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 lesion found on colonoscopy.
• 3. Previous history of pelvic radiotherapy.
• 4. History of concurrent, active malignancy, other than non metastatic skin cancer within the last 5 years.
• 5. Symptomatic congestive heart failure of New York Heart Association Class III or IV, unstable angina pectoris or serious uncontrolled 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. Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control (CDC) definition or known HIV seropositivity; note, however, HIV testing is not required for entry into this protocol. The need to exclude patients with HIV/AIDS from this protocol is based on the fact that the treatments involved in this protocol may be significantly immunosuppressive.
• 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).