A Phase II Study of Treatment De-Intensification in Favorable Squamous Cell Carcinoma of the Oropharynx
Johns Hopkins Kimmel Cancer Center in Baltimore
This research is being done to try to reduce radiation side effects that happen with the standard radiation methods. Generally surgery, radiation therapy, and sometimes chemotherapy are standard treatment for people with Squamous Cell Carcinoma of the Oropharynx. The study will look at giving a slightly smaller dose of radiation (de-Intensification) to see if regularly expected late toxicities (two years after receiving treatment) can be reduced. This study will also try to see if the smaller dose of radiation is equally effective at treating the cancer and to see if it improves quality of life. Along with this radiation treatment plan some participants in this study will have surgery on their tumor and or receive chemotherapy (cisplatin). The possible surgery and or chemotherapy will be up to the participantâ??s doctor. Study participants will be tested for the Human Papillomavirus (HPV). This tissue test is required for this study. Some studies have suggested that HPV-related cancer is biologically and clinically different as compared to non-HPV-related cancer. Some studies have found that patients with HPV-related oropharynx cancer have a better response to treatment. This test will help researchers learn more about HPV-related cancer.
Inclusion Criteria: * Biopsy-proven SCC of the oropharynx (tonsil, base of tongue, pharyngeal wall or palate). * Tumor positive for infection with HPV virus type 16 or other types (section 8.0). * T stage: 1, 2. T3 tumors are allowed if the tumor is arising from the tonsillar fossa and/or is exophytic based on both clinical exam and CT; Surgery of the primary tumor is limited to incisional or excisional biopsies (i.e tonsillectomy) even without macroscopic disease left. Positive resection margins and/or gross residual disease at the primary site are allowed. * Any N stage, but resectable; lymph nodes in both sides of the neck are at risk of metastatic disease, according to clinical judgment, and require irradiation; pre-treatment surgery in the neck in the forms of incisional/excisional biopsy or a multilevel neck dissection is allowed only if there is gross tumor left at the primary site. * M0. * ECOG performance status 0-1. * Patient's nutritional and general physical condition must be considered compatible with the proposed radiotherapeutic treatment and/or amenable to be corrected before the start of treatment. * Patient is judged to be mentally reliable to follow instructions and to keep appointments. * Patient is on no other treatment for head and neck cancer. * Signed study-specific informed consent prior to registration. Exclusion Criteria: * Evidence of distant metastases. * Evidence of extracapsular nodal extension on pathology. * Absence of macroscopic disease after upfront surgery, i.e., TxNx and TxN0. TxN+ and T1-3Nx are eligible if the T/N stage categories meet the criteria of 3.1.1. * Previous irradiation for head and neck tumor; concurrent chemotherapy other than the treatment per protocol; previous chemotherapy ï¿½ 3 months from start of RT. * Other malignancy except non-melanomatous skin cancer or a carcinoma not of head and neck origin and controlled at least 5 years. * Active untreated infection. * Major medical or psychiatric illness, which in the investigators' opinions would interfere with either completion of therapy and follow-up or with full and complete understanding of the risks and potential complications of the therapy. * Prophylactic use of amifostine or pilocarpine is not allowed.
Radiation: IMRT 70 Gy, 63 Gy and 58.1 Gy to primary tumor and whole neck (PTV1-3) in 35 fractions. The Px to each PTV is reported in table 6. Now we have 4 dose levels, 70, 63, 58.1 and 50.75 Gy. In cases after primary tumor surgery where there is no residual macroscopic disease left, the total dose to PTV1 can be reduced from 70 Gy to 68.25 Gy. In this case PTV68.25 is treated as PTV70 regarding overlap with the various OAR's. Chemotherapy: The first dose of cisplatin 40mg/m2 IV will be administered within the first 3 days of the start of RT and repeated weekly for the duration of RT. If RT is held, cisplatin will also be held. Switch to Carboplatin: In case of any of the followings, cisplatin will be substituted to carboplatin: serum creatinine above the upper limit of normal and creatinine clearance less than 60; refractory magnesium and electrolyte wasting; ototoxicity; peripheral neuropathy grade 2. Weekly carboplatin dosing would be at AUC equal to 2; q 3wk dosing at AUC equal to 5.
07/28/2015 09:39 AM