This project involves conducting a phase II trial of extracranial stereotactic radioablation (ESR) for treatment of patients with medically inoperable early stage non-small cell lung cancer (NSCLC). Surgical resection of stage I NSCLC results in 5-year survival rates of approximately 60-70%, and remains the treatment of choice for this population. Some patients with early stage NSCLC are unable to tolerate the rigors of surgery or the post-operative recovery period due to lack of adequate respiratory reserve, cardiac dysfunction, diabetes mellitus, vascular disease, or other co-morbidities. Currently available non-surgical alternatives including fractionated radiotherapy have reported 5-year survival rates ranging from 10-30%. There is both a high rate of local failure and significant toxicity with standard fractionated radiotherapy limiting its utility in this population. A new generation radiation delivery technique called ESR allows precise stereotactic targeting and radiation delivery. ESR incorporates a variety of systems for decreasing the effects of lung and other organ motion that would otherwise translate into target motion. These systems allow even more dramatic reduction of treatment volumes facilitating markedly increased daily doses and significantly reduced overall treatment time. A previously conducted phase I trial demonstrated that very high doses per treatment can be safely delivered using ESR in this population. As with the historical experience with stereotactic radiosurgery for treating brain tumors, high doses per treatment may be associated with enhanced tumor control as compared to standard fractionated radiotherapy. With enhanced tumor control, it is postulated that this population with limited NSCLC may enjoy an improvement in survival more comparable to surgically treated patients. A prospective phase II trial is the best mechanism to evaluate the logistics, toxicity, and efficacy of ESR. It also affords the opportunity for allowing evaluation of baseline and post-treatment functional imaging correlative investigation aimed at achieving a better understanding of tumor response characteristics and patient tolerance. Finally, the outcome and survival after treatment with ESR in this trial employing uniform selection, evaluation, treatment and follow-up will best determine whether further resources are warranted for eventually testing this emerging technology against more standard therapy in a phase III randomized trial. ? ?
