AVAHO

A New Mexico oncologist has once again found himself at odds with the law.    

Mohamed Aswad, MD, was still under probation for a past misdemeanor involving misbranded cancer drugs when he allegedly underdosed chemotherapy in a patient with colon cancer. The patient later died.

In a wrongful death case, a jury has awarded $2.3 million in damages to the patient’s wife. The patient, James Hoag, was diagnosed with stage IIIB colon cancer in 2015. He underwent surgery and then went for chemotherapy to Dr. Aswad, who was the only oncologist in the area.

Mr. Hoag’s attorneys alleged that Dr. Aswad “recklessly administered” abnormally low doses of chemotherapy, and dragged out the normal 6-month regimen to 14 months, in an attempt to “unduly profit.”

“It was statistically likely that James would beat his cancer with proper treatment,” said his lawyers during the trial, according to a report in the Albuquerque Journal.

The jury deliberated for only 4 hours, and found that negligence by Dr. Aswad was a proximate cause of the patient’s “lost chance to avoid the loss of his life and resulting damages,” and the jury further described Dr. Aswad’s actions as “wanton,” according to a verdict form filed in the case.

The form also shows that the jury decided Dr. Aswad had obtained Mr. Hoag’s informed consent as to the treatment, but still felt that negligence was a cause of Mr. Hoag’s injury and damages. The original judgment of $2.9 million in damages was subsequently reduced to $2.3 million as the jury found Mr. Hoag was 30% responsible for his injuries.

Dr. Aswad could not be reached for comment. The Albuquerque Journal reports that he plans to appeal the verdict.
 

Only oncologist in the county

The patient had lived in the rural community of Deming, N.M. following his retirement from a career in law enforcement in Michigan. He was diagnosed with colon cancer in 2015, underwent surgical resection, and then went to Dr. Aswad for follow-up chemotherapy.

Dr. Aswad was the only oncologist in the area. Like many other rural communities throughout the United States, this region has a severe shortage of medical specialists.

Sheila Hoag, the patient’s widow, testified during the trial that following her husband’s surgery in August 2015, which removed the tumor, his “prognosis was very good because they had caught it before it spread.” He had an estimated 5-year survival of about 69%.

However, even though Dr. Aswad followed the National Comprehensive Cancer Network (NCCN) guidelines for adjuvant chemotherapy, he did not use the proper dosing. According to trial testimony, he administered “woefully lower doses” than are recommended, and also exceeded the recommended 6-month duration of chemotherapy by more than double. In addition, Dr. Aswad also failed to adequately monitor the disease during treatment, said Hoag’s lawyers.

Aswad has denied the charges and says that he prescribed a modified regimen spread out over a longer period of time because his patient had requested it. He said that Mr. Hoag did not want to undergo chemotherapy that could cause significant side effects, and this was the reason for the altered treatment plan.

However, the chemotherapy failed to slow the cancer’s progression, and Mr. Hoag never returned to see him after November 2016.

By December 2017, Mr. Hoag had been hospitalized and was being treated by another oncologist, located in Las Cruces, 62 miles away from his home. The new oncologist administered the standard treatment, but by then his cancer had metastasized. Mr. Hoag died in 2020 at age 59.
 

Previous misdemeanor with misbranded drugs

At the time he was treating Mr. Hoag, Dr. Aswad was on federal probation after pleading guilty in 2014 to one misdemeanor count of the unlawful introduction of misbranded drugs into interstate commerce.

Dr. Aswad had treated cancer patients with a “misbranded” drug imported from abroad and not approved by the U.S. Food and Drug Administration (FDA). Altuzan is a form of bevacizumab that is approved for use in Turkey but not the United States. Between July 2010 and April 2012, Dr. Aswad ordered prescription cancer drugs, including Altuzan, from a Canadian company and then administered the “misbranded” drugs to his patients.

A prescription drug is considered to be “misbranded” if it is manufactured in a facility that has not been registered with the FDA for commercial distribution within the United States.

According to various media reports, Dr. Aswad paid significantly less for these drugs than he would have if had he purchased the U.S.-approved product bearing the same brand or generic name, and then billed federal programs such as Medicare for the full price. He has admitted to making just under $1.3 million in profits.

Under the terms of the plea agreement, he was sentenced to three years of probation, required to pay just under $1.3 million in restitution to Medicare and Tricare, the victims of his criminal conduct, and also to forfeit $750,000, which represented part of his net criminal proceeds, to the United States.

At the trial, Dr. Aswad denied that there was any profit motive in extending Mr. Hoag’s treatment, and in a 2019 deposition, he also denied he was under financial pressure to increase his billings because of the $2 million debt that he owed because of the misbranded drugs fine.
 

Allowed to resume practice

In late 2015, Dr. Aswad was essentially barred by the federal government from accepting any reimbursement from Medicaid or Medicare for a minimum of 13 years. But because of the urgent need for medical specialists, the New Mexico Human Services Department requested a waiver that would permit him to continuing treating cancer patients since he is the only oncologist in Luna County.

He is currently allowed to treat Medicaid and Medicare patients in four other medically underserved New Mexico counties.

Dr. Aswad, a graduate of the University of Aleppo, in Syria, had an internal medicine residency at Our Lady of Mercy Hospital in New York City, where he also had a fellowship in oncology and hematology. He then settled in Deming and has been licensed in New Mexico since 2003.

With the onset of the COVID-19 pandemic, which caused major disruption to healthcare services, Medicare & Medicaid Services officials requested that Dr. Aswad also be allowed to provide internal medicine services for Medicare patients in Catron and Hildalgo counties for the “duration of the Coronavirus Disease 2019 public health emergency declared by the federal government in January 2020.”

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

A New Mexico oncologist has once again found himself at odds with the law.    

Mohamed Aswad, MD, was still under probation for a past misdemeanor involving misbranded cancer drugs when he allegedly underdosed chemotherapy in a patient with colon cancer. The patient later died.

In a wrongful death case, a jury has awarded $2.3 million in damages to the patient’s wife. The patient, James Hoag, was diagnosed with stage IIIB colon cancer in 2015. He underwent surgery and then went for chemotherapy to Dr. Aswad, who was the only oncologist in the area.

Mr. Hoag’s attorneys alleged that Dr. Aswad “recklessly administered” abnormally low doses of chemotherapy, and dragged out the normal 6-month regimen to 14 months, in an attempt to “unduly profit.”

“It was statistically likely that James would beat his cancer with proper treatment,” said his lawyers during the trial, according to a report in the Albuquerque Journal.

The jury deliberated for only 4 hours, and found that negligence by Dr. Aswad was a proximate cause of the patient’s “lost chance to avoid the loss of his life and resulting damages,” and the jury further described Dr. Aswad’s actions as “wanton,” according to a verdict form filed in the case.

The form also shows that the jury decided Dr. Aswad had obtained Mr. Hoag’s informed consent as to the treatment, but still felt that negligence was a cause of Mr. Hoag’s injury and damages. The original judgment of $2.9 million in damages was subsequently reduced to $2.3 million as the jury found Mr. Hoag was 30% responsible for his injuries.

Dr. Aswad could not be reached for comment. The Albuquerque Journal reports that he plans to appeal the verdict.
 

Only oncologist in the county

The patient had lived in the rural community of Deming, N.M. following his retirement from a career in law enforcement in Michigan. He was diagnosed with colon cancer in 2015, underwent surgical resection, and then went to Dr. Aswad for follow-up chemotherapy.

Dr. Aswad was the only oncologist in the area. Like many other rural communities throughout the United States, this region has a severe shortage of medical specialists.

Sheila Hoag, the patient’s widow, testified during the trial that following her husband’s surgery in August 2015, which removed the tumor, his “prognosis was very good because they had caught it before it spread.” He had an estimated 5-year survival of about 69%.

However, even though Dr. Aswad followed the National Comprehensive Cancer Network (NCCN) guidelines for adjuvant chemotherapy, he did not use the proper dosing. According to trial testimony, he administered “woefully lower doses” than are recommended, and also exceeded the recommended 6-month duration of chemotherapy by more than double. In addition, Dr. Aswad also failed to adequately monitor the disease during treatment, said Hoag’s lawyers.

Aswad has denied the charges and says that he prescribed a modified regimen spread out over a longer period of time because his patient had requested it. He said that Mr. Hoag did not want to undergo chemotherapy that could cause significant side effects, and this was the reason for the altered treatment plan.

However, the chemotherapy failed to slow the cancer’s progression, and Mr. Hoag never returned to see him after November 2016.

By December 2017, Mr. Hoag had been hospitalized and was being treated by another oncologist, located in Las Cruces, 62 miles away from his home. The new oncologist administered the standard treatment, but by then his cancer had metastasized. Mr. Hoag died in 2020 at age 59.
 

Previous misdemeanor with misbranded drugs

At the time he was treating Mr. Hoag, Dr. Aswad was on federal probation after pleading guilty in 2014 to one misdemeanor count of the unlawful introduction of misbranded drugs into interstate commerce.

Dr. Aswad had treated cancer patients with a “misbranded” drug imported from abroad and not approved by the U.S. Food and Drug Administration (FDA). Altuzan is a form of bevacizumab that is approved for use in Turkey but not the United States. Between July 2010 and April 2012, Dr. Aswad ordered prescription cancer drugs, including Altuzan, from a Canadian company and then administered the “misbranded” drugs to his patients.

A prescription drug is considered to be “misbranded” if it is manufactured in a facility that has not been registered with the FDA for commercial distribution within the United States.

According to various media reports, Dr. Aswad paid significantly less for these drugs than he would have if had he purchased the U.S.-approved product bearing the same brand or generic name, and then billed federal programs such as Medicare for the full price. He has admitted to making just under $1.3 million in profits.

Under the terms of the plea agreement, he was sentenced to three years of probation, required to pay just under $1.3 million in restitution to Medicare and Tricare, the victims of his criminal conduct, and also to forfeit $750,000, which represented part of his net criminal proceeds, to the United States.

At the trial, Dr. Aswad denied that there was any profit motive in extending Mr. Hoag’s treatment, and in a 2019 deposition, he also denied he was under financial pressure to increase his billings because of the $2 million debt that he owed because of the misbranded drugs fine.
 

Allowed to resume practice

In late 2015, Dr. Aswad was essentially barred by the federal government from accepting any reimbursement from Medicaid or Medicare for a minimum of 13 years. But because of the urgent need for medical specialists, the New Mexico Human Services Department requested a waiver that would permit him to continuing treating cancer patients since he is the only oncologist in Luna County.

He is currently allowed to treat Medicaid and Medicare patients in four other medically underserved New Mexico counties.

Dr. Aswad, a graduate of the University of Aleppo, in Syria, had an internal medicine residency at Our Lady of Mercy Hospital in New York City, where he also had a fellowship in oncology and hematology. He then settled in Deming and has been licensed in New Mexico since 2003.

With the onset of the COVID-19 pandemic, which caused major disruption to healthcare services, Medicare & Medicaid Services officials requested that Dr. Aswad also be allowed to provide internal medicine services for Medicare patients in Catron and Hildalgo counties for the “duration of the Coronavirus Disease 2019 public health emergency declared by the federal government in January 2020.”

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

A New Mexico oncologist has once again found himself at odds with the law.    

Mohamed Aswad, MD, was still under probation for a past misdemeanor involving misbranded cancer drugs when he allegedly underdosed chemotherapy in a patient with colon cancer. The patient later died.

In a wrongful death case, a jury has awarded $2.3 million in damages to the patient’s wife. The patient, James Hoag, was diagnosed with stage IIIB colon cancer in 2015. He underwent surgery and then went for chemotherapy to Dr. Aswad, who was the only oncologist in the area.

Mr. Hoag’s attorneys alleged that Dr. Aswad “recklessly administered” abnormally low doses of chemotherapy, and dragged out the normal 6-month regimen to 14 months, in an attempt to “unduly profit.”

“It was statistically likely that James would beat his cancer with proper treatment,” said his lawyers during the trial, according to a report in the Albuquerque Journal.

The jury deliberated for only 4 hours, and found that negligence by Dr. Aswad was a proximate cause of the patient’s “lost chance to avoid the loss of his life and resulting damages,” and the jury further described Dr. Aswad’s actions as “wanton,” according to a verdict form filed in the case.

The form also shows that the jury decided Dr. Aswad had obtained Mr. Hoag’s informed consent as to the treatment, but still felt that negligence was a cause of Mr. Hoag’s injury and damages. The original judgment of $2.9 million in damages was subsequently reduced to $2.3 million as the jury found Mr. Hoag was 30% responsible for his injuries.

Dr. Aswad could not be reached for comment. The Albuquerque Journal reports that he plans to appeal the verdict.
 

Only oncologist in the county

The patient had lived in the rural community of Deming, N.M. following his retirement from a career in law enforcement in Michigan. He was diagnosed with colon cancer in 2015, underwent surgical resection, and then went to Dr. Aswad for follow-up chemotherapy.

Dr. Aswad was the only oncologist in the area. Like many other rural communities throughout the United States, this region has a severe shortage of medical specialists.

Sheila Hoag, the patient’s widow, testified during the trial that following her husband’s surgery in August 2015, which removed the tumor, his “prognosis was very good because they had caught it before it spread.” He had an estimated 5-year survival of about 69%.

However, even though Dr. Aswad followed the National Comprehensive Cancer Network (NCCN) guidelines for adjuvant chemotherapy, he did not use the proper dosing. According to trial testimony, he administered “woefully lower doses” than are recommended, and also exceeded the recommended 6-month duration of chemotherapy by more than double. In addition, Dr. Aswad also failed to adequately monitor the disease during treatment, said Hoag’s lawyers.

Aswad has denied the charges and says that he prescribed a modified regimen spread out over a longer period of time because his patient had requested it. He said that Mr. Hoag did not want to undergo chemotherapy that could cause significant side effects, and this was the reason for the altered treatment plan.

However, the chemotherapy failed to slow the cancer’s progression, and Mr. Hoag never returned to see him after November 2016.

By December 2017, Mr. Hoag had been hospitalized and was being treated by another oncologist, located in Las Cruces, 62 miles away from his home. The new oncologist administered the standard treatment, but by then his cancer had metastasized. Mr. Hoag died in 2020 at age 59.
 

Previous misdemeanor with misbranded drugs

At the time he was treating Mr. Hoag, Dr. Aswad was on federal probation after pleading guilty in 2014 to one misdemeanor count of the unlawful introduction of misbranded drugs into interstate commerce.

Dr. Aswad had treated cancer patients with a “misbranded” drug imported from abroad and not approved by the U.S. Food and Drug Administration (FDA). Altuzan is a form of bevacizumab that is approved for use in Turkey but not the United States. Between July 2010 and April 2012, Dr. Aswad ordered prescription cancer drugs, including Altuzan, from a Canadian company and then administered the “misbranded” drugs to his patients.

A prescription drug is considered to be “misbranded” if it is manufactured in a facility that has not been registered with the FDA for commercial distribution within the United States.

According to various media reports, Dr. Aswad paid significantly less for these drugs than he would have if had he purchased the U.S.-approved product bearing the same brand or generic name, and then billed federal programs such as Medicare for the full price. He has admitted to making just under $1.3 million in profits.

Under the terms of the plea agreement, he was sentenced to three years of probation, required to pay just under $1.3 million in restitution to Medicare and Tricare, the victims of his criminal conduct, and also to forfeit $750,000, which represented part of his net criminal proceeds, to the United States.

At the trial, Dr. Aswad denied that there was any profit motive in extending Mr. Hoag’s treatment, and in a 2019 deposition, he also denied he was under financial pressure to increase his billings because of the $2 million debt that he owed because of the misbranded drugs fine.
 

Allowed to resume practice

In late 2015, Dr. Aswad was essentially barred by the federal government from accepting any reimbursement from Medicaid or Medicare for a minimum of 13 years. But because of the urgent need for medical specialists, the New Mexico Human Services Department requested a waiver that would permit him to continuing treating cancer patients since he is the only oncologist in Luna County.

He is currently allowed to treat Medicaid and Medicare patients in four other medically underserved New Mexico counties.

Dr. Aswad, a graduate of the University of Aleppo, in Syria, had an internal medicine residency at Our Lady of Mercy Hospital in New York City, where he also had a fellowship in oncology and hematology. He then settled in Deming and has been licensed in New Mexico since 2003.

With the onset of the COVID-19 pandemic, which caused major disruption to healthcare services, Medicare & Medicaid Services officials requested that Dr. Aswad also be allowed to provide internal medicine services for Medicare patients in Catron and Hildalgo counties for the “duration of the Coronavirus Disease 2019 public health emergency declared by the federal government in January 2020.”

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

Cumulative annual revenue from cancer drug sales increased by 70% among the world’s largest pharmaceutical companies over the past decade, a retrospective analysis shows.

By comparison, revenues from other types of medications decreased by 18% during the same period.

“Cancer drugs now account for approximately 27% of new drug approvals in the United States, compared to 4% in the 1980s. During this period, there has also been a substantial increase in the price of cancer medicines,” Daniel E. Myers, MD, of the University of Calgary, Canada, and colleagues explain in their report, published online October 6 in Cancer.

To investigate the impact of these trends on pharmaceutical earnings, the investigators performed a retrospective analysis of the revenue generated from oncology drugs in comparison with total drug revenue among 10 large pharmaceutical companies between 2010 and 2019, using itemized product-sales data publicly available through company websites or annual filings.

The data, adjusted for inflation and converted to 2019 U.S. dollars, revealed that annual revenue for the 10 companies increased from $55.8 billion to $95.1 billion during the study period. Most of the growth in revenue occurred in the past 5 years. Over the decade, non-oncology drug revenue decreased by 18% – from $342.2 billion to $281.5 billion.

Overall, revenues from cancer drugs accounted for 25% of the net revenues generated by these companies in 2019, up from 14% in 2010. Roche had both the highest net revenue – $23.9 billion in 2010 and $27.7 billion in 2019 – and the greatest proportion of revenue from cancer drugs – 63.5% in 2016 and 57% in 2019.

Merck saw substantial growth in revenue from cancer drug sales, particularly between 2016 and 2019. In 2016, the company generated $2.4 billion from these medicines, representing 6% of total revenue. By 2019, that amount had grown to $12.3 billion, representing almost 30% of total revenue. This increase was driven largely by their drug pembrolizumab, which alone drew in about $11 billion in 2019, or 12% of total oncology revenue, the investigators note.

Sanofi and GSK had some of the lowest net revenues from cancer drugs during the study period. For instance, in 2019, GSK generated $300 million in revenue from oncology drugs, representing less than 1% of the company’s total revenue, down from 3% of its total revenue in 2010.

“With the cost of cancer drugs rapidly rising, further work is needed to understand how this [overall] increase in sales revenue reflects industry profit, and how this is linked (or not) to improvements in patient and population outcomes,” they conclude. Although data regarding how cancer drug development affects population mortality rates are limited, “there is a notion within biomedicine that rising corporate profitability may not translate into proportional societal gains.”

No funding for the study has been disclosed. The authors have disclosed no relevant financial relationships.

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

Cumulative annual revenue from cancer drug sales increased by 70% among the world’s largest pharmaceutical companies over the past decade, a retrospective analysis shows.

By comparison, revenues from other types of medications decreased by 18% during the same period.

“Cancer drugs now account for approximately 27% of new drug approvals in the United States, compared to 4% in the 1980s. During this period, there has also been a substantial increase in the price of cancer medicines,” Daniel E. Myers, MD, of the University of Calgary, Canada, and colleagues explain in their report, published online October 6 in Cancer.

To investigate the impact of these trends on pharmaceutical earnings, the investigators performed a retrospective analysis of the revenue generated from oncology drugs in comparison with total drug revenue among 10 large pharmaceutical companies between 2010 and 2019, using itemized product-sales data publicly available through company websites or annual filings.

The data, adjusted for inflation and converted to 2019 U.S. dollars, revealed that annual revenue for the 10 companies increased from $55.8 billion to $95.1 billion during the study period. Most of the growth in revenue occurred in the past 5 years. Over the decade, non-oncology drug revenue decreased by 18% – from $342.2 billion to $281.5 billion.

Overall, revenues from cancer drugs accounted for 25% of the net revenues generated by these companies in 2019, up from 14% in 2010. Roche had both the highest net revenue – $23.9 billion in 2010 and $27.7 billion in 2019 – and the greatest proportion of revenue from cancer drugs – 63.5% in 2016 and 57% in 2019.

Merck saw substantial growth in revenue from cancer drug sales, particularly between 2016 and 2019. In 2016, the company generated $2.4 billion from these medicines, representing 6% of total revenue. By 2019, that amount had grown to $12.3 billion, representing almost 30% of total revenue. This increase was driven largely by their drug pembrolizumab, which alone drew in about $11 billion in 2019, or 12% of total oncology revenue, the investigators note.

Sanofi and GSK had some of the lowest net revenues from cancer drugs during the study period. For instance, in 2019, GSK generated $300 million in revenue from oncology drugs, representing less than 1% of the company’s total revenue, down from 3% of its total revenue in 2010.

“With the cost of cancer drugs rapidly rising, further work is needed to understand how this [overall] increase in sales revenue reflects industry profit, and how this is linked (or not) to improvements in patient and population outcomes,” they conclude. Although data regarding how cancer drug development affects population mortality rates are limited, “there is a notion within biomedicine that rising corporate profitability may not translate into proportional societal gains.”

No funding for the study has been disclosed. The authors have disclosed no relevant financial relationships.

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

Cumulative annual revenue from cancer drug sales increased by 70% among the world’s largest pharmaceutical companies over the past decade, a retrospective analysis shows.

By comparison, revenues from other types of medications decreased by 18% during the same period.

“Cancer drugs now account for approximately 27% of new drug approvals in the United States, compared to 4% in the 1980s. During this period, there has also been a substantial increase in the price of cancer medicines,” Daniel E. Myers, MD, of the University of Calgary, Canada, and colleagues explain in their report, published online October 6 in Cancer.

To investigate the impact of these trends on pharmaceutical earnings, the investigators performed a retrospective analysis of the revenue generated from oncology drugs in comparison with total drug revenue among 10 large pharmaceutical companies between 2010 and 2019, using itemized product-sales data publicly available through company websites or annual filings.

The data, adjusted for inflation and converted to 2019 U.S. dollars, revealed that annual revenue for the 10 companies increased from $55.8 billion to $95.1 billion during the study period. Most of the growth in revenue occurred in the past 5 years. Over the decade, non-oncology drug revenue decreased by 18% – from $342.2 billion to $281.5 billion.

Overall, revenues from cancer drugs accounted for 25% of the net revenues generated by these companies in 2019, up from 14% in 2010. Roche had both the highest net revenue – $23.9 billion in 2010 and $27.7 billion in 2019 – and the greatest proportion of revenue from cancer drugs – 63.5% in 2016 and 57% in 2019.

Merck saw substantial growth in revenue from cancer drug sales, particularly between 2016 and 2019. In 2016, the company generated $2.4 billion from these medicines, representing 6% of total revenue. By 2019, that amount had grown to $12.3 billion, representing almost 30% of total revenue. This increase was driven largely by their drug pembrolizumab, which alone drew in about $11 billion in 2019, or 12% of total oncology revenue, the investigators note.

Sanofi and GSK had some of the lowest net revenues from cancer drugs during the study period. For instance, in 2019, GSK generated $300 million in revenue from oncology drugs, representing less than 1% of the company’s total revenue, down from 3% of its total revenue in 2010.

“With the cost of cancer drugs rapidly rising, further work is needed to understand how this [overall] increase in sales revenue reflects industry profit, and how this is linked (or not) to improvements in patient and population outcomes,” they conclude. Although data regarding how cancer drug development affects population mortality rates are limited, “there is a notion within biomedicine that rising corporate profitability may not translate into proportional societal gains.”

No funding for the study has been disclosed. The authors have disclosed no relevant financial relationships.

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

A potential new urine biomarker for prostate cancer not only spots the presence of aggressive tumors, it also indicates the amount of these tumors, according to a recent report.

In a study of biopsy and prostatectomy samples, researchers found that the multigene Prostate Urine Risk-4 (PUR-4) signature was strongly associated with the presence and amount of Gleason pattern 4 tumors, but not tumors of less aggressive histology.

Given that increased Gleason pattern 4 tumor burden is associated with disease progression in men at intermediate risk, the results suggest that “PUR can show us which men at intermediate risk may require treatment and which may instead be managed conservatively with surveillance,” said senior author Jeremy Clark, PhD, of the University of East Anglia, Norwich, England. “PUR will also be useful for monitoring disease in men that do not currently require treatment and flag up the emergence and expansion of aggressive disease.”

The study by Dr. Clark and colleagues was published online on Nov. 3, 2021, in Life.

Tests using the traditional blood-based biomarker for prostate cancer – prostate-specific antigen (PSA) – have limited sensitivity and specificity, leading to unnecessary biopsies and overtreatment.

The PUR biomarker, one of several emerging alternatives to PSA, is a four-group classifier based on 36 genes, Dr. Clark and colleagues explained. Its categories correspond to the probabilities of the presence of normal tissue (PUR-1), and D’Amico low-risk (PUR-2), intermediate-risk (PUR-3), and high-risk (PUR-4) prostate cancer.

Dr. Clark’s team found in earlier research that the PUR-4 signature was able to predict disease progression in men on active surveillance for prostate cancer up to 5 years after a single urine sample. For their latest study, they sought to understand the relationship between PUR-4 and the amount and grade of tumor.

On the basis of biopsy samples from 215 men with prostate cancer, the researchers found that PUR-4 signature values correlated significantly with increasing Gleason grade.

There was no significant difference in PSA level by tumor volume for Gleason grade 1, 2, or 3. The same was true for PUR-4 and Gleason grade 1 tumors, which only contain less clinically significant Gleason pattern 3 cancer. However, PUR-4 values in men with Gleason grade 2 tumors larger than the median were significantly greater than for smaller tumors. PUR-4 values for large Gleason grade 3 tumors were also greater than for smaller ones, although the difference did not reach statistical significance.

“Since [Gleason grade] 2 and [Gleason grade] 3 contain both Gleason pattern 3 and 4 cancer these observations suggest that Gleason Pattern 4 cancer may be contributing to PUR-4 status,” the authors wrote.

The researchers also examined radical-prostatectomy specimens from nine men – three with Gleason grade 1, four with Gleason grade 2, and two with Gleason grade 3 tumors, as determined on the basis of presurgical biopsy.

There was no significant correlation between PUR-4 and PSA levels, nor were PUR-4 values linked to total tumor area or Gleason pattern 3 tumor area. But the amount of Gleason pattern 4 tumors showed a strong correlation with PUR-4 values, which did not change after adjusting for total prostate size.

“Our study shows that the PUR test can assess the amount of Gleason pattern 4 without the need for a biopsy,” Dr. Clark said in an interview. “It could therefore be a very useful tool indeed for assessing a man’s risk of dying from prostate cancer.”

Jack Schalken, PhD, a professor of experimental urology at Radboud University Medical Center in Nijmegen, the Netherlands, called PUR “another test” for prostate cancer the performance of which is in the same range as that of existing products.

“In fact, several tests are commercially available, but the clinical use is surprisingly low,” he told this news organization. Dr. Schalken, who was not involved in the new study, has reviewed several biomarkers for prostate cancer.

The PUR test is now undergoing validation in an international study that is expected to last another 2 years, Dr. Clark said. If successful, the test would stand out for several reasons.

First, it is based on many genes, so it is able to spot malignancies that other tests, which rely on just a few genes, may not pick up. In addition, although it is sensitive to the amount of Gleason pattern 4 tumor, it does not seem to detect the clinically less significant Gleason pattern 3 cancers.

“We have an at-home collection kit – the men do not have to come to a hospital to provide a urine sample,” Dr. Clark said.

The study did not receive commercial funding. Dr. Clark and two coauthors have filed a patent application related to their research.
 

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

A potential new urine biomarker for prostate cancer not only spots the presence of aggressive tumors, it also indicates the amount of these tumors, according to a recent report.

In a study of biopsy and prostatectomy samples, researchers found that the multigene Prostate Urine Risk-4 (PUR-4) signature was strongly associated with the presence and amount of Gleason pattern 4 tumors, but not tumors of less aggressive histology.

Given that increased Gleason pattern 4 tumor burden is associated with disease progression in men at intermediate risk, the results suggest that “PUR can show us which men at intermediate risk may require treatment and which may instead be managed conservatively with surveillance,” said senior author Jeremy Clark, PhD, of the University of East Anglia, Norwich, England. “PUR will also be useful for monitoring disease in men that do not currently require treatment and flag up the emergence and expansion of aggressive disease.”

The study by Dr. Clark and colleagues was published online on Nov. 3, 2021, in Life.

Tests using the traditional blood-based biomarker for prostate cancer – prostate-specific antigen (PSA) – have limited sensitivity and specificity, leading to unnecessary biopsies and overtreatment.

The PUR biomarker, one of several emerging alternatives to PSA, is a four-group classifier based on 36 genes, Dr. Clark and colleagues explained. Its categories correspond to the probabilities of the presence of normal tissue (PUR-1), and D’Amico low-risk (PUR-2), intermediate-risk (PUR-3), and high-risk (PUR-4) prostate cancer.

Dr. Clark’s team found in earlier research that the PUR-4 signature was able to predict disease progression in men on active surveillance for prostate cancer up to 5 years after a single urine sample. For their latest study, they sought to understand the relationship between PUR-4 and the amount and grade of tumor.

On the basis of biopsy samples from 215 men with prostate cancer, the researchers found that PUR-4 signature values correlated significantly with increasing Gleason grade.

There was no significant difference in PSA level by tumor volume for Gleason grade 1, 2, or 3. The same was true for PUR-4 and Gleason grade 1 tumors, which only contain less clinically significant Gleason pattern 3 cancer. However, PUR-4 values in men with Gleason grade 2 tumors larger than the median were significantly greater than for smaller tumors. PUR-4 values for large Gleason grade 3 tumors were also greater than for smaller ones, although the difference did not reach statistical significance.

“Since [Gleason grade] 2 and [Gleason grade] 3 contain both Gleason pattern 3 and 4 cancer these observations suggest that Gleason Pattern 4 cancer may be contributing to PUR-4 status,” the authors wrote.

The researchers also examined radical-prostatectomy specimens from nine men – three with Gleason grade 1, four with Gleason grade 2, and two with Gleason grade 3 tumors, as determined on the basis of presurgical biopsy.

There was no significant correlation between PUR-4 and PSA levels, nor were PUR-4 values linked to total tumor area or Gleason pattern 3 tumor area. But the amount of Gleason pattern 4 tumors showed a strong correlation with PUR-4 values, which did not change after adjusting for total prostate size.

“Our study shows that the PUR test can assess the amount of Gleason pattern 4 without the need for a biopsy,” Dr. Clark said in an interview. “It could therefore be a very useful tool indeed for assessing a man’s risk of dying from prostate cancer.”

Jack Schalken, PhD, a professor of experimental urology at Radboud University Medical Center in Nijmegen, the Netherlands, called PUR “another test” for prostate cancer the performance of which is in the same range as that of existing products.

“In fact, several tests are commercially available, but the clinical use is surprisingly low,” he told this news organization. Dr. Schalken, who was not involved in the new study, has reviewed several biomarkers for prostate cancer.

The PUR test is now undergoing validation in an international study that is expected to last another 2 years, Dr. Clark said. If successful, the test would stand out for several reasons.

First, it is based on many genes, so it is able to spot malignancies that other tests, which rely on just a few genes, may not pick up. In addition, although it is sensitive to the amount of Gleason pattern 4 tumor, it does not seem to detect the clinically less significant Gleason pattern 3 cancers.

“We have an at-home collection kit – the men do not have to come to a hospital to provide a urine sample,” Dr. Clark said.

The study did not receive commercial funding. Dr. Clark and two coauthors have filed a patent application related to their research.
 

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

A potential new urine biomarker for prostate cancer not only spots the presence of aggressive tumors, it also indicates the amount of these tumors, according to a recent report.

In a study of biopsy and prostatectomy samples, researchers found that the multigene Prostate Urine Risk-4 (PUR-4) signature was strongly associated with the presence and amount of Gleason pattern 4 tumors, but not tumors of less aggressive histology.

Given that increased Gleason pattern 4 tumor burden is associated with disease progression in men at intermediate risk, the results suggest that “PUR can show us which men at intermediate risk may require treatment and which may instead be managed conservatively with surveillance,” said senior author Jeremy Clark, PhD, of the University of East Anglia, Norwich, England. “PUR will also be useful for monitoring disease in men that do not currently require treatment and flag up the emergence and expansion of aggressive disease.”

The study by Dr. Clark and colleagues was published online on Nov. 3, 2021, in Life.

Tests using the traditional blood-based biomarker for prostate cancer – prostate-specific antigen (PSA) – have limited sensitivity and specificity, leading to unnecessary biopsies and overtreatment.

The PUR biomarker, one of several emerging alternatives to PSA, is a four-group classifier based on 36 genes, Dr. Clark and colleagues explained. Its categories correspond to the probabilities of the presence of normal tissue (PUR-1), and D’Amico low-risk (PUR-2), intermediate-risk (PUR-3), and high-risk (PUR-4) prostate cancer.

Dr. Clark’s team found in earlier research that the PUR-4 signature was able to predict disease progression in men on active surveillance for prostate cancer up to 5 years after a single urine sample. For their latest study, they sought to understand the relationship between PUR-4 and the amount and grade of tumor.

On the basis of biopsy samples from 215 men with prostate cancer, the researchers found that PUR-4 signature values correlated significantly with increasing Gleason grade.

There was no significant difference in PSA level by tumor volume for Gleason grade 1, 2, or 3. The same was true for PUR-4 and Gleason grade 1 tumors, which only contain less clinically significant Gleason pattern 3 cancer. However, PUR-4 values in men with Gleason grade 2 tumors larger than the median were significantly greater than for smaller tumors. PUR-4 values for large Gleason grade 3 tumors were also greater than for smaller ones, although the difference did not reach statistical significance.

“Since [Gleason grade] 2 and [Gleason grade] 3 contain both Gleason pattern 3 and 4 cancer these observations suggest that Gleason Pattern 4 cancer may be contributing to PUR-4 status,” the authors wrote.

The researchers also examined radical-prostatectomy specimens from nine men – three with Gleason grade 1, four with Gleason grade 2, and two with Gleason grade 3 tumors, as determined on the basis of presurgical biopsy.

There was no significant correlation between PUR-4 and PSA levels, nor were PUR-4 values linked to total tumor area or Gleason pattern 3 tumor area. But the amount of Gleason pattern 4 tumors showed a strong correlation with PUR-4 values, which did not change after adjusting for total prostate size.

“Our study shows that the PUR test can assess the amount of Gleason pattern 4 without the need for a biopsy,” Dr. Clark said in an interview. “It could therefore be a very useful tool indeed for assessing a man’s risk of dying from prostate cancer.”

Jack Schalken, PhD, a professor of experimental urology at Radboud University Medical Center in Nijmegen, the Netherlands, called PUR “another test” for prostate cancer the performance of which is in the same range as that of existing products.

“In fact, several tests are commercially available, but the clinical use is surprisingly low,” he told this news organization. Dr. Schalken, who was not involved in the new study, has reviewed several biomarkers for prostate cancer.

The PUR test is now undergoing validation in an international study that is expected to last another 2 years, Dr. Clark said. If successful, the test would stand out for several reasons.

First, it is based on many genes, so it is able to spot malignancies that other tests, which rely on just a few genes, may not pick up. In addition, although it is sensitive to the amount of Gleason pattern 4 tumor, it does not seem to detect the clinically less significant Gleason pattern 3 cancers.

“We have an at-home collection kit – the men do not have to come to a hospital to provide a urine sample,” Dr. Clark said.

The study did not receive commercial funding. Dr. Clark and two coauthors have filed a patent application related to their research.
 

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

The risk of occult gastric adenocarcinoma is highly prevalent in hereditary lobular breast cancer (HLBC) families who harbor any type of CDH1 variant and this risk remains high in patients with no family history of gastric cancer, a prospective cohort study has shown.

“In short, what we are putting forward with these data is that pathogenic/likely pathogenic (P/LP) variants in the CDH1 gene confer a very high risk, at the very least, of occult early-stage gastric cancer in patients with HLBC,” said Jeremy Davis, MD, of the surgical oncology program, Center for Cancer Research at the National Cancer Institute.

“So patients that are referred to as ‘HLBC’ due to a CDH1 variant should at least undergo annual endoscopic surveillance but the real questions is whether or not they should also consider prophylactic total gastrectomy – as many patients in our study did,” he said.

The study, which was published online Oct. 13, 2021, in JAMA Surgery, included a cohort of 151 families totaling 283 patients with a CDH1 pathogenic or likely pathogenic (P/LP) variant. Analyses were conducted on three patient groups, which included those with HLBC and a family history of breast cancer but no gastric cancer, those with hereditary diffuse gastric cancer (HDGC) but no history of breast cancer, and those with a family history of both gastric and breast cancer in the mixed group. Of these, 15.5% had a history of HLBC, 16.2% had a history of HDGC, and 52.6% made up the mixed group.

“We examined the HLBC group with specific attention to CDH1 genotype and prevalence of occult gastric cancer,” the authors explained. The group consisted of 31 families with 19 CDH1 variants, 10 of which were also present in the HDGC and mixed groups.

Among this group of patients, almost 73% underwent one or more surveillance endoscopies and on endoscopy, occult signet ring cell carcinoma was detected in over one-third of patients.

The median age at the time of endoscopic carcinoma detection was only 33 years.

“Nearly all of the patients with HLBC (93.8%) ... who elected for risk-reducing total gastrectomy owing to their underlying CDH1 P/LP variant harbored occult signet ring cell gastric adenocarcinoma on final pathology,” investigators observed.

The median age at the time patients elected to undergo total gastrectomy was 50 years.

The prevalence of occult gastric cancer among asymptomatic patients in the HDGC group was similarly high, affecting almost 95% of this group of patients.

Some 18 out of 19 CDH1 P/LP variants were responsible for this high prevalence of occult gastric cancer, as the investigators pointed out.

“Hereditary cancer risk is informed by the presence of a germline gene variant more so than by family history of cancer,” the authors stressed. “[And we found that] germline CDH1 P/LP variants appear to have a highly penetrant gastric phenotype irrespective of family history.”

Given this finding, the authors stressed that it is “paramount” patients previously assigned a diagnosis of HLBC not be excluded from undergoing gastric cancer risk assessment and counseling.

Furthermore, “the mere presence of a germline CDH1 P/LP variant, regardless of family history, may be reason enough to consider prophylactic total gastrectomy,” the authors wrote.

Limitations of the study included the fact that the disease phenotype was established from family pedigrees which has the potential for recall bias by family members.

The study was supported in part by the Intramural Research Program of the National Cancer Institute. None of the authors had conflicts of interest to disclose.

The risk of occult gastric adenocarcinoma is highly prevalent in hereditary lobular breast cancer (HLBC) families who harbor any type of CDH1 variant and this risk remains high in patients with no family history of gastric cancer, a prospective cohort study has shown.

“In short, what we are putting forward with these data is that pathogenic/likely pathogenic (P/LP) variants in the CDH1 gene confer a very high risk, at the very least, of occult early-stage gastric cancer in patients with HLBC,” said Jeremy Davis, MD, of the surgical oncology program, Center for Cancer Research at the National Cancer Institute.

“So patients that are referred to as ‘HLBC’ due to a CDH1 variant should at least undergo annual endoscopic surveillance but the real questions is whether or not they should also consider prophylactic total gastrectomy – as many patients in our study did,” he said.

The study, which was published online Oct. 13, 2021, in JAMA Surgery, included a cohort of 151 families totaling 283 patients with a CDH1 pathogenic or likely pathogenic (P/LP) variant. Analyses were conducted on three patient groups, which included those with HLBC and a family history of breast cancer but no gastric cancer, those with hereditary diffuse gastric cancer (HDGC) but no history of breast cancer, and those with a family history of both gastric and breast cancer in the mixed group. Of these, 15.5% had a history of HLBC, 16.2% had a history of HDGC, and 52.6% made up the mixed group.

“We examined the HLBC group with specific attention to CDH1 genotype and prevalence of occult gastric cancer,” the authors explained. The group consisted of 31 families with 19 CDH1 variants, 10 of which were also present in the HDGC and mixed groups.

Among this group of patients, almost 73% underwent one or more surveillance endoscopies and on endoscopy, occult signet ring cell carcinoma was detected in over one-third of patients.

The median age at the time of endoscopic carcinoma detection was only 33 years.

“Nearly all of the patients with HLBC (93.8%) ... who elected for risk-reducing total gastrectomy owing to their underlying CDH1 P/LP variant harbored occult signet ring cell gastric adenocarcinoma on final pathology,” investigators observed.

The median age at the time patients elected to undergo total gastrectomy was 50 years.

The prevalence of occult gastric cancer among asymptomatic patients in the HDGC group was similarly high, affecting almost 95% of this group of patients.

Some 18 out of 19 CDH1 P/LP variants were responsible for this high prevalence of occult gastric cancer, as the investigators pointed out.

“Hereditary cancer risk is informed by the presence of a germline gene variant more so than by family history of cancer,” the authors stressed. “[And we found that] germline CDH1 P/LP variants appear to have a highly penetrant gastric phenotype irrespective of family history.”

Given this finding, the authors stressed that it is “paramount” patients previously assigned a diagnosis of HLBC not be excluded from undergoing gastric cancer risk assessment and counseling.

Furthermore, “the mere presence of a germline CDH1 P/LP variant, regardless of family history, may be reason enough to consider prophylactic total gastrectomy,” the authors wrote.

Limitations of the study included the fact that the disease phenotype was established from family pedigrees which has the potential for recall bias by family members.

The study was supported in part by the Intramural Research Program of the National Cancer Institute. None of the authors had conflicts of interest to disclose.

The risk of occult gastric adenocarcinoma is highly prevalent in hereditary lobular breast cancer (HLBC) families who harbor any type of CDH1 variant and this risk remains high in patients with no family history of gastric cancer, a prospective cohort study has shown.

“In short, what we are putting forward with these data is that pathogenic/likely pathogenic (P/LP) variants in the CDH1 gene confer a very high risk, at the very least, of occult early-stage gastric cancer in patients with HLBC,” said Jeremy Davis, MD, of the surgical oncology program, Center for Cancer Research at the National Cancer Institute.

“So patients that are referred to as ‘HLBC’ due to a CDH1 variant should at least undergo annual endoscopic surveillance but the real questions is whether or not they should also consider prophylactic total gastrectomy – as many patients in our study did,” he said.

The study, which was published online Oct. 13, 2021, in JAMA Surgery, included a cohort of 151 families totaling 283 patients with a CDH1 pathogenic or likely pathogenic (P/LP) variant. Analyses were conducted on three patient groups, which included those with HLBC and a family history of breast cancer but no gastric cancer, those with hereditary diffuse gastric cancer (HDGC) but no history of breast cancer, and those with a family history of both gastric and breast cancer in the mixed group. Of these, 15.5% had a history of HLBC, 16.2% had a history of HDGC, and 52.6% made up the mixed group.

“We examined the HLBC group with specific attention to CDH1 genotype and prevalence of occult gastric cancer,” the authors explained. The group consisted of 31 families with 19 CDH1 variants, 10 of which were also present in the HDGC and mixed groups.

Among this group of patients, almost 73% underwent one or more surveillance endoscopies and on endoscopy, occult signet ring cell carcinoma was detected in over one-third of patients.

The median age at the time of endoscopic carcinoma detection was only 33 years.

“Nearly all of the patients with HLBC (93.8%) ... who elected for risk-reducing total gastrectomy owing to their underlying CDH1 P/LP variant harbored occult signet ring cell gastric adenocarcinoma on final pathology,” investigators observed.

The median age at the time patients elected to undergo total gastrectomy was 50 years.

The prevalence of occult gastric cancer among asymptomatic patients in the HDGC group was similarly high, affecting almost 95% of this group of patients.

Some 18 out of 19 CDH1 P/LP variants were responsible for this high prevalence of occult gastric cancer, as the investigators pointed out.

“Hereditary cancer risk is informed by the presence of a germline gene variant more so than by family history of cancer,” the authors stressed. “[And we found that] germline CDH1 P/LP variants appear to have a highly penetrant gastric phenotype irrespective of family history.”

Given this finding, the authors stressed that it is “paramount” patients previously assigned a diagnosis of HLBC not be excluded from undergoing gastric cancer risk assessment and counseling.

Furthermore, “the mere presence of a germline CDH1 P/LP variant, regardless of family history, may be reason enough to consider prophylactic total gastrectomy,” the authors wrote.

Limitations of the study included the fact that the disease phenotype was established from family pedigrees which has the potential for recall bias by family members.

The study was supported in part by the Intramural Research Program of the National Cancer Institute. None of the authors had conflicts of interest to disclose.

LAS VEGAS – People with obesity may be able to reduce their risk of colorectal cancer with weight loss surgery or medication, researchers say.

“We need to have conversations with our patients in the clinic and educate them that they have these resources available,” said Aakash Desai, MD, a hospitalist at MetroHealth Medical Center, Cleveland, in an interview with this news organization.

Dr. Desai and colleagues found that sleeve gastrectomy and four medications were associated with a reduced risk of colorectal cancer but Roux-en-Y gastrojejunostomy and orlistat were not.

Coauthor Zryan Shwani, MD, a gastroenterology fellow at Sibley Memorial Hospital, Washington, D.C., presented the findings here at the American College of Gastroenterology (ACG) 2021 Annual Scientific Meeting.

Working with an underserved population with high rates of obesity in northeastern Ohio, the researchers wondered how surgery and medication could affect these patients.

They analyzed data from the IBM Explorys clinical database, which compiles and standardizes data from electronic medical records on about 74 million patients from more than 300 U.S. hospitals. Consistent with previous studies, they determined that patients with obesity in the database were 2.5 times more likely than people with a healthy weight to be diagnosed with colorectal cancer (odds ratio, 2.48; 95% CI, 2.45-2.51).

Zeroing in on people who had weight loss interventions, they included adults aged 18-75 years who had undergone either Roux-en-Y gastrojejunostomy or sleeve gastrectomy, or had taken the medications liraglutide, orlistat, phentermine/topiramate, bupropion/naltrexone, or lorcaserin.

They excluded patients with Lynch syndrome, intestinal polyposis syndrome, a family history of gastrointestinal malignancy, inflammatory bowel disease, or tobacco or alcohol abuse. Patients who had taken one of the weight loss medications and also had type 2 diabetes were excluded. They did not include patients who had undergone gastric banding because it has become less popular.

For the weight loss medication group, they found 117,730 patients who met their criteria. For the surgery group, 43,050 patients met the criteria.

In analyzing the colorectal cancer rates, they included only diagnoses of malignant neoplasms made 2 years after the interventions.

They compared these patients to a control group of 52,540 people matched in age, with a body mass index (BMI) greater than 30 kg/m² who did not undergo weight loss surgery or take weight loss medication.

Among the 9,370 patients who underwent Roux-en-Y gastrojejunostomy, 50 were diagnosed with colorectal cancer and 400 had benign polyps. Their rate of colorectal cancer was not statistically different from people who didn’t have surgery (OR, 1.09; 95% CI, 0.82-1.43). The rate of benign polyps after Roux-en-Y gastrojejunostomy was greater (OR, 1.72; 95% CI, 1.55-1.90).

On the other hand, among the 33,680 patients who underwent sleeve gastrectomy, 50 were diagnosed with colorectal cancer, a lower rate than in the population who didn’t have surgery (OR, 0.30; 95% CI, 0.22-0.39). Their risk of benign polyps was also reduced (OR, 0.45; 95% CI, 0.40-0.50).

All of the medications were significantly associated with a lower risk of colorectal cancer, except orlistat (OR, 0.94; 95% CI, 0.72-1.25).

The finding on Roux-en-Y gastrojejunostomy agreed with studies from England and Nordic countries showing double the risk of colorectal cancer in those patients but conflicted with a French study showing decreased risk, Dr. Shwani said.

While the study doesn’t establish a reason why Roux-en-Y gastrojejunostomy was less beneficial, other researchers have associated the procedure with biomarkers of inflammation, Dr. Shwani said. “It’s inconsistent, and I don’t think we have a clear answer why.”

As a retrospective analysis, the study could not establish a cause-and-effect relationship between surgery or medication and cancer, or adjust for such factors as diet, exercise, or genes, he acknowledged.

Colorectal cancer is just one outcome to consider when deciding whether to undergo weight loss surgery or take weight loss drugs, said session moderator Mohammad Yaghoobi, MD, an associate professor of medicine at McMaster University, Hamilton, Ont.

“The most important outcome that should be investigated is the survival of the patients after obesity surgery,” he told this news organization. “The second would be the quality of life of those patients. Colon cancer is preventable if you are having regular colonoscopies.”

Other studies have not shown much difference between patients who have weight loss surgery and those who don’t, he added.

The study was funded by Merck. Dr. Desai and Dr. Shwani have reported receiving grant funding from Merck. Dr. Yaghoobi has reported no relevant financial relationships.

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

LAS VEGAS – People with obesity may be able to reduce their risk of colorectal cancer with weight loss surgery or medication, researchers say.

“We need to have conversations with our patients in the clinic and educate them that they have these resources available,” said Aakash Desai, MD, a hospitalist at MetroHealth Medical Center, Cleveland, in an interview with this news organization.

Dr. Desai and colleagues found that sleeve gastrectomy and four medications were associated with a reduced risk of colorectal cancer but Roux-en-Y gastrojejunostomy and orlistat were not.

Coauthor Zryan Shwani, MD, a gastroenterology fellow at Sibley Memorial Hospital, Washington, D.C., presented the findings here at the American College of Gastroenterology (ACG) 2021 Annual Scientific Meeting.

Working with an underserved population with high rates of obesity in northeastern Ohio, the researchers wondered how surgery and medication could affect these patients.

They analyzed data from the IBM Explorys clinical database, which compiles and standardizes data from electronic medical records on about 74 million patients from more than 300 U.S. hospitals. Consistent with previous studies, they determined that patients with obesity in the database were 2.5 times more likely than people with a healthy weight to be diagnosed with colorectal cancer (odds ratio, 2.48; 95% CI, 2.45-2.51).

Zeroing in on people who had weight loss interventions, they included adults aged 18-75 years who had undergone either Roux-en-Y gastrojejunostomy or sleeve gastrectomy, or had taken the medications liraglutide, orlistat, phentermine/topiramate, bupropion/naltrexone, or lorcaserin.

They excluded patients with Lynch syndrome, intestinal polyposis syndrome, a family history of gastrointestinal malignancy, inflammatory bowel disease, or tobacco or alcohol abuse. Patients who had taken one of the weight loss medications and also had type 2 diabetes were excluded. They did not include patients who had undergone gastric banding because it has become less popular.

For the weight loss medication group, they found 117,730 patients who met their criteria. For the surgery group, 43,050 patients met the criteria.

In analyzing the colorectal cancer rates, they included only diagnoses of malignant neoplasms made 2 years after the interventions.

They compared these patients to a control group of 52,540 people matched in age, with a body mass index (BMI) greater than 30 kg/m² who did not undergo weight loss surgery or take weight loss medication.

Among the 9,370 patients who underwent Roux-en-Y gastrojejunostomy, 50 were diagnosed with colorectal cancer and 400 had benign polyps. Their rate of colorectal cancer was not statistically different from people who didn’t have surgery (OR, 1.09; 95% CI, 0.82-1.43). The rate of benign polyps after Roux-en-Y gastrojejunostomy was greater (OR, 1.72; 95% CI, 1.55-1.90).

On the other hand, among the 33,680 patients who underwent sleeve gastrectomy, 50 were diagnosed with colorectal cancer, a lower rate than in the population who didn’t have surgery (OR, 0.30; 95% CI, 0.22-0.39). Their risk of benign polyps was also reduced (OR, 0.45; 95% CI, 0.40-0.50).

All of the medications were significantly associated with a lower risk of colorectal cancer, except orlistat (OR, 0.94; 95% CI, 0.72-1.25).

The finding on Roux-en-Y gastrojejunostomy agreed with studies from England and Nordic countries showing double the risk of colorectal cancer in those patients but conflicted with a French study showing decreased risk, Dr. Shwani said.

While the study doesn’t establish a reason why Roux-en-Y gastrojejunostomy was less beneficial, other researchers have associated the procedure with biomarkers of inflammation, Dr. Shwani said. “It’s inconsistent, and I don’t think we have a clear answer why.”

As a retrospective analysis, the study could not establish a cause-and-effect relationship between surgery or medication and cancer, or adjust for such factors as diet, exercise, or genes, he acknowledged.

Colorectal cancer is just one outcome to consider when deciding whether to undergo weight loss surgery or take weight loss drugs, said session moderator Mohammad Yaghoobi, MD, an associate professor of medicine at McMaster University, Hamilton, Ont.

“The most important outcome that should be investigated is the survival of the patients after obesity surgery,” he told this news organization. “The second would be the quality of life of those patients. Colon cancer is preventable if you are having regular colonoscopies.”

Other studies have not shown much difference between patients who have weight loss surgery and those who don’t, he added.

The study was funded by Merck. Dr. Desai and Dr. Shwani have reported receiving grant funding from Merck. Dr. Yaghoobi has reported no relevant financial relationships.

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

LAS VEGAS – People with obesity may be able to reduce their risk of colorectal cancer with weight loss surgery or medication, researchers say.

“We need to have conversations with our patients in the clinic and educate them that they have these resources available,” said Aakash Desai, MD, a hospitalist at MetroHealth Medical Center, Cleveland, in an interview with this news organization.

Dr. Desai and colleagues found that sleeve gastrectomy and four medications were associated with a reduced risk of colorectal cancer but Roux-en-Y gastrojejunostomy and orlistat were not.

Coauthor Zryan Shwani, MD, a gastroenterology fellow at Sibley Memorial Hospital, Washington, D.C., presented the findings here at the American College of Gastroenterology (ACG) 2021 Annual Scientific Meeting.

Working with an underserved population with high rates of obesity in northeastern Ohio, the researchers wondered how surgery and medication could affect these patients.

They analyzed data from the IBM Explorys clinical database, which compiles and standardizes data from electronic medical records on about 74 million patients from more than 300 U.S. hospitals. Consistent with previous studies, they determined that patients with obesity in the database were 2.5 times more likely than people with a healthy weight to be diagnosed with colorectal cancer (odds ratio, 2.48; 95% CI, 2.45-2.51).

Zeroing in on people who had weight loss interventions, they included adults aged 18-75 years who had undergone either Roux-en-Y gastrojejunostomy or sleeve gastrectomy, or had taken the medications liraglutide, orlistat, phentermine/topiramate, bupropion/naltrexone, or lorcaserin.

They excluded patients with Lynch syndrome, intestinal polyposis syndrome, a family history of gastrointestinal malignancy, inflammatory bowel disease, or tobacco or alcohol abuse. Patients who had taken one of the weight loss medications and also had type 2 diabetes were excluded. They did not include patients who had undergone gastric banding because it has become less popular.

For the weight loss medication group, they found 117,730 patients who met their criteria. For the surgery group, 43,050 patients met the criteria.

In analyzing the colorectal cancer rates, they included only diagnoses of malignant neoplasms made 2 years after the interventions.

They compared these patients to a control group of 52,540 people matched in age, with a body mass index (BMI) greater than 30 kg/m² who did not undergo weight loss surgery or take weight loss medication.

Among the 9,370 patients who underwent Roux-en-Y gastrojejunostomy, 50 were diagnosed with colorectal cancer and 400 had benign polyps. Their rate of colorectal cancer was not statistically different from people who didn’t have surgery (OR, 1.09; 95% CI, 0.82-1.43). The rate of benign polyps after Roux-en-Y gastrojejunostomy was greater (OR, 1.72; 95% CI, 1.55-1.90).

On the other hand, among the 33,680 patients who underwent sleeve gastrectomy, 50 were diagnosed with colorectal cancer, a lower rate than in the population who didn’t have surgery (OR, 0.30; 95% CI, 0.22-0.39). Their risk of benign polyps was also reduced (OR, 0.45; 95% CI, 0.40-0.50).

All of the medications were significantly associated with a lower risk of colorectal cancer, except orlistat (OR, 0.94; 95% CI, 0.72-1.25).

The finding on Roux-en-Y gastrojejunostomy agreed with studies from England and Nordic countries showing double the risk of colorectal cancer in those patients but conflicted with a French study showing decreased risk, Dr. Shwani said.

While the study doesn’t establish a reason why Roux-en-Y gastrojejunostomy was less beneficial, other researchers have associated the procedure with biomarkers of inflammation, Dr. Shwani said. “It’s inconsistent, and I don’t think we have a clear answer why.”

As a retrospective analysis, the study could not establish a cause-and-effect relationship between surgery or medication and cancer, or adjust for such factors as diet, exercise, or genes, he acknowledged.

Colorectal cancer is just one outcome to consider when deciding whether to undergo weight loss surgery or take weight loss drugs, said session moderator Mohammad Yaghoobi, MD, an associate professor of medicine at McMaster University, Hamilton, Ont.

“The most important outcome that should be investigated is the survival of the patients after obesity surgery,” he told this news organization. “The second would be the quality of life of those patients. Colon cancer is preventable if you are having regular colonoscopies.”

Other studies have not shown much difference between patients who have weight loss surgery and those who don’t, he added.

The study was funded by Merck. Dr. Desai and Dr. Shwani have reported receiving grant funding from Merck. Dr. Yaghoobi has reported no relevant financial relationships.

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

Stereotactic body radiation therapy (SBRT) directed at progressive lesions in patients with oligoprogressive metastatic non–small cell lung cancer (NSCLC) was beneficial and significantly improved progression-free survival (PFS), suggest clinical trial results presented this week.

Patients treated with SBRT had a median PFS of 44 weeks, compared with 9 weeks for those who received standard care.

However, no benefit was observed in patients with metastatic breast cancer. There was no significant difference in PFS between the two groups (18 weeks with SBRT vs. 19 weeks with standard care).

“In this preplanned interim analysis, we demonstrated the benefit of SBRT to sites of oligoprogression on overall progression-free survival, which was the primary endpoint,” said lead author C. Jillian Tsai, MD, PhD, a radiation oncologist and director of metastatic disease radiation oncology research at Memorial Sloan Kettering Cancer Center in New York. “The difference was driven by the substantial response in [this] NSCLC cohort.”

There was no benefit of SBRT seen in the breast cohort, she noted, and most breast patients developed new lesions upon further progression.

Dr. Tsai and colleagues are planning to close the trial early, after the interim analysis established the benefit of SBRT. They are now investigating why SBRT was beneficial in NSCLC but not in breast cancer.

The findings were presented at the American Society for Radiation Oncology (ASTRO) annual meeting.

Dr. Tsai explained that the current standard of care for patients with oligoprogressive metastatic NSCLC is to switch to a different targeted therapy or chemotherapy following progression, but options may be limited. Efficacy for second-line therapy can be poor, with PFS ranging from about 4 months to 10 months for NSCLC, “and after second line, efficacy for third and fourth lines is even poorer,” she said.

Similarly, for breast cancer, PFS ranges from about 9 months to 20 months for estrogen-receptor positive patients. “But for triple negative patients, there really is no standard of care and PFS is poor,” Dr. Tsai said.
 

SBRT superior to standard of care

The authors hypothesized that there is an oligoprogressive state in metastatic cancer, in which disease control can be improved by applying local therapy to progressive lesions only.

The cohort included 102 patients with metastatic NSCLC or breast cancer who had received one or more lines of systemic therapy and had oligoprogressive lesions amenable to SBRT. There was no upper limit of nonprogressive lesions.

Oligoprogression was defined as Response Evaluation or Positron Emission Tomography Response Criteria in Solid Tumors documented progression ≤5 individual lesions.

Patients were randomly assigned to receive either SBRT to all progressive sites plus palliative standard of care or systemic SOC only. Systemic therapy was per physician’s discretion.

There were 58 patients with NSCLC (30 in the SBRT group) and 44 patients with breast cancer (22 in each group).

Most patients (75%) had more than one site of oligoprogression and 47% had more than 5 total metastatic lesions. About half of patients (54%) had received immunotherapy and the majority of those with NSCLC (86%) did not harbor an actionable driver mutation. About one-third (32%) of the breast cancer cohort were triple negative.

Patients were followed for a median of 45 weeks (58 weeks for living patients), by which time 78 (74%) had experienced further tumor progression and 39 (37%) had died.

Median progression-free survival for the entire cohort was 31 weeks for SBRT and 11 weeks for palliative SOC (P = .002).

In multivariable analysis that stratified for factors including age, sex, lines of systemic therapy, and change of systemic therapy, the progression-free survival benefit of SBRT continued to remain substantial in the NSCLC cohort (hazard ratio: 0.38; P = .007).

Adverse events were higher in the SBRT group. Grade 2 or higher adverse events occurred in 23 (61%) of SBRT patients, and 15 (40%) of SOC patients (P = .13).
 

Hoped-for results, with a few caveats

Approached for comment on the new findings, Clifford Robinson, MD, professor of radiation oncology, chief of SBRT service, and director of clinical trials and informatics at Washington University, St. Louis, said the results tie in with previous findings.

There are multiple published or presented prospective randomized phase 2 and 3 trials in various disease sites that have explored the role of local therapy, including SBRT, for patients who present with oligometastatic disease.

“These studies have nearly uniformly shown improvements in progression-free and/or overall survival with the inclusion of local therapy,” he told this news organization. Dr. Robinson was not involved with the study.

He explained that relatively few patients present with oligometastatic disease. However, many patients present with more advanced disease, but after an initial course of systemic therapy, develop oligoprogression.

“There is tremendous appeal to using local therapy at the time of oligoprogression in lieu of switching systemic therapy,” said Dr. Robinson. “It allows patients to stay on systemic therapy that is otherwise effective for the remainder of their disease.”

First-line systemic therapies are the most effective and the most tolerable, he continued, and switching systemic therapy introduces the potential for more toxicity and less efficacy. Therefore, it has become increasingly popular to offer SBRT to one or a few sites of oligoprogressive disease based on the results of oligometastatic disease.

“However, there is no established prospective data to guide this practice,” he said. “This trial is the first to examine this carefully in lung and breast cancer patients, and this trial shows what we hoped to see – that use of SBRT after oligoprogression results in improved progression-free survival as compared with standard of care alone. And this was accomplished with limited toxicity.”

There are a few caveats, though, he pointed out. “Progression-free survival is defined as time to first progression or death,” he said. “Since we don’t know what the overall survival is in this abstract, it’s entirely possible that patients live for the same length of time, but just take longer to progress.”

Another caveat is that this was a planned interim analysis. “Typically, planned interim analyses occur to see if the trial should be stopped or to adjust the study based on results,” he said. “It’s unclear what the investigators will do with this information.”

“But overall, these are very exciting data and lend support to the increasingly common practice of treating oligoprogressive disease,” Dr. Robinson added. “Since most of the serious adverse events of SBRT occur later, longer follow-up is needed, although the median survival of patients may not reach that timepoint.”

“For now, practice should not be altered based on these interim results,” he added.

Dr. Tsai reported acting as a consultant/advisor for Varian and Galera and also receiving research funding from Varian. Dr. Robinson reports stock/ownership in Radialogica, acting as a consultant/advisor for Varian, AstraZeneca, EMD Serono, Quantitative Radiology Solutions, research funding from Varian and Merck, and owning patents on systems for cardiac arrhythmias and ablation.

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

Stereotactic body radiation therapy (SBRT) directed at progressive lesions in patients with oligoprogressive metastatic non–small cell lung cancer (NSCLC) was beneficial and significantly improved progression-free survival (PFS), suggest clinical trial results presented this week.

Patients treated with SBRT had a median PFS of 44 weeks, compared with 9 weeks for those who received standard care.

However, no benefit was observed in patients with metastatic breast cancer. There was no significant difference in PFS between the two groups (18 weeks with SBRT vs. 19 weeks with standard care).

“In this preplanned interim analysis, we demonstrated the benefit of SBRT to sites of oligoprogression on overall progression-free survival, which was the primary endpoint,” said lead author C. Jillian Tsai, MD, PhD, a radiation oncologist and director of metastatic disease radiation oncology research at Memorial Sloan Kettering Cancer Center in New York. “The difference was driven by the substantial response in [this] NSCLC cohort.”

There was no benefit of SBRT seen in the breast cohort, she noted, and most breast patients developed new lesions upon further progression.

Dr. Tsai and colleagues are planning to close the trial early, after the interim analysis established the benefit of SBRT. They are now investigating why SBRT was beneficial in NSCLC but not in breast cancer.

The findings were presented at the American Society for Radiation Oncology (ASTRO) annual meeting.

Dr. Tsai explained that the current standard of care for patients with oligoprogressive metastatic NSCLC is to switch to a different targeted therapy or chemotherapy following progression, but options may be limited. Efficacy for second-line therapy can be poor, with PFS ranging from about 4 months to 10 months for NSCLC, “and after second line, efficacy for third and fourth lines is even poorer,” she said.

Similarly, for breast cancer, PFS ranges from about 9 months to 20 months for estrogen-receptor positive patients. “But for triple negative patients, there really is no standard of care and PFS is poor,” Dr. Tsai said.
 

SBRT superior to standard of care

The authors hypothesized that there is an oligoprogressive state in metastatic cancer, in which disease control can be improved by applying local therapy to progressive lesions only.

The cohort included 102 patients with metastatic NSCLC or breast cancer who had received one or more lines of systemic therapy and had oligoprogressive lesions amenable to SBRT. There was no upper limit of nonprogressive lesions.

Oligoprogression was defined as Response Evaluation or Positron Emission Tomography Response Criteria in Solid Tumors documented progression ≤5 individual lesions.

Patients were randomly assigned to receive either SBRT to all progressive sites plus palliative standard of care or systemic SOC only. Systemic therapy was per physician’s discretion.

There were 58 patients with NSCLC (30 in the SBRT group) and 44 patients with breast cancer (22 in each group).

Most patients (75%) had more than one site of oligoprogression and 47% had more than 5 total metastatic lesions. About half of patients (54%) had received immunotherapy and the majority of those with NSCLC (86%) did not harbor an actionable driver mutation. About one-third (32%) of the breast cancer cohort were triple negative.

Patients were followed for a median of 45 weeks (58 weeks for living patients), by which time 78 (74%) had experienced further tumor progression and 39 (37%) had died.

Median progression-free survival for the entire cohort was 31 weeks for SBRT and 11 weeks for palliative SOC (P = .002).

In multivariable analysis that stratified for factors including age, sex, lines of systemic therapy, and change of systemic therapy, the progression-free survival benefit of SBRT continued to remain substantial in the NSCLC cohort (hazard ratio: 0.38; P = .007).

Adverse events were higher in the SBRT group. Grade 2 or higher adverse events occurred in 23 (61%) of SBRT patients, and 15 (40%) of SOC patients (P = .13).
 

Hoped-for results, with a few caveats

Approached for comment on the new findings, Clifford Robinson, MD, professor of radiation oncology, chief of SBRT service, and director of clinical trials and informatics at Washington University, St. Louis, said the results tie in with previous findings.

There are multiple published or presented prospective randomized phase 2 and 3 trials in various disease sites that have explored the role of local therapy, including SBRT, for patients who present with oligometastatic disease.

“These studies have nearly uniformly shown improvements in progression-free and/or overall survival with the inclusion of local therapy,” he told this news organization. Dr. Robinson was not involved with the study.

He explained that relatively few patients present with oligometastatic disease. However, many patients present with more advanced disease, but after an initial course of systemic therapy, develop oligoprogression.

“There is tremendous appeal to using local therapy at the time of oligoprogression in lieu of switching systemic therapy,” said Dr. Robinson. “It allows patients to stay on systemic therapy that is otherwise effective for the remainder of their disease.”

First-line systemic therapies are the most effective and the most tolerable, he continued, and switching systemic therapy introduces the potential for more toxicity and less efficacy. Therefore, it has become increasingly popular to offer SBRT to one or a few sites of oligoprogressive disease based on the results of oligometastatic disease.

“However, there is no established prospective data to guide this practice,” he said. “This trial is the first to examine this carefully in lung and breast cancer patients, and this trial shows what we hoped to see – that use of SBRT after oligoprogression results in improved progression-free survival as compared with standard of care alone. And this was accomplished with limited toxicity.”

There are a few caveats, though, he pointed out. “Progression-free survival is defined as time to first progression or death,” he said. “Since we don’t know what the overall survival is in this abstract, it’s entirely possible that patients live for the same length of time, but just take longer to progress.”

Another caveat is that this was a planned interim analysis. “Typically, planned interim analyses occur to see if the trial should be stopped or to adjust the study based on results,” he said. “It’s unclear what the investigators will do with this information.”

“But overall, these are very exciting data and lend support to the increasingly common practice of treating oligoprogressive disease,” Dr. Robinson added. “Since most of the serious adverse events of SBRT occur later, longer follow-up is needed, although the median survival of patients may not reach that timepoint.”

“For now, practice should not be altered based on these interim results,” he added.

Dr. Tsai reported acting as a consultant/advisor for Varian and Galera and also receiving research funding from Varian. Dr. Robinson reports stock/ownership in Radialogica, acting as a consultant/advisor for Varian, AstraZeneca, EMD Serono, Quantitative Radiology Solutions, research funding from Varian and Merck, and owning patents on systems for cardiac arrhythmias and ablation.

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

Stereotactic body radiation therapy (SBRT) directed at progressive lesions in patients with oligoprogressive metastatic non–small cell lung cancer (NSCLC) was beneficial and significantly improved progression-free survival (PFS), suggest clinical trial results presented this week.

Patients treated with SBRT had a median PFS of 44 weeks, compared with 9 weeks for those who received standard care.

However, no benefit was observed in patients with metastatic breast cancer. There was no significant difference in PFS between the two groups (18 weeks with SBRT vs. 19 weeks with standard care).

“In this preplanned interim analysis, we demonstrated the benefit of SBRT to sites of oligoprogression on overall progression-free survival, which was the primary endpoint,” said lead author C. Jillian Tsai, MD, PhD, a radiation oncologist and director of metastatic disease radiation oncology research at Memorial Sloan Kettering Cancer Center in New York. “The difference was driven by the substantial response in [this] NSCLC cohort.”

There was no benefit of SBRT seen in the breast cohort, she noted, and most breast patients developed new lesions upon further progression.

Dr. Tsai and colleagues are planning to close the trial early, after the interim analysis established the benefit of SBRT. They are now investigating why SBRT was beneficial in NSCLC but not in breast cancer.

The findings were presented at the American Society for Radiation Oncology (ASTRO) annual meeting.

Dr. Tsai explained that the current standard of care for patients with oligoprogressive metastatic NSCLC is to switch to a different targeted therapy or chemotherapy following progression, but options may be limited. Efficacy for second-line therapy can be poor, with PFS ranging from about 4 months to 10 months for NSCLC, “and after second line, efficacy for third and fourth lines is even poorer,” she said.

Similarly, for breast cancer, PFS ranges from about 9 months to 20 months for estrogen-receptor positive patients. “But for triple negative patients, there really is no standard of care and PFS is poor,” Dr. Tsai said.
 

SBRT superior to standard of care

The authors hypothesized that there is an oligoprogressive state in metastatic cancer, in which disease control can be improved by applying local therapy to progressive lesions only.

The cohort included 102 patients with metastatic NSCLC or breast cancer who had received one or more lines of systemic therapy and had oligoprogressive lesions amenable to SBRT. There was no upper limit of nonprogressive lesions.

Oligoprogression was defined as Response Evaluation or Positron Emission Tomography Response Criteria in Solid Tumors documented progression ≤5 individual lesions.

Patients were randomly assigned to receive either SBRT to all progressive sites plus palliative standard of care or systemic SOC only. Systemic therapy was per physician’s discretion.

There were 58 patients with NSCLC (30 in the SBRT group) and 44 patients with breast cancer (22 in each group).

Most patients (75%) had more than one site of oligoprogression and 47% had more than 5 total metastatic lesions. About half of patients (54%) had received immunotherapy and the majority of those with NSCLC (86%) did not harbor an actionable driver mutation. About one-third (32%) of the breast cancer cohort were triple negative.

Patients were followed for a median of 45 weeks (58 weeks for living patients), by which time 78 (74%) had experienced further tumor progression and 39 (37%) had died.

Median progression-free survival for the entire cohort was 31 weeks for SBRT and 11 weeks for palliative SOC (P = .002).

In multivariable analysis that stratified for factors including age, sex, lines of systemic therapy, and change of systemic therapy, the progression-free survival benefit of SBRT continued to remain substantial in the NSCLC cohort (hazard ratio: 0.38; P = .007).

Adverse events were higher in the SBRT group. Grade 2 or higher adverse events occurred in 23 (61%) of SBRT patients, and 15 (40%) of SOC patients (P = .13).
 

Hoped-for results, with a few caveats

Approached for comment on the new findings, Clifford Robinson, MD, professor of radiation oncology, chief of SBRT service, and director of clinical trials and informatics at Washington University, St. Louis, said the results tie in with previous findings.

There are multiple published or presented prospective randomized phase 2 and 3 trials in various disease sites that have explored the role of local therapy, including SBRT, for patients who present with oligometastatic disease.

“These studies have nearly uniformly shown improvements in progression-free and/or overall survival with the inclusion of local therapy,” he told this news organization. Dr. Robinson was not involved with the study.

He explained that relatively few patients present with oligometastatic disease. However, many patients present with more advanced disease, but after an initial course of systemic therapy, develop oligoprogression.

“There is tremendous appeal to using local therapy at the time of oligoprogression in lieu of switching systemic therapy,” said Dr. Robinson. “It allows patients to stay on systemic therapy that is otherwise effective for the remainder of their disease.”

First-line systemic therapies are the most effective and the most tolerable, he continued, and switching systemic therapy introduces the potential for more toxicity and less efficacy. Therefore, it has become increasingly popular to offer SBRT to one or a few sites of oligoprogressive disease based on the results of oligometastatic disease.

“However, there is no established prospective data to guide this practice,” he said. “This trial is the first to examine this carefully in lung and breast cancer patients, and this trial shows what we hoped to see – that use of SBRT after oligoprogression results in improved progression-free survival as compared with standard of care alone. And this was accomplished with limited toxicity.”

There are a few caveats, though, he pointed out. “Progression-free survival is defined as time to first progression or death,” he said. “Since we don’t know what the overall survival is in this abstract, it’s entirely possible that patients live for the same length of time, but just take longer to progress.”

Another caveat is that this was a planned interim analysis. “Typically, planned interim analyses occur to see if the trial should be stopped or to adjust the study based on results,” he said. “It’s unclear what the investigators will do with this information.”

“But overall, these are very exciting data and lend support to the increasingly common practice of treating oligoprogressive disease,” Dr. Robinson added. “Since most of the serious adverse events of SBRT occur later, longer follow-up is needed, although the median survival of patients may not reach that timepoint.”

“For now, practice should not be altered based on these interim results,” he added.

Dr. Tsai reported acting as a consultant/advisor for Varian and Galera and also receiving research funding from Varian. Dr. Robinson reports stock/ownership in Radialogica, acting as a consultant/advisor for Varian, AstraZeneca, EMD Serono, Quantitative Radiology Solutions, research funding from Varian and Merck, and owning patents on systems for cardiac arrhythmias and ablation.

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

The largest-ever breast cancer screening trial in the United States, which is federally funded with costs expected to reach $100 million, is a “waste,” says prominent radiologist Daniel Kopans, MD, from Harvard Medical School, Boston. Funding for this trial is largely misspent money, it may produce misleading results, and it should be abandoned, he says.

Dr. Kopans has been an outspoken critic of the trial, describing it as a “huge waste of money” in comments made last year. Now he has set out his criticisms of the trial in an essay published in the October issue of Clinical Imaging, which outlines his objections and concerns for the first time in a peer-reviewed journal.

The Tomosynthesis Mammographic Imaging Screening Trial (TMIST) is comparing digital breast tomosynthesis (DBT), also known as 3-D mammography, with the older 2-D technology or full-field digital mammography (FFDM).

Dr. Kopans coined the term DBT and formerly held a now-expired patent on the first version of this technology.

“It could be argued that the imaging part of TMIST is a waste of valuable resources,” he writes in the essay.

The “imaging part” of the trial refers to the primary outcome measure and driving purpose of the trial, which is designed to learn which technology is better at finding – and reducing the rate of – potentially lethal “advanced” cancers.

These cancers include larger HER2-positive and triple-negative malignancies; those associated with positive nodes; and metastatic disease. These malignancies correlate with breast cancer mortality, TMIST’s principal investigator Etta Pisano, MD, of the American College of Radiology, has said in the past.

However, Dr. Kopans says that this surrogate endpoint is problematic. “TMIST will only investigate whether or not digital breast tomography results in a decline in advanced cancers, ignoring the fact that many women still die from cancers that are not advanced at the time of diagnosis,” he writes.

“Clearly reducing the rate of advanced cancers is not the only way that early detection saves lives. Lives are also saved by finding cancers at a smaller size within stages,” Dr. Kopans writes. He adds that DBT has been proven in observational cohort studies to find more smaller breast cancers than FFDM.

Dr. Kopans’ opinion that TMIST is largely a waste of resources is not shared by the National Cancer Institute. “We feel strongly that TMIST is a critical study,” an NCI spokesperson told this news organization.
 

Study power concerns

Another concern is that TMIST “may be underpowered,” Dr. Kopans writes. That concern arises in part from a recent review of TMIST by an advisory committee (that was prompted by low patient accrual rates), which proposed reducing the size of the trial. Dr. Kopans says this would result in “a reduction of the planned power of the trial.”  

The NCI says that reducing the study size has been discussed but has not yet been implemented. “Any reduction in size would, of course, have appropriate statistical considerations in mind,” according to the NCI spokesperson.

Dr. Kopans’ concern about statistical power extends beyond downsizing the trial. An advanced cancer in TMIST is counted “if it occurs at any time while the participant is on study,” according to the NCI. Dr. Kopans says that is a problem.

“Since DBT cannot have any effect on advanced cancers in the prevalence year (they are already there), data from the first year (prevalence cancers are likely the largest number) will be unusable, and if used will, inappropriately, dilute the results,” he writes.

Dr. Kopans hopes that the investigators address the statistical power issues with the trial because, if not, “its results may be grossly misleading.”
 

American radiology practice

Dr. Kopans praises one aspect of TMIST – the trial’s effort to create a repository of blood and oral swab specimens, along with participant genetic data. The goal, say TMIST investigators, is to individualize or optimize screening strategies by tying molecular data to clinical outcomes in the trial.

However, apart from that one aspect, Dr. Kopans is highly critical of the trial.

It is now too late to compare the two technologies, he suggests, as DBT is already replacing FFDM for breast cancer screening in the U.S.

He notes that 76% of mammography facilities in the United States have 3-D devices (as of April 2021). That percentage has climbed steadily in recent years. “By the time the TMIST study is completed, DBT will, almost certainly, have become the ‘standard of care,’” he asserts, echoing others who have commented on the trial, including some participating physicians.

The money being spent on TMIST “should not be used for looking backwards,” says Dr. Kopans.

The NCI responded to that criticism. “TMIST is looking to clarify the best screening for women based on the science and is not solely about access. We are seeking to determine which technology is better and [are] providing access to the trial across the country in diverse practices and populations,” the NCI said in an email.

In his essay, Dr. Kopans says it is time to stop TMIST and put the money into other pressing breast cancer issues and questions. “... it makes no sense to continue this flawed trial whose results will be obsolete by the time they become available,” he writes.

Dr. Kopans reports consulting with DART Imaging in China, which is developing a digital breast tomosynthesis machine.

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

The largest-ever breast cancer screening trial in the United States, which is federally funded with costs expected to reach $100 million, is a “waste,” says prominent radiologist Daniel Kopans, MD, from Harvard Medical School, Boston. Funding for this trial is largely misspent money, it may produce misleading results, and it should be abandoned, he says.

Dr. Kopans has been an outspoken critic of the trial, describing it as a “huge waste of money” in comments made last year. Now he has set out his criticisms of the trial in an essay published in the October issue of Clinical Imaging, which outlines his objections and concerns for the first time in a peer-reviewed journal.

The Tomosynthesis Mammographic Imaging Screening Trial (TMIST) is comparing digital breast tomosynthesis (DBT), also known as 3-D mammography, with the older 2-D technology or full-field digital mammography (FFDM).

Dr. Kopans coined the term DBT and formerly held a now-expired patent on the first version of this technology.

“It could be argued that the imaging part of TMIST is a waste of valuable resources,” he writes in the essay.

The “imaging part” of the trial refers to the primary outcome measure and driving purpose of the trial, which is designed to learn which technology is better at finding – and reducing the rate of – potentially lethal “advanced” cancers.

These cancers include larger HER2-positive and triple-negative malignancies; those associated with positive nodes; and metastatic disease. These malignancies correlate with breast cancer mortality, TMIST’s principal investigator Etta Pisano, MD, of the American College of Radiology, has said in the past.

However, Dr. Kopans says that this surrogate endpoint is problematic. “TMIST will only investigate whether or not digital breast tomography results in a decline in advanced cancers, ignoring the fact that many women still die from cancers that are not advanced at the time of diagnosis,” he writes.

“Clearly reducing the rate of advanced cancers is not the only way that early detection saves lives. Lives are also saved by finding cancers at a smaller size within stages,” Dr. Kopans writes. He adds that DBT has been proven in observational cohort studies to find more smaller breast cancers than FFDM.

Dr. Kopans’ opinion that TMIST is largely a waste of resources is not shared by the National Cancer Institute. “We feel strongly that TMIST is a critical study,” an NCI spokesperson told this news organization.
 

Study power concerns

Another concern is that TMIST “may be underpowered,” Dr. Kopans writes. That concern arises in part from a recent review of TMIST by an advisory committee (that was prompted by low patient accrual rates), which proposed reducing the size of the trial. Dr. Kopans says this would result in “a reduction of the planned power of the trial.”  

The NCI says that reducing the study size has been discussed but has not yet been implemented. “Any reduction in size would, of course, have appropriate statistical considerations in mind,” according to the NCI spokesperson.

Dr. Kopans’ concern about statistical power extends beyond downsizing the trial. An advanced cancer in TMIST is counted “if it occurs at any time while the participant is on study,” according to the NCI. Dr. Kopans says that is a problem.

“Since DBT cannot have any effect on advanced cancers in the prevalence year (they are already there), data from the first year (prevalence cancers are likely the largest number) will be unusable, and if used will, inappropriately, dilute the results,” he writes.

Dr. Kopans hopes that the investigators address the statistical power issues with the trial because, if not, “its results may be grossly misleading.”
 

American radiology practice

Dr. Kopans praises one aspect of TMIST – the trial’s effort to create a repository of blood and oral swab specimens, along with participant genetic data. The goal, say TMIST investigators, is to individualize or optimize screening strategies by tying molecular data to clinical outcomes in the trial.

However, apart from that one aspect, Dr. Kopans is highly critical of the trial.

It is now too late to compare the two technologies, he suggests, as DBT is already replacing FFDM for breast cancer screening in the U.S.

He notes that 76% of mammography facilities in the United States have 3-D devices (as of April 2021). That percentage has climbed steadily in recent years. “By the time the TMIST study is completed, DBT will, almost certainly, have become the ‘standard of care,’” he asserts, echoing others who have commented on the trial, including some participating physicians.

The money being spent on TMIST “should not be used for looking backwards,” says Dr. Kopans.

The NCI responded to that criticism. “TMIST is looking to clarify the best screening for women based on the science and is not solely about access. We are seeking to determine which technology is better and [are] providing access to the trial across the country in diverse practices and populations,” the NCI said in an email.

In his essay, Dr. Kopans says it is time to stop TMIST and put the money into other pressing breast cancer issues and questions. “... it makes no sense to continue this flawed trial whose results will be obsolete by the time they become available,” he writes.

Dr. Kopans reports consulting with DART Imaging in China, which is developing a digital breast tomosynthesis machine.

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

The largest-ever breast cancer screening trial in the United States, which is federally funded with costs expected to reach $100 million, is a “waste,” says prominent radiologist Daniel Kopans, MD, from Harvard Medical School, Boston. Funding for this trial is largely misspent money, it may produce misleading results, and it should be abandoned, he says.

Dr. Kopans has been an outspoken critic of the trial, describing it as a “huge waste of money” in comments made last year. Now he has set out his criticisms of the trial in an essay published in the October issue of Clinical Imaging, which outlines his objections and concerns for the first time in a peer-reviewed journal.

The Tomosynthesis Mammographic Imaging Screening Trial (TMIST) is comparing digital breast tomosynthesis (DBT), also known as 3-D mammography, with the older 2-D technology or full-field digital mammography (FFDM).

Dr. Kopans coined the term DBT and formerly held a now-expired patent on the first version of this technology.

“It could be argued that the imaging part of TMIST is a waste of valuable resources,” he writes in the essay.

The “imaging part” of the trial refers to the primary outcome measure and driving purpose of the trial, which is designed to learn which technology is better at finding – and reducing the rate of – potentially lethal “advanced” cancers.

These cancers include larger HER2-positive and triple-negative malignancies; those associated with positive nodes; and metastatic disease. These malignancies correlate with breast cancer mortality, TMIST’s principal investigator Etta Pisano, MD, of the American College of Radiology, has said in the past.

However, Dr. Kopans says that this surrogate endpoint is problematic. “TMIST will only investigate whether or not digital breast tomography results in a decline in advanced cancers, ignoring the fact that many women still die from cancers that are not advanced at the time of diagnosis,” he writes.

“Clearly reducing the rate of advanced cancers is not the only way that early detection saves lives. Lives are also saved by finding cancers at a smaller size within stages,” Dr. Kopans writes. He adds that DBT has been proven in observational cohort studies to find more smaller breast cancers than FFDM.

Dr. Kopans’ opinion that TMIST is largely a waste of resources is not shared by the National Cancer Institute. “We feel strongly that TMIST is a critical study,” an NCI spokesperson told this news organization.
 

Study power concerns

Another concern is that TMIST “may be underpowered,” Dr. Kopans writes. That concern arises in part from a recent review of TMIST by an advisory committee (that was prompted by low patient accrual rates), which proposed reducing the size of the trial. Dr. Kopans says this would result in “a reduction of the planned power of the trial.”  

The NCI says that reducing the study size has been discussed but has not yet been implemented. “Any reduction in size would, of course, have appropriate statistical considerations in mind,” according to the NCI spokesperson.

Dr. Kopans’ concern about statistical power extends beyond downsizing the trial. An advanced cancer in TMIST is counted “if it occurs at any time while the participant is on study,” according to the NCI. Dr. Kopans says that is a problem.

“Since DBT cannot have any effect on advanced cancers in the prevalence year (they are already there), data from the first year (prevalence cancers are likely the largest number) will be unusable, and if used will, inappropriately, dilute the results,” he writes.

Dr. Kopans hopes that the investigators address the statistical power issues with the trial because, if not, “its results may be grossly misleading.”
 

American radiology practice

Dr. Kopans praises one aspect of TMIST – the trial’s effort to create a repository of blood and oral swab specimens, along with participant genetic data. The goal, say TMIST investigators, is to individualize or optimize screening strategies by tying molecular data to clinical outcomes in the trial.

However, apart from that one aspect, Dr. Kopans is highly critical of the trial.

It is now too late to compare the two technologies, he suggests, as DBT is already replacing FFDM for breast cancer screening in the U.S.

He notes that 76% of mammography facilities in the United States have 3-D devices (as of April 2021). That percentage has climbed steadily in recent years. “By the time the TMIST study is completed, DBT will, almost certainly, have become the ‘standard of care,’” he asserts, echoing others who have commented on the trial, including some participating physicians.

The money being spent on TMIST “should not be used for looking backwards,” says Dr. Kopans.

The NCI responded to that criticism. “TMIST is looking to clarify the best screening for women based on the science and is not solely about access. We are seeking to determine which technology is better and [are] providing access to the trial across the country in diverse practices and populations,” the NCI said in an email.

In his essay, Dr. Kopans says it is time to stop TMIST and put the money into other pressing breast cancer issues and questions. “... it makes no sense to continue this flawed trial whose results will be obsolete by the time they become available,” he writes.

Dr. Kopans reports consulting with DART Imaging in China, which is developing a digital breast tomosynthesis machine.

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

A new systematic review and meta-analysis finds that unvaccinated cancer patients who contracted COVID-19 last year, were more than two times more likely – than people without cancer – to develop a case of COVID-19 so severe it required hospitalization in an intensive care unit.

“Our study provides the most precise measure to date of the effect of COVID-19 in cancer patients,” wrote researchers who were led by Paolo Boffetta, MD, MPH, a specialist in population science with the Stony Brook Cancer Center in New York.

Dr. Boffetta and colleagues also found that patients with hematologic neoplasms had a higher mortality rate from COVID-19 comparable to that of all cancers combined.

Cancer patients have long been considered to be among those patients who are at high risk of developing COVID-19, and if they contract the disease, they are at high risk of having poor outcomes. Other high-risk patients include those with hypertension, diabetes, chronic kidney disease, or COPD, or the elderly. But how high the risk of developing severe COVID-19 disease is for cancer patients hasn’t yet been documented on a wide scale.

The study, which was made available as a preprint on medRxiv on Oct. 23, is based on an analysis of COVID-19 cases that were documented in 35 reviews, meta-analyses, case reports, and studies indexed in PubMed from authors in North America, Europe, and Asia.

In this study, the pooled odds ratio for mortality for all patients with any cancer was 2.32 (95% confidence interval, 1.82-2.94; 24 studies). For ICU admission, the odds ratio was 2.39 (95% CI, 1.90-3.02; I2 0.0%; 5 studies). And, for disease severity or hospitalization, it was 2.08 (95% CI, 1.60-2.72; I2 92.1%; 15 studies). The pooled mortality odds ratio for hematologic neoplasms was 2.14 (95% CI, 1.87-2.44; I2 20.8%; 8 studies).

Their findings, which have not yet been peer reviewed, confirmed the results of a similar analysis from China published as a preprint in May 2020. The analysis included 181,323 patients (23,736 cancer patients) from 26 studies reported an odds ratio of 2.54 (95% CI, 1.47-4.42). “Cancer patients with COVID-19 have an increased likelihood of death compared to non-cancer COVID-19 patients,” Venkatesulu et al. wrote. And a systematic review and meta-analysis of five studies of 2,619 patients published in October 2020 in Medicine also found a significantly higher risk of death from COVID-19 among cancer patients (odds ratio, 2.63; 95% confidence interval, 1.14-6.06; P = .023; I2 = 26.4%).

Fakih et al., writing in the journal Hematology/Oncology and Stem Cell Therapy conducted a meta-analysis early last year finding a threefold increase for admission to the intensive care unit, an almost fourfold increase for a severe SARS-CoV-2 infection, and a fivefold increase for being intubated.

The three studies show that mortality rates were higher early in the pandemic “when diagnosis and treatment for SARS-CoV-2 might have been delayed, resulting in higher death rate,” Boffetta et al. wrote, adding that their analysis showed only a twofold increase most likely because it was a year-long analysis.

“Future studies will be able to better analyze this association for the different subtypes of cancer. Furthermore, they will eventually be able to evaluate whether the difference among vaccinated population is reduced,” Boffetta et al. wrote.

The authors noted several limitations for the study, including the fact that many of the studies included in the analysis did not include sex, age, comorbidities, and therapy. Nor were the authors able to analyze specific cancers other than hematologic neoplasms.

The authors declared no conflicts of interest.

A new systematic review and meta-analysis finds that unvaccinated cancer patients who contracted COVID-19 last year, were more than two times more likely – than people without cancer – to develop a case of COVID-19 so severe it required hospitalization in an intensive care unit.

“Our study provides the most precise measure to date of the effect of COVID-19 in cancer patients,” wrote researchers who were led by Paolo Boffetta, MD, MPH, a specialist in population science with the Stony Brook Cancer Center in New York.

Dr. Boffetta and colleagues also found that patients with hematologic neoplasms had a higher mortality rate from COVID-19 comparable to that of all cancers combined.

Cancer patients have long been considered to be among those patients who are at high risk of developing COVID-19, and if they contract the disease, they are at high risk of having poor outcomes. Other high-risk patients include those with hypertension, diabetes, chronic kidney disease, or COPD, or the elderly. But how high the risk of developing severe COVID-19 disease is for cancer patients hasn’t yet been documented on a wide scale.

The study, which was made available as a preprint on medRxiv on Oct. 23, is based on an analysis of COVID-19 cases that were documented in 35 reviews, meta-analyses, case reports, and studies indexed in PubMed from authors in North America, Europe, and Asia.

In this study, the pooled odds ratio for mortality for all patients with any cancer was 2.32 (95% confidence interval, 1.82-2.94; 24 studies). For ICU admission, the odds ratio was 2.39 (95% CI, 1.90-3.02; I2 0.0%; 5 studies). And, for disease severity or hospitalization, it was 2.08 (95% CI, 1.60-2.72; I2 92.1%; 15 studies). The pooled mortality odds ratio for hematologic neoplasms was 2.14 (95% CI, 1.87-2.44; I2 20.8%; 8 studies).

Their findings, which have not yet been peer reviewed, confirmed the results of a similar analysis from China published as a preprint in May 2020. The analysis included 181,323 patients (23,736 cancer patients) from 26 studies reported an odds ratio of 2.54 (95% CI, 1.47-4.42). “Cancer patients with COVID-19 have an increased likelihood of death compared to non-cancer COVID-19 patients,” Venkatesulu et al. wrote. And a systematic review and meta-analysis of five studies of 2,619 patients published in October 2020 in Medicine also found a significantly higher risk of death from COVID-19 among cancer patients (odds ratio, 2.63; 95% confidence interval, 1.14-6.06; P = .023; I2 = 26.4%).

Fakih et al., writing in the journal Hematology/Oncology and Stem Cell Therapy conducted a meta-analysis early last year finding a threefold increase for admission to the intensive care unit, an almost fourfold increase for a severe SARS-CoV-2 infection, and a fivefold increase for being intubated.

The three studies show that mortality rates were higher early in the pandemic “when diagnosis and treatment for SARS-CoV-2 might have been delayed, resulting in higher death rate,” Boffetta et al. wrote, adding that their analysis showed only a twofold increase most likely because it was a year-long analysis.

“Future studies will be able to better analyze this association for the different subtypes of cancer. Furthermore, they will eventually be able to evaluate whether the difference among vaccinated population is reduced,” Boffetta et al. wrote.

The authors noted several limitations for the study, including the fact that many of the studies included in the analysis did not include sex, age, comorbidities, and therapy. Nor were the authors able to analyze specific cancers other than hematologic neoplasms.

The authors declared no conflicts of interest.

A new systematic review and meta-analysis finds that unvaccinated cancer patients who contracted COVID-19 last year, were more than two times more likely – than people without cancer – to develop a case of COVID-19 so severe it required hospitalization in an intensive care unit.

“Our study provides the most precise measure to date of the effect of COVID-19 in cancer patients,” wrote researchers who were led by Paolo Boffetta, MD, MPH, a specialist in population science with the Stony Brook Cancer Center in New York.

Dr. Boffetta and colleagues also found that patients with hematologic neoplasms had a higher mortality rate from COVID-19 comparable to that of all cancers combined.

Cancer patients have long been considered to be among those patients who are at high risk of developing COVID-19, and if they contract the disease, they are at high risk of having poor outcomes. Other high-risk patients include those with hypertension, diabetes, chronic kidney disease, or COPD, or the elderly. But how high the risk of developing severe COVID-19 disease is for cancer patients hasn’t yet been documented on a wide scale.

The study, which was made available as a preprint on medRxiv on Oct. 23, is based on an analysis of COVID-19 cases that were documented in 35 reviews, meta-analyses, case reports, and studies indexed in PubMed from authors in North America, Europe, and Asia.

In this study, the pooled odds ratio for mortality for all patients with any cancer was 2.32 (95% confidence interval, 1.82-2.94; 24 studies). For ICU admission, the odds ratio was 2.39 (95% CI, 1.90-3.02; I2 0.0%; 5 studies). And, for disease severity or hospitalization, it was 2.08 (95% CI, 1.60-2.72; I2 92.1%; 15 studies). The pooled mortality odds ratio for hematologic neoplasms was 2.14 (95% CI, 1.87-2.44; I2 20.8%; 8 studies).

Their findings, which have not yet been peer reviewed, confirmed the results of a similar analysis from China published as a preprint in May 2020. The analysis included 181,323 patients (23,736 cancer patients) from 26 studies reported an odds ratio of 2.54 (95% CI, 1.47-4.42). “Cancer patients with COVID-19 have an increased likelihood of death compared to non-cancer COVID-19 patients,” Venkatesulu et al. wrote. And a systematic review and meta-analysis of five studies of 2,619 patients published in October 2020 in Medicine also found a significantly higher risk of death from COVID-19 among cancer patients (odds ratio, 2.63; 95% confidence interval, 1.14-6.06; P = .023; I2 = 26.4%).

Fakih et al., writing in the journal Hematology/Oncology and Stem Cell Therapy conducted a meta-analysis early last year finding a threefold increase for admission to the intensive care unit, an almost fourfold increase for a severe SARS-CoV-2 infection, and a fivefold increase for being intubated.

The three studies show that mortality rates were higher early in the pandemic “when diagnosis and treatment for SARS-CoV-2 might have been delayed, resulting in higher death rate,” Boffetta et al. wrote, adding that their analysis showed only a twofold increase most likely because it was a year-long analysis.

“Future studies will be able to better analyze this association for the different subtypes of cancer. Furthermore, they will eventually be able to evaluate whether the difference among vaccinated population is reduced,” Boffetta et al. wrote.

The authors noted several limitations for the study, including the fact that many of the studies included in the analysis did not include sex, age, comorbidities, and therapy. Nor were the authors able to analyze specific cancers other than hematologic neoplasms.

The authors declared no conflicts of interest.

Mary Lou McMaster, MD, has spent her entire career at the National Cancer Institute (NCI) searching for the genetic underpinnings that give rise to Waldenstrom's macroglobulinemia (WM). 
After searching for decades, she has yet to uncover a "smoking gun," though a few tantalizing clues have emerged along the way. 
"Our questions are pretty basic: Why are some people more susceptible to developing WM, and why does WM sometimes cluster in families?" she explained. It turns out that the answers are not at all simple. 
Dr. McMaster described some of the clues that her team at the Clinical Genetics Branch of the NCI has unearthed in a presentation at the recent International Waldenstrom's Macroglobulinemia Foundation (IWMF) 2021 Virtual Educational Forum. 
Commenting after the presentation, Steven Treon, MD, PhD, professor of medicine, Harvard Medical School, Boston, who is collaborating with Dr. McMaster on this work, said: "From these familial studies, we can learn how familial genomics may give us insights into disease prevention and treatment." 

Identifying affected families  

Work began in 2001 to identify families in which two or more family members had been diagnosed with WM or in which there was one patient with WM and at least one other relative with a related B-cell cancer, such as chronic lymphocytic leukemia. 
For a frame of reference, they enrolled some families with only one member with WM and in which there was no known family history of the disease. 
"Overall, we have learned that familial WM is a rare disease but not nearly as rare as we first thought," Dr. McMaster said. 
For example, in a referral hospital setting, 5% of WM patients will report having a family member with the same disorder, and up to 20% of WM patients report having a family member with a related but different B-cell cancer, she noted. 
NCI researchers also discovered that environmental factors contribute to the development of WM. Notable chemical or occupational exposures include exposures to pesticides, herbicides, and fertilizers. Infections and autoimmune disease are additional factors. 
"This was not a surprise," Dr. McMaster commented regarding the role of occupational exposures. The research community has known for decades that a "lymphoma belt" cuts through the Midwest farming states. 
Focusing on genetic susceptibility, Dr. McMaster and colleagues first tried to identify a rare germline variant that can be passed down to offspring and that might confer high risk for the disease. 
"We used our high-risk families to study these types of changes, although they may be modified by other genes and environmental factors," Dr. McMaster explained. 
Much to their collective disappointment, the research team has been unable to identify any rare germline variant that could account for WM in many families. What they did find were many small changes in genes that are known to be important in B-cell development and function, but all of those would lead to only a small increase in WM risk. 
"What is holding us back is that, so far, we are not seeing the same gene affected in more than one family, so this suggests to us either that this is not the mechanism behind the development of WM in families, or we have an unfortunate situation where each family is going to have a genetic change that is private to that family and which is not found in other families," Dr. McMaster acknowledged. 

Sheer difficulty  

Given the difficulty of determining whether these small genetic changes had any detrimental functional effect in each and every family with a member who had WM, Dr. McMaster and colleagues have now turned their attention to genes that exert only a small effect on disease risk. 
"Here, we focused on specific genes that we knew were important in the function of the immune system," she explained. "We did find a few genes that may contribute to risk, but those have not yet been confirmed by us or others, and we cannot say they are causative without that confirmation," she said. 
The team has gone on to scan the highway of our genetic material so as to isolate genetic "mile markers." They then examine the area around a particular marker that they suspect contains genes that may be involved in WM. 
One study they conducted involved a cohort of 217 patients with WM in which numerous family members had WM and so was enriched with susceptibility genes. A second cohort comprised 312 WM patients in which there were few WM cases among family members. Both of these cohorts were compared with a group of healthy control persons. 
From these genome studies, "we found there are at least two regions of the genome that can contribute to WM susceptibility, the largest effect being on the short arm of chromosome 6, and the other on the long arm of chromosome 14," Dr. McMaster reported. Dr. McMaster feels that there are probably more regions on the genome that also contribute to WM, although they do not yet understand how these regions contribute to susceptibility. 
"It's more evidence that WM likely results from a combination of events rather than one single gene variant," she observed. Dr. McMaster and colleagues are now collaborating with a large consortium of WM researchers to confirm and extend their findings. Plans are underway to analyze data from approximately 1,350 WM patients and more than 20,000 control persons within the next year. 
"Our hope is that we will confirm our original findings and, because we now have a much larger sample, we will be able to discover additional regions of the genome that are contributing to susceptibility," Dr. McMaster said. 
"A single gene is not likely to account for all WM, as we've looked carefully and others have looked too," she commented. 
"So the risk for WM depends on a combination of genes and environmental exposures and possibly lifestyle factors as well, although we still estimate that approximately 25% of the heritability of WM can be attributed to these kinds of genetic changes," Dr. McMaster predicted. 
Dr. McMaster has disclosed no relevant financial relationships. Dr. Treon has served as a director, officer, partner, employee, advisor, consultant, or trustee for Janssen, Pfizer, PCYC, and BioGene.  

A version of this article first appeared on Medscape.com

Mary Lou McMaster, MD, has spent her entire career at the National Cancer Institute (NCI) searching for the genetic underpinnings that give rise to Waldenstrom's macroglobulinemia (WM). 
After searching for decades, she has yet to uncover a "smoking gun," though a few tantalizing clues have emerged along the way. 
"Our questions are pretty basic: Why are some people more susceptible to developing WM, and why does WM sometimes cluster in families?" she explained. It turns out that the answers are not at all simple. 
Dr. McMaster described some of the clues that her team at the Clinical Genetics Branch of the NCI has unearthed in a presentation at the recent International Waldenstrom's Macroglobulinemia Foundation (IWMF) 2021 Virtual Educational Forum. 
Commenting after the presentation, Steven Treon, MD, PhD, professor of medicine, Harvard Medical School, Boston, who is collaborating with Dr. McMaster on this work, said: "From these familial studies, we can learn how familial genomics may give us insights into disease prevention and treatment." 

Identifying affected families  

Work began in 2001 to identify families in which two or more family members had been diagnosed with WM or in which there was one patient with WM and at least one other relative with a related B-cell cancer, such as chronic lymphocytic leukemia. 
For a frame of reference, they enrolled some families with only one member with WM and in which there was no known family history of the disease. 
"Overall, we have learned that familial WM is a rare disease but not nearly as rare as we first thought," Dr. McMaster said. 
For example, in a referral hospital setting, 5% of WM patients will report having a family member with the same disorder, and up to 20% of WM patients report having a family member with a related but different B-cell cancer, she noted. 
NCI researchers also discovered that environmental factors contribute to the development of WM. Notable chemical or occupational exposures include exposures to pesticides, herbicides, and fertilizers. Infections and autoimmune disease are additional factors. 
"This was not a surprise," Dr. McMaster commented regarding the role of occupational exposures. The research community has known for decades that a "lymphoma belt" cuts through the Midwest farming states. 
Focusing on genetic susceptibility, Dr. McMaster and colleagues first tried to identify a rare germline variant that can be passed down to offspring and that might confer high risk for the disease. 
"We used our high-risk families to study these types of changes, although they may be modified by other genes and environmental factors," Dr. McMaster explained. 
Much to their collective disappointment, the research team has been unable to identify any rare germline variant that could account for WM in many families. What they did find were many small changes in genes that are known to be important in B-cell development and function, but all of those would lead to only a small increase in WM risk. 
"What is holding us back is that, so far, we are not seeing the same gene affected in more than one family, so this suggests to us either that this is not the mechanism behind the development of WM in families, or we have an unfortunate situation where each family is going to have a genetic change that is private to that family and which is not found in other families," Dr. McMaster acknowledged. 

Sheer difficulty  

Given the difficulty of determining whether these small genetic changes had any detrimental functional effect in each and every family with a member who had WM, Dr. McMaster and colleagues have now turned their attention to genes that exert only a small effect on disease risk. 
"Here, we focused on specific genes that we knew were important in the function of the immune system," she explained. "We did find a few genes that may contribute to risk, but those have not yet been confirmed by us or others, and we cannot say they are causative without that confirmation," she said. 
The team has gone on to scan the highway of our genetic material so as to isolate genetic "mile markers." They then examine the area around a particular marker that they suspect contains genes that may be involved in WM. 
One study they conducted involved a cohort of 217 patients with WM in which numerous family members had WM and so was enriched with susceptibility genes. A second cohort comprised 312 WM patients in which there were few WM cases among family members. Both of these cohorts were compared with a group of healthy control persons. 
From these genome studies, "we found there are at least two regions of the genome that can contribute to WM susceptibility, the largest effect being on the short arm of chromosome 6, and the other on the long arm of chromosome 14," Dr. McMaster reported. Dr. McMaster feels that there are probably more regions on the genome that also contribute to WM, although they do not yet understand how these regions contribute to susceptibility. 
"It's more evidence that WM likely results from a combination of events rather than one single gene variant," she observed. Dr. McMaster and colleagues are now collaborating with a large consortium of WM researchers to confirm and extend their findings. Plans are underway to analyze data from approximately 1,350 WM patients and more than 20,000 control persons within the next year. 
"Our hope is that we will confirm our original findings and, because we now have a much larger sample, we will be able to discover additional regions of the genome that are contributing to susceptibility," Dr. McMaster said. 
"A single gene is not likely to account for all WM, as we've looked carefully and others have looked too," she commented. 
"So the risk for WM depends on a combination of genes and environmental exposures and possibly lifestyle factors as well, although we still estimate that approximately 25% of the heritability of WM can be attributed to these kinds of genetic changes," Dr. McMaster predicted. 
Dr. McMaster has disclosed no relevant financial relationships. Dr. Treon has served as a director, officer, partner, employee, advisor, consultant, or trustee for Janssen, Pfizer, PCYC, and BioGene.  

A version of this article first appeared on Medscape.com

Mary Lou McMaster, MD, has spent her entire career at the National Cancer Institute (NCI) searching for the genetic underpinnings that give rise to Waldenstrom's macroglobulinemia (WM). 
After searching for decades, she has yet to uncover a "smoking gun," though a few tantalizing clues have emerged along the way. 
"Our questions are pretty basic: Why are some people more susceptible to developing WM, and why does WM sometimes cluster in families?" she explained. It turns out that the answers are not at all simple. 
Dr. McMaster described some of the clues that her team at the Clinical Genetics Branch of the NCI has unearthed in a presentation at the recent International Waldenstrom's Macroglobulinemia Foundation (IWMF) 2021 Virtual Educational Forum. 
Commenting after the presentation, Steven Treon, MD, PhD, professor of medicine, Harvard Medical School, Boston, who is collaborating with Dr. McMaster on this work, said: "From these familial studies, we can learn how familial genomics may give us insights into disease prevention and treatment." 

Identifying affected families  

Work began in 2001 to identify families in which two or more family members had been diagnosed with WM or in which there was one patient with WM and at least one other relative with a related B-cell cancer, such as chronic lymphocytic leukemia. 
For a frame of reference, they enrolled some families with only one member with WM and in which there was no known family history of the disease. 
"Overall, we have learned that familial WM is a rare disease but not nearly as rare as we first thought," Dr. McMaster said. 
For example, in a referral hospital setting, 5% of WM patients will report having a family member with the same disorder, and up to 20% of WM patients report having a family member with a related but different B-cell cancer, she noted. 
NCI researchers also discovered that environmental factors contribute to the development of WM. Notable chemical or occupational exposures include exposures to pesticides, herbicides, and fertilizers. Infections and autoimmune disease are additional factors. 
"This was not a surprise," Dr. McMaster commented regarding the role of occupational exposures. The research community has known for decades that a "lymphoma belt" cuts through the Midwest farming states. 
Focusing on genetic susceptibility, Dr. McMaster and colleagues first tried to identify a rare germline variant that can be passed down to offspring and that might confer high risk for the disease. 
"We used our high-risk families to study these types of changes, although they may be modified by other genes and environmental factors," Dr. McMaster explained. 
Much to their collective disappointment, the research team has been unable to identify any rare germline variant that could account for WM in many families. What they did find were many small changes in genes that are known to be important in B-cell development and function, but all of those would lead to only a small increase in WM risk. 
"What is holding us back is that, so far, we are not seeing the same gene affected in more than one family, so this suggests to us either that this is not the mechanism behind the development of WM in families, or we have an unfortunate situation where each family is going to have a genetic change that is private to that family and which is not found in other families," Dr. McMaster acknowledged. 

Sheer difficulty  

Given the difficulty of determining whether these small genetic changes had any detrimental functional effect in each and every family with a member who had WM, Dr. McMaster and colleagues have now turned their attention to genes that exert only a small effect on disease risk. 
"Here, we focused on specific genes that we knew were important in the function of the immune system," she explained. "We did find a few genes that may contribute to risk, but those have not yet been confirmed by us or others, and we cannot say they are causative without that confirmation," she said. 
The team has gone on to scan the highway of our genetic material so as to isolate genetic "mile markers." They then examine the area around a particular marker that they suspect contains genes that may be involved in WM. 
One study they conducted involved a cohort of 217 patients with WM in which numerous family members had WM and so was enriched with susceptibility genes. A second cohort comprised 312 WM patients in which there were few WM cases among family members. Both of these cohorts were compared with a group of healthy control persons. 
From these genome studies, "we found there are at least two regions of the genome that can contribute to WM susceptibility, the largest effect being on the short arm of chromosome 6, and the other on the long arm of chromosome 14," Dr. McMaster reported. Dr. McMaster feels that there are probably more regions on the genome that also contribute to WM, although they do not yet understand how these regions contribute to susceptibility. 
"It's more evidence that WM likely results from a combination of events rather than one single gene variant," she observed. Dr. McMaster and colleagues are now collaborating with a large consortium of WM researchers to confirm and extend their findings. Plans are underway to analyze data from approximately 1,350 WM patients and more than 20,000 control persons within the next year. 
"Our hope is that we will confirm our original findings and, because we now have a much larger sample, we will be able to discover additional regions of the genome that are contributing to susceptibility," Dr. McMaster said. 
"A single gene is not likely to account for all WM, as we've looked carefully and others have looked too," she commented. 
"So the risk for WM depends on a combination of genes and environmental exposures and possibly lifestyle factors as well, although we still estimate that approximately 25% of the heritability of WM can be attributed to these kinds of genetic changes," Dr. McMaster predicted. 
Dr. McMaster has disclosed no relevant financial relationships. Dr. Treon has served as a director, officer, partner, employee, advisor, consultant, or trustee for Janssen, Pfizer, PCYC, and BioGene.  

A version of this article first appeared on Medscape.com

New data from England show the success of the national program for vaccinating girls against human papillomavirus (HPV) to prevent cervical cancer.

Among young women who received the HPV vaccine when they were 12-13 years old (before their sexual debut), cervical cancer rates are 87% lower than among previous nonvaccinated generations.

“It’s been incredible to see the impact of HPV vaccination, and now we can prove it prevented hundreds of women from developing cancer in England,” senior author Peter Sasieni, MD, King’s College London, said in a statement. “To see the real-life impact of the vaccine has been truly rewarding.”

“This study provides the first direct evidence of the impact of the UK HPV vaccination campaign on cervical cancer incidence, showing a large reduction in cervical cancer rates in vaccinated cohorts,” Kate Soldan, MD, U.K. Health Security Agency, London, commented in a statement.

Vanessa Saliba, MD, a consultant epidemiologist for the U.K. Health Security Agency, agreed, saying that “these remarkable findings confirm that the HPV vaccine saves lives by dramatically reducing cervical cancer rates among women.

“This reminds us that vaccines are one of the most important tools we have to help us live longer, healthier lives,” she added.

The study was published online Nov. 3, 2021, in The Lancet.

Approached for comment on the new study, Maurice Markman, MD, president, Medicine and Science Cancer Treatment Centers of America, noted that the results of the English study are very similar to those of a Swedish study of the quadrivalent vaccine alone.

“You can put any superlatives you want in here, but these are stunningly positive results,” Dr. Markman said in an interview. He said that, as an oncologist who has been treating cervical cancer for 40 years, particularly patients with advanced cervical cancer, “I can tell you this is one of the most devastating diseases to women, and the ability to eliminate this cancer with something as simple as a vaccine is the goal of cancer therapy, and it’s been remarkably successful.

“I can only emphasize the critical importance of all parents to see that their children who are eligible for the vaccine receive it. This is a cancer prevention strategy that is unbelievably, remarkably effective and safe,” Dr. Markman added.
 

National vaccination program

The national HPV vaccination program in England began in 2008. Initially, the bivalent Cervarix vaccine against HPV 16 and 18 was used. HPV 16 and 18 are responsible for 70% to 80% of all cervical cancers in England, the researchers note in their article.

In 2012, the program switched to the quadrivalent HPV vaccine (Gardasil), which is effective against two additional HPV types, HPV 6 and 11. Those strains cause genital warts.

The prevention program originally recommended a three-dose regimen in which both HPV vaccines were used. Currently, two doses are given to girls younger than 15 years. In addition, a single dose of the HPV vaccine provides good protection against persistent infection. The efficacy rate of a single dose is similar to that of three doses, the authors comment.
 

Population-based registry

The new data come from a population-based cancer registry that shows the incidence of cervical cancer and noninvasive cervical carcinoma (CIN3) in England between January 2006 and June 2019.

The study included seven cohorts of women who were aged 20-64 years at the end of 2019. Three of these cohorts composed the vaccinated population.

The team reports that overall, from January 2006 to June 2019, there were 27,946 cases of cervical cancer and 318,058 cases of CIN3.

In the three vaccinated cohorts, there were around 450 fewer cases of cervical cancer and 17,200 fewer cases of CIN3 than would be expected in a nonvaccinated population.

The three vaccinated cohorts had been eligible to receive Cervarix when they were aged 12-13 years. A catch-up scheme aimed at 14- to 16-year-olds and 16- to 18-year-olds. Most of these persons were vaccinated through a school vaccination program.

The team analyzed the data for each of these cohorts.

Among the cohort eligible for vaccination at 12-13 years of age, 89% received at least one dose of the HPV vaccine; 85% received three shots and were fully vaccinated. Among these persons, the rate of cervical cancer was 87% lower than expected in a nonvaccinated population, and the rate of CIN3 was 97% lower than expected.

For the cohort that was eligible to be vaccinated between the ages of 14 and 16 years, the corresponding reductions were 62% for cervical cancer and 75% for CIN3.

For the cohort eligible for vaccination between the ages of 16 and 18 years (of whom 60% had received at least one dose and 45% were fully vaccinated), the corresponding reduction were 34% for cervical cancer and 39% for CIN3.

The authors acknowledge some limitations with the study, principally that cervical cancer is rare in young women, and these vaccinated populations are still young. The youngest would have been vaccinated at age 12 in 2008 and so would be only 23 years old in 2019, when the follow-up in this current study ended. The authors emphasize that because the vaccinated populations are still young, it is too early to assess the full impact of HPV vaccination on cervical cancer rates.
 

Editorial commentary

“The relative reductions in cervical cancer, expected as a result of the HPV vaccination program, support the anticipated vaccine effectiveness,” commented two authors of an accompanying editorial, Maggie Cruickshank, MD, University of Aberdeen (Scotland), and Mihaela Grigore, MD, University of Medicine and Pharmacy, Lasi, Romania.

“The scale of the HPV vaccination effect reported by this study should also stimulate vaccination programs in low-income and middle-income countries where the problem of cervical cancer is a far greater public health issue than in those with well established systems of vaccination and screening,” they comment.

“The most important issue, besides the availability of the vaccine ... is the education of the population to accept the vaccination because a high rate of immunization is a key element of success,” they emphasize. “Even in a wealthy country, such as England with free access to HPV immunization, uptake has not reached the 90% vaccination target of girls aged 15 years set by WHO [World Health Organization].”

The authors and editorialists disclosed no relevant financial relationships. Dr. Markman is a regular contributor to Medscape Oncology. He has received income of $250 or more from Genentech, AstraZeneca, Celgene, Clovis, and Amgen.

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

New data from England show the success of the national program for vaccinating girls against human papillomavirus (HPV) to prevent cervical cancer.

Among young women who received the HPV vaccine when they were 12-13 years old (before their sexual debut), cervical cancer rates are 87% lower than among previous nonvaccinated generations.

“It’s been incredible to see the impact of HPV vaccination, and now we can prove it prevented hundreds of women from developing cancer in England,” senior author Peter Sasieni, MD, King’s College London, said in a statement. “To see the real-life impact of the vaccine has been truly rewarding.”

“This study provides the first direct evidence of the impact of the UK HPV vaccination campaign on cervical cancer incidence, showing a large reduction in cervical cancer rates in vaccinated cohorts,” Kate Soldan, MD, U.K. Health Security Agency, London, commented in a statement.

Vanessa Saliba, MD, a consultant epidemiologist for the U.K. Health Security Agency, agreed, saying that “these remarkable findings confirm that the HPV vaccine saves lives by dramatically reducing cervical cancer rates among women.

“This reminds us that vaccines are one of the most important tools we have to help us live longer, healthier lives,” she added.

The study was published online Nov. 3, 2021, in The Lancet.

Approached for comment on the new study, Maurice Markman, MD, president, Medicine and Science Cancer Treatment Centers of America, noted that the results of the English study are very similar to those of a Swedish study of the quadrivalent vaccine alone.

“You can put any superlatives you want in here, but these are stunningly positive results,” Dr. Markman said in an interview. He said that, as an oncologist who has been treating cervical cancer for 40 years, particularly patients with advanced cervical cancer, “I can tell you this is one of the most devastating diseases to women, and the ability to eliminate this cancer with something as simple as a vaccine is the goal of cancer therapy, and it’s been remarkably successful.

“I can only emphasize the critical importance of all parents to see that their children who are eligible for the vaccine receive it. This is a cancer prevention strategy that is unbelievably, remarkably effective and safe,” Dr. Markman added.
 

National vaccination program

The national HPV vaccination program in England began in 2008. Initially, the bivalent Cervarix vaccine against HPV 16 and 18 was used. HPV 16 and 18 are responsible for 70% to 80% of all cervical cancers in England, the researchers note in their article.

In 2012, the program switched to the quadrivalent HPV vaccine (Gardasil), which is effective against two additional HPV types, HPV 6 and 11. Those strains cause genital warts.

The prevention program originally recommended a three-dose regimen in which both HPV vaccines were used. Currently, two doses are given to girls younger than 15 years. In addition, a single dose of the HPV vaccine provides good protection against persistent infection. The efficacy rate of a single dose is similar to that of three doses, the authors comment.
 

Population-based registry

The new data come from a population-based cancer registry that shows the incidence of cervical cancer and noninvasive cervical carcinoma (CIN3) in England between January 2006 and June 2019.

The study included seven cohorts of women who were aged 20-64 years at the end of 2019. Three of these cohorts composed the vaccinated population.

The team reports that overall, from January 2006 to June 2019, there were 27,946 cases of cervical cancer and 318,058 cases of CIN3.

In the three vaccinated cohorts, there were around 450 fewer cases of cervical cancer and 17,200 fewer cases of CIN3 than would be expected in a nonvaccinated population.

The three vaccinated cohorts had been eligible to receive Cervarix when they were aged 12-13 years. A catch-up scheme aimed at 14- to 16-year-olds and 16- to 18-year-olds. Most of these persons were vaccinated through a school vaccination program.

The team analyzed the data for each of these cohorts.

Among the cohort eligible for vaccination at 12-13 years of age, 89% received at least one dose of the HPV vaccine; 85% received three shots and were fully vaccinated. Among these persons, the rate of cervical cancer was 87% lower than expected in a nonvaccinated population, and the rate of CIN3 was 97% lower than expected.

For the cohort that was eligible to be vaccinated between the ages of 14 and 16 years, the corresponding reductions were 62% for cervical cancer and 75% for CIN3.

For the cohort eligible for vaccination between the ages of 16 and 18 years (of whom 60% had received at least one dose and 45% were fully vaccinated), the corresponding reduction were 34% for cervical cancer and 39% for CIN3.

The authors acknowledge some limitations with the study, principally that cervical cancer is rare in young women, and these vaccinated populations are still young. The youngest would have been vaccinated at age 12 in 2008 and so would be only 23 years old in 2019, when the follow-up in this current study ended. The authors emphasize that because the vaccinated populations are still young, it is too early to assess the full impact of HPV vaccination on cervical cancer rates.
 

Editorial commentary

“The relative reductions in cervical cancer, expected as a result of the HPV vaccination program, support the anticipated vaccine effectiveness,” commented two authors of an accompanying editorial, Maggie Cruickshank, MD, University of Aberdeen (Scotland), and Mihaela Grigore, MD, University of Medicine and Pharmacy, Lasi, Romania.

“The scale of the HPV vaccination effect reported by this study should also stimulate vaccination programs in low-income and middle-income countries where the problem of cervical cancer is a far greater public health issue than in those with well established systems of vaccination and screening,” they comment.

“The most important issue, besides the availability of the vaccine ... is the education of the population to accept the vaccination because a high rate of immunization is a key element of success,” they emphasize. “Even in a wealthy country, such as England with free access to HPV immunization, uptake has not reached the 90% vaccination target of girls aged 15 years set by WHO [World Health Organization].”

The authors and editorialists disclosed no relevant financial relationships. Dr. Markman is a regular contributor to Medscape Oncology. He has received income of $250 or more from Genentech, AstraZeneca, Celgene, Clovis, and Amgen.

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

New data from England show the success of the national program for vaccinating girls against human papillomavirus (HPV) to prevent cervical cancer.

Among young women who received the HPV vaccine when they were 12-13 years old (before their sexual debut), cervical cancer rates are 87% lower than among previous nonvaccinated generations.

“It’s been incredible to see the impact of HPV vaccination, and now we can prove it prevented hundreds of women from developing cancer in England,” senior author Peter Sasieni, MD, King’s College London, said in a statement. “To see the real-life impact of the vaccine has been truly rewarding.”

“This study provides the first direct evidence of the impact of the UK HPV vaccination campaign on cervical cancer incidence, showing a large reduction in cervical cancer rates in vaccinated cohorts,” Kate Soldan, MD, U.K. Health Security Agency, London, commented in a statement.

Vanessa Saliba, MD, a consultant epidemiologist for the U.K. Health Security Agency, agreed, saying that “these remarkable findings confirm that the HPV vaccine saves lives by dramatically reducing cervical cancer rates among women.

“This reminds us that vaccines are one of the most important tools we have to help us live longer, healthier lives,” she added.

The study was published online Nov. 3, 2021, in The Lancet.

Approached for comment on the new study, Maurice Markman, MD, president, Medicine and Science Cancer Treatment Centers of America, noted that the results of the English study are very similar to those of a Swedish study of the quadrivalent vaccine alone.

“You can put any superlatives you want in here, but these are stunningly positive results,” Dr. Markman said in an interview. He said that, as an oncologist who has been treating cervical cancer for 40 years, particularly patients with advanced cervical cancer, “I can tell you this is one of the most devastating diseases to women, and the ability to eliminate this cancer with something as simple as a vaccine is the goal of cancer therapy, and it’s been remarkably successful.

“I can only emphasize the critical importance of all parents to see that their children who are eligible for the vaccine receive it. This is a cancer prevention strategy that is unbelievably, remarkably effective and safe,” Dr. Markman added.
 

National vaccination program

The national HPV vaccination program in England began in 2008. Initially, the bivalent Cervarix vaccine against HPV 16 and 18 was used. HPV 16 and 18 are responsible for 70% to 80% of all cervical cancers in England, the researchers note in their article.

In 2012, the program switched to the quadrivalent HPV vaccine (Gardasil), which is effective against two additional HPV types, HPV 6 and 11. Those strains cause genital warts.

The prevention program originally recommended a three-dose regimen in which both HPV vaccines were used. Currently, two doses are given to girls younger than 15 years. In addition, a single dose of the HPV vaccine provides good protection against persistent infection. The efficacy rate of a single dose is similar to that of three doses, the authors comment.
 

Population-based registry

The new data come from a population-based cancer registry that shows the incidence of cervical cancer and noninvasive cervical carcinoma (CIN3) in England between January 2006 and June 2019.

The study included seven cohorts of women who were aged 20-64 years at the end of 2019. Three of these cohorts composed the vaccinated population.

The team reports that overall, from January 2006 to June 2019, there were 27,946 cases of cervical cancer and 318,058 cases of CIN3.

In the three vaccinated cohorts, there were around 450 fewer cases of cervical cancer and 17,200 fewer cases of CIN3 than would be expected in a nonvaccinated population.

The three vaccinated cohorts had been eligible to receive Cervarix when they were aged 12-13 years. A catch-up scheme aimed at 14- to 16-year-olds and 16- to 18-year-olds. Most of these persons were vaccinated through a school vaccination program.

The team analyzed the data for each of these cohorts.

Among the cohort eligible for vaccination at 12-13 years of age, 89% received at least one dose of the HPV vaccine; 85% received three shots and were fully vaccinated. Among these persons, the rate of cervical cancer was 87% lower than expected in a nonvaccinated population, and the rate of CIN3 was 97% lower than expected.

For the cohort that was eligible to be vaccinated between the ages of 14 and 16 years, the corresponding reductions were 62% for cervical cancer and 75% for CIN3.

For the cohort eligible for vaccination between the ages of 16 and 18 years (of whom 60% had received at least one dose and 45% were fully vaccinated), the corresponding reduction were 34% for cervical cancer and 39% for CIN3.

The authors acknowledge some limitations with the study, principally that cervical cancer is rare in young women, and these vaccinated populations are still young. The youngest would have been vaccinated at age 12 in 2008 and so would be only 23 years old in 2019, when the follow-up in this current study ended. The authors emphasize that because the vaccinated populations are still young, it is too early to assess the full impact of HPV vaccination on cervical cancer rates.
 

Editorial commentary

“The relative reductions in cervical cancer, expected as a result of the HPV vaccination program, support the anticipated vaccine effectiveness,” commented two authors of an accompanying editorial, Maggie Cruickshank, MD, University of Aberdeen (Scotland), and Mihaela Grigore, MD, University of Medicine and Pharmacy, Lasi, Romania.

“The scale of the HPV vaccination effect reported by this study should also stimulate vaccination programs in low-income and middle-income countries where the problem of cervical cancer is a far greater public health issue than in those with well established systems of vaccination and screening,” they comment.

“The most important issue, besides the availability of the vaccine ... is the education of the population to accept the vaccination because a high rate of immunization is a key element of success,” they emphasize. “Even in a wealthy country, such as England with free access to HPV immunization, uptake has not reached the 90% vaccination target of girls aged 15 years set by WHO [World Health Organization].”

The authors and editorialists disclosed no relevant financial relationships. Dr. Markman is a regular contributor to Medscape Oncology. He has received income of $250 or more from Genentech, AstraZeneca, Celgene, Clovis, and Amgen.

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