Adaptive Radiotherapy for the Treatment of Patients with Locally Advanced 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 TN stage T2 > 4 cm, T3-4 or N1; based upon the following diagnostic workup: physical exam; anal examination by one of the following: anoscopy, sigmoidoscopy, rigid proctoscopy or colonoscopy; biopsy confirmation required prior to enrollment, and CT scan, MRI, or PET/CT scan of the abdomen/pelvis. The listed work-up is standard of care
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
• Life expectancy of greater than 12 months
• Leukocytes ≥ 3,000/mcL
• Absolute neutrophil count ≥ 1,500/mcL
• Platelets >= 100,000/mcL
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT]) / alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
• Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
• Study treatments are teratogenic or abortogenic; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of study therapy
• 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-FU 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 human immunodeficiency virus (HIV) with CD4 count < 200 or symptomatic cardiac disease
• Women who are pregnant or lactating