The researchers are doing this study is to find out if lower doses (given in fewer treatments over a shorter period of time) of radiation therapy in combination with standard-of-care chemotherapy is an effective treatment for people with Human Papilloma Virus (HPV)-positive throat cancer and works as well as the standard doses of radiation therapy in combination with standard-of-care chemotherapy. The chemotherapy drugs used in combination with radiation therapy in this study include cisplatin, carboplatin, and 5-fluorouracil (5-FU).
Pathologically (histologically or cytologically) proven diagnosis of HPV associated squamous cell carcinoma of the oropharynx (tonsil, base of tongue, or oropharyngeal walls) from biopsy, surgical resection or excisional biopsy regardless of margin status.
Squamous cell carcinoma of the neck of unknown primary is allowed with excision biopsy of a lymph node (or core biopsy) or consent from the PI or co-PI. Patient must have excisional biopsy or core biopsy done in order to be on protocol.
Subjects must have clinically or radiographically evident measurable gross disease at either the primary tumor site or nodal stations.
T3-4/N0-2c or any N3 regardless of Tstage (AJCC 7th Edition) HPV+ OPC* or HPV associated squamous cell carcinoma with nodal metastasis (es) but unknown primary sites without evidence of distant metastasis based on FDG PET/CT.
Subjects with prior head and neck radiation therapy
Subjects with simultaneous primary cancers outside of the oropharynx if determined by the PI/Co-PI the patient can proceed with protocol activities.
Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for 3 years or if cure rate from treatment at 5 years to be 90% or greater
Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable
Single group
18F-FMISO PET/CT Scan
Diagnostic testThe 18F-FMISO PET/CT Scan Protocol consists first of an IV bolus injection of approximately 5-10 mCi of the radiotracer. Subjects will undergo 18F-FMISO scan (only 1 injection) occurs at 8-10 treatment days\* into chemoradiation. Each patient will have a baseline staging FDG PET scan which is used to localize the tumor at the primary site and all suspicious cervical neck nodes (\> 1 cm in short axis diameter with focal abnormal increased FDG avidity). These lesions are then assessed on the respective 18F-FMISO PET/CT.
Chemoradiation
Combination productPatients will start with induction chemotherapy of carboplatin, paclitaxel and cetuximab for 6 weeks and when downstaged to T1-2 and \< N3, the patient is eligible to receive concurrent chemoradiation per protocol. All subjects will undergo radiation treatments (IMRT and/or proton therapy). A total radiation therapy of 30Gy will be delivered to the oropharynx and neck at 2Gy per fraction per day over 15 days for patients who exhibited no evidence of hypoxia on the intra-treatment 18F-FMISO PET/CT. Concurrent chemotherapy (2 cycles) will be given. After completion of chemotherapy and radiation therapy, a 4 month (+/-4 weeks)
Questionnaires
Other interventionEQ-5D-5L, MDADI-HN, COST-FACIT
Locoregional control
Researchers will test the null hypothesis H0: P=78% vs the alternative hypothesis H1:P=91%, where P represents the 2-year locoregional control (LRC). We will use the Kaplan-Meier method to estimate the LRC rate at 2 years and construct a 0.975 1-sided confidence interval in order to achieve a test size alpha = 0.05 (this is based on a finite-sample correction using 100,000 simulations).
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