Prediction of Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer.

In recent years, treatment with NCRT has revolutionised management of LARC. In addition to downstaging the tumour in 62% of cases, half of which decrease by more than 1 T stage; pathological complete response (pCR), with no viable tumour cells left in resected specimens, was demonstrated in up to 30% of patients. Only 3% of patients showed progressive disease. It has recently been shown that those with pathological complete response survive longer than those with partial response, with figures for 5-year disease free survival quoted between 83 and 91% for pCR; versus 65% for non pCR. Furthermore, it has been argued that those tumours which are sensitive to radiotherapy have a favourable biological tumour profile, with fewer propensities to recur or to metastasise than aggressive non-radiosensitive tumours. The key is to accurately be able to identify patients who exhibit complete response to radiotherapy, or to predict those who might show complete response.

Positron Emission Tomography (18-F-FDG-PET-CT) as a tumour biomarker after radiotherapy has been shown to be able to predict patients who have responded to chemo radiotherapy, with a sensitivity of 79% and specificity of 88%. Texture Analysis (TA) assesses the aggressiveness of the tumour by assessing intra-tumoural heterogeneity. It has already been shown to be effective in assessing biological characteristics of solid tumours, including the oesophagus, breast, and liver.

The aim of this study is to utilise these two novel molecular imaging techniques to identify rectal cancer patients who have responded completely from neoadjuvant chemo-radiotherapy. Parameters will be calculated as changes in measurable variables from baseline to post treatment scans.

Pilot data The watch-and-wait approach could potentially reduce treatment-related toxicity in selected rectal cancer patients who have a clinical complete response (cCR) after chemoradiation. The "watch & wait" protocol has been adopted from studies performed in Brazil, United Kingdom, and the Netherlands.

Studies indicate that accurate assessment of response to neoadjuvant therapy is the key to selecting patients who will benefit from the watch & wait approach. Therefore, determining the modality with highest accuracy and cost-effectiveness has been the holy grail of managing locally advanced rectal cancers.