Association between Body Mass Index and Cancer Survival in a Pooled Analysis of 22 Clinical Trials

Abstract

Background: Data are inconsistent on the association between body mass index (BMI) at time of cancer diagnosis and prognosis. We used data from 22 clinical treatment trials to examine the association between BMI and survival across multiple cancer types and stages.

Methods: Trials with ≥5 years of follow-up were selected. Patients with BMI < 18.5 kg/m² were excluded. Within a disease, analyses were limited to patients on similar treatment regimens. Variable cutpoint analysis identified a BMI cutpoint that maximized differences in survival. Multivariable Cox regression analyses compared survival between patients with BMI above versus below the cutpoint, adjusting for age, race, sex, and important disease-specific clinical prognostic factors.

Results: A total of 11,724 patients from 22 trials were identified. Fourteen analyses were performed by disease site and treatment regimen. A cutpoint of BMI = 25 kg/m² maximized survival differences. No statistically significant trend across all 14 analyses was observed (mean HR = 0.96; P = 0.06). In no cancer/treatment combination was elevated BMI associated with an increased risk of death; for some cancers there was a survival advantage for higher BMI. In sex-stratified analyses, BMI ≥ 25 kg/m² was associated with better overall survival among men (HR = 0.82; P = 0.003), but not women (HR = 1.04; P = 0.86). The association persisted when sex-specific cancers were excluded, when treatment regimens were restricted to dose based on body surface area, and when early-stage cancers were excluded.

Conclusion: The association between BMI and survival is not consistent across cancer types and stages.

Impact: Our findings suggest that disease, stage, and gender-specific body size recommendations for cancer survivors may be warranted. Cancer Epidemiol Biomarkers Prev; 26(1); 21-29. ©2016 AACR SEE ALL THE ARTICLES IN THIS CEBP FOCUS SECTION, "THE OBESITY PARADOX IN CANCER EVIDENCE AND NEW DIRECTIONS".

Figure 1. Mean Chi Square by Body Mass Index Cutpoint Level

Results for different amounts of allowed followup (1 to 10 years) The average of all results, by cutpoint Each observation in the plot represents the average chi-square statistic for the association of BMI status and overall survival for a given BMI cutpoint, averaged across the 14 different treatment analyses. The dashed lines indicate results for different amounts of allowed followup (1 to 10 years). The solid heavy line shows the average of all results by cutpoint, and indicates that a BMI level of 25 kg/m², which distinguishes normal weight patients from overweight patients, maximizes the association of BMI and overall survival.

Figure 2. Kaplan Meier Survival Curves, by Cancer and Treatment

Dashed line = BMI≥25 kg/m² Solid line = BMI<25 kg/m² Kaplan Meier survival curves of 14 separate cancer and treatment combinations using data from 22 different SWOG clinical trials. Abbreviations: 5FU, 5-fluorouracil; a-IFN, interferon alpha; AC, doxorubicin, cyclophosphamide; ADT, androgen deprivation therapy; AML, acute myelogenous leukemia; ara-C, cytarabine; BCG, bacillus Calmette-Guerin; BMI, body mass index; CAF, cyclophosphamide, doxorubicin, and 5-fluorouracil; CHOP, cyclophosphamide, hydroxydaunomycin, oncovin, and prednisone; CMF, cyclophosphamide, methotrexate, and 5-fluorouracil; DNR, daunorubicin; GIST, gastrointestinal stromal tumor; NHL, non-Hodgkin’s lymphoma; NSCLC, non-small cell lung cancer; P, paclitaxel

Figure 3. Association of BMI and Overall Survival, Based on BMI=25 kg/m² Cutpoint

A forest plot displaying hazard ratio (HR) estimates across 14 different cancer and treatment combinations. HR <1 indicates that BMI ≥25 kg/m² is associated with decreased risk of death, while HR >1 indicates that BMI ≤25 kg/m² is associated with increased risk of death. Abbreviations: 5FU, 5-fluorouracil; a-IFN, interferon alpha; AC, doxorubicin, cyclophosphamide; ADT, androgen deprivation therapy; AML, acute myelogenous leukemia; ara-C, cytarabine; BCG, bacillus Calmette-Guerin; BMI, body mass index; CAF, cyclophosphamide, doxorubicin, and 5-fluorouracil; CHOP, cyclophosphamide, hydroxydaunomycin, oncovin, and prednisone; CMF, cyclophosphamide, methotrexate, and 5-fluorouracil; DNR, daunorubicin; GIST, gastrointestinal stromal tumor; NHL, non-Hodgkin’s lymphoma; NSCLC, non-small cell lung cancer; P, paclitaxel

Figure 4. Association of BMI and Overall Survival, By Sex and Regimens, Based on BMI=25 kg/m² Cutpoint

Forest plots displaying hazard ratio (HR) estimates across 14 different cancer and treatment combinations. HR <1 indicates that BMI ≥25 kg/m² is associated with decreased risk of death, while HR >1 indicates that BMI ≤25 kg/m² is associated with increased risk of death. Panel A displays forest plots by sex; Panel B displays analyses restricted to treatment regimens using doses based upon body surface area, by sex; and Panel C displays analyses excluding sex-specific analyses, by sex. Abbreviations: 5FU, 5-fluorouracil; a-IFN, interferon alpha; AC, doxorubicin, cyclophosphamide; ADT, androgen deprivation therapy; AML, acute myelogenous leukemia; ara-C, cytarabine; BCG, bacillus Calmette-Guerin; BMI, body mass index; BSA, body surface area; CAF, cyclophosphamide, doxorubicin, and 5-fluorouracil; CHOP, cyclophosphamide, hydroxydaunomycin, oncovin, and prednisone; CMF, cyclophosphamide, methotrexate, and 5-fluorouracil; DNR, daunorubicin; GIST, gastrointestinal stromal tumor; NHL, non-Hodgkin’s lymphoma; NSCLC, non-small cell lung cancer; P, paclitaxel

Figure 5. Association of BMI and Overall Survival, Advanced Cancers Only, Based on BMI=25 kg/m² Cutpoint

Forest plots displaying hazard ratio (HR) estimates across 14 different cancer and treatment combinations, restricting analyses to patients with advanced cancers. HR <1 indicates that BMI ≥25 kg/m² is associated with decreased risk of death, while HR >1 indicates that BMI ≤25 kg/m² is associated with increased risk of death. Panel A displays forest plots restricted to men and Panel B displays analyses restricted to women. Abbreviations: 5FU, 5-fluorouracil; a-IFN, interferon alpha; AC, doxorubicin, cyclophosphamide; ADT, androgen deprivation therapy; AML, acute myelogenous leukemia; ara-C, cytarabine; BCG, bacillus Calmette-Guerin; BMI, body mass index; CAF, cyclophosphamide, doxorubicin, and 5-fluorouracil; CHOP, cyclophosphamide, hydroxydaunomycin, oncovin, and prednisone; CMF, cyclophosphamide, methotrexate, and 5-fluorouracil; DNR, daunorubicin; GIST, gastrointestinal stromal tumor; NHL, non-Hodgkin’s lymphoma; NSCLC, non-small cell lung cancer; P, paclitaxel