Radiation Therapy with or without Cetuximab in Treating Patients Who Have Undergone Surgery for Locally Advanced Head and Neck Cancer

Inclusion Criteria

• Pathologically (histologically) proven diagnosis of squamous cell carcinoma (including variants such as verrucous carcinoma, spindle cell carcinoma, carcinoma not otherwise specified [NOS], etc.) of the head/neck (oral cavity, oropharynx or larynx); note: hypopharynx primaries are excluded
• Clinical stage T1, N1-2 or T2-4a, N0-2, M0 including no distant metastases, based upon the following minimum diagnostic workup: * General history and physical examination by a radiation oncologist and/or medical oncologist within 8 weeks prior to registration * Examination by an ear, nose and throat (ENT) or head & neck surgeon, within 8 weeks prior to registration; a laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure) is recommended but not required * Chest x-ray (at a minimum) or chest computed tomography (CT) scan (with or without contrast) or CT/positron emission tomography (PET) of chest (with or without contrast) within 8 weeks prior to registration
• Gross total resection of the primary tumor with curative intent must be completed within 7 weeks of registration with surgical pathology demonstrating one or more of the following “intermediate” risk factors: * Perineural invasion * Lymphovascular invasion * Single lymph node > 3 cm or >= 2 lymph nodes (all < 6 cm) (no extracapsular extension) * Close margin(s) of resection, defined as cancer extending to within 5 mm of a surgical margin, and/or an initially focally positive margin that is subsequently superseded by intraoperative negative margins; similarly, patients whose tumors had focally positive margins in the main specimen but negative margins from re-excised samples in the region of the positive margin are eligible; for questions or ambiguities about an individual case, contact Dr. Machtay and/or Dr. Holsinger prior to enrolling the patient * Pathologically confirmed T3 or T4a primary tumor; for questions or ambiguities about an individual case, contact Dr. Machtay and/or Dr. Holsinger prior to enrolling the patient * T2 oral cavity cancer with > 5 mm depth of invasion
• Zubrod performance status 0-1
• Absolute granulocyte count (AGC) >= 1,500/mm³
• Platelet count >= 100,000/mm³
• Hemoglobin >= 8.0 g/dL (note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dl is acceptable)
• Total bilirubin < 2 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 x institutional ULN
• Serum creatinine < 2 x institutional ULN or; creatinine clearance (CC) >= 50 mL/min determined by 24-hour collection or estimated by Cockcroft-Gault formula
• Negative serum pregnancy test within 2 weeks prior to registration for women of childbearing potential
• The following assessments are required within 2 weeks prior to the start of registration: sodium (Na), potassium (K), chloride (Cl), glucose, calcium (Ca), magnesium (Mg), and albumin; note: patients with an initial magnesium < 0.5 mmol/L (1.2 mg/dl) may receive corrective magnesium supplementation but should continue to receive either prophylactic weekly infusion of magnesium and/or oral magnesium supplementation (e.g., magnesium oxide) at the investigator’s discretion
• Women of childbearing potential and male participants who are sexually active must agree to use a medically effective means of birth control
• Patients must provide study specific informed consent prior to study entry, including consent for mandatory tissue submission for EGFR and for oropharyngeal patients, HPV analyses

Exclusion Criteria

• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; noninvasive cancers (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible) are permitted even if diagnosed and treated < 3 years ago; patients with simultaneous primaries or bilateral tumors are excluded, with the exception of patients with bilateral tonsil cancers or patients with primary tumor (T)1-2, nearby lymph nodes (N)0, metastasis (M)0 resected differentiated thyroid carcinoma, who are eligible
• Per the operative and/or pathology report, positive margin(s) (defined as tumor present at the cut or inked edge of the tumor), nodal extracapsular extension, and/or gross residual disease after surgery; note: patients whose tumors had focally positive margins in the main specimen but negative margins from re-excised samples in the region of the positive margin are eligible; for questions or ambiguities about an individual case, contact Dr. Machtay and/or Dr. Holsinger prior to enrolling the patient
• Prior systemic chemotherapy or anti-EGF therapy for the study cancer; note: prior chemotherapy or anti-EGF therapy for a different cancer is allowable
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
• Severe, active co-morbidity, defined as follows: * Unstable angina and/or congestive heart failure requiring hospitalization within 6 months prior to registration * Transmural myocardial infarction within 6 months prior to registration * 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 * Idiopathic pulmonary fibrosis or other severe interstitial lung disease that requires oxygen therapy or is thought to require oxygen therapy within 1 year prior to registration * Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for coagulation parameters are not required for entry into this protocol * Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note: human immunodeficiency virus (HIV) testing is not required for entry into this protocol; protocol-specific requirements may also exclude immuno-compromised patients * Grade 3-4 electrolyte abnormalities (CTCAE, v. 4): ** Serum calcium (ionized or adjusted for albumin) < 7 mg/dl (1.75 mmol/L) or > 12.5 mg/dl (> 3.1 mmol/L) despite intervention to normalize levels ** Glucose < 40 mg/dl (< 2.2 mmol/L) or > 250 mg/dl (> 14 mmol/L) ** Magnesium < 0.9 mg/dl (< 0.4 mmol/L) or > 3 mg/dl (> 1.23 mmol/L) despite intervention to normalize levels ** Potassium < 3.0 mmol/L or > 6 mmol/L despite intervention to normalize levels ** Sodium < 130 mmol/L or > 155 mmol/L despite intervention to normalize levels
• Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
• Prior allergic reaction to cetuximab