This pilot study aims to trial multimodal early response assessment to enable therapy adaptions in the context of non-operative therapy strategies of locally advanced rectal cancer (LARC) for development of a non-invasive response prediction model.

Patients with LARC, receiving neoadjuvant chemoradiotherapy (CRT) are followed by at least 4 multiparametric MRI-scans (diffusion weighted imaging and hypoxia-sensitive sequences) as well as repeated blood samples in order to analyse circulating tumour cells (CTCs). A standard pelvis radiotherapy (RT, 5040 cGy) will be performed in combination with a 5-Fluorouracil / Oxaliplatin regimen in all patients (planned: N = 50), succeeded by consolidation CTx (FOLFOX4) if feasible. Additional histologic markers, such as tumour-infiltrating lymphocytes (TILs) or PD-L1 status will be analysed before and after CRT. Resection is standard after completion of preoperative treatment. In case of complete regression and patient's request, a non-operative management ("watch and wait") is offered alternatively. The primary endpoint is response, defined by tumor regression grading, secondary endpoints comprise longitudinal changes in MRI as well as in CTCs and TILs.

Inclusion Criteria:

• locally advanced rectal cancer (LARC): UICC Stage II/III
• no severe cardiac or lung disease
• no severe hepatic disorders (liver enzymes <2.5 NR) or restrictions of renal function (GFR > 30ml/min)
• no severe cytopenia (Neutrocytes >= 3 Gpt/l; Thrombocytes >= 100 Gpt/l; Hemoglobin >6mmol/l)
• no homozygotic DPD deficiency
• no other neoplasms requiring therapy
• no earlier radiotherapy of the pelvis or earlier chemotherapy
• no contraindications for MRI

Patients with locally advanced rectal cancer (LARC), receiving neoadjuvant chemoradiotherapy (CRT).