Short-course Radiotherapy Followed by Consolidation Chemotherapy. 2021-001206-29

Inclusion Criteria: * Written informed consent to study procedures and to translational analyses; * Age 18-70 years; * Histologically proven diagnosis of rectal adenocarcinoma; * Patients with locally advanced rectal cancer defined by the presence of at least one of the following features: * cN2 (defined as at least 4 positive lymphnodes at pelvic MRI) * cT4 * tumor extending to within 1 mm of or beyond mesorectal fascia (i.e., circumferential radial margin threatened or involved) * cT3, N1 * Distal border of the tumour located between 5 and 12 cm from the anal verge (as measured by pelvic MRI); * Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤1; * No evidence of metastatic disease by total body CT-scan; * Available tumour samples at baseline (archival biopsy); * Tumour amenable to curative resection (including pelvic exenteration); * No history of invasive rectal malignancy, regardless of disease-free interval; * No other rectal cancers (i.e., sarcoma, lymphoma, carcinoid, squamous cell carcinoma, or cloacogenic carcinoma) or synchronous colon cancer; * No clear involvement of the pelvic side walls by imaging; * Life expectancy of at least 5 years (excluding diagnosis of cancer); * Hematopoietic function: absolute neutrophil count ≥ 1,500/mm3; platelet count ≥100,000/mm3; haemoglobin level ≥ 9 g/dL; * Liver function: total bilirubin ≤ 1.5 times upper limit of normal (ULN); alkaline phosphatase ≤ 2 times ULN; AST ≤ 2 times ULN; * Renal function:…