Linear Energy Transfer (LET)-Optimized Intensity Modulated Proton Therapy (IMPT) as a Component of Definitive Chemoradiation for Newly Diagnosed Squamous Cell Carcinoma of the Anal Canal: a Feasibility Trial

Inclusion Criteria

• Histologically-proven, non-metastatic invasive primary squamous cell carcinoma of the anal canal (stages I, II, and III)
• History/physical examination including documentation of the primary anal lesion size, distance from the anal verge and anal sphincter tone within 60 days prior to registration
• Anal examination with biopsy on either colonoscopy, sigmoidoscopy, rigid proctoscopy or anoscopy
• Computed tomography (CT) scan of the chest and abdomen with contrast or contrast-enhanced positron emission tomography (PET)/CT scan within 60 days of registration unless the patient has a documented contrast allergy
• CT scan of pelvis with contrast or contrast-enhanced PET/CT scan within 60 days of registration unless the patient has a documented contrast allergy
• Zubrod performance status of 0-1 within 60 days prior to registration
• Absolute neutrophil count (ANC) >=1.8 K/ul, cannot be achieved through granulocyte-colony stimulating factor (GCSF) (within 30 days prior to study registration)
• Platelets >= 100 K/uL, cannot be achieved through transfusion (within 30 days prior to study registration)
• Hemoglobin >= 8 g/dL, cannot be achieved through transfusion (within 30 days prior to study registration)
• Serum creatinine = = 3000/microliter (within 30 days prior to study registration)
• Aspartate transaminase (AST)/alanine transaminase (ALT) 400 cells/mm^3
• The patient must either have insurance authorization or otherwise secure funding to cover IMPT
• The patient must be able to receive concurrent chemotherapy

Exclusion Criteria

• Prior invasive malignancy (except non-melanomatous skin cancer), unless disease free for a minimum of 3 years
• Prior systemic chemotherapy for anal cancer
• Prior radiotherapy to the pelvis that would result in overlap of radiation fields
• Evidence of distant metastatic disease (M1)
• Prior surgery to the anal canal that removed all macroscopic anal cancer
• Women of childbearing potential or men who do not agree to use a medically effective form of birth control throughout their participation in the treatment phase of the study
• Severe, active co-morbidity defined as follows: unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months; transmural myocardial infarction within the last 6 months; acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration; hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; HIV positive with a CD4 count < 400 cells/mm^3; other immuno-compromised status; women who are pregnant or lactating; uncontrolled infection as deemed by the principal investigator (PI); patient incarceration