Adaptive Radiation in Anal Cancer

Inclusion Criteria: Histologically proven, invasive primary squamous, basaloid or cloacogenic carcinoma of the anal canal. American Joint Committee on Cancer (AJCC) 8th edition stage T2 > 4 cm, T3-4 or N1. Age ≥18 years. Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Karnofsky ≥60%). Life expectancy of greater than 12 months. Patients must have normal organ and marrow function as defined below: leukocytes greater than or equal to 3,000/microliter absolute neutrophil count greater than or equal to 1,500/microliter platelets greater than or equal to 100,000/microliter total bilirubin within normal institutional limits Aspartate transaminase (AST)(SGOT)/Alanine transaminase (ALT)(SGPT) ≤ 2.5 × institutional upper limit of normal creatinine within normal institutional limits OR creatinine clearance ≥60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal. Females of childbearing potential and males must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 months after completion of study therapy. All pregnancies must be reported. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Prior or co-existing invasive malignancy (except non-melanomatous skin cancer) unless disease free ≥ 2 years. Prior chemotherapy or radiation for anal cancer. Patients who have undergone complete surgical resection. Presence of recurrent/metastatic disease. Prior allergic reaction to 5-Fluorouracil or mitomycin C. Artificial organ prosthetics, pacemakers or other implantable devices. Prior radiotherapy to the pelvis that would result in overlap of radiation therapy fields. Uncontrolled inter-current illness including but not limited to known history of HIV with cluster of differentiation 4 (CD4) count less than 200 or symptomatic cardiac disease. Women who are pregnant or lactating.