Adaptive Radiation BOost for Rectal Cancer: a Phase I Dose Escalation Study (ARBOR)

Inclusion Criteria: 1. Subjects must have histologically or cytologically confirmed rectal adenocarcinoma. 2. Subjects must have T2-3, N0-1, M0 rectal cancer. Staging will be done by MRI pelvis and CT chest and abdomen with contrast. PET-CT will be an acceptable alternative for the CT chest and abdomen. 3. Subjects must be willing to undergo MRI scans. 4. Age ≥18 years. 5. ECOG performance status 0 or 1. 6. Estimated survival of ≥ 12 months. 7. Subjects must have normal organ and marrow function as defined below * Absolute neutrophil count \> =1,000/mcL * Platelets \>= 75,000/mcL * Total bilirubin \< 3 mg/dL 8. Subjects must be able to tolerate the chemotherapy regimens outlined in the treatment plan (Section 5.0), both before and after ART. * Before ART: Capecitabine at a dose of 825 mg/m² * After ART: FOLFOX combination chemotherapy, or 5-FU, or capecitabine 9. Subjects must possess the ability to understand and willingness to sign a written informed consent and HIPAA consent document. Translation services including translation of informed consent documents will be provided, as feasible, to encourage diversity of inclusion of eligible patients. Exclusion Criteria: 1. Subjects who have been previously treated for rectal cancer are excluded. 2. Subjects with rectal cancer involving the anal canal are excluded. (Rectal cancer abutting the anal canal will be allowed.) 3. Subjects must not be receiving any other investigational agents. 4. Subjects may not have had prior pelvic radiation. 5. Subjects should not have had a cancer actively treated within the last 3 years, excluding non-melanoma skin cancer. 6. Subjects must not have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. 7. Any condition or significant co-morbidity that prevents safe delivery of ART per the discretion of the treating physician(s). 8. Subjects must not be pregnant or breast-feeding.