Pathological and molecular predictors of the response of rectal cancer to neoadjuvant radiochemotherapy

Combined analysis of VEGF and EGFR predicts complete tumour response in rectal cancer treated with preoperative radiotherapy

“…Recently, microarray gene expression profiling was successfully used to predict complete responses to preoperative chemoradiotherapy with advanced-stage rectal cancer (Ghadimi et al, 2005;Kim et al, 2007). Epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), the p53 tumour suppressor and key mediators of cell-cycle arrest (p21, p27) and apoptosis (Bcl-2, apoptosis protease-activating factor-1 (APAF-1)) are among the immunohistochemical protein markers currently of interest as potential predictors of pathologic response, prognosis and recurrence-free survival in rectal cancer following neoadjuvant therapy (Giralt et al, 2005(Giralt et al, , 2007Lopez-Crapez et al, 2005;Kim et al, 2006;Lin et al, 2006;Smith et al, 2006;Bertolini et al, 2007).…”

Inhibitory effects of oxaliplatin in experimental radiation treatment of colorectal carcinoma: does oxaliplatin improve 5-fluorouracil-dependent radiosensitivity?

“…The level of spontaneous apoptosis in pretreatment rectal cancer biopsies has been evaluated in seven studies. In six of those, a high apoptotic index was associated with good response after CRT (70). Furthermore, survivin, an inhibitor of apoptosis, was inversely correlated to the apoptotic level, and was also correlated to disease-free survival and metastasis development (91).…”

“…Patients with no response after CRT might probably go straight to surgery omitting CRT or be candidates for alternative or more intensive CRT regimens (71), and patients with a complete remission would benefit from omitting surgery (72). At present, no reliable technique (radiological or clinical) for predicting tumor response after CRT is available (42,73), and it has been concluded that pre-treatment T stage, N stage, histological grade, differentiation, age and gender do not reliably predict histological response to CRT (70).…”

“…Three studies did not show any predictive value of microsatellite instability for treatment response in LARC (70), but high expression of the DNA double-strand break (dsb) repair proteins Ku70 and Ku86 was associated with decreased response to CRT in a single study (89).…”

“…It is not known why such large differences in response occur, but the phenomenon may reflect diverse intrinsic biology of tumors or yet undetected external factors. CRT delays surgery by several months, is expensive, has acute and long-term side effects, and may increase perioperative morbidity (36,48,70), thus, the possibility to predict response either before or in the early stages of treatment may spare poorly responding patients from undergoing treatment that is not beneficial. Patients with no response after CRT might probably go straight to surgery omitting CRT or be candidates for alternative or more intensive CRT regimens (71), and patients with a complete remission would benefit from omitting surgery (72).…”