Radiation Therapy With or Without Chemotherapy in Treating Patients With High-Risk Malignant Salivary Gland Tumors That Have Been Removed By Surgery

OBJECTIVES:

Primary

Phase II

• Determine the feasibility of conducting a cooperative group prospective clinical trial in patients with resected malignant salivary gland tumors.
• Acquire preliminary efficacy data comparing postoperative radiotherapy alone to concurrent chemotherapy and radiation using weekly cisplatin.

Phase III

• Compare overall survival rates among patients receiving cisplatin and radiation to those receiving radiation alone.

Secondary

Phase II/III

• Compare the acute toxicities of these 2 adjuvant treatments.
• Compare late treatment-related adverse events in patients receiving postoperative radiation to those receiving concurrent chemoradiation.
• Compare progression-free survival rates among patients receiving cisplatin and radiation to those receiving radiation alone in both the cohort of patients with pathologically high-risk disease (high-grade adenocarcinoma, high-grade mucoepidermoid carcinoma, salivary duct carcinoma), and the patient cohort with pathologically intermediate-risk disease (all other eligible diagnoses).
• Investigate quality of life and patient-reported outcomes in patients enrolled in the study.
• Identify the histopathology and tumor marker expression from patients enrolled on this trial and assemble a tissue bank for future correlative studies.
• Establish a NRG Oncology baseline database for salivary gland malignancies to serve as a resource for future exploration of innovative and/or targeted approaches for this disease.

OUTLINE: This is a multicenter study. Patients are stratified according to histology (high-grade mucoepidermoid carcinoma vs salivary duct carcinoma vs high-grade adenocarcinoma) and nodal status (N0 vs N1-3). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo 3-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) 5 days a week for 6-6.5 weeks. Patients also receive cisplatin IV over 60 minutes on days 1, 8, 15, 22, 29, 36, and 43 during radiotherapy.
• Arm II: Patients undergo 3D-CRT or IMRT as in Arm I. Tissue and blood samples may be collected for translational research studies. Patients may complete quality-of-life assessments periodically.

After completion of study treatment, patients are followed up at 3, 6, 9, 12, and 24 months, every 6 months for 2 years, and then annually thereafter.

DISEASE CHARACTERISTICS:

• Pathologically proven diagnosis of a malignant major salivary gland tumor or malignant minor salivary gland tumor of the head and neck of the following histologic subtypes:

• Intermediate-grade adenocarcinoma or intermediate-grade mucoepidermoid carcinoma
• High-grade acinic cell carcinoma or high-grade (>30% solid component) adenoid cystic carcinoma
• Surgical resection with curative intent within 8 weeks prior to registration
• All patients must have a Medical Oncology evaluation within 4 weeks prior to registration
• Pathologic stage T3-4 or N1-3 or T1-2, N0 with a close (≤ 1mm) or microscopically positive surgical margin; patients must be free of distant metastases based upon the following minimum diagnostic workup:

• History/physical examination within 8 weeks prior to registration
• Radiologic confirmation of the absence of hematogenous metastasis within 12 weeks prior to registration; at a minimum, contrast CT imaging of the chest is required (PET/CT is acceptable)
• No patients with residual macroscopic disease after surgery
• No prior systemic chemotherapy or radiation therapy for salivary gland malignancy

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-1
• Absolute neutrophil count (ANC) ≥ 1,800 cells/mm^3
• Platelets ≥ 100,000 cells/mm^3
• Hemoglobin ≥ 8.0 g/dL (the use of transfusion or other intervention to achieve hemoglobin ≥ 8.0 g/dL is acceptable)
• Serum creatinine < 2.0 mg/dL
• Total bilirubin < 2 x the institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 x the institutional ULN
• Negative serum pregnancy test within 2 weeks prior to registration for women of childbearing potential
• Women of childbearing potential and male participants who are sexually active must practice adequate contraception during treatment and for 6 weeks following treatment
• Not pregnant or nursing
• Patients must be deemed able to comply with the treatment plan and follow-up schedule
• Patients must provide study specific informed consent prior to study entry, including consent for mandatory tissue submission for central review
• No prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
• No 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 (coagulation parameters are not required for entry into this protocol)
• Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control (CDC) definition (HIV testing is not required for entry into this protocol)

• Protocol-specific requirements may also exclude immunocompromised patients
• Pre-existing ≥ grade 2 neuropathy
• No significant pre-existing hearing loss, as defined by the patient or treating physician

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior systemic chemotherapy or radiation therapy for salivary gland malignancy (prior chemotherapy for a different cancer is allowable)
• No prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
• No prior organ transplant
• No concurrent hematopoietic growth factors (e.g., G-CSF or pegfilgrastim) during radiotherapy
• No concurrent erythropoiesis-stimulating agents