Predicting the Response to Radiotherapy for Rectal Cancer

Abstract

Aim To investigate predictors of pathological response to radiotherapy for rectal cancer by reviewing the evidence, exploring clinicopathological predictors in a local cohort and investigating markers of oxidative stress as novel biomarker predictors. Method A systematic review of the literature was undertaken. A retrospective study of patients treated with neoadjuvant chemoradiotherapy (nCRT) and total mesorectal excision at Christchurch Hospital 2013-2018 was performed by reviewing patients clinical records. A literature review of the role of antioxidants including peroxiredoxins on the effect of ionising radiation was performed. A prospective observational pilot study was then performed investigating markers of oxidative stress including peroxiredoxin oxidation status and protein carbonyls as novel predictors of the response to radiotherapy for rectal cancer. Results Based on currently available evidence the predictors of pathological response to nCRT for rectal cancer with the most clinical utility currently are clinical T and N stage, tumour size and CEA level. In a cohort of 164 patients treated with nCRT and total mesorectal excision there was a pathological complete response (pCR) rate of 14.6%; shorter tumour length on MRI and lower clinical N stage were independent predictors of pCR on logistic regression. Higher BMI, anterior or circumferential tumours and lower haemoglobin were independent predictors of minimal-poor response as determined by tumour regression grade. The markers of oxidative stress peroxiredoxin 2 and peroxiredoxin 3 percentage oxidation and protein carbonyl levels did not predict response to radiotherapy for rectal cancer in seven patients treated with nCRT, of which two patients experienced a pCR and one patient experienced a complete clinical response. Conclusion The pathological response to radiotherapy for rectal cancer is complex and numerous factors appear to play a role. Predictors can be classified as clinicopathological, biomarker or radiological predictors. Although there are several clinical predictors of use currently, none have a high predictive ability. Neither peroxiredoxin oxidation status or protein carbonyls appear to predict the response to radiotherapy for rectal cancer. A composite scoring system comprised of clinicopathological, biomarker and radiological factors is most likely to yield a useful predictive tool in the future.