta.” However, in the two boys, tumors were observed only in the lungs and were localized along the bronchi.

That peribronchial pattern of tumor growth “suggested that the tumors arose from mother-to-infant vaginal transmission through aspiration of tumor-contaminated vaginal fluids during birth.”

In addition, the tumors in both boys lacked the Y chromosome and shared multiple somatic mutations, an HPV genome, and SNP alleles with tumors from the mothers.

“The identical molecular profiles of maternal and pediatric tumors demonstrated by next-generation sequencing, as well as the location of the tumors in the children, provides strong evidence for cancer transmission during delivery,” Dr. Zakhour summarized.
 

C-section question

The first of the cases reported by the Japanese team was a toddler (23 months) who presented to a local hospital with a 2-week history of a productive cough. Computed tomography revealed multiple masses scattered along the bronchi in both lungs, and a biopsy revealed neuroendocrine carcinoma of the lung.

Notably, the mother’s cervical cancer was not diagnosed during her pregnancy. A cervical cytologic test performed in the mother 7 months before the birth was negative. The infant was delivered transvaginally at 39 weeks of gestation.

It was only 3 months after the birth that the 35-year-old mother received a diagnosis of squamous cell carcinoma of the cervix. She then underwent radical hysterectomy with pelvic lymphadenectomy, followed by chemotherapy.

Had it been known that she had cervical cancer, she may have been advised to have a cesarean section.

The study authors propose, on the basis of their paper, that all women with cervical cancer should have a cesarean section.

But a U.S. expert questioned this, and said the situation is “a bit nuanced.”

William Grobman, MD, of Northwestern University in Chicago, said the current standard recommendation for many pregnant women known to have cervical cancer is to have a cesarean section and that “the strength of the recommendation is dependent on factors such as stage and size.”

However, in an interview, he added that “it may be premature to make a blanket recommendation for all people based on two reports without any idea of the frequency of this event, and with such uncertainty, it seems that disclosure of all information and shared decision-making would be a key approach.”

In this case report, the authors also noted that the cancer found in the toddler looked similar to the cancer in the mother.

“Histologic similarities between the tumor samples from the mother and child prompted us to compare the results of their next-generation sequencing tests,” they said.

The result? “The comparison of the gene profiles in the samples of tumor and normal tissue confirmed that transmission of maternal tumor to the child had occurred.”

The lung cancer in the toddler progressed despite two chemotherapy regimens, so he was enrolled in a clinical trial of nivolumab therapy. He had a response that continued for 7 months, with no appearance of new lesions. Lobectomy was performed to resect a single remaining nodule. The boy had no evidence of disease recurrence at 12 months after lobectomy.

His mother was also enrolled in a nivolumab trial, but her cervical cancer had spread, and she died 5 months after disease progression.
 

Second case

In the second reported case, a 6-year-old boy presented to a local hospital with chest pain on the left side. Computed tomography revealed a mass in the left lung, and mucinous adenocarcinoma was eventually diagnosed.

In this case, the mother had a cervical polypoid tumor detected during pregnancy. But, as in the other case, cervical cytologic analysis was negative. Because the tumor was stable without any intervention, the mother delivered the boy vaginally at 38 weeks of gestation.

However, after the delivery, biopsy of the cervical lesion revealed adenocarcinoma. The mother underwent radical hysterectomy and bilateral salpingo-oophorectomy 3 months after delivery. She died of the disease 2 years after the surgery.

The boy received chemotherapy and had a partial response, with a reduction in levels of the tumor marker CA19-9 to normal levels. But 3 months later, the disease recurred in the left lung. After more chemotherapy, he underwent total left pneumonectomy and was subsequently free of disease.

The study authors said that they did not suspect maternal transmission of the cancer when her child received a diagnosis at 6 years of age. They explained that metastatic cervical cancer is typically a fast-growing tumor and the slow growth in the child seemed inconsistent with the idea that the cancer had been transmitted to him.

However, the pathology exam showed that the boy had mucinous adenocarcinoma, “which is an unusual morphologic finding for a primary lung tumor, but it was similar to the uterine cervical tumor in the mother,” the authors reported.

Samples of the cervical tumor from the mother and from the lung tumor of the child were submitted for next-generation sequencing tests and, said the authors, indicated mother-to-infant transmission.

The study was supported by grants from the Japan Agency for Medical Research and Development; the National Cancer Center Research and Development Fund; and the Ministry of Education, Culture, Sports, Science and Technology; and funding from Ono Pharmaceutical.

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

Cancer can be transmitted from a mother with cervical cancer to a newborn when the baby passes through the birth canal.

That’s the conclusion of two ground-breaking cases from Japan in which investigators describe lung cancer in two boys that “probably developed” from their respective mothers via vaginal transmission during birth.

“Transmission of maternal cancer to offspring is extremely rare and is estimated to occur in approximately 1 infant per every 500,000 mothers with cancer,” wrote Ayumu Arakawa, MD, of the National Cancer Center Hospital in Japan, and colleagues, in a paper published Jan. 7 in The New England Journal of Medicine.

Previous cases, of which only 18 have been recorded, have been presumed to occur via transplacental transmission, they said.

In the two new cases, genetic analyses and other evidence suggest that both boys’ lung cancers developed after aspirating uterine cervical cancer tumor cells into their lungs during passage through the birth canal.

Tragically, both mothers, each of whom was diagnosed with cervical cancer after the births, died while their boys were still infants.

“Most of the maternal-to-infant cases reported have been leukemia or melanoma,” said Mel Greaves, PhD, of the Institute of Cancer Research, London, who was asked for comment. In 2009, Dr. Greaves and colleagues published a case study of maternal-to-infant cancer transmission (presumably via the placenta). “It attracted an enormous amount of publicity and no doubt some alarm,” he said in an interview. He emphasized that the phenomenon is “incredibly rare.”

Dr. Greaves explains why such transmission is so rare. “We suspect that cancer cells do transit from mum to unborn child more often, but the foreign (aka paternal) antigens (HLA) on the tumor cells prompt immunological rejection. The extremely rare cases of successful transmission probably do depend on the fortuitous loss of paternal HLA.”

Advances in genetic technology may allow such cases, which have been recorded since 1950, to be rapidly identified now, he said.

“Where there is an adult-type cancer in an infant or child whose mother carried cancer when pregnant, then whole-genome sequencing should quickly tell if the infant’s tumor was of maternal origin,” Dr. Greaves explained.

“I think we will be seeing more reports like this in the future, now that this phenomenon has been described and next-generation sequencing is more readily available,” added Mae Zakhour, MD, of the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, when asked for comment.

In the case of the Japanese boys, both cases were discovered incidentally during an analysis of the results of routine next-generation sequencing testing in a prospective gene-profiling trial in cancer patients, known as TOP-GEAR.

How do the investigators know that the spread happened vaginally and not via the placenta?

They explained that, in other cases of mother-to-fetus transmission, the offspring presented with multiple metastases in the brain, bones, liver, lungs, and soft tissues, which were “consistent with presumed hematogenous spread from the placenta.” However, in the two boys, tumors were observed only in the lungs and were localized along the bronchi.

That peribronchial pattern of tumor growth “suggested that the tumors arose from mother-to-infant vaginal transmission through aspiration of tumor-contaminated vaginal fluids during birth.”

In addition, the tumors in both boys lacked the Y chromosome and shared multiple somatic mutations, an HPV genome, and SNP alleles with tumors from the mothers.

“The identical molecular profiles of maternal and pediatric tumors demonstrated by next-generation sequencing, as well as the location of the tumors in the children, provides strong evidence for cancer transmission during delivery,” Dr. Zakhour summarized.
 

C-section question

The first of the cases reported by the Japanese team was a toddler (23 months) who presented to a local hospital with a 2-week history of a productive cough. Computed tomography revealed multiple masses scattered along the bronchi in both lungs, and a biopsy revealed neuroendocrine carcinoma of the lung.

Notably, the mother’s cervical cancer was not diagnosed during her pregnancy. A cervical cytologic test performed in the mother 7 months before the birth was negative. The infant was delivered transvaginally at 39 weeks of gestation.

It was only 3 months after the birth that the 35-year-old mother received a diagnosis of squamous cell carcinoma of the cervix. She then underwent radical hysterectomy with pelvic lymphadenectomy, followed by chemotherapy.

Had it been known that she had cervical cancer, she may have been advised to have a cesarean section.

The study authors propose, on the basis of their paper, that all women with cervical cancer should have a cesarean section.

But a U.S. expert questioned this, and said the situation is “a bit nuanced.”

William Grobman, MD, of Northwestern University in Chicago, said the current standard recommendation for many pregnant women known to have cervical cancer is to have a cesarean section and that “the strength of the recommendation is dependent on factors such as stage and size.”

However, in an interview, he added that “it may be premature to make a blanket recommendation for all people based on two reports without any idea of the frequency of this event, and with such uncertainty, it seems that disclosure of all information and shared decision-making would be a key approach.”

In this case report, the authors also noted that the cancer found in the toddler looked similar to the cancer in the mother.

“Histologic similarities between the tumor samples from the mother and child prompted us to compare the results of their next-generation sequencing tests,” they said.

The result? “The comparison of the gene profiles in the samples of tumor and normal tissue confirmed that transmission of maternal tumor to the child had occurred.”

The lung cancer in the toddler progressed despite two chemotherapy regimens, so he was enrolled in a clinical trial of nivolumab therapy. He had a response that continued for 7 months, with no appearance of new lesions. Lobectomy was performed to resect a single remaining nodule. The boy had no evidence of disease recurrence at 12 months after lobectomy.

His mother was also enrolled in a nivolumab trial, but her cervical cancer had spread, and she died 5 months after disease progression.
 

Second case

In the second reported case, a 6-year-old boy presented to a local hospital with chest pain on the left side. Computed tomography revealed a mass in the left lung, and mucinous adenocarcinoma was eventually diagnosed.

In this case, the mother had a cervical polypoid tumor detected during pregnancy. But, as in the other case, cervical cytologic analysis was negative. Because the tumor was stable without any intervention, the mother delivered the boy vaginally at 38 weeks of gestation.

However, after the delivery, biopsy of the cervical lesion revealed adenocarcinoma. The mother underwent radical hysterectomy and bilateral salpingo-oophorectomy 3 months after delivery. She died of the disease 2 years after the surgery.

The boy received chemotherapy and had a partial response, with a reduction in levels of the tumor marker CA19-9 to normal levels. But 3 months later, the disease recurred in the left lung. After more chemotherapy, he underwent total left pneumonectomy and was subsequently free of disease.

The study authors said that they did not suspect maternal transmission of the cancer when her child received a diagnosis at 6 years of age. They explained that metastatic cervical cancer is typically a fast-growing tumor and the slow growth in the child seemed inconsistent with the idea that the cancer had been transmitted to him.

However, the pathology exam showed that the boy had mucinous adenocarcinoma, “which is an unusual morphologic finding for a primary lung tumor, but it was similar to the uterine cervical tumor in the mother,” the authors reported.

Samples of the cervical tumor from the mother and from the lung tumor of the child were submitted for next-generation sequencing tests and, said the authors, indicated mother-to-infant transmission.

The study was supported by grants from the Japan Agency for Medical Research and Development; the National Cancer Center Research and Development Fund; and the Ministry of Education, Culture, Sports, Science and Technology; and funding from Ono Pharmaceutical.

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

For the second year in a row, mortality from cancer has fallen in the United States, driven largely by reductions in the incidence of, and death from, non–small cell lung cancer (NSCLC) in men and women, according to a new report from the American Cancer Society.

The study was published online Jan. 12 in CA: A Cancer Journal for Clinicians.

“Mortality rates are a better indicator of progress against cancer than incidence or survival because they are less affected by biases resulting from changes in detection practices,” wrote the authors, led by Rebecca Siegel, MPH, American Cancer Society, Atlanta.  

“The overall drop of 31% as of 2018 [since the early 1990s] translates to an estimated 3,188,500 fewer cancer deaths (2,170,700 in men and 1,017,800 in women) than what would have occurred if mortality rates had remained at their peak,” the researchers added.

Lung cancer accounted for 46% of the total decline in cancer mortality in the past 5 years, with a record, single-year drop of 2.4% between 2017 and 2018.

The recent and rapid reductions in lung cancer mortality reflect better treatments for NSCLC, the authors suggested. For example, survival rates at 2 years have increased from 34% for patients diagnosed with NSCLC between 2009 and 2010 to 42% for those diagnosed during 2015 and 2016 – an absolute gain of 5%-6% in survival odds for every stage of diagnosis.

On a more somber note, the authors warned that COVID-19 is predicted to have a negative impact on both the diagnosis and outcomes of patients with cancer in the near future.  

“We anticipate that disruptions in access to cancer care in 2020 will lead to downstream increases in advanced stage diagnoses that may impede progress in reducing cancer mortality rates in the years to come,” Ms. Siegel said in a statement.
 

New cancer cases

The report provides an estimated number of new cancer cases and deaths in 2021 in the United States (nationally and state-by-state) based on the most current population-based data for cancer incidence through 2017 and for mortality through 2018. “An estimated 608,570 Americans will die from cancer in 2021, corresponding to more than 1600 deaths per day,” Ms. Siegel and colleagues reported.

The greatest number of deaths are predicted to be from the most common cancers: Lung, prostate, and colorectal cancer in men and lung, breast, and colorectal cancer in women, they added. However, the mortality rates for all four cancers are continuing to fall.

As of 2018, the death rate from lung cancer had dropped by 54% among males and by 30% among females over the past few decades, the investigators noted.

Mortality from female breast cancer has dropped by 41% since 1989; by 52% for prostate cancer since 1993; and by 53% and 59% for colorectal cancer for men (since 1980) and women (since 1969), respectively.

“However, in recent years, mortality declines have slowed for breast cancer and [colorectal cancer] and have halted for prostate cancer,” the researchers noted.

In contrast, the pace of the annual decline in lung cancer mortality doubled among men from 3.1% between 2009 and 2013 to 5.5% between 2014 and 2018, and from 1.8% to 4.4% among women during the same time intervals.
 

Increase in incidence at common sites

Despite the steady progress in mortality for most cancers, “rates continue to increase for some common sites,” Ms. Siegel and colleagues reported.

For example, death rates from uterine corpus cancer have accelerated from the late 1990s at twice the pace of the increase in its incidence. Death rates also have increased for cancers of the oral cavity and pharynx – although in this cancer, increases in mortality parallel an increase in its incidence. 

“Pancreatic cancer death rates [in turn] continued to increase slowly in men ... but remained stable in women, despite incidence [rates] rising by about 1% per year in both sexes,” the authors observed.

Meanwhile, the incidence of cervical cancer, although declining for decades overall, is increasing for patients who present with more distant-stage disease as well as cervical adenocarcinoma, both of which are often undetected by cytology.

“These findings underscore the need for more targeted efforts to increase both HPV [human papillomavirus] vaccination among all individuals aged [26 and younger] and primary HPV testing or HPV/cytology co-testing every 5 years among women beginning at age 25,” the authors emphasized.

On a more positive note, the long-term increase in mortality from liver cancer has recently slowed among women and has stabilized among men, they added.

Once again, disparities in both cancer occurrence and outcomes varied considerably between racial and ethnic groups. For example, cancer is the leading cause of death in people who are Hispanic, Asian American, and Alaska Native. Survival rates at 5 years for almost all cancers are still higher for White patients than for Black patients, although the disparity in cancer mortality between Black persons and White persons has declined to 13% from a peak of 33% in 1993.

Geographic disparities in cancer mortality rates still prevail; the rates are largest for preventable cancers such as lung and cervical cancer, for which mortality varies by as much as fivefold across states.

And although cancer remains the second most common cause of death among children, death rates from cancer have continuously declined over time among both children and adolescents, largely the result of dramatic declines in death rates from leukemia in both age groups.

The study authors have disclosed no relevant financial relationships.

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

For the second year in a row, mortality from cancer has fallen in the United States, driven largely by reductions in the incidence of, and death from, non–small cell lung cancer (NSCLC) in men and women, according to a new report from the American Cancer Society.

The study was published online Jan. 12 in CA: A Cancer Journal for Clinicians.

“Mortality rates are a better indicator of progress against cancer than incidence or survival because they are less affected by biases resulting from changes in detection practices,” wrote the authors, led by Rebecca Siegel, MPH, American Cancer Society, Atlanta.  

“The overall drop of 31% as of 2018 [since the early 1990s] translates to an estimated 3,188,500 fewer cancer deaths (2,170,700 in men and 1,017,800 in women) than what would have occurred if mortality rates had remained at their peak,” the researchers added.

Lung cancer accounted for 46% of the total decline in cancer mortality in the past 5 years, with a record, single-year drop of 2.4% between 2017 and 2018.

The recent and rapid reductions in lung cancer mortality reflect better treatments for NSCLC, the authors suggested. For example, survival rates at 2 years have increased from 34% for patients diagnosed with NSCLC between 2009 and 2010 to 42% for those diagnosed during 2015 and 2016 – an absolute gain of 5%-6% in survival odds for every stage of diagnosis.

On a more somber note, the authors warned that COVID-19 is predicted to have a negative impact on both the diagnosis and outcomes of patients with cancer in the near future.  

“We anticipate that disruptions in access to cancer care in 2020 will lead to downstream increases in advanced stage diagnoses that may impede progress in reducing cancer mortality rates in the years to come,” Ms. Siegel said in a statement.
 

New cancer cases

The report provides an estimated number of new cancer cases and deaths in 2021 in the United States (nationally and state-by-state) based on the most current population-based data for cancer incidence through 2017 and for mortality through 2018. “An estimated 608,570 Americans will die from cancer in 2021, corresponding to more than 1600 deaths per day,” Ms. Siegel and colleagues reported.

The greatest number of deaths are predicted to be from the most common cancers: Lung, prostate, and colorectal cancer in men and lung, breast, and colorectal cancer in women, they added. However, the mortality rates for all four cancers are continuing to fall.

As of 2018, the death rate from lung cancer had dropped by 54% among males and by 30% among females over the past few decades, the investigators noted.

Mortality from female breast cancer has dropped by 41% since 1989; by 52% for prostate cancer since 1993; and by 53% and 59% for colorectal cancer for men (since 1980) and women (since 1969), respectively.

“However, in recent years, mortality declines have slowed for breast cancer and [colorectal cancer] and have halted for prostate cancer,” the researchers noted.

In contrast, the pace of the annual decline in lung cancer mortality doubled among men from 3.1% between 2009 and 2013 to 5.5% between 2014 and 2018, and from 1.8% to 4.4% among women during the same time intervals.
 

Increase in incidence at common sites

Despite the steady progress in mortality for most cancers, “rates continue to increase for some common sites,” Ms. Siegel and colleagues reported.

For example, death rates from uterine corpus cancer have accelerated from the late 1990s at twice the pace of the increase in its incidence. Death rates also have increased for cancers of the oral cavity and pharynx – although in this cancer, increases in mortality parallel an increase in its incidence. 

“Pancreatic cancer death rates [in turn] continued to increase slowly in men ... but remained stable in women, despite incidence [rates] rising by about 1% per year in both sexes,” the authors observed.

Meanwhile, the incidence of cervical cancer, although declining for decades overall, is increasing for patients who present with more distant-stage disease as well as cervical adenocarcinoma, both of which are often undetected by cytology.

“These findings underscore the need for more targeted efforts to increase both HPV [human papillomavirus] vaccination among all individuals aged [26 and younger] and primary HPV testing or HPV/cytology co-testing every 5 years among women beginning at age 25,” the authors emphasized.

On a more positive note, the long-term increase in mortality from liver cancer has recently slowed among women and has stabilized among men, they added.

Once again, disparities in both cancer occurrence and outcomes varied considerably between racial and ethnic groups. For example, cancer is the leading cause of death in people who are Hispanic, Asian American, and Alaska Native. Survival rates at 5 years for almost all cancers are still higher for White patients than for Black patients, although the disparity in cancer mortality between Black persons and White persons has declined to 13% from a peak of 33% in 1993.

Geographic disparities in cancer mortality rates still prevail; the rates are largest for preventable cancers such as lung and cervical cancer, for which mortality varies by as much as fivefold across states.

And although cancer remains the second most common cause of death among children, death rates from cancer have continuously declined over time among both children and adolescents, largely the result of dramatic declines in death rates from leukemia in both age groups.

The study authors have disclosed no relevant financial relationships.

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

For the second year in a row, mortality from cancer has fallen in the United States, driven largely by reductions in the incidence of, and death from, non–small cell lung cancer (NSCLC) in men and women, according to a new report from the American Cancer Society.

The study was published online Jan. 12 in CA: A Cancer Journal for Clinicians.

“Mortality rates are a better indicator of progress against cancer than incidence or survival because they are less affected by biases resulting from changes in detection practices,” wrote the authors, led by Rebecca Siegel, MPH, American Cancer Society, Atlanta.  

“The overall drop of 31% as of 2018 [since the early 1990s] translates to an estimated 3,188,500 fewer cancer deaths (2,170,700 in men and 1,017,800 in women) than what would have occurred if mortality rates had remained at their peak,” the researchers added.

Lung cancer accounted for 46% of the total decline in cancer mortality in the past 5 years, with a record, single-year drop of 2.4% between 2017 and 2018.

The recent and rapid reductions in lung cancer mortality reflect better treatments for NSCLC, the authors suggested. For example, survival rates at 2 years have increased from 34% for patients diagnosed with NSCLC between 2009 and 2010 to 42% for those diagnosed during 2015 and 2016 – an absolute gain of 5%-6% in survival odds for every stage of diagnosis.

On a more somber note, the authors warned that COVID-19 is predicted to have a negative impact on both the diagnosis and outcomes of patients with cancer in the near future.  

“We anticipate that disruptions in access to cancer care in 2020 will lead to downstream increases in advanced stage diagnoses that may impede progress in reducing cancer mortality rates in the years to come,” Ms. Siegel said in a statement.
 

New cancer cases

The report provides an estimated number of new cancer cases and deaths in 2021 in the United States (nationally and state-by-state) based on the most current population-based data for cancer incidence through 2017 and for mortality through 2018. “An estimated 608,570 Americans will die from cancer in 2021, corresponding to more than 1600 deaths per day,” Ms. Siegel and colleagues reported.

The greatest number of deaths are predicted to be from the most common cancers: Lung, prostate, and colorectal cancer in men and lung, breast, and colorectal cancer in women, they added. However, the mortality rates for all four cancers are continuing to fall.

As of 2018, the death rate from lung cancer had dropped by 54% among males and by 30% among females over the past few decades, the investigators noted.

Mortality from female breast cancer has dropped by 41% since 1989; by 52% for prostate cancer since 1993; and by 53% and 59% for colorectal cancer for men (since 1980) and women (since 1969), respectively.

“However, in recent years, mortality declines have slowed for breast cancer and [colorectal cancer] and have halted for prostate cancer,” the researchers noted.

In contrast, the pace of the annual decline in lung cancer mortality doubled among men from 3.1% between 2009 and 2013 to 5.5% between 2014 and 2018, and from 1.8% to 4.4% among women during the same time intervals.
 

Increase in incidence at common sites

Despite the steady progress in mortality for most cancers, “rates continue to increase for some common sites,” Ms. Siegel and colleagues reported.

For example, death rates from uterine corpus cancer have accelerated from the late 1990s at twice the pace of the increase in its incidence. Death rates also have increased for cancers of the oral cavity and pharynx – although in this cancer, increases in mortality parallel an increase in its incidence. 

“Pancreatic cancer death rates [in turn] continued to increase slowly in men ... but remained stable in women, despite incidence [rates] rising by about 1% per year in both sexes,” the authors observed.

Meanwhile, the incidence of cervical cancer, although declining for decades overall, is increasing for patients who present with more distant-stage disease as well as cervical adenocarcinoma, both of which are often undetected by cytology.

“These findings underscore the need for more targeted efforts to increase both HPV [human papillomavirus] vaccination among all individuals aged [26 and younger] and primary HPV testing or HPV/cytology co-testing every 5 years among women beginning at age 25,” the authors emphasized.

On a more positive note, the long-term increase in mortality from liver cancer has recently slowed among women and has stabilized among men, they added.

Once again, disparities in both cancer occurrence and outcomes varied considerably between racial and ethnic groups. For example, cancer is the leading cause of death in people who are Hispanic, Asian American, and Alaska Native. Survival rates at 5 years for almost all cancers are still higher for White patients than for Black patients, although the disparity in cancer mortality between Black persons and White persons has declined to 13% from a peak of 33% in 1993.

Geographic disparities in cancer mortality rates still prevail; the rates are largest for preventable cancers such as lung and cervical cancer, for which mortality varies by as much as fivefold across states.

And although cancer remains the second most common cause of death among children, death rates from cancer have continuously declined over time among both children and adolescents, largely the result of dramatic declines in death rates from leukemia in both age groups.

The study authors have disclosed no relevant financial relationships.

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

The advent of liquid biopsies targeting genetic mutations in solid tumors is a major milestone in the field of precision oncology.¹ Conventional methods of obtaining tissue for molecular studies are limited by sample size and often do not represent the entire bulk of the tumor.² This newer minimally invasive, revolutionary technique analyzes circulating cell-free DNA carrying tumor-specific alterations (circulating tumor DNA [ctDNA]) in peripheral blood and detects signature genomic alterations.¹ Tp53 mutations have been reported in 25 to 40% of prostatic cancers and > 50% of non-small cell lung cancers (NSCLC), being more common in late-stage and hormone refractory prostate cancers.^3,4 Tp53 mutation has been found to be associated with poor prognosis and increased germline mutations.⁵

The veteran patient population has distinct demographic characteristics that make veterans more vulnerable to genetic mutations and malignancies, including risk of exposure to Agent Orange, smoking, substance abuse, and asbestos. This area is understudied and extremely sparse in the literature for frequency of genetic mutations, risk factors in solid malignancies occurring in the veteran patient population, and the clinical impact of these risk factors. We herein present a quality assurance study for the utility of liquid biopsies regarding the frequency of DNA damage repair (DDR) gene, Tp53, and androgen receptor (AR) mutations. The clinical impact in advanced lung and prostate cancers in the veteran patient population and frequency are the quality assurance observations that are the study endpoints.

Methods

We reviewed for quality assurance documentation from the Foundation Medicine (www.foundationmedicine.com) cancer biomarker tests on liquid biopsies performed at the Corporal Michael J. Crescenz Veteran Affairs Medical Center in Philadelphia, Pennsylvania from May 2019 to April 15, 2020. All biopsies were performed on cancers with biochemical, imaging or tissue evidence of advanced tumor progression. The testing was performed on advanced solid malignancies, including NSCLC, prostate adenocarcinoma, and metastatic colon cancer. Statistical data for adequacy; cases with notable mutations; frequency; and type of mutations of AR, DDR, and Tp53 were noted. General and specific risk factors associated with the veteran patient population were studied and matched with the type of mutations (Table 1).

Results

Thirty-one liquid biopsies were performed over this period—23 for prostate cancer, 7 for patients with lung cancer patients, and 1 for a patient with colon cancer. Of 31 cases, sensitivity/adequacy of liquid biopsy for genetic mutation was detected in 29 (93.5%) cases (Figure 1). Two inadequate biopsies (both from patients with prostate cancer) were excluded from the study, leaving 29 liquid biopsies with adequate ctDNA for analysis that were considered for further statistical purpose—21 prostate, 7 lung, and 1 colon cancer.

Multiple (common and different) genetic mutations were identified; however, our study subcategorized the mutations into the those that were related to prostate cancer, lung cancer, and some common mutations that occur in both cancers. Only the significant ones will be discussed in this review and equivocal result for AR is excluded from this study. Of the 21 prostate cancers, 4 (19.0%) had directed the targeted therapy to driver mutation (AR being most common in prostate cancer), while KRAS mutation, which was more common in lung cancer, was detected in 2/7 (28.6%) lung cancers. Mutations common to both cancer types were DDR gene mutations, which is a broad name for numerous genes including CDK12, ATM, and CHEK2.

Of all cases irrespective of the cancer type, 23/29 (79.3%) showed notable mutations. DDR gene mutations were found in 6 of 21 (28.5%) patients with prostate cancer and 8 of 23 (34.7%) patients with advanced prostate and lung cancers, indicating poor outcome and possible resistance to the current therapy. Of 23 patients showing mutations irrespective of the cancer type, 15 (65.2%) harbored Tp53 mutations, which is much more frequent in veteran patient population when compared with the literature. Fifteen of the 31 (48.4%) total patients were Vietnam War-era veterans who were potentially exposed to Agent Orange and 20 (64.5%) patients who were not Vietnam War-era veterans had a history that included smoking (Figure 2).

Discussion

The veteran patient population is a unique cohort due to its distinct demographic characteristics with a high volume of cancer cases diagnosed each year. According to data from VA Central Cancer Registry (VACCR), the most frequently diagnosed cancers are prostate (29%) and lung (18%).⁶

Liquid biopsy is a novel, promising technology that uses ctDNA and circulating tumor cells in peripheral blood for detecting genetic alterations through next generation sequencing.^7-9 The advent of this minimally invasive, revolutionary technology has been a breakthrough in the field of precision oncology for prognosis, to monitor treatment response or resistance to therapy and further personalize cancer therapy.^9,10

Comprehensive genomic profiling by liquid biopsy has many advantages over the molecular studies performed on tissue biopsy. Due to the tumor heterogeneity, tissue samples may not represent the full profile of the tumor genomics of cancer, while liquid biopsy has full presentation of the disease.^11,12 Many times, tissue biopsy may be limited by a sample size that precludes full genetic profiling in addition to higher total cost, potential technical issues during processing, and possible side effects of the biopsy procedure.^7,13 Additionally, as the tumor progresses, new driver mutations other than the ones previously detected on the primary tissue may emerge, which can confer resistance to the existing therapy.^7,13

Advanced prostatic and lung carcinomas with biochemical, distant organ, or bony progression harbor unique signature genetic mutations indicating poor prognosis, lack of response or resistance to the existing therapy, and high risk of relapse.^14,15 Some of the unique characteristics of the veteran patient population include a more aged patient population multiple comorbidities, higher frequency of > 1 type of cancer, advanced cancer stage at presentation, and specific risks factors such as exposure to Agent Orange in veterans who served during the Vietnam War era.^16,17 We studied the utility of liquid biopsy in cancer care, including type and incidence of genomic alterations associated with advanced prostate and lung cancers, in this unique patient population.

The amount of cell-free DNA (cfDNA), also known as ctDNA varies widely in cancer patients. Some of the factors associated with low concentration of cfDNA are disease stage, intervening therapy, proliferation rates, and tumor vascularization.^18,19 In the peripheral blood, of the total cfDNA, fractions of cfDNA varies from 0.01 to 90%.^18,19 All samples containing ≥ 20 ng cfDNA (20 - 100 ng) were subjected to the hybrid capture-based NGS FoundationACT assay.²⁰ In our study, 2 specimens did not meet the minimum criteria of adequacy (20 ng cfDNA); however, the overall adequacy rate for the detection of mutation, irrespective of the cancer type was 29 of 31 (93.5%) with only 2 inadequate samples. This rate is higher than the rate reported in the literature, which is about 70%.²⁰

Significant differences were encountered in the incidence of DNA damage repair genes including Tp53 mutations when compared with those in the general patient population (Table 2). According to recent National Comprehensive Cancer Network (NCCN) guidelines, all prostate cancers should be screened for DDR gene mutations as these genes are common in aggressive prostate cancers and strongly associated with poor outcomes and shortened survival. Due to relatively high frequency of DDR gene mutations in advanced prostatic cancers, liquid biopsy in patients with these advanced stage prostate cancers may be a useful tool in clinical decision making and exploring targeted therapy.²⁰

We also evaluated the frequency of the most commonly occurring genetic mutations, Tp53 in advanced solid malignancies, especially advanced prostate and NSCLC. Previous studies have reported Tp53 mutation in association with risk factors (carcinogens) of cancer and have been a surrogate marker of poor survival or lack of response of therapy.²⁵ Knowledge of Tp53 mutation is crucial for closer disease monitoring, preparing the patient for rapid progression, and encouraging the physician to prepare future lines of therapy.^25-27 Although Tp53 mutation varies with histologic type and tissue of origin, Beltran and colleagues reported it in 30 to 40% of tumors, while Robles and colleagues reported about 40 to 42% incidence.^25,27

Our study showed notable mutations in 23 of 29 adequate cases. Further, our study showed a high frequency of mutated Tp53 in 65.2% of combined advanced prostate and NSCLC cases. We then correlated cases of Vietnam War-era veterans with risk potential of Agent Orange exposure and Tp53 mutation. We found 7 of 15 Vietnam War-era veterans were positive for Tp53 mutations irrespective of the cancer type. The high incidence of Tp53 mutations in advanced prostate and lung carcinomas in the veteran patient population makes this tumor marker an aspiration not only as a surrogate of aggressive disease and tumor progression, but also as a key marker for targeted therapy in advanced prostate and lung cancers with loss of Tp53 function (Figure 3).

Conclusions

Liquid biopsy successfully provides precision-based oncology and information for decision making in this unique population of veterans. Difference in frequency of the genetic mutations in this cohort can provide future insight into disease progression, lack of response, and mechanism of resistance to the implemented therapy. Future studies focused on this veteran patient population are needed for developing targeted therapies and patient tailored oncologic therapy. ctDNA has a high potential for monitoring clinically relevant cancer-related genetic and epigenetic modifications for discovering more detailed information on the tumor characterization. Although larger cohort trial with longitudinal analyses are needed, high prevalence of DDR gene and Tp53 mutation in our study instills promising hope for therapeutic interventions in this unique cohort.

The minimally invasive liquid biopsy shows a great promise as both diagnostic and prognostic tool in the personalized clinical management of advanced prostate, and NSCLC in the veteran patient population with unique demographic characteristics. De novo metastatic prostate cancer is more common in veterans when compared with the general population, and therefore veterans may benefit by liquid biopsy. Differences in the frequency of genetic mutations (DDR, TP53, AR) in this cohort provides valuable information for disease progression, lack of response, mechanism of resistance to the implemented therapy and clinical decision making. Precision oncology can be further tailored for this cohort by focusing on DNA repair genes and Tp53 mutations for future targeted therapy.

The advent of liquid biopsies targeting genetic mutations in solid tumors is a major milestone in the field of precision oncology.¹ Conventional methods of obtaining tissue for molecular studies are limited by sample size and often do not represent the entire bulk of the tumor.² This newer minimally invasive, revolutionary technique analyzes circulating cell-free DNA carrying tumor-specific alterations (circulating tumor DNA [ctDNA]) in peripheral blood and detects signature genomic alterations.¹ Tp53 mutations have been reported in 25 to 40% of prostatic cancers and > 50% of non-small cell lung cancers (NSCLC), being more common in late-stage and hormone refractory prostate cancers.^3,4 Tp53 mutation has been found to be associated with poor prognosis and increased germline mutations.⁵

The veteran patient population has distinct demographic characteristics that make veterans more vulnerable to genetic mutations and malignancies, including risk of exposure to Agent Orange, smoking, substance abuse, and asbestos. This area is understudied and extremely sparse in the literature for frequency of genetic mutations, risk factors in solid malignancies occurring in the veteran patient population, and the clinical impact of these risk factors. We herein present a quality assurance study for the utility of liquid biopsies regarding the frequency of DNA damage repair (DDR) gene, Tp53, and androgen receptor (AR) mutations. The clinical impact in advanced lung and prostate cancers in the veteran patient population and frequency are the quality assurance observations that are the study endpoints.

Methods

We reviewed for quality assurance documentation from the Foundation Medicine (www.foundationmedicine.com) cancer biomarker tests on liquid biopsies performed at the Corporal Michael J. Crescenz Veteran Affairs Medical Center in Philadelphia, Pennsylvania from May 2019 to April 15, 2020. All biopsies were performed on cancers with biochemical, imaging or tissue evidence of advanced tumor progression. The testing was performed on advanced solid malignancies, including NSCLC, prostate adenocarcinoma, and metastatic colon cancer. Statistical data for adequacy; cases with notable mutations; frequency; and type of mutations of AR, DDR, and Tp53 were noted. General and specific risk factors associated with the veteran patient population were studied and matched with the type of mutations (Table 1).

Results

Thirty-one liquid biopsies were performed over this period—23 for prostate cancer, 7 for patients with lung cancer patients, and 1 for a patient with colon cancer. Of 31 cases, sensitivity/adequacy of liquid biopsy for genetic mutation was detected in 29 (93.5%) cases (Figure 1). Two inadequate biopsies (both from patients with prostate cancer) were excluded from the study, leaving 29 liquid biopsies with adequate ctDNA for analysis that were considered for further statistical purpose—21 prostate, 7 lung, and 1 colon cancer.

Multiple (common and different) genetic mutations were identified; however, our study subcategorized the mutations into the those that were related to prostate cancer, lung cancer, and some common mutations that occur in both cancers. Only the significant ones will be discussed in this review and equivocal result for AR is excluded from this study. Of the 21 prostate cancers, 4 (19.0%) had directed the targeted therapy to driver mutation (AR being most common in prostate cancer), while KRAS mutation, which was more common in lung cancer, was detected in 2/7 (28.6%) lung cancers. Mutations common to both cancer types were DDR gene mutations, which is a broad name for numerous genes including CDK12, ATM, and CHEK2.

Of all cases irrespective of the cancer type, 23/29 (79.3%) showed notable mutations. DDR gene mutations were found in 6 of 21 (28.5%) patients with prostate cancer and 8 of 23 (34.7%) patients with advanced prostate and lung cancers, indicating poor outcome and possible resistance to the current therapy. Of 23 patients showing mutations irrespective of the cancer type, 15 (65.2%) harbored Tp53 mutations, which is much more frequent in veteran patient population when compared with the literature. Fifteen of the 31 (48.4%) total patients were Vietnam War-era veterans who were potentially exposed to Agent Orange and 20 (64.5%) patients who were not Vietnam War-era veterans had a history that included smoking (Figure 2).

Discussion

The veteran patient population is a unique cohort due to its distinct demographic characteristics with a high volume of cancer cases diagnosed each year. According to data from VA Central Cancer Registry (VACCR), the most frequently diagnosed cancers are prostate (29%) and lung (18%).⁶

Liquid biopsy is a novel, promising technology that uses ctDNA and circulating tumor cells in peripheral blood for detecting genetic alterations through next generation sequencing.^7-9 The advent of this minimally invasive, revolutionary technology has been a breakthrough in the field of precision oncology for prognosis, to monitor treatment response or resistance to therapy and further personalize cancer therapy.^9,10

Comprehensive genomic profiling by liquid biopsy has many advantages over the molecular studies performed on tissue biopsy. Due to the tumor heterogeneity, tissue samples may not represent the full profile of the tumor genomics of cancer, while liquid biopsy has full presentation of the disease.^11,12 Many times, tissue biopsy may be limited by a sample size that precludes full genetic profiling in addition to higher total cost, potential technical issues during processing, and possible side effects of the biopsy procedure.^7,13 Additionally, as the tumor progresses, new driver mutations other than the ones previously detected on the primary tissue may emerge, which can confer resistance to the existing therapy.^7,13

Advanced prostatic and lung carcinomas with biochemical, distant organ, or bony progression harbor unique signature genetic mutations indicating poor prognosis, lack of response or resistance to the existing therapy, and high risk of relapse.^14,15 Some of the unique characteristics of the veteran patient population include a more aged patient population multiple comorbidities, higher frequency of > 1 type of cancer, advanced cancer stage at presentation, and specific risks factors such as exposure to Agent Orange in veterans who served during the Vietnam War era.^16,17 We studied the utility of liquid biopsy in cancer care, including type and incidence of genomic alterations associated with advanced prostate and lung cancers, in this unique patient population.

The amount of cell-free DNA (cfDNA), also known as ctDNA varies widely in cancer patients. Some of the factors associated with low concentration of cfDNA are disease stage, intervening therapy, proliferation rates, and tumor vascularization.^18,19 In the peripheral blood, of the total cfDNA, fractions of cfDNA varies from 0.01 to 90%.^18,19 All samples containing ≥ 20 ng cfDNA (20 - 100 ng) were subjected to the hybrid capture-based NGS FoundationACT assay.²⁰ In our study, 2 specimens did not meet the minimum criteria of adequacy (20 ng cfDNA); however, the overall adequacy rate for the detection of mutation, irrespective of the cancer type was 29 of 31 (93.5%) with only 2 inadequate samples. This rate is higher than the rate reported in the literature, which is about 70%.²⁰

Significant differences were encountered in the incidence of DNA damage repair genes including Tp53 mutations when compared with those in the general patient population (Table 2). According to recent National Comprehensive Cancer Network (NCCN) guidelines, all prostate cancers should be screened for DDR gene mutations as these genes are common in aggressive prostate cancers and strongly associated with poor outcomes and shortened survival. Due to relatively high frequency of DDR gene mutations in advanced prostatic cancers, liquid biopsy in patients with these advanced stage prostate cancers may be a useful tool in clinical decision making and exploring targeted therapy.²⁰

We also evaluated the frequency of the most commonly occurring genetic mutations, Tp53 in advanced solid malignancies, especially advanced prostate and NSCLC. Previous studies have reported Tp53 mutation in association with risk factors (carcinogens) of cancer and have been a surrogate marker of poor survival or lack of response of therapy.²⁵ Knowledge of Tp53 mutation is crucial for closer disease monitoring, preparing the patient for rapid progression, and encouraging the physician to prepare future lines of therapy.^25-27 Although Tp53 mutation varies with histologic type and tissue of origin, Beltran and colleagues reported it in 30 to 40% of tumors, while Robles and colleagues reported about 40 to 42% incidence.^25,27

Our study showed notable mutations in 23 of 29 adequate cases. Further, our study showed a high frequency of mutated Tp53 in 65.2% of combined advanced prostate and NSCLC cases. We then correlated cases of Vietnam War-era veterans with risk potential of Agent Orange exposure and Tp53 mutation. We found 7 of 15 Vietnam War-era veterans were positive for Tp53 mutations irrespective of the cancer type. The high incidence of Tp53 mutations in advanced prostate and lung carcinomas in the veteran patient population makes this tumor marker an aspiration not only as a surrogate of aggressive disease and tumor progression, but also as a key marker for targeted therapy in advanced prostate and lung cancers with loss of Tp53 function (Figure 3).

Conclusions

Liquid biopsy successfully provides precision-based oncology and information for decision making in this unique population of veterans. Difference in frequency of the genetic mutations in this cohort can provide future insight into disease progression, lack of response, and mechanism of resistance to the implemented therapy. Future studies focused on this veteran patient population are needed for developing targeted therapies and patient tailored oncologic therapy. ctDNA has a high potential for monitoring clinically relevant cancer-related genetic and epigenetic modifications for discovering more detailed information on the tumor characterization. Although larger cohort trial with longitudinal analyses are needed, high prevalence of DDR gene and Tp53 mutation in our study instills promising hope for therapeutic interventions in this unique cohort.

The minimally invasive liquid biopsy shows a great promise as both diagnostic and prognostic tool in the personalized clinical management of advanced prostate, and NSCLC in the veteran patient population with unique demographic characteristics. De novo metastatic prostate cancer is more common in veterans when compared with the general population, and therefore veterans may benefit by liquid biopsy. Differences in the frequency of genetic mutations (DDR, TP53, AR) in this cohort provides valuable information for disease progression, lack of response, mechanism of resistance to the implemented therapy and clinical decision making. Precision oncology can be further tailored for this cohort by focusing on DNA repair genes and Tp53 mutations for future targeted therapy.

The advent of liquid biopsies targeting genetic mutations in solid tumors is a major milestone in the field of precision oncology.¹ Conventional methods of obtaining tissue for molecular studies are limited by sample size and often do not represent the entire bulk of the tumor.² This newer minimally invasive, revolutionary technique analyzes circulating cell-free DNA carrying tumor-specific alterations (circulating tumor DNA [ctDNA]) in peripheral blood and detects signature genomic alterations.¹ Tp53 mutations have been reported in 25 to 40% of prostatic cancers and > 50% of non-small cell lung cancers (NSCLC), being more common in late-stage and hormone refractory prostate cancers.^3,4 Tp53 mutation has been found to be associated with poor prognosis and increased germline mutations.⁵

The veteran patient population has distinct demographic characteristics that make veterans more vulnerable to genetic mutations and malignancies, including risk of exposure to Agent Orange, smoking, substance abuse, and asbestos. This area is understudied and extremely sparse in the literature for frequency of genetic mutations, risk factors in solid malignancies occurring in the veteran patient population, and the clinical impact of these risk factors. We herein present a quality assurance study for the utility of liquid biopsies regarding the frequency of DNA damage repair (DDR) gene, Tp53, and androgen receptor (AR) mutations. The clinical impact in advanced lung and prostate cancers in the veteran patient population and frequency are the quality assurance observations that are the study endpoints.

Methods

We reviewed for quality assurance documentation from the Foundation Medicine (www.foundationmedicine.com) cancer biomarker tests on liquid biopsies performed at the Corporal Michael J. Crescenz Veteran Affairs Medical Center in Philadelphia, Pennsylvania from May 2019 to April 15, 2020. All biopsies were performed on cancers with biochemical, imaging or tissue evidence of advanced tumor progression. The testing was performed on advanced solid malignancies, including NSCLC, prostate adenocarcinoma, and metastatic colon cancer. Statistical data for adequacy; cases with notable mutations; frequency; and type of mutations of AR, DDR, and Tp53 were noted. General and specific risk factors associated with the veteran patient population were studied and matched with the type of mutations (Table 1).

Results

Thirty-one liquid biopsies were performed over this period—23 for prostate cancer, 7 for patients with lung cancer patients, and 1 for a patient with colon cancer. Of 31 cases, sensitivity/adequacy of liquid biopsy for genetic mutation was detected in 29 (93.5%) cases (Figure 1). Two inadequate biopsies (both from patients with prostate cancer) were excluded from the study, leaving 29 liquid biopsies with adequate ctDNA for analysis that were considered for further statistical purpose—21 prostate, 7 lung, and 1 colon cancer.

Multiple (common and different) genetic mutations were identified; however, our study subcategorized the mutations into the those that were related to prostate cancer, lung cancer, and some common mutations that occur in both cancers. Only the significant ones will be discussed in this review and equivocal result for AR is excluded from this study. Of the 21 prostate cancers, 4 (19.0%) had directed the targeted therapy to driver mutation (AR being most common in prostate cancer), while KRAS mutation, which was more common in lung cancer, was detected in 2/7 (28.6%) lung cancers. Mutations common to both cancer types were DDR gene mutations, which is a broad name for numerous genes including CDK12, ATM, and CHEK2.

Of all cases irrespective of the cancer type, 23/29 (79.3%) showed notable mutations. DDR gene mutations were found in 6 of 21 (28.5%) patients with prostate cancer and 8 of 23 (34.7%) patients with advanced prostate and lung cancers, indicating poor outcome and possible resistance to the current therapy. Of 23 patients showing mutations irrespective of the cancer type, 15 (65.2%) harbored Tp53 mutations, which is much more frequent in veteran patient population when compared with the literature. Fifteen of the 31 (48.4%) total patients were Vietnam War-era veterans who were potentially exposed to Agent Orange and 20 (64.5%) patients who were not Vietnam War-era veterans had a history that included smoking (Figure 2).

Discussion

The veteran patient population is a unique cohort due to its distinct demographic characteristics with a high volume of cancer cases diagnosed each year. According to data from VA Central Cancer Registry (VACCR), the most frequently diagnosed cancers are prostate (29%) and lung (18%).⁶

Liquid biopsy is a novel, promising technology that uses ctDNA and circulating tumor cells in peripheral blood for detecting genetic alterations through next generation sequencing.^7-9 The advent of this minimally invasive, revolutionary technology has been a breakthrough in the field of precision oncology for prognosis, to monitor treatment response or resistance to therapy and further personalize cancer therapy.^9,10

Comprehensive genomic profiling by liquid biopsy has many advantages over the molecular studies performed on tissue biopsy. Due to the tumor heterogeneity, tissue samples may not represent the full profile of the tumor genomics of cancer, while liquid biopsy has full presentation of the disease.^11,12 Many times, tissue biopsy may be limited by a sample size that precludes full genetic profiling in addition to higher total cost, potential technical issues during processing, and possible side effects of the biopsy procedure.^7,13 Additionally, as the tumor progresses, new driver mutations other than the ones previously detected on the primary tissue may emerge, which can confer resistance to the existing therapy.^7,13

Advanced prostatic and lung carcinomas with biochemical, distant organ, or bony progression harbor unique signature genetic mutations indicating poor prognosis, lack of response or resistance to the existing therapy, and high risk of relapse.^14,15 Some of the unique characteristics of the veteran patient population include a more aged patient population multiple comorbidities, higher frequency of > 1 type of cancer, advanced cancer stage at presentation, and specific risks factors such as exposure to Agent Orange in veterans who served during the Vietnam War era.^16,17 We studied the utility of liquid biopsy in cancer care, including type and incidence of genomic alterations associated with advanced prostate and lung cancers, in this unique patient population.

The amount of cell-free DNA (cfDNA), also known as ctDNA varies widely in cancer patients. Some of the factors associated with low concentration of cfDNA are disease stage, intervening therapy, proliferation rates, and tumor vascularization.^18,19 In the peripheral blood, of the total cfDNA, fractions of cfDNA varies from 0.01 to 90%.^18,19 All samples containing ≥ 20 ng cfDNA (20 - 100 ng) were subjected to the hybrid capture-based NGS FoundationACT assay.²⁰ In our study, 2 specimens did not meet the minimum criteria of adequacy (20 ng cfDNA); however, the overall adequacy rate for the detection of mutation, irrespective of the cancer type was 29 of 31 (93.5%) with only 2 inadequate samples. This rate is higher than the rate reported in the literature, which is about 70%.²⁰

Significant differences were encountered in the incidence of DNA damage repair genes including Tp53 mutations when compared with those in the general patient population (Table 2). According to recent National Comprehensive Cancer Network (NCCN) guidelines, all prostate cancers should be screened for DDR gene mutations as these genes are common in aggressive prostate cancers and strongly associated with poor outcomes and shortened survival. Due to relatively high frequency of DDR gene mutations in advanced prostatic cancers, liquid biopsy in patients with these advanced stage prostate cancers may be a useful tool in clinical decision making and exploring targeted therapy.²⁰

We also evaluated the frequency of the most commonly occurring genetic mutations, Tp53 in advanced solid malignancies, especially advanced prostate and NSCLC. Previous studies have reported Tp53 mutation in association with risk factors (carcinogens) of cancer and have been a surrogate marker of poor survival or lack of response of therapy.²⁵ Knowledge of Tp53 mutation is crucial for closer disease monitoring, preparing the patient for rapid progression, and encouraging the physician to prepare future lines of therapy.^25-27 Although Tp53 mutation varies with histologic type and tissue of origin, Beltran and colleagues reported it in 30 to 40% of tumors, while Robles and colleagues reported about 40 to 42% incidence.^25,27

Our study showed notable mutations in 23 of 29 adequate cases. Further, our study showed a high frequency of mutated Tp53 in 65.2% of combined advanced prostate and NSCLC cases. We then correlated cases of Vietnam War-era veterans with risk potential of Agent Orange exposure and Tp53 mutation. We found 7 of 15 Vietnam War-era veterans were positive for Tp53 mutations irrespective of the cancer type. The high incidence of Tp53 mutations in advanced prostate and lung carcinomas in the veteran patient population makes this tumor marker an aspiration not only as a surrogate of aggressive disease and tumor progression, but also as a key marker for targeted therapy in advanced prostate and lung cancers with loss of Tp53 function (Figure 3).

Conclusions

Liquid biopsy successfully provides precision-based oncology and information for decision making in this unique population of veterans. Difference in frequency of the genetic mutations in this cohort can provide future insight into disease progression, lack of response, and mechanism of resistance to the implemented therapy. Future studies focused on this veteran patient population are needed for developing targeted therapies and patient tailored oncologic therapy. ctDNA has a high potential for monitoring clinically relevant cancer-related genetic and epigenetic modifications for discovering more detailed information on the tumor characterization. Although larger cohort trial with longitudinal analyses are needed, high prevalence of DDR gene and Tp53 mutation in our study instills promising hope for therapeutic interventions in this unique cohort.

The minimally invasive liquid biopsy shows a great promise as both diagnostic and prognostic tool in the personalized clinical management of advanced prostate, and NSCLC in the veteran patient population with unique demographic characteristics. De novo metastatic prostate cancer is more common in veterans when compared with the general population, and therefore veterans may benefit by liquid biopsy. Differences in the frequency of genetic mutations (DDR, TP53, AR) in this cohort provides valuable information for disease progression, lack of response, mechanism of resistance to the implemented therapy and clinical decision making. Precision oncology can be further tailored for this cohort by focusing on DNA repair genes and Tp53 mutations for future targeted therapy.