A RANDOMISED CONTROLLED TRIAL OF PERIOPERATIVE ORAL NUTRITION SUPPLEMENTATION IN PATIENTS UNDERGOING ELECTIVE SURGERY FOR BREAST AND COLORECTAL CANCER

Abstract

Introduction: Breast and colorectal cancers are ranked first and second among the most common cancers in Malaysia, contributing to 49.3% and 19.6% of cancer incidence in 2020, respectively. Meanwhile, surgery remains the mainstay of cancer treatment. Patients with breast and colorectal cancers are predominantly obese and non-severely malnourished. Perioperative use of oral nutrition supplementation (ONS) improves nutrition status and clinical outcomes of malnourished cancer patients undergoing elective surgery but the evidence for non-severely malnourished patients requires further substantiation. This study aimed to explore the effects of preoperative ONS and postoperative ONS for an extended 90-days after discharge from hospital on nutritional and clinical outcomes among patients undergoing elective surgery for breast and colorectal cancers. Methods: In this open-label, multiple arms, parallel-group randomised controlled trial, 91 patients were enrolled and randomised into one of the three intervention arms: i)Group SS who received ONS in addition to their normal diet up to 14 days preoperatively and postoperatively up to discharge from hospital, ii) Group SS-E whoreceived ONS in addition to their normal diet up to 14 days preoperatively, postoperatively up to discharge and for an extended 90 days after discharge from hospital, iii) Group DS who followed their normal diet preoperatively and only received ONS in addition to their normal diet postoperatively up to discharge from hospital. The primary outcomes were body weight, body mass index (BMI), serum albumin and prealbumin levels. The secondary outcomes were body composition in terms of muscle and fat mass, handgrip strength, energy and protein intake, highsensitivity C-reactive protein (hsCRP), Interleukin-6 (IL-6), inflammatory prognostic markers such as C-reactive protein to albumin ratio (CAR), modified Prognostic and Nutritional Index (mPINI), modified Glasgow Prognostic Score (mGPS) and neutrophil to lymphocyte ratio (NLR), length of hospital stay and postoperative complications. Data were collected at baseline, 1-day prior to surgery, 1-day prior to discharge, 30-days and 90-days post-discharge. Results: The baseline characteristics of the three groups were comparable. Two-thirds of the patients were well nourished or mild-to-moderately malnourished. Preoperative supplementation duration received by Group SS and SS-E did not differ significantly (SS: 8 (IQR: 6-14) days; SS-E: 7 (IQR: 4-13) days) and the compliance was good (SS: 84 ± 19%; SS-E: 92 ± 17%). Preoperatively, Group SS showed significantly higher body weight (SS: 65.1 ± 0.2 kg; SS-E: 64.8 ± 0.2 kg; DS: 64.3 ± 0.2 kg; p = 0.010)and BMI (SS: 26.6 ± 0.1 kg/m2; SS-E: 26.5 ± 0.1 kg/m2; DS: 26.3 ± 0.1 kg/m2; p = 0.022) than Group DS after adjustment for baseline values. When adjusted for baseline values, the mean ± SD energy intake was the highest in Group SS, followed by Group SS-E and Group DS (SS: 1920 ± 66 kcal/d; SS-E: 1671 ± 66 kcal/d; DS: 1158 ± 66 kcal/d; p < 0.001). The mean ± SD protein intake in Group SS and SS-E was significantly higher than that in Group DS (SS: 79 ± 3 g/d; SS-E: 71 ± 3 g/d; DS: 47 ± 3 g/d; p < 0.001). Postoperative supplementation duration received by Group SS-E was 97 (IQR: 85-103) days and the compliance was 75 ± 16%. Postoperatively, Group SS-E had significantly higher BMI (SS: 26.3 ± 0.3 kg/m2; SS-E: 26.7 ± 0.3 kg/m2; DS: 25.6 ± 0.3 kg/m2; p = 0.046)and handgrip strength (SS: 26 ± 1 kgF; SS-E: 28 ± 1 kgF; DS: 25 ± 1 kgF; p = 0.044) than Group DS at 90-days post-discharge after adjustment for baseline values. The mean ± SD energy and protein intake in Group SS-E were significantly higher than that in Group SS and DS at 90-days post-discharge after adjustment for baseline values (SS: 1299 ± 64 kcal/d, 52 ± 3 g/d; SS-E: 1965 ± 71 kcal/d, 85 ± 4 g/d; DS: 1348 ± 67 kcal/d, 52 ± 3 g/d; p < 0.001). The proportions of patients with elevated inflammatory markers and inflammation-based prognostic markers in all groups increased at discharge in response to the surgery but reduced at 30-days post-discharge. At 90-days post-discharge, the proportions of patients in SS with albumin <35 g/d, CAR ≥ 0.1, mPINI ≥ 0.4, mGPS score 1 or 2 were significantly reduced compared to upon discharge while in SS-E, the reduction in proportions of patients with high hsCRP and mPINI ≥ 0.4 was significant. No significant differences between the groups were noted in albumin, prealbumin, muscle mass, fat mass, hsCRP, and IL-6 at any timepoint during the study period. Perioperative ONS also had no effect on the length of hospital stay and postoperative complications. Conclusion: Among patients undergoing surgery for breast and colorectal cancers, preoperative ONS conferred modest benefits in improving weight status prior to surgery. Meanwhile, postoperative ONS up to 90-days post discharge improved handgrip strength, maintained BMI and improved inflammatory prognostic markers. In addition, the provision of ONS improved energy and protein intake pre- and postoperatively without suppression of normal dietary intake. These findings provide evidence on the role of nutrition intervention among cancer patients preparing for surgery.