Mei Jiang1, Aline F Fares2, Daniel Shepshelovich3, Ping Yang4, David Christiani5, Jie Zhang6, Kouya Shiraishi7, Brid M Ryan8, Chu Chen9, Ann G Schwartz10, Adonina Tardon11, Sanjay Shete12, Matthew B Schabath13, M Dawn Teare14, Loic Le Marchand15, Zuo-Feng Zhang16, John K Field17, Hermann Brenner18, Nancy Diao5, Juntao Xie19, Takashi Kohno7, Curtis C Harris8, Angela S Wenzlaff10, Guillermo Fernandez-Tardon11, Yuanqing Ye12, Fiona Taylor14, Lynne R Wilkens15, Michael Davies17, Yi Liu20, Matt J Barnett21, Gary E Goodman22, Hal Morgenstern23, Bernd Holleczek24, Sera Thomas25, M Catherine Brown26, Rayjean J Hung27, Wei Xu28, Geoffrey Liu29. 1. Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, ON, Canada; State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. 2. Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada; Hospital de Base, São José do Rio Preto, São Paulo, Brazil. 3. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. 4. Mayo Clinic, Rochester, MI, USA. 5. Environmental Health Department, Harvard TH Chan School of Public Health and Harvard Medical School, Boston, MA, USA. 6. Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, USA; Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. 7. Division of Genome Biology, National Cancer Research Institute, Tokyo, Japan. 8. Centre for Cancer Research, National Institutes of Health, Bethesda, MD, USA. 9. Program in Epidemiology, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Epidemiology and Department of Otolaryngology: Head and Neck Surgery, University of Washington, Seattle, WA, USA. 10. Barbara Ann Karmanos Cancer Institute, Wayne State University Detroit, MI, USA. 11. IUOPA, University of Oviedo and CIBERESP, Oviedo, Spain. 12. University of Texas MD Anderson Cancer Center, Texas, USA. 13. H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. 14. University of Sheffield, Sheffield, UK. 15. University of Hawaii Cancer Centre, Honolulu, HI, USA. 16. University of California Los Angeles School of Public Health, CA, USA. 17. The Roy Castle Lung Cancer Programme, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, UK. 18. Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. 19. Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. 20. Mayo Clinic, Rochester, MI, USA; PLA Hospital, Beijing, China. 21. Cancer Prevention Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 22. Swedish Cancer Institute, Seattle, WA, USA. 23. Departments of Epidemiology and Environmental Health Sciences, School of Public Health and Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA. 24. Saarland Cancer Registry, Saarbrücken, Germany. 25. Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada. 26. Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada. 27. Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada; Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada. 28. Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, ON, Canada; Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada. Electronic address: Wei.Xu@uhnresearch.ca. 29. Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada; Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada; Departments of Medical Biophysics, Pharmacology and Toxicity, and IMS, University of Toronto, Toronto, ON, Canada. Electronic address: Geoffrey.liu@uhn.ca.
Abstract
INTRODUCTION: The relationship between Body-Mass-Index (BMI) and lung cancer prognosis is heterogeneous. We evaluated the impact of sex, smoking and race on the relationship between BMI and overall survival (OS) in non-small-cell-lung-cancer (NSCLC). METHODS: Data from 16 individual ILCCO studies were pooled to assess interactions between BMI and the following factors on OS: self-reported race, smoking status and sex, using Cox models (adjusted hazard ratios; aHR) with interaction terms and adjusted penalized smoothing spline plots in stratified analyses. RESULTS: Among 20,937 NSCLC patients with BMI values, females = 47 %; never-smokers = 14 %; White-patients = 76 %. BMI showed differential survival according to race whereby compared to normal-BMI patients, being underweight was associated with poor survival among white patients (OS, aHR = 1.66) but not among black patients (aHR = 1.06; pinteraction = 0.02). Comparing overweight/obese to normal weight patients, Black NSCLC patients who were overweight/obese also had relatively better OS (pinteraction = 0.06) when compared to White-patients. BMI was least associated with survival in Asian-patients and never-smokers. The outcomes of female ever-smokers at the extremes of BMI were associated with worse outcomes in both the underweight (pinteraction<0.001) and obese categories (pinteraction = 0.004) relative to the normal-BMI category, when compared to male ever-smokers. CONCLUSION: Underweight and obese female ever-smokers were associated with worse outcomes in White-patients. These BMI associations were not observed in Asian-patients and never-smokers. Black-patients had more favorable outcomes in the extremes of BMI when compared to White-patients. Body composition in Black-patients, and NSCLC subtypes more commonly seen in Asian-patients and never-smokers, may account for differences in these BMI-OS relationships.
INTRODUCTION: The relationship between Body-Mass-Index (BMI) and lung cancer prognosis is heterogeneous. We evaluated the impact of sex, smoking and race on the relationship between BMI and overall survival (OS) in non-small-cell-lung-cancer (NSCLC). METHODS: Data from 16 individual ILCCO studies were pooled to assess interactions between BMI and the following factors on OS: self-reported race, smoking status and sex, using Cox models (adjusted hazard ratios; aHR) with interaction terms and adjusted penalized smoothing spline plots in stratified analyses. RESULTS: Among 20,937 NSCLC patients with BMI values, females = 47 %; never-smokers = 14 %; White-patients = 76 %. BMI showed differential survival according to race whereby compared to normal-BMI patients, being underweight was associated with poor survival among white patients (OS, aHR = 1.66) but not among black patients (aHR = 1.06; pinteraction = 0.02). Comparing overweight/obese to normal weight patients, Black NSCLC patients who were overweight/obese also had relatively better OS (pinteraction = 0.06) when compared to White-patients. BMI was least associated with survival in Asian-patients and never-smokers. The outcomes of female ever-smokers at the extremes of BMI were associated with worse outcomes in both the underweight (pinteraction<0.001) and obese categories (pinteraction = 0.004) relative to the normal-BMI category, when compared to male ever-smokers. CONCLUSION: Underweight and obese female ever-smokers were associated with worse outcomes in White-patients. These BMI associations were not observed in Asian-patients and never-smokers. Black-patients had more favorable outcomes in the extremes of BMI when compared to White-patients. Body composition in Black-patients, and NSCLC subtypes more commonly seen in Asian-patients and never-smokers, may account for differences in these BMI-OS relationships.
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