Obesity paradox in patients with cancer: A systematic review and meta-analysis of 6,320,365 patients

Abstract

BACKGROUND. Obesity, defined as a body mass index (BMI) ≥ 30 kg/m2, is associated with a significant increase in risk of many cancers. In last years, various studies suggested that obese cancer patients have better outcomes than non obese patients. This phenomenon, also known as the obesity paradox, is not well understood and presents controversial explanations. We performed a systematic review and metaanalysis to assess the association between obesity and outcome after a diagnosis of cancer. PATIENTS AND METHODS. PubMed, the Cochrane Library, and EMBASE were searched from inception to January 2020, for studies reporting prognosis of patients with obesity and cancer. Risk of death, cancer specific survival (CSS) and progression were pooled to provide an adjusted hazard ratio with a 95% confidence interval (HR 95%CI). The primary outcome of the study refers to overall survival (OS) in obese vs non obese patients with malignancies. Secondary endpoints were CSS and progression or disease free survival (PFS or RFS). RESULTS. Mortality and relapse associated with obesity in patients with cancer were evaluated among n=6,320,365 participants (n=203 studies). Overall, association of obesity and cancer was associated with a reduced OS (HR =1.14, 95% CI: 1.09 1.19; P<.01) and CSS (HR=1.17, 95%CI 1.12 1.23; P<.01). Patients were also at increased risk for relapse (HR=1.13, 95%CI 1.07 1.19; P<.01). Patients with breast, colorectal and uterine tumors were at increased risk of death. Conversely, obese with lung cancer, renal cell carcinoma and melanoma survived longer that non obese. CONCLUSIONS. In many cancer patients, obesity reduces survival and increases the risk of relapse. In lung cancer, renal cell carcinoma and melanoma obesity was protective in terms of outcome. More intensive follow up, adequate dosing of oncological treatments, calories intake restrictions, physical activity and monitoring of obesity related complications are effective measures for reducing mortality in these subjects.

Transcriptome Analysis of Subcutaneous Adipose Tissue from Severely Obese Patients Highlights Deregulation Profiles in Coding and Non-Coding Oncogenes

“…Indeed, Ringel et al investigated how obesity shifts the metabolic landscape of the tumor microenvironment to inhibit T cell function and promote tumor growth [ 90 ]. Although, in most cases, an excessive body weight is associated with carcinogenesis development and poor outcome, some new studies are now highlighting how this might not always be the case [ 67 , 91 , 92 ] and this is in line with our evidence highlighting a correlation with both a favorable and an unfavorable gene expression signature.…”

Baseline BMI and BMI variation during first line pembrolizumab in NSCLC patients with a PD-L1 expression ≥ 50%: a multicenter study with external validation

“…From this perspective, the analysis of the chemotherapy cohort collides with the evidences suggesting that also in NSCLC patients receiving chemotherapy a higher BMI is associated with an improved survival. 11 Additional limitations include the data lack availability regarding comorbidities, the different sample size of the two cohorts, as well as the median follow-up which was different. The chemotherapy cohort was not powered to detect statistically significant differences according to weight categories, moreover, being a historic cohort, we did not have data regarding PD-L1 expression for the subset of patients treated with chemotherapy.…”

“… 9 10 In a recent meta-analysis including 203 articles, more than 6,000,000 patients across 15 different malignancies, the association between obesity and improved clinical outcomes was confirmed in those tumor types in which programmed death-1 (PD-1)/PD-L1 checkpoint inhibitors have proven to be more effective (such as lung cancer and renal cell carcinoma), despite studies involving patients who received immune checkpoint inhibitors were poorly represented in the meta-analysis itself. 11 Therefore, assuming that the adipose tissue has somehow a role in the antitumor immune response, evaluating whether the variation of the BMI in patients receiving immune checkpoint inhibitors affects the clinical outcomes represents an interesting area of research.…”

Clinical Risk and Overall Survival in Patients with Diabetes Mellitus, Hyperglycemia and Glioblastoma Multiforme. A Review of the Current Literature

“…In their series of 392 patients with GBM [ 45 ], the median OS was 13.5 months in normal subjects, 15.4 months in overweight subjects and 15.1 months in obese subjects, concluding that patients with GBM and elevated BMIs had a significantly better OS. Even if not well understood, this phenomenon, also known as “the obesity paradox”, seems to be more and more common in the last years in patients with tumors, as various studies suggested that obese patients with lung cancer, renal cell carcinoma and melanoma have a better outcomes compared to non-obese patients [ 66 ]. From this review, the weighted mean OS results 14.46 months in patients with normal weight compared to 12.39 months in obese patients.…”