BACKGROUND: The authors previously demonstrated that never-smokers with stage IIIB/IV nonsmall cell lung cancer (NSCLC) lived 50% longer than former/current smokers. This observation persisted after adjusting for age, performance status, and sex. In this study, the authors hypothesized that smoking-dependent differences in the distribution of driver mutations may explain differences in prognosis between these subgroups. METHODS: In total, 293 never-smokers and 382 former/current smokers with lung adenocarcinoma who underwent testing for epidermal growth factor receptor (EGFR) mutations and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations and rearrangements in anaplastic lymphoma kinase (ALK) between 2009 and 2010 were investigated. Clinical outcomes and patient characteristics were collected. Survival probabilities were estimated using the Kaplan-Meier method. Group comparison was performed with log-rank tests and Cox proportional hazards methods. RESULTS: Although the overall incidence of these mutations was nearly identical (55% never-smokers vs 57% current/former smokers; P = .48), there were significant differences in the distribution of mutations between these groups for EGFR mutations (37% never-smokers vs 14% former/current smokers; P < .0001), KRAS mutations (4% never-smokers vs 43% former/current smokers; P < .0001), and ALK rearrangements (12% never-smokers vs 2% former/current smokers; P < .0001). Among never-smokers and former/current smokers, the prognosis differed significantly by genotype. Patients who had KRAS mutations had the poorest survival. Smoking status, however, had no influence on survival within each genotype. CONCLUSIONS: Never-smokers and former/current smokers with lung adenocarcinomas were not homogeneous subgroups. Each was made up of individuals whose tumors had a unique distribution of driver mutations, which were associated with different prognoses, irrespective of smoking history.
BACKGROUND: The authors previously demonstrated that never-smokers with stage IIIB/IV nonsmall cell lung cancer (NSCLC) lived 50% longer than former/current smokers. This observation persisted after adjusting for age, performance status, and sex. In this study, the authors hypothesized that smoking-dependent differences in the distribution of driver mutations may explain differences in prognosis between these subgroups. METHODS: In total, 293 never-smokers and 382 former/current smokers with lung adenocarcinoma who underwent testing for epidermal growth factor receptor (EGFR) mutations and v-Ki-ras2 Kirsten ratsarcoma viral oncogene homolog (KRAS) mutations and rearrangements in anaplastic lymphoma kinase (ALK) between 2009 and 2010 were investigated. Clinical outcomes and patient characteristics were collected. Survival probabilities were estimated using the Kaplan-Meier method. Group comparison was performed with log-rank tests and Cox proportional hazards methods. RESULTS: Although the overall incidence of these mutations was nearly identical (55% never-smokers vs 57% current/former smokers; P = .48), there were significant differences in the distribution of mutations between these groups for EGFR mutations (37% never-smokers vs 14% former/current smokers; P < .0001), KRAS mutations (4% never-smokers vs 43% former/current smokers; P < .0001), and ALK rearrangements (12% never-smokers vs 2% former/current smokers; P < .0001). Among never-smokers and former/current smokers, the prognosis differed significantly by genotype. Patients who had KRAS mutations had the poorest survival. Smoking status, however, had no influence on survival within each genotype. CONCLUSIONS: Never-smokers and former/current smokers with lung adenocarcinomas were not homogeneous subgroups. Each was made up of individuals whose tumors had a unique distribution of driver mutations, which were associated with different prognoses, irrespective of smoking history.
Authors: William Lee; Zhaoshi Jiang; Jinfeng Liu; Peter M Haverty; Yinghui Guan; Jeremy Stinson; Peng Yue; Yan Zhang; Krishna P Pant; Deepali Bhatt; Connie Ha; Stephanie Johnson; Michael I Kennemer; Sankar Mohan; Igor Nazarenko; Colin Watanabe; Andrew B Sparks; David S Shames; Robert Gentleman; Frederic J de Sauvage; Howard Stern; Ajay Pandita; Dennis G Ballinger; Radoje Drmanac; Zora Modrusan; Somasekar Seshagiri; Zemin Zhang Journal: Nature Date: 2010-05-27 Impact factor: 49.962
Authors: Yelena Y Janjigian; Kevin McDonnell; Mark G Kris; Ronglai Shen; Camelia S Sima; Peter B Bach; Naiyer A Rizvi; Gregory J Riely Journal: Cancer Date: 2010-02-01 Impact factor: 6.860
Authors: Alice T Shaw; Beow Y Yeap; Mari Mino-Kenudson; Subba R Digumarthy; Daniel B Costa; Rebecca S Heist; Benjamin Solomon; Hannah Stubbs; Sonal Admane; Ultan McDermott; Jeffrey Settleman; Susumu Kobayashi; Eugene J Mark; Scott J Rodig; Lucian R Chirieac; Eunice L Kwak; Thomas J Lynch; A John Iafrate Journal: J Clin Oncol Date: 2009-08-10 Impact factor: 44.544
Authors: Fred R Hirsch; Marileila Varella-Garcia; Paul A Bunn; Wilbur A Franklin; Rafal Dziadziuszko; Nick Thatcher; Alex Chang; Purvish Parikh; José Rodrigues Pereira; Tudor Ciuleanu; Joachim von Pawel; Claire Watkins; Angela Flannery; Gillian Ellison; Emma Donald; Lucy Knight; Dinah Parums; Nicholas Botwood; Brian Holloway Journal: J Clin Oncol Date: 2006-11-01 Impact factor: 44.544
Authors: Gregory J Riely; Mark G Kris; Daniel Rosenbaum; Jenifer Marks; Allan Li; Dhananjay A Chitale; Khedoudja Nafa; Elyn R Riedel; Meier Hsu; William Pao; Vincent A Miller; Marc Ladanyi Journal: Clin Cancer Res Date: 2008-09-15 Impact factor: 12.531
Authors: Rodney J Landreneau; Daniel P Normolle; Neil A Christie; Omar Awais; Joseph J Wizorek; Ghulam Abbas; Arjun Pennathur; Manisha Shende; Benny Weksler; James D Luketich; Matthew J Schuchert Journal: J Clin Oncol Date: 2014-06-30 Impact factor: 44.544
Authors: Melissa L Johnson; Camelia S Sima; Jamie Chaft; Paul K Paik; William Pao; Mark G Kris; Marc Ladanyi; Gregory J Riely Journal: Cancer Date: 2012-07-18 Impact factor: 6.860
Authors: Adrian G Sacher; Suzanne E Dahlberg; Jennifer Heng; Stacy Mach; Pasi A Jänne; Geoffrey R Oxnard Journal: JAMA Oncol Date: 2016-03 Impact factor: 31.777
Authors: Muhammad Furrukh; Shiyam Kumar; Khawaja F Zahid; Hanan S Al-Shamly; Zainab A Al-Jabri; Ikram A Burney; Mansour S Al-Moundhri Journal: Sultan Qaboos Univ Med J Date: 2017-10-10
Authors: Vijaya Raj Bhatt; Rishi Batra; Peter T Silberstein; Fausto R Loberiza; Apar Kishor Ganti Journal: Med Oncol Date: 2014-11-28 Impact factor: 3.064