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TOPLINE:
A comprehensive review of 92 studies found that 15% to 20% of lung cancers occurred among nonsmokers and were associated with environmental and germline risk factors. These cancers frequently harbored actionable genomic drivers, and targeted EGFR and ALK therapies produced significant diseasefree survival (DFS) and overall survival benefits.
METHODOLOGY:
- Lung cancer continues to be the leading cause of cancer death worldwide, causing about 1.8 million deaths in 2022, with smoking remaining the predominant risk factor. However, the incidence of lung cancer among nonsmokers (those who have smoked less than 100 cigarettes in their lifetime) is rising, varies by sex and geography, and is linked to environmental exposures and family history. The misperception that lung cancer is almost invariably caused by smoking may delay assessment and diagnosis.
- Researchers conducted a review of 92 studies on lung cancer in nonsmokers: 6 meta-analyses or systematic reviews, 16 randomized clinical trials, eight prospective cohort studies, seven retrospective cohort studies, three cross-sectional studies, four observational or case-control studies, 13 genomic studies, and 35 other studies.
- Overall, lung cancer among nonsmokers accounted for 15% to 20% of all lung cancer cases. Most lung cancers in nonsmokers were adenocarcinomas (60% to 80%), with a median age at diagnosis of 67 years in this group compared with 70 years in people with a history of smoking.
- Data analysis from three US hospital networks showed that the proportion of lung cancer among nonsmokers increased from 8.0% to 14.9% between 1990 and 2013. A pooled analysis of seven Finnish cohorts reported an absolute increase in lung cancer among nonsmokers from 6.9 per 100,000 person-years in 1972 to 12.9 per 100,000 person-years in 2015.
- The age-adjusted incidence rate of lung cancer in the US between 2000 and 2013 was 17.5 per 100,000 individuals among Asian female nonsmokers compared with 10.1 per 100,000 among non-Hispanic White female nonsmokers.
TAKEAWAY:
- Environmental and occupational risk factors were secondhand smoke, residential radon, outdoor and household air pollution (PM2.5), asbestos and silica exposure, and prior thoracic radiotherapy. Having a first-degree relative with lung cancer increased the risk of developing lung cancer, and genome-wide association studies identified susceptibility loci associated with lung cancer risk in nonsmokers.
- Family history and inherited susceptibility increased lung cancer risk in never smokers (odds ratio [OR] for lung cancer in those with a first–degree relative, 1.51), and clonal hematopoiesis was also associated with higher risk (OR, 1.43). Importantly, tumors in nonsmokers were frequently driven by actionable somatic alterations (EGFR mutations, 40% to 60% in nonsmokers compared with 10% in smokers) and enrichment of ALK/ROS1/RET/ERBB2/NTRK/NRG1 fusions; 78% to 92% of adenocarcinomas in nonsmokers harbored actionable drivers (compared with 49.5% in ever smokers), and nonsmokers had a substantially lower tumor mutational burden (10–fold lower).
- Similar to individuals with a history of smoking, nonsmokers with lung cancer presented with cough, pain, dyspnea, or weight loss or had disease detected incidentally. Surgical resection remained the preferred treatment for anatomically resectable lung cancer (stages I-III) in medically eligible patients, with follow-up CT screening recommended every 6 months for 2 to 3 years and then annually.
- Targeted adjuvant therapy substantially improved outcomes for resected EGFR–mutant or ALK–rearranged non-small cell lung cancer (NSCLC). Four-year DFS was increased to 70% with osimertinib compared with 29% with placebo (hazard ratio [HR], 0.23) and 5–year overall survival was increased to 85% compared with 73% (HR, 0.49). Two–year DFS was 93.8% with alectinib compared with 63% with placebo (HR, 0.24). In unresectable EGFR-mutated stage III NSCLC, median progression-free survival was 39.1 months with adjuvant osimertinib compared with 5.6 months with placebo. For resected ALKpositive disease, 2–year DFS was 93.8% with adjuvant alectinib compared with 63.0% with chemotherapy (HR, 0.24).
- However, singleagent single agent programmed cell death protein 1 inhibitors or programmed death-ligand 1 inhibitors demonstrated limited efficacy in EGFR or ALK–driven tumors, and benefit was attenuated in never smokers. Regarding screening and early detection, the US Preventive Services Task Force did not recommend lowdose CT screening for nonsmokers, whereas Taiwan implemented a biennial screening program for selected nonsmoking high–risk groups.
IN PRACTICE:
“Among patients with lung cancer, nonsmoking individuals are more likely to have genomic alterations, such as EGFR mutations or ALK gene rearrangements, and these patients have improved survival when treated with TKIs compared with chemotherapy,” the authors of the study wrote.
SOURCE:
The study, led by Cian Murphy, PhD, Cancer Evolution and Genome Instability Laboratory, Francis Crick Institute, London, England, was published online in JAMA.
LIMITATIONS:
Becausesmoking history was often not included in many databases, cancer registries, and trials, the incidence and prevalence of lung cancer in nonsmokers could not be accurately determined. Additionally, accurate quantification of environmental exposures, such as air pollution, presented significant challenges. The quality of the evidence was not formally evaluated, and some relevant articles may have been missed in the literature review.
DISCLOSURES:
The study received support from multiple organizations, including the Rosetrees Trust, Ruth Strauss Foundation, Cancer Research UK, and the National Health and Medical Research Council. Several authors reported receiving grants or personal fees from and having other ties with various sources. Full disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
TOPLINE:
A comprehensive review of 92 studies found that 15% to 20% of lung cancers occurred among nonsmokers and were associated with environmental and germline risk factors. These cancers frequently harbored actionable genomic drivers, and targeted EGFR and ALK therapies produced significant diseasefree survival (DFS) and overall survival benefits.
METHODOLOGY:
- Lung cancer continues to be the leading cause of cancer death worldwide, causing about 1.8 million deaths in 2022, with smoking remaining the predominant risk factor. However, the incidence of lung cancer among nonsmokers (those who have smoked less than 100 cigarettes in their lifetime) is rising, varies by sex and geography, and is linked to environmental exposures and family history. The misperception that lung cancer is almost invariably caused by smoking may delay assessment and diagnosis.
- Researchers conducted a review of 92 studies on lung cancer in nonsmokers: 6 meta-analyses or systematic reviews, 16 randomized clinical trials, eight prospective cohort studies, seven retrospective cohort studies, three cross-sectional studies, four observational or case-control studies, 13 genomic studies, and 35 other studies.
- Overall, lung cancer among nonsmokers accounted for 15% to 20% of all lung cancer cases. Most lung cancers in nonsmokers were adenocarcinomas (60% to 80%), with a median age at diagnosis of 67 years in this group compared with 70 years in people with a history of smoking.
- Data analysis from three US hospital networks showed that the proportion of lung cancer among nonsmokers increased from 8.0% to 14.9% between 1990 and 2013. A pooled analysis of seven Finnish cohorts reported an absolute increase in lung cancer among nonsmokers from 6.9 per 100,000 person-years in 1972 to 12.9 per 100,000 person-years in 2015.
- The age-adjusted incidence rate of lung cancer in the US between 2000 and 2013 was 17.5 per 100,000 individuals among Asian female nonsmokers compared with 10.1 per 100,000 among non-Hispanic White female nonsmokers.
TAKEAWAY:
- Environmental and occupational risk factors were secondhand smoke, residential radon, outdoor and household air pollution (PM2.5), asbestos and silica exposure, and prior thoracic radiotherapy. Having a first-degree relative with lung cancer increased the risk of developing lung cancer, and genome-wide association studies identified susceptibility loci associated with lung cancer risk in nonsmokers.
- Family history and inherited susceptibility increased lung cancer risk in never smokers (odds ratio [OR] for lung cancer in those with a first–degree relative, 1.51), and clonal hematopoiesis was also associated with higher risk (OR, 1.43). Importantly, tumors in nonsmokers were frequently driven by actionable somatic alterations (EGFR mutations, 40% to 60% in nonsmokers compared with 10% in smokers) and enrichment of ALK/ROS1/RET/ERBB2/NTRK/NRG1 fusions; 78% to 92% of adenocarcinomas in nonsmokers harbored actionable drivers (compared with 49.5% in ever smokers), and nonsmokers had a substantially lower tumor mutational burden (10–fold lower).
- Similar to individuals with a history of smoking, nonsmokers with lung cancer presented with cough, pain, dyspnea, or weight loss or had disease detected incidentally. Surgical resection remained the preferred treatment for anatomically resectable lung cancer (stages I-III) in medically eligible patients, with follow-up CT screening recommended every 6 months for 2 to 3 years and then annually.
- Targeted adjuvant therapy substantially improved outcomes for resected EGFR–mutant or ALK–rearranged non-small cell lung cancer (NSCLC). Four-year DFS was increased to 70% with osimertinib compared with 29% with placebo (hazard ratio [HR], 0.23) and 5–year overall survival was increased to 85% compared with 73% (HR, 0.49). Two–year DFS was 93.8% with alectinib compared with 63% with placebo (HR, 0.24). In unresectable EGFR-mutated stage III NSCLC, median progression-free survival was 39.1 months with adjuvant osimertinib compared with 5.6 months with placebo. For resected ALKpositive disease, 2–year DFS was 93.8% with adjuvant alectinib compared with 63.0% with chemotherapy (HR, 0.24).
- However, singleagent single agent programmed cell death protein 1 inhibitors or programmed death-ligand 1 inhibitors demonstrated limited efficacy in EGFR or ALK–driven tumors, and benefit was attenuated in never smokers. Regarding screening and early detection, the US Preventive Services Task Force did not recommend lowdose CT screening for nonsmokers, whereas Taiwan implemented a biennial screening program for selected nonsmoking high–risk groups.
IN PRACTICE:
“Among patients with lung cancer, nonsmoking individuals are more likely to have genomic alterations, such as EGFR mutations or ALK gene rearrangements, and these patients have improved survival when treated with TKIs compared with chemotherapy,” the authors of the study wrote.
SOURCE:
The study, led by Cian Murphy, PhD, Cancer Evolution and Genome Instability Laboratory, Francis Crick Institute, London, England, was published online in JAMA.
LIMITATIONS:
Becausesmoking history was often not included in many databases, cancer registries, and trials, the incidence and prevalence of lung cancer in nonsmokers could not be accurately determined. Additionally, accurate quantification of environmental exposures, such as air pollution, presented significant challenges. The quality of the evidence was not formally evaluated, and some relevant articles may have been missed in the literature review.
DISCLOSURES:
The study received support from multiple organizations, including the Rosetrees Trust, Ruth Strauss Foundation, Cancer Research UK, and the National Health and Medical Research Council. Several authors reported receiving grants or personal fees from and having other ties with various sources. Full disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
TOPLINE:
A comprehensive review of 92 studies found that 15% to 20% of lung cancers occurred among nonsmokers and were associated with environmental and germline risk factors. These cancers frequently harbored actionable genomic drivers, and targeted EGFR and ALK therapies produced significant diseasefree survival (DFS) and overall survival benefits.
METHODOLOGY:
- Lung cancer continues to be the leading cause of cancer death worldwide, causing about 1.8 million deaths in 2022, with smoking remaining the predominant risk factor. However, the incidence of lung cancer among nonsmokers (those who have smoked less than 100 cigarettes in their lifetime) is rising, varies by sex and geography, and is linked to environmental exposures and family history. The misperception that lung cancer is almost invariably caused by smoking may delay assessment and diagnosis.
- Researchers conducted a review of 92 studies on lung cancer in nonsmokers: 6 meta-analyses or systematic reviews, 16 randomized clinical trials, eight prospective cohort studies, seven retrospective cohort studies, three cross-sectional studies, four observational or case-control studies, 13 genomic studies, and 35 other studies.
- Overall, lung cancer among nonsmokers accounted for 15% to 20% of all lung cancer cases. Most lung cancers in nonsmokers were adenocarcinomas (60% to 80%), with a median age at diagnosis of 67 years in this group compared with 70 years in people with a history of smoking.
- Data analysis from three US hospital networks showed that the proportion of lung cancer among nonsmokers increased from 8.0% to 14.9% between 1990 and 2013. A pooled analysis of seven Finnish cohorts reported an absolute increase in lung cancer among nonsmokers from 6.9 per 100,000 person-years in 1972 to 12.9 per 100,000 person-years in 2015.
- The age-adjusted incidence rate of lung cancer in the US between 2000 and 2013 was 17.5 per 100,000 individuals among Asian female nonsmokers compared with 10.1 per 100,000 among non-Hispanic White female nonsmokers.
TAKEAWAY:
- Environmental and occupational risk factors were secondhand smoke, residential radon, outdoor and household air pollution (PM2.5), asbestos and silica exposure, and prior thoracic radiotherapy. Having a first-degree relative with lung cancer increased the risk of developing lung cancer, and genome-wide association studies identified susceptibility loci associated with lung cancer risk in nonsmokers.
- Family history and inherited susceptibility increased lung cancer risk in never smokers (odds ratio [OR] for lung cancer in those with a first–degree relative, 1.51), and clonal hematopoiesis was also associated with higher risk (OR, 1.43). Importantly, tumors in nonsmokers were frequently driven by actionable somatic alterations (EGFR mutations, 40% to 60% in nonsmokers compared with 10% in smokers) and enrichment of ALK/ROS1/RET/ERBB2/NTRK/NRG1 fusions; 78% to 92% of adenocarcinomas in nonsmokers harbored actionable drivers (compared with 49.5% in ever smokers), and nonsmokers had a substantially lower tumor mutational burden (10–fold lower).
- Similar to individuals with a history of smoking, nonsmokers with lung cancer presented with cough, pain, dyspnea, or weight loss or had disease detected incidentally. Surgical resection remained the preferred treatment for anatomically resectable lung cancer (stages I-III) in medically eligible patients, with follow-up CT screening recommended every 6 months for 2 to 3 years and then annually.
- Targeted adjuvant therapy substantially improved outcomes for resected EGFR–mutant or ALK–rearranged non-small cell lung cancer (NSCLC). Four-year DFS was increased to 70% with osimertinib compared with 29% with placebo (hazard ratio [HR], 0.23) and 5–year overall survival was increased to 85% compared with 73% (HR, 0.49). Two–year DFS was 93.8% with alectinib compared with 63% with placebo (HR, 0.24). In unresectable EGFR-mutated stage III NSCLC, median progression-free survival was 39.1 months with adjuvant osimertinib compared with 5.6 months with placebo. For resected ALKpositive disease, 2–year DFS was 93.8% with adjuvant alectinib compared with 63.0% with chemotherapy (HR, 0.24).
- However, singleagent single agent programmed cell death protein 1 inhibitors or programmed death-ligand 1 inhibitors demonstrated limited efficacy in EGFR or ALK–driven tumors, and benefit was attenuated in never smokers. Regarding screening and early detection, the US Preventive Services Task Force did not recommend lowdose CT screening for nonsmokers, whereas Taiwan implemented a biennial screening program for selected nonsmoking high–risk groups.
IN PRACTICE:
“Among patients with lung cancer, nonsmoking individuals are more likely to have genomic alterations, such as EGFR mutations or ALK gene rearrangements, and these patients have improved survival when treated with TKIs compared with chemotherapy,” the authors of the study wrote.
SOURCE:
The study, led by Cian Murphy, PhD, Cancer Evolution and Genome Instability Laboratory, Francis Crick Institute, London, England, was published online in JAMA.
LIMITATIONS:
Becausesmoking history was often not included in many databases, cancer registries, and trials, the incidence and prevalence of lung cancer in nonsmokers could not be accurately determined. Additionally, accurate quantification of environmental exposures, such as air pollution, presented significant challenges. The quality of the evidence was not formally evaluated, and some relevant articles may have been missed in the literature review.
DISCLOSURES:
The study received support from multiple organizations, including the Rosetrees Trust, Ruth Strauss Foundation, Cancer Research UK, and the National Health and Medical Research Council. Several authors reported receiving grants or personal fees from and having other ties with various sources. Full disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.