Daniel Shepshelovich1, Wei Xu2, Lin Lu3, Aline Fares4, Ping Yang5, David Christiani6, Jie Zhang7, Kouya Shiraishi8, Brid M Ryan9, Chu Chen10, Ann G Schwartz11, Adonina Tardon12, Xifeng Wu13, Matthew B Schabath14, M Dawn Teare15, Loic Le Marchand16, Zuo-Feng Zhang17, John K Field18, Hermann Brenner19, Nancy Diao6, Juntao Xie20, Takashi Kohno8, Curtis C Harris9, Angela S Wenzlaff11, Guillermo Fernandez-Tardon12, Yuanqing Ye13, Fiona Taylor15, Lynne R Wilkens16, Michael Davies18, Yi Liu21, Matt J Barnett22, Gary E Goodman23, Hal Morgenstern24, Bernd Holleczek25, M Catherine Brown4, Geoffrey Liu26, Rayjean J Hung27. 1. Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre; University of Toronto, Toronto, Ontario, Canada; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. 2. Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada. 3. Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, Ontario, Canada. 4. Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre; University of Toronto, Toronto, Ontario, Canada. 5. Mayo Clinic, Rochester, Minnesota. 6. Environmental Health Department, Harvard TH Chan School of Public Health and Harvard Medical School, Boston, Massachusetts. 7. Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. 8. Division of Genome Biology, National Cancer Research Institute, Tokyo, Japan. 9. Centre for Cancer Research, National Institutes of Health, Bethesda, Maryland. 10. Program in Epidemiology, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Epidemiology and Department of Otolaryngology: Head and Neck Surgery, University of Washington, Seattle, Washington. 11. Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, Michigan. 12. IUOPA, University of Oviedo and CIBERESP, Oviedo, Spain. 13. University of Texas MD Anderson Cancer Center, Houston, Texas. 14. H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida. 15. University of Sheffield, Sheffield, United Kingdom. 16. University of Hawaii Cancer Centre, Honolulu, Hawaii. 17. University of California Los Angeles School of Public Health, California. 18. The Roy Castle Lung Cancer Programme, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, United Kingdom. 19. Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; Division of Preventive Oncology, German Cancer Research Center (DKFZ), National Center for Tumor Diseases (NCT), Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. 20. Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. 21. PLA Hospital, Beijing, China. 22. Cancer Prevention Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. 23. Swedish Cancer Institute, Seattle, Washington. 24. Departments of Epidemiology and Environmental Health Sciences, School of Public Health and Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan. 25. Saarland Cancer Registry, Saarbrücken, Germany. 26. Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre; University of Toronto, Toronto, Ontario, Canada; Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. Electronic address: geoffrey.liu@uhn.ca. 27. Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.
Abstract
INTRODUCTION: The relationships between morbid obesity, changes in body mass index (BMI) before cancer diagnosis, and lung cancer outcomes by histology (SCLC and NSCLC) have not been well studied. METHODS: Individual level data analysis was performed on 25,430 patients with NSCLC and 2787 patients with SCLC from 16 studies of the International Lung Cancer Consortium evaluating the association between various BMI variables and lung cancer overall survival, reported as adjusted hazard ratios (aHRs) from Cox proportional hazards models and adjusted penalized smoothing spline plots. RESULTS: Overall survival of NSCLC had putative U-shaped hazard ratio relationships with BMI based on spline plots: being underweight (BMI < 18.5 kg/m2; aHR = 1.56; 95% confidence interval [CI]:1.43-1.70) or morbidly overweight (BMI > 40 kg/m2; aHR = 1.09; 95% CI: 0.95-1.26) at the time of diagnosis was associated with worse stage-specific prognosis, whereas being overweight (25 kg/m2 ≤ BMI < 30 kg/m2; aHR = 0.89; 95% CI: 0.85-0.95) or obese (30 kg/m2 ≤ BMI ≤ 40 kg/m2; aHR = 0.86; 95% CI: 0.82-0.91) was associated with improved survival. Although not significant, a similar pattern was seen with SCLC. Compared with an increased or stable BMI from the period between young adulthood until date of diagnosis, a decreased BMI was associated with worse outcomes in NSCLC (aHR = 1.24; 95% CI: 1.2-1.3) and SCLC patients (aHR=1.26 (95% CI: 1.0-1.6). Decreased BMI was consistently associated with worse outcome, across clinicodemographic subsets. CONCLUSIONS: Both being underweight or morbidly obese at time of diagnosis is associated with lower stage-specific survival in independent assessments of NSCLC and SCLC patients. In addition, a decrease in BMI at lung cancer diagnosis relative to early adulthood is a consistent marker of poor survival.
INTRODUCTION: The relationships between morbid obesity, changes in body mass index (BMI) before cancer diagnosis, and lung cancer outcomes by histology (SCLC and NSCLC) have not been well studied. METHODS: Individual level data analysis was performed on 25,430 patients with NSCLC and 2787 patients with SCLC from 16 studies of the International Lung Cancer Consortium evaluating the association between various BMI variables and lung cancer overall survival, reported as adjusted hazard ratios (aHRs) from Cox proportional hazards models and adjusted penalized smoothing spline plots. RESULTS: Overall survival of NSCLC had putative U-shaped hazard ratio relationships with BMI based on spline plots: being underweight (BMI < 18.5 kg/m2; aHR = 1.56; 95% confidence interval [CI]:1.43-1.70) or morbidly overweight (BMI > 40 kg/m2; aHR = 1.09; 95% CI: 0.95-1.26) at the time of diagnosis was associated with worse stage-specific prognosis, whereas being overweight (25 kg/m2 ≤ BMI < 30 kg/m2; aHR = 0.89; 95% CI: 0.85-0.95) or obese (30 kg/m2 ≤ BMI ≤ 40 kg/m2; aHR = 0.86; 95% CI: 0.82-0.91) was associated with improved survival. Although not significant, a similar pattern was seen with SCLC. Compared with an increased or stable BMI from the period between young adulthood until date of diagnosis, a decreased BMI was associated with worse outcomes in NSCLC (aHR = 1.24; 95% CI: 1.2-1.3) and SCLCpatients (aHR=1.26 (95% CI: 1.0-1.6). Decreased BMI was consistently associated with worse outcome, across clinicodemographic subsets. CONCLUSIONS: Both being underweight or morbidly obese at time of diagnosis is associated with lower stage-specific survival in independent assessments of NSCLC and SCLCpatients. In addition, a decrease in BMI at lung cancer diagnosis relative to early adulthood is a consistent marker of poor survival.
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