This project is a phase I study which will explore the use of helical tomotherapy in the treatment of non-small cell lung cancer (NSCLC). The overall hypothesis is that dose escalation in the NSCLC will improve local control and disease-specific survival rates, and that this can be achieved safely and effectively with dose-per-fraction escalation rather than the conventional approach of the increasing number of fractions. However, survival cannot be tested with sufficient statistical power within the time frame of this proposal, so we shall concentrate instead on the essential prerequisite of dose escalation to determine maximum tolerated dose (MTD) in specified volumes of lung irradiated. The strategy of dose-per-fraction escalation used in this study is based on modeling done here by Fowler and Chappel which showed that cell doubling times in large detriments in local control due to proliferation are avoided. More modest increase of dose per fraction can be utilized than if increasing overall times were used, but still are expected to increase local control and can be utilized than if increasing overall times were used, but still are expected to increase local control and survival when eventually tested. We have designed a step-wise approach to safely determine MTDs of a series of volume categories, employing both NTD mean and V20. The first phase will involve developing a consistent, reproducible method of delivering radiotherapy using helical tomotherapy during breathholding. The second phase will be to shorten the overall treatment in NSCLC from 6 to 5 weeks by increasing the dose per fraction. The daily and total doses are first chosen to have the same predicted risk of late effects as the standard dose fractionation (60 Gy at 2 Gy per fraction). The third phase will involve dose escalation in a classic Phase I manner. Patients will be stratified into 5 groups on the basis of mean lung dose and patients in each group will undergo semi-independent dose escalation process will involve an increase in dose per fraction while the total number of fractions (25) and overall time (5 weeks) will remain constant. Escalation will be permitted if the incidence if the incidence of pneumonitis doses not exceed 20%. The ultra-conformal dose delivery, verification and adaptation made possible by helical tomotherapy with its intra-treatment megavoltage CT imaging will allow this dose escalation strategy to be tested with a minimized risk of normal tissue damage.
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