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Survival the same for younger and older patients with metastatic CRC
, according to a large phase 3 randomized trial.
“Colorectal cancer is on track to be the leading cause of cancer death in patients 20 to 49 by the year 2040, so it is important to understand survival in this population,” lead author Marla Lipsyc-Sharf, MD, Young-Onset Colorectal Cancer Center, Dana-Farber Cancer Center, Boston, said in an interview. “The most important point for oncologists to take away from our study is that the survival of young-onset colorectal cancer does not seem to be different from that in older patients.”
Previous studies comparing survival in younger versus older patients with metastatic CRC have yielded conflicting results. Dr. Lipsyc-Sharf and colleagues set out to clarify the literature in their large randomized study, published online on Oct. 12 in the Journal of the National Cancer Institute.
Dr. Lipsyc-Sharf and colleagues enrolled 2,326 eligible patients in the Cancer and Leukemia Group B (CALGB)/SWOG 80405 (Alliance) trial to evaluate the efficacy of chemotherapy plus a biologic to treat metastatic CRC. Slightly over 22% of participants (514 patients) were under age 50 at study enrollment, with a median age of 44.3 years vs. 62.5 in those patients older than 50.
The primary outcome was OS and secondary outcomes included PFS, defined as time from study entry until disease progression or death from any cause. At a follow-up of 6 years, median OS was 27.07 months in the young CRC cohort compared with 26.12 months in the older CRC cohort.
Similarly, median PFS in both younger and older cohorts was virtually identical at 10.87 months versus 10.55 months, respectively. Patients younger than age 35 did have a shorter median OS of 21.95 months and PFS of 9.33 months compared with 26.12 months and 10.55 months, respectively, for those 50 and older, but neither difference was significant.
The similar OS between the younger and older patients with metastatic CRC is “particularly interesting,” the authors noted, given that younger patients should, in theory, have done better than their older peers. Younger patients tend to have better overall health (less diabetes, greater physical activity), have more left-sided CRC, (which is associated with a better prognosis), and receive more intensive therapy.
“It’s not clear at this time why the young-onset CRC patients – despite having these more favorable characteristics – did not have improved survival compared to older patients,” Dr. Lipsyc-Sharf said.
The authors suggest that this similar survival may be because younger patients tend to be diagnosed at more advanced stages, due to differences in underlying tumor biology, or due to other unknown factors. However, “additional investigation into the tumor biology, clinical characteristics, and optimal treatment of patients with [early onset] CRC is essential,” the authors concluded.
The work was supported by the National Cancer Institute of the National Institutes of Health and, in part, by Bristol Myers Squibb, Genentech, Pfizer, and Sanofi. Dr. Lipsyc-Sharf has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, according to a large phase 3 randomized trial.
“Colorectal cancer is on track to be the leading cause of cancer death in patients 20 to 49 by the year 2040, so it is important to understand survival in this population,” lead author Marla Lipsyc-Sharf, MD, Young-Onset Colorectal Cancer Center, Dana-Farber Cancer Center, Boston, said in an interview. “The most important point for oncologists to take away from our study is that the survival of young-onset colorectal cancer does not seem to be different from that in older patients.”
Previous studies comparing survival in younger versus older patients with metastatic CRC have yielded conflicting results. Dr. Lipsyc-Sharf and colleagues set out to clarify the literature in their large randomized study, published online on Oct. 12 in the Journal of the National Cancer Institute.
Dr. Lipsyc-Sharf and colleagues enrolled 2,326 eligible patients in the Cancer and Leukemia Group B (CALGB)/SWOG 80405 (Alliance) trial to evaluate the efficacy of chemotherapy plus a biologic to treat metastatic CRC. Slightly over 22% of participants (514 patients) were under age 50 at study enrollment, with a median age of 44.3 years vs. 62.5 in those patients older than 50.
The primary outcome was OS and secondary outcomes included PFS, defined as time from study entry until disease progression or death from any cause. At a follow-up of 6 years, median OS was 27.07 months in the young CRC cohort compared with 26.12 months in the older CRC cohort.
Similarly, median PFS in both younger and older cohorts was virtually identical at 10.87 months versus 10.55 months, respectively. Patients younger than age 35 did have a shorter median OS of 21.95 months and PFS of 9.33 months compared with 26.12 months and 10.55 months, respectively, for those 50 and older, but neither difference was significant.
The similar OS between the younger and older patients with metastatic CRC is “particularly interesting,” the authors noted, given that younger patients should, in theory, have done better than their older peers. Younger patients tend to have better overall health (less diabetes, greater physical activity), have more left-sided CRC, (which is associated with a better prognosis), and receive more intensive therapy.
“It’s not clear at this time why the young-onset CRC patients – despite having these more favorable characteristics – did not have improved survival compared to older patients,” Dr. Lipsyc-Sharf said.
The authors suggest that this similar survival may be because younger patients tend to be diagnosed at more advanced stages, due to differences in underlying tumor biology, or due to other unknown factors. However, “additional investigation into the tumor biology, clinical characteristics, and optimal treatment of patients with [early onset] CRC is essential,” the authors concluded.
The work was supported by the National Cancer Institute of the National Institutes of Health and, in part, by Bristol Myers Squibb, Genentech, Pfizer, and Sanofi. Dr. Lipsyc-Sharf has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, according to a large phase 3 randomized trial.
“Colorectal cancer is on track to be the leading cause of cancer death in patients 20 to 49 by the year 2040, so it is important to understand survival in this population,” lead author Marla Lipsyc-Sharf, MD, Young-Onset Colorectal Cancer Center, Dana-Farber Cancer Center, Boston, said in an interview. “The most important point for oncologists to take away from our study is that the survival of young-onset colorectal cancer does not seem to be different from that in older patients.”
Previous studies comparing survival in younger versus older patients with metastatic CRC have yielded conflicting results. Dr. Lipsyc-Sharf and colleagues set out to clarify the literature in their large randomized study, published online on Oct. 12 in the Journal of the National Cancer Institute.
Dr. Lipsyc-Sharf and colleagues enrolled 2,326 eligible patients in the Cancer and Leukemia Group B (CALGB)/SWOG 80405 (Alliance) trial to evaluate the efficacy of chemotherapy plus a biologic to treat metastatic CRC. Slightly over 22% of participants (514 patients) were under age 50 at study enrollment, with a median age of 44.3 years vs. 62.5 in those patients older than 50.
The primary outcome was OS and secondary outcomes included PFS, defined as time from study entry until disease progression or death from any cause. At a follow-up of 6 years, median OS was 27.07 months in the young CRC cohort compared with 26.12 months in the older CRC cohort.
Similarly, median PFS in both younger and older cohorts was virtually identical at 10.87 months versus 10.55 months, respectively. Patients younger than age 35 did have a shorter median OS of 21.95 months and PFS of 9.33 months compared with 26.12 months and 10.55 months, respectively, for those 50 and older, but neither difference was significant.
The similar OS between the younger and older patients with metastatic CRC is “particularly interesting,” the authors noted, given that younger patients should, in theory, have done better than their older peers. Younger patients tend to have better overall health (less diabetes, greater physical activity), have more left-sided CRC, (which is associated with a better prognosis), and receive more intensive therapy.
“It’s not clear at this time why the young-onset CRC patients – despite having these more favorable characteristics – did not have improved survival compared to older patients,” Dr. Lipsyc-Sharf said.
The authors suggest that this similar survival may be because younger patients tend to be diagnosed at more advanced stages, due to differences in underlying tumor biology, or due to other unknown factors. However, “additional investigation into the tumor biology, clinical characteristics, and optimal treatment of patients with [early onset] CRC is essential,” the authors concluded.
The work was supported by the National Cancer Institute of the National Institutes of Health and, in part, by Bristol Myers Squibb, Genentech, Pfizer, and Sanofi. Dr. Lipsyc-Sharf has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
One-quarter of lung cancer patients alive at 5 years
In recent years, the survival rate for patients with lung cancer has increased to the point where now, almost one-quarter of patients with lung cancer are alive 5 years after being diagnosed.
This new statistic is highlighted in the State of Lung Cancer report from the American Lung Association (ALA), published online on Nov. 16.
“If you look back, the 5-year survival rate has been very slowly eking up at about 1% over the years,” Andrea McKee, MD, volunteer spokesperson at the ALA, told this news organization. “To see this big jump is truly remarkable, so that is something we are all celebrating,” she added.
“But we have to change the fatalistic thinking that both patients and primary care physicians still have about lung cancer. Most people say, ‘Everybody I know who had lung cancer died,’ and that was the way it used to be,” she commented, “but that has now changed. Lung cancer is highly curable in its early stages, and even if not early-stage, there are treatments that are making an impact now.”
“So we’ve got to change that perception, as it does exist, even on the part of primary care providers, too,” Dr. McKee emphasized.
Lung cancer decreasing but still being diagnosed late
The report notes that the risk of being diagnosed with lung cancer varies considerably across the United States. For example, rates of lung cancer diagnoses are almost 2.5 times higher in Kentucky than in Utah.
Overall, the incidence is decreasing. “Over the last 5 years, the rate of new cases decreased 10% nationally,” the authors point out.
However, in almost half of the cases, the disease is diagnosed in late stages.
When diagnosed at a late stage, the 5-year survival rate for lung cancer drops to only 6%, whereas when the disease is diagnosed early, the 5-year survival rate is 60%.
At present, around 24% of cases of lung cancer are diagnosed at early stages, the report notes, but again, this varies across the United States. The highest rate (30%) is in Massachusetts, and the lowest rate (19%) is in Hawaii.
The percentage of lung cancer cases diagnosed early has been steadily increasing, presumably in part because of the introduction of low-dose CT screening for individuals at highest risk (such as smokers).
However, across the nation, only 5.7% of individuals at high risk for lung cancer underwent annual low-dose CT screening, the report notes.
“CT screening is so powerful at saving lives that even with only 5.7% of people that we’ve been able to screen, I believe it’s making a difference,” Dr. McKee commented. That small national percentage still represents a considerable number of patients, she noted, “so even with what we’ve done so far, I believe that screening is making a difference, at least within my own practice, where I’m definitely seeing it,” Dr. McKee emphasized.
Recent changes to the recommendations as to who should undergo lung cancer screening “have almost doubled the size of the screening population in the U.S.,” Dr. McKee commented. “So there are now about 15 million people who need to get screened, and it again helps that primary care physicians know that screening is very powerful at detecting early-stage lung cancer,” she said.
In her hospital’s own screening program, among the individuals who regularly undergo screening, the majority (88%) of lung cancer cases are detected at stage I or II, for which the cure rate is approximately 90%, she noted.
Another misconception of primary care physicians is that lung cancer screening has an unacceptably high false positive rate. Previous reports in the medical literature suggested the rate could be as high as 96%. “This is absolutely, positively wrong. That is not the false positive rate; the false positive rate for lung cancer screening is less than 10%,” Dr. McKee emphasized.
“So we have to change that in the minds of primary care providers as well,” she underscored.
Report highlights racial disparities
The report also highlights the racial disparities that persist in all aspects of lung cancer management – early diagnosis, surgical treatment, lack of treatment, and survival.
For example, Black Americans are 18% less likely to be diagnosed with early-stage disease and are 23% less likely to receive surgical treatment than their White counterparts. They are also 9% more likely to receive no treatment at all, and mortality from lung cancer among Black patients is 21% worse than it is for White patients.
The same trend is seen among Latinx persons, although they are just as likely as White patients to undergo surgical treatment.
First and foremost, “we have to make sure that the [Black and Latinx persons] are screened in an equal fashion,” Dr. McKee said. Providing screening for communities of color is one strategy that might improve screening rates, she suggested.
So, too, can outreach programs in which lung cancer experts work with leaders within these communities, because people are more likely to listen to their leaders regarding the importance of screening for early detection of lung cancer.
Physicians also need to emphasize that even for people who quit smoking decades ago, once those persons are in their 70s, “there is a spike again in lung cancer diagnoses, and that is true for both Black and White patients,” Dr. McKee stressed.
“Again, this is something that many doctors are not aware of,” she emphasized.
Dr. McKee has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In recent years, the survival rate for patients with lung cancer has increased to the point where now, almost one-quarter of patients with lung cancer are alive 5 years after being diagnosed.
This new statistic is highlighted in the State of Lung Cancer report from the American Lung Association (ALA), published online on Nov. 16.
“If you look back, the 5-year survival rate has been very slowly eking up at about 1% over the years,” Andrea McKee, MD, volunteer spokesperson at the ALA, told this news organization. “To see this big jump is truly remarkable, so that is something we are all celebrating,” she added.
“But we have to change the fatalistic thinking that both patients and primary care physicians still have about lung cancer. Most people say, ‘Everybody I know who had lung cancer died,’ and that was the way it used to be,” she commented, “but that has now changed. Lung cancer is highly curable in its early stages, and even if not early-stage, there are treatments that are making an impact now.”
“So we’ve got to change that perception, as it does exist, even on the part of primary care providers, too,” Dr. McKee emphasized.
Lung cancer decreasing but still being diagnosed late
The report notes that the risk of being diagnosed with lung cancer varies considerably across the United States. For example, rates of lung cancer diagnoses are almost 2.5 times higher in Kentucky than in Utah.
Overall, the incidence is decreasing. “Over the last 5 years, the rate of new cases decreased 10% nationally,” the authors point out.
However, in almost half of the cases, the disease is diagnosed in late stages.
When diagnosed at a late stage, the 5-year survival rate for lung cancer drops to only 6%, whereas when the disease is diagnosed early, the 5-year survival rate is 60%.
At present, around 24% of cases of lung cancer are diagnosed at early stages, the report notes, but again, this varies across the United States. The highest rate (30%) is in Massachusetts, and the lowest rate (19%) is in Hawaii.
The percentage of lung cancer cases diagnosed early has been steadily increasing, presumably in part because of the introduction of low-dose CT screening for individuals at highest risk (such as smokers).
However, across the nation, only 5.7% of individuals at high risk for lung cancer underwent annual low-dose CT screening, the report notes.
“CT screening is so powerful at saving lives that even with only 5.7% of people that we’ve been able to screen, I believe it’s making a difference,” Dr. McKee commented. That small national percentage still represents a considerable number of patients, she noted, “so even with what we’ve done so far, I believe that screening is making a difference, at least within my own practice, where I’m definitely seeing it,” Dr. McKee emphasized.
Recent changes to the recommendations as to who should undergo lung cancer screening “have almost doubled the size of the screening population in the U.S.,” Dr. McKee commented. “So there are now about 15 million people who need to get screened, and it again helps that primary care physicians know that screening is very powerful at detecting early-stage lung cancer,” she said.
In her hospital’s own screening program, among the individuals who regularly undergo screening, the majority (88%) of lung cancer cases are detected at stage I or II, for which the cure rate is approximately 90%, she noted.
Another misconception of primary care physicians is that lung cancer screening has an unacceptably high false positive rate. Previous reports in the medical literature suggested the rate could be as high as 96%. “This is absolutely, positively wrong. That is not the false positive rate; the false positive rate for lung cancer screening is less than 10%,” Dr. McKee emphasized.
“So we have to change that in the minds of primary care providers as well,” she underscored.
Report highlights racial disparities
The report also highlights the racial disparities that persist in all aspects of lung cancer management – early diagnosis, surgical treatment, lack of treatment, and survival.
For example, Black Americans are 18% less likely to be diagnosed with early-stage disease and are 23% less likely to receive surgical treatment than their White counterparts. They are also 9% more likely to receive no treatment at all, and mortality from lung cancer among Black patients is 21% worse than it is for White patients.
The same trend is seen among Latinx persons, although they are just as likely as White patients to undergo surgical treatment.
First and foremost, “we have to make sure that the [Black and Latinx persons] are screened in an equal fashion,” Dr. McKee said. Providing screening for communities of color is one strategy that might improve screening rates, she suggested.
So, too, can outreach programs in which lung cancer experts work with leaders within these communities, because people are more likely to listen to their leaders regarding the importance of screening for early detection of lung cancer.
Physicians also need to emphasize that even for people who quit smoking decades ago, once those persons are in their 70s, “there is a spike again in lung cancer diagnoses, and that is true for both Black and White patients,” Dr. McKee stressed.
“Again, this is something that many doctors are not aware of,” she emphasized.
Dr. McKee has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In recent years, the survival rate for patients with lung cancer has increased to the point where now, almost one-quarter of patients with lung cancer are alive 5 years after being diagnosed.
This new statistic is highlighted in the State of Lung Cancer report from the American Lung Association (ALA), published online on Nov. 16.
“If you look back, the 5-year survival rate has been very slowly eking up at about 1% over the years,” Andrea McKee, MD, volunteer spokesperson at the ALA, told this news organization. “To see this big jump is truly remarkable, so that is something we are all celebrating,” she added.
“But we have to change the fatalistic thinking that both patients and primary care physicians still have about lung cancer. Most people say, ‘Everybody I know who had lung cancer died,’ and that was the way it used to be,” she commented, “but that has now changed. Lung cancer is highly curable in its early stages, and even if not early-stage, there are treatments that are making an impact now.”
“So we’ve got to change that perception, as it does exist, even on the part of primary care providers, too,” Dr. McKee emphasized.
Lung cancer decreasing but still being diagnosed late
The report notes that the risk of being diagnosed with lung cancer varies considerably across the United States. For example, rates of lung cancer diagnoses are almost 2.5 times higher in Kentucky than in Utah.
Overall, the incidence is decreasing. “Over the last 5 years, the rate of new cases decreased 10% nationally,” the authors point out.
However, in almost half of the cases, the disease is diagnosed in late stages.
When diagnosed at a late stage, the 5-year survival rate for lung cancer drops to only 6%, whereas when the disease is diagnosed early, the 5-year survival rate is 60%.
At present, around 24% of cases of lung cancer are diagnosed at early stages, the report notes, but again, this varies across the United States. The highest rate (30%) is in Massachusetts, and the lowest rate (19%) is in Hawaii.
The percentage of lung cancer cases diagnosed early has been steadily increasing, presumably in part because of the introduction of low-dose CT screening for individuals at highest risk (such as smokers).
However, across the nation, only 5.7% of individuals at high risk for lung cancer underwent annual low-dose CT screening, the report notes.
“CT screening is so powerful at saving lives that even with only 5.7% of people that we’ve been able to screen, I believe it’s making a difference,” Dr. McKee commented. That small national percentage still represents a considerable number of patients, she noted, “so even with what we’ve done so far, I believe that screening is making a difference, at least within my own practice, where I’m definitely seeing it,” Dr. McKee emphasized.
Recent changes to the recommendations as to who should undergo lung cancer screening “have almost doubled the size of the screening population in the U.S.,” Dr. McKee commented. “So there are now about 15 million people who need to get screened, and it again helps that primary care physicians know that screening is very powerful at detecting early-stage lung cancer,” she said.
In her hospital’s own screening program, among the individuals who regularly undergo screening, the majority (88%) of lung cancer cases are detected at stage I or II, for which the cure rate is approximately 90%, she noted.
Another misconception of primary care physicians is that lung cancer screening has an unacceptably high false positive rate. Previous reports in the medical literature suggested the rate could be as high as 96%. “This is absolutely, positively wrong. That is not the false positive rate; the false positive rate for lung cancer screening is less than 10%,” Dr. McKee emphasized.
“So we have to change that in the minds of primary care providers as well,” she underscored.
Report highlights racial disparities
The report also highlights the racial disparities that persist in all aspects of lung cancer management – early diagnosis, surgical treatment, lack of treatment, and survival.
For example, Black Americans are 18% less likely to be diagnosed with early-stage disease and are 23% less likely to receive surgical treatment than their White counterparts. They are also 9% more likely to receive no treatment at all, and mortality from lung cancer among Black patients is 21% worse than it is for White patients.
The same trend is seen among Latinx persons, although they are just as likely as White patients to undergo surgical treatment.
First and foremost, “we have to make sure that the [Black and Latinx persons] are screened in an equal fashion,” Dr. McKee said. Providing screening for communities of color is one strategy that might improve screening rates, she suggested.
So, too, can outreach programs in which lung cancer experts work with leaders within these communities, because people are more likely to listen to their leaders regarding the importance of screening for early detection of lung cancer.
Physicians also need to emphasize that even for people who quit smoking decades ago, once those persons are in their 70s, “there is a spike again in lung cancer diagnoses, and that is true for both Black and White patients,” Dr. McKee stressed.
“Again, this is something that many doctors are not aware of,” she emphasized.
Dr. McKee has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Substantial declines in mortality for most cancers
according to a new analysis.
Researchers found that rates for all cancers combined declined by 27% overall between 1971 and 2019 and decreased significantly for 12 of the 15 top cancer sites analyzed.
The data revealed even greater mortality declines for certain cancers in particular years. For example, mortality from lung cancer was 44% lower in 2019, compared with its peak rate in 1993, whereas it was only 13% lower, compared with morality rates in 1971.
“The cancer mortality rate has reduced considerably since 1971 overall and for most cancer sites because of improvements in prevention, early detection, and treatment,” lead author Ahmedin Jemal, DVM, PhD, American Cancer Society, Kennesaw, Ga., and colleagues wrote.
Advances in surgery, radiotherapy, chemotherapy, precision medicine, and combinations therapies over the past 5 decades have contributed to these significant declines in mortality, Dr. Jemal and colleagues explained. The researchers also credit the “expanded investment” in the National Cancer Institute’s annual budget following the 1971 National Cancer Act, which increased the budget 25-fold from $227 million in 1971 to $6 billion in 2019.
The report, published online Nov. 11, 2021, in JAMA Oncology, analyzed mortality rates for all cancers as well as the top 15 sites using the National Center for Health Statistics.
The researchers found that, overall, deaths declined significantly for all cancers over the study period. Some of the biggest headway since 1971 occurred for stomach and cervical cancers – with 72% and 69% lower mortality rates, respectively – as well as colorectal cancer (56%), oral cavity and pharynx cancer (43%), and ovarian cancer (41%). Mortality rates of female breast cancer and prostate cancer also dropped considerably – both by 39%.
“The decline in mortality for female breast, cervical, colorectal, and prostate cancer in part reflects increased detection (and removal) of premalignant lesions and early-stage cancers,” Dr. Jemal and colleagues noted.
Data suggest that screening likely explains about half of the observed decline in mortality from colorectal cancer between 1975 and 2002. A 2018 study also found that the use of adjuvant chemotherapy was responsible for 63% of the decline in mortality from female breast cancer between 2000 and 2012.
In addition, the authors noted, “the decline in lung, oral cavity and bladder cancers largely reflects reductions in smoking because of enhanced public awareness of the health consequences, implementation of increased cigarette excise taxes, and comprehensive smoke-free laws.”
However, mortality did increase in a few categories. For instance, the mortality rate from pancreatic cancer increased by 3% between 1971 and 2019, and by 8% for both esophageal and brain cancers. Mortality rates from cancer were also greater for 29% of the U.S. counties included in the analysis, mostly those in the South.
The increase in mortality from pancreatic cancer likely reflects the growing rates of obesity in the United States, along with no real advances in pancreatic cancer prevention, early detection, or treatment, the authors suggested. In addition, lack of progress in regions of the south may be related to unequal access to improvements in treatment compared with other parts of the country.
“Improving equity through investment in the social determinants of health and implementation research is critical to furthering the national cancer-control agenda,” the authors concluded.
The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to a new analysis.
Researchers found that rates for all cancers combined declined by 27% overall between 1971 and 2019 and decreased significantly for 12 of the 15 top cancer sites analyzed.
The data revealed even greater mortality declines for certain cancers in particular years. For example, mortality from lung cancer was 44% lower in 2019, compared with its peak rate in 1993, whereas it was only 13% lower, compared with morality rates in 1971.
“The cancer mortality rate has reduced considerably since 1971 overall and for most cancer sites because of improvements in prevention, early detection, and treatment,” lead author Ahmedin Jemal, DVM, PhD, American Cancer Society, Kennesaw, Ga., and colleagues wrote.
Advances in surgery, radiotherapy, chemotherapy, precision medicine, and combinations therapies over the past 5 decades have contributed to these significant declines in mortality, Dr. Jemal and colleagues explained. The researchers also credit the “expanded investment” in the National Cancer Institute’s annual budget following the 1971 National Cancer Act, which increased the budget 25-fold from $227 million in 1971 to $6 billion in 2019.
The report, published online Nov. 11, 2021, in JAMA Oncology, analyzed mortality rates for all cancers as well as the top 15 sites using the National Center for Health Statistics.
The researchers found that, overall, deaths declined significantly for all cancers over the study period. Some of the biggest headway since 1971 occurred for stomach and cervical cancers – with 72% and 69% lower mortality rates, respectively – as well as colorectal cancer (56%), oral cavity and pharynx cancer (43%), and ovarian cancer (41%). Mortality rates of female breast cancer and prostate cancer also dropped considerably – both by 39%.
“The decline in mortality for female breast, cervical, colorectal, and prostate cancer in part reflects increased detection (and removal) of premalignant lesions and early-stage cancers,” Dr. Jemal and colleagues noted.
Data suggest that screening likely explains about half of the observed decline in mortality from colorectal cancer between 1975 and 2002. A 2018 study also found that the use of adjuvant chemotherapy was responsible for 63% of the decline in mortality from female breast cancer between 2000 and 2012.
In addition, the authors noted, “the decline in lung, oral cavity and bladder cancers largely reflects reductions in smoking because of enhanced public awareness of the health consequences, implementation of increased cigarette excise taxes, and comprehensive smoke-free laws.”
However, mortality did increase in a few categories. For instance, the mortality rate from pancreatic cancer increased by 3% between 1971 and 2019, and by 8% for both esophageal and brain cancers. Mortality rates from cancer were also greater for 29% of the U.S. counties included in the analysis, mostly those in the South.
The increase in mortality from pancreatic cancer likely reflects the growing rates of obesity in the United States, along with no real advances in pancreatic cancer prevention, early detection, or treatment, the authors suggested. In addition, lack of progress in regions of the south may be related to unequal access to improvements in treatment compared with other parts of the country.
“Improving equity through investment in the social determinants of health and implementation research is critical to furthering the national cancer-control agenda,” the authors concluded.
The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to a new analysis.
Researchers found that rates for all cancers combined declined by 27% overall between 1971 and 2019 and decreased significantly for 12 of the 15 top cancer sites analyzed.
The data revealed even greater mortality declines for certain cancers in particular years. For example, mortality from lung cancer was 44% lower in 2019, compared with its peak rate in 1993, whereas it was only 13% lower, compared with morality rates in 1971.
“The cancer mortality rate has reduced considerably since 1971 overall and for most cancer sites because of improvements in prevention, early detection, and treatment,” lead author Ahmedin Jemal, DVM, PhD, American Cancer Society, Kennesaw, Ga., and colleagues wrote.
Advances in surgery, radiotherapy, chemotherapy, precision medicine, and combinations therapies over the past 5 decades have contributed to these significant declines in mortality, Dr. Jemal and colleagues explained. The researchers also credit the “expanded investment” in the National Cancer Institute’s annual budget following the 1971 National Cancer Act, which increased the budget 25-fold from $227 million in 1971 to $6 billion in 2019.
The report, published online Nov. 11, 2021, in JAMA Oncology, analyzed mortality rates for all cancers as well as the top 15 sites using the National Center for Health Statistics.
The researchers found that, overall, deaths declined significantly for all cancers over the study period. Some of the biggest headway since 1971 occurred for stomach and cervical cancers – with 72% and 69% lower mortality rates, respectively – as well as colorectal cancer (56%), oral cavity and pharynx cancer (43%), and ovarian cancer (41%). Mortality rates of female breast cancer and prostate cancer also dropped considerably – both by 39%.
“The decline in mortality for female breast, cervical, colorectal, and prostate cancer in part reflects increased detection (and removal) of premalignant lesions and early-stage cancers,” Dr. Jemal and colleagues noted.
Data suggest that screening likely explains about half of the observed decline in mortality from colorectal cancer between 1975 and 2002. A 2018 study also found that the use of adjuvant chemotherapy was responsible for 63% of the decline in mortality from female breast cancer between 2000 and 2012.
In addition, the authors noted, “the decline in lung, oral cavity and bladder cancers largely reflects reductions in smoking because of enhanced public awareness of the health consequences, implementation of increased cigarette excise taxes, and comprehensive smoke-free laws.”
However, mortality did increase in a few categories. For instance, the mortality rate from pancreatic cancer increased by 3% between 1971 and 2019, and by 8% for both esophageal and brain cancers. Mortality rates from cancer were also greater for 29% of the U.S. counties included in the analysis, mostly those in the South.
The increase in mortality from pancreatic cancer likely reflects the growing rates of obesity in the United States, along with no real advances in pancreatic cancer prevention, early detection, or treatment, the authors suggested. In addition, lack of progress in regions of the south may be related to unequal access to improvements in treatment compared with other parts of the country.
“Improving equity through investment in the social determinants of health and implementation research is critical to furthering the national cancer-control agenda,” the authors concluded.
The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA ONCOLOGY
Gastric cancer prevalent in hereditary breast cancer patients
a prospective cohort study has shown.
“In short, what we are putting forward with these data is that pathogenic/likely pathogenic (P/LP) variants in the CDH1 gene confer a very high risk, at the very least, of occult early-stage gastric cancer in patients with HLBC,” said Jeremy Davis, MD, of the surgical oncology program, Center for Cancer Research at the National Cancer Institute.
“So patients that are referred to as ‘HLBC’ due to a CDH1 variant should at least undergo annual endoscopic surveillance but the real questions is whether or not they should also consider prophylactic total gastrectomy – as many patients in our study did,” he said.
The study, which was published online Oct. 13, 2021, in JAMA Surgery, included a cohort of 151 families totaling 283 patients with a CDH1 pathogenic or likely pathogenic (P/LP) variant. Analyses were conducted on three patient groups, which included those with HLBC and a family history of breast cancer but no gastric cancer, those with hereditary diffuse gastric cancer (HDGC) but no history of breast cancer, and those with a family history of both gastric and breast cancer in the mixed group. Of these, 15.5% had a history of HLBC, 16.2% had a history of HDGC, and 52.6% made up the mixed group.
“We examined the HLBC group with specific attention to CDH1 genotype and prevalence of occult gastric cancer,” the authors explained. The group consisted of 31 families with 19 CDH1 variants, 10 of which were also present in the HDGC and mixed groups.
Among this group of patients, almost 73% underwent one or more surveillance endoscopies and on endoscopy, occult signet ring cell carcinoma was detected in over one-third of patients.
The median age at the time of endoscopic carcinoma detection was only 33 years.
“Nearly all of the patients with HLBC (93.8%) ... who elected for risk-reducing total gastrectomy owing to their underlying CDH1 P/LP variant harbored occult signet ring cell gastric adenocarcinoma on final pathology,” investigators observed.
The median age at the time patients elected to undergo total gastrectomy was 50 years.
The prevalence of occult gastric cancer among asymptomatic patients in the HDGC group was similarly high, affecting almost 95% of this group of patients.
Some 18 out of 19 CDH1 P/LP variants were responsible for this high prevalence of occult gastric cancer, as the investigators pointed out.
“Hereditary cancer risk is informed by the presence of a germline gene variant more so than by family history of cancer,” the authors stressed. “[And we found that] germline CDH1 P/LP variants appear to have a highly penetrant gastric phenotype irrespective of family history.”
Given this finding, the authors stressed that it is “paramount” patients previously assigned a diagnosis of HLBC not be excluded from undergoing gastric cancer risk assessment and counseling.
Furthermore, “the mere presence of a germline CDH1 P/LP variant, regardless of family history, may be reason enough to consider prophylactic total gastrectomy,” the authors wrote.
Limitations of the study included the fact that the disease phenotype was established from family pedigrees which has the potential for recall bias by family members.
The study was supported in part by the Intramural Research Program of the National Cancer Institute. None of the authors had conflicts of interest to disclose.
a prospective cohort study has shown.
“In short, what we are putting forward with these data is that pathogenic/likely pathogenic (P/LP) variants in the CDH1 gene confer a very high risk, at the very least, of occult early-stage gastric cancer in patients with HLBC,” said Jeremy Davis, MD, of the surgical oncology program, Center for Cancer Research at the National Cancer Institute.
“So patients that are referred to as ‘HLBC’ due to a CDH1 variant should at least undergo annual endoscopic surveillance but the real questions is whether or not they should also consider prophylactic total gastrectomy – as many patients in our study did,” he said.
The study, which was published online Oct. 13, 2021, in JAMA Surgery, included a cohort of 151 families totaling 283 patients with a CDH1 pathogenic or likely pathogenic (P/LP) variant. Analyses were conducted on three patient groups, which included those with HLBC and a family history of breast cancer but no gastric cancer, those with hereditary diffuse gastric cancer (HDGC) but no history of breast cancer, and those with a family history of both gastric and breast cancer in the mixed group. Of these, 15.5% had a history of HLBC, 16.2% had a history of HDGC, and 52.6% made up the mixed group.
“We examined the HLBC group with specific attention to CDH1 genotype and prevalence of occult gastric cancer,” the authors explained. The group consisted of 31 families with 19 CDH1 variants, 10 of which were also present in the HDGC and mixed groups.
Among this group of patients, almost 73% underwent one or more surveillance endoscopies and on endoscopy, occult signet ring cell carcinoma was detected in over one-third of patients.
The median age at the time of endoscopic carcinoma detection was only 33 years.
“Nearly all of the patients with HLBC (93.8%) ... who elected for risk-reducing total gastrectomy owing to their underlying CDH1 P/LP variant harbored occult signet ring cell gastric adenocarcinoma on final pathology,” investigators observed.
The median age at the time patients elected to undergo total gastrectomy was 50 years.
The prevalence of occult gastric cancer among asymptomatic patients in the HDGC group was similarly high, affecting almost 95% of this group of patients.
Some 18 out of 19 CDH1 P/LP variants were responsible for this high prevalence of occult gastric cancer, as the investigators pointed out.
“Hereditary cancer risk is informed by the presence of a germline gene variant more so than by family history of cancer,” the authors stressed. “[And we found that] germline CDH1 P/LP variants appear to have a highly penetrant gastric phenotype irrespective of family history.”
Given this finding, the authors stressed that it is “paramount” patients previously assigned a diagnosis of HLBC not be excluded from undergoing gastric cancer risk assessment and counseling.
Furthermore, “the mere presence of a germline CDH1 P/LP variant, regardless of family history, may be reason enough to consider prophylactic total gastrectomy,” the authors wrote.
Limitations of the study included the fact that the disease phenotype was established from family pedigrees which has the potential for recall bias by family members.
The study was supported in part by the Intramural Research Program of the National Cancer Institute. None of the authors had conflicts of interest to disclose.
a prospective cohort study has shown.
“In short, what we are putting forward with these data is that pathogenic/likely pathogenic (P/LP) variants in the CDH1 gene confer a very high risk, at the very least, of occult early-stage gastric cancer in patients with HLBC,” said Jeremy Davis, MD, of the surgical oncology program, Center for Cancer Research at the National Cancer Institute.
“So patients that are referred to as ‘HLBC’ due to a CDH1 variant should at least undergo annual endoscopic surveillance but the real questions is whether or not they should also consider prophylactic total gastrectomy – as many patients in our study did,” he said.
The study, which was published online Oct. 13, 2021, in JAMA Surgery, included a cohort of 151 families totaling 283 patients with a CDH1 pathogenic or likely pathogenic (P/LP) variant. Analyses were conducted on three patient groups, which included those with HLBC and a family history of breast cancer but no gastric cancer, those with hereditary diffuse gastric cancer (HDGC) but no history of breast cancer, and those with a family history of both gastric and breast cancer in the mixed group. Of these, 15.5% had a history of HLBC, 16.2% had a history of HDGC, and 52.6% made up the mixed group.
“We examined the HLBC group with specific attention to CDH1 genotype and prevalence of occult gastric cancer,” the authors explained. The group consisted of 31 families with 19 CDH1 variants, 10 of which were also present in the HDGC and mixed groups.
Among this group of patients, almost 73% underwent one or more surveillance endoscopies and on endoscopy, occult signet ring cell carcinoma was detected in over one-third of patients.
The median age at the time of endoscopic carcinoma detection was only 33 years.
“Nearly all of the patients with HLBC (93.8%) ... who elected for risk-reducing total gastrectomy owing to their underlying CDH1 P/LP variant harbored occult signet ring cell gastric adenocarcinoma on final pathology,” investigators observed.
The median age at the time patients elected to undergo total gastrectomy was 50 years.
The prevalence of occult gastric cancer among asymptomatic patients in the HDGC group was similarly high, affecting almost 95% of this group of patients.
Some 18 out of 19 CDH1 P/LP variants were responsible for this high prevalence of occult gastric cancer, as the investigators pointed out.
“Hereditary cancer risk is informed by the presence of a germline gene variant more so than by family history of cancer,” the authors stressed. “[And we found that] germline CDH1 P/LP variants appear to have a highly penetrant gastric phenotype irrespective of family history.”
Given this finding, the authors stressed that it is “paramount” patients previously assigned a diagnosis of HLBC not be excluded from undergoing gastric cancer risk assessment and counseling.
Furthermore, “the mere presence of a germline CDH1 P/LP variant, regardless of family history, may be reason enough to consider prophylactic total gastrectomy,” the authors wrote.
Limitations of the study included the fact that the disease phenotype was established from family pedigrees which has the potential for recall bias by family members.
The study was supported in part by the Intramural Research Program of the National Cancer Institute. None of the authors had conflicts of interest to disclose.
FROM JAMA SURGERY
Chemotherapy with FOLFOX superior to TACE in liver cancer
Hepatic arterial infusion chemotherapy (HAIC) with FOLFOX led to superior patient outcomes and less toxicity than standard of care transarterial chemoembolization (TACE) for patients with large, unresectable hepatocellular carcinoma (HCC), a randomized, phase 3 trial has shown.
In a group of 315 patients with unresectable tumors at least 7 cm in diameter and no macrovascular invasion or extrahepatic spread, overall survival (OS) was 42% longer at 23.1 months for patients treated with FOLFOX-HAIC, compared with 16.1 months for TACE, at a hazard ratio of 0.58 (P < .001), Ming Shi, MD, Sun Yat-sen University, Guangzhou, China, and colleagues reported recently in the Journal of Clinical Oncology.
Similarly, median progression-free survival (PFS) was also longer for FOLFOX-HAIC patients at 9.6 months, compared with 5.4 months for TACE patients, as was median symptomatic PFS at 17.9 months, compared with 10.4 months, respectively (P < .001).
The frequency of grade 3-4 elevated liver ALT at 8% versus 19% (P = .005), elevated AST at 18% versus 28%, and hyperbilirubinemia at 1% versus 6% (P = .01) were all significantly higher in the TACE group than in the FOLFOX-HAIC group as was the overall incidence of serious adverse events at 30% versus 19%, respectively (P = .03).
The frequency of treatment delay and discontinuation of TACE because of adverse events were also higher than that in the FOLFOX-HAIC group.
“Transarterial chemoembolization (TACE) is the current standard of care for intermediate-stage hepatocellular carcinoma ... but the efficacy of TACE is largely dependent upon tumor size ... and for patients with particularly large tumors (>7 cm), the OS after TACE is only 11.2-13.2 months,” Dr. Shi and colleagues explained.
“Although the need for technical expertise may limit its generalizability, hepatic arterial infusion chemotherapy represents an appropriate frontline locoregional intervention in select patients with large unresectable hepatocellular carcinoma,” they observed.
TACE vs. HAIC
During TACE, a catheter was inserted into the celiac trunk or superior mesenteric artery for arteriography, after which a microcatheter was selectively placed into the feeding arteries of the tumors.
“Chemolipiodolization was performed using 50 mg of epirubicin and 50 mg of lobaplatin mixed with lipiodol,” the investigators noted, and subsequent embolization was done with the injection of polyvinyl alcohol particles.
TACE was repeated every 6 weeks.
HAIC in turn was divided into 3-week cycles during which a microcatheter was advanced into the hepatic artery on day 1 of each treatment cycle and FOLFOX was infused via the hepatic artery. FOLFOX consisted of oxaliplatin, 130 mg/m2; leucovorin, 400 mg/m2; and fluorouracil, 400 mg/m2, all given on day 1.
Subgroup analyses showed that HAIC provided a clinical benefit for PFS in most subgroups except females; those with a Child-Pug score of 6, and those who were negative for HBV.
The main drawback to the FOLFOX-HAIC regimen appears to be abdominal pain which some patients experienced when oxaliplatin was injected but which subsequently resolved when the injection was stopped.
As the authors pointed out, the overall response rate at 46% among patients treated with FOLFOX-HAIC was more than twice that with TACE at 18%.
“One possible reason is that FOLFOX-HAIC can provide stable local high concentrations of the chemotherapy agents in the tumor for more than 24 hours,” they speculated, “whereas most chemotherapeutic agents delivered through TACE ... will be released into the systemic circulation within less than 1 hour.”
Recently, drugs such as atezolizumab (Tecentriq, Roche) plus bevacizumab (Avastin, Genentech) have been shown to lead to high response rates in intermediate-stage HCC, as shown by the IMbrave 150 study.
“Therefore, in some latest practice guidelines and expert consensus statements, a switch of first-line treatment modality from TACE to systemic treatment is proposed for these patients,” the researchers noted.
Limitations of the study include its open-label design and the fact that more patients in the FOLFOX-HAIC group underwent hepatic resection whereas more patients in the TACE group crossed over to the other treatment arm.
Dr. Shi declared no conflicts of interest.
Hepatic arterial infusion chemotherapy (HAIC) with FOLFOX led to superior patient outcomes and less toxicity than standard of care transarterial chemoembolization (TACE) for patients with large, unresectable hepatocellular carcinoma (HCC), a randomized, phase 3 trial has shown.
In a group of 315 patients with unresectable tumors at least 7 cm in diameter and no macrovascular invasion or extrahepatic spread, overall survival (OS) was 42% longer at 23.1 months for patients treated with FOLFOX-HAIC, compared with 16.1 months for TACE, at a hazard ratio of 0.58 (P < .001), Ming Shi, MD, Sun Yat-sen University, Guangzhou, China, and colleagues reported recently in the Journal of Clinical Oncology.
Similarly, median progression-free survival (PFS) was also longer for FOLFOX-HAIC patients at 9.6 months, compared with 5.4 months for TACE patients, as was median symptomatic PFS at 17.9 months, compared with 10.4 months, respectively (P < .001).
The frequency of grade 3-4 elevated liver ALT at 8% versus 19% (P = .005), elevated AST at 18% versus 28%, and hyperbilirubinemia at 1% versus 6% (P = .01) were all significantly higher in the TACE group than in the FOLFOX-HAIC group as was the overall incidence of serious adverse events at 30% versus 19%, respectively (P = .03).
The frequency of treatment delay and discontinuation of TACE because of adverse events were also higher than that in the FOLFOX-HAIC group.
“Transarterial chemoembolization (TACE) is the current standard of care for intermediate-stage hepatocellular carcinoma ... but the efficacy of TACE is largely dependent upon tumor size ... and for patients with particularly large tumors (>7 cm), the OS after TACE is only 11.2-13.2 months,” Dr. Shi and colleagues explained.
“Although the need for technical expertise may limit its generalizability, hepatic arterial infusion chemotherapy represents an appropriate frontline locoregional intervention in select patients with large unresectable hepatocellular carcinoma,” they observed.
TACE vs. HAIC
During TACE, a catheter was inserted into the celiac trunk or superior mesenteric artery for arteriography, after which a microcatheter was selectively placed into the feeding arteries of the tumors.
“Chemolipiodolization was performed using 50 mg of epirubicin and 50 mg of lobaplatin mixed with lipiodol,” the investigators noted, and subsequent embolization was done with the injection of polyvinyl alcohol particles.
TACE was repeated every 6 weeks.
HAIC in turn was divided into 3-week cycles during which a microcatheter was advanced into the hepatic artery on day 1 of each treatment cycle and FOLFOX was infused via the hepatic artery. FOLFOX consisted of oxaliplatin, 130 mg/m2; leucovorin, 400 mg/m2; and fluorouracil, 400 mg/m2, all given on day 1.
Subgroup analyses showed that HAIC provided a clinical benefit for PFS in most subgroups except females; those with a Child-Pug score of 6, and those who were negative for HBV.
The main drawback to the FOLFOX-HAIC regimen appears to be abdominal pain which some patients experienced when oxaliplatin was injected but which subsequently resolved when the injection was stopped.
As the authors pointed out, the overall response rate at 46% among patients treated with FOLFOX-HAIC was more than twice that with TACE at 18%.
“One possible reason is that FOLFOX-HAIC can provide stable local high concentrations of the chemotherapy agents in the tumor for more than 24 hours,” they speculated, “whereas most chemotherapeutic agents delivered through TACE ... will be released into the systemic circulation within less than 1 hour.”
Recently, drugs such as atezolizumab (Tecentriq, Roche) plus bevacizumab (Avastin, Genentech) have been shown to lead to high response rates in intermediate-stage HCC, as shown by the IMbrave 150 study.
“Therefore, in some latest practice guidelines and expert consensus statements, a switch of first-line treatment modality from TACE to systemic treatment is proposed for these patients,” the researchers noted.
Limitations of the study include its open-label design and the fact that more patients in the FOLFOX-HAIC group underwent hepatic resection whereas more patients in the TACE group crossed over to the other treatment arm.
Dr. Shi declared no conflicts of interest.
Hepatic arterial infusion chemotherapy (HAIC) with FOLFOX led to superior patient outcomes and less toxicity than standard of care transarterial chemoembolization (TACE) for patients with large, unresectable hepatocellular carcinoma (HCC), a randomized, phase 3 trial has shown.
In a group of 315 patients with unresectable tumors at least 7 cm in diameter and no macrovascular invasion or extrahepatic spread, overall survival (OS) was 42% longer at 23.1 months for patients treated with FOLFOX-HAIC, compared with 16.1 months for TACE, at a hazard ratio of 0.58 (P < .001), Ming Shi, MD, Sun Yat-sen University, Guangzhou, China, and colleagues reported recently in the Journal of Clinical Oncology.
Similarly, median progression-free survival (PFS) was also longer for FOLFOX-HAIC patients at 9.6 months, compared with 5.4 months for TACE patients, as was median symptomatic PFS at 17.9 months, compared with 10.4 months, respectively (P < .001).
The frequency of grade 3-4 elevated liver ALT at 8% versus 19% (P = .005), elevated AST at 18% versus 28%, and hyperbilirubinemia at 1% versus 6% (P = .01) were all significantly higher in the TACE group than in the FOLFOX-HAIC group as was the overall incidence of serious adverse events at 30% versus 19%, respectively (P = .03).
The frequency of treatment delay and discontinuation of TACE because of adverse events were also higher than that in the FOLFOX-HAIC group.
“Transarterial chemoembolization (TACE) is the current standard of care for intermediate-stage hepatocellular carcinoma ... but the efficacy of TACE is largely dependent upon tumor size ... and for patients with particularly large tumors (>7 cm), the OS after TACE is only 11.2-13.2 months,” Dr. Shi and colleagues explained.
“Although the need for technical expertise may limit its generalizability, hepatic arterial infusion chemotherapy represents an appropriate frontline locoregional intervention in select patients with large unresectable hepatocellular carcinoma,” they observed.
TACE vs. HAIC
During TACE, a catheter was inserted into the celiac trunk or superior mesenteric artery for arteriography, after which a microcatheter was selectively placed into the feeding arteries of the tumors.
“Chemolipiodolization was performed using 50 mg of epirubicin and 50 mg of lobaplatin mixed with lipiodol,” the investigators noted, and subsequent embolization was done with the injection of polyvinyl alcohol particles.
TACE was repeated every 6 weeks.
HAIC in turn was divided into 3-week cycles during which a microcatheter was advanced into the hepatic artery on day 1 of each treatment cycle and FOLFOX was infused via the hepatic artery. FOLFOX consisted of oxaliplatin, 130 mg/m2; leucovorin, 400 mg/m2; and fluorouracil, 400 mg/m2, all given on day 1.
Subgroup analyses showed that HAIC provided a clinical benefit for PFS in most subgroups except females; those with a Child-Pug score of 6, and those who were negative for HBV.
The main drawback to the FOLFOX-HAIC regimen appears to be abdominal pain which some patients experienced when oxaliplatin was injected but which subsequently resolved when the injection was stopped.
As the authors pointed out, the overall response rate at 46% among patients treated with FOLFOX-HAIC was more than twice that with TACE at 18%.
“One possible reason is that FOLFOX-HAIC can provide stable local high concentrations of the chemotherapy agents in the tumor for more than 24 hours,” they speculated, “whereas most chemotherapeutic agents delivered through TACE ... will be released into the systemic circulation within less than 1 hour.”
Recently, drugs such as atezolizumab (Tecentriq, Roche) plus bevacizumab (Avastin, Genentech) have been shown to lead to high response rates in intermediate-stage HCC, as shown by the IMbrave 150 study.
“Therefore, in some latest practice guidelines and expert consensus statements, a switch of first-line treatment modality from TACE to systemic treatment is proposed for these patients,” the researchers noted.
Limitations of the study include its open-label design and the fact that more patients in the FOLFOX-HAIC group underwent hepatic resection whereas more patients in the TACE group crossed over to the other treatment arm.
Dr. Shi declared no conflicts of interest.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Prostate cancer risk higher with Lynch syndrome variants
Men who carry certain pathogenic variants in mismatch repair genes that characterize Lynch syndrome may have a higher risk of prostate cancer, shows a new study. However, for men who carry MSH2 and MSH6 variants, the risk of contracting cancer rises significantly.
Called IMPACT, the study, which was published online in The Lancet Oncology, is an international, prospective study of 828 men aged between 40 and 69 years who were prostate cancer free, but they carried germline pathogenic variants in one of the mismatch repair genes MLH1, MSH2, or MSH6.
The researchers, who were led by Rosalind A. Eeles, PhD, a specialist in oncogenetics with the Institute of Cancer Research, London, found that after one screening “a higher incidence of prostate cancer was detected in men with MSH2 and MHS6 pathogenic variants, compared with age-matched noncarrier controls.”
She and her team also found that MSH2 carriers “were diagnosed at a nonsignificantly younger age and had more clinically significant disease at diagnosis, compared with noncarriers. These data add evidence that prostate screening in this higher-risk context has potential to detect tumors that are highly likely to need treatment.”
The findings suggest that targeted prostate-specific antigen (PSA) screening in men with mismatch repair gene pathogenic variants is justifiable. “Testing for mismatch repair variants will likely become routine practice at diagnosis over the coming years,” the authors wrote.
Lynch syndrome can increase the risk of prostate cancer by 2-10 times, yet there is no international consensus for screening. The 2019 National Comprehensive Cancer Network guidelines recommend considering tumor testing for deficient mismatch repair in men with regional or metastatic prostate cancer. The NCCN also recommends germline testing for all newly diagnosed men with high-risk, very-high-risk, regional, or metastatic prostate cancer.
Currently, the PSA test is the most commonly used test, however, it is not recommended as a routine screening tool because of the negative consequences of overdetection. The American Cancer Society and European Association of Urology recommend PSA screening for men with a strong family history of prostate cancer. The EAU also supports annual PSA screening for men with BRCA2 variants.
“From a treatment perspective, knowledge of mismatch repair pathogenic variant status is increasingly important because of the evidence that mismatch repair-deficient prostate tumors can be sensitive to immune checkpoint inhibitors,” the investigators wrote.
NCCN guidelines support the use of the progressive death–1 inhibitor pembrolizumab (Keytruda, Merck) in these patients, among others.
Although immune checkpoint inhibitors are predominantly used to treat metastatic disease, “this field is rapidly evolving and we will likely see these treatments move earlier in the treatment pathway,” the authors predicted.
The findings in detail
The IMPACT study was established in 2005 to assess targeted PSA screening in men with BRCA1 or BRCA2 pathogenic variants. It was extended in 2012 to include men from families with MLH1, MSH2, and MSH6 pathogenic variants.
In this new report, within the first round of screening, 6% of the cohort had a PSA concentration higher than 3.0 ng/mL and the overall incidence of prostate cancer was 1.9%, the investigators noted.
MSH2 carriers were diagnosed at 58 years old on average, compared with 66 years old for the control group. MSH2-positive men had more clinically significant disease, compared with noncarriers. The incidence of prostate cancer was higher at 4.3% in MSH2 carriers than in controls at 0.5%. In MSH6 carriers, the incidence of prostate cancer was 3.0%, compared with 0% for controls.
Only 4% of men underwent a biopsy and only one cancer was found among the MSH2 noncarriers while no cancers were found in MLH1 carriers, MLH1 noncarriers, or MSH6 noncarriers.
The overall positive predictive value of using a PSA threshold of 3.0 ng/mL was 51.4%; separated by genetic status, the PPV in MSH2 carriers was higher at 72.2% and in MSH6 carriers, the PPV was 80%, the researchers noted.
Limitations of the study include the fact that the number of cancers detected in the study was relatively small, thus requiring further data from subsequent screening rounds.
One study coauthor disclosed a potential conflict of interest by holding a PSA test patent.
Men who carry certain pathogenic variants in mismatch repair genes that characterize Lynch syndrome may have a higher risk of prostate cancer, shows a new study. However, for men who carry MSH2 and MSH6 variants, the risk of contracting cancer rises significantly.
Called IMPACT, the study, which was published online in The Lancet Oncology, is an international, prospective study of 828 men aged between 40 and 69 years who were prostate cancer free, but they carried germline pathogenic variants in one of the mismatch repair genes MLH1, MSH2, or MSH6.
The researchers, who were led by Rosalind A. Eeles, PhD, a specialist in oncogenetics with the Institute of Cancer Research, London, found that after one screening “a higher incidence of prostate cancer was detected in men with MSH2 and MHS6 pathogenic variants, compared with age-matched noncarrier controls.”
She and her team also found that MSH2 carriers “were diagnosed at a nonsignificantly younger age and had more clinically significant disease at diagnosis, compared with noncarriers. These data add evidence that prostate screening in this higher-risk context has potential to detect tumors that are highly likely to need treatment.”
The findings suggest that targeted prostate-specific antigen (PSA) screening in men with mismatch repair gene pathogenic variants is justifiable. “Testing for mismatch repair variants will likely become routine practice at diagnosis over the coming years,” the authors wrote.
Lynch syndrome can increase the risk of prostate cancer by 2-10 times, yet there is no international consensus for screening. The 2019 National Comprehensive Cancer Network guidelines recommend considering tumor testing for deficient mismatch repair in men with regional or metastatic prostate cancer. The NCCN also recommends germline testing for all newly diagnosed men with high-risk, very-high-risk, regional, or metastatic prostate cancer.
Currently, the PSA test is the most commonly used test, however, it is not recommended as a routine screening tool because of the negative consequences of overdetection. The American Cancer Society and European Association of Urology recommend PSA screening for men with a strong family history of prostate cancer. The EAU also supports annual PSA screening for men with BRCA2 variants.
“From a treatment perspective, knowledge of mismatch repair pathogenic variant status is increasingly important because of the evidence that mismatch repair-deficient prostate tumors can be sensitive to immune checkpoint inhibitors,” the investigators wrote.
NCCN guidelines support the use of the progressive death–1 inhibitor pembrolizumab (Keytruda, Merck) in these patients, among others.
Although immune checkpoint inhibitors are predominantly used to treat metastatic disease, “this field is rapidly evolving and we will likely see these treatments move earlier in the treatment pathway,” the authors predicted.
The findings in detail
The IMPACT study was established in 2005 to assess targeted PSA screening in men with BRCA1 or BRCA2 pathogenic variants. It was extended in 2012 to include men from families with MLH1, MSH2, and MSH6 pathogenic variants.
In this new report, within the first round of screening, 6% of the cohort had a PSA concentration higher than 3.0 ng/mL and the overall incidence of prostate cancer was 1.9%, the investigators noted.
MSH2 carriers were diagnosed at 58 years old on average, compared with 66 years old for the control group. MSH2-positive men had more clinically significant disease, compared with noncarriers. The incidence of prostate cancer was higher at 4.3% in MSH2 carriers than in controls at 0.5%. In MSH6 carriers, the incidence of prostate cancer was 3.0%, compared with 0% for controls.
Only 4% of men underwent a biopsy and only one cancer was found among the MSH2 noncarriers while no cancers were found in MLH1 carriers, MLH1 noncarriers, or MSH6 noncarriers.
The overall positive predictive value of using a PSA threshold of 3.0 ng/mL was 51.4%; separated by genetic status, the PPV in MSH2 carriers was higher at 72.2% and in MSH6 carriers, the PPV was 80%, the researchers noted.
Limitations of the study include the fact that the number of cancers detected in the study was relatively small, thus requiring further data from subsequent screening rounds.
One study coauthor disclosed a potential conflict of interest by holding a PSA test patent.
Men who carry certain pathogenic variants in mismatch repair genes that characterize Lynch syndrome may have a higher risk of prostate cancer, shows a new study. However, for men who carry MSH2 and MSH6 variants, the risk of contracting cancer rises significantly.
Called IMPACT, the study, which was published online in The Lancet Oncology, is an international, prospective study of 828 men aged between 40 and 69 years who were prostate cancer free, but they carried germline pathogenic variants in one of the mismatch repair genes MLH1, MSH2, or MSH6.
The researchers, who were led by Rosalind A. Eeles, PhD, a specialist in oncogenetics with the Institute of Cancer Research, London, found that after one screening “a higher incidence of prostate cancer was detected in men with MSH2 and MHS6 pathogenic variants, compared with age-matched noncarrier controls.”
She and her team also found that MSH2 carriers “were diagnosed at a nonsignificantly younger age and had more clinically significant disease at diagnosis, compared with noncarriers. These data add evidence that prostate screening in this higher-risk context has potential to detect tumors that are highly likely to need treatment.”
The findings suggest that targeted prostate-specific antigen (PSA) screening in men with mismatch repair gene pathogenic variants is justifiable. “Testing for mismatch repair variants will likely become routine practice at diagnosis over the coming years,” the authors wrote.
Lynch syndrome can increase the risk of prostate cancer by 2-10 times, yet there is no international consensus for screening. The 2019 National Comprehensive Cancer Network guidelines recommend considering tumor testing for deficient mismatch repair in men with regional or metastatic prostate cancer. The NCCN also recommends germline testing for all newly diagnosed men with high-risk, very-high-risk, regional, or metastatic prostate cancer.
Currently, the PSA test is the most commonly used test, however, it is not recommended as a routine screening tool because of the negative consequences of overdetection. The American Cancer Society and European Association of Urology recommend PSA screening for men with a strong family history of prostate cancer. The EAU also supports annual PSA screening for men with BRCA2 variants.
“From a treatment perspective, knowledge of mismatch repair pathogenic variant status is increasingly important because of the evidence that mismatch repair-deficient prostate tumors can be sensitive to immune checkpoint inhibitors,” the investigators wrote.
NCCN guidelines support the use of the progressive death–1 inhibitor pembrolizumab (Keytruda, Merck) in these patients, among others.
Although immune checkpoint inhibitors are predominantly used to treat metastatic disease, “this field is rapidly evolving and we will likely see these treatments move earlier in the treatment pathway,” the authors predicted.
The findings in detail
The IMPACT study was established in 2005 to assess targeted PSA screening in men with BRCA1 or BRCA2 pathogenic variants. It was extended in 2012 to include men from families with MLH1, MSH2, and MSH6 pathogenic variants.
In this new report, within the first round of screening, 6% of the cohort had a PSA concentration higher than 3.0 ng/mL and the overall incidence of prostate cancer was 1.9%, the investigators noted.
MSH2 carriers were diagnosed at 58 years old on average, compared with 66 years old for the control group. MSH2-positive men had more clinically significant disease, compared with noncarriers. The incidence of prostate cancer was higher at 4.3% in MSH2 carriers than in controls at 0.5%. In MSH6 carriers, the incidence of prostate cancer was 3.0%, compared with 0% for controls.
Only 4% of men underwent a biopsy and only one cancer was found among the MSH2 noncarriers while no cancers were found in MLH1 carriers, MLH1 noncarriers, or MSH6 noncarriers.
The overall positive predictive value of using a PSA threshold of 3.0 ng/mL was 51.4%; separated by genetic status, the PPV in MSH2 carriers was higher at 72.2% and in MSH6 carriers, the PPV was 80%, the researchers noted.
Limitations of the study include the fact that the number of cancers detected in the study was relatively small, thus requiring further data from subsequent screening rounds.
One study coauthor disclosed a potential conflict of interest by holding a PSA test patent.
FROM LANCET ONCOLOGY
Decades spent searching for genes linked to rare blood cancer
Mary Lou McMaster, MD, has spent her entire career at the National Cancer Institute (NCI) searching for the genetic underpinnings that give rise to Waldenstrom's macroglobulinemia (WM).
After searching for decades, she has yet to uncover a "smoking gun," though a few tantalizing clues have emerged along the way.
"Our questions are pretty basic: Why are some people more susceptible to developing WM, and why does WM sometimes cluster in families?" she explained. It turns out that the answers are not at all simple.
Dr. McMaster described some of the clues that her team at the Clinical Genetics Branch of the NCI has unearthed in a presentation at the recent International Waldenstrom's Macroglobulinemia Foundation (IWMF) 2021 Virtual Educational Forum.
Commenting after the presentation, Steven Treon, MD, PhD, professor of medicine, Harvard Medical School, Boston, who is collaborating with Dr. McMaster on this work, said: "From these familial studies, we can learn how familial genomics may give us insights into disease prevention and treatment."
Identifying affected families
Work began in 2001 to identify families in which two or more family members had been diagnosed with WM or in which there was one patient with WM and at least one other relative with a related B-cell cancer, such as chronic lymphocytic leukemia.
For a frame of reference, they enrolled some families with only one member with WM and in which there was no known family history of the disease.
"Overall, we have learned that familial WM is a rare disease but not nearly as rare as we first thought," Dr. McMaster said.
For example, in a referral hospital setting, 5% of WM patients will report having a family member with the same disorder, and up to 20% of WM patients report having a family member with a related but different B-cell cancer, she noted.
NCI researchers also discovered that environmental factors contribute to the development of WM. Notable chemical or occupational exposures include exposures to pesticides, herbicides, and fertilizers. Infections and autoimmune disease are additional factors.
"This was not a surprise," Dr. McMaster commented regarding the role of occupational exposures. The research community has known for decades that a "lymphoma belt" cuts through the Midwest farming states.
Focusing on genetic susceptibility, Dr. McMaster and colleagues first tried to identify a rare germline variant that can be passed down to offspring and that might confer high risk for the disease.
"We used our high-risk families to study these types of changes, although they may be modified by other genes and environmental factors," Dr. McMaster explained.
Much to their collective disappointment, the research team has been unable to identify any rare germline variant that could account for WM in many families. What they did find were many small changes in genes that are known to be important in B-cell development and function, but all of those would lead to only a small increase in WM risk.
"What is holding us back is that, so far, we are not seeing the same gene affected in more than one family, so this suggests to us either that this is not the mechanism behind the development of WM in families, or we have an unfortunate situation where each family is going to have a genetic change that is private to that family and which is not found in other families," Dr. McMaster acknowledged.
Sheer difficulty
Given the difficulty of determining whether these small genetic changes had any detrimental functional effect in each and every family with a member who had WM, Dr. McMaster and colleagues have now turned their attention to genes that exert only a small effect on disease risk.
"Here, we focused on specific genes that we knew were important in the function of the immune system," she explained. "We did find a few genes that may contribute to risk, but those have not yet been confirmed by us or others, and we cannot say they are causative without that confirmation," she said.
The team has gone on to scan the highway of our genetic material so as to isolate genetic "mile markers." They then examine the area around a particular marker that they suspect contains genes that may be involved in WM.
One study they conducted involved a cohort of 217 patients with WM in which numerous family members had WM and so was enriched with susceptibility genes. A second cohort comprised 312 WM patients in which there were few WM cases among family members. Both of these cohorts were compared with a group of healthy control persons.
From these genome studies, "we found there are at least two regions of the genome that can contribute to WM susceptibility, the largest effect being on the short arm of chromosome 6, and the other on the long arm of chromosome 14," Dr. McMaster reported. Dr. McMaster feels that there are probably more regions on the genome that also contribute to WM, although they do not yet understand how these regions contribute to susceptibility.
"It's more evidence that WM likely results from a combination of events rather than one single gene variant," she observed. Dr. McMaster and colleagues are now collaborating with a large consortium of WM researchers to confirm and extend their findings. Plans are underway to analyze data from approximately 1,350 WM patients and more than 20,000 control persons within the next year.
"Our hope is that we will confirm our original findings and, because we now have a much larger sample, we will be able to discover additional regions of the genome that are contributing to susceptibility," Dr. McMaster said.
"A single gene is not likely to account for all WM, as we've looked carefully and others have looked too," she commented.
"So the risk for WM depends on a combination of genes and environmental exposures and possibly lifestyle factors as well, although we still estimate that approximately 25% of the heritability of WM can be attributed to these kinds of genetic changes," Dr. McMaster predicted.
Dr. McMaster has disclosed no relevant financial relationships. Dr. Treon has served as a director, officer, partner, employee, advisor, consultant, or trustee for Janssen, Pfizer, PCYC, and BioGene.
A version of this article first appeared on Medscape.com
Mary Lou McMaster, MD, has spent her entire career at the National Cancer Institute (NCI) searching for the genetic underpinnings that give rise to Waldenstrom's macroglobulinemia (WM).
After searching for decades, she has yet to uncover a "smoking gun," though a few tantalizing clues have emerged along the way.
"Our questions are pretty basic: Why are some people more susceptible to developing WM, and why does WM sometimes cluster in families?" she explained. It turns out that the answers are not at all simple.
Dr. McMaster described some of the clues that her team at the Clinical Genetics Branch of the NCI has unearthed in a presentation at the recent International Waldenstrom's Macroglobulinemia Foundation (IWMF) 2021 Virtual Educational Forum.
Commenting after the presentation, Steven Treon, MD, PhD, professor of medicine, Harvard Medical School, Boston, who is collaborating with Dr. McMaster on this work, said: "From these familial studies, we can learn how familial genomics may give us insights into disease prevention and treatment."
Identifying affected families
Work began in 2001 to identify families in which two or more family members had been diagnosed with WM or in which there was one patient with WM and at least one other relative with a related B-cell cancer, such as chronic lymphocytic leukemia.
For a frame of reference, they enrolled some families with only one member with WM and in which there was no known family history of the disease.
"Overall, we have learned that familial WM is a rare disease but not nearly as rare as we first thought," Dr. McMaster said.
For example, in a referral hospital setting, 5% of WM patients will report having a family member with the same disorder, and up to 20% of WM patients report having a family member with a related but different B-cell cancer, she noted.
NCI researchers also discovered that environmental factors contribute to the development of WM. Notable chemical or occupational exposures include exposures to pesticides, herbicides, and fertilizers. Infections and autoimmune disease are additional factors.
"This was not a surprise," Dr. McMaster commented regarding the role of occupational exposures. The research community has known for decades that a "lymphoma belt" cuts through the Midwest farming states.
Focusing on genetic susceptibility, Dr. McMaster and colleagues first tried to identify a rare germline variant that can be passed down to offspring and that might confer high risk for the disease.
"We used our high-risk families to study these types of changes, although they may be modified by other genes and environmental factors," Dr. McMaster explained.
Much to their collective disappointment, the research team has been unable to identify any rare germline variant that could account for WM in many families. What they did find were many small changes in genes that are known to be important in B-cell development and function, but all of those would lead to only a small increase in WM risk.
"What is holding us back is that, so far, we are not seeing the same gene affected in more than one family, so this suggests to us either that this is not the mechanism behind the development of WM in families, or we have an unfortunate situation where each family is going to have a genetic change that is private to that family and which is not found in other families," Dr. McMaster acknowledged.
Sheer difficulty
Given the difficulty of determining whether these small genetic changes had any detrimental functional effect in each and every family with a member who had WM, Dr. McMaster and colleagues have now turned their attention to genes that exert only a small effect on disease risk.
"Here, we focused on specific genes that we knew were important in the function of the immune system," she explained. "We did find a few genes that may contribute to risk, but those have not yet been confirmed by us or others, and we cannot say they are causative without that confirmation," she said.
The team has gone on to scan the highway of our genetic material so as to isolate genetic "mile markers." They then examine the area around a particular marker that they suspect contains genes that may be involved in WM.
One study they conducted involved a cohort of 217 patients with WM in which numerous family members had WM and so was enriched with susceptibility genes. A second cohort comprised 312 WM patients in which there were few WM cases among family members. Both of these cohorts were compared with a group of healthy control persons.
From these genome studies, "we found there are at least two regions of the genome that can contribute to WM susceptibility, the largest effect being on the short arm of chromosome 6, and the other on the long arm of chromosome 14," Dr. McMaster reported. Dr. McMaster feels that there are probably more regions on the genome that also contribute to WM, although they do not yet understand how these regions contribute to susceptibility.
"It's more evidence that WM likely results from a combination of events rather than one single gene variant," she observed. Dr. McMaster and colleagues are now collaborating with a large consortium of WM researchers to confirm and extend their findings. Plans are underway to analyze data from approximately 1,350 WM patients and more than 20,000 control persons within the next year.
"Our hope is that we will confirm our original findings and, because we now have a much larger sample, we will be able to discover additional regions of the genome that are contributing to susceptibility," Dr. McMaster said.
"A single gene is not likely to account for all WM, as we've looked carefully and others have looked too," she commented.
"So the risk for WM depends on a combination of genes and environmental exposures and possibly lifestyle factors as well, although we still estimate that approximately 25% of the heritability of WM can be attributed to these kinds of genetic changes," Dr. McMaster predicted.
Dr. McMaster has disclosed no relevant financial relationships. Dr. Treon has served as a director, officer, partner, employee, advisor, consultant, or trustee for Janssen, Pfizer, PCYC, and BioGene.
A version of this article first appeared on Medscape.com
Mary Lou McMaster, MD, has spent her entire career at the National Cancer Institute (NCI) searching for the genetic underpinnings that give rise to Waldenstrom's macroglobulinemia (WM).
After searching for decades, she has yet to uncover a "smoking gun," though a few tantalizing clues have emerged along the way.
"Our questions are pretty basic: Why are some people more susceptible to developing WM, and why does WM sometimes cluster in families?" she explained. It turns out that the answers are not at all simple.
Dr. McMaster described some of the clues that her team at the Clinical Genetics Branch of the NCI has unearthed in a presentation at the recent International Waldenstrom's Macroglobulinemia Foundation (IWMF) 2021 Virtual Educational Forum.
Commenting after the presentation, Steven Treon, MD, PhD, professor of medicine, Harvard Medical School, Boston, who is collaborating with Dr. McMaster on this work, said: "From these familial studies, we can learn how familial genomics may give us insights into disease prevention and treatment."
Identifying affected families
Work began in 2001 to identify families in which two or more family members had been diagnosed with WM or in which there was one patient with WM and at least one other relative with a related B-cell cancer, such as chronic lymphocytic leukemia.
For a frame of reference, they enrolled some families with only one member with WM and in which there was no known family history of the disease.
"Overall, we have learned that familial WM is a rare disease but not nearly as rare as we first thought," Dr. McMaster said.
For example, in a referral hospital setting, 5% of WM patients will report having a family member with the same disorder, and up to 20% of WM patients report having a family member with a related but different B-cell cancer, she noted.
NCI researchers also discovered that environmental factors contribute to the development of WM. Notable chemical or occupational exposures include exposures to pesticides, herbicides, and fertilizers. Infections and autoimmune disease are additional factors.
"This was not a surprise," Dr. McMaster commented regarding the role of occupational exposures. The research community has known for decades that a "lymphoma belt" cuts through the Midwest farming states.
Focusing on genetic susceptibility, Dr. McMaster and colleagues first tried to identify a rare germline variant that can be passed down to offspring and that might confer high risk for the disease.
"We used our high-risk families to study these types of changes, although they may be modified by other genes and environmental factors," Dr. McMaster explained.
Much to their collective disappointment, the research team has been unable to identify any rare germline variant that could account for WM in many families. What they did find were many small changes in genes that are known to be important in B-cell development and function, but all of those would lead to only a small increase in WM risk.
"What is holding us back is that, so far, we are not seeing the same gene affected in more than one family, so this suggests to us either that this is not the mechanism behind the development of WM in families, or we have an unfortunate situation where each family is going to have a genetic change that is private to that family and which is not found in other families," Dr. McMaster acknowledged.
Sheer difficulty
Given the difficulty of determining whether these small genetic changes had any detrimental functional effect in each and every family with a member who had WM, Dr. McMaster and colleagues have now turned their attention to genes that exert only a small effect on disease risk.
"Here, we focused on specific genes that we knew were important in the function of the immune system," she explained. "We did find a few genes that may contribute to risk, but those have not yet been confirmed by us or others, and we cannot say they are causative without that confirmation," she said.
The team has gone on to scan the highway of our genetic material so as to isolate genetic "mile markers." They then examine the area around a particular marker that they suspect contains genes that may be involved in WM.
One study they conducted involved a cohort of 217 patients with WM in which numerous family members had WM and so was enriched with susceptibility genes. A second cohort comprised 312 WM patients in which there were few WM cases among family members. Both of these cohorts were compared with a group of healthy control persons.
From these genome studies, "we found there are at least two regions of the genome that can contribute to WM susceptibility, the largest effect being on the short arm of chromosome 6, and the other on the long arm of chromosome 14," Dr. McMaster reported. Dr. McMaster feels that there are probably more regions on the genome that also contribute to WM, although they do not yet understand how these regions contribute to susceptibility.
"It's more evidence that WM likely results from a combination of events rather than one single gene variant," she observed. Dr. McMaster and colleagues are now collaborating with a large consortium of WM researchers to confirm and extend their findings. Plans are underway to analyze data from approximately 1,350 WM patients and more than 20,000 control persons within the next year.
"Our hope is that we will confirm our original findings and, because we now have a much larger sample, we will be able to discover additional regions of the genome that are contributing to susceptibility," Dr. McMaster said.
"A single gene is not likely to account for all WM, as we've looked carefully and others have looked too," she commented.
"So the risk for WM depends on a combination of genes and environmental exposures and possibly lifestyle factors as well, although we still estimate that approximately 25% of the heritability of WM can be attributed to these kinds of genetic changes," Dr. McMaster predicted.
Dr. McMaster has disclosed no relevant financial relationships. Dr. Treon has served as a director, officer, partner, employee, advisor, consultant, or trustee for Janssen, Pfizer, PCYC, and BioGene.
A version of this article first appeared on Medscape.com
Success of HPV vaccination: ‘Dramatic’ reduction in cervical cancer
Among young women who received the HPV vaccine when they were 12-13 years old (before their sexual debut), cervical cancer rates are 87% lower than among previous nonvaccinated generations.
“It’s been incredible to see the impact of HPV vaccination, and now we can prove it prevented hundreds of women from developing cancer in England,” senior author Peter Sasieni, MD, King’s College London, said in a statement. “To see the real-life impact of the vaccine has been truly rewarding.”
“This study provides the first direct evidence of the impact of the UK HPV vaccination campaign on cervical cancer incidence, showing a large reduction in cervical cancer rates in vaccinated cohorts,” Kate Soldan, MD, U.K. Health Security Agency, London, commented in a statement.
Vanessa Saliba, MD, a consultant epidemiologist for the U.K. Health Security Agency, agreed, saying that “these remarkable findings confirm that the HPV vaccine saves lives by dramatically reducing cervical cancer rates among women.
“This reminds us that vaccines are one of the most important tools we have to help us live longer, healthier lives,” she added.
The study was published online Nov. 3, 2021, in The Lancet.
Approached for comment on the new study, Maurice Markman, MD, president, Medicine and Science Cancer Treatment Centers of America, noted that the results of the English study are very similar to those of a Swedish study of the quadrivalent vaccine alone.
“You can put any superlatives you want in here, but these are stunningly positive results,” Dr. Markman said in an interview. He said that, as an oncologist who has been treating cervical cancer for 40 years, particularly patients with advanced cervical cancer, “I can tell you this is one of the most devastating diseases to women, and the ability to eliminate this cancer with something as simple as a vaccine is the goal of cancer therapy, and it’s been remarkably successful.
“I can only emphasize the critical importance of all parents to see that their children who are eligible for the vaccine receive it. This is a cancer prevention strategy that is unbelievably, remarkably effective and safe,” Dr. Markman added.
National vaccination program
The national HPV vaccination program in England began in 2008. Initially, the bivalent Cervarix vaccine against HPV 16 and 18 was used. HPV 16 and 18 are responsible for 70% to 80% of all cervical cancers in England, the researchers note in their article.
In 2012, the program switched to the quadrivalent HPV vaccine (Gardasil), which is effective against two additional HPV types, HPV 6 and 11. Those strains cause genital warts.
The prevention program originally recommended a three-dose regimen in which both HPV vaccines were used. Currently, two doses are given to girls younger than 15 years. In addition, a single dose of the HPV vaccine provides good protection against persistent infection. The efficacy rate of a single dose is similar to that of three doses, the authors comment.
Population-based registry
The new data come from a population-based cancer registry that shows the incidence of cervical cancer and noninvasive cervical carcinoma (CIN3) in England between January 2006 and June 2019.
The study included seven cohorts of women who were aged 20-64 years at the end of 2019. Three of these cohorts composed the vaccinated population.
The team reports that overall, from January 2006 to June 2019, there were 27,946 cases of cervical cancer and 318,058 cases of CIN3.
In the three vaccinated cohorts, there were around 450 fewer cases of cervical cancer and 17,200 fewer cases of CIN3 than would be expected in a nonvaccinated population.
The three vaccinated cohorts had been eligible to receive Cervarix when they were aged 12-13 years. A catch-up scheme aimed at 14- to 16-year-olds and 16- to 18-year-olds. Most of these persons were vaccinated through a school vaccination program.
The team analyzed the data for each of these cohorts.
Among the cohort eligible for vaccination at 12-13 years of age, 89% received at least one dose of the HPV vaccine; 85% received three shots and were fully vaccinated. Among these persons, the rate of cervical cancer was 87% lower than expected in a nonvaccinated population, and the rate of CIN3 was 97% lower than expected.
For the cohort that was eligible to be vaccinated between the ages of 14 and 16 years, the corresponding reductions were 62% for cervical cancer and 75% for CIN3.
For the cohort eligible for vaccination between the ages of 16 and 18 years (of whom 60% had received at least one dose and 45% were fully vaccinated), the corresponding reduction were 34% for cervical cancer and 39% for CIN3.
The authors acknowledge some limitations with the study, principally that cervical cancer is rare in young women, and these vaccinated populations are still young. The youngest would have been vaccinated at age 12 in 2008 and so would be only 23 years old in 2019, when the follow-up in this current study ended. The authors emphasize that because the vaccinated populations are still young, it is too early to assess the full impact of HPV vaccination on cervical cancer rates.
Editorial commentary
“The relative reductions in cervical cancer, expected as a result of the HPV vaccination program, support the anticipated vaccine effectiveness,” commented two authors of an accompanying editorial, Maggie Cruickshank, MD, University of Aberdeen (Scotland), and Mihaela Grigore, MD, University of Medicine and Pharmacy, Lasi, Romania.
“The scale of the HPV vaccination effect reported by this study should also stimulate vaccination programs in low-income and middle-income countries where the problem of cervical cancer is a far greater public health issue than in those with well established systems of vaccination and screening,” they comment.
“The most important issue, besides the availability of the vaccine ... is the education of the population to accept the vaccination because a high rate of immunization is a key element of success,” they emphasize. “Even in a wealthy country, such as England with free access to HPV immunization, uptake has not reached the 90% vaccination target of girls aged 15 years set by WHO [World Health Organization].”
The authors and editorialists disclosed no relevant financial relationships. Dr. Markman is a regular contributor to Medscape Oncology. He has received income of $250 or more from Genentech, AstraZeneca, Celgene, Clovis, and Amgen.
A version of this article first appeared on Medscape.com.
Among young women who received the HPV vaccine when they were 12-13 years old (before their sexual debut), cervical cancer rates are 87% lower than among previous nonvaccinated generations.
“It’s been incredible to see the impact of HPV vaccination, and now we can prove it prevented hundreds of women from developing cancer in England,” senior author Peter Sasieni, MD, King’s College London, said in a statement. “To see the real-life impact of the vaccine has been truly rewarding.”
“This study provides the first direct evidence of the impact of the UK HPV vaccination campaign on cervical cancer incidence, showing a large reduction in cervical cancer rates in vaccinated cohorts,” Kate Soldan, MD, U.K. Health Security Agency, London, commented in a statement.
Vanessa Saliba, MD, a consultant epidemiologist for the U.K. Health Security Agency, agreed, saying that “these remarkable findings confirm that the HPV vaccine saves lives by dramatically reducing cervical cancer rates among women.
“This reminds us that vaccines are one of the most important tools we have to help us live longer, healthier lives,” she added.
The study was published online Nov. 3, 2021, in The Lancet.
Approached for comment on the new study, Maurice Markman, MD, president, Medicine and Science Cancer Treatment Centers of America, noted that the results of the English study are very similar to those of a Swedish study of the quadrivalent vaccine alone.
“You can put any superlatives you want in here, but these are stunningly positive results,” Dr. Markman said in an interview. He said that, as an oncologist who has been treating cervical cancer for 40 years, particularly patients with advanced cervical cancer, “I can tell you this is one of the most devastating diseases to women, and the ability to eliminate this cancer with something as simple as a vaccine is the goal of cancer therapy, and it’s been remarkably successful.
“I can only emphasize the critical importance of all parents to see that their children who are eligible for the vaccine receive it. This is a cancer prevention strategy that is unbelievably, remarkably effective and safe,” Dr. Markman added.
National vaccination program
The national HPV vaccination program in England began in 2008. Initially, the bivalent Cervarix vaccine against HPV 16 and 18 was used. HPV 16 and 18 are responsible for 70% to 80% of all cervical cancers in England, the researchers note in their article.
In 2012, the program switched to the quadrivalent HPV vaccine (Gardasil), which is effective against two additional HPV types, HPV 6 and 11. Those strains cause genital warts.
The prevention program originally recommended a three-dose regimen in which both HPV vaccines were used. Currently, two doses are given to girls younger than 15 years. In addition, a single dose of the HPV vaccine provides good protection against persistent infection. The efficacy rate of a single dose is similar to that of three doses, the authors comment.
Population-based registry
The new data come from a population-based cancer registry that shows the incidence of cervical cancer and noninvasive cervical carcinoma (CIN3) in England between January 2006 and June 2019.
The study included seven cohorts of women who were aged 20-64 years at the end of 2019. Three of these cohorts composed the vaccinated population.
The team reports that overall, from January 2006 to June 2019, there were 27,946 cases of cervical cancer and 318,058 cases of CIN3.
In the three vaccinated cohorts, there were around 450 fewer cases of cervical cancer and 17,200 fewer cases of CIN3 than would be expected in a nonvaccinated population.
The three vaccinated cohorts had been eligible to receive Cervarix when they were aged 12-13 years. A catch-up scheme aimed at 14- to 16-year-olds and 16- to 18-year-olds. Most of these persons were vaccinated through a school vaccination program.
The team analyzed the data for each of these cohorts.
Among the cohort eligible for vaccination at 12-13 years of age, 89% received at least one dose of the HPV vaccine; 85% received three shots and were fully vaccinated. Among these persons, the rate of cervical cancer was 87% lower than expected in a nonvaccinated population, and the rate of CIN3 was 97% lower than expected.
For the cohort that was eligible to be vaccinated between the ages of 14 and 16 years, the corresponding reductions were 62% for cervical cancer and 75% for CIN3.
For the cohort eligible for vaccination between the ages of 16 and 18 years (of whom 60% had received at least one dose and 45% were fully vaccinated), the corresponding reduction were 34% for cervical cancer and 39% for CIN3.
The authors acknowledge some limitations with the study, principally that cervical cancer is rare in young women, and these vaccinated populations are still young. The youngest would have been vaccinated at age 12 in 2008 and so would be only 23 years old in 2019, when the follow-up in this current study ended. The authors emphasize that because the vaccinated populations are still young, it is too early to assess the full impact of HPV vaccination on cervical cancer rates.
Editorial commentary
“The relative reductions in cervical cancer, expected as a result of the HPV vaccination program, support the anticipated vaccine effectiveness,” commented two authors of an accompanying editorial, Maggie Cruickshank, MD, University of Aberdeen (Scotland), and Mihaela Grigore, MD, University of Medicine and Pharmacy, Lasi, Romania.
“The scale of the HPV vaccination effect reported by this study should also stimulate vaccination programs in low-income and middle-income countries where the problem of cervical cancer is a far greater public health issue than in those with well established systems of vaccination and screening,” they comment.
“The most important issue, besides the availability of the vaccine ... is the education of the population to accept the vaccination because a high rate of immunization is a key element of success,” they emphasize. “Even in a wealthy country, such as England with free access to HPV immunization, uptake has not reached the 90% vaccination target of girls aged 15 years set by WHO [World Health Organization].”
The authors and editorialists disclosed no relevant financial relationships. Dr. Markman is a regular contributor to Medscape Oncology. He has received income of $250 or more from Genentech, AstraZeneca, Celgene, Clovis, and Amgen.
A version of this article first appeared on Medscape.com.
Among young women who received the HPV vaccine when they were 12-13 years old (before their sexual debut), cervical cancer rates are 87% lower than among previous nonvaccinated generations.
“It’s been incredible to see the impact of HPV vaccination, and now we can prove it prevented hundreds of women from developing cancer in England,” senior author Peter Sasieni, MD, King’s College London, said in a statement. “To see the real-life impact of the vaccine has been truly rewarding.”
“This study provides the first direct evidence of the impact of the UK HPV vaccination campaign on cervical cancer incidence, showing a large reduction in cervical cancer rates in vaccinated cohorts,” Kate Soldan, MD, U.K. Health Security Agency, London, commented in a statement.
Vanessa Saliba, MD, a consultant epidemiologist for the U.K. Health Security Agency, agreed, saying that “these remarkable findings confirm that the HPV vaccine saves lives by dramatically reducing cervical cancer rates among women.
“This reminds us that vaccines are one of the most important tools we have to help us live longer, healthier lives,” she added.
The study was published online Nov. 3, 2021, in The Lancet.
Approached for comment on the new study, Maurice Markman, MD, president, Medicine and Science Cancer Treatment Centers of America, noted that the results of the English study are very similar to those of a Swedish study of the quadrivalent vaccine alone.
“You can put any superlatives you want in here, but these are stunningly positive results,” Dr. Markman said in an interview. He said that, as an oncologist who has been treating cervical cancer for 40 years, particularly patients with advanced cervical cancer, “I can tell you this is one of the most devastating diseases to women, and the ability to eliminate this cancer with something as simple as a vaccine is the goal of cancer therapy, and it’s been remarkably successful.
“I can only emphasize the critical importance of all parents to see that their children who are eligible for the vaccine receive it. This is a cancer prevention strategy that is unbelievably, remarkably effective and safe,” Dr. Markman added.
National vaccination program
The national HPV vaccination program in England began in 2008. Initially, the bivalent Cervarix vaccine against HPV 16 and 18 was used. HPV 16 and 18 are responsible for 70% to 80% of all cervical cancers in England, the researchers note in their article.
In 2012, the program switched to the quadrivalent HPV vaccine (Gardasil), which is effective against two additional HPV types, HPV 6 and 11. Those strains cause genital warts.
The prevention program originally recommended a three-dose regimen in which both HPV vaccines were used. Currently, two doses are given to girls younger than 15 years. In addition, a single dose of the HPV vaccine provides good protection against persistent infection. The efficacy rate of a single dose is similar to that of three doses, the authors comment.
Population-based registry
The new data come from a population-based cancer registry that shows the incidence of cervical cancer and noninvasive cervical carcinoma (CIN3) in England between January 2006 and June 2019.
The study included seven cohorts of women who were aged 20-64 years at the end of 2019. Three of these cohorts composed the vaccinated population.
The team reports that overall, from January 2006 to June 2019, there were 27,946 cases of cervical cancer and 318,058 cases of CIN3.
In the three vaccinated cohorts, there were around 450 fewer cases of cervical cancer and 17,200 fewer cases of CIN3 than would be expected in a nonvaccinated population.
The three vaccinated cohorts had been eligible to receive Cervarix when they were aged 12-13 years. A catch-up scheme aimed at 14- to 16-year-olds and 16- to 18-year-olds. Most of these persons were vaccinated through a school vaccination program.
The team analyzed the data for each of these cohorts.
Among the cohort eligible for vaccination at 12-13 years of age, 89% received at least one dose of the HPV vaccine; 85% received three shots and were fully vaccinated. Among these persons, the rate of cervical cancer was 87% lower than expected in a nonvaccinated population, and the rate of CIN3 was 97% lower than expected.
For the cohort that was eligible to be vaccinated between the ages of 14 and 16 years, the corresponding reductions were 62% for cervical cancer and 75% for CIN3.
For the cohort eligible for vaccination between the ages of 16 and 18 years (of whom 60% had received at least one dose and 45% were fully vaccinated), the corresponding reduction were 34% for cervical cancer and 39% for CIN3.
The authors acknowledge some limitations with the study, principally that cervical cancer is rare in young women, and these vaccinated populations are still young. The youngest would have been vaccinated at age 12 in 2008 and so would be only 23 years old in 2019, when the follow-up in this current study ended. The authors emphasize that because the vaccinated populations are still young, it is too early to assess the full impact of HPV vaccination on cervical cancer rates.
Editorial commentary
“The relative reductions in cervical cancer, expected as a result of the HPV vaccination program, support the anticipated vaccine effectiveness,” commented two authors of an accompanying editorial, Maggie Cruickshank, MD, University of Aberdeen (Scotland), and Mihaela Grigore, MD, University of Medicine and Pharmacy, Lasi, Romania.
“The scale of the HPV vaccination effect reported by this study should also stimulate vaccination programs in low-income and middle-income countries where the problem of cervical cancer is a far greater public health issue than in those with well established systems of vaccination and screening,” they comment.
“The most important issue, besides the availability of the vaccine ... is the education of the population to accept the vaccination because a high rate of immunization is a key element of success,” they emphasize. “Even in a wealthy country, such as England with free access to HPV immunization, uptake has not reached the 90% vaccination target of girls aged 15 years set by WHO [World Health Organization].”
The authors and editorialists disclosed no relevant financial relationships. Dr. Markman is a regular contributor to Medscape Oncology. He has received income of $250 or more from Genentech, AstraZeneca, Celgene, Clovis, and Amgen.
A version of this article first appeared on Medscape.com.
Some diuretics tied to increased skin cancer risk
The findings were originally reported in two Danish case-control studies in which physicians reported a fourfold increased risk of squamous cell carcinoma, and a moderate increased risk of basal cell carcinoma and cutaneous malignant melanoma in patients who used hydrochlorothiazide long-term.
And, while the new study did not find an increased risk of basal cell carcinoma and cutaneous malignant melanoma among long-term users of hydrochlorothiazide, they suggest that bendroflumethiazide “may be a safer alternative for patients at increased risk of skin cancer.” The long-term use of indapamide was associated with a moderately increased risk of cutaneous malignant melanoma but did not alter the risk of either squamous cell or basal cell carcinoma
“Our results suggest that bendroflumethiazide may be a safer alternative to hydrochlorothiazide and indapamide, especially for patients at increased risk of skin cancer, but future studies are needed to rule out a causal association between bendroflumethiazide and cutaneous malignant melanoma,” wrote authors who were led by Christoph R. Meier, PhD, a professor in pharmacy with University Hospital Basel (Switzerland) and a contributor to the Boston Collaborative Drug Surveillance Program.
This study adds to existing evidence that there is a dose-dependent increased risk of squamous cell carcinoma in users of high cumulative doses of hydrochlorothiazide, compared with non–hydrochlorothiazide users.
The study, an observational cohort study, was published earlier this year. It is based on data from the U.K.-based Clinical Practice Research Datalink. It included 271,154 new users of thiazides and thiazidelike diuretics, the majority at 87.6% having been prescribed bendroflumethiazide, 5.8% indapamide, and 3.6% hydrochlorothiazide. Outcomes were compared to those observed in 275,263 users of calcium channel blockers.
“The three primary outcomes of interest were a first-time diagnosis of cutaneous malignant melanoma, basal cell carcinoma, or squamous cell carcinoma,” the authors wrote.
Incidence rates and incidence rate ratios were estimated for both short-term and long-term users of thiazidelike diuretics and calcium channel blockers, while a propensity score (PS) analysis was done in order to control for 23 baseline covariates. The mean follow-up after PS weighting was 3.9 years for indapamide users and 5.5 years for hydrochlorothiazide users. Overall, the incidence rate ratios of squamous cell carcinoma were not markedly increased for either short-term or long-term users of thiazidelike diuretics, the authors reported.
In contrast, the incidence rate ratios of squamous cell carcinoma for hydrochlorothiazide users were increased by 29% for short-term users at an IRR of 1.29 while they were increased by almost twofold for long-term hydrochlorothiazide users at an IRR of 1.95.
Long-term use of hydrochlorothiazide was again associated with a 64% increased risk of basal cell carcinoma, compared with users of a renin-angiotensin inhibitor at a weighted IRR of 1.64.
In contrast, weighted incident rate ratios for basal cell carcinoma for both short-term and long-term thiazide users were not significantly different and results were similar for patients who took hydrochlorothiazide, indapamide, or bendroflumethiazide.
Weighted overall incident rate ratios for cutaneous malignant melanoma were not significantly different for either short-term or long-term users of thiazidelike diuretics, compared with calcium channel blocker users.
However, there was a 43% increased risk of cutaneous malignant melanoma among long-term indapamide users at a weighted IRR of 1.43, compared with calcium channel blocker users, the authors reported.
“Given the biological plausibility and the severe clinical implications of cutaneous malignant melanoma, this finding should be considered carefully,” they cautioned.
Limitations to the study include the fact that the database analyzed does not have information on sun exposure, skin characteristics, or socioeconomic status which may affect the amount of sun exposure participants received.
The authors had no conflicts of interest to declare.
The findings were originally reported in two Danish case-control studies in which physicians reported a fourfold increased risk of squamous cell carcinoma, and a moderate increased risk of basal cell carcinoma and cutaneous malignant melanoma in patients who used hydrochlorothiazide long-term.
And, while the new study did not find an increased risk of basal cell carcinoma and cutaneous malignant melanoma among long-term users of hydrochlorothiazide, they suggest that bendroflumethiazide “may be a safer alternative for patients at increased risk of skin cancer.” The long-term use of indapamide was associated with a moderately increased risk of cutaneous malignant melanoma but did not alter the risk of either squamous cell or basal cell carcinoma
“Our results suggest that bendroflumethiazide may be a safer alternative to hydrochlorothiazide and indapamide, especially for patients at increased risk of skin cancer, but future studies are needed to rule out a causal association between bendroflumethiazide and cutaneous malignant melanoma,” wrote authors who were led by Christoph R. Meier, PhD, a professor in pharmacy with University Hospital Basel (Switzerland) and a contributor to the Boston Collaborative Drug Surveillance Program.
This study adds to existing evidence that there is a dose-dependent increased risk of squamous cell carcinoma in users of high cumulative doses of hydrochlorothiazide, compared with non–hydrochlorothiazide users.
The study, an observational cohort study, was published earlier this year. It is based on data from the U.K.-based Clinical Practice Research Datalink. It included 271,154 new users of thiazides and thiazidelike diuretics, the majority at 87.6% having been prescribed bendroflumethiazide, 5.8% indapamide, and 3.6% hydrochlorothiazide. Outcomes were compared to those observed in 275,263 users of calcium channel blockers.
“The three primary outcomes of interest were a first-time diagnosis of cutaneous malignant melanoma, basal cell carcinoma, or squamous cell carcinoma,” the authors wrote.
Incidence rates and incidence rate ratios were estimated for both short-term and long-term users of thiazidelike diuretics and calcium channel blockers, while a propensity score (PS) analysis was done in order to control for 23 baseline covariates. The mean follow-up after PS weighting was 3.9 years for indapamide users and 5.5 years for hydrochlorothiazide users. Overall, the incidence rate ratios of squamous cell carcinoma were not markedly increased for either short-term or long-term users of thiazidelike diuretics, the authors reported.
In contrast, the incidence rate ratios of squamous cell carcinoma for hydrochlorothiazide users were increased by 29% for short-term users at an IRR of 1.29 while they were increased by almost twofold for long-term hydrochlorothiazide users at an IRR of 1.95.
Long-term use of hydrochlorothiazide was again associated with a 64% increased risk of basal cell carcinoma, compared with users of a renin-angiotensin inhibitor at a weighted IRR of 1.64.
In contrast, weighted incident rate ratios for basal cell carcinoma for both short-term and long-term thiazide users were not significantly different and results were similar for patients who took hydrochlorothiazide, indapamide, or bendroflumethiazide.
Weighted overall incident rate ratios for cutaneous malignant melanoma were not significantly different for either short-term or long-term users of thiazidelike diuretics, compared with calcium channel blocker users.
However, there was a 43% increased risk of cutaneous malignant melanoma among long-term indapamide users at a weighted IRR of 1.43, compared with calcium channel blocker users, the authors reported.
“Given the biological plausibility and the severe clinical implications of cutaneous malignant melanoma, this finding should be considered carefully,” they cautioned.
Limitations to the study include the fact that the database analyzed does not have information on sun exposure, skin characteristics, or socioeconomic status which may affect the amount of sun exposure participants received.
The authors had no conflicts of interest to declare.
The findings were originally reported in two Danish case-control studies in which physicians reported a fourfold increased risk of squamous cell carcinoma, and a moderate increased risk of basal cell carcinoma and cutaneous malignant melanoma in patients who used hydrochlorothiazide long-term.
And, while the new study did not find an increased risk of basal cell carcinoma and cutaneous malignant melanoma among long-term users of hydrochlorothiazide, they suggest that bendroflumethiazide “may be a safer alternative for patients at increased risk of skin cancer.” The long-term use of indapamide was associated with a moderately increased risk of cutaneous malignant melanoma but did not alter the risk of either squamous cell or basal cell carcinoma
“Our results suggest that bendroflumethiazide may be a safer alternative to hydrochlorothiazide and indapamide, especially for patients at increased risk of skin cancer, but future studies are needed to rule out a causal association between bendroflumethiazide and cutaneous malignant melanoma,” wrote authors who were led by Christoph R. Meier, PhD, a professor in pharmacy with University Hospital Basel (Switzerland) and a contributor to the Boston Collaborative Drug Surveillance Program.
This study adds to existing evidence that there is a dose-dependent increased risk of squamous cell carcinoma in users of high cumulative doses of hydrochlorothiazide, compared with non–hydrochlorothiazide users.
The study, an observational cohort study, was published earlier this year. It is based on data from the U.K.-based Clinical Practice Research Datalink. It included 271,154 new users of thiazides and thiazidelike diuretics, the majority at 87.6% having been prescribed bendroflumethiazide, 5.8% indapamide, and 3.6% hydrochlorothiazide. Outcomes were compared to those observed in 275,263 users of calcium channel blockers.
“The three primary outcomes of interest were a first-time diagnosis of cutaneous malignant melanoma, basal cell carcinoma, or squamous cell carcinoma,” the authors wrote.
Incidence rates and incidence rate ratios were estimated for both short-term and long-term users of thiazidelike diuretics and calcium channel blockers, while a propensity score (PS) analysis was done in order to control for 23 baseline covariates. The mean follow-up after PS weighting was 3.9 years for indapamide users and 5.5 years for hydrochlorothiazide users. Overall, the incidence rate ratios of squamous cell carcinoma were not markedly increased for either short-term or long-term users of thiazidelike diuretics, the authors reported.
In contrast, the incidence rate ratios of squamous cell carcinoma for hydrochlorothiazide users were increased by 29% for short-term users at an IRR of 1.29 while they were increased by almost twofold for long-term hydrochlorothiazide users at an IRR of 1.95.
Long-term use of hydrochlorothiazide was again associated with a 64% increased risk of basal cell carcinoma, compared with users of a renin-angiotensin inhibitor at a weighted IRR of 1.64.
In contrast, weighted incident rate ratios for basal cell carcinoma for both short-term and long-term thiazide users were not significantly different and results were similar for patients who took hydrochlorothiazide, indapamide, or bendroflumethiazide.
Weighted overall incident rate ratios for cutaneous malignant melanoma were not significantly different for either short-term or long-term users of thiazidelike diuretics, compared with calcium channel blocker users.
However, there was a 43% increased risk of cutaneous malignant melanoma among long-term indapamide users at a weighted IRR of 1.43, compared with calcium channel blocker users, the authors reported.
“Given the biological plausibility and the severe clinical implications of cutaneous malignant melanoma, this finding should be considered carefully,” they cautioned.
Limitations to the study include the fact that the database analyzed does not have information on sun exposure, skin characteristics, or socioeconomic status which may affect the amount of sun exposure participants received.
The authors had no conflicts of interest to declare.
FROM BRITISH JOURNAL OF DERMATOLOGY
Wearable sensors pick up infection before symptoms occur
A simple wristband containing biometric monitoring sensors is able to pick up early infection from both influenza and the common cold before symptoms develop. Moreover, it can predict the severity of the illness once it becomes symptomatic, new research shows.
“Prior to the development of symptoms, people are still infectious and can potentially infect others,” senior author Jessilyn Dunn, PhD, Duke University, Durham, N.C., told this news organization.
“That’s why it’s so important to be able to detect infection even when a person doesn’t feel symptomatic, as this would help prevent the spread of pathogens that occur before somebody knows they are sick – and which is why it is important from a public health perspective,” she added.
The study was published online Sept. 29, 2021, in JAMA Network Open.
Two challenge studies
The study involved 31 participants who were inoculated with the H1N1 influenza virus and 18 others who were inoculated with rhinovirus. The rhinovirus challenge study was conducted in 2015, and the H1N1 challenge study was carried out in 2018. Both groups of patients were inoculated via intranasal drops of either the diluted H1N1 virus or the diluted rhinovirus strain type 16.
Participants in both challenge studies wore the E4 wristband (Empatica). Those in the influenza study wore the wristband 1 day before and 11 days after being inoculated, and those in the rhinovirus study wore the wristband for 4 days before and 5 days after inoculation. The E4 wristband measures heart rate, skin temperature, electrodermal activity, and movement.
Symptoms were typical of each infection and were classified as both observable events, such as runny nose, cough, and wheezy chest, or unobservable events, such as muscle soreness and fatigue. Infection status was classified as asymptomatic or noninfectious (AON), mild, or moderate.
The biosensors contained within the wristband were able to detect the presence or absence of H1N1 infection with an accuracy of 79% within 12 hours after participants had been inoculated and an accuracy of 92% within 24 hours of being inoculated, the authors report. Thus, “we could assess whether or not a participant was infected with H1N1 between 24 and 36 hours before symptom onset,” the investigators noted.
The median time for symptom onset following the rhinovirus challenge was 36 hours after inoculation. The biosensors predicted the presence or absence of rhinovirus infection with an accuracy of 88%, the authors wrote. And when both viral challenges were combined, models predicting infection had an accuracy of 76% at 24 hours after participants being inoculated.
Prediction of severity
Twelve hours after participants had been inoculated, the technology was also able to predict the development of either AON or moderate H1N1 infection with 83% accuracy. For rhinovirus, the predictive accuracy of distinguishing AON versus moderate infection was slightly higher at 92% whereas for both viruses combined, the technology predicted the future development of AON versus moderate infection with an 84% accuracy rate.
As the authors pointed out, the ability to identify individuals during the early critical stage of viral infection could have wide-ranging effects. “In the midst of the global SARS-CoV-2 pandemic, the need for novel approaches like this has never been more apparent,” they suggested.
And in point of fact, in a not-yet peer-reviewed study using a real-time smartwatch-based alerting system again designed to detect aberrant physiologic and activity signals associated with early infection, Stanford (Calif.) University investigators found that alerts were generated for presymptomatic and asymptomatic COVID-19 infections in 78% of cases in over 3200 participants tested at a median of 3 days prior to symptom onset.
The authors also noted that their system is scalable to millions of users, thus offering a personal health monitoring system that can operate in real time.
In a comment, Steven Steinhubl, MD, a research scientist and formerly the director of digital medicine at Scripps Research’s Translational Institute, La Jolla, Calif., told this news organization that he personally has a lot of faith in this type of technology.
“Unfortunately, COVID-19 has changed our perspective about respiratory infections but if you think of the bad flu seasons we’ve had in the past, people do die from influenza, so I think there is a lot of value [in this technology], although the degree of value depends on the severity of the infection,” he said.
For example, if people actually ever go back into work together, early recognition that an employee might have influenza or another highly contagious infection could alert them to the necessity to stay home and self-isolate.
“We have a bit to go before we get there,” Dr. Steinhubl acknowledged, “but you could have a really big impact on the spread of any infectious disease that would be better for everybody.”
Dr. Dunn has disclosed no relevant financial relationships. Dr. Steinhubl is chief medical officer at physIQ, a company involved in the development of personalized analytics.
A version of this article first appeared on Medscape.com.
A simple wristband containing biometric monitoring sensors is able to pick up early infection from both influenza and the common cold before symptoms develop. Moreover, it can predict the severity of the illness once it becomes symptomatic, new research shows.
“Prior to the development of symptoms, people are still infectious and can potentially infect others,” senior author Jessilyn Dunn, PhD, Duke University, Durham, N.C., told this news organization.
“That’s why it’s so important to be able to detect infection even when a person doesn’t feel symptomatic, as this would help prevent the spread of pathogens that occur before somebody knows they are sick – and which is why it is important from a public health perspective,” she added.
The study was published online Sept. 29, 2021, in JAMA Network Open.
Two challenge studies
The study involved 31 participants who were inoculated with the H1N1 influenza virus and 18 others who were inoculated with rhinovirus. The rhinovirus challenge study was conducted in 2015, and the H1N1 challenge study was carried out in 2018. Both groups of patients were inoculated via intranasal drops of either the diluted H1N1 virus or the diluted rhinovirus strain type 16.
Participants in both challenge studies wore the E4 wristband (Empatica). Those in the influenza study wore the wristband 1 day before and 11 days after being inoculated, and those in the rhinovirus study wore the wristband for 4 days before and 5 days after inoculation. The E4 wristband measures heart rate, skin temperature, electrodermal activity, and movement.
Symptoms were typical of each infection and were classified as both observable events, such as runny nose, cough, and wheezy chest, or unobservable events, such as muscle soreness and fatigue. Infection status was classified as asymptomatic or noninfectious (AON), mild, or moderate.
The biosensors contained within the wristband were able to detect the presence or absence of H1N1 infection with an accuracy of 79% within 12 hours after participants had been inoculated and an accuracy of 92% within 24 hours of being inoculated, the authors report. Thus, “we could assess whether or not a participant was infected with H1N1 between 24 and 36 hours before symptom onset,” the investigators noted.
The median time for symptom onset following the rhinovirus challenge was 36 hours after inoculation. The biosensors predicted the presence or absence of rhinovirus infection with an accuracy of 88%, the authors wrote. And when both viral challenges were combined, models predicting infection had an accuracy of 76% at 24 hours after participants being inoculated.
Prediction of severity
Twelve hours after participants had been inoculated, the technology was also able to predict the development of either AON or moderate H1N1 infection with 83% accuracy. For rhinovirus, the predictive accuracy of distinguishing AON versus moderate infection was slightly higher at 92% whereas for both viruses combined, the technology predicted the future development of AON versus moderate infection with an 84% accuracy rate.
As the authors pointed out, the ability to identify individuals during the early critical stage of viral infection could have wide-ranging effects. “In the midst of the global SARS-CoV-2 pandemic, the need for novel approaches like this has never been more apparent,” they suggested.
And in point of fact, in a not-yet peer-reviewed study using a real-time smartwatch-based alerting system again designed to detect aberrant physiologic and activity signals associated with early infection, Stanford (Calif.) University investigators found that alerts were generated for presymptomatic and asymptomatic COVID-19 infections in 78% of cases in over 3200 participants tested at a median of 3 days prior to symptom onset.
The authors also noted that their system is scalable to millions of users, thus offering a personal health monitoring system that can operate in real time.
In a comment, Steven Steinhubl, MD, a research scientist and formerly the director of digital medicine at Scripps Research’s Translational Institute, La Jolla, Calif., told this news organization that he personally has a lot of faith in this type of technology.
“Unfortunately, COVID-19 has changed our perspective about respiratory infections but if you think of the bad flu seasons we’ve had in the past, people do die from influenza, so I think there is a lot of value [in this technology], although the degree of value depends on the severity of the infection,” he said.
For example, if people actually ever go back into work together, early recognition that an employee might have influenza or another highly contagious infection could alert them to the necessity to stay home and self-isolate.
“We have a bit to go before we get there,” Dr. Steinhubl acknowledged, “but you could have a really big impact on the spread of any infectious disease that would be better for everybody.”
Dr. Dunn has disclosed no relevant financial relationships. Dr. Steinhubl is chief medical officer at physIQ, a company involved in the development of personalized analytics.
A version of this article first appeared on Medscape.com.
A simple wristband containing biometric monitoring sensors is able to pick up early infection from both influenza and the common cold before symptoms develop. Moreover, it can predict the severity of the illness once it becomes symptomatic, new research shows.
“Prior to the development of symptoms, people are still infectious and can potentially infect others,” senior author Jessilyn Dunn, PhD, Duke University, Durham, N.C., told this news organization.
“That’s why it’s so important to be able to detect infection even when a person doesn’t feel symptomatic, as this would help prevent the spread of pathogens that occur before somebody knows they are sick – and which is why it is important from a public health perspective,” she added.
The study was published online Sept. 29, 2021, in JAMA Network Open.
Two challenge studies
The study involved 31 participants who were inoculated with the H1N1 influenza virus and 18 others who were inoculated with rhinovirus. The rhinovirus challenge study was conducted in 2015, and the H1N1 challenge study was carried out in 2018. Both groups of patients were inoculated via intranasal drops of either the diluted H1N1 virus or the diluted rhinovirus strain type 16.
Participants in both challenge studies wore the E4 wristband (Empatica). Those in the influenza study wore the wristband 1 day before and 11 days after being inoculated, and those in the rhinovirus study wore the wristband for 4 days before and 5 days after inoculation. The E4 wristband measures heart rate, skin temperature, electrodermal activity, and movement.
Symptoms were typical of each infection and were classified as both observable events, such as runny nose, cough, and wheezy chest, or unobservable events, such as muscle soreness and fatigue. Infection status was classified as asymptomatic or noninfectious (AON), mild, or moderate.
The biosensors contained within the wristband were able to detect the presence or absence of H1N1 infection with an accuracy of 79% within 12 hours after participants had been inoculated and an accuracy of 92% within 24 hours of being inoculated, the authors report. Thus, “we could assess whether or not a participant was infected with H1N1 between 24 and 36 hours before symptom onset,” the investigators noted.
The median time for symptom onset following the rhinovirus challenge was 36 hours after inoculation. The biosensors predicted the presence or absence of rhinovirus infection with an accuracy of 88%, the authors wrote. And when both viral challenges were combined, models predicting infection had an accuracy of 76% at 24 hours after participants being inoculated.
Prediction of severity
Twelve hours after participants had been inoculated, the technology was also able to predict the development of either AON or moderate H1N1 infection with 83% accuracy. For rhinovirus, the predictive accuracy of distinguishing AON versus moderate infection was slightly higher at 92% whereas for both viruses combined, the technology predicted the future development of AON versus moderate infection with an 84% accuracy rate.
As the authors pointed out, the ability to identify individuals during the early critical stage of viral infection could have wide-ranging effects. “In the midst of the global SARS-CoV-2 pandemic, the need for novel approaches like this has never been more apparent,” they suggested.
And in point of fact, in a not-yet peer-reviewed study using a real-time smartwatch-based alerting system again designed to detect aberrant physiologic and activity signals associated with early infection, Stanford (Calif.) University investigators found that alerts were generated for presymptomatic and asymptomatic COVID-19 infections in 78% of cases in over 3200 participants tested at a median of 3 days prior to symptom onset.
The authors also noted that their system is scalable to millions of users, thus offering a personal health monitoring system that can operate in real time.
In a comment, Steven Steinhubl, MD, a research scientist and formerly the director of digital medicine at Scripps Research’s Translational Institute, La Jolla, Calif., told this news organization that he personally has a lot of faith in this type of technology.
“Unfortunately, COVID-19 has changed our perspective about respiratory infections but if you think of the bad flu seasons we’ve had in the past, people do die from influenza, so I think there is a lot of value [in this technology], although the degree of value depends on the severity of the infection,” he said.
For example, if people actually ever go back into work together, early recognition that an employee might have influenza or another highly contagious infection could alert them to the necessity to stay home and self-isolate.
“We have a bit to go before we get there,” Dr. Steinhubl acknowledged, “but you could have a really big impact on the spread of any infectious disease that would be better for everybody.”
Dr. Dunn has disclosed no relevant financial relationships. Dr. Steinhubl is chief medical officer at physIQ, a company involved in the development of personalized analytics.
A version of this article first appeared on Medscape.com.