AVAHO

New findings of breast cancer gene mutations in women who have no family history of the disease offer a new way of estimating risk and may change the way in which these women are advised on risk management.

The findings come from two large studies, both published on Jan. 20 in the New England Journal of Medicine.

The two articles are “extraordinary” for broadening and validating the genomic panel to help screen women at risk for breast cancer in the future, commented Eric Topol, MD, professor of molecular medicine, Scripps Research, La Jolla, Calif., and Medscape editor in chief.

“Traditionally, genetic testing of inherited breast cancer genes has focused on women at high risk who have a strong family history of breast cancer or those who were diagnosed at an early age, such as under 45 years,” commented the lead investigator of one of the studies, Fergus Couch, PhD, a pathologist at the Mayo Clinic, Rochester, Minn.

“[Although] the risk of developing breast cancer is generally lower for women without a family history of the disease ... when we looked at all women, we found that 30% of breast cancer mutations occurred in women who are not high risk,” he said.

In both studies, mutations or variants in eight genes – BRCA1, BRCA2, PALB2, BARD1, RAD51C, RAD51D, ATM, and CHEK2 – were found to be significantly associated with breast cancer risk.

However, the distribution of mutations among women with breast cancer differed from the distribution among unaffected women, noted Steven Narod, MD, from the Women’s College Research Institute, Toronto, in an accompanying editorial.

“What this means to clinicians, now that we are expanding the use of gene-panel testing to include unaffected women with a moderate risk of breast cancer in the family history, is that our time will increasingly be spent counseling women with CHEK2 and ATM mutations,” he wrote. Currently, these two are “clumped in with ‘other genes.’ ... Most of the pretest discussion is currently focused on the implications of finding a BRCA1 or BRCA2 mutation.”

The new findings may lead to new risk management strategies, he suggested. “Most breast cancers that occur in women with a mutation in ATM or CHEK2 are estrogen receptor positive, so these women may be candidates for antiestrogen therapies such as tamoxifen, raloxifene, or aromatase inhibitors,” he wrote.

Dr. Narod observed that, for now, the management of most women with either mutation will consist of screening alone, starting with MRI at age 40 years.

The medical community is not ready yet to expand genetic screening to the general population, cautions Walton Taylor, MD, past president of the American Society of Breast Surgeons.

The ASBrS currently recommends that all patients with breast cancer as well as those at high risk for breast cancer be offered genetic testing. “All women at risk should be tested, and all patients with pathogenic variants need to be managed appropriately – it saves lives,” Dr. Taylor emphasized.

However, “unaffected people with no family history do not need genetic testing at this time,” he said in an interview.

As to what physicians might do to better manage patients with mutations that predispose to breast cancer, Dr. Taylor said, “It’s surprisingly easy.”

Every genetic testing company provides genetic counselors to guide patients through next steps, Dr. Taylor pointed out, and most cancer patients have nurse navigators who make sure patients get tested and followed appropriately.

Members of the ASBrS follow the National Comprehensive Cancer Network guidelines when they identify carriers of a pathogenic variant. Dr. Taylor said these are very useful guidelines for virtually all mutations identified thus far.

“This research is not necessarily new, but it is confirmatory for what we are doing, and that helps us make sure we are going down the right pathway,” Dr. Taylor said. “It confirms that what we think is right is right – and that matters,.”
 

CARRIERS consortium findings

The study led by Dr. Couch was carried out by the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. It involved analyzing data from 17 epidemiology studies that focused on women in the general population who develop breast cancer. For the studies, which were conducted in the United States, pathogenic variants in 28 cancer-predisposition genes were sequenced from 32,247 women with breast cancer (case patients) and 32,544 unaffected women (control persons).

In the overall CARRIERS analysis, the prevalence of pathogenic variants in 12 clinically actionable genes was 5.03% among case patients and 1.63% among control persons. The prevalence was similar in non-Hispanic White women, non-Hispanic Black women, and Hispanic case patients, as well as control persons, they added. The prevalence of pathogenic variants among Asian American case patients was lower, at only 1.64%.

Among patients who had breast cancer, the most common pathogenic variants included BRCA2, which occurred in 1.29% of case patients, followed by CHEK2, at a prevalence of 1.08%, and BRCA1, at a prevalence of 0.85%.

Mutations in BRCA1 increased the risk for breast cancer more than 7.5-fold; mutations in BRCA2 increased that risk more than fivefold, the investigators stated.

Mutations in PALB2 increased the risk of breast cancer approximately fourfold, they added.

Prevalence rates for both BRCA1 and BRCA2 among breast cancer patients declined rapidly after the age of 40. The decline in other variants, including ATM, CHEK2, and PALB2, was limited with increasing age.

Indeed, mutations in all five of these genes were associated with a lifetime absolute risk for breast cancer greater than 20% by the age of 85 years among non-Hispanic Whites.

Pathogenic variants in BRCA1 or BRCA2 yielded a lifetime risk for breast cancer of approximately 50%. Mutations in PALB2 yielded a lifetime breast cancer risk of approximately 32%.

The risk of having a mutation in specific genes varied depending on the type of breast cancer. For example, mutations in BARD1, RAD51C, and RAD51D increased the risk for estrogen receptor (ER)–negative breast cancer as well as triple-negative breast cancer, the authors noted, whereas mutations in ATM, CDH1, and CHEK2 increased the risk for ER-positive breast cancer.

“These refined estimates of the prevalences of pathogenic variants among women with breast cancer in the overall population, as opposed to selected high-risk patients, may inform ongoing discussions regarding testing in patients with breast cancer,” the CARRIERS authors observed.

“The risks of breast cancer associated with pathogenic variants in the genes evaluated in the population-based CARRIERS analysis also provide important information for risk assessment and counseling of women with breast cancer who do not meet high-risk selection criteria,” they suggested.
 

Similar findings in second study

The second study was conducted by the Breast Cancer Association Consortium under lead author Leila Dorling, PhD, University of Cambridge (England). This group sequenced 34 susceptibility genes from 60,466 women with breast cancer and 53,461 unaffected control persons.

“Protein-truncating variants in five genes (ATM, BRCA1, BRCA2, CHEK2, and PALB2) were associated with a significant risk of breast cancer overall (P < .0001),” the BCAC members reported. “For these genes, odds ratios ranged from 2.10 to 10.57.”

The association between overall breast cancer risk and mutations in seven other genes was more modest, conferring approximately twice the risk for breast cancer overall, although that risk was threefold higher for the TP53 mutation.

For the 12 genes the consortium singled out as being associated with either a significant or a more modest risk for breast cancer, the effect size did not vary significantly between European and Asian women, the authors noted. Again, the risk for ER-positive breast cancer was over two times greater for those who had either the ATM or the CHEK2 mutation. Having mutations in BARD1, BRCA1, BRCA1, PALB2, RAD51C, and RAD51D conferred a higher risk for ER-negative disease than for ER-positive disease.

There was also an association between rare missense variants in six genes – CHEK2, ATM, TP53, BRCA1, CDH1, and RECQL – and overall breast cancer risk, with the clearest evidence being for CHEK2.

“The absolute risk estimates place protein-truncating variants in BRCA1, BRCA2, and PALB2 in the high-risk category and place protein-truncating variants in ATM, BARD1, CHEK2, RAD51CC, and RAD51D in the moderate-risk category,” Dr. Dorling and colleagues reaffirmed.

“These results may guide screening as well as prevention with risk-reducing surgery or medication, in accordance with national guidelines,” the authors suggested.

The CARRIERS study was supported by the National Institutes of Health. The study by Dr. Dorling and colleagues was supported by the European Union Horizon 2020 research and innovation programs, among others. Dr. Narod disclosed no relevant financial relationships.

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

New findings of breast cancer gene mutations in women who have no family history of the disease offer a new way of estimating risk and may change the way in which these women are advised on risk management.

The findings come from two large studies, both published on Jan. 20 in the New England Journal of Medicine.

The two articles are “extraordinary” for broadening and validating the genomic panel to help screen women at risk for breast cancer in the future, commented Eric Topol, MD, professor of molecular medicine, Scripps Research, La Jolla, Calif., and Medscape editor in chief.

“Traditionally, genetic testing of inherited breast cancer genes has focused on women at high risk who have a strong family history of breast cancer or those who were diagnosed at an early age, such as under 45 years,” commented the lead investigator of one of the studies, Fergus Couch, PhD, a pathologist at the Mayo Clinic, Rochester, Minn.

“[Although] the risk of developing breast cancer is generally lower for women without a family history of the disease ... when we looked at all women, we found that 30% of breast cancer mutations occurred in women who are not high risk,” he said.

In both studies, mutations or variants in eight genes – BRCA1, BRCA2, PALB2, BARD1, RAD51C, RAD51D, ATM, and CHEK2 – were found to be significantly associated with breast cancer risk.

However, the distribution of mutations among women with breast cancer differed from the distribution among unaffected women, noted Steven Narod, MD, from the Women’s College Research Institute, Toronto, in an accompanying editorial.

“What this means to clinicians, now that we are expanding the use of gene-panel testing to include unaffected women with a moderate risk of breast cancer in the family history, is that our time will increasingly be spent counseling women with CHEK2 and ATM mutations,” he wrote. Currently, these two are “clumped in with ‘other genes.’ ... Most of the pretest discussion is currently focused on the implications of finding a BRCA1 or BRCA2 mutation.”

The new findings may lead to new risk management strategies, he suggested. “Most breast cancers that occur in women with a mutation in ATM or CHEK2 are estrogen receptor positive, so these women may be candidates for antiestrogen therapies such as tamoxifen, raloxifene, or aromatase inhibitors,” he wrote.

Dr. Narod observed that, for now, the management of most women with either mutation will consist of screening alone, starting with MRI at age 40 years.

The medical community is not ready yet to expand genetic screening to the general population, cautions Walton Taylor, MD, past president of the American Society of Breast Surgeons.

The ASBrS currently recommends that all patients with breast cancer as well as those at high risk for breast cancer be offered genetic testing. “All women at risk should be tested, and all patients with pathogenic variants need to be managed appropriately – it saves lives,” Dr. Taylor emphasized.

However, “unaffected people with no family history do not need genetic testing at this time,” he said in an interview.

As to what physicians might do to better manage patients with mutations that predispose to breast cancer, Dr. Taylor said, “It’s surprisingly easy.”

Every genetic testing company provides genetic counselors to guide patients through next steps, Dr. Taylor pointed out, and most cancer patients have nurse navigators who make sure patients get tested and followed appropriately.

Members of the ASBrS follow the National Comprehensive Cancer Network guidelines when they identify carriers of a pathogenic variant. Dr. Taylor said these are very useful guidelines for virtually all mutations identified thus far.

“This research is not necessarily new, but it is confirmatory for what we are doing, and that helps us make sure we are going down the right pathway,” Dr. Taylor said. “It confirms that what we think is right is right – and that matters,.”
 

CARRIERS consortium findings

The study led by Dr. Couch was carried out by the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. It involved analyzing data from 17 epidemiology studies that focused on women in the general population who develop breast cancer. For the studies, which were conducted in the United States, pathogenic variants in 28 cancer-predisposition genes were sequenced from 32,247 women with breast cancer (case patients) and 32,544 unaffected women (control persons).

In the overall CARRIERS analysis, the prevalence of pathogenic variants in 12 clinically actionable genes was 5.03% among case patients and 1.63% among control persons. The prevalence was similar in non-Hispanic White women, non-Hispanic Black women, and Hispanic case patients, as well as control persons, they added. The prevalence of pathogenic variants among Asian American case patients was lower, at only 1.64%.

Among patients who had breast cancer, the most common pathogenic variants included BRCA2, which occurred in 1.29% of case patients, followed by CHEK2, at a prevalence of 1.08%, and BRCA1, at a prevalence of 0.85%.

Mutations in BRCA1 increased the risk for breast cancer more than 7.5-fold; mutations in BRCA2 increased that risk more than fivefold, the investigators stated.

Mutations in PALB2 increased the risk of breast cancer approximately fourfold, they added.

Prevalence rates for both BRCA1 and BRCA2 among breast cancer patients declined rapidly after the age of 40. The decline in other variants, including ATM, CHEK2, and PALB2, was limited with increasing age.

Indeed, mutations in all five of these genes were associated with a lifetime absolute risk for breast cancer greater than 20% by the age of 85 years among non-Hispanic Whites.

Pathogenic variants in BRCA1 or BRCA2 yielded a lifetime risk for breast cancer of approximately 50%. Mutations in PALB2 yielded a lifetime breast cancer risk of approximately 32%.

The risk of having a mutation in specific genes varied depending on the type of breast cancer. For example, mutations in BARD1, RAD51C, and RAD51D increased the risk for estrogen receptor (ER)–negative breast cancer as well as triple-negative breast cancer, the authors noted, whereas mutations in ATM, CDH1, and CHEK2 increased the risk for ER-positive breast cancer.

“These refined estimates of the prevalences of pathogenic variants among women with breast cancer in the overall population, as opposed to selected high-risk patients, may inform ongoing discussions regarding testing in patients with breast cancer,” the CARRIERS authors observed.

“The risks of breast cancer associated with pathogenic variants in the genes evaluated in the population-based CARRIERS analysis also provide important information for risk assessment and counseling of women with breast cancer who do not meet high-risk selection criteria,” they suggested.
 

Similar findings in second study

The second study was conducted by the Breast Cancer Association Consortium under lead author Leila Dorling, PhD, University of Cambridge (England). This group sequenced 34 susceptibility genes from 60,466 women with breast cancer and 53,461 unaffected control persons.

“Protein-truncating variants in five genes (ATM, BRCA1, BRCA2, CHEK2, and PALB2) were associated with a significant risk of breast cancer overall (P < .0001),” the BCAC members reported. “For these genes, odds ratios ranged from 2.10 to 10.57.”

The association between overall breast cancer risk and mutations in seven other genes was more modest, conferring approximately twice the risk for breast cancer overall, although that risk was threefold higher for the TP53 mutation.

For the 12 genes the consortium singled out as being associated with either a significant or a more modest risk for breast cancer, the effect size did not vary significantly between European and Asian women, the authors noted. Again, the risk for ER-positive breast cancer was over two times greater for those who had either the ATM or the CHEK2 mutation. Having mutations in BARD1, BRCA1, BRCA1, PALB2, RAD51C, and RAD51D conferred a higher risk for ER-negative disease than for ER-positive disease.

There was also an association between rare missense variants in six genes – CHEK2, ATM, TP53, BRCA1, CDH1, and RECQL – and overall breast cancer risk, with the clearest evidence being for CHEK2.

“The absolute risk estimates place protein-truncating variants in BRCA1, BRCA2, and PALB2 in the high-risk category and place protein-truncating variants in ATM, BARD1, CHEK2, RAD51CC, and RAD51D in the moderate-risk category,” Dr. Dorling and colleagues reaffirmed.

“These results may guide screening as well as prevention with risk-reducing surgery or medication, in accordance with national guidelines,” the authors suggested.

The CARRIERS study was supported by the National Institutes of Health. The study by Dr. Dorling and colleagues was supported by the European Union Horizon 2020 research and innovation programs, among others. Dr. Narod disclosed no relevant financial relationships.

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

New findings of breast cancer gene mutations in women who have no family history of the disease offer a new way of estimating risk and may change the way in which these women are advised on risk management.

The findings come from two large studies, both published on Jan. 20 in the New England Journal of Medicine.

The two articles are “extraordinary” for broadening and validating the genomic panel to help screen women at risk for breast cancer in the future, commented Eric Topol, MD, professor of molecular medicine, Scripps Research, La Jolla, Calif., and Medscape editor in chief.

“Traditionally, genetic testing of inherited breast cancer genes has focused on women at high risk who have a strong family history of breast cancer or those who were diagnosed at an early age, such as under 45 years,” commented the lead investigator of one of the studies, Fergus Couch, PhD, a pathologist at the Mayo Clinic, Rochester, Minn.

“[Although] the risk of developing breast cancer is generally lower for women without a family history of the disease ... when we looked at all women, we found that 30% of breast cancer mutations occurred in women who are not high risk,” he said.

In both studies, mutations or variants in eight genes – BRCA1, BRCA2, PALB2, BARD1, RAD51C, RAD51D, ATM, and CHEK2 – were found to be significantly associated with breast cancer risk.

However, the distribution of mutations among women with breast cancer differed from the distribution among unaffected women, noted Steven Narod, MD, from the Women’s College Research Institute, Toronto, in an accompanying editorial.

“What this means to clinicians, now that we are expanding the use of gene-panel testing to include unaffected women with a moderate risk of breast cancer in the family history, is that our time will increasingly be spent counseling women with CHEK2 and ATM mutations,” he wrote. Currently, these two are “clumped in with ‘other genes.’ ... Most of the pretest discussion is currently focused on the implications of finding a BRCA1 or BRCA2 mutation.”

The new findings may lead to new risk management strategies, he suggested. “Most breast cancers that occur in women with a mutation in ATM or CHEK2 are estrogen receptor positive, so these women may be candidates for antiestrogen therapies such as tamoxifen, raloxifene, or aromatase inhibitors,” he wrote.

Dr. Narod observed that, for now, the management of most women with either mutation will consist of screening alone, starting with MRI at age 40 years.

The medical community is not ready yet to expand genetic screening to the general population, cautions Walton Taylor, MD, past president of the American Society of Breast Surgeons.

The ASBrS currently recommends that all patients with breast cancer as well as those at high risk for breast cancer be offered genetic testing. “All women at risk should be tested, and all patients with pathogenic variants need to be managed appropriately – it saves lives,” Dr. Taylor emphasized.

However, “unaffected people with no family history do not need genetic testing at this time,” he said in an interview.

As to what physicians might do to better manage patients with mutations that predispose to breast cancer, Dr. Taylor said, “It’s surprisingly easy.”

Every genetic testing company provides genetic counselors to guide patients through next steps, Dr. Taylor pointed out, and most cancer patients have nurse navigators who make sure patients get tested and followed appropriately.

Members of the ASBrS follow the National Comprehensive Cancer Network guidelines when they identify carriers of a pathogenic variant. Dr. Taylor said these are very useful guidelines for virtually all mutations identified thus far.

“This research is not necessarily new, but it is confirmatory for what we are doing, and that helps us make sure we are going down the right pathway,” Dr. Taylor said. “It confirms that what we think is right is right – and that matters,.”
 

CARRIERS consortium findings

The study led by Dr. Couch was carried out by the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. It involved analyzing data from 17 epidemiology studies that focused on women in the general population who develop breast cancer. For the studies, which were conducted in the United States, pathogenic variants in 28 cancer-predisposition genes were sequenced from 32,247 women with breast cancer (case patients) and 32,544 unaffected women (control persons).

In the overall CARRIERS analysis, the prevalence of pathogenic variants in 12 clinically actionable genes was 5.03% among case patients and 1.63% among control persons. The prevalence was similar in non-Hispanic White women, non-Hispanic Black women, and Hispanic case patients, as well as control persons, they added. The prevalence of pathogenic variants among Asian American case patients was lower, at only 1.64%.

Among patients who had breast cancer, the most common pathogenic variants included BRCA2, which occurred in 1.29% of case patients, followed by CHEK2, at a prevalence of 1.08%, and BRCA1, at a prevalence of 0.85%.

Mutations in BRCA1 increased the risk for breast cancer more than 7.5-fold; mutations in BRCA2 increased that risk more than fivefold, the investigators stated.

Mutations in PALB2 increased the risk of breast cancer approximately fourfold, they added.

Prevalence rates for both BRCA1 and BRCA2 among breast cancer patients declined rapidly after the age of 40. The decline in other variants, including ATM, CHEK2, and PALB2, was limited with increasing age.

Indeed, mutations in all five of these genes were associated with a lifetime absolute risk for breast cancer greater than 20% by the age of 85 years among non-Hispanic Whites.

Pathogenic variants in BRCA1 or BRCA2 yielded a lifetime risk for breast cancer of approximately 50%. Mutations in PALB2 yielded a lifetime breast cancer risk of approximately 32%.

The risk of having a mutation in specific genes varied depending on the type of breast cancer. For example, mutations in BARD1, RAD51C, and RAD51D increased the risk for estrogen receptor (ER)–negative breast cancer as well as triple-negative breast cancer, the authors noted, whereas mutations in ATM, CDH1, and CHEK2 increased the risk for ER-positive breast cancer.

“These refined estimates of the prevalences of pathogenic variants among women with breast cancer in the overall population, as opposed to selected high-risk patients, may inform ongoing discussions regarding testing in patients with breast cancer,” the CARRIERS authors observed.

“The risks of breast cancer associated with pathogenic variants in the genes evaluated in the population-based CARRIERS analysis also provide important information for risk assessment and counseling of women with breast cancer who do not meet high-risk selection criteria,” they suggested.
 

Similar findings in second study

The second study was conducted by the Breast Cancer Association Consortium under lead author Leila Dorling, PhD, University of Cambridge (England). This group sequenced 34 susceptibility genes from 60,466 women with breast cancer and 53,461 unaffected control persons.

“Protein-truncating variants in five genes (ATM, BRCA1, BRCA2, CHEK2, and PALB2) were associated with a significant risk of breast cancer overall (P < .0001),” the BCAC members reported. “For these genes, odds ratios ranged from 2.10 to 10.57.”

The association between overall breast cancer risk and mutations in seven other genes was more modest, conferring approximately twice the risk for breast cancer overall, although that risk was threefold higher for the TP53 mutation.

For the 12 genes the consortium singled out as being associated with either a significant or a more modest risk for breast cancer, the effect size did not vary significantly between European and Asian women, the authors noted. Again, the risk for ER-positive breast cancer was over two times greater for those who had either the ATM or the CHEK2 mutation. Having mutations in BARD1, BRCA1, BRCA1, PALB2, RAD51C, and RAD51D conferred a higher risk for ER-negative disease than for ER-positive disease.

There was also an association between rare missense variants in six genes – CHEK2, ATM, TP53, BRCA1, CDH1, and RECQL – and overall breast cancer risk, with the clearest evidence being for CHEK2.

“The absolute risk estimates place protein-truncating variants in BRCA1, BRCA2, and PALB2 in the high-risk category and place protein-truncating variants in ATM, BARD1, CHEK2, RAD51CC, and RAD51D in the moderate-risk category,” Dr. Dorling and colleagues reaffirmed.

“These results may guide screening as well as prevention with risk-reducing surgery or medication, in accordance with national guidelines,” the authors suggested.

The CARRIERS study was supported by the National Institutes of Health. The study by Dr. Dorling and colleagues was supported by the European Union Horizon 2020 research and innovation programs, among others. Dr. Narod disclosed no relevant financial relationships.

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

The relationship between obesity and overweight and breast cancer has some elements of mystery. But this is not one of them: in metastatic breast cancer (MBC), excess body weight does not negatively influence outcomes.

Multiple small studies have demonstrated this point, and now, for the first time, a large multicenter cohort analysis indicates the same.

Using medical records from 18 French comprehensive cancer centers, investigators reviewed body mass index (BMI) and overall survival (OS) data for nearly 13,000 women. The median OS was 47.4 months, and the median follow-up was about the same length of time. The team reports that obesity and overweight “were clearly not associated with prognosis.”

However, underweight was independently associated with worse OS (median, 33 months; hazard ratio, 1.14; 95% confidence interval, 1.02-1.27), report Khalil Saleh, MD, of Gustave Roussy in Villejuif, France, and colleagues.

In short, obesity or overweight had no effect on the primary outcome of OS, but underweight did.

“Underweight should be the subject of clinical attention at the time of diagnosis of MBC, and specific management should be implemented,” said study author Elise Deluche, MD, of CHU de Limoges, in an email to this news organization.

The study was published online Dec. 1 in The Breast.

“It’s really wonderful to have such a large cohort to look at this question,” said Jennifer Ligibel, MD, of the Dana-Farber Cancer Institute, Boston, who was asked for comment.

Is this another case of obesity paradox in cancer (as in renal cell carcinoma and melanoma, where excess weight is tied to better cancer-specific survival)?

No, said Dr. Ligibel: “There’s no hint at all [in this study] that people with obesity and overweight did better. … They just didn’t have worse outcomes.”

The study authors point out that the opposite is true in early-stage breast cancer. In this patient population, excess weight is associated with worse outcomes.

For example, in a 2014 meta-analysis of 82 follow-up studies in early-stage disease, obesity was associated with higher total mortality (relative risk, 1.41) and breast cancer–specific mortality (RR, 1.35) as compared to normal weight.

Why is there such a contrast between early- and late-stage disease?

“I don’t think we know exactly,” answered Dr. Ligibel. “It may be that, with breast cancer, as disease progresses, the pathways through which lifestyle may impact breast cancer may become less important.

“Obesity and overweight are associated with cancer risk in general,” said Dr. Ligibel, citing more than a dozen malignancies, including breast cancer.

But there is also an age element. Overweight or obesity is an independent predictor of breast cancer risk in postmenopausal women, but in premenopausal women, it appears to be protective. “Historically, there has been a lower risk of hormone receptor–positive breast cancer in women with obesity at younger ages that we don’t completely understand,” Dr. Ligibel noted.

That age-based difference is a conundrum, said Dr. Ligibel: “People have been trying to figure that out for a long time.”

Dr. Ligibel summarized as follows:

“There is a clear relationship between obesity and the risk of developing breast cancer; there is a clear relationship in early breast cancer that obesity is related to an increased risk of occurrence and mortality. What we are seeing from this study is that, by the time you get to metastatic breast cancer, body weight does not seem to play as important a role.”
 

More study details

The findings come from the French National Epidemiological Strategy and Medical Economics–Metastatic Breast Cancer observational cohort, which includes 22,000-plus consecutive patients who were newly diagnosed with metastatic disease between 2008 and 2016.

A total of 12,999 women for whom BMI data were available when they were diagnosed with metastatic breast cancer were selected for analysis. They were divided into four groups, according to World Health Organization classification: underweight (BMI <18.5 kg/m²), normal weight (18.5-24.9), overweight (25.0-29.9), and obese (≥30.0).

A total of 20% of women were obese, which is a much lower percentage than the 40%-50% that would be expected in a comparable American cohort, said Dr. Ligibel. Also, 5% of the French cohort was underweight.

Multivariate Cox analyses were carried out for OS and for first-line progression-free survival (PFS).

As noted above, underweight was independently associated with a worse OS. It was also tied to worse first-line PFS (HR, 1.11; 95% CI, 1.01-1.22). Overweight or obesity had no effect.

“Patients with a low BMI had more visceral metastases and a greater number of metastatic sites,” pointed out study author Dr. Deluche. “We attribute the fat loss in patients with metastatic breast cancer to aggressive tumor behavior with a higher energy requirement.”

The study authors also observe that in early-stage breast cancer, underweight is not associated with overall or breast cancer–specific survival. “Underweight at metastatic diagnosis seems to have a different significance and impact,” they write. The French team also observes that, in other cancers, underweight is also an adverse prognostic factor and has been associated with a higher risk for death.

The study authors acknowledge that BMI has limitations as a measure of body type. “BMI alone cannot estimate a woman’s muscle mass and adiposity,” they observe. The suggestion is that, among women with a similar BMI, some might be muscular, whereas others might have more body fat.

Multiple study authors report financial ties to industry, including pharmaceutical companies with drugs used in breast cancer. The database used in the study receives financial support from AstraZeneca, Daiichi Sankyo, Eisai, MSD, Pfizer, and Roche. Dr. Ligibel reports no relevant financial relationships.

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

The relationship between obesity and overweight and breast cancer has some elements of mystery. But this is not one of them: in metastatic breast cancer (MBC), excess body weight does not negatively influence outcomes.

Multiple small studies have demonstrated this point, and now, for the first time, a large multicenter cohort analysis indicates the same.

Using medical records from 18 French comprehensive cancer centers, investigators reviewed body mass index (BMI) and overall survival (OS) data for nearly 13,000 women. The median OS was 47.4 months, and the median follow-up was about the same length of time. The team reports that obesity and overweight “were clearly not associated with prognosis.”

However, underweight was independently associated with worse OS (median, 33 months; hazard ratio, 1.14; 95% confidence interval, 1.02-1.27), report Khalil Saleh, MD, of Gustave Roussy in Villejuif, France, and colleagues.

In short, obesity or overweight had no effect on the primary outcome of OS, but underweight did.

“Underweight should be the subject of clinical attention at the time of diagnosis of MBC, and specific management should be implemented,” said study author Elise Deluche, MD, of CHU de Limoges, in an email to this news organization.

The study was published online Dec. 1 in The Breast.

“It’s really wonderful to have such a large cohort to look at this question,” said Jennifer Ligibel, MD, of the Dana-Farber Cancer Institute, Boston, who was asked for comment.

Is this another case of obesity paradox in cancer (as in renal cell carcinoma and melanoma, where excess weight is tied to better cancer-specific survival)?

No, said Dr. Ligibel: “There’s no hint at all [in this study] that people with obesity and overweight did better. … They just didn’t have worse outcomes.”

The study authors point out that the opposite is true in early-stage breast cancer. In this patient population, excess weight is associated with worse outcomes.

For example, in a 2014 meta-analysis of 82 follow-up studies in early-stage disease, obesity was associated with higher total mortality (relative risk, 1.41) and breast cancer–specific mortality (RR, 1.35) as compared to normal weight.

Why is there such a contrast between early- and late-stage disease?

“I don’t think we know exactly,” answered Dr. Ligibel. “It may be that, with breast cancer, as disease progresses, the pathways through which lifestyle may impact breast cancer may become less important.

“Obesity and overweight are associated with cancer risk in general,” said Dr. Ligibel, citing more than a dozen malignancies, including breast cancer.

But there is also an age element. Overweight or obesity is an independent predictor of breast cancer risk in postmenopausal women, but in premenopausal women, it appears to be protective. “Historically, there has been a lower risk of hormone receptor–positive breast cancer in women with obesity at younger ages that we don’t completely understand,” Dr. Ligibel noted.

That age-based difference is a conundrum, said Dr. Ligibel: “People have been trying to figure that out for a long time.”

Dr. Ligibel summarized as follows:

“There is a clear relationship between obesity and the risk of developing breast cancer; there is a clear relationship in early breast cancer that obesity is related to an increased risk of occurrence and mortality. What we are seeing from this study is that, by the time you get to metastatic breast cancer, body weight does not seem to play as important a role.”
 

More study details

The findings come from the French National Epidemiological Strategy and Medical Economics–Metastatic Breast Cancer observational cohort, which includes 22,000-plus consecutive patients who were newly diagnosed with metastatic disease between 2008 and 2016.

A total of 12,999 women for whom BMI data were available when they were diagnosed with metastatic breast cancer were selected for analysis. They were divided into four groups, according to World Health Organization classification: underweight (BMI <18.5 kg/m²), normal weight (18.5-24.9), overweight (25.0-29.9), and obese (≥30.0).

A total of 20% of women were obese, which is a much lower percentage than the 40%-50% that would be expected in a comparable American cohort, said Dr. Ligibel. Also, 5% of the French cohort was underweight.

Multivariate Cox analyses were carried out for OS and for first-line progression-free survival (PFS).

As noted above, underweight was independently associated with a worse OS. It was also tied to worse first-line PFS (HR, 1.11; 95% CI, 1.01-1.22). Overweight or obesity had no effect.

“Patients with a low BMI had more visceral metastases and a greater number of metastatic sites,” pointed out study author Dr. Deluche. “We attribute the fat loss in patients with metastatic breast cancer to aggressive tumor behavior with a higher energy requirement.”

The study authors also observe that in early-stage breast cancer, underweight is not associated with overall or breast cancer–specific survival. “Underweight at metastatic diagnosis seems to have a different significance and impact,” they write. The French team also observes that, in other cancers, underweight is also an adverse prognostic factor and has been associated with a higher risk for death.

The study authors acknowledge that BMI has limitations as a measure of body type. “BMI alone cannot estimate a woman’s muscle mass and adiposity,” they observe. The suggestion is that, among women with a similar BMI, some might be muscular, whereas others might have more body fat.

Multiple study authors report financial ties to industry, including pharmaceutical companies with drugs used in breast cancer. The database used in the study receives financial support from AstraZeneca, Daiichi Sankyo, Eisai, MSD, Pfizer, and Roche. Dr. Ligibel reports no relevant financial relationships.

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

The relationship between obesity and overweight and breast cancer has some elements of mystery. But this is not one of them: in metastatic breast cancer (MBC), excess body weight does not negatively influence outcomes.

Multiple small studies have demonstrated this point, and now, for the first time, a large multicenter cohort analysis indicates the same.

Using medical records from 18 French comprehensive cancer centers, investigators reviewed body mass index (BMI) and overall survival (OS) data for nearly 13,000 women. The median OS was 47.4 months, and the median follow-up was about the same length of time. The team reports that obesity and overweight “were clearly not associated with prognosis.”

However, underweight was independently associated with worse OS (median, 33 months; hazard ratio, 1.14; 95% confidence interval, 1.02-1.27), report Khalil Saleh, MD, of Gustave Roussy in Villejuif, France, and colleagues.

In short, obesity or overweight had no effect on the primary outcome of OS, but underweight did.

“Underweight should be the subject of clinical attention at the time of diagnosis of MBC, and specific management should be implemented,” said study author Elise Deluche, MD, of CHU de Limoges, in an email to this news organization.

The study was published online Dec. 1 in The Breast.

“It’s really wonderful to have such a large cohort to look at this question,” said Jennifer Ligibel, MD, of the Dana-Farber Cancer Institute, Boston, who was asked for comment.

Is this another case of obesity paradox in cancer (as in renal cell carcinoma and melanoma, where excess weight is tied to better cancer-specific survival)?

No, said Dr. Ligibel: “There’s no hint at all [in this study] that people with obesity and overweight did better. … They just didn’t have worse outcomes.”

The study authors point out that the opposite is true in early-stage breast cancer. In this patient population, excess weight is associated with worse outcomes.

For example, in a 2014 meta-analysis of 82 follow-up studies in early-stage disease, obesity was associated with higher total mortality (relative risk, 1.41) and breast cancer–specific mortality (RR, 1.35) as compared to normal weight.

Why is there such a contrast between early- and late-stage disease?

“I don’t think we know exactly,” answered Dr. Ligibel. “It may be that, with breast cancer, as disease progresses, the pathways through which lifestyle may impact breast cancer may become less important.

“Obesity and overweight are associated with cancer risk in general,” said Dr. Ligibel, citing more than a dozen malignancies, including breast cancer.

But there is also an age element. Overweight or obesity is an independent predictor of breast cancer risk in postmenopausal women, but in premenopausal women, it appears to be protective. “Historically, there has been a lower risk of hormone receptor–positive breast cancer in women with obesity at younger ages that we don’t completely understand,” Dr. Ligibel noted.

That age-based difference is a conundrum, said Dr. Ligibel: “People have been trying to figure that out for a long time.”

Dr. Ligibel summarized as follows:

“There is a clear relationship between obesity and the risk of developing breast cancer; there is a clear relationship in early breast cancer that obesity is related to an increased risk of occurrence and mortality. What we are seeing from this study is that, by the time you get to metastatic breast cancer, body weight does not seem to play as important a role.”
 

More study details

The findings come from the French National Epidemiological Strategy and Medical Economics–Metastatic Breast Cancer observational cohort, which includes 22,000-plus consecutive patients who were newly diagnosed with metastatic disease between 2008 and 2016.

A total of 12,999 women for whom BMI data were available when they were diagnosed with metastatic breast cancer were selected for analysis. They were divided into four groups, according to World Health Organization classification: underweight (BMI <18.5 kg/m²), normal weight (18.5-24.9), overweight (25.0-29.9), and obese (≥30.0).

A total of 20% of women were obese, which is a much lower percentage than the 40%-50% that would be expected in a comparable American cohort, said Dr. Ligibel. Also, 5% of the French cohort was underweight.

Multivariate Cox analyses were carried out for OS and for first-line progression-free survival (PFS).

As noted above, underweight was independently associated with a worse OS. It was also tied to worse first-line PFS (HR, 1.11; 95% CI, 1.01-1.22). Overweight or obesity had no effect.

“Patients with a low BMI had more visceral metastases and a greater number of metastatic sites,” pointed out study author Dr. Deluche. “We attribute the fat loss in patients with metastatic breast cancer to aggressive tumor behavior with a higher energy requirement.”

The study authors also observe that in early-stage breast cancer, underweight is not associated with overall or breast cancer–specific survival. “Underweight at metastatic diagnosis seems to have a different significance and impact,” they write. The French team also observes that, in other cancers, underweight is also an adverse prognostic factor and has been associated with a higher risk for death.

The study authors acknowledge that BMI has limitations as a measure of body type. “BMI alone cannot estimate a woman’s muscle mass and adiposity,” they observe. The suggestion is that, among women with a similar BMI, some might be muscular, whereas others might have more body fat.

Multiple study authors report financial ties to industry, including pharmaceutical companies with drugs used in breast cancer. The database used in the study receives financial support from AstraZeneca, Daiichi Sankyo, Eisai, MSD, Pfizer, and Roche. Dr. Ligibel reports no relevant financial relationships.

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

Dramatic changes in the use of radiotherapy for cancer were seen during the first wave of the COVID-19 pandemic in England. Some radiotherapy regimens were shortened, but others were intensified, suggesting that they were being used as a replacement for surgery.

The findings come from an analysis of National Health Service data in England, which also indicated that overall there was a reduction in the amount of radiotherapy delivered.

“Radiotherapy is a very important treatment option for cancer, and our study shows that, across the English NHS, there was a rapid shift in how radiotherapy was used,” said lead author Katie Spencer, PhD, faculty of medicine and health, University of Leeds (England).

“It is impressive to see that the data closely follow the guidelines published at the start of the pandemic,” she said. For instance, for patients with breast and colorectal cancers, treatment regimens were shorter and more intensive, whereas for patients with prostate cancer, treatments were delayed to reduce exposure to COVID-19.

“In other cases, such as head and neck cancers and anal cancers, we saw that the number of radiotherapy treatments hardly changed during the first wave. This was really reassuring, as we know that it is vital that these treatments are not delayed,” Dr. Spencer added.

The study was published online in The Lancet Oncology on Jan. 22 (doi: 10.1016/S1470-2045[20]30743-9).

Researchers examined data from the National Radiotherapy Dataset on all radiotherapy delivered for cancer in the NHS in England between Feb. 4, 2019, and June 28, 2020.

On interrupted time-series analysis, the introduction of lockdown in response to the COVID-19 pandemic was associated with a significant reduction in both radiotherapy courses and attendances (P < .0001).

Overall, the team estimated that there were 3,263 fewer radiotherapy treatment courses and 119,050 fewer attendances than would have taken place had the pandemic not occurred.

The largest reduction in treatment courses was seen for prostate cancer, with a 77% reduction in April 2020 in comparison with April 2019, and in nonmelanoma skin cancer, for which there was a decrease of 72.4% over the same period.

There were, however, marked increases in the number of radiotherapy courses given for some disorders in April 2020 in comparison with April 2019. Radiotherapy for bladder cancer increased by 64.2%; for esophageal cancer, it increased by 41.2%; and for rectal cancer, it increased by 36.3%.

This likely reflects the fact that, during the pandemic, “surgical capacity dropped dramatically,” Dr. Spencer said in an interview.

“To try to mitigate the consequences of that, working with their multidisciplinary teams, doctors increased the use of radiotherapy to provide a timely alternative curative treatment and help mitigate the consequences of not having access to surgery,” she said.

“This is a cohort of patients who would otherwise have had their treatment delayed, and we know that’s detrimental, so having an alternative strategy that, in specific cases, can offer similar outcomes is fantastic,” she added.

The analysis shows the “incredible speed with which radiotherapy services within the NHS were able to adapt their treatment patterns to help protect patients with cancer whilst coping with reduced surgical capacity due to the global pandemic,” coauthor Tom Roques, MD, medical director of professional practice for clinical oncology at the Royal College of Radiologists, commented in a statement.
 

Shorter radiotherapy regimen for breast cancer

In addition to the pandemic, two other events led to changes in the way that radiotherapy was delivered in the period analyzed.

One was the publication in April 2020 of the FAST-Forward trial of radiotherapy for breast cancer. This showed that radiotherapy with 26 Gy in 5 fractions administered over 1 week following primary surgery for early breast cancer was noninferior to the standard 40 Gy delivered in 15 fractions over 3 weeks.

These results led to immediate changes in practice, and quick implementation across the NHS “massively freed up capacity in terms of the number of fractions being delivered but also really helped to keep patients safe by ensuring they were only visiting the hospital on 5 occasions instead of the standard 15,” Spencer said.

Indeed, the analysis showed that the proportion of all breast radiotherapy courses given as the ultrahypofractionated regimen of 26 Gy in five fractions increased from 0.2% in April 2019 to 60.0% in April 2020 (P < .0001), which the authors noted “contributed to the substantial reduction” in radiotherapy attendances.

The other event occurred in March 2020, when NHS England “dramatically changed commissioning” from a tariff-based system in which radiotherapy was paid for every fraction delivered to a “payment that reflects the amount of money that was spent the previous year.

“That supported radiotherapy providers to do what was necessary to continue to deliver the best possible care to patients with cancer despite COVID,” Dr. Spencer added. “We saw this in our study, with doctors shortening radiotherapy courses to keep patients safe and departments running.”

The question now is whether the changes resulting from these two events will be maintained once the COVID-19 pandemic lifts.

What will happen to radiotherapy service commissioning beyond the end of the financial year is currently “unclear,” Dr. Spencer commented.

“There’s strong clinical support for continuing to use the shorter treatment courses in breast cancer, although it’s hard to know how any change in commissioning and reduction in COVID risk will influence their use over the next year and beyond,” she said.

“The data we used in this study, that Public Health England collect, will be really valuable in helping us to assess this in future,” Dr. Spencer said.
 

Radiotherapy remains reduced

Dr. Spencer taid that, “whilst in April and May 2020 we saw that the fall in radiotherapy was in cancers where it›s safe to delay treatment, in June we could see that radiotherapy activity was not back up to where it was previously, and that was across a wider range of cancers.

“This looks likely to be because of a fall in the number of people being diagnosed with cancer,” she said.

“The pandemic continues to cause severe disruption for cancer diagnosis and some national screening programs,” she commented. “This has meant that fewer patients were diagnosed with cancer during the first wave of the pandemic, and this is likely to have led to the persistent fall in treatments we are seeing.”

By November 2020, some referral pathways were back up to the volume of patients that was seen before the pandemic, but “it’s very variable across different diagnoses.”

The fear is that the resurgence of COVID-19 over the past month has made the situation worse, which is “very worrying,” Dr. Spencer said.

No funding for the study was declared. The authors disclosed no relevant financial relationships.

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

Dramatic changes in the use of radiotherapy for cancer were seen during the first wave of the COVID-19 pandemic in England. Some radiotherapy regimens were shortened, but others were intensified, suggesting that they were being used as a replacement for surgery.

The findings come from an analysis of National Health Service data in England, which also indicated that overall there was a reduction in the amount of radiotherapy delivered.

“Radiotherapy is a very important treatment option for cancer, and our study shows that, across the English NHS, there was a rapid shift in how radiotherapy was used,” said lead author Katie Spencer, PhD, faculty of medicine and health, University of Leeds (England).

“It is impressive to see that the data closely follow the guidelines published at the start of the pandemic,” she said. For instance, for patients with breast and colorectal cancers, treatment regimens were shorter and more intensive, whereas for patients with prostate cancer, treatments were delayed to reduce exposure to COVID-19.

“In other cases, such as head and neck cancers and anal cancers, we saw that the number of radiotherapy treatments hardly changed during the first wave. This was really reassuring, as we know that it is vital that these treatments are not delayed,” Dr. Spencer added.

The study was published online in The Lancet Oncology on Jan. 22 (doi: 10.1016/S1470-2045[20]30743-9).

Researchers examined data from the National Radiotherapy Dataset on all radiotherapy delivered for cancer in the NHS in England between Feb. 4, 2019, and June 28, 2020.

On interrupted time-series analysis, the introduction of lockdown in response to the COVID-19 pandemic was associated with a significant reduction in both radiotherapy courses and attendances (P < .0001).

Overall, the team estimated that there were 3,263 fewer radiotherapy treatment courses and 119,050 fewer attendances than would have taken place had the pandemic not occurred.

The largest reduction in treatment courses was seen for prostate cancer, with a 77% reduction in April 2020 in comparison with April 2019, and in nonmelanoma skin cancer, for which there was a decrease of 72.4% over the same period.

There were, however, marked increases in the number of radiotherapy courses given for some disorders in April 2020 in comparison with April 2019. Radiotherapy for bladder cancer increased by 64.2%; for esophageal cancer, it increased by 41.2%; and for rectal cancer, it increased by 36.3%.

This likely reflects the fact that, during the pandemic, “surgical capacity dropped dramatically,” Dr. Spencer said in an interview.

“To try to mitigate the consequences of that, working with their multidisciplinary teams, doctors increased the use of radiotherapy to provide a timely alternative curative treatment and help mitigate the consequences of not having access to surgery,” she said.

“This is a cohort of patients who would otherwise have had their treatment delayed, and we know that’s detrimental, so having an alternative strategy that, in specific cases, can offer similar outcomes is fantastic,” she added.

The analysis shows the “incredible speed with which radiotherapy services within the NHS were able to adapt their treatment patterns to help protect patients with cancer whilst coping with reduced surgical capacity due to the global pandemic,” coauthor Tom Roques, MD, medical director of professional practice for clinical oncology at the Royal College of Radiologists, commented in a statement.
 

Shorter radiotherapy regimen for breast cancer

In addition to the pandemic, two other events led to changes in the way that radiotherapy was delivered in the period analyzed.

One was the publication in April 2020 of the FAST-Forward trial of radiotherapy for breast cancer. This showed that radiotherapy with 26 Gy in 5 fractions administered over 1 week following primary surgery for early breast cancer was noninferior to the standard 40 Gy delivered in 15 fractions over 3 weeks.

These results led to immediate changes in practice, and quick implementation across the NHS “massively freed up capacity in terms of the number of fractions being delivered but also really helped to keep patients safe by ensuring they were only visiting the hospital on 5 occasions instead of the standard 15,” Spencer said.

Indeed, the analysis showed that the proportion of all breast radiotherapy courses given as the ultrahypofractionated regimen of 26 Gy in five fractions increased from 0.2% in April 2019 to 60.0% in April 2020 (P < .0001), which the authors noted “contributed to the substantial reduction” in radiotherapy attendances.

The other event occurred in March 2020, when NHS England “dramatically changed commissioning” from a tariff-based system in which radiotherapy was paid for every fraction delivered to a “payment that reflects the amount of money that was spent the previous year.

“That supported radiotherapy providers to do what was necessary to continue to deliver the best possible care to patients with cancer despite COVID,” Dr. Spencer added. “We saw this in our study, with doctors shortening radiotherapy courses to keep patients safe and departments running.”

The question now is whether the changes resulting from these two events will be maintained once the COVID-19 pandemic lifts.

What will happen to radiotherapy service commissioning beyond the end of the financial year is currently “unclear,” Dr. Spencer commented.

“There’s strong clinical support for continuing to use the shorter treatment courses in breast cancer, although it’s hard to know how any change in commissioning and reduction in COVID risk will influence their use over the next year and beyond,” she said.

“The data we used in this study, that Public Health England collect, will be really valuable in helping us to assess this in future,” Dr. Spencer said.
 

Radiotherapy remains reduced

Dr. Spencer taid that, “whilst in April and May 2020 we saw that the fall in radiotherapy was in cancers where it›s safe to delay treatment, in June we could see that radiotherapy activity was not back up to where it was previously, and that was across a wider range of cancers.

“This looks likely to be because of a fall in the number of people being diagnosed with cancer,” she said.

“The pandemic continues to cause severe disruption for cancer diagnosis and some national screening programs,” she commented. “This has meant that fewer patients were diagnosed with cancer during the first wave of the pandemic, and this is likely to have led to the persistent fall in treatments we are seeing.”

By November 2020, some referral pathways were back up to the volume of patients that was seen before the pandemic, but “it’s very variable across different diagnoses.”

The fear is that the resurgence of COVID-19 over the past month has made the situation worse, which is “very worrying,” Dr. Spencer said.

No funding for the study was declared. The authors disclosed no relevant financial relationships.

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

Dramatic changes in the use of radiotherapy for cancer were seen during the first wave of the COVID-19 pandemic in England. Some radiotherapy regimens were shortened, but others were intensified, suggesting that they were being used as a replacement for surgery.

The findings come from an analysis of National Health Service data in England, which also indicated that overall there was a reduction in the amount of radiotherapy delivered.

“Radiotherapy is a very important treatment option for cancer, and our study shows that, across the English NHS, there was a rapid shift in how radiotherapy was used,” said lead author Katie Spencer, PhD, faculty of medicine and health, University of Leeds (England).

“It is impressive to see that the data closely follow the guidelines published at the start of the pandemic,” she said. For instance, for patients with breast and colorectal cancers, treatment regimens were shorter and more intensive, whereas for patients with prostate cancer, treatments were delayed to reduce exposure to COVID-19.

“In other cases, such as head and neck cancers and anal cancers, we saw that the number of radiotherapy treatments hardly changed during the first wave. This was really reassuring, as we know that it is vital that these treatments are not delayed,” Dr. Spencer added.

The study was published online in The Lancet Oncology on Jan. 22 (doi: 10.1016/S1470-2045[20]30743-9).

Researchers examined data from the National Radiotherapy Dataset on all radiotherapy delivered for cancer in the NHS in England between Feb. 4, 2019, and June 28, 2020.

On interrupted time-series analysis, the introduction of lockdown in response to the COVID-19 pandemic was associated with a significant reduction in both radiotherapy courses and attendances (P < .0001).

Overall, the team estimated that there were 3,263 fewer radiotherapy treatment courses and 119,050 fewer attendances than would have taken place had the pandemic not occurred.

The largest reduction in treatment courses was seen for prostate cancer, with a 77% reduction in April 2020 in comparison with April 2019, and in nonmelanoma skin cancer, for which there was a decrease of 72.4% over the same period.

There were, however, marked increases in the number of radiotherapy courses given for some disorders in April 2020 in comparison with April 2019. Radiotherapy for bladder cancer increased by 64.2%; for esophageal cancer, it increased by 41.2%; and for rectal cancer, it increased by 36.3%.

This likely reflects the fact that, during the pandemic, “surgical capacity dropped dramatically,” Dr. Spencer said in an interview.

“To try to mitigate the consequences of that, working with their multidisciplinary teams, doctors increased the use of radiotherapy to provide a timely alternative curative treatment and help mitigate the consequences of not having access to surgery,” she said.

“This is a cohort of patients who would otherwise have had their treatment delayed, and we know that’s detrimental, so having an alternative strategy that, in specific cases, can offer similar outcomes is fantastic,” she added.

The analysis shows the “incredible speed with which radiotherapy services within the NHS were able to adapt their treatment patterns to help protect patients with cancer whilst coping with reduced surgical capacity due to the global pandemic,” coauthor Tom Roques, MD, medical director of professional practice for clinical oncology at the Royal College of Radiologists, commented in a statement.
 

Shorter radiotherapy regimen for breast cancer

In addition to the pandemic, two other events led to changes in the way that radiotherapy was delivered in the period analyzed.

One was the publication in April 2020 of the FAST-Forward trial of radiotherapy for breast cancer. This showed that radiotherapy with 26 Gy in 5 fractions administered over 1 week following primary surgery for early breast cancer was noninferior to the standard 40 Gy delivered in 15 fractions over 3 weeks.

These results led to immediate changes in practice, and quick implementation across the NHS “massively freed up capacity in terms of the number of fractions being delivered but also really helped to keep patients safe by ensuring they were only visiting the hospital on 5 occasions instead of the standard 15,” Spencer said.

Indeed, the analysis showed that the proportion of all breast radiotherapy courses given as the ultrahypofractionated regimen of 26 Gy in five fractions increased from 0.2% in April 2019 to 60.0% in April 2020 (P < .0001), which the authors noted “contributed to the substantial reduction” in radiotherapy attendances.

The other event occurred in March 2020, when NHS England “dramatically changed commissioning” from a tariff-based system in which radiotherapy was paid for every fraction delivered to a “payment that reflects the amount of money that was spent the previous year.

“That supported radiotherapy providers to do what was necessary to continue to deliver the best possible care to patients with cancer despite COVID,” Dr. Spencer added. “We saw this in our study, with doctors shortening radiotherapy courses to keep patients safe and departments running.”

The question now is whether the changes resulting from these two events will be maintained once the COVID-19 pandemic lifts.

What will happen to radiotherapy service commissioning beyond the end of the financial year is currently “unclear,” Dr. Spencer commented.

“There’s strong clinical support for continuing to use the shorter treatment courses in breast cancer, although it’s hard to know how any change in commissioning and reduction in COVID risk will influence their use over the next year and beyond,” she said.

“The data we used in this study, that Public Health England collect, will be really valuable in helping us to assess this in future,” Dr. Spencer said.
 

Radiotherapy remains reduced

Dr. Spencer taid that, “whilst in April and May 2020 we saw that the fall in radiotherapy was in cancers where it›s safe to delay treatment, in June we could see that radiotherapy activity was not back up to where it was previously, and that was across a wider range of cancers.

“This looks likely to be because of a fall in the number of people being diagnosed with cancer,” she said.

“The pandemic continues to cause severe disruption for cancer diagnosis and some national screening programs,” she commented. “This has meant that fewer patients were diagnosed with cancer during the first wave of the pandemic, and this is likely to have led to the persistent fall in treatments we are seeing.”

By November 2020, some referral pathways were back up to the volume of patients that was seen before the pandemic, but “it’s very variable across different diagnoses.”

The fear is that the resurgence of COVID-19 over the past month has made the situation worse, which is “very worrying,” Dr. Spencer said.

No funding for the study was declared. The authors disclosed no relevant financial relationships.

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

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

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

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

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

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

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

Unique concerns in patients with cancer

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

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

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

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

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

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

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

Additional vaccine considerations

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

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

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

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

[email protected]

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

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

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

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

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

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

Unique concerns in patients with cancer

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

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

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

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

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

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

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

Additional vaccine considerations

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

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

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

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

[email protected]

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

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

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

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

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

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

Unique concerns in patients with cancer

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

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

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

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

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

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

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

Additional vaccine considerations

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

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

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

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

[email protected]

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The first guidelines ever released for screening mammography for older survivors of breast cancer (>75 years) recommend that routine mammography be discontinued for women whose life expectancy is less than 5 years but that screening continue for those whose life expectancy is more than 10 years.

For women who have a life expectancy of 5-10 years, the guidelines recommend that consideration be given to discontinuing mammography.

Overall, the guidelines encourage shared decision-making that is individualized for each woman after weighing the benefits and harms associated with surveillance mammography and patient preferences.

The panel also recommended that patients with clinical findings and symptoms receive ongoing clinical breast examinations and diagnostic mammography and that patients be reassured that these practices will continue.

Guidelines on breast cancer screening for healthy women already “acknowledge the limitations of mammograms and the need to consider one’s health status and preferences when making decisions on how and when to stop routine mammograms,” said the article’s first author, Rachel A. Freedman, MD, MPH, of the Dana-Farber Cancer Institute, Boston.

However, “we don’t have this kind of consensus for women with a history of breast cancer,” she continued. “Current follow-up care guidelines simply state that women with a history of breast cancer with intact breasts should have annual mammography without any guidance.

“In practice, the use of mammograms is highly variable, with less than 50% of breast cancer survivors who have limited life expectancy having annual mammograms, according to survey data we have from prior work,” Dr. Freedman said in an interview.

The guidelines were published online Jan. 28 in JAMA Oncology.
 

Clinicians discuss how to have these discussions

As part of the process of developing these expert consensus guidelines, the researchers held several clinical focus groups that involved primary care physicians from Brigham and Women’s Hospital and oncology clinicians (including breast surgeons and medical oncologists) from the Dana-Farber Cancer Institute.

All clinicians felt that having expert guidelines and talking points to guide discussions would be helpful, the researchers report.

“However, some oncology clinicians felt that 75 years is often ‘too young’ to stop surveillance mammography and that 80 years may be a more comfortable age to stop routine testing,” they write. “Most clinicians felt that estimations of life expectancy, more than age, should inform the timing of this discussion.”

In contrast to primary and geriatric care clinicians, oncology clinicians reported discomfort with such discussions. They appreciated having the information but “felt it was easier to communicate findings indirectly, without specifically revealing life expectancy to patients. One oncology clinician, however, felt it would be ‘sneaky’ to calculate life expectancy without communicating this to patients, supporting more open discussions,” the authors report.

“All clinicians acknowledged that framing the conversation around patients’ low risk for in-breast cancer events and how mammography will not benefit them was more appealing than discussing life expectancy,” the researchers continue. Their literature review found that the risk of these individuals developing second breast cancers was similar to that of a healthy woman developing a first breast cancer, leading one clinician to comment: “If their risk is really equivalent to the general population – that is very powerful.”

“Some clinicians reported that they ‘focus on the risks’ or frame such discussions by asking: ‘If you were to find something on [a] mammogram, would you do anything about it?’ If a patient answered no, clinicians felt this was a signal to stop mammography,” they noted.
 

Literature review finds very low risk

Dr. Freedman and colleagues conducted a literature review of the risk for ipsilateral and contralateral breast cancer events among survivors and of the harms and benefits associated with mammography. Following the literature review, a multidisciplinary expert panel, which included patients and patient advocates, was convened to develop consensus guidelines.

The literature review confirmed that there was a low risk for in-breast cancer events in this population and that the risk was particularly low among patients who undergo treatment with endocrine therapy. Among those who did not receive systemic therapy for ERBB2-positive or triple-negative cancers, the rates of ipsilateral recurrence were estimated to be higher.

On the basis of the literature review, the estimated 10-year risk for in-breast cancer events ranged from 1% to 15% for ipsilateral breast cancers and from 1% to 5% for contralateral cancers. Among women in the same age group who did not have a history of breast cancer, the 5-year risk of developing the disease (average risk) was 2.2%.

The authors note that these findings mirror their estimates for new breast cancers among survivors who had low-risk disease. The findings are also similar to those cited in a large-scale mammography study, in which breast cancer survivors aged 70-80 years had a 1.1% annual risk for in-breast cancers. The risk was 0.7%-0.9% for similarly aged patients who did not have a history of breast cancer.

The benefits associated with mammography for older women are not well defined, but the literature suggests that mammography offers little to modest clinical benefit for patients in this age group. The limited benefits are likely because of the more than 10-year time lag that is needed to detect the small improvements in breast cancer mortality; slow-growing tumors generally do not affect the life expectancy of older women, they point out.

“Through our expert consensus process and after iterative feedback from clinicians, we created guidelines to support patients and clinicians in making individualized decisions on how and when to stop mammography,” said Dr. Freedman. “These guidelines are based on the risk of a breast cancer returning in the breast, one’s underlying health, and one’s preferences.”

The guidelines are also intended to provide information to patients on the benefits and harms of mammography in this setting, in addition to “how much we anticipate a mammogram may or may not continue to help a woman over time,” she said.

A companion guide for patients on these guidelines will be published in the coming months.

Dr. Freedman has received institutional clinical trial funding from Eisai and Puma Biotechnology outside the submitted work.

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

The first guidelines ever released for screening mammography for older survivors of breast cancer (>75 years) recommend that routine mammography be discontinued for women whose life expectancy is less than 5 years but that screening continue for those whose life expectancy is more than 10 years.

For women who have a life expectancy of 5-10 years, the guidelines recommend that consideration be given to discontinuing mammography.

Overall, the guidelines encourage shared decision-making that is individualized for each woman after weighing the benefits and harms associated with surveillance mammography and patient preferences.

The panel also recommended that patients with clinical findings and symptoms receive ongoing clinical breast examinations and diagnostic mammography and that patients be reassured that these practices will continue.

Guidelines on breast cancer screening for healthy women already “acknowledge the limitations of mammograms and the need to consider one’s health status and preferences when making decisions on how and when to stop routine mammograms,” said the article’s first author, Rachel A. Freedman, MD, MPH, of the Dana-Farber Cancer Institute, Boston.

However, “we don’t have this kind of consensus for women with a history of breast cancer,” she continued. “Current follow-up care guidelines simply state that women with a history of breast cancer with intact breasts should have annual mammography without any guidance.

“In practice, the use of mammograms is highly variable, with less than 50% of breast cancer survivors who have limited life expectancy having annual mammograms, according to survey data we have from prior work,” Dr. Freedman said in an interview.

The guidelines were published online Jan. 28 in JAMA Oncology.
 

Clinicians discuss how to have these discussions

As part of the process of developing these expert consensus guidelines, the researchers held several clinical focus groups that involved primary care physicians from Brigham and Women’s Hospital and oncology clinicians (including breast surgeons and medical oncologists) from the Dana-Farber Cancer Institute.

All clinicians felt that having expert guidelines and talking points to guide discussions would be helpful, the researchers report.

“However, some oncology clinicians felt that 75 years is often ‘too young’ to stop surveillance mammography and that 80 years may be a more comfortable age to stop routine testing,” they write. “Most clinicians felt that estimations of life expectancy, more than age, should inform the timing of this discussion.”

In contrast to primary and geriatric care clinicians, oncology clinicians reported discomfort with such discussions. They appreciated having the information but “felt it was easier to communicate findings indirectly, without specifically revealing life expectancy to patients. One oncology clinician, however, felt it would be ‘sneaky’ to calculate life expectancy without communicating this to patients, supporting more open discussions,” the authors report.

“All clinicians acknowledged that framing the conversation around patients’ low risk for in-breast cancer events and how mammography will not benefit them was more appealing than discussing life expectancy,” the researchers continue. Their literature review found that the risk of these individuals developing second breast cancers was similar to that of a healthy woman developing a first breast cancer, leading one clinician to comment: “If their risk is really equivalent to the general population – that is very powerful.”

“Some clinicians reported that they ‘focus on the risks’ or frame such discussions by asking: ‘If you were to find something on [a] mammogram, would you do anything about it?’ If a patient answered no, clinicians felt this was a signal to stop mammography,” they noted.
 

Literature review finds very low risk

Dr. Freedman and colleagues conducted a literature review of the risk for ipsilateral and contralateral breast cancer events among survivors and of the harms and benefits associated with mammography. Following the literature review, a multidisciplinary expert panel, which included patients and patient advocates, was convened to develop consensus guidelines.

The literature review confirmed that there was a low risk for in-breast cancer events in this population and that the risk was particularly low among patients who undergo treatment with endocrine therapy. Among those who did not receive systemic therapy for ERBB2-positive or triple-negative cancers, the rates of ipsilateral recurrence were estimated to be higher.

On the basis of the literature review, the estimated 10-year risk for in-breast cancer events ranged from 1% to 15% for ipsilateral breast cancers and from 1% to 5% for contralateral cancers. Among women in the same age group who did not have a history of breast cancer, the 5-year risk of developing the disease (average risk) was 2.2%.

The authors note that these findings mirror their estimates for new breast cancers among survivors who had low-risk disease. The findings are also similar to those cited in a large-scale mammography study, in which breast cancer survivors aged 70-80 years had a 1.1% annual risk for in-breast cancers. The risk was 0.7%-0.9% for similarly aged patients who did not have a history of breast cancer.

The benefits associated with mammography for older women are not well defined, but the literature suggests that mammography offers little to modest clinical benefit for patients in this age group. The limited benefits are likely because of the more than 10-year time lag that is needed to detect the small improvements in breast cancer mortality; slow-growing tumors generally do not affect the life expectancy of older women, they point out.

“Through our expert consensus process and after iterative feedback from clinicians, we created guidelines to support patients and clinicians in making individualized decisions on how and when to stop mammography,” said Dr. Freedman. “These guidelines are based on the risk of a breast cancer returning in the breast, one’s underlying health, and one’s preferences.”

The guidelines are also intended to provide information to patients on the benefits and harms of mammography in this setting, in addition to “how much we anticipate a mammogram may or may not continue to help a woman over time,” she said.

A companion guide for patients on these guidelines will be published in the coming months.

Dr. Freedman has received institutional clinical trial funding from Eisai and Puma Biotechnology outside the submitted work.

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

The first guidelines ever released for screening mammography for older survivors of breast cancer (>75 years) recommend that routine mammography be discontinued for women whose life expectancy is less than 5 years but that screening continue for those whose life expectancy is more than 10 years.

For women who have a life expectancy of 5-10 years, the guidelines recommend that consideration be given to discontinuing mammography.

Overall, the guidelines encourage shared decision-making that is individualized for each woman after weighing the benefits and harms associated with surveillance mammography and patient preferences.

The panel also recommended that patients with clinical findings and symptoms receive ongoing clinical breast examinations and diagnostic mammography and that patients be reassured that these practices will continue.

Guidelines on breast cancer screening for healthy women already “acknowledge the limitations of mammograms and the need to consider one’s health status and preferences when making decisions on how and when to stop routine mammograms,” said the article’s first author, Rachel A. Freedman, MD, MPH, of the Dana-Farber Cancer Institute, Boston.

However, “we don’t have this kind of consensus for women with a history of breast cancer,” she continued. “Current follow-up care guidelines simply state that women with a history of breast cancer with intact breasts should have annual mammography without any guidance.

“In practice, the use of mammograms is highly variable, with less than 50% of breast cancer survivors who have limited life expectancy having annual mammograms, according to survey data we have from prior work,” Dr. Freedman said in an interview.

The guidelines were published online Jan. 28 in JAMA Oncology.
 

Clinicians discuss how to have these discussions

As part of the process of developing these expert consensus guidelines, the researchers held several clinical focus groups that involved primary care physicians from Brigham and Women’s Hospital and oncology clinicians (including breast surgeons and medical oncologists) from the Dana-Farber Cancer Institute.

All clinicians felt that having expert guidelines and talking points to guide discussions would be helpful, the researchers report.

“However, some oncology clinicians felt that 75 years is often ‘too young’ to stop surveillance mammography and that 80 years may be a more comfortable age to stop routine testing,” they write. “Most clinicians felt that estimations of life expectancy, more than age, should inform the timing of this discussion.”

In contrast to primary and geriatric care clinicians, oncology clinicians reported discomfort with such discussions. They appreciated having the information but “felt it was easier to communicate findings indirectly, without specifically revealing life expectancy to patients. One oncology clinician, however, felt it would be ‘sneaky’ to calculate life expectancy without communicating this to patients, supporting more open discussions,” the authors report.

“All clinicians acknowledged that framing the conversation around patients’ low risk for in-breast cancer events and how mammography will not benefit them was more appealing than discussing life expectancy,” the researchers continue. Their literature review found that the risk of these individuals developing second breast cancers was similar to that of a healthy woman developing a first breast cancer, leading one clinician to comment: “If their risk is really equivalent to the general population – that is very powerful.”

“Some clinicians reported that they ‘focus on the risks’ or frame such discussions by asking: ‘If you were to find something on [a] mammogram, would you do anything about it?’ If a patient answered no, clinicians felt this was a signal to stop mammography,” they noted.
 

Literature review finds very low risk

Dr. Freedman and colleagues conducted a literature review of the risk for ipsilateral and contralateral breast cancer events among survivors and of the harms and benefits associated with mammography. Following the literature review, a multidisciplinary expert panel, which included patients and patient advocates, was convened to develop consensus guidelines.

The literature review confirmed that there was a low risk for in-breast cancer events in this population and that the risk was particularly low among patients who undergo treatment with endocrine therapy. Among those who did not receive systemic therapy for ERBB2-positive or triple-negative cancers, the rates of ipsilateral recurrence were estimated to be higher.

On the basis of the literature review, the estimated 10-year risk for in-breast cancer events ranged from 1% to 15% for ipsilateral breast cancers and from 1% to 5% for contralateral cancers. Among women in the same age group who did not have a history of breast cancer, the 5-year risk of developing the disease (average risk) was 2.2%.

The authors note that these findings mirror their estimates for new breast cancers among survivors who had low-risk disease. The findings are also similar to those cited in a large-scale mammography study, in which breast cancer survivors aged 70-80 years had a 1.1% annual risk for in-breast cancers. The risk was 0.7%-0.9% for similarly aged patients who did not have a history of breast cancer.

The benefits associated with mammography for older women are not well defined, but the literature suggests that mammography offers little to modest clinical benefit for patients in this age group. The limited benefits are likely because of the more than 10-year time lag that is needed to detect the small improvements in breast cancer mortality; slow-growing tumors generally do not affect the life expectancy of older women, they point out.

“Through our expert consensus process and after iterative feedback from clinicians, we created guidelines to support patients and clinicians in making individualized decisions on how and when to stop mammography,” said Dr. Freedman. “These guidelines are based on the risk of a breast cancer returning in the breast, one’s underlying health, and one’s preferences.”

The guidelines are also intended to provide information to patients on the benefits and harms of mammography in this setting, in addition to “how much we anticipate a mammogram may or may not continue to help a woman over time,” she said.

A companion guide for patients on these guidelines will be published in the coming months.

Dr. Freedman has received institutional clinical trial funding from Eisai and Puma Biotechnology outside the submitted work.

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

First-line trifluridine/tipiracil plus bevacizumab (TT-B) offered a slight survival benefit over capecitabine plus bevacizumab (C-B) in patients with unresectable metastatic colorectal cancer in the final analysis of the TASCO1 trial.

The median progression-free survival (PFS) in the phase 2 trial showed a difference of 1.41 months favoring TT-B over C-B, but this difference was not statistically significant.

The median overall survival was 4.64 months longer with TT-B than with C-B. However, the final analysis of TASCO1 was not designed to be comparative for overall survival, “so no formal statistical analysis is presented, and survival is a secondary endpoint,” noted investigator Eric Van Cutsem, MD, PhD, of University Hospital Gasthuisberg in Leuven, Belgium.

Dr. Van Cutsem presented the final results of TASCO1 at the 2021 Gastrointestinal Cancers Symposium (abstract 14).

Prior results from the trial were reported last year (Ann Oncol. 2020 Sep;31[9]:1160-68).
 

About trifluridine/tipiracil

Trifluridine/tipiracil is an oral drug combining the thymidine analogue trifluridine with tipiracil, an inhibitor of trifluridine degradation. The drug was approved by the Food and Drug Administration in 2015 under the trade name Lonsurf for the treatment of refractory metastatic colorectal cancer, and in 2019 for patients with metastatic gastric cancer or gastroesophageal junction cancer that had been treated with at least two lines of chemotherapy.

Trifluridine/tipiracil was associated with a brief but statistically significant survival benefit when compared with placebo in patients with heavily pretreated metastatic gastric cancer in the TAS-102 Gastric Study (Lancet Oncol. 2018 Nov;19[11]:1437-48).

In a separate analysis of the study, trifluridine/tipiracil was associated with significantly better overall survival and PFS than placebo in patients who had undergone gastrectomy (JAMA Oncol. 2019 Oct 10;6[1]:e193531).
 

TASCO1 details

In TASCO1, investigators enrolled patients with colorectal cancer who had never received systemic therapy for unresectable metastatic disease, and who were judged to be ineligible for intensive therapy due to advanced age, low tumor burden, poor performance status, comorbidities, or other clinical reasons.

After stratification by RAS status, performance status, and region, patients were randomly assigned to receive TT-B (n = 77) or C-B (n = 76).

TT-B consisted of oral trifluridine/tipiracil at 35 mg/m² twice daily on days 1-5 and 8-12 every 4 weeks plus bevacizumab at 5 mg/kg intravenously on days 1 and 15 every 4 weeks.

C-B consisted of oral capecitabine at 1,250 or 1,000 mg/m² twice a day on days 1-14 every 3 weeks plus bevacizumab at 7.5 mg/kg IV on day 1 every 3 weeks.
 

Final results

The median PFS, the primary endpoint, was 9.23 months with TT-B and 7.82 months with C-B. The difference was not statistically significant, with the upper limit of the 95% confidence interval crossing 1.

The median overall survival was 22.31 months with TT-B and 17.67 months with C-B (hazard ratio, 0.78; 95% CI, 0.55-1.10).

Dr. Van Cutsem pointed out that more patients in the TT-B arm had subsequent therapies compared with patients in the C-B arm – 59.7% vs. 40.8%.

He also noted that the safety profile of TT-B “remains unchanged from the initial analysis.”

Grade 3 or greater neutropenia, decreased neutrophil count, anemia, and decreased white blood cell count were all higher among patients on TT-B, but grade 3 or greater febrile neutropenia was similar between the groups.

Patients in the TT-B arm had more frequent grade 3 or greater nausea, vomiting, and hypertension. Grade 3 or higher hand-foot syndrome and diarrhea were both more common with C-B.

At the study cutoff date in September 2020, 66 patients in each arm had died.

Dr. Van Cutsem said more data on the efficacy of TT-B vs. C-B will come from the ongoing phase 3 SOLSTICE trial. Results from this trial are expected in late 2022.
 

‘The jury is still out’

The final results from TASCO1 suggest there may be some benefit from TT-B in patients with treatment-naive metastatic colorectal cancer, “but we don’t use it in the first line,” said Jeffery Clark, MD, an oncologist who was not involved in the study.

The trial supports the benefit of combining trifluridine/tipiracil with bevacizumab, and the results were “somewhat better” than he had expected, said Dr. Clark, director of clinical trials support at Mass General Cancer Center in Boston.

“Even though the results are encouraging, there were a couple of things about the trial that one has to at least think about,” Dr. Clark said in an interview.

He noted, for example, that a higher proportion of patients assigned to TT-B had prior adjuvant therapy (27.3% vs. 19.7%), and patients in the TT-B arm were also more likely to have second lines of systemic therapy, which could have skewed the results in favor of the experimental arm.

“I think, basically, the jury is still out until we see the results of the SOLSTICE trial,” he said.

The TASCO1 study was funded by Servier and Taiho. Dr. Van Cutsem has received research funding and served on an advisory board for Servier and other companies. Dr. Clark reported no relevant disclosures.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

First-line trifluridine/tipiracil plus bevacizumab (TT-B) offered a slight survival benefit over capecitabine plus bevacizumab (C-B) in patients with unresectable metastatic colorectal cancer in the final analysis of the TASCO1 trial.

The median progression-free survival (PFS) in the phase 2 trial showed a difference of 1.41 months favoring TT-B over C-B, but this difference was not statistically significant.

The median overall survival was 4.64 months longer with TT-B than with C-B. However, the final analysis of TASCO1 was not designed to be comparative for overall survival, “so no formal statistical analysis is presented, and survival is a secondary endpoint,” noted investigator Eric Van Cutsem, MD, PhD, of University Hospital Gasthuisberg in Leuven, Belgium.

Dr. Van Cutsem presented the final results of TASCO1 at the 2021 Gastrointestinal Cancers Symposium (abstract 14).

Prior results from the trial were reported last year (Ann Oncol. 2020 Sep;31[9]:1160-68).
 

About trifluridine/tipiracil

Trifluridine/tipiracil is an oral drug combining the thymidine analogue trifluridine with tipiracil, an inhibitor of trifluridine degradation. The drug was approved by the Food and Drug Administration in 2015 under the trade name Lonsurf for the treatment of refractory metastatic colorectal cancer, and in 2019 for patients with metastatic gastric cancer or gastroesophageal junction cancer that had been treated with at least two lines of chemotherapy.

Trifluridine/tipiracil was associated with a brief but statistically significant survival benefit when compared with placebo in patients with heavily pretreated metastatic gastric cancer in the TAS-102 Gastric Study (Lancet Oncol. 2018 Nov;19[11]:1437-48).

In a separate analysis of the study, trifluridine/tipiracil was associated with significantly better overall survival and PFS than placebo in patients who had undergone gastrectomy (JAMA Oncol. 2019 Oct 10;6[1]:e193531).
 

TASCO1 details

In TASCO1, investigators enrolled patients with colorectal cancer who had never received systemic therapy for unresectable metastatic disease, and who were judged to be ineligible for intensive therapy due to advanced age, low tumor burden, poor performance status, comorbidities, or other clinical reasons.

After stratification by RAS status, performance status, and region, patients were randomly assigned to receive TT-B (n = 77) or C-B (n = 76).

TT-B consisted of oral trifluridine/tipiracil at 35 mg/m² twice daily on days 1-5 and 8-12 every 4 weeks plus bevacizumab at 5 mg/kg intravenously on days 1 and 15 every 4 weeks.

C-B consisted of oral capecitabine at 1,250 or 1,000 mg/m² twice a day on days 1-14 every 3 weeks plus bevacizumab at 7.5 mg/kg IV on day 1 every 3 weeks.
 

Final results

The median PFS, the primary endpoint, was 9.23 months with TT-B and 7.82 months with C-B. The difference was not statistically significant, with the upper limit of the 95% confidence interval crossing 1.

The median overall survival was 22.31 months with TT-B and 17.67 months with C-B (hazard ratio, 0.78; 95% CI, 0.55-1.10).

Dr. Van Cutsem pointed out that more patients in the TT-B arm had subsequent therapies compared with patients in the C-B arm – 59.7% vs. 40.8%.

He also noted that the safety profile of TT-B “remains unchanged from the initial analysis.”

Grade 3 or greater neutropenia, decreased neutrophil count, anemia, and decreased white blood cell count were all higher among patients on TT-B, but grade 3 or greater febrile neutropenia was similar between the groups.

Patients in the TT-B arm had more frequent grade 3 or greater nausea, vomiting, and hypertension. Grade 3 or higher hand-foot syndrome and diarrhea were both more common with C-B.

At the study cutoff date in September 2020, 66 patients in each arm had died.

Dr. Van Cutsem said more data on the efficacy of TT-B vs. C-B will come from the ongoing phase 3 SOLSTICE trial. Results from this trial are expected in late 2022.
 

‘The jury is still out’

The final results from TASCO1 suggest there may be some benefit from TT-B in patients with treatment-naive metastatic colorectal cancer, “but we don’t use it in the first line,” said Jeffery Clark, MD, an oncologist who was not involved in the study.

The trial supports the benefit of combining trifluridine/tipiracil with bevacizumab, and the results were “somewhat better” than he had expected, said Dr. Clark, director of clinical trials support at Mass General Cancer Center in Boston.

“Even though the results are encouraging, there were a couple of things about the trial that one has to at least think about,” Dr. Clark said in an interview.

He noted, for example, that a higher proportion of patients assigned to TT-B had prior adjuvant therapy (27.3% vs. 19.7%), and patients in the TT-B arm were also more likely to have second lines of systemic therapy, which could have skewed the results in favor of the experimental arm.

“I think, basically, the jury is still out until we see the results of the SOLSTICE trial,” he said.

The TASCO1 study was funded by Servier and Taiho. Dr. Van Cutsem has received research funding and served on an advisory board for Servier and other companies. Dr. Clark reported no relevant disclosures.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

First-line trifluridine/tipiracil plus bevacizumab (TT-B) offered a slight survival benefit over capecitabine plus bevacizumab (C-B) in patients with unresectable metastatic colorectal cancer in the final analysis of the TASCO1 trial.

The median progression-free survival (PFS) in the phase 2 trial showed a difference of 1.41 months favoring TT-B over C-B, but this difference was not statistically significant.

The median overall survival was 4.64 months longer with TT-B than with C-B. However, the final analysis of TASCO1 was not designed to be comparative for overall survival, “so no formal statistical analysis is presented, and survival is a secondary endpoint,” noted investigator Eric Van Cutsem, MD, PhD, of University Hospital Gasthuisberg in Leuven, Belgium.

Dr. Van Cutsem presented the final results of TASCO1 at the 2021 Gastrointestinal Cancers Symposium (abstract 14).

Prior results from the trial were reported last year (Ann Oncol. 2020 Sep;31[9]:1160-68).
 

About trifluridine/tipiracil

Trifluridine/tipiracil is an oral drug combining the thymidine analogue trifluridine with tipiracil, an inhibitor of trifluridine degradation. The drug was approved by the Food and Drug Administration in 2015 under the trade name Lonsurf for the treatment of refractory metastatic colorectal cancer, and in 2019 for patients with metastatic gastric cancer or gastroesophageal junction cancer that had been treated with at least two lines of chemotherapy.

Trifluridine/tipiracil was associated with a brief but statistically significant survival benefit when compared with placebo in patients with heavily pretreated metastatic gastric cancer in the TAS-102 Gastric Study (Lancet Oncol. 2018 Nov;19[11]:1437-48).

In a separate analysis of the study, trifluridine/tipiracil was associated with significantly better overall survival and PFS than placebo in patients who had undergone gastrectomy (JAMA Oncol. 2019 Oct 10;6[1]:e193531).
 

TASCO1 details

In TASCO1, investigators enrolled patients with colorectal cancer who had never received systemic therapy for unresectable metastatic disease, and who were judged to be ineligible for intensive therapy due to advanced age, low tumor burden, poor performance status, comorbidities, or other clinical reasons.

After stratification by RAS status, performance status, and region, patients were randomly assigned to receive TT-B (n = 77) or C-B (n = 76).

TT-B consisted of oral trifluridine/tipiracil at 35 mg/m² twice daily on days 1-5 and 8-12 every 4 weeks plus bevacizumab at 5 mg/kg intravenously on days 1 and 15 every 4 weeks.

C-B consisted of oral capecitabine at 1,250 or 1,000 mg/m² twice a day on days 1-14 every 3 weeks plus bevacizumab at 7.5 mg/kg IV on day 1 every 3 weeks.
 

Final results

The median PFS, the primary endpoint, was 9.23 months with TT-B and 7.82 months with C-B. The difference was not statistically significant, with the upper limit of the 95% confidence interval crossing 1.

The median overall survival was 22.31 months with TT-B and 17.67 months with C-B (hazard ratio, 0.78; 95% CI, 0.55-1.10).

Dr. Van Cutsem pointed out that more patients in the TT-B arm had subsequent therapies compared with patients in the C-B arm – 59.7% vs. 40.8%.

He also noted that the safety profile of TT-B “remains unchanged from the initial analysis.”

Grade 3 or greater neutropenia, decreased neutrophil count, anemia, and decreased white blood cell count were all higher among patients on TT-B, but grade 3 or greater febrile neutropenia was similar between the groups.

Patients in the TT-B arm had more frequent grade 3 or greater nausea, vomiting, and hypertension. Grade 3 or higher hand-foot syndrome and diarrhea were both more common with C-B.

At the study cutoff date in September 2020, 66 patients in each arm had died.

Dr. Van Cutsem said more data on the efficacy of TT-B vs. C-B will come from the ongoing phase 3 SOLSTICE trial. Results from this trial are expected in late 2022.
 

‘The jury is still out’

The final results from TASCO1 suggest there may be some benefit from TT-B in patients with treatment-naive metastatic colorectal cancer, “but we don’t use it in the first line,” said Jeffery Clark, MD, an oncologist who was not involved in the study.

The trial supports the benefit of combining trifluridine/tipiracil with bevacizumab, and the results were “somewhat better” than he had expected, said Dr. Clark, director of clinical trials support at Mass General Cancer Center in Boston.

“Even though the results are encouraging, there were a couple of things about the trial that one has to at least think about,” Dr. Clark said in an interview.

He noted, for example, that a higher proportion of patients assigned to TT-B had prior adjuvant therapy (27.3% vs. 19.7%), and patients in the TT-B arm were also more likely to have second lines of systemic therapy, which could have skewed the results in favor of the experimental arm.

“I think, basically, the jury is still out until we see the results of the SOLSTICE trial,” he said.

The TASCO1 study was funded by Servier and Taiho. Dr. Van Cutsem has received research funding and served on an advisory board for Servier and other companies. Dr. Clark reported no relevant disclosures.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

Offering a combination of colonoscopy and fecal immunochemical testing (FIT), either in sequence or by choice, may significantly increase participation in colorectal cancer (CRC) screening, according to a prospective study involving more than 12,000 individuals in Poland.

Still, greater participation did not lead to significantly higher rates of advanced disease detection, reported lead author Nastazja Dagny Pilonis, MD, of the Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, and colleagues in Gastroenterology.

According to the investigators, screening programs that offer colonoscopy and FIT are more effective than those that offer colonoscopy alone, but an optimal combination protocol has yet to be established, and some parts of the world still rely upon a single diagnostic method.

“In Europe, CRC screening programs often implement only one screening modality: colonoscopy, sigmoidoscopy, or stool testing, depending on the health care provider,” the investigators wrote in Gastroenterology. They noted, however, that national guidelines in the United States recommend strategies that include more than one screening method. “‘One-size-fits-all’ approaches to CRC screening do not result in satisfactory participation” because of behavioral, cultural, and socioeconomic variation among individuals.

To improve understanding of the best ways to improve participation, the investigators conducted a prospective randomized trial, PICCOLINO, via the Polish Colonoscopy Screening Program. In total, 12,485 eligible individuals aged between 55 and 64 years received postal invitations to participate in CRC screening. Individuals were randomized in a 1:1:1 ratio into one of three mailing protocols, each of which involved an initial invitation, and, if needed, a second invitation that offered the following:

• Control group: colonoscopy, with nonresponders receiving the same invitation again
• Sequential group: colonoscopy, with nonresponders or refusers receiving a second invitation that offered FIT
• Choice group: choice between colonoscopy or FIT, with nonresponders receiving the same invitation again

The primary outcome was participation in screening within 18 weeks of enrollment. The secondary outcome was diagnostic yield for either advanced adenoma or CRC.

Out of the three groups, the control group had the lowest participation rate, at 17.5%, compared with 25.8% for the sequential group and 26.5% for the choice group. Multivariable logistic regression showed that individuals in the sequential and choice groups had 64% and 70% higher rates of participation, respectively. Across all groups, age of 60 years or older predicted 12% higher likelihood of participation; in contrast, location more than 40 kilometers from a testing center was associated with an 18% decrease in participation, compared with individuals who lived less than 20 kilometers away.

While the control and sequential groups had similar rates of colonoscopy participation, at 17.5% and 15.9%, respectively (P = .788), this rate was significantly lower, at 8.5%, in the choice group (P = .001). Conversely, the sequential group had a significantly lower rate of FITs than the choice group, at 9.9% versus 17.9%, respectively (P = .001). Among participants with a positive FIT, diagnostic work-up colonoscopies were performed in 70.0% of those in the sequential group and 73.3% in the choice group, “despite active call-recall efforts.”

Across all invited individuals, advanced disease detection rates were similar across groups, at 1.1% for both the control and the sequential group and 1.2% for the choice group. Among those who were actually screened, the control group had a slightly higher diagnostic yield for advanced neoplasia, at 6.5%, compared with 4.2% in the sequential group and 4.4% in the choice group; however, these differences were not statistically significant. In contrast, significantly more adenomas of any kind were detected in the control and sequential groups (5.6% for both) than the choice group (3.9%) (P < .001).

“Although the strategies which included FIT showed higher participation rates than the strategy of offering colonoscopy alone, these strategies did not result in increased detection rates of advanced neoplasia in the intention to screen analysis,” the investigators wrote. “An absolute increase in participation rates of 8%-10% seems insufficient to translate into higher advanced neoplasia detection at the population level.”

Dr. Pilonis and colleagues also suggested that the relatively low rate of diagnostic colonoscopy after positive FIT contributed to the suboptimal diagnostic yield.

“These rates are unsatisfactory taking into account significant call-recall efforts, but are within the range reported in other studies,” they wrote.

They also wrote that their study compared participation and detection between one-time colonoscopy and one-time screening strategies combining colonoscopy and FIT. In acknowledging this, they noted that these approaches have different screening intervals and uptake over time: “FIT has been shown to achieve higher participation rates than colonoscopy for one time screening, but its uptake over several rounds may not be superior to one time colonoscopy.” Furthermore, detection rates of the sequential or choice strategies for advanced disease may rise over time with further implementation, so the one-time screening may not be sufficient to reveal what could become significant differences.

The study was funded by the Polish Ministry of Health, the Polish Foundation of Gastroenterology, and the Centre of Postgraduate Medical Education in Warsaw. FITs, materials, and reagents were provided by Eiken Chemical. The investigators disclosed relationships with Boston Scientific, AbbVie, Olympus, and others.

Offering a combination of colonoscopy and fecal immunochemical testing (FIT), either in sequence or by choice, may significantly increase participation in colorectal cancer (CRC) screening, according to a prospective study involving more than 12,000 individuals in Poland.

Still, greater participation did not lead to significantly higher rates of advanced disease detection, reported lead author Nastazja Dagny Pilonis, MD, of the Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, and colleagues in Gastroenterology.

According to the investigators, screening programs that offer colonoscopy and FIT are more effective than those that offer colonoscopy alone, but an optimal combination protocol has yet to be established, and some parts of the world still rely upon a single diagnostic method.

“In Europe, CRC screening programs often implement only one screening modality: colonoscopy, sigmoidoscopy, or stool testing, depending on the health care provider,” the investigators wrote in Gastroenterology. They noted, however, that national guidelines in the United States recommend strategies that include more than one screening method. “‘One-size-fits-all’ approaches to CRC screening do not result in satisfactory participation” because of behavioral, cultural, and socioeconomic variation among individuals.

To improve understanding of the best ways to improve participation, the investigators conducted a prospective randomized trial, PICCOLINO, via the Polish Colonoscopy Screening Program. In total, 12,485 eligible individuals aged between 55 and 64 years received postal invitations to participate in CRC screening. Individuals were randomized in a 1:1:1 ratio into one of three mailing protocols, each of which involved an initial invitation, and, if needed, a second invitation that offered the following:

• Control group: colonoscopy, with nonresponders receiving the same invitation again
• Sequential group: colonoscopy, with nonresponders or refusers receiving a second invitation that offered FIT
• Choice group: choice between colonoscopy or FIT, with nonresponders receiving the same invitation again

The primary outcome was participation in screening within 18 weeks of enrollment. The secondary outcome was diagnostic yield for either advanced adenoma or CRC.

Out of the three groups, the control group had the lowest participation rate, at 17.5%, compared with 25.8% for the sequential group and 26.5% for the choice group. Multivariable logistic regression showed that individuals in the sequential and choice groups had 64% and 70% higher rates of participation, respectively. Across all groups, age of 60 years or older predicted 12% higher likelihood of participation; in contrast, location more than 40 kilometers from a testing center was associated with an 18% decrease in participation, compared with individuals who lived less than 20 kilometers away.

While the control and sequential groups had similar rates of colonoscopy participation, at 17.5% and 15.9%, respectively (P = .788), this rate was significantly lower, at 8.5%, in the choice group (P = .001). Conversely, the sequential group had a significantly lower rate of FITs than the choice group, at 9.9% versus 17.9%, respectively (P = .001). Among participants with a positive FIT, diagnostic work-up colonoscopies were performed in 70.0% of those in the sequential group and 73.3% in the choice group, “despite active call-recall efforts.”

Across all invited individuals, advanced disease detection rates were similar across groups, at 1.1% for both the control and the sequential group and 1.2% for the choice group. Among those who were actually screened, the control group had a slightly higher diagnostic yield for advanced neoplasia, at 6.5%, compared with 4.2% in the sequential group and 4.4% in the choice group; however, these differences were not statistically significant. In contrast, significantly more adenomas of any kind were detected in the control and sequential groups (5.6% for both) than the choice group (3.9%) (P < .001).

“Although the strategies which included FIT showed higher participation rates than the strategy of offering colonoscopy alone, these strategies did not result in increased detection rates of advanced neoplasia in the intention to screen analysis,” the investigators wrote. “An absolute increase in participation rates of 8%-10% seems insufficient to translate into higher advanced neoplasia detection at the population level.”

Dr. Pilonis and colleagues also suggested that the relatively low rate of diagnostic colonoscopy after positive FIT contributed to the suboptimal diagnostic yield.

“These rates are unsatisfactory taking into account significant call-recall efforts, but are within the range reported in other studies,” they wrote.

They also wrote that their study compared participation and detection between one-time colonoscopy and one-time screening strategies combining colonoscopy and FIT. In acknowledging this, they noted that these approaches have different screening intervals and uptake over time: “FIT has been shown to achieve higher participation rates than colonoscopy for one time screening, but its uptake over several rounds may not be superior to one time colonoscopy.” Furthermore, detection rates of the sequential or choice strategies for advanced disease may rise over time with further implementation, so the one-time screening may not be sufficient to reveal what could become significant differences.

The study was funded by the Polish Ministry of Health, the Polish Foundation of Gastroenterology, and the Centre of Postgraduate Medical Education in Warsaw. FITs, materials, and reagents were provided by Eiken Chemical. The investigators disclosed relationships with Boston Scientific, AbbVie, Olympus, and others.

Offering a combination of colonoscopy and fecal immunochemical testing (FIT), either in sequence or by choice, may significantly increase participation in colorectal cancer (CRC) screening, according to a prospective study involving more than 12,000 individuals in Poland.

Still, greater participation did not lead to significantly higher rates of advanced disease detection, reported lead author Nastazja Dagny Pilonis, MD, of the Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, and colleagues in Gastroenterology.

According to the investigators, screening programs that offer colonoscopy and FIT are more effective than those that offer colonoscopy alone, but an optimal combination protocol has yet to be established, and some parts of the world still rely upon a single diagnostic method.

“In Europe, CRC screening programs often implement only one screening modality: colonoscopy, sigmoidoscopy, or stool testing, depending on the health care provider,” the investigators wrote in Gastroenterology. They noted, however, that national guidelines in the United States recommend strategies that include more than one screening method. “‘One-size-fits-all’ approaches to CRC screening do not result in satisfactory participation” because of behavioral, cultural, and socioeconomic variation among individuals.

To improve understanding of the best ways to improve participation, the investigators conducted a prospective randomized trial, PICCOLINO, via the Polish Colonoscopy Screening Program. In total, 12,485 eligible individuals aged between 55 and 64 years received postal invitations to participate in CRC screening. Individuals were randomized in a 1:1:1 ratio into one of three mailing protocols, each of which involved an initial invitation, and, if needed, a second invitation that offered the following:

• Control group: colonoscopy, with nonresponders receiving the same invitation again
• Sequential group: colonoscopy, with nonresponders or refusers receiving a second invitation that offered FIT
• Choice group: choice between colonoscopy or FIT, with nonresponders receiving the same invitation again

The primary outcome was participation in screening within 18 weeks of enrollment. The secondary outcome was diagnostic yield for either advanced adenoma or CRC.

Out of the three groups, the control group had the lowest participation rate, at 17.5%, compared with 25.8% for the sequential group and 26.5% for the choice group. Multivariable logistic regression showed that individuals in the sequential and choice groups had 64% and 70% higher rates of participation, respectively. Across all groups, age of 60 years or older predicted 12% higher likelihood of participation; in contrast, location more than 40 kilometers from a testing center was associated with an 18% decrease in participation, compared with individuals who lived less than 20 kilometers away.

While the control and sequential groups had similar rates of colonoscopy participation, at 17.5% and 15.9%, respectively (P = .788), this rate was significantly lower, at 8.5%, in the choice group (P = .001). Conversely, the sequential group had a significantly lower rate of FITs than the choice group, at 9.9% versus 17.9%, respectively (P = .001). Among participants with a positive FIT, diagnostic work-up colonoscopies were performed in 70.0% of those in the sequential group and 73.3% in the choice group, “despite active call-recall efforts.”

Across all invited individuals, advanced disease detection rates were similar across groups, at 1.1% for both the control and the sequential group and 1.2% for the choice group. Among those who were actually screened, the control group had a slightly higher diagnostic yield for advanced neoplasia, at 6.5%, compared with 4.2% in the sequential group and 4.4% in the choice group; however, these differences were not statistically significant. In contrast, significantly more adenomas of any kind were detected in the control and sequential groups (5.6% for both) than the choice group (3.9%) (P < .001).

“Although the strategies which included FIT showed higher participation rates than the strategy of offering colonoscopy alone, these strategies did not result in increased detection rates of advanced neoplasia in the intention to screen analysis,” the investigators wrote. “An absolute increase in participation rates of 8%-10% seems insufficient to translate into higher advanced neoplasia detection at the population level.”

Dr. Pilonis and colleagues also suggested that the relatively low rate of diagnostic colonoscopy after positive FIT contributed to the suboptimal diagnostic yield.

“These rates are unsatisfactory taking into account significant call-recall efforts, but are within the range reported in other studies,” they wrote.

They also wrote that their study compared participation and detection between one-time colonoscopy and one-time screening strategies combining colonoscopy and FIT. In acknowledging this, they noted that these approaches have different screening intervals and uptake over time: “FIT has been shown to achieve higher participation rates than colonoscopy for one time screening, but its uptake over several rounds may not be superior to one time colonoscopy.” Furthermore, detection rates of the sequential or choice strategies for advanced disease may rise over time with further implementation, so the one-time screening may not be sufficient to reveal what could become significant differences.

The study was funded by the Polish Ministry of Health, the Polish Foundation of Gastroenterology, and the Centre of Postgraduate Medical Education in Warsaw. FITs, materials, and reagents were provided by Eiken Chemical. The investigators disclosed relationships with Boston Scientific, AbbVie, Olympus, and others.

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

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

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

Rationale

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

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

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

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

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

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

Results

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

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

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

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

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

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

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

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

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

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

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

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

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

Rationale

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

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

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

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

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

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

Results

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

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

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

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

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

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

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

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

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

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

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

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

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

Rationale

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

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

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

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

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

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

Results

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

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

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

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

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

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

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

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

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

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

Federal Practitioner is inviting VA, DoD, and PHS health care providers and researchers to contribute to a future special issue on hematology topics, including myelomas, lymphomas, leukemias, and other bloodborne dieases.

Interested authors should submit a brief 2 to 3 sentence abstract to [email protected]. Federal Practitioner welcomes case studies, literature reviews, original research, program profiles, guest editorials, and other evidence-based articles. The updated and complete submission guidelines, including details about the style and format, can be found here:

http://www.mdedge.com/fedprac/page/submission-guidelines

Federal Practitioner uses Editorial Manager , a web-based manuscript submission and review system. All manuscripts must be submitted through this system.

All manuscripts submitted to Federal Practitioner for both special and regular issues will be subject to peer review. Peer reviews are conducted in a double-blind fashion, and the reviewers are asked to comment on the manuscript’s importance, accuracy, relevance, clarity, timeliness, balance, and reference citation. Final decisions on all submitted manuscripts are made by the Editor-in-Chief (or, in the event of a potential conflict of interest, a designated surrogate from the journal’s Editorial Advisory Association).

Federal Practitioner is inviting VA, DoD, and PHS health care providers and researchers to contribute to a future special issue on hematology topics, including myelomas, lymphomas, leukemias, and other bloodborne dieases.

Interested authors should submit a brief 2 to 3 sentence abstract to [email protected]. Federal Practitioner welcomes case studies, literature reviews, original research, program profiles, guest editorials, and other evidence-based articles. The updated and complete submission guidelines, including details about the style and format, can be found here:

http://www.mdedge.com/fedprac/page/submission-guidelines

Federal Practitioner uses Editorial Manager , a web-based manuscript submission and review system. All manuscripts must be submitted through this system.

All manuscripts submitted to Federal Practitioner for both special and regular issues will be subject to peer review. Peer reviews are conducted in a double-blind fashion, and the reviewers are asked to comment on the manuscript’s importance, accuracy, relevance, clarity, timeliness, balance, and reference citation. Final decisions on all submitted manuscripts are made by the Editor-in-Chief (or, in the event of a potential conflict of interest, a designated surrogate from the journal’s Editorial Advisory Association).

Federal Practitioner is inviting VA, DoD, and PHS health care providers and researchers to contribute to a future special issue on hematology topics, including myelomas, lymphomas, leukemias, and other bloodborne dieases.

Interested authors should submit a brief 2 to 3 sentence abstract to [email protected]. Federal Practitioner welcomes case studies, literature reviews, original research, program profiles, guest editorials, and other evidence-based articles. The updated and complete submission guidelines, including details about the style and format, can be found here:

http://www.mdedge.com/fedprac/page/submission-guidelines

Federal Practitioner uses Editorial Manager , a web-based manuscript submission and review system. All manuscripts must be submitted through this system.

All manuscripts submitted to Federal Practitioner for both special and regular issues will be subject to peer review. Peer reviews are conducted in a double-blind fashion, and the reviewers are asked to comment on the manuscript’s importance, accuracy, relevance, clarity, timeliness, balance, and reference citation. Final decisions on all submitted manuscripts are made by the Editor-in-Chief (or, in the event of a potential conflict of interest, a designated surrogate from the journal’s Editorial Advisory Association).