This randomized phase II trial studies radiation therapy and cisplatin with or without surgery in treating patients with stage III-IV oropharyngeal cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy with radiation therapy may kill more tumor cells. It is not yet known whether radiation therapy and cisplatin are more effective with or without surgery in treating patients with oropharyngeal cancer.
PRIMARY OBJECTIVES: I. To determine if primary treatment with transoral endoscopic head and neck surgery will improve progression free survival (PFS) for patients with human papilloma virus negative (HPV-) oropharyngeal cancer (OPC). SECONDARY OBJECTIVES: I. To compare patterns of failure (local-regional relapse versus distant) and survival (overall and progression-free). II. To determine the safety and efficacy (rate of positive surgical margins) of using transoral robotic surgery for patients with T3 tumors of the tonsil, tongue-base, or glossopharyngeal sulcus. III. To compare head and neck cancer-specific quality of life (QOL) short-term (\< 6 months) and long-term (2 years) relating to swallowing function. IV. To compare subjective (patient reported) and objective (physiologic) measures of swallowing function short-term and long-term. V. To assess effect of neck dissection on shoulder function using a validated QOL instrument for patients undergoing neck dissection VI. To assess the correlation of physician derived clinical target volumes (CTV's) with locoregional control or failure. VII. To determine whether specific molecular profiles are associated with overall or progression-free survival or other clinical endpoints. VIII. To determine the sensitivity and specificity of pre-treatment computed tomography (CT) scans detecting the presence of lymph node extracapsular extension by examining the surgically dissected lymph nodes. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients undergo transoral endoscopic head and neck surgery (eHNS). Depending on post-operative pathology findings, patients may undergo intensity modulated radiation therapy (IMRT) once daily (QD) five days a week for 6 weeks. High-risk patients also receive cisplatin intravenously (IV) on days 1, 8, 15, 22, 29, and 36 during radiation therapy. ARM II: Patients undergo IMRT QD five days a week for 7 weeks. Patients also receive cisplatin IV on days 1, 8, 15, 22, 29, and 36 during radiation therapy. After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Stanford University Hospitals and Clinics
Stanford, California, United States
Progression-free survival (PFS)
Estimated for both arms using the Kaplan-Meier method. The distribution will be compared between arms with a one-sided log rank test.
Time frame: Up to 5 years
Patterns of local, regional, and distant failure
The cumulative incidence method will be used to estimate local-regional and distant failure rates and the failure rates for the experimental treatment will be compared against the control using a failure specific log rank test.
Time frame: Up to 5 years
Overall survival (OS)
Estimated for both arms using the Kaplan-Meier method. The distribution will be compared between arms with a one-sided log rank test.
Time frame: Up to 5 years
Rate of grade 4-5 oropharyngeal hemorrhage and involved surgical margin for all patients and patients with selected T3 tumors
Time frame: Up to 5 years
Objective swallowing function
Time frame: Up to 2 years
Shoulder function
Time frame: Up to 2 years
Short-term quality of life: head and neck-specific (swallowing domain and shoulder function) using the M. D. Anderson Dysphagia Inventory (MDADI)
Compared using a two-sample independent t test and paired t test if the comparison is within the experimental arm between different time points. Overall score and change from baseline will be summarized using mean and standard deviation at each time point for each arm. Binary endpoints will be compared using Fisher's exact test.
Time frame: Up to 6 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Ancillary studies
Correlative studies
Long-term quality of life: head and neck-specific (swallowing domain and shoulder function) using the MDADI
Compared using a two-sample independent t test and paired t test if the comparison is within the experimental arm between different time points. Overall score and change from baseline will be summarized using mean and standard deviation at each time point for each arm. Binary endpoints will be compared using Fisher's exact test.
Time frame: At 2 years