Lung Cancer

In the United States, the risk of death from cancer overall has been continuously dropping since 1991, the American Cancer Society (ACS) noted in its latest report.

There has been an overall decline of 32% in cancer deaths as of 2019, or approximately 3.5 million cancer deaths averted, the report noted.

“This success is largely because of reductions in smoking that resulted in downstream declines in lung and other smoking-related cancers,” lead author Rebecca L. Siegel of the ACS, and colleagues, noted in the latest edition of the society’s annual report on cancer rates and trends.

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

In particular, there has been a fall in both the incidence of and mortality from lung cancer, largely due to successful efforts to get people to quit smoking, but also from earlier diagnosis at a stage when the disease is far more amenable to treatment, noted the authors.

For example, the incidence of lung cancer declined by almost 3% per year in men between the years 2009 and 2018 and by 1% a year in women. Currently, the historically large gender gap in lung cancer incidence is disappearing such that in 2018, lung cancer rates were 24% higher in men than they were in women, and rates in women were actually higher in some younger age groups than they were in men.

Moreover, 28% of lung cancers detected in 2018 were found at a localized stage of disease compared with 17% in 2004.

Patients diagnosed with lung cancer are also living longer, with almost one-third of lung cancer patients still alive 3 years after their diagnosis compared with 21% a decade ago.

However, lung cancer is still the biggest contributor to cancer-related mortality overall, at a death toll of 350 per day – more than breast, prostate, and pancreatic cancer combined, the authors wrote.

This is 2.5 times higher than the death rate from colorectal cancer (CRC), the second leading cause of cancer death in the United States, they added.

Nevertheless, the decrease in lung cancer mortality accelerated from 3.1% per year between 2010 and 2014 to 5.4% per year during 2015 to 2019 in men and from 1.8% to 4.3% in women. “Overall, the lung cancer death rate has dropped by 56% from 1990 to 2019 in men and by 32% from 2002 to 2019 in women,” Ms. Siegel and colleagues emphasized.

Overall, the ACS projects there will be over 1.9 million new cancer cases and over 600,000 cancer deaths across the United States in 2022.


 

Patterns are changing

With prostate cancer now accounting for some 27% of all cancer diagnoses in men, recent trends in the incidence of prostate cancer are somewhat worrisome, the authors wrote. While the incidence for local-stage disease remained stable from 2014 through to 2018, the incidence of advanced-stage disease has increased by 6% a year since 2011. “Consequently, the proportion of distant-stage diagnoses has more than doubled,” the authors noted, “from a low of 3.9% in 2007 to 8.2% in 2018.”

The incidence of breast cancer among women has been slowly increasing by 0.5% per year since about the mid-2000s. This increase is due at least in part to declines in fertility and increases in body weight among women, the authors suggested. Declines in breast cancer mortality have slowed in recent years, dropping from 1% per year from 2013 to 2019 from 2%-3% per year seen during the 1990s and the early 2000s.

As for CRC, incidence patterns are similar by sex but differ by age. For example, incidence rates of CRC declined by about 2% per year between 2014 and 2018 in individuals 50 years and older, but they increased by 1.5% per year in adults under the age of 50. Overall, however, mortality from CRC decreased by about 2% per year between 2010 and 2019, although this trend again masks increasing mortality from CRC among younger adults, where death rates rose by 1.2% per year from 2005 through 2019 in patients under the age of 50.

The third leading cause of death in men and women combined is pancreatic cancer. Here again, mortality rates slowly increased in men between 2000 and 2013 but have remained relatively stable in women.

Between 2010 and 2019, cancers of the tongue, tonsils, and oropharynx caused by human papilloma virus (HPV) increased by about 2% per year in men and by 1% per year in women.

Death from cervical cancer – despite its being one of the most preventable cancers overall – is still the second leading cause of cancer death in women between 20 and 39 years of age. “Most of these women have never been screened so this is low-hanging fruit easily addressed by increasing access to screening and [HPV] vaccination among underserved women,” Ms. Siegel said in a statement.

On the other hand, mortality from liver cancer – having increased rapidly over the past number of decades – appears to have stabilized in more recent years.
 

Survival at 5 years

For all cancers combined, survival at 5 years between the mid-1970s and 2011 through 2017 increased from 50% to 68% for White patients and by 39% to 63% for Black patients. “For all stages combined, survival is highest for prostate cancer (98%), melanoma of the skin (93%) and female breast cancer (90%),” the authors pointed out.

In contrast, survival at 5 years is lowest, at 11% for pancreatic cancer, 20% for cancers of the liver and esophagus, and 22% for lung cancer.

Indeed, for most of the common cancers, cancer survival has improved since the mid-1970s with the exception or uterine and cervical cancer, the latter because there have been few advancements in treatment.

Even among the more rare blood and lymphoid malignancies, improvements in treatment strategies, including the use of targeted therapies, have resulted in major survival gains from around 20% in the mid-1970s for chronic myeloid leukemia (CML) patients to over 70% for CML patients diagnosed between 2011 and 2017.

Similarly, the discovery and use of immunotherapy has doubled 5-year survival rates to 30% for patients with metastatic melanoma from 15% in 2004. On the other hand, racial disparities in survival odds continue to persist. For every cancer type except for cancer of the pancreas and kidney, survival rates were lower for Black patients than for White patients, the researchers pointed out.

“Black individuals also have lower stage-specific survival for most cancer types,” the report authors noted. Indeed, after adjustment for sex, age, and stage at diagnosis, the risk of death is 33% higher in Black patients than White patients and 51% higher in American Indian/Alaska Natives compared to White patients.

That said, the overall incidence of cancer is still highest among White individuals, in part because of high rates of breast cancer in White women, which may in part reflect overdiagnosis of breast cancer in this patient population, as the authors suggested.

“However, Black women have the highest cancer mortality rates – 12% higher than White women,” they observed. Even more striking, Black women have a 4% lower incidence of breast cancer than White women but a 41% higher mortality risk from it.

As for pediatric and adolescent cancers, incidence rates may be increasing slightly among both age groups, but dramatic reductions in death by 71% among children and by 61% among adolescents from the mid-70s until now continue as a singular success story in the treatment of cancer overall.

All the authors are employed by the ACS.

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

In the United States, the risk of death from cancer overall has been continuously dropping since 1991, the American Cancer Society (ACS) noted in its latest report.

There has been an overall decline of 32% in cancer deaths as of 2019, or approximately 3.5 million cancer deaths averted, the report noted.

“This success is largely because of reductions in smoking that resulted in downstream declines in lung and other smoking-related cancers,” lead author Rebecca L. Siegel of the ACS, and colleagues, noted in the latest edition of the society’s annual report on cancer rates and trends.

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

In particular, there has been a fall in both the incidence of and mortality from lung cancer, largely due to successful efforts to get people to quit smoking, but also from earlier diagnosis at a stage when the disease is far more amenable to treatment, noted the authors.

For example, the incidence of lung cancer declined by almost 3% per year in men between the years 2009 and 2018 and by 1% a year in women. Currently, the historically large gender gap in lung cancer incidence is disappearing such that in 2018, lung cancer rates were 24% higher in men than they were in women, and rates in women were actually higher in some younger age groups than they were in men.

Moreover, 28% of lung cancers detected in 2018 were found at a localized stage of disease compared with 17% in 2004.

Patients diagnosed with lung cancer are also living longer, with almost one-third of lung cancer patients still alive 3 years after their diagnosis compared with 21% a decade ago.

However, lung cancer is still the biggest contributor to cancer-related mortality overall, at a death toll of 350 per day – more than breast, prostate, and pancreatic cancer combined, the authors wrote.

This is 2.5 times higher than the death rate from colorectal cancer (CRC), the second leading cause of cancer death in the United States, they added.

Nevertheless, the decrease in lung cancer mortality accelerated from 3.1% per year between 2010 and 2014 to 5.4% per year during 2015 to 2019 in men and from 1.8% to 4.3% in women. “Overall, the lung cancer death rate has dropped by 56% from 1990 to 2019 in men and by 32% from 2002 to 2019 in women,” Ms. Siegel and colleagues emphasized.

Overall, the ACS projects there will be over 1.9 million new cancer cases and over 600,000 cancer deaths across the United States in 2022.


 

Patterns are changing

With prostate cancer now accounting for some 27% of all cancer diagnoses in men, recent trends in the incidence of prostate cancer are somewhat worrisome, the authors wrote. While the incidence for local-stage disease remained stable from 2014 through to 2018, the incidence of advanced-stage disease has increased by 6% a year since 2011. “Consequently, the proportion of distant-stage diagnoses has more than doubled,” the authors noted, “from a low of 3.9% in 2007 to 8.2% in 2018.”

The incidence of breast cancer among women has been slowly increasing by 0.5% per year since about the mid-2000s. This increase is due at least in part to declines in fertility and increases in body weight among women, the authors suggested. Declines in breast cancer mortality have slowed in recent years, dropping from 1% per year from 2013 to 2019 from 2%-3% per year seen during the 1990s and the early 2000s.

As for CRC, incidence patterns are similar by sex but differ by age. For example, incidence rates of CRC declined by about 2% per year between 2014 and 2018 in individuals 50 years and older, but they increased by 1.5% per year in adults under the age of 50. Overall, however, mortality from CRC decreased by about 2% per year between 2010 and 2019, although this trend again masks increasing mortality from CRC among younger adults, where death rates rose by 1.2% per year from 2005 through 2019 in patients under the age of 50.

The third leading cause of death in men and women combined is pancreatic cancer. Here again, mortality rates slowly increased in men between 2000 and 2013 but have remained relatively stable in women.

Between 2010 and 2019, cancers of the tongue, tonsils, and oropharynx caused by human papilloma virus (HPV) increased by about 2% per year in men and by 1% per year in women.

Death from cervical cancer – despite its being one of the most preventable cancers overall – is still the second leading cause of cancer death in women between 20 and 39 years of age. “Most of these women have never been screened so this is low-hanging fruit easily addressed by increasing access to screening and [HPV] vaccination among underserved women,” Ms. Siegel said in a statement.

On the other hand, mortality from liver cancer – having increased rapidly over the past number of decades – appears to have stabilized in more recent years.
 

Survival at 5 years

For all cancers combined, survival at 5 years between the mid-1970s and 2011 through 2017 increased from 50% to 68% for White patients and by 39% to 63% for Black patients. “For all stages combined, survival is highest for prostate cancer (98%), melanoma of the skin (93%) and female breast cancer (90%),” the authors pointed out.

In contrast, survival at 5 years is lowest, at 11% for pancreatic cancer, 20% for cancers of the liver and esophagus, and 22% for lung cancer.

Indeed, for most of the common cancers, cancer survival has improved since the mid-1970s with the exception or uterine and cervical cancer, the latter because there have been few advancements in treatment.

Even among the more rare blood and lymphoid malignancies, improvements in treatment strategies, including the use of targeted therapies, have resulted in major survival gains from around 20% in the mid-1970s for chronic myeloid leukemia (CML) patients to over 70% for CML patients diagnosed between 2011 and 2017.

Similarly, the discovery and use of immunotherapy has doubled 5-year survival rates to 30% for patients with metastatic melanoma from 15% in 2004. On the other hand, racial disparities in survival odds continue to persist. For every cancer type except for cancer of the pancreas and kidney, survival rates were lower for Black patients than for White patients, the researchers pointed out.

“Black individuals also have lower stage-specific survival for most cancer types,” the report authors noted. Indeed, after adjustment for sex, age, and stage at diagnosis, the risk of death is 33% higher in Black patients than White patients and 51% higher in American Indian/Alaska Natives compared to White patients.

That said, the overall incidence of cancer is still highest among White individuals, in part because of high rates of breast cancer in White women, which may in part reflect overdiagnosis of breast cancer in this patient population, as the authors suggested.

“However, Black women have the highest cancer mortality rates – 12% higher than White women,” they observed. Even more striking, Black women have a 4% lower incidence of breast cancer than White women but a 41% higher mortality risk from it.

As for pediatric and adolescent cancers, incidence rates may be increasing slightly among both age groups, but dramatic reductions in death by 71% among children and by 61% among adolescents from the mid-70s until now continue as a singular success story in the treatment of cancer overall.

All the authors are employed by the ACS.

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

In the United States, the risk of death from cancer overall has been continuously dropping since 1991, the American Cancer Society (ACS) noted in its latest report.

There has been an overall decline of 32% in cancer deaths as of 2019, or approximately 3.5 million cancer deaths averted, the report noted.

“This success is largely because of reductions in smoking that resulted in downstream declines in lung and other smoking-related cancers,” lead author Rebecca L. Siegel of the ACS, and colleagues, noted in the latest edition of the society’s annual report on cancer rates and trends.

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

In particular, there has been a fall in both the incidence of and mortality from lung cancer, largely due to successful efforts to get people to quit smoking, but also from earlier diagnosis at a stage when the disease is far more amenable to treatment, noted the authors.

For example, the incidence of lung cancer declined by almost 3% per year in men between the years 2009 and 2018 and by 1% a year in women. Currently, the historically large gender gap in lung cancer incidence is disappearing such that in 2018, lung cancer rates were 24% higher in men than they were in women, and rates in women were actually higher in some younger age groups than they were in men.

Moreover, 28% of lung cancers detected in 2018 were found at a localized stage of disease compared with 17% in 2004.

Patients diagnosed with lung cancer are also living longer, with almost one-third of lung cancer patients still alive 3 years after their diagnosis compared with 21% a decade ago.

However, lung cancer is still the biggest contributor to cancer-related mortality overall, at a death toll of 350 per day – more than breast, prostate, and pancreatic cancer combined, the authors wrote.

This is 2.5 times higher than the death rate from colorectal cancer (CRC), the second leading cause of cancer death in the United States, they added.

Nevertheless, the decrease in lung cancer mortality accelerated from 3.1% per year between 2010 and 2014 to 5.4% per year during 2015 to 2019 in men and from 1.8% to 4.3% in women. “Overall, the lung cancer death rate has dropped by 56% from 1990 to 2019 in men and by 32% from 2002 to 2019 in women,” Ms. Siegel and colleagues emphasized.

Overall, the ACS projects there will be over 1.9 million new cancer cases and over 600,000 cancer deaths across the United States in 2022.


 

Patterns are changing

With prostate cancer now accounting for some 27% of all cancer diagnoses in men, recent trends in the incidence of prostate cancer are somewhat worrisome, the authors wrote. While the incidence for local-stage disease remained stable from 2014 through to 2018, the incidence of advanced-stage disease has increased by 6% a year since 2011. “Consequently, the proportion of distant-stage diagnoses has more than doubled,” the authors noted, “from a low of 3.9% in 2007 to 8.2% in 2018.”

The incidence of breast cancer among women has been slowly increasing by 0.5% per year since about the mid-2000s. This increase is due at least in part to declines in fertility and increases in body weight among women, the authors suggested. Declines in breast cancer mortality have slowed in recent years, dropping from 1% per year from 2013 to 2019 from 2%-3% per year seen during the 1990s and the early 2000s.

As for CRC, incidence patterns are similar by sex but differ by age. For example, incidence rates of CRC declined by about 2% per year between 2014 and 2018 in individuals 50 years and older, but they increased by 1.5% per year in adults under the age of 50. Overall, however, mortality from CRC decreased by about 2% per year between 2010 and 2019, although this trend again masks increasing mortality from CRC among younger adults, where death rates rose by 1.2% per year from 2005 through 2019 in patients under the age of 50.

The third leading cause of death in men and women combined is pancreatic cancer. Here again, mortality rates slowly increased in men between 2000 and 2013 but have remained relatively stable in women.

Between 2010 and 2019, cancers of the tongue, tonsils, and oropharynx caused by human papilloma virus (HPV) increased by about 2% per year in men and by 1% per year in women.

Death from cervical cancer – despite its being one of the most preventable cancers overall – is still the second leading cause of cancer death in women between 20 and 39 years of age. “Most of these women have never been screened so this is low-hanging fruit easily addressed by increasing access to screening and [HPV] vaccination among underserved women,” Ms. Siegel said in a statement.

On the other hand, mortality from liver cancer – having increased rapidly over the past number of decades – appears to have stabilized in more recent years.
 

Survival at 5 years

For all cancers combined, survival at 5 years between the mid-1970s and 2011 through 2017 increased from 50% to 68% for White patients and by 39% to 63% for Black patients. “For all stages combined, survival is highest for prostate cancer (98%), melanoma of the skin (93%) and female breast cancer (90%),” the authors pointed out.

In contrast, survival at 5 years is lowest, at 11% for pancreatic cancer, 20% for cancers of the liver and esophagus, and 22% for lung cancer.

Indeed, for most of the common cancers, cancer survival has improved since the mid-1970s with the exception or uterine and cervical cancer, the latter because there have been few advancements in treatment.

Even among the more rare blood and lymphoid malignancies, improvements in treatment strategies, including the use of targeted therapies, have resulted in major survival gains from around 20% in the mid-1970s for chronic myeloid leukemia (CML) patients to over 70% for CML patients diagnosed between 2011 and 2017.

Similarly, the discovery and use of immunotherapy has doubled 5-year survival rates to 30% for patients with metastatic melanoma from 15% in 2004. On the other hand, racial disparities in survival odds continue to persist. For every cancer type except for cancer of the pancreas and kidney, survival rates were lower for Black patients than for White patients, the researchers pointed out.

“Black individuals also have lower stage-specific survival for most cancer types,” the report authors noted. Indeed, after adjustment for sex, age, and stage at diagnosis, the risk of death is 33% higher in Black patients than White patients and 51% higher in American Indian/Alaska Natives compared to White patients.

That said, the overall incidence of cancer is still highest among White individuals, in part because of high rates of breast cancer in White women, which may in part reflect overdiagnosis of breast cancer in this patient population, as the authors suggested.

“However, Black women have the highest cancer mortality rates – 12% higher than White women,” they observed. Even more striking, Black women have a 4% lower incidence of breast cancer than White women but a 41% higher mortality risk from it.

As for pediatric and adolescent cancers, incidence rates may be increasing slightly among both age groups, but dramatic reductions in death by 71% among children and by 61% among adolescents from the mid-70s until now continue as a singular success story in the treatment of cancer overall.

All the authors are employed by the ACS.

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

To reduce risks of lung cancer mortality, interventions designed to improve high-risk groups’ uptake of low-dose CT (LDCT) lung cancer screening should focus on perceptions of lung cancer controllability, survival, and perceived effectiveness of changes in behavior, according to analysis of data from the SUMMIT study recently published in the Journal of Thoracic Oncology. Such an approach may be more effective than trying to change risk perceptions.

While 1-year survival among patients diagnosed with early-stage lung cancer is 88%, it is only 19% for those diagnosed with advanced disease. But only 27% of patients are diagnosed with early-stage disease. Screening high-risk asymptomatic adults using LDCT detects early-stage disease and significantly reduces lung cancer mortality, according to Samantha L. Quaife, PhD, of the Wolfson Institute of Population Health at Queen Mary University of London, and associates.

The effectiveness and equity of LDCT lung cancer screening as a population-level early detection strategy is compromised by low uptake among high-risk groups, the authors wrote.

In the United States, only 2% of eligible smokers have been screened since screening was first recommended in 2013. To provide a scientific evidence base for intervention, an understanding of factors making high-risk groups less likely to participate in LDCT screening is critical, Dr. Quaife and colleagues wrote.

Their longitudinal cohort study evaluating psychological correlates of lung cancer screening uptake included 44,000 ever-smokers (aged 55-77 years) who were invited to mail a self-regulatory questionnaire for lung cancer screening. Eligibility for LDCT lung cancer screening and inclusion in the SUMMIT study were further determined through telephone and in-person Lung Health Check (LHC) appointments. The primary outcome was uptake of the invitation to book an LHC appointment by telephone.

Of those invited, 7,966 (18.1%) returned the questionnaire with 7,730 (45% female; mean age, about 64 years) linked to screening uptake data. About 30% reported being current smokers with high tobacco dependence (60.3% smoking within 30 minutes of waking). The analysis from Dr. Quaife and colleagues looked at psychological correlates of lung cancer screening uptake using a psychometrically validated self-regulatory questionnaire for lung cancer screening (SRQ-LCS) to measure psychological constructs hypothesized to be associated with uptake which included consequences, emotional representation, coherence (lung cancer knowledge), treatment control, personal control, risk perception, perceived stigma, response efficacy of smoking cessation, early diagnosis behavioral response, survival from lung cancer, and treatment intention.

Among those who perceived early diagnosis to be more beneficial as a behavioral response, the positive association with uptake was strongest (adjusted odds ratio, 1.37; 95% confidence interval, 1.33-1.41). Those who perceived greater personal control (aOR, 1.09; 95% CI, 1.05-1.11) or believed their risk of lung cancer was high (aOR, 1.08; 95% CI, 1.05-1.10) were also more likely to respond. Other uptake increases were found for those who perceived smoking cessation as an effective means of reducing lung cancer risk or thought the chances of surviving early-stage lung cancer were good or fair (P < .01), and for those who perceived lung cancer as stigmatized (aOR, 1.26; 95% CI, 1.14-1.40). Most of these constructs were also perceived more negatively by current than former smokers.

Income, employment, education, social class, and housing conditions were significantly associated with many of the constructs. Greater affluence correlated with perceived personal control and benefit from early diagnosis, but more negative perceptions of the consequences of lung cancer. Also, those from more affluent areas were more likely to perceive lung cancer to be stigmatized and perceive smoking cessation to be less effective in reducing risk. Current daily smokers were less willing to be treated for early-stage disease, more pessimistic about survival, but had the highest-risk perception scores, at odds with their lower participation in lung screening trials. This contradiction, Dr. Quaife and colleagues suggested, may be explained by current smokers also holding more negative perceptions associated with lower uptake, including negative perceptions of lung cancer controllability, early diagnosis and survival, lower willingness to be treated, and belief that smoking cessation is less effective in reducing risk. All of these undermine positive responses to their high perceived risk.

“These findings pinpoint specific psychological targets for intervention,” the authors wrote. Experimental studies investigating the methods and mechanisms through which these perceptions could be changed are needed.

The study was funded by Cancer Research UK Population Research Fellowship (C50664/A24460) awarded to Dr. Quaife. The study investigators declared no support from financial organizations that might have an interest in the submitted work in the previous 3 years.

To reduce risks of lung cancer mortality, interventions designed to improve high-risk groups’ uptake of low-dose CT (LDCT) lung cancer screening should focus on perceptions of lung cancer controllability, survival, and perceived effectiveness of changes in behavior, according to analysis of data from the SUMMIT study recently published in the Journal of Thoracic Oncology. Such an approach may be more effective than trying to change risk perceptions.

While 1-year survival among patients diagnosed with early-stage lung cancer is 88%, it is only 19% for those diagnosed with advanced disease. But only 27% of patients are diagnosed with early-stage disease. Screening high-risk asymptomatic adults using LDCT detects early-stage disease and significantly reduces lung cancer mortality, according to Samantha L. Quaife, PhD, of the Wolfson Institute of Population Health at Queen Mary University of London, and associates.

The effectiveness and equity of LDCT lung cancer screening as a population-level early detection strategy is compromised by low uptake among high-risk groups, the authors wrote.

In the United States, only 2% of eligible smokers have been screened since screening was first recommended in 2013. To provide a scientific evidence base for intervention, an understanding of factors making high-risk groups less likely to participate in LDCT screening is critical, Dr. Quaife and colleagues wrote.

Their longitudinal cohort study evaluating psychological correlates of lung cancer screening uptake included 44,000 ever-smokers (aged 55-77 years) who were invited to mail a self-regulatory questionnaire for lung cancer screening. Eligibility for LDCT lung cancer screening and inclusion in the SUMMIT study were further determined through telephone and in-person Lung Health Check (LHC) appointments. The primary outcome was uptake of the invitation to book an LHC appointment by telephone.

Of those invited, 7,966 (18.1%) returned the questionnaire with 7,730 (45% female; mean age, about 64 years) linked to screening uptake data. About 30% reported being current smokers with high tobacco dependence (60.3% smoking within 30 minutes of waking). The analysis from Dr. Quaife and colleagues looked at psychological correlates of lung cancer screening uptake using a psychometrically validated self-regulatory questionnaire for lung cancer screening (SRQ-LCS) to measure psychological constructs hypothesized to be associated with uptake which included consequences, emotional representation, coherence (lung cancer knowledge), treatment control, personal control, risk perception, perceived stigma, response efficacy of smoking cessation, early diagnosis behavioral response, survival from lung cancer, and treatment intention.

Among those who perceived early diagnosis to be more beneficial as a behavioral response, the positive association with uptake was strongest (adjusted odds ratio, 1.37; 95% confidence interval, 1.33-1.41). Those who perceived greater personal control (aOR, 1.09; 95% CI, 1.05-1.11) or believed their risk of lung cancer was high (aOR, 1.08; 95% CI, 1.05-1.10) were also more likely to respond. Other uptake increases were found for those who perceived smoking cessation as an effective means of reducing lung cancer risk or thought the chances of surviving early-stage lung cancer were good or fair (P < .01), and for those who perceived lung cancer as stigmatized (aOR, 1.26; 95% CI, 1.14-1.40). Most of these constructs were also perceived more negatively by current than former smokers.

Income, employment, education, social class, and housing conditions were significantly associated with many of the constructs. Greater affluence correlated with perceived personal control and benefit from early diagnosis, but more negative perceptions of the consequences of lung cancer. Also, those from more affluent areas were more likely to perceive lung cancer to be stigmatized and perceive smoking cessation to be less effective in reducing risk. Current daily smokers were less willing to be treated for early-stage disease, more pessimistic about survival, but had the highest-risk perception scores, at odds with their lower participation in lung screening trials. This contradiction, Dr. Quaife and colleagues suggested, may be explained by current smokers also holding more negative perceptions associated with lower uptake, including negative perceptions of lung cancer controllability, early diagnosis and survival, lower willingness to be treated, and belief that smoking cessation is less effective in reducing risk. All of these undermine positive responses to their high perceived risk.

“These findings pinpoint specific psychological targets for intervention,” the authors wrote. Experimental studies investigating the methods and mechanisms through which these perceptions could be changed are needed.

The study was funded by Cancer Research UK Population Research Fellowship (C50664/A24460) awarded to Dr. Quaife. The study investigators declared no support from financial organizations that might have an interest in the submitted work in the previous 3 years.

To reduce risks of lung cancer mortality, interventions designed to improve high-risk groups’ uptake of low-dose CT (LDCT) lung cancer screening should focus on perceptions of lung cancer controllability, survival, and perceived effectiveness of changes in behavior, according to analysis of data from the SUMMIT study recently published in the Journal of Thoracic Oncology. Such an approach may be more effective than trying to change risk perceptions.

While 1-year survival among patients diagnosed with early-stage lung cancer is 88%, it is only 19% for those diagnosed with advanced disease. But only 27% of patients are diagnosed with early-stage disease. Screening high-risk asymptomatic adults using LDCT detects early-stage disease and significantly reduces lung cancer mortality, according to Samantha L. Quaife, PhD, of the Wolfson Institute of Population Health at Queen Mary University of London, and associates.

The effectiveness and equity of LDCT lung cancer screening as a population-level early detection strategy is compromised by low uptake among high-risk groups, the authors wrote.

In the United States, only 2% of eligible smokers have been screened since screening was first recommended in 2013. To provide a scientific evidence base for intervention, an understanding of factors making high-risk groups less likely to participate in LDCT screening is critical, Dr. Quaife and colleagues wrote.

Their longitudinal cohort study evaluating psychological correlates of lung cancer screening uptake included 44,000 ever-smokers (aged 55-77 years) who were invited to mail a self-regulatory questionnaire for lung cancer screening. Eligibility for LDCT lung cancer screening and inclusion in the SUMMIT study were further determined through telephone and in-person Lung Health Check (LHC) appointments. The primary outcome was uptake of the invitation to book an LHC appointment by telephone.

Of those invited, 7,966 (18.1%) returned the questionnaire with 7,730 (45% female; mean age, about 64 years) linked to screening uptake data. About 30% reported being current smokers with high tobacco dependence (60.3% smoking within 30 minutes of waking). The analysis from Dr. Quaife and colleagues looked at psychological correlates of lung cancer screening uptake using a psychometrically validated self-regulatory questionnaire for lung cancer screening (SRQ-LCS) to measure psychological constructs hypothesized to be associated with uptake which included consequences, emotional representation, coherence (lung cancer knowledge), treatment control, personal control, risk perception, perceived stigma, response efficacy of smoking cessation, early diagnosis behavioral response, survival from lung cancer, and treatment intention.

Among those who perceived early diagnosis to be more beneficial as a behavioral response, the positive association with uptake was strongest (adjusted odds ratio, 1.37; 95% confidence interval, 1.33-1.41). Those who perceived greater personal control (aOR, 1.09; 95% CI, 1.05-1.11) or believed their risk of lung cancer was high (aOR, 1.08; 95% CI, 1.05-1.10) were also more likely to respond. Other uptake increases were found for those who perceived smoking cessation as an effective means of reducing lung cancer risk or thought the chances of surviving early-stage lung cancer were good or fair (P < .01), and for those who perceived lung cancer as stigmatized (aOR, 1.26; 95% CI, 1.14-1.40). Most of these constructs were also perceived more negatively by current than former smokers.

Income, employment, education, social class, and housing conditions were significantly associated with many of the constructs. Greater affluence correlated with perceived personal control and benefit from early diagnosis, but more negative perceptions of the consequences of lung cancer. Also, those from more affluent areas were more likely to perceive lung cancer to be stigmatized and perceive smoking cessation to be less effective in reducing risk. Current daily smokers were less willing to be treated for early-stage disease, more pessimistic about survival, but had the highest-risk perception scores, at odds with their lower participation in lung screening trials. This contradiction, Dr. Quaife and colleagues suggested, may be explained by current smokers also holding more negative perceptions associated with lower uptake, including negative perceptions of lung cancer controllability, early diagnosis and survival, lower willingness to be treated, and belief that smoking cessation is less effective in reducing risk. All of these undermine positive responses to their high perceived risk.

“These findings pinpoint specific psychological targets for intervention,” the authors wrote. Experimental studies investigating the methods and mechanisms through which these perceptions could be changed are needed.

The study was funded by Cancer Research UK Population Research Fellowship (C50664/A24460) awarded to Dr. Quaife. The study investigators declared no support from financial organizations that might have an interest in the submitted work in the previous 3 years.

A new analysis of cardiovascular adverse drug reactions for non–small cell lung cancer (NCSLC)–targeted therapies finds that ALK and ROS1 inhibitors are associated with higher odds of conduction disease and QT prolongation than BRAF and EGFR inhibitors.

The findings are especially important because cardiovascular disease is known to be associated with NSCLC. Even before the start of therapy, 14%-22% of patients with stage I-IV NSCLC have heart failure and 26%-31% of patients have arrhythmias. No other study to date has described cardiovascular effects to this extent as a result of treatment.

The findings were published in the Journal of Thoracic Oncology.

Led by Joel W. Neal, MD, PhD, a medical oncologist at Stanford (Calif.) Health Care, researchers evaluated the association between NSCLC-targeted agents with arrhythmia and heart failure. Their findings are based on analysis of data from the World Health Organization pharmacovigilance database VigiBase. They found that of 98,765 adverse reactions, 61,383 occurred in patients treated with EGFR inhibitors, 15,540 were associated with ALK inhibitors, and 21,842 were associated with BRAF and MEK inhibitors. Arrhythmias occurred in 1,783 patients and 1,146 patients had heart failure.
 

The specifics

Strong associations with conduction disease and QT prolongation were found for ALK and ROS1 inhibitors, especially crizotinib. Of QT prolongation cases, 38.5% of patients on ceritinib and 18.4% of patients on crizotinib also had conduction disease and 7.9% of alectinib-associated conduction disease cases also had prolongation.

BRAF and MEK inhibitors had stronger associations with heart failure, while osimertinib, a third-generation EGFR tyrosine kinase inhibitor, was strongly associated with QT prolongation, supraventricular tachycardia, and heart failure.

ALK inhibitors were found to be 13 times more likely to lead to conduction disease and five times more likely to lead to lead to long QT syndrome as compared to all NSCLC-targeted therapies together. ALK inhibitor crizotinib had significantly higher odds of conduction disease, compared with all other targeted therapies, but of all ALK inhibitors, ceritinib and lorlatinib had the lowest odds of conduction disease. Crizotinib was 1.9 times more likely to lead to QT prolongation than other ALK inhibitors.

The EGFR inhibitor osimertinib was associated with 49 times more like to lead to long QT syndrome than other EGFR inhibitors and 6 times more likely as compared with all other targeted therapies. The EGFR inhibitor gefitinib was twice as likely than other EGFR inhibitors to lead to conduction disease. The third-generation EGFR inhibitor osimertinib had approximately two times higher odds of supraventricular tachycardia than other EGFR inhibitors.

Osimertinib was associated with 6.8 times higher chances of heart failure, compared with other EGFR inhibitors, and 3.6 times more than other targeted therapies. Dabrafenib and trametinib were associated with two to three times higher odds of heart failure as compared with other targeted therapies.

“There is a need for an understanding of the mechanisms underlying these toxicities and for additional studies to establish standardized guidelines for monitoring, particularly for osimertinib, crizotinib, and alectinib,” the authors wrote

The authors disclosed a number of paid advisory roles with various pharmaceutical companies.

A new analysis of cardiovascular adverse drug reactions for non–small cell lung cancer (NCSLC)–targeted therapies finds that ALK and ROS1 inhibitors are associated with higher odds of conduction disease and QT prolongation than BRAF and EGFR inhibitors.

The findings are especially important because cardiovascular disease is known to be associated with NSCLC. Even before the start of therapy, 14%-22% of patients with stage I-IV NSCLC have heart failure and 26%-31% of patients have arrhythmias. No other study to date has described cardiovascular effects to this extent as a result of treatment.

The findings were published in the Journal of Thoracic Oncology.

Led by Joel W. Neal, MD, PhD, a medical oncologist at Stanford (Calif.) Health Care, researchers evaluated the association between NSCLC-targeted agents with arrhythmia and heart failure. Their findings are based on analysis of data from the World Health Organization pharmacovigilance database VigiBase. They found that of 98,765 adverse reactions, 61,383 occurred in patients treated with EGFR inhibitors, 15,540 were associated with ALK inhibitors, and 21,842 were associated with BRAF and MEK inhibitors. Arrhythmias occurred in 1,783 patients and 1,146 patients had heart failure.
 

The specifics

Strong associations with conduction disease and QT prolongation were found for ALK and ROS1 inhibitors, especially crizotinib. Of QT prolongation cases, 38.5% of patients on ceritinib and 18.4% of patients on crizotinib also had conduction disease and 7.9% of alectinib-associated conduction disease cases also had prolongation.

BRAF and MEK inhibitors had stronger associations with heart failure, while osimertinib, a third-generation EGFR tyrosine kinase inhibitor, was strongly associated with QT prolongation, supraventricular tachycardia, and heart failure.

ALK inhibitors were found to be 13 times more likely to lead to conduction disease and five times more likely to lead to lead to long QT syndrome as compared to all NSCLC-targeted therapies together. ALK inhibitor crizotinib had significantly higher odds of conduction disease, compared with all other targeted therapies, but of all ALK inhibitors, ceritinib and lorlatinib had the lowest odds of conduction disease. Crizotinib was 1.9 times more likely to lead to QT prolongation than other ALK inhibitors.

The EGFR inhibitor osimertinib was associated with 49 times more like to lead to long QT syndrome than other EGFR inhibitors and 6 times more likely as compared with all other targeted therapies. The EGFR inhibitor gefitinib was twice as likely than other EGFR inhibitors to lead to conduction disease. The third-generation EGFR inhibitor osimertinib had approximately two times higher odds of supraventricular tachycardia than other EGFR inhibitors.

Osimertinib was associated with 6.8 times higher chances of heart failure, compared with other EGFR inhibitors, and 3.6 times more than other targeted therapies. Dabrafenib and trametinib were associated with two to three times higher odds of heart failure as compared with other targeted therapies.

“There is a need for an understanding of the mechanisms underlying these toxicities and for additional studies to establish standardized guidelines for monitoring, particularly for osimertinib, crizotinib, and alectinib,” the authors wrote

The authors disclosed a number of paid advisory roles with various pharmaceutical companies.

A new analysis of cardiovascular adverse drug reactions for non–small cell lung cancer (NCSLC)–targeted therapies finds that ALK and ROS1 inhibitors are associated with higher odds of conduction disease and QT prolongation than BRAF and EGFR inhibitors.

The findings are especially important because cardiovascular disease is known to be associated with NSCLC. Even before the start of therapy, 14%-22% of patients with stage I-IV NSCLC have heart failure and 26%-31% of patients have arrhythmias. No other study to date has described cardiovascular effects to this extent as a result of treatment.

The findings were published in the Journal of Thoracic Oncology.

Led by Joel W. Neal, MD, PhD, a medical oncologist at Stanford (Calif.) Health Care, researchers evaluated the association between NSCLC-targeted agents with arrhythmia and heart failure. Their findings are based on analysis of data from the World Health Organization pharmacovigilance database VigiBase. They found that of 98,765 adverse reactions, 61,383 occurred in patients treated with EGFR inhibitors, 15,540 were associated with ALK inhibitors, and 21,842 were associated with BRAF and MEK inhibitors. Arrhythmias occurred in 1,783 patients and 1,146 patients had heart failure.
 

The specifics

Strong associations with conduction disease and QT prolongation were found for ALK and ROS1 inhibitors, especially crizotinib. Of QT prolongation cases, 38.5% of patients on ceritinib and 18.4% of patients on crizotinib also had conduction disease and 7.9% of alectinib-associated conduction disease cases also had prolongation.

BRAF and MEK inhibitors had stronger associations with heart failure, while osimertinib, a third-generation EGFR tyrosine kinase inhibitor, was strongly associated with QT prolongation, supraventricular tachycardia, and heart failure.

ALK inhibitors were found to be 13 times more likely to lead to conduction disease and five times more likely to lead to lead to long QT syndrome as compared to all NSCLC-targeted therapies together. ALK inhibitor crizotinib had significantly higher odds of conduction disease, compared with all other targeted therapies, but of all ALK inhibitors, ceritinib and lorlatinib had the lowest odds of conduction disease. Crizotinib was 1.9 times more likely to lead to QT prolongation than other ALK inhibitors.

The EGFR inhibitor osimertinib was associated with 49 times more like to lead to long QT syndrome than other EGFR inhibitors and 6 times more likely as compared with all other targeted therapies. The EGFR inhibitor gefitinib was twice as likely than other EGFR inhibitors to lead to conduction disease. The third-generation EGFR inhibitor osimertinib had approximately two times higher odds of supraventricular tachycardia than other EGFR inhibitors.

Osimertinib was associated with 6.8 times higher chances of heart failure, compared with other EGFR inhibitors, and 3.6 times more than other targeted therapies. Dabrafenib and trametinib were associated with two to three times higher odds of heart failure as compared with other targeted therapies.

“There is a need for an understanding of the mechanisms underlying these toxicities and for additional studies to establish standardized guidelines for monitoring, particularly for osimertinib, crizotinib, and alectinib,” the authors wrote

The authors disclosed a number of paid advisory roles with various pharmaceutical companies.

Two cancer drugs and one drug to treat sickle cell disease will likely reach the European market soon, following approval recommendations from a European Medicines Agency panel.

The drugs are enfortumab vedotin (Padcev, Astellas/Seagen) for urothelial cancer, tepotinib (Tepmetko, Merck) for non–small cell lung cancer (NSCLC), and voxelotor (Oxbryta, Global Blood Therapeutics) for sickle cell hemolytic anemia.

EMA’s Committee for Medicinal Products for Human Use gave the nod for marketing authorization on Dec. 16, 2021, and agency approval generally follows about 6 weeks later. All three products are already approved in the United States.
 

Enfortumab vedotin for urothelial cancer

The recommendation for Astellas’ antibody-drug conjugate infusion was based on the phase 3 EV-301 trial, which found about a 4-month median overall survival benefit with the antibody-drug conjugate versus investigator-chosen chemotherapy across 608 patients with locally advanced or metastatic urothelial carcinoma previously treated with platinum-based chemotherapy and a programmed death 1 or PD–ligand 1 inhibitor.

The planned European indication is for adults with locally advanced or metastatic disease who met the same criteria – previous platinum-based chemotherapy plus a PD-1 or PD-L1 inhibitor.

The Food and Drug Administration approval came in December 2019, and with the same indication as well as for patients ineligible for cisplatin-containing chemotherapy who have had one or more prior lines of therapy. The U.S. labeling carries a boxed warning of severe and fatal skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis.
 

Tepotinib for NSCLC

The recommendation for Merck’s tepotinib, a once-daily oral MET inhibitor, followed results from the phase 2 VISION study. The study found an investigator-assessed response rate of 56% across 152 patients with advanced or metastatic NSCLC with a confirmed MET exon 14 skipping mutation, regardless of previous therapy.

The planned European indication will be for monotherapy in adults with advanced disease harboring the mutation who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy.

The FDA approved the drug in February 2021, and carries the same indication, minus the prior therapy requirement.
 

Voxelotor for sickle cell disease

Voxelotor is an oral hemoglobin S polymerization inhibitor from Global Blood Therapeutics.

The European approval recommendation was based on a phase 3 trial in 274 patients with sickle cell disease that found a greater than 1 g/dL increase in hemoglobin levels at 24 weeks in 51.1% of patients versus 6.5% randomized to placebo, regardless of whether patients were on concomitant hydroxyurea.

The small molecule binds and stabilizes hemoglobin, preventing the hemoglobin polymerization that causes red blood cells to sickle.

“There is a high unmet need for medicines to treat hemolytic anemia” in sickle cell disease because available treatment options are limited to blood transfusions and allogenic hematopoietic stem cell transplantation,” the EMA explained in a press release announcing the approval recommendation.

The planned European indication is for treating hemolytic anemia in sickle cell disease in patients 12 years or older either alone or in combination with hydroxycarbamide (hydroxyurea).

The FDA approved the agent in November 2019 for the same indication, but can be given to children as young as 4 years old.

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

Two cancer drugs and one drug to treat sickle cell disease will likely reach the European market soon, following approval recommendations from a European Medicines Agency panel.

The drugs are enfortumab vedotin (Padcev, Astellas/Seagen) for urothelial cancer, tepotinib (Tepmetko, Merck) for non–small cell lung cancer (NSCLC), and voxelotor (Oxbryta, Global Blood Therapeutics) for sickle cell hemolytic anemia.

EMA’s Committee for Medicinal Products for Human Use gave the nod for marketing authorization on Dec. 16, 2021, and agency approval generally follows about 6 weeks later. All three products are already approved in the United States.
 

Enfortumab vedotin for urothelial cancer

The recommendation for Astellas’ antibody-drug conjugate infusion was based on the phase 3 EV-301 trial, which found about a 4-month median overall survival benefit with the antibody-drug conjugate versus investigator-chosen chemotherapy across 608 patients with locally advanced or metastatic urothelial carcinoma previously treated with platinum-based chemotherapy and a programmed death 1 or PD–ligand 1 inhibitor.

The planned European indication is for adults with locally advanced or metastatic disease who met the same criteria – previous platinum-based chemotherapy plus a PD-1 or PD-L1 inhibitor.

The Food and Drug Administration approval came in December 2019, and with the same indication as well as for patients ineligible for cisplatin-containing chemotherapy who have had one or more prior lines of therapy. The U.S. labeling carries a boxed warning of severe and fatal skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis.
 

Tepotinib for NSCLC

The recommendation for Merck’s tepotinib, a once-daily oral MET inhibitor, followed results from the phase 2 VISION study. The study found an investigator-assessed response rate of 56% across 152 patients with advanced or metastatic NSCLC with a confirmed MET exon 14 skipping mutation, regardless of previous therapy.

The planned European indication will be for monotherapy in adults with advanced disease harboring the mutation who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy.

The FDA approved the drug in February 2021, and carries the same indication, minus the prior therapy requirement.
 

Voxelotor for sickle cell disease

Voxelotor is an oral hemoglobin S polymerization inhibitor from Global Blood Therapeutics.

The European approval recommendation was based on a phase 3 trial in 274 patients with sickle cell disease that found a greater than 1 g/dL increase in hemoglobin levels at 24 weeks in 51.1% of patients versus 6.5% randomized to placebo, regardless of whether patients were on concomitant hydroxyurea.

The small molecule binds and stabilizes hemoglobin, preventing the hemoglobin polymerization that causes red blood cells to sickle.

“There is a high unmet need for medicines to treat hemolytic anemia” in sickle cell disease because available treatment options are limited to blood transfusions and allogenic hematopoietic stem cell transplantation,” the EMA explained in a press release announcing the approval recommendation.

The planned European indication is for treating hemolytic anemia in sickle cell disease in patients 12 years or older either alone or in combination with hydroxycarbamide (hydroxyurea).

The FDA approved the agent in November 2019 for the same indication, but can be given to children as young as 4 years old.

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

Two cancer drugs and one drug to treat sickle cell disease will likely reach the European market soon, following approval recommendations from a European Medicines Agency panel.

The drugs are enfortumab vedotin (Padcev, Astellas/Seagen) for urothelial cancer, tepotinib (Tepmetko, Merck) for non–small cell lung cancer (NSCLC), and voxelotor (Oxbryta, Global Blood Therapeutics) for sickle cell hemolytic anemia.

EMA’s Committee for Medicinal Products for Human Use gave the nod for marketing authorization on Dec. 16, 2021, and agency approval generally follows about 6 weeks later. All three products are already approved in the United States.
 

Enfortumab vedotin for urothelial cancer

The recommendation for Astellas’ antibody-drug conjugate infusion was based on the phase 3 EV-301 trial, which found about a 4-month median overall survival benefit with the antibody-drug conjugate versus investigator-chosen chemotherapy across 608 patients with locally advanced or metastatic urothelial carcinoma previously treated with platinum-based chemotherapy and a programmed death 1 or PD–ligand 1 inhibitor.

The planned European indication is for adults with locally advanced or metastatic disease who met the same criteria – previous platinum-based chemotherapy plus a PD-1 or PD-L1 inhibitor.

The Food and Drug Administration approval came in December 2019, and with the same indication as well as for patients ineligible for cisplatin-containing chemotherapy who have had one or more prior lines of therapy. The U.S. labeling carries a boxed warning of severe and fatal skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis.
 

Tepotinib for NSCLC

The recommendation for Merck’s tepotinib, a once-daily oral MET inhibitor, followed results from the phase 2 VISION study. The study found an investigator-assessed response rate of 56% across 152 patients with advanced or metastatic NSCLC with a confirmed MET exon 14 skipping mutation, regardless of previous therapy.

The planned European indication will be for monotherapy in adults with advanced disease harboring the mutation who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy.

The FDA approved the drug in February 2021, and carries the same indication, minus the prior therapy requirement.
 

Voxelotor for sickle cell disease

Voxelotor is an oral hemoglobin S polymerization inhibitor from Global Blood Therapeutics.

The European approval recommendation was based on a phase 3 trial in 274 patients with sickle cell disease that found a greater than 1 g/dL increase in hemoglobin levels at 24 weeks in 51.1% of patients versus 6.5% randomized to placebo, regardless of whether patients were on concomitant hydroxyurea.

The small molecule binds and stabilizes hemoglobin, preventing the hemoglobin polymerization that causes red blood cells to sickle.

“There is a high unmet need for medicines to treat hemolytic anemia” in sickle cell disease because available treatment options are limited to blood transfusions and allogenic hematopoietic stem cell transplantation,” the EMA explained in a press release announcing the approval recommendation.

The planned European indication is for treating hemolytic anemia in sickle cell disease in patients 12 years or older either alone or in combination with hydroxycarbamide (hydroxyurea).

The FDA approved the agent in November 2019 for the same indication, but can be given to children as young as 4 years old.

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

In non–small cell lung cancer (NSCLC), earlier detection may be an under-appreciated factor in recent trends of declining mortality, according to a new analysis of data from the Surveillance, Epidemiology, and End Results (SEER) registries published in JAMA Network Open. Between 2006 and 2016, a stage shift occurred with an increase in stage 1 and 2 diagnoses and a decrease in stage 3 and 4 diagnoses.

While targeted therapy and immunotherapy have rightfully been credited with improved NSCLC survival, the new results underline the importance of screening, according to study author Emanuela Taioli, MD, PhD, director of the Institute for Translational Epidemiology and the associate director for population science at the Tisch Cancer Institute at Mount Sinai, New York.

She noted that the average survival for stage 1 or stage 2 patients was 57 months, but just 7 months when the stage diagnosis was 3 or 4. “So being diagnosed with stage 1 and 2 is a major driver of better survival,” said Dr. Taioli in an interview.

The study included 312,382 individuals diagnosed with NSCLC (53.4% male; median age, 68). Incidence-based, 5-year mortality declined by 3.7% (95% confidence interval, 3.4%-4.1%). Stage 1 or 2 diagnoses increased from 26.5% to 31.2% of diagnoses between 2006 and 2016 (average annual percentage change, 1.5%; 95% CI, 0.5%-2.5%).

“Immunotherapy is a very exciting field. And it is an important contributor for people who have a disease that can be treated with immunotherapy, so that’s why people focus on that. But if you can diagnose the cancer earlier, that’s the best bet,” Dr. Taioli said.

Unfortunately, many patients and physicians haven’t received that message. Even though computed tomography lung cancer screening is covered by Medicare for current or former smokers, only about 7% of eligible patients undergo annual screening. Dr. Taioli said that a belief persists that lung cancer is so deadly that early detection isn’t effective.

But advances in therapy and surgery have changed that outlook. “It’s not true anymore. People don’t know, and physicians are not educated to the idea that lung cancer can be diagnosed earlier and save lives,” she said.

People who have quit smoking may be relatively easy to convince. “They made a big step, because quitting smoking is incredibly hard. I think they will be amenable to screening because they are in a phase [of life] in which they want to take care of themselves. The physician should really explain the benefits, and I don’t think they do it very clearly now,” Dr. Taioli said.

The study is limited by its retrospective nature, and it did not include information on diagnostic method or many NSCLC risk factors.

Dr. Taioli has no relevant financial disclosures.

In non–small cell lung cancer (NSCLC), earlier detection may be an under-appreciated factor in recent trends of declining mortality, according to a new analysis of data from the Surveillance, Epidemiology, and End Results (SEER) registries published in JAMA Network Open. Between 2006 and 2016, a stage shift occurred with an increase in stage 1 and 2 diagnoses and a decrease in stage 3 and 4 diagnoses.

While targeted therapy and immunotherapy have rightfully been credited with improved NSCLC survival, the new results underline the importance of screening, according to study author Emanuela Taioli, MD, PhD, director of the Institute for Translational Epidemiology and the associate director for population science at the Tisch Cancer Institute at Mount Sinai, New York.

She noted that the average survival for stage 1 or stage 2 patients was 57 months, but just 7 months when the stage diagnosis was 3 or 4. “So being diagnosed with stage 1 and 2 is a major driver of better survival,” said Dr. Taioli in an interview.

The study included 312,382 individuals diagnosed with NSCLC (53.4% male; median age, 68). Incidence-based, 5-year mortality declined by 3.7% (95% confidence interval, 3.4%-4.1%). Stage 1 or 2 diagnoses increased from 26.5% to 31.2% of diagnoses between 2006 and 2016 (average annual percentage change, 1.5%; 95% CI, 0.5%-2.5%).

“Immunotherapy is a very exciting field. And it is an important contributor for people who have a disease that can be treated with immunotherapy, so that’s why people focus on that. But if you can diagnose the cancer earlier, that’s the best bet,” Dr. Taioli said.

Unfortunately, many patients and physicians haven’t received that message. Even though computed tomography lung cancer screening is covered by Medicare for current or former smokers, only about 7% of eligible patients undergo annual screening. Dr. Taioli said that a belief persists that lung cancer is so deadly that early detection isn’t effective.

But advances in therapy and surgery have changed that outlook. “It’s not true anymore. People don’t know, and physicians are not educated to the idea that lung cancer can be diagnosed earlier and save lives,” she said.

People who have quit smoking may be relatively easy to convince. “They made a big step, because quitting smoking is incredibly hard. I think they will be amenable to screening because they are in a phase [of life] in which they want to take care of themselves. The physician should really explain the benefits, and I don’t think they do it very clearly now,” Dr. Taioli said.

The study is limited by its retrospective nature, and it did not include information on diagnostic method or many NSCLC risk factors.

Dr. Taioli has no relevant financial disclosures.

In non–small cell lung cancer (NSCLC), earlier detection may be an under-appreciated factor in recent trends of declining mortality, according to a new analysis of data from the Surveillance, Epidemiology, and End Results (SEER) registries published in JAMA Network Open. Between 2006 and 2016, a stage shift occurred with an increase in stage 1 and 2 diagnoses and a decrease in stage 3 and 4 diagnoses.

While targeted therapy and immunotherapy have rightfully been credited with improved NSCLC survival, the new results underline the importance of screening, according to study author Emanuela Taioli, MD, PhD, director of the Institute for Translational Epidemiology and the associate director for population science at the Tisch Cancer Institute at Mount Sinai, New York.

She noted that the average survival for stage 1 or stage 2 patients was 57 months, but just 7 months when the stage diagnosis was 3 or 4. “So being diagnosed with stage 1 and 2 is a major driver of better survival,” said Dr. Taioli in an interview.

The study included 312,382 individuals diagnosed with NSCLC (53.4% male; median age, 68). Incidence-based, 5-year mortality declined by 3.7% (95% confidence interval, 3.4%-4.1%). Stage 1 or 2 diagnoses increased from 26.5% to 31.2% of diagnoses between 2006 and 2016 (average annual percentage change, 1.5%; 95% CI, 0.5%-2.5%).

“Immunotherapy is a very exciting field. And it is an important contributor for people who have a disease that can be treated with immunotherapy, so that’s why people focus on that. But if you can diagnose the cancer earlier, that’s the best bet,” Dr. Taioli said.

Unfortunately, many patients and physicians haven’t received that message. Even though computed tomography lung cancer screening is covered by Medicare for current or former smokers, only about 7% of eligible patients undergo annual screening. Dr. Taioli said that a belief persists that lung cancer is so deadly that early detection isn’t effective.

But advances in therapy and surgery have changed that outlook. “It’s not true anymore. People don’t know, and physicians are not educated to the idea that lung cancer can be diagnosed earlier and save lives,” she said.

People who have quit smoking may be relatively easy to convince. “They made a big step, because quitting smoking is incredibly hard. I think they will be amenable to screening because they are in a phase [of life] in which they want to take care of themselves. The physician should really explain the benefits, and I don’t think they do it very clearly now,” Dr. Taioli said.

The study is limited by its retrospective nature, and it did not include information on diagnostic method or many NSCLC risk factors.

Dr. Taioli has no relevant financial disclosures.

People with cancer are often desperate to know what caused their disease. Was it something they did? Something they could have prevented?

vitanovski/Thinkstock.com

In a recent analysis, experts estimated that about 40% of cancers can be explained by known, often modifiable risk factors. Smoking and obesity represent the primary drivers, though a host of other factors – germline mutations, alcohol, infections, or environmental pollutants like asbestos – contribute to cancer risk as well.

But what about the remaining 60% of cancers?

The study suggests that, although many of these cases likely have an underlying lifestyle or environmental component, experts still do not fully understand their origin story. And a small but significant number may simply be caused by chance.

Here’s what experts suspect those missing causes might be, and why they can be so difficult to confirm.
 

Possibility 1: Known risk factors contribute more than we realize

For certain factors, a straight line can be drawn to cancer.

Take smoking, for instance. Decades of research have helped scientists clearly delineate tobacco’s carcinogenic effects. Researchers have pinpointed a unique set of mutations in the tumors of smokers that can be seen when cells grown in a dish are exposed to the carcinogens present in tobacco.

In addition, experts have been able to collect robust data from epidemiologic studies on smoking prevalence as well as associated cancer risks and deaths, in large part because an individual’s lifetime tobacco exposure is fairly easy to measure.

“The evidence for smoking is incredibly consistent,” Paul Brennan, PhD, a cancer epidemiologist at the World Health Organization’s International Agency for Research on Cancer, said in an interview.

For other known risk factors, such as obesity and air pollution, many more questions than answers remain.

Because of the limitations in how such factors are measured, we are likely downplaying their effects, said Richard Martin, PhD, a professor of clinical epidemiology at the University of Bristol (England).

Take obesity. Excess body weight is associated with an increased risk of at least 13 cancers. Although risk estimates vary by study and cancer type, according to a global snapshot from 2012, being overweight or obese accounted for about 4% of all cancers worldwide – 1% in low-income countries and as high as 8% in high-income countries.

However, Dr. Brennan believes “we have underestimated the effect of obesity [on cancer].”

A key reason, he said, is most studies use body mass index to determine whether someone is overweight or obese, but BMI is a poor measure of body fat. BMI does not differentiate between fat and muscle, which means two people with the same height and weight can have the same BMI, even if one is an athlete who eats lean meats and vegetables while the other lives a sedentary life and consumes large quantities of processed foods and alcohol.

On top of that, studies often only calculate a person’s BMI once, and a single measurement can’t tell you how a person’s weight has fluctuated in recent years or across different stages of their life. However, recent analyses suggest that obesity status over time may be more relevant to cancer risk than one-off measures.

In addition, many studies now suggest that alterations to our gut microbes and high blood insulin level – often seen in people who are overweight or obese – may increase the risk of cancer and speed the growth of tumors.

When these additional factors are considered, the impact of excess body fat may ultimately play a much more significant role in cancer risk. In fact, according to Dr. Brennan, “if we estimate [the effects of obesity] properly, it might at some point become the main cause of cancer.”
 

Possibility 2: Environmental or lifestyle factors remain under the radar

Researchers have linked many substances we consume or are exposed to in our daily lives – air pollution, toxins from industrial waste, and highly processed foods – to cancer. But the extent or contribution of potential carcinogens in our surroundings, particularly those found almost everywhere at low levels, is still largely unknown.

One simple reason is the effects of many of these substances remain difficult to assess. For instance, it is much harder to study the impact of pollutants found in food or water, in which a given population will share similar exposure levels versus tobacco, where it is possible to compare a person who smokes a pack of cigarettes a day with a person who does not smoke.

“If you’ve got exposures that are ubiquitous, it can be difficult to discern their [individual] roles,” Dr. Martin said. “There are many causes that we [likely] don’t really know because everyone has been exposed.”

On the flip side, some carcinogenic substances that people encounter for limited periods might be missed if studies are not performed at the time of exposure.

“What’s in the body at age 40 may not reflect what you were exposed at age 5-10 on the playground or soccer field,” said Graham Colditz, MD, PhD, an epidemiologist and public health expert at Washington University, St. Louis. “The technology keeps changing so we can get better measures of what you’ve got exposure to today, but how that relates to 5, 10, 15 years ago is probably very variable.”

In addition, researchers have found that many carcinogens do not cause specific mutations in a cell’s DNA; rather, studies suggest that most carcinogens lead to cancer-promoting changes in cells, such as inflammation.

“We need to think of how potential carcinogens are causing cancer,” Dr. Brennan said. Instead of provoking mutations, potential carcinogens may use a “whole other kind of pathway.” When, for instance, inflammation becomes chronic, it may spur a cascade of events that ultimately leads to cancer.

Finally, not much is known about what causes cancers in low- and middle-income countries. Most of the research to date has been in high-income countries, such the United States, Australia, and parts of Europe.

“There’s a real lack of robust epidemiological studies in other parts of the world, Latin America, Africa, parts of Asia,” Marc Gunter, PhD, a molecular epidemiologist at the IARC, told this news organization.
 

Possibility 3: Some cancers occur by chance

When it comes to cancer risk, an element of chance may be at play. Cancer can occur in individuals who have very little exposure to known carcinogens or have no family history of cancer.

“We all know there are people who get cancer who eat very healthy diets, are never overweight, and never smoke,” Dr. Gunter said. “Then there are people on the other end of the extreme who don’t get cancer.”

But what fraction of cancers are attributable to chance?

A controversial 2017 study published in Science suggested that, based on the rate of cell turnover in healthy tissues in the lung, pancreas, and other parts of the body, only about one-third of cancers could be linked to environmental or genetic factors. The rest, the authors claimed, occurred because of random mutations that accumulated in a person’s DNA – in other words, bad luck.

That study brought on a flood of criticism from scientists who pointed to serious flaws in the work that led the researchers to significantly overestimate the share of chance-related cancers.

The actual proportion of cancers that occur by chance is much lower, according to Dr. Brennan. “If you look at international comparisons [of cancer rates] and take a conservative estimate, you see that maybe 10% or 15% of cancers are really chance.”

Whether some cancers are caused by bad luck or undiscovered risk factors remains an open question.

But the bottom line is many unknown causes of cancer are likely environmental or lifestyle related, which means that, in theory, they can be altered, even prevented.

“There is always going to be some element of chance, but you can modify your chance, depending on your lifestyle and maybe other factors, which we don’t fully understand yet,” Dr. Gunter said.

The good news is that, when it comes to prevention, there are many ways to modify our behaviors – such as consuming fewer processed meats, going for a daily walk, or getting vaccinated against cancer-causing viruses – to improve our chances of living cancer free. And as scientists better understand more about what causes cancer, possibilities for prevention will only grow.

“There is a constant, slow growth [in knowledge] that is lowering the overall risk of cancer,” Dr. Brennan said. “We’re never going to eliminate cancer, but we will be able to control it as a disease.”

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

People with cancer are often desperate to know what caused their disease. Was it something they did? Something they could have prevented?

vitanovski/Thinkstock.com

In a recent analysis, experts estimated that about 40% of cancers can be explained by known, often modifiable risk factors. Smoking and obesity represent the primary drivers, though a host of other factors – germline mutations, alcohol, infections, or environmental pollutants like asbestos – contribute to cancer risk as well.

But what about the remaining 60% of cancers?

The study suggests that, although many of these cases likely have an underlying lifestyle or environmental component, experts still do not fully understand their origin story. And a small but significant number may simply be caused by chance.

Here’s what experts suspect those missing causes might be, and why they can be so difficult to confirm.
 

Possibility 1: Known risk factors contribute more than we realize

For certain factors, a straight line can be drawn to cancer.

Take smoking, for instance. Decades of research have helped scientists clearly delineate tobacco’s carcinogenic effects. Researchers have pinpointed a unique set of mutations in the tumors of smokers that can be seen when cells grown in a dish are exposed to the carcinogens present in tobacco.

In addition, experts have been able to collect robust data from epidemiologic studies on smoking prevalence as well as associated cancer risks and deaths, in large part because an individual’s lifetime tobacco exposure is fairly easy to measure.

“The evidence for smoking is incredibly consistent,” Paul Brennan, PhD, a cancer epidemiologist at the World Health Organization’s International Agency for Research on Cancer, said in an interview.

For other known risk factors, such as obesity and air pollution, many more questions than answers remain.

Because of the limitations in how such factors are measured, we are likely downplaying their effects, said Richard Martin, PhD, a professor of clinical epidemiology at the University of Bristol (England).

Take obesity. Excess body weight is associated with an increased risk of at least 13 cancers. Although risk estimates vary by study and cancer type, according to a global snapshot from 2012, being overweight or obese accounted for about 4% of all cancers worldwide – 1% in low-income countries and as high as 8% in high-income countries.

However, Dr. Brennan believes “we have underestimated the effect of obesity [on cancer].”

A key reason, he said, is most studies use body mass index to determine whether someone is overweight or obese, but BMI is a poor measure of body fat. BMI does not differentiate between fat and muscle, which means two people with the same height and weight can have the same BMI, even if one is an athlete who eats lean meats and vegetables while the other lives a sedentary life and consumes large quantities of processed foods and alcohol.

On top of that, studies often only calculate a person’s BMI once, and a single measurement can’t tell you how a person’s weight has fluctuated in recent years or across different stages of their life. However, recent analyses suggest that obesity status over time may be more relevant to cancer risk than one-off measures.

In addition, many studies now suggest that alterations to our gut microbes and high blood insulin level – often seen in people who are overweight or obese – may increase the risk of cancer and speed the growth of tumors.

When these additional factors are considered, the impact of excess body fat may ultimately play a much more significant role in cancer risk. In fact, according to Dr. Brennan, “if we estimate [the effects of obesity] properly, it might at some point become the main cause of cancer.”
 

Possibility 2: Environmental or lifestyle factors remain under the radar

Researchers have linked many substances we consume or are exposed to in our daily lives – air pollution, toxins from industrial waste, and highly processed foods – to cancer. But the extent or contribution of potential carcinogens in our surroundings, particularly those found almost everywhere at low levels, is still largely unknown.

One simple reason is the effects of many of these substances remain difficult to assess. For instance, it is much harder to study the impact of pollutants found in food or water, in which a given population will share similar exposure levels versus tobacco, where it is possible to compare a person who smokes a pack of cigarettes a day with a person who does not smoke.

“If you’ve got exposures that are ubiquitous, it can be difficult to discern their [individual] roles,” Dr. Martin said. “There are many causes that we [likely] don’t really know because everyone has been exposed.”

On the flip side, some carcinogenic substances that people encounter for limited periods might be missed if studies are not performed at the time of exposure.

“What’s in the body at age 40 may not reflect what you were exposed at age 5-10 on the playground or soccer field,” said Graham Colditz, MD, PhD, an epidemiologist and public health expert at Washington University, St. Louis. “The technology keeps changing so we can get better measures of what you’ve got exposure to today, but how that relates to 5, 10, 15 years ago is probably very variable.”

In addition, researchers have found that many carcinogens do not cause specific mutations in a cell’s DNA; rather, studies suggest that most carcinogens lead to cancer-promoting changes in cells, such as inflammation.

“We need to think of how potential carcinogens are causing cancer,” Dr. Brennan said. Instead of provoking mutations, potential carcinogens may use a “whole other kind of pathway.” When, for instance, inflammation becomes chronic, it may spur a cascade of events that ultimately leads to cancer.

Finally, not much is known about what causes cancers in low- and middle-income countries. Most of the research to date has been in high-income countries, such the United States, Australia, and parts of Europe.

“There’s a real lack of robust epidemiological studies in other parts of the world, Latin America, Africa, parts of Asia,” Marc Gunter, PhD, a molecular epidemiologist at the IARC, told this news organization.
 

Possibility 3: Some cancers occur by chance

When it comes to cancer risk, an element of chance may be at play. Cancer can occur in individuals who have very little exposure to known carcinogens or have no family history of cancer.

“We all know there are people who get cancer who eat very healthy diets, are never overweight, and never smoke,” Dr. Gunter said. “Then there are people on the other end of the extreme who don’t get cancer.”

But what fraction of cancers are attributable to chance?

A controversial 2017 study published in Science suggested that, based on the rate of cell turnover in healthy tissues in the lung, pancreas, and other parts of the body, only about one-third of cancers could be linked to environmental or genetic factors. The rest, the authors claimed, occurred because of random mutations that accumulated in a person’s DNA – in other words, bad luck.

That study brought on a flood of criticism from scientists who pointed to serious flaws in the work that led the researchers to significantly overestimate the share of chance-related cancers.

The actual proportion of cancers that occur by chance is much lower, according to Dr. Brennan. “If you look at international comparisons [of cancer rates] and take a conservative estimate, you see that maybe 10% or 15% of cancers are really chance.”

Whether some cancers are caused by bad luck or undiscovered risk factors remains an open question.

But the bottom line is many unknown causes of cancer are likely environmental or lifestyle related, which means that, in theory, they can be altered, even prevented.

“There is always going to be some element of chance, but you can modify your chance, depending on your lifestyle and maybe other factors, which we don’t fully understand yet,” Dr. Gunter said.

The good news is that, when it comes to prevention, there are many ways to modify our behaviors – such as consuming fewer processed meats, going for a daily walk, or getting vaccinated against cancer-causing viruses – to improve our chances of living cancer free. And as scientists better understand more about what causes cancer, possibilities for prevention will only grow.

“There is a constant, slow growth [in knowledge] that is lowering the overall risk of cancer,” Dr. Brennan said. “We’re never going to eliminate cancer, but we will be able to control it as a disease.”

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

People with cancer are often desperate to know what caused their disease. Was it something they did? Something they could have prevented?

vitanovski/Thinkstock.com

In a recent analysis, experts estimated that about 40% of cancers can be explained by known, often modifiable risk factors. Smoking and obesity represent the primary drivers, though a host of other factors – germline mutations, alcohol, infections, or environmental pollutants like asbestos – contribute to cancer risk as well.

But what about the remaining 60% of cancers?

The study suggests that, although many of these cases likely have an underlying lifestyle or environmental component, experts still do not fully understand their origin story. And a small but significant number may simply be caused by chance.

Here’s what experts suspect those missing causes might be, and why they can be so difficult to confirm.
 

Possibility 1: Known risk factors contribute more than we realize

For certain factors, a straight line can be drawn to cancer.

Take smoking, for instance. Decades of research have helped scientists clearly delineate tobacco’s carcinogenic effects. Researchers have pinpointed a unique set of mutations in the tumors of smokers that can be seen when cells grown in a dish are exposed to the carcinogens present in tobacco.

In addition, experts have been able to collect robust data from epidemiologic studies on smoking prevalence as well as associated cancer risks and deaths, in large part because an individual’s lifetime tobacco exposure is fairly easy to measure.

“The evidence for smoking is incredibly consistent,” Paul Brennan, PhD, a cancer epidemiologist at the World Health Organization’s International Agency for Research on Cancer, said in an interview.

For other known risk factors, such as obesity and air pollution, many more questions than answers remain.

Because of the limitations in how such factors are measured, we are likely downplaying their effects, said Richard Martin, PhD, a professor of clinical epidemiology at the University of Bristol (England).

Take obesity. Excess body weight is associated with an increased risk of at least 13 cancers. Although risk estimates vary by study and cancer type, according to a global snapshot from 2012, being overweight or obese accounted for about 4% of all cancers worldwide – 1% in low-income countries and as high as 8% in high-income countries.

However, Dr. Brennan believes “we have underestimated the effect of obesity [on cancer].”

A key reason, he said, is most studies use body mass index to determine whether someone is overweight or obese, but BMI is a poor measure of body fat. BMI does not differentiate between fat and muscle, which means two people with the same height and weight can have the same BMI, even if one is an athlete who eats lean meats and vegetables while the other lives a sedentary life and consumes large quantities of processed foods and alcohol.

On top of that, studies often only calculate a person’s BMI once, and a single measurement can’t tell you how a person’s weight has fluctuated in recent years or across different stages of their life. However, recent analyses suggest that obesity status over time may be more relevant to cancer risk than one-off measures.

In addition, many studies now suggest that alterations to our gut microbes and high blood insulin level – often seen in people who are overweight or obese – may increase the risk of cancer and speed the growth of tumors.

When these additional factors are considered, the impact of excess body fat may ultimately play a much more significant role in cancer risk. In fact, according to Dr. Brennan, “if we estimate [the effects of obesity] properly, it might at some point become the main cause of cancer.”
 

Possibility 2: Environmental or lifestyle factors remain under the radar

Researchers have linked many substances we consume or are exposed to in our daily lives – air pollution, toxins from industrial waste, and highly processed foods – to cancer. But the extent or contribution of potential carcinogens in our surroundings, particularly those found almost everywhere at low levels, is still largely unknown.

One simple reason is the effects of many of these substances remain difficult to assess. For instance, it is much harder to study the impact of pollutants found in food or water, in which a given population will share similar exposure levels versus tobacco, where it is possible to compare a person who smokes a pack of cigarettes a day with a person who does not smoke.

“If you’ve got exposures that are ubiquitous, it can be difficult to discern their [individual] roles,” Dr. Martin said. “There are many causes that we [likely] don’t really know because everyone has been exposed.”

On the flip side, some carcinogenic substances that people encounter for limited periods might be missed if studies are not performed at the time of exposure.

“What’s in the body at age 40 may not reflect what you were exposed at age 5-10 on the playground or soccer field,” said Graham Colditz, MD, PhD, an epidemiologist and public health expert at Washington University, St. Louis. “The technology keeps changing so we can get better measures of what you’ve got exposure to today, but how that relates to 5, 10, 15 years ago is probably very variable.”

In addition, researchers have found that many carcinogens do not cause specific mutations in a cell’s DNA; rather, studies suggest that most carcinogens lead to cancer-promoting changes in cells, such as inflammation.

“We need to think of how potential carcinogens are causing cancer,” Dr. Brennan said. Instead of provoking mutations, potential carcinogens may use a “whole other kind of pathway.” When, for instance, inflammation becomes chronic, it may spur a cascade of events that ultimately leads to cancer.

Finally, not much is known about what causes cancers in low- and middle-income countries. Most of the research to date has been in high-income countries, such the United States, Australia, and parts of Europe.

“There’s a real lack of robust epidemiological studies in other parts of the world, Latin America, Africa, parts of Asia,” Marc Gunter, PhD, a molecular epidemiologist at the IARC, told this news organization.
 

Possibility 3: Some cancers occur by chance

When it comes to cancer risk, an element of chance may be at play. Cancer can occur in individuals who have very little exposure to known carcinogens or have no family history of cancer.

“We all know there are people who get cancer who eat very healthy diets, are never overweight, and never smoke,” Dr. Gunter said. “Then there are people on the other end of the extreme who don’t get cancer.”

But what fraction of cancers are attributable to chance?

A controversial 2017 study published in Science suggested that, based on the rate of cell turnover in healthy tissues in the lung, pancreas, and other parts of the body, only about one-third of cancers could be linked to environmental or genetic factors. The rest, the authors claimed, occurred because of random mutations that accumulated in a person’s DNA – in other words, bad luck.

That study brought on a flood of criticism from scientists who pointed to serious flaws in the work that led the researchers to significantly overestimate the share of chance-related cancers.

The actual proportion of cancers that occur by chance is much lower, according to Dr. Brennan. “If you look at international comparisons [of cancer rates] and take a conservative estimate, you see that maybe 10% or 15% of cancers are really chance.”

Whether some cancers are caused by bad luck or undiscovered risk factors remains an open question.

But the bottom line is many unknown causes of cancer are likely environmental or lifestyle related, which means that, in theory, they can be altered, even prevented.

“There is always going to be some element of chance, but you can modify your chance, depending on your lifestyle and maybe other factors, which we don’t fully understand yet,” Dr. Gunter said.

The good news is that, when it comes to prevention, there are many ways to modify our behaviors – such as consuming fewer processed meats, going for a daily walk, or getting vaccinated against cancer-causing viruses – to improve our chances of living cancer free. And as scientists better understand more about what causes cancer, possibilities for prevention will only grow.

“There is a constant, slow growth [in knowledge] that is lowering the overall risk of cancer,” Dr. Brennan said. “We’re never going to eliminate cancer, but we will be able to control it as a disease.”

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

On the basis of the patient's presentation and imaging results, the likely diagnosis is non–small cell cancer (NSCLC) of an adenocarcinoma subtype. NSCLC makes up about 80% of all lung cancer cases. Adenocarcinoma in particular is the most common type of lung cancer in the United States, accounting for about 40% of cases, and it is the most common histology among nonsmokers. Women are more likely to develop this subtype of NSCLC and are generally younger when they present with symptoms. This type of cancer arises from the bronchial mucosal glands and usually develops in a peripheral location within the lung. 

In the course of workup, immunohistochemical (IHC) analyses are used to identify tumor type and lineage (adenocarcinoma, squamous cell carcinoma, metastatic malignancy, or primary pleural mesothelioma). Separate IHC analyses are then used to guide treatment decisions, identifying whether ALK inhibitor therapy or programmed cell death protein ligand 1 (PD-L1) inhibitor therapy would be appropriate.

Tissue should also be conserved for molecular testing. NCCN guidelines advise that all patients with adenocarcinoma should be tested for EGFR mutations, and DNA mutational analysis is the preferred method for assessment. Patients should also undergo routine biomarker testing, with an eye toward ALK, RET, and ROS1 rearrangements, BRAF mutations, c-MET and exon 14 skipping mutations, and PD-L1 expression levels. For patients with metastatic NSCLC, PD-L1 IHC testing is recommended.

Most cases of lung cancer are diagnosed at a late stage, when symptoms have already begun to manifest. Of note, however, women with adenocarcinoma are more likely to present with localized disease. Treatment is largely influenced by the presence of targetable mutations. Among adenocarcinoma cases, the most common mutations are in the EGFR and KRAS genes.

For patients who are EGFR mutation positive (exon 10 deletion or L858R), osimertinib is the recommended first-line therapy. For patients who are positive for the EGFR exon 20 insertion mutation, initial systemic therapy options for adenocarcinoma are appropriate; the preferred regimen being pembrolizumab-carboplatin-pemetrexed if there are no contraindications to programmed cell death protein 1 (PD-1) or PD-L1 inhibitors.

KRAS mutations, unlike EGFR mutations, are associated with smoking. Because overlapping targetable alterations are uncommon, identification of KRAS mutations suggests that these patients will not benefit from additional molecular testing. Again, initial systemic therapy options for adenocarcinoma are appropriate, but the presence of KRAS mutation predicts a poor response to EGFR tyrosine kinase inhibitors. The FDA approved a KRAS inhibitor in June 2021 and immune checkpoint inhibitors appear to be beneficial in this population.

Maurie Markman, MD, President, Department of Medical Oncology, Cancer Treatment Centers of America.

Maurie Markman, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Merck
Serve(d) as a speaker or a member of a speakers bureau for: AstraZeneca; Novis; Glaxo Smith Kline
Received research grant from: AstraZeneca; Novis; GSK; Merck

On the basis of the patient's presentation and imaging results, the likely diagnosis is non–small cell cancer (NSCLC) of an adenocarcinoma subtype. NSCLC makes up about 80% of all lung cancer cases. Adenocarcinoma in particular is the most common type of lung cancer in the United States, accounting for about 40% of cases, and it is the most common histology among nonsmokers. Women are more likely to develop this subtype of NSCLC and are generally younger when they present with symptoms. This type of cancer arises from the bronchial mucosal glands and usually develops in a peripheral location within the lung. 

In the course of workup, immunohistochemical (IHC) analyses are used to identify tumor type and lineage (adenocarcinoma, squamous cell carcinoma, metastatic malignancy, or primary pleural mesothelioma). Separate IHC analyses are then used to guide treatment decisions, identifying whether ALK inhibitor therapy or programmed cell death protein ligand 1 (PD-L1) inhibitor therapy would be appropriate.

Tissue should also be conserved for molecular testing. NCCN guidelines advise that all patients with adenocarcinoma should be tested for EGFR mutations, and DNA mutational analysis is the preferred method for assessment. Patients should also undergo routine biomarker testing, with an eye toward ALK, RET, and ROS1 rearrangements, BRAF mutations, c-MET and exon 14 skipping mutations, and PD-L1 expression levels. For patients with metastatic NSCLC, PD-L1 IHC testing is recommended.

Most cases of lung cancer are diagnosed at a late stage, when symptoms have already begun to manifest. Of note, however, women with adenocarcinoma are more likely to present with localized disease. Treatment is largely influenced by the presence of targetable mutations. Among adenocarcinoma cases, the most common mutations are in the EGFR and KRAS genes.

For patients who are EGFR mutation positive (exon 10 deletion or L858R), osimertinib is the recommended first-line therapy. For patients who are positive for the EGFR exon 20 insertion mutation, initial systemic therapy options for adenocarcinoma are appropriate; the preferred regimen being pembrolizumab-carboplatin-pemetrexed if there are no contraindications to programmed cell death protein 1 (PD-1) or PD-L1 inhibitors.

KRAS mutations, unlike EGFR mutations, are associated with smoking. Because overlapping targetable alterations are uncommon, identification of KRAS mutations suggests that these patients will not benefit from additional molecular testing. Again, initial systemic therapy options for adenocarcinoma are appropriate, but the presence of KRAS mutation predicts a poor response to EGFR tyrosine kinase inhibitors. The FDA approved a KRAS inhibitor in June 2021 and immune checkpoint inhibitors appear to be beneficial in this population.

Maurie Markman, MD, President, Department of Medical Oncology, Cancer Treatment Centers of America.

Maurie Markman, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Merck
Serve(d) as a speaker or a member of a speakers bureau for: AstraZeneca; Novis; Glaxo Smith Kline
Received research grant from: AstraZeneca; Novis; GSK; Merck

On the basis of the patient's presentation and imaging results, the likely diagnosis is non–small cell cancer (NSCLC) of an adenocarcinoma subtype. NSCLC makes up about 80% of all lung cancer cases. Adenocarcinoma in particular is the most common type of lung cancer in the United States, accounting for about 40% of cases, and it is the most common histology among nonsmokers. Women are more likely to develop this subtype of NSCLC and are generally younger when they present with symptoms. This type of cancer arises from the bronchial mucosal glands and usually develops in a peripheral location within the lung. 

In the course of workup, immunohistochemical (IHC) analyses are used to identify tumor type and lineage (adenocarcinoma, squamous cell carcinoma, metastatic malignancy, or primary pleural mesothelioma). Separate IHC analyses are then used to guide treatment decisions, identifying whether ALK inhibitor therapy or programmed cell death protein ligand 1 (PD-L1) inhibitor therapy would be appropriate.

Tissue should also be conserved for molecular testing. NCCN guidelines advise that all patients with adenocarcinoma should be tested for EGFR mutations, and DNA mutational analysis is the preferred method for assessment. Patients should also undergo routine biomarker testing, with an eye toward ALK, RET, and ROS1 rearrangements, BRAF mutations, c-MET and exon 14 skipping mutations, and PD-L1 expression levels. For patients with metastatic NSCLC, PD-L1 IHC testing is recommended.

Most cases of lung cancer are diagnosed at a late stage, when symptoms have already begun to manifest. Of note, however, women with adenocarcinoma are more likely to present with localized disease. Treatment is largely influenced by the presence of targetable mutations. Among adenocarcinoma cases, the most common mutations are in the EGFR and KRAS genes.

For patients who are EGFR mutation positive (exon 10 deletion or L858R), osimertinib is the recommended first-line therapy. For patients who are positive for the EGFR exon 20 insertion mutation, initial systemic therapy options for adenocarcinoma are appropriate; the preferred regimen being pembrolizumab-carboplatin-pemetrexed if there are no contraindications to programmed cell death protein 1 (PD-1) or PD-L1 inhibitors.

KRAS mutations, unlike EGFR mutations, are associated with smoking. Because overlapping targetable alterations are uncommon, identification of KRAS mutations suggests that these patients will not benefit from additional molecular testing. Again, initial systemic therapy options for adenocarcinoma are appropriate, but the presence of KRAS mutation predicts a poor response to EGFR tyrosine kinase inhibitors. The FDA approved a KRAS inhibitor in June 2021 and immune checkpoint inhibitors appear to be beneficial in this population.

Maurie Markman, MD, President, Department of Medical Oncology, Cancer Treatment Centers of America.

Maurie Markman, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Merck
Serve(d) as a speaker or a member of a speakers bureau for: AstraZeneca; Novis; Glaxo Smith Kline
Received research grant from: AstraZeneca; Novis; GSK; Merck

According to the Centers for Disease Control and Prevention, lung cancer is the third-most common cancer in the United States and the leading cause of cancer deaths in both men and women. Approximately, 150,000 Americans die every year from this disease.

For many years, no effective screening tests were available for lung cancer. This has changed with the advent of low-dose CT scanning as a screening method. In fact, it has been shown that low-dose CT scan screening can reduce lung cancer deaths by 20%-30% in high-risk populations.

In the United States, low-dose CT scan screening for lung cancer has largely become the norm. In July 2021, CHEST released new clinical guidelines. These guidelines cover 18 evidence-based recommendations as well as inclusion of further evidence regarding the benefits, risks, and use of CT screening.

In doing the risk assessment of low-dose CT scan as a method of lung cancer screening, meta-analyses were performed on evidence obtained through a literature search using PubMed, Embase, and the Cochrane Library. It was concluded that the benefits outweigh the risks as a method of lung cancer screening and can be utilized in reducing lung cancer deaths.

Low-dose CT scan screening was recommended for the following patients:

• Asymptomatic individuals aged 55-77 years with a history of smoking 30 or more pack-years. (This includes those who continue to smoke or who have quit in the previous 15 years. Annual screening is advised.)
• Asymptomatic individuals aged 55-80 years with a history of smoking 20-30 pack-years who either continue to smoke or have quit in the previous 15 years.
• For asymptomatic individuals who do not meet the above criteria but are predicted to benefit based on life-year gained calculations.

Don’t screen these patients

CT scan screening should not be performed on any person who does not meet any of the above three criteria.

Additionally, if a person has significant comorbidities that would limit their life expectancy, it is recommended not to do CT scan screening. Symptomatic patients should have appropriate diagnostic testing rather than screening.

Additional recommendations from the updated guidelines include developing appropriate counseling strategies as well as deciding what constitutes a positive test.

A positive test should be anything that warrants further evaluation rather than a return to annual screening. It was also advised that overtreatment strategies should be implemented. Additionally, smoking cessation treatment should be provided.

CHEST suggested undertaking a comprehensive approach involving multiple specialists including pulmonologists, radiologists, oncologists, etc. Strategies to ensure compliance with annual screening should also be devised, the guidelines say.
 

USPSTF’s updated guidelines

It should be noted that the U.S. Preventative Task Force released their own set of updated guidelines in March 2021. In these guidelines, the age at which lung cancer screening should be started was lowered from 55 years to 50 years.

Also, the USPSTF lowered the minimum required smoking history in order to be screened from 30 to 20 pack-years. Their purpose for doing this was to include more high-risk women as well as minorities.

With the changes, 14.5 million individuals living in the United States would be eligible for lung cancer screening by low-dose CT scan, an increase of 6.5 million people, compared with the previous guidelines.

While only small differences exist between the set of guidelines issued by CHEST and the ones issues by the USPSTF, lung cancer screening is still largely underutilized.

One of the barriers to screening may be patients’ lacking insurance coverage for it. As physicians, we need to advocate for these screening tools to be covered.

Other barriers include lack of patient knowledge regarding low-dose CT scans as a screening tool, patient time, and patient visits with their doctors being too short.
 

Key message

Part of the duties of physicians is to give our patients the best information. We can reduce lung cancer mortality in high risk patients by performing annual low-dose CT scans.

Whichever set of guidelines we chose to follow, we fail our patients if we don’t follow either set of them. The evidence is clear that a low-dose CT scan is a valuable screening tool to add to our practice of medicine.

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].

According to the Centers for Disease Control and Prevention, lung cancer is the third-most common cancer in the United States and the leading cause of cancer deaths in both men and women. Approximately, 150,000 Americans die every year from this disease.

For many years, no effective screening tests were available for lung cancer. This has changed with the advent of low-dose CT scanning as a screening method. In fact, it has been shown that low-dose CT scan screening can reduce lung cancer deaths by 20%-30% in high-risk populations.

In the United States, low-dose CT scan screening for lung cancer has largely become the norm. In July 2021, CHEST released new clinical guidelines. These guidelines cover 18 evidence-based recommendations as well as inclusion of further evidence regarding the benefits, risks, and use of CT screening.

In doing the risk assessment of low-dose CT scan as a method of lung cancer screening, meta-analyses were performed on evidence obtained through a literature search using PubMed, Embase, and the Cochrane Library. It was concluded that the benefits outweigh the risks as a method of lung cancer screening and can be utilized in reducing lung cancer deaths.

Low-dose CT scan screening was recommended for the following patients:

• Asymptomatic individuals aged 55-77 years with a history of smoking 30 or more pack-years. (This includes those who continue to smoke or who have quit in the previous 15 years. Annual screening is advised.)
• Asymptomatic individuals aged 55-80 years with a history of smoking 20-30 pack-years who either continue to smoke or have quit in the previous 15 years.
• For asymptomatic individuals who do not meet the above criteria but are predicted to benefit based on life-year gained calculations.

Don’t screen these patients

CT scan screening should not be performed on any person who does not meet any of the above three criteria.

Additionally, if a person has significant comorbidities that would limit their life expectancy, it is recommended not to do CT scan screening. Symptomatic patients should have appropriate diagnostic testing rather than screening.

Additional recommendations from the updated guidelines include developing appropriate counseling strategies as well as deciding what constitutes a positive test.

A positive test should be anything that warrants further evaluation rather than a return to annual screening. It was also advised that overtreatment strategies should be implemented. Additionally, smoking cessation treatment should be provided.

CHEST suggested undertaking a comprehensive approach involving multiple specialists including pulmonologists, radiologists, oncologists, etc. Strategies to ensure compliance with annual screening should also be devised, the guidelines say.
 

USPSTF’s updated guidelines

It should be noted that the U.S. Preventative Task Force released their own set of updated guidelines in March 2021. In these guidelines, the age at which lung cancer screening should be started was lowered from 55 years to 50 years.

Also, the USPSTF lowered the minimum required smoking history in order to be screened from 30 to 20 pack-years. Their purpose for doing this was to include more high-risk women as well as minorities.

With the changes, 14.5 million individuals living in the United States would be eligible for lung cancer screening by low-dose CT scan, an increase of 6.5 million people, compared with the previous guidelines.

While only small differences exist between the set of guidelines issued by CHEST and the ones issues by the USPSTF, lung cancer screening is still largely underutilized.

One of the barriers to screening may be patients’ lacking insurance coverage for it. As physicians, we need to advocate for these screening tools to be covered.

Other barriers include lack of patient knowledge regarding low-dose CT scans as a screening tool, patient time, and patient visits with their doctors being too short.
 

Key message

Part of the duties of physicians is to give our patients the best information. We can reduce lung cancer mortality in high risk patients by performing annual low-dose CT scans.

Whichever set of guidelines we chose to follow, we fail our patients if we don’t follow either set of them. The evidence is clear that a low-dose CT scan is a valuable screening tool to add to our practice of medicine.

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].

According to the Centers for Disease Control and Prevention, lung cancer is the third-most common cancer in the United States and the leading cause of cancer deaths in both men and women. Approximately, 150,000 Americans die every year from this disease.

For many years, no effective screening tests were available for lung cancer. This has changed with the advent of low-dose CT scanning as a screening method. In fact, it has been shown that low-dose CT scan screening can reduce lung cancer deaths by 20%-30% in high-risk populations.

In the United States, low-dose CT scan screening for lung cancer has largely become the norm. In July 2021, CHEST released new clinical guidelines. These guidelines cover 18 evidence-based recommendations as well as inclusion of further evidence regarding the benefits, risks, and use of CT screening.

In doing the risk assessment of low-dose CT scan as a method of lung cancer screening, meta-analyses were performed on evidence obtained through a literature search using PubMed, Embase, and the Cochrane Library. It was concluded that the benefits outweigh the risks as a method of lung cancer screening and can be utilized in reducing lung cancer deaths.

Low-dose CT scan screening was recommended for the following patients:

• Asymptomatic individuals aged 55-77 years with a history of smoking 30 or more pack-years. (This includes those who continue to smoke or who have quit in the previous 15 years. Annual screening is advised.)
• Asymptomatic individuals aged 55-80 years with a history of smoking 20-30 pack-years who either continue to smoke or have quit in the previous 15 years.
• For asymptomatic individuals who do not meet the above criteria but are predicted to benefit based on life-year gained calculations.

Don’t screen these patients

CT scan screening should not be performed on any person who does not meet any of the above three criteria.

Additionally, if a person has significant comorbidities that would limit their life expectancy, it is recommended not to do CT scan screening. Symptomatic patients should have appropriate diagnostic testing rather than screening.

Additional recommendations from the updated guidelines include developing appropriate counseling strategies as well as deciding what constitutes a positive test.

A positive test should be anything that warrants further evaluation rather than a return to annual screening. It was also advised that overtreatment strategies should be implemented. Additionally, smoking cessation treatment should be provided.

CHEST suggested undertaking a comprehensive approach involving multiple specialists including pulmonologists, radiologists, oncologists, etc. Strategies to ensure compliance with annual screening should also be devised, the guidelines say.
 

USPSTF’s updated guidelines

It should be noted that the U.S. Preventative Task Force released their own set of updated guidelines in March 2021. In these guidelines, the age at which lung cancer screening should be started was lowered from 55 years to 50 years.

Also, the USPSTF lowered the minimum required smoking history in order to be screened from 30 to 20 pack-years. Their purpose for doing this was to include more high-risk women as well as minorities.

With the changes, 14.5 million individuals living in the United States would be eligible for lung cancer screening by low-dose CT scan, an increase of 6.5 million people, compared with the previous guidelines.

While only small differences exist between the set of guidelines issued by CHEST and the ones issues by the USPSTF, lung cancer screening is still largely underutilized.

One of the barriers to screening may be patients’ lacking insurance coverage for it. As physicians, we need to advocate for these screening tools to be covered.

Other barriers include lack of patient knowledge regarding low-dose CT scans as a screening tool, patient time, and patient visits with their doctors being too short.
 

Key message

Part of the duties of physicians is to give our patients the best information. We can reduce lung cancer mortality in high risk patients by performing annual low-dose CT scans.

Whichever set of guidelines we chose to follow, we fail our patients if we don’t follow either set of them. The evidence is clear that a low-dose CT scan is a valuable screening tool to add to our practice of medicine.

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].

On a recent Friday, oncologist Christine Berg, MD, devoted 3 hours to a webinar about electrification of heavy- and medium-duty trucks in Maryland.

It’s not the way most cancer specialists choose to spend their time. But Dr. Berg, who is board certified in medical oncology, radiation oncology, and internal medicine, has made air pollution her current focus. Through organizations such as the Public Employees for Environmental Responsibility, she is working to raise awareness of the huge impact it can have on cancer.

“I think oncologists can make a difference,” she said.

That’s why Dr. Berg took a keen interest in a recent study by ProPublica, the nonprofit journalism organization, that identified previously ignored “hot spots of cancer-causing air.” While the ProPublica report gives an incomplete picture of airborne carcinogens, it puts an important spotlight on industrial air pollution, Dr. Berg and other experts say.

Relying on data from the Environmental Protection Agency’s Risk-Screening Environmental Indicators (RSEI), ProPublica researchers estimated the effects of industrial air pollution around the country and found problems the EPA overlooked, they reported. “The EPA collects data on each individual facility, but it doesn’t consider the excess cancer risk from all of the facilities’ combined emissions,” reporter Lylla Younes and colleagues wrote. “ProPublica did.”

The ProPublica team produced a map of cancer-causing industrial air pollution hot spots. They estimated that 256,000 people in the United States live in areas where incidences of cancer caused by air pollution exceed the EPA’s upper limit of acceptable risk.

While some of the spots are scattered around the country, they are concentrated along the Gulf Coast of Texas and Louisiana. For example, near the Equistar Chemicals Bayport Chemical Plant in Pasadena, Texas, ProPublica calculated the increased risk of cancer at 1 in 220, “46 times the EPA’s acceptable risk.” (The agency defines an acceptable risk as less than a 1 in 10,000 chance of developing cancer.)

Almost all the hot spots with the highest level of risk are in southern United States “known for having weaker environmental regulations,” the report said.

The researchers also identified race as a risk factor. In predominantly Black census tracts, they estimated the risk from toxic air pollution is more than double the risk in predominantly White census tracts. It attributed this pattern to deliberate policies of redlining that segregated neighborhoods and to zoning ordinances that encouraged industry in communities of color.
 

Measuring risk not straightforward

In response to a query from this news organization, an EPA spokesperson provided a statement saying the RSEI data are not intended for the purpose used by ProPublica. “RSEI does not provide a risk assessment (e.g., excess cancer case estimates),” the statement said. The RSEI data are poorly suited to this purpose because they use “worst-case assumptions about toxicity and potential exposure where data are lacking, and also use simplifying assumptions to reduce the complexity of the calculations,” the statement said.

Instead, the data are meant as a kind of index to compare one place to another, or show changes over time, the agency said. In this way, it can prompt regulators to investigate further. “A more refined assessment is required before any conclusions about health impacts can be drawn.” The agency is working on just such a refined approach, per the EPA statement.

That’s not just bureaucratic stonewalling, said Stan Meiberg, PhD, MA, a former EPA official and director of graduate studies in sustainability at Wake Forest University in Winston-Salem, N.C. “To say that you can speak with great precision, that the risk of individuals getting cancer is 1 in 100, may be a little overstating the date on which that statement is based.”

Risk estimates are improving as citizens gain access to more sophisticated monitoring devices, he said. And the primary point of the ProPublica report, that the EPA has underestimated risk by looking at individual sources of pollution rather than combining them, is not an original one, Dr. Meiberg said. “This is an issue that’s been kicking around for quite some time.”

Still, it’s one that demands attention. EPA regulations have succeeded in reducing the overall risk from industrial air pollution over the past few decades. “But there remain areas of particular geographic concentrations,” he said. “And the ProPublica article hit two of them, which have been the subject of discussion for many years, the Houston Ship Channel area and the Baton Rouge to New Orleans industrial corridor where you have a significant proportion of all the chemical petrochemical industry in the United States.”

Improvements in containment of the pollutants, and changes to the industrial processes that produce them, can also help reduce exposure. These changes should occur in the context of dialogue within the communities exposed to the pollution, Dr. Meiberg said.
 

The role of cancer-causing airborne particulate matter

But even if measures are perfectly implemented, Joan Schiller, MD, will not breathe easy. An adjunct professor of oncology at the University of Virginia in Charlottesville, Dr. Schiller has researched the role of airborne particulate matter in causing cancer, a correlation barely mentioned in the ProPublica analysis, she pointed out.

Particulate matter contains a wide range of toxic substances, she said. Researchers have focused on particles 2.5 microns in diameter, or PM 2.5. Some studies have indicated that it’s responsible for one in seven deaths from lung cancer, Dr. Schiller said. “Air pollution also causes lung cancer in never smokers, people who’ve never smoked, not just in smokers.”

Power plants and automobile traffic may be more significant sources of PM 2.5 than industry, and wildfires have recently emerged as increasingly important source, a result of climate change and poor forest management, she said.

PM 2.5 doesn’t affect just lung cancer, said Alexandra White, PhD, an investigator at the National Institute of Environmental Health Sciences in Research Triangle Park, N.C. “My work, as well as work of others, is increasingly suggesting that air pollution is also related to breast cancer risk, in particular, air pollution that is arising from traffic related forces.” And more research is needed on other cancers, she said. “I think that the lack of findings of other cancer sites reflects a lack of study.”

Other pollutants not analyzed in the ProPublica report are also correlated to cancer risk. In a recent meta-analysis, researcher Stephan Gabet, PhD, PharmD, and colleagues at the University of Grenoble, France, estimated that 3.15% of new breast cancer cases in that country could be attributed to nitrogen dioxide and 2.15% to PM 10.

Sources of nitrogen dioxide, PM 2.5, and PM 10 in France include automobile traffic, inefficient wood-burning stoves, and coal-burning power plants in neighboring countries, Dr. Gabet said.

A good approach to reducing pollution from road traffic is the implementation of low-emission zones that prohibit the most polluting vehicles, he said. But a 2019 United Kingdom government study found that brake wear, tire wear, and road surface wear account for 72% of the PM 10 and 60% of the PM 2.5 pollution from road traffic, suggesting that a transition to electric vehicles won’t fix the problem. Better yet, is “the promotion of active modes like walking, cycling, etc., because like this, you can bring additional health gains due to the increase in physical activity,” he said.

Oncologists can help their patients reduce their exposure to air pollution, Dr. Schiller said. “If you have lung cancer, air pollution will hasten your demise. It makes you sicker. Oncologists should be telling their patients about this and advising them to move away from air pollution if possible, and also making sure they know to monitor the health of the air.”

On days when air pollution is high, patients may want to avoid exercising outdoors, or stay indoors altogether, Dr. Berg said. Air purifiers and N95 masks may also help.

And physicians can make a difference by speaking out in their communities, Dr. Schiller said. She is inviting oncologists to join a new group, Oncologists Understanding for Climate and Health. Through this group or on their own, oncologists can speak to their local legislatures or city councils in support of measures to reduce pollution, she said. “Doctors are trusted messengers.”

Dr. Berg disclosed affiliations with Grail, Mercy BioAnalytics and Lucid Diagnostics.

On a recent Friday, oncologist Christine Berg, MD, devoted 3 hours to a webinar about electrification of heavy- and medium-duty trucks in Maryland.

It’s not the way most cancer specialists choose to spend their time. But Dr. Berg, who is board certified in medical oncology, radiation oncology, and internal medicine, has made air pollution her current focus. Through organizations such as the Public Employees for Environmental Responsibility, she is working to raise awareness of the huge impact it can have on cancer.

“I think oncologists can make a difference,” she said.

That’s why Dr. Berg took a keen interest in a recent study by ProPublica, the nonprofit journalism organization, that identified previously ignored “hot spots of cancer-causing air.” While the ProPublica report gives an incomplete picture of airborne carcinogens, it puts an important spotlight on industrial air pollution, Dr. Berg and other experts say.

Relying on data from the Environmental Protection Agency’s Risk-Screening Environmental Indicators (RSEI), ProPublica researchers estimated the effects of industrial air pollution around the country and found problems the EPA overlooked, they reported. “The EPA collects data on each individual facility, but it doesn’t consider the excess cancer risk from all of the facilities’ combined emissions,” reporter Lylla Younes and colleagues wrote. “ProPublica did.”

The ProPublica team produced a map of cancer-causing industrial air pollution hot spots. They estimated that 256,000 people in the United States live in areas where incidences of cancer caused by air pollution exceed the EPA’s upper limit of acceptable risk.

While some of the spots are scattered around the country, they are concentrated along the Gulf Coast of Texas and Louisiana. For example, near the Equistar Chemicals Bayport Chemical Plant in Pasadena, Texas, ProPublica calculated the increased risk of cancer at 1 in 220, “46 times the EPA’s acceptable risk.” (The agency defines an acceptable risk as less than a 1 in 10,000 chance of developing cancer.)

Almost all the hot spots with the highest level of risk are in southern United States “known for having weaker environmental regulations,” the report said.

The researchers also identified race as a risk factor. In predominantly Black census tracts, they estimated the risk from toxic air pollution is more than double the risk in predominantly White census tracts. It attributed this pattern to deliberate policies of redlining that segregated neighborhoods and to zoning ordinances that encouraged industry in communities of color.
 

Measuring risk not straightforward

In response to a query from this news organization, an EPA spokesperson provided a statement saying the RSEI data are not intended for the purpose used by ProPublica. “RSEI does not provide a risk assessment (e.g., excess cancer case estimates),” the statement said. The RSEI data are poorly suited to this purpose because they use “worst-case assumptions about toxicity and potential exposure where data are lacking, and also use simplifying assumptions to reduce the complexity of the calculations,” the statement said.

Instead, the data are meant as a kind of index to compare one place to another, or show changes over time, the agency said. In this way, it can prompt regulators to investigate further. “A more refined assessment is required before any conclusions about health impacts can be drawn.” The agency is working on just such a refined approach, per the EPA statement.

That’s not just bureaucratic stonewalling, said Stan Meiberg, PhD, MA, a former EPA official and director of graduate studies in sustainability at Wake Forest University in Winston-Salem, N.C. “To say that you can speak with great precision, that the risk of individuals getting cancer is 1 in 100, may be a little overstating the date on which that statement is based.”

Risk estimates are improving as citizens gain access to more sophisticated monitoring devices, he said. And the primary point of the ProPublica report, that the EPA has underestimated risk by looking at individual sources of pollution rather than combining them, is not an original one, Dr. Meiberg said. “This is an issue that’s been kicking around for quite some time.”

Still, it’s one that demands attention. EPA regulations have succeeded in reducing the overall risk from industrial air pollution over the past few decades. “But there remain areas of particular geographic concentrations,” he said. “And the ProPublica article hit two of them, which have been the subject of discussion for many years, the Houston Ship Channel area and the Baton Rouge to New Orleans industrial corridor where you have a significant proportion of all the chemical petrochemical industry in the United States.”

Improvements in containment of the pollutants, and changes to the industrial processes that produce them, can also help reduce exposure. These changes should occur in the context of dialogue within the communities exposed to the pollution, Dr. Meiberg said.
 

The role of cancer-causing airborne particulate matter

But even if measures are perfectly implemented, Joan Schiller, MD, will not breathe easy. An adjunct professor of oncology at the University of Virginia in Charlottesville, Dr. Schiller has researched the role of airborne particulate matter in causing cancer, a correlation barely mentioned in the ProPublica analysis, she pointed out.

Particulate matter contains a wide range of toxic substances, she said. Researchers have focused on particles 2.5 microns in diameter, or PM 2.5. Some studies have indicated that it’s responsible for one in seven deaths from lung cancer, Dr. Schiller said. “Air pollution also causes lung cancer in never smokers, people who’ve never smoked, not just in smokers.”

Power plants and automobile traffic may be more significant sources of PM 2.5 than industry, and wildfires have recently emerged as increasingly important source, a result of climate change and poor forest management, she said.

PM 2.5 doesn’t affect just lung cancer, said Alexandra White, PhD, an investigator at the National Institute of Environmental Health Sciences in Research Triangle Park, N.C. “My work, as well as work of others, is increasingly suggesting that air pollution is also related to breast cancer risk, in particular, air pollution that is arising from traffic related forces.” And more research is needed on other cancers, she said. “I think that the lack of findings of other cancer sites reflects a lack of study.”

Other pollutants not analyzed in the ProPublica report are also correlated to cancer risk. In a recent meta-analysis, researcher Stephan Gabet, PhD, PharmD, and colleagues at the University of Grenoble, France, estimated that 3.15% of new breast cancer cases in that country could be attributed to nitrogen dioxide and 2.15% to PM 10.

Sources of nitrogen dioxide, PM 2.5, and PM 10 in France include automobile traffic, inefficient wood-burning stoves, and coal-burning power plants in neighboring countries, Dr. Gabet said.

A good approach to reducing pollution from road traffic is the implementation of low-emission zones that prohibit the most polluting vehicles, he said. But a 2019 United Kingdom government study found that brake wear, tire wear, and road surface wear account for 72% of the PM 10 and 60% of the PM 2.5 pollution from road traffic, suggesting that a transition to electric vehicles won’t fix the problem. Better yet, is “the promotion of active modes like walking, cycling, etc., because like this, you can bring additional health gains due to the increase in physical activity,” he said.

Oncologists can help their patients reduce their exposure to air pollution, Dr. Schiller said. “If you have lung cancer, air pollution will hasten your demise. It makes you sicker. Oncologists should be telling their patients about this and advising them to move away from air pollution if possible, and also making sure they know to monitor the health of the air.”

On days when air pollution is high, patients may want to avoid exercising outdoors, or stay indoors altogether, Dr. Berg said. Air purifiers and N95 masks may also help.

And physicians can make a difference by speaking out in their communities, Dr. Schiller said. She is inviting oncologists to join a new group, Oncologists Understanding for Climate and Health. Through this group or on their own, oncologists can speak to their local legislatures or city councils in support of measures to reduce pollution, she said. “Doctors are trusted messengers.”

Dr. Berg disclosed affiliations with Grail, Mercy BioAnalytics and Lucid Diagnostics.

On a recent Friday, oncologist Christine Berg, MD, devoted 3 hours to a webinar about electrification of heavy- and medium-duty trucks in Maryland.

It’s not the way most cancer specialists choose to spend their time. But Dr. Berg, who is board certified in medical oncology, radiation oncology, and internal medicine, has made air pollution her current focus. Through organizations such as the Public Employees for Environmental Responsibility, she is working to raise awareness of the huge impact it can have on cancer.

“I think oncologists can make a difference,” she said.

That’s why Dr. Berg took a keen interest in a recent study by ProPublica, the nonprofit journalism organization, that identified previously ignored “hot spots of cancer-causing air.” While the ProPublica report gives an incomplete picture of airborne carcinogens, it puts an important spotlight on industrial air pollution, Dr. Berg and other experts say.

Relying on data from the Environmental Protection Agency’s Risk-Screening Environmental Indicators (RSEI), ProPublica researchers estimated the effects of industrial air pollution around the country and found problems the EPA overlooked, they reported. “The EPA collects data on each individual facility, but it doesn’t consider the excess cancer risk from all of the facilities’ combined emissions,” reporter Lylla Younes and colleagues wrote. “ProPublica did.”

The ProPublica team produced a map of cancer-causing industrial air pollution hot spots. They estimated that 256,000 people in the United States live in areas where incidences of cancer caused by air pollution exceed the EPA’s upper limit of acceptable risk.

While some of the spots are scattered around the country, they are concentrated along the Gulf Coast of Texas and Louisiana. For example, near the Equistar Chemicals Bayport Chemical Plant in Pasadena, Texas, ProPublica calculated the increased risk of cancer at 1 in 220, “46 times the EPA’s acceptable risk.” (The agency defines an acceptable risk as less than a 1 in 10,000 chance of developing cancer.)

Almost all the hot spots with the highest level of risk are in southern United States “known for having weaker environmental regulations,” the report said.

The researchers also identified race as a risk factor. In predominantly Black census tracts, they estimated the risk from toxic air pollution is more than double the risk in predominantly White census tracts. It attributed this pattern to deliberate policies of redlining that segregated neighborhoods and to zoning ordinances that encouraged industry in communities of color.
 

Measuring risk not straightforward

In response to a query from this news organization, an EPA spokesperson provided a statement saying the RSEI data are not intended for the purpose used by ProPublica. “RSEI does not provide a risk assessment (e.g., excess cancer case estimates),” the statement said. The RSEI data are poorly suited to this purpose because they use “worst-case assumptions about toxicity and potential exposure where data are lacking, and also use simplifying assumptions to reduce the complexity of the calculations,” the statement said.

Instead, the data are meant as a kind of index to compare one place to another, or show changes over time, the agency said. In this way, it can prompt regulators to investigate further. “A more refined assessment is required before any conclusions about health impacts can be drawn.” The agency is working on just such a refined approach, per the EPA statement.

That’s not just bureaucratic stonewalling, said Stan Meiberg, PhD, MA, a former EPA official and director of graduate studies in sustainability at Wake Forest University in Winston-Salem, N.C. “To say that you can speak with great precision, that the risk of individuals getting cancer is 1 in 100, may be a little overstating the date on which that statement is based.”

Risk estimates are improving as citizens gain access to more sophisticated monitoring devices, he said. And the primary point of the ProPublica report, that the EPA has underestimated risk by looking at individual sources of pollution rather than combining them, is not an original one, Dr. Meiberg said. “This is an issue that’s been kicking around for quite some time.”

Still, it’s one that demands attention. EPA regulations have succeeded in reducing the overall risk from industrial air pollution over the past few decades. “But there remain areas of particular geographic concentrations,” he said. “And the ProPublica article hit two of them, which have been the subject of discussion for many years, the Houston Ship Channel area and the Baton Rouge to New Orleans industrial corridor where you have a significant proportion of all the chemical petrochemical industry in the United States.”

Improvements in containment of the pollutants, and changes to the industrial processes that produce them, can also help reduce exposure. These changes should occur in the context of dialogue within the communities exposed to the pollution, Dr. Meiberg said.
 

The role of cancer-causing airborne particulate matter

But even if measures are perfectly implemented, Joan Schiller, MD, will not breathe easy. An adjunct professor of oncology at the University of Virginia in Charlottesville, Dr. Schiller has researched the role of airborne particulate matter in causing cancer, a correlation barely mentioned in the ProPublica analysis, she pointed out.

Particulate matter contains a wide range of toxic substances, she said. Researchers have focused on particles 2.5 microns in diameter, or PM 2.5. Some studies have indicated that it’s responsible for one in seven deaths from lung cancer, Dr. Schiller said. “Air pollution also causes lung cancer in never smokers, people who’ve never smoked, not just in smokers.”

Power plants and automobile traffic may be more significant sources of PM 2.5 than industry, and wildfires have recently emerged as increasingly important source, a result of climate change and poor forest management, she said.

PM 2.5 doesn’t affect just lung cancer, said Alexandra White, PhD, an investigator at the National Institute of Environmental Health Sciences in Research Triangle Park, N.C. “My work, as well as work of others, is increasingly suggesting that air pollution is also related to breast cancer risk, in particular, air pollution that is arising from traffic related forces.” And more research is needed on other cancers, she said. “I think that the lack of findings of other cancer sites reflects a lack of study.”

Other pollutants not analyzed in the ProPublica report are also correlated to cancer risk. In a recent meta-analysis, researcher Stephan Gabet, PhD, PharmD, and colleagues at the University of Grenoble, France, estimated that 3.15% of new breast cancer cases in that country could be attributed to nitrogen dioxide and 2.15% to PM 10.

Sources of nitrogen dioxide, PM 2.5, and PM 10 in France include automobile traffic, inefficient wood-burning stoves, and coal-burning power plants in neighboring countries, Dr. Gabet said.

A good approach to reducing pollution from road traffic is the implementation of low-emission zones that prohibit the most polluting vehicles, he said. But a 2019 United Kingdom government study found that brake wear, tire wear, and road surface wear account for 72% of the PM 10 and 60% of the PM 2.5 pollution from road traffic, suggesting that a transition to electric vehicles won’t fix the problem. Better yet, is “the promotion of active modes like walking, cycling, etc., because like this, you can bring additional health gains due to the increase in physical activity,” he said.

Oncologists can help their patients reduce their exposure to air pollution, Dr. Schiller said. “If you have lung cancer, air pollution will hasten your demise. It makes you sicker. Oncologists should be telling their patients about this and advising them to move away from air pollution if possible, and also making sure they know to monitor the health of the air.”

On days when air pollution is high, patients may want to avoid exercising outdoors, or stay indoors altogether, Dr. Berg said. Air purifiers and N95 masks may also help.

And physicians can make a difference by speaking out in their communities, Dr. Schiller said. She is inviting oncologists to join a new group, Oncologists Understanding for Climate and Health. Through this group or on their own, oncologists can speak to their local legislatures or city councils in support of measures to reduce pollution, she said. “Doctors are trusted messengers.”

Dr. Berg disclosed affiliations with Grail, Mercy BioAnalytics and Lucid Diagnostics.