Short RT Versus RCT,Followed by Chemo.and Organ Preservation for Interm and High-risk Rectal Cancer Patients

Inclusion Criteria:

• diagnosis of rectal adenocarcinoma localised 0 - 12 cm from the anocutaneous line asmeasured by rigid rectoscopy (i.e. lower and middle third of the rectum)

• Staging requirements: High-resolution, thin-sliced (i.e. 3mm) magnetic resonanceimaging (MRI) of the pelvis is the mandatory local staging procedure.

• MRI-defined inclusion criteria: presence of at least one of the following high-riskconditions:

• any cT3 if the distal extent of the tumor is < 6 cm from the anocutaneous line, or

• cT3c/d in the middle third of the rectum (≥ 6-12 cm) with MRI evidence of extramuraltumor spread into the mesorectal fat of more than 5 mm (>cT3b), or

• cT3 with clear cN+ based on strict MRI-criteria

• cT4 tumors, or

• Tany middle/low third of rectum with clear MRI criteria for N+

• mrCRM+ (< 1mm), or

• Extramural venous invasion (EMVI+)

• Trans-rectal endoscopic ultrasound (EUS) is additionally used when MRI is notdefinitive to exclude early cT1/T2 disease in the lower third of the rectum or earlycT3a/b tumors in the middle third of the rectum.

• Spiral-CT of the abdomen and chest to exclude distant metastases.

• Aged at least 18 years. No upper age limit.

• WHO/ECOG Performance Status 0-1

• Adequate haematological, hepatic, renal and metabolic function parameters:

• Leukocytes ≥ 3.000/mm^3, ANC ≥ 1.500/mm^3, platelets ≥ 100.000/mm^3, Hb > 9 g/dl

• Serum creatinine ≤ 1.5 x upper limit of normal

• Bilirubin ≤ 2.0 mg/dl, SGOT-SGPT, and AP ≤ 3 x upper limit of normal • Informedconsent of the patient

Exclusion Criteria:

• Lower border of the tumor localised more than 12 cm from the anocutaneous line asmeasured by rigid rectoscopy

• Distant metastases (to be excluded by CT scan of the thorax and abdomen)

• Prior antineoplastic therapy for rectal cancer

• Prior radiotherapy of the pelvic region

• Major surgery within the last 4 weeks prior to inclusion

• Subject pregnant or breast feeding, or planning to become pregnant within 6 monthsafter the end of treatment.

• Subject (male or female) is not willing to use highly effective methods ofContraception during treatment and for 6 months after the end of treatment.

• On-treatment participation in a clinical study in the period 30 days prior toinclusion

• Previous or current drug abuse

• Other concomitant antineoplastic therapy

• Serious concurrent diseases, including neurologic or psychiatric disorders (incl.dementia and uncontrolled seizures), active, uncontrolled infections, active,disseminated coagulation disorder

• Clinically significant cardiovascular disease in (incl. myocardial infarction,unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiacarrhythmia) < 6 months before enrolment

• Prior or concurrent malignancy < 3 years prior to enrolment in study (Exception:non-melanoma Skin cancer or cervical carcinoma FIGO stage 0-1), if the patient iscontinuously disease-free

• Known allergic reactions on study medication

• Known dihydropyrimidine dehydrogenase deficiency

• Psychological, familial, sociological or geographical condition potentiallyhampering compliance with the study protocol and follow-up schedule (theseconditions should be discussed with the patient before registration in the trial).