Intensity-Modulated Proton Beam Therapy or Intensity-Modulated Photon Therapy in Treating Patients With Stage III-IVB Oropharyngeal Cancer

PRIMARY OBJECTIVES:

To compare the progression-free survival (PFS) between concurrent chemo-radiation strategies with IMRT and IMPT following the treatment of oropharyngeal tumors.

SECONDARY OBJECTIVES:

• To assess and compare overall survival between IMRT and IMPT along with estimating disease-related outcomes such as: [2-year progression-free survival, patterns of failure, 2-year overall survival, 2-year distant metastasis free survival, and second primary cancers]
• To assess acute and chronic/late side effects, and to compare the rates of Grade 3-5 toxicity between IMRT and IMPT following the treatment of oropharyngeal tumors.
• To assess Patient Reported Outcome (PRO) measures of symptoms using MD Anderson Symptom Inventory (MDASI), MD Anderson Dysphagia Inventory (MDADI), FACT-HN, Xerostomia and Health Questionnaire (EQ-5D-3L), Work status (WPAI: SHP)
• To assess Physician Reported Toxicity using Common Terminology Criteria for Adverse Events (CTCAE)-4.0
• To evaluate and compare Quality-Adjusted-Life-Years (QALY) between IMPT and IMRT;
• To perform Cost-benefit economic analysis of treatment;
• To determine whether specific molecular profiles are associated with overall or progression-free survival;
• To investigate associations between changes in blood biomarkers, or HPV-specific cellular immune responses, or HPV ctDNA (measured at baseline and three months and at each follow-up visit for up to 10 years) with overall or progression-free survival;
• To bank peripheral blood at time of enrollment, weeks 2, 4, and 6 during treatment and at each follow up visits for up to 10 years to explore the ability of circulating markers to predict outcome;
• To bank head and neck tissues to explore the ability of tissue-based markers to predict outcome;
• To bank peripheral blood and tissues for future interrogations; Finally, all additional secondary endpoints

EXPLORATORY OBJECTIVE:

I. To assess potential differences between patients on study and patients who were considered eligible for randomized, were randomized to a treatment arm, but were denied insurance coverage for the treatment arm she/he was randomized to; or may have dropped out of the study for other reasons after being randomized. These patients will compromise Group 3: consisting of patients randomized to Protons but not treated and Group 4: consisting of patients randomized to IMRT but not treated at the designated institution. Furthermore, these patients will only be followed for recurrence and survival.(Phase III)

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients undergo IMRT once daily (QD) five days a week for approximately 6.5 weeks.

ARM II: Patients undergo IMPT QD five days a week for approximately 6.5 weeks.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, and then every 6 months for 5 years.

Inclusion criteria

• Histologically documented squamous cell carcinoma of the oropharynx (American Joint Committee on Cancer [AJCC] version [v]7 stage III-IV A,B)
• Tumor tissue (primary or cervical metastasis) available for human papilloma virus (HPV) and/or p16 (in situ hybridization [ISH], immunohistochemistry [IHC] or genotyping testing); if you do not have enough leftover tumor tissue available, you will have a tumor biopsy for tumor marker testing
• Eastern Cooperative Oncology Group (ECOG) performance status = 0, 1, or 2
• Negative pregnancy test for women of child bearing potential
• Concurrent chemotherapy
• Bilateral neck radiation

Exclusion criteria

• Previous radiation treatment for head and neck mucosal primary cancers within the past 5 years (i.e. oropharynx, nasopharynx, hypopharynx, larynx, and oral cavity)
• Pregnant or breast-feeding females
• Clinically significant uncontrolled major cardiac, respiratory, renal, hepatic, gastrointestinal or hematologic disease but not limited to:

• Symptomatic congestive heart failure, unstable angina, or cardiac dysrhythmia not controlled by pacer device
• Myocardial infarction within 3 months of registration
• Distant metastases (stage IV C, any T, any N and M1)
• Previous surgical resection or neck dissection for oropharyngeal cancer, administered with therapeutic intent