The relationship between body-mass index and overall survival in non-small cell lung cancer by sex, smoking status, and race: A pooled analysis of 20,937 International lung Cancer consortium (ILCCO) patients

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; p_interaction = 0.02). Comparing overweight/obese to normal weight patients, Black NSCLC patients who were overweight/obese also had relatively better OS (p_interaction = 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 (p_interaction<0.001) and obese categories (p_interaction = 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.

Keywords: Body mass index; Interaction; Lung cancer; Obesity.

Fig. 1.

Multivariable analysis showing the association of Body Mass Index and Overall Survival stratified by specific variables (subgroups of sex, race, smoking status, stage, and combinations of sex and smoking status (“SEX*Smoking”)). Models were adjusted for age, educational level, year of diagnosis, and histology. Normal weight is the reference group: between 18.5–24.9 kg/m²; Underweight: BMI < 18.5 kg/m²; Overweight: BMI between 25–29.9 kg/m ²; Obese: BMI ≥ 30 kg/m². HR, hazard ratio; CI = confidence interval; p = p-value; p-interaction = p-value for interaction term of the subgroup with BMI category on overall survival.

Fig. 2.

Hazard ratios of overall survival by Body Mass Index (BMI) at the time of diagnosis, using penalized smoothing spline, in specific subgroups of patients based on race. In each model, hazard ratios are adjusted for age, sex, smoking status, stage, educational level, year of diagnosis, and histology N = number of patients analyzed; NL = normal weight (BMI between 18.5–24.9 kg/m²), UW = underweight (BMI < 18.5 kg/m²), OW = overweight (BMI between 25–29.9 kg/m²); OB = obese (BMI ≥ 30 kg/m²).

Fig. 3.

Hazard ratios of overall survival by Body Mass Index (BMI) at the time of diagnosis, using penalized smoothing spline, in specific subgroups of patients based on combinations of sex and smoking status. In each model, hazard ratios are adjusted for age, race, stage, educational level, year of diagnosis, and histology. N = number of patients analyzed; NL = normal weight (BMI between 18.5–24.9 kg/m²); UW = underweight (BMI < 18.5 kg/m²), OW = overweight (BMI between 25–29.9 kg/m²); OB = obese (BMI ≥ 30 kg/m²).