Loss of subcutaneous adipose tissue during chemotherapy predicts reduced survival in patients with incurable colorectal cancer undergoing palliative therapy

Abstract

Rationale: Obesity is an established risk factor for colorectal cancer (CRC), however little is known about the impact on survival of changes in body composition during chemotherapy. Methods: A prospective study of adult CRC patients undergoing chemotherapy between 2012 and 2016 was conducted. Baseline body composition and longitudinal changes were examined using computed tomography (CT) images at two timepoints (interval 7 months, IQR: 5–9 months) using paired t-tests. Sarcopenia and low muscle attenuation (MA) were defined using published cut-offs. Cox models were used to estimate mortality hazard ratios, adjusted for known prognostic covariates –age, sex, performance status & systemic inflammation. Results: In total, 268 patients were recruited (66% male, mean age 63 years) and 51% were undergoing chemotherapy with a palliative intent. At baseline, 4% had BMI <20 kg/m2 & 58% had BMI ≥ 25 kg/m2. However, 38%, 34% & 43% had cachexia, sarcopenia & low MA, respectively. Over 100 days, 68% were muscle stable (±1 kg), while 25% lost >1 kg and 7% gained >1 kg. Fat mass remained stable ±1 kg in 49%, while 28% lost >1 kg and 23% gained >1 kg. On multivariate analysis, baseline BMI and subcutaneous fat (SAT) loss predicted survival in patients treated with palliative intent. Normal BMI (20–25 kg/m2) predicted reduced survival compared to overweight (25–30 kg/m2) [HR:1.80 (95% CI:1.04–3.14), p = 0.037]. Loss of >6.4% SAT over 100 days was predictive of poor survival versus gain/<6.4% loss, independent of changes in muscle mass [HR:2.2 (95% CI:1.07–4.62), p = 0.033]. Conclusions: Patients with CRC experience significant losses in muscle and fat mass during chemotherapy. Loss of SAT mass during palliative chemotherapy is prognostic of poor survival, independent of changes in muscle mass. Baseline BMI in the overweight range confers a survival advantage. Nutritional strategies to prevent or attenuate weight loss during chemotherapy are advisable especially in the context of advanced CRC.