Squamous Cell Carcinoma of the Head and Neck T1/2N0-2 Clinical Trial
Official title:
A Phase I Study of Reduced-Volume Hypofractionated, PET-directed Intensity Modulated Radiotherapy Concurrent With Weekly Cisplatin Chemotherapy for T1/2N0-2 Squamous Cell Carcinoma of the Head and Neck
Primary Objectives: To determine whether patients with T1/2N0-2 Squamous Cell Carcinoma of the oropharynx, hypopharynx or larynx can tolerate treatment with cisplatin chemoradiation in three weeks using reduced volume IMRT Secondary Objectives: To describe the adverse events associated with hypofractionated, reduced volume cisplatin chemoradiation. To estimate response rates and progression-free survival rates of hypofractionated, reduced volume cisplatin chemoradiation. To determine HRQOL following hypofractionated, reduced volume cisplatin chemoradiation. If patients can safely be treated in three weeks rather than six weeks, such a schedule would provide a much more convenient alternative for patients and result in a significant reduction in the health care resources currently expended on cure of these patients.
Head and neck squamous cell carcinomas (HNSCC) are frequently occurring tumors with more than 500,000 new cases worldwide and 45,000 in the USA yearly . Most patients present with local-regionally advanced diseases. Chemotherapy given concurrently with radiation is an integrated treatment component in the management of these patients. Concurrent chemoradiation can be given in unresectable diseases, in organ preservation to avoid surgery and preserve functions, and in high risk patients after surgery . Randomized clinical trials and meta-analyses have shown that concurrent chemoradiation are superior to radiation alone in these settings. One way of reducing overall treatment time and toxicity is to reduce the number of fractions by increasing the daily radiotherapy dose. The consequence of increased daily dose is both an increase in acute side effects as well as an increase in late toxicity. A widely accepted model of these radiobiologic effects over the range of typical 2-4 Gy daily fractions is the alpha-beta model that distinguishes acute responses and late responses based on a linear-quadratic fitting of extrapolated clonogenic survival curves. A time factor can be incorporated to account for the effect of repopulation. Equivalent biologically effective dose schedules using a reduced number of fractions may be calculated for any conventionally fractionated course. Because 70Gy/35/6 weeks with chemoradiation has been demonstrated to be tolerable, and because 66Gy/30/6 weeks has been shown with IMRT to produce 90% control for T1/2 oropharyngeal primary tumors, we will take the biological equivalent of 66Gy/33 fractions over six weeks as the biologic equivalent standard we wish to maintain in hypofractionated courses of radiation. Because 54Gy/30 over six weeks is a well-known elective radiation dose schedule producing 95% control of occult nodal disease, we will take this as the biologically equivalent standard we wish to maintain in our hypofractionated schedules. ;