Hyperthermia With Chemoradiotherapy in Rectal Cancer

Inclusion Criteria: * Male and female patients with histologically confirmed diagnosis of rectal cancer localized 0-12 cm from the anocutaneous line (i.e. lower and middle third of the rectum) * Indication for total neoadjuvant therapy irrespective of participation in the current study. * Any MRI staged rectal cancer with one of the following high-risk features: * cT4 * cN2 (see Appendix) * Distance to mesorectal fascia 1mm or less. * Involved Lateral pelvic lymph nodes * EMVI (extramural venous invasion) positivity * Staging requirements: High-resolution, thin-sliced (i.e. 3mm) magnetic resonance imaging (MRI) of the pelvis is the mandatory local staging procedure. * Cross-sectional imaging of the abdomen and chest to exclude distant metastases. * Aged at least 18 years. No upper age limit. * WHO/ECOG Performance Status ≤ 1 * Adequate hematological, hepatic, renal and metabolic function parameters * Informed consent of the patient Exclusion Criteria: * Lower border of the tumor localised more than 12 cm from the anocutaneous line as measured by rigid rectoscopy * Tumors with microsatellite instability ("MSI-High Tumors") and the possibility for treatment with immune checkpoint inhibition. * Contraindication for hyperthermia such as metal implants or pacemakers * Distant metastases (to be excluded by CT scan of the thorax and abdomen) * Preexisting fecal incontinence for solid stool * 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 breastfeeding, or planning to become pregnant within 6 months after the end of treatment * Subject (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment (adequate: oral contraceptives, intrauterine device or barrier method in conjunction with spermicidal jelly) * 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 (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 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 is continuously disease-free * Known allergic reactions on study medication * Known dihydropyrimidine dehydrogenase deficiency * Psychological, familial, sociological or geographical conditions potentially hampering compliance with the study protocol and follow-up schedule (these conditions should be discussed with the patient before registration in the trial)