SMART TNT for the Conservative Management of Locally Advanced Rectal Cancer

Inclusion Criteria: 1. Patients with newly diagnosed, biopsy proven, rectal adenocarcinoma. 2. Primary tumor located ≤18 cm from margin verge. 3. Primary tumor either a T3N0 or T1-4 N positive (as defined per pelvic MRI; nodes ≤ 15 mm). 4. ≥ 18 years of age. 5. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. 6. Serum liver function tests values within the range of 1.5 x Upper Limit of Normal (within 6 weeks of enrollment). 7. Negative pregnancy test for women of child-bearing potential (within 4 weeks of enrollment). 8. Ability to understand and the willingness to sign a written informed consent document. 9. Patient is assessed by a surgeon, medical oncologist and a radiation oncologist and deemed fit for Total Neoadjuvant ChemoTherapy (TNT) and surgery. Exclusion Criteria: 1. Metastatic disease on initial work up (Chest and abdomen contrast enhanced CT scan). 2. Synchronous cancer found on colonoscopy. 3. Previous history of pelvic radiotherapy. 4. History of concurrent, active malignancy other than non-metastatic skin cancer within the last 2 years. 5. Symptomatic congestive heart failure of New York Heart Association Class III or IV, unstable angina pectoris or uncontrolled severe cardiac arrhythmia, myocardial infarction within the last 6 months. 6. Psychiatric illness/social situations that would limit compliance with study requirements. 7. Active (acute or chronic) or uncontrolled severe infections requiring intravenous antibiotics or active tuberculosis (TB). 8. Patients with poorly controlled acquired immune deficiency syndrome (AIDS) who are not deemed candidates for FOLFOX, mFOLFIRINOX or CAPOX chemotherapy. Active connective tissue disorders, such as lupus or scleroderma, that, in the opinion of the treating physician may put the patient at high risk for radiation toxicity. 9. Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity 10. Sensory or motor neuropathy ≥ grade 2. 11. Women who are breast feeding. 12. Exclusions due to MRI use in study: ferromagnetic metal in body/eye, pacemaker, defibrillator, other mechanical device, or extreme claustrophobia (medication with anti-anxiety agents, such as Ativan, may be attempted).