Shria Kumar1, Nadim Mahmud1, David S Goldberg2, Jashodeep Datta3, David E Kaplan4. 1. Division of Gastroenterology and Hepatology, Perelman School of Medicine at the University of Pennsylvania, United States. 2. Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine, United States. 3. Division of Surgical Oncology, Department of Surgery, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, United States. 4. Division of Gastroenterology and Hepatology, Perelman School of Medicine at the University of Pennsylvania, United States; Gastroenterology Section, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, United States. Electronic address: dakaplan@pennmedicine.upenn.edu.
Abstract
OBJECTIVES: The obesity paradox, whereby obesity appears to confer protection against cancer-related mortality, remains controversial. This has not yet been evaluated in upper gastrointestinal cancers. DESIGNS: We identified esophageal, cardia, and non-cardia gastric adenocarcinomas in the Veterans Health Administration between 2006-2016. Multivariable Cox proportional hazard models evaluate the impact of BMI at- and prior to- cancer diagnosis on mortality, adjusting for demographics, clinical characteristics, weight loss, and clinical stage (early: T1B/2N0; locally advanced: ≥T2N+). RESULTS: We identify 1308 patients: 99 % male, median 66 years. In early disease, relative to BMI 30, BMI 18 and 20 at diagnosis had increased risk of death (HR 1.83, 95 %CI: 1.38-2.44 and HR 1.50, 95 %CI: 1.20-1.87, respectively, p < 0.0001). Patients with BMI > 30 did not. In locally advanced disease, at diagnosis BMI 18 (HR 1.58, 95 %CI: 1.0001-1.48, p = 0.05), BMI 20 (HR 1.46, 95 %CI: 1.01-2.09, p = 0.04), and BMI 25 (HR 1.20, 95 %CI: 1.04-1.38, p = 0.01) had increased risk of death, but BMI > 30 did not. In models assessing premorbid BMI and weight loss, increasing amounts of weight loss were associated with mortality independent of BMI in early cancers. For locally advanced cancers, without weight loss, there was no association with death, regardless of BMI. CONCLUSION: The predominant driver of mortality across clinical stages is weight loss. The obesity paradox appears to exist in early stage disease only. Future studies should investigate mechanisms for the obesity paradox, accompanying physiologic changes with weight loss preceding diagnosis, and if patients with low BMI and weight loss benefit from early nutritional support.
OBJECTIVES: The obesity paradox, whereby obesity appears to confer protection against cancer-related mortality, remains controversial. This has not yet been evaluated in upper gastrointestinal cancers. DESIGNS: We identified esophageal, cardia, and non-cardia gastric adenocarcinomas in the Veterans Health Administration between 2006-2016. Multivariable Cox proportional hazard models evaluate the impact of BMI at- and prior to- cancer diagnosis on mortality, adjusting for demographics, clinical characteristics, weight loss, and clinical stage (early: T1B/2N0; locally advanced: ≥T2N+). RESULTS: We identify 1308 patients: 99 % male, median 66 years. In early disease, relative to BMI 30, BMI 18 and 20 at diagnosis had increased risk of death (HR 1.83, 95 %CI: 1.38-2.44 and HR 1.50, 95 %CI: 1.20-1.87, respectively, p < 0.0001). Patients with BMI > 30 did not. In locally advanced disease, at diagnosis BMI 18 (HR 1.58, 95 %CI: 1.0001-1.48, p = 0.05), BMI 20 (HR 1.46, 95 %CI: 1.01-2.09, p = 0.04), and BMI 25 (HR 1.20, 95 %CI: 1.04-1.38, p = 0.01) had increased risk of death, but BMI > 30 did not. In models assessing premorbid BMI and weight loss, increasing amounts of weight loss were associated with mortality independent of BMI in early cancers. For locally advanced cancers, without weight loss, there was no association with death, regardless of BMI. CONCLUSION: The predominant driver of mortality across clinical stages is weight loss. The obesity paradox appears to exist in early stage disease only. Future studies should investigate mechanisms for the obesity paradox, accompanying physiologic changes with weight loss preceding diagnosis, and if patients with low BMI and weight loss benefit from early nutritional support.
Authors: K L Prenzel; A H Hölscher; U Drebber; M Agavonova; C A Gutschow; E Bollschweiler Journal: Eur J Surg Oncol Date: 2012-01-25 Impact factor: 4.424
Authors: Kenneth F Adams; Arthur Schatzkin; Tamara B Harris; Victor Kipnis; Traci Mouw; Rachel Ballard-Barbash; Albert Hollenbeck; Michael F Leitzmann Journal: N Engl J Med Date: 2006-08-22 Impact factor: 91.245
Authors: Thomas Gilbert; Jenny Neuburger; Joshua Kraindler; Eilis Keeble; Paul Smith; Cono Ariti; Sandeepa Arora; Andrew Street; Stuart Parker; Helen C Roberts; Martin Bardsley; Simon Conroy Journal: Lancet Date: 2018-04-26 Impact factor: 79.321
Authors: Wendy Demark-Wahnefried; Laura Q Rogers; Justin T Gibson; Shuko Harada; Andrew D Frugé; Robert A Oster; William E Grizzle; Lyse A Norian; Eddy S Yang; Deborah Della Manna; Lee W Jones; Maria Azrad; Helen Krontiras Journal: Int J Cancer Date: 2019-09-05 Impact factor: 7.396