Oncologic and Functional Hazards of Obesity Among Patients With Locally Advanced Rectal Cancer Following Neoadjuvant Chemoradiation Therapy

Abstract

Objective Obesity is a major health concern and risk factor for colorectal cancer that may also impact cancer treatment and outcomes. Rectal cancer response to chemoradiotherapy (CXRT) is associated with long-term survival and sphincter preservation. The purpose of this study was to evaluate the impact of obesity on treatment outcomes after neoadjuvant CXRT for rectal cancer. Methods A retrospective cohort study of patients diagnosed (1993–2010) with cT3-4 or cN+ (by EUS, CT, or MRI) rectal carcinoma and treated with CXRT and TME was performed. Patients were classified as obese (BMI≥30 kg/m2) or non-obese (BMI<30 kg/m2),and by response to CXRT: complete (ypCR) or incomplete (ypIR). Associations between obesity, tumor response, and sphincter preservation were evaluated using multivariate logistic regression analysis and survival outcomes by Cox regression. Results 753 patients met criteria and 28.7% (n=216) patients were obese. Obese and non-obese groups did not differ in age, gender, tumor location, grade, or number of examined lymph nodes. However, obesity was associated with a lower rate of ypCR (ORmulti=0.60; 95% CI:0.38–0.94, p=.04) and among mid-to-low rectal cancer patients, a lower rate of sphincter preservation (ORmulti=.67; 95% CI:.45 to.99). Both among obese and non-obese patients, CR was associated with more favorable recurrence-free survival than iCR. Conclusions Considering the increasing obesity prevalence and its association with CXRT response, oncologic outcomes, and sphincter preservation, further study is needed regarding the impact of obesity on neoadjuvant treatment response. Moreover, obesity should be targeted as a modifiable risk factor for adverse outcomes following multimodality treatment for rectal cancer.

The Effect of Obesity on Response to Neoadjuvant Therapy in Locally Advanced Gastric Cancer

“…Previous studies have reported that the obesity affects the response to NACT in various solid tumors such as prostate cancer, rectal cancer, breast cancer, and pancreas cancer (Farr et al, 2017;Park et al, 2017;Duconseil et al, 2019;Sun et al, 2020). Park et al, (2017) reported that obesity reduced the complete response rate by 40% in their study with rectal cancer patients receiving neoadjuvant CRT. Likewise, another study of pancreatic cancer by Duconseil et al, (2019) has reported that obesity is determined as the factor affecting survival.…”

Obesity as an independent predictive factor for pathologic complete response after neoadjuvant chemoradiation in rectal cancer

“…Also, obesity may decrease the possibility of sphincter preservation [89]. In addition, some studies reported a relationship between obesity and oncologic outcomes of patients with rectal cancer following nCRT, although their results were controversial [1011121314]. Given the fact that obesity is associated with inflammation and angiogenesis [15] and is associated with the chronic oxidative stress [16], it is possible to consider the possibility that obesity is related to the response of radiotherapy.…”

Radiation-induced Bystander Effect (RIBE) alters mitochondrial metabolism using a human rectal cancer ex vivo explant model

“…Of note, this observation only occurred in the bystander cells treated with TCM from irradiated rectal cancer biopsies, perhaps suggesting that obesity status may influence the behaviour of bystander cells following radiation. This is an interesting and clinically relevant result as it has been reported that overweight and obese patients have poorer responses to neoadjuvant treatment and worse outcomes in rectal cancer [ [20] , [21] , [22] ]. Moreover, when we correlated levels of metabolites in the secretome of mock-irradiated rectal cancer tissue we found significant correlations between VFA and leucine and ethanol.…”

“…It has been reported that overweight or obese rectal cancer patients have a poorer response to neoadjuvant treatment compared to their counterparts of a normal weight [ 20 , 21 ] as well as worse local control following neoadjuvant treatment and surgery [ 22 ]. We sought to understand the relationship between body composition and bystander cellular response to TCM from both irradiated and mock-irradiated rectal cancer biopsies.…”