The Pathophysiological effects of adjuvant preoperativechemotherapy and/or radiotherapy on patients with advanced rectal cancer

Introduction The modern treatment of colorectal cancer consists of surgery, with or without adjuvant pre-operative radiotherapy, chemotherapy or chemoradiotherapy (APT) for selected cases. In the United Kingdom, therapy may be given prior to surgery in an attempt to facilitate surgical excision and improve survival. However, there is some evidence that APT in other cancers may adversely affect the patient’s health and increase the risk of operative morbidity. The association between functional capacity, represented by the maximum oxygen consumption per unit time (VO2max) as measured by cardiopulmonary exercise testing (CPEX), and the perioperative outcome is well established. A reduction in cardiopulmonary reserve may increase the perioperative mortality and morbidity; however, sufficient data to demonstrate this are not available yet. This study examined the affect of APT on the cardiopulmonary status, body composition, cytokines assay, nutritional status and quality of life in patients with colorectal cancer. Methods This is a pilot observational study performed on two groups of patients, no intervention was used at this stage. Group one received combined ChemoRadiotherapy and Group two received only pelvic radiotherapy. Cardiopulmonary function was measured with exercise bicycle to achieve Anaerobic Threshold (AT) and Maximum Oxygen consumption (VO2max) using CPEX testing. Anthropometric parameters such as mid-arm circumference (MAC), Triceps skin fold (TSF), grip strength measurements (GS), Body weight, height and body mass index as well as extracellular water (ECW), intracellular water (ICW), total body water (TBW) and fat free mass (FFM) were measured using a Bio-electrical impedance analyser. 9 cytokines were measured using a Luminex assay in addition to CRP and albumin assessment. Nutritional status and quality of life were evaluated using two validated questionnaires (EORTC QLQ-C30 and PG-SGA). These assessments were made before and within two weeks after the administration of APT. Wilcoxon rank sum test represented in median and interquartile range was used to compare results before and after the exposure to APT. Results Between January 2010 and January 2011, a total of 36 patients with rectal cancer were recruited, 24 patients in group 1 had combined chemoradiotherapy (mean age 59.4, 18 males and 6 females) and 12 patient in group 2 had radiotherapy only (mean age 71.8, 10 males and 2 females). Group 1 had a significant decline in VO2max with p=0.005, an increase in the ventilatory equivalent ratio for CO2 (VE/VCO2) with p= 0.001, a reduction in TSF, MAC, GS and TBW with p- values of 0.007, 0.006, 0.010 and 0.000 respectively after APT exposure. Group 2 had no significant changes in their CPEX data, however, they showed a marked decline in TSF, MAC, GS, TBW and FFM with p- values of 0.013, 0.013, 0.002 and 0.034 respectively after APT exposure. Both groups showed a highly significant overall reduction in the health related quality of life data with no significant changes in their plasma cytokines, CRP and albumin post APT. Conclusions These data suggest that APT has a significant effect upon the cardiopulmonary capacity with reduced VO2max as well as an increased VE/VCO2. There were also signs of fluid depletion and reduced muscle bulk represented by a significant reduction in TBW, FFM, MAC and TSF. Therefore, these important physiological changes could be deleterious and affect the peri and post-operative recovery and increase the morbidity of surgery in colorectal cancer patients. In view of this, a period of optimisation following APT and prior to surgery may serve to minimise the risk of such complications.