Protons have a physical dose advantage over photons (x-rays), the most commonly used type ofradiation therapy for cancer patients, because they do not exit beyond the tumor target and thus irradiateless normal tissue. Irradiation of normal tissue yields no possible benefit for the patient; it can only increasethe risk of treatment related side effects during and long after the end of treatment. While proton radiationtherapy has been used in selective clinical sites with significant improvements in clinical outcome, we believethat research into better control of the finite range of the proton in the patient can yield additional clinicalgains. The major objective of this project, Improving the Therapeutic Ratio of Proton Radiation Therapy inChallenging Clinical Sites, is to perform clinical trials employing improved control of the proton range inchallenging clinical scenarios. We believe that these research advances should translate into furtherimprovement in outcome in not only these particular diseases, but at multiple other anatomic sites whereproton radiation therapy is increasingly being employed. The potential impact for public health is highercancer cure rates and/or reduced treatment side effects, particularly in children, who are at the highest risk oflate radiation therapy-induced side effects, which can be reduced with the use of protons.
The specific aims are to conduct phase II clinical studies in patients with unresectable liver tumors,pediatric medulloblastoma and rhabdomyosarcoma, spine and skull base sarcomas, and paranasal sinustumors in which we will (1) use the end of range of the proton more effectively, (2) investigate the clinical useof magnetically scanned proton beams and intensity-modulated proton therapy, (3) confirm the tolerabilityand effectiveness of hypofractionated radiation dose escalation for unresectable liver tumors, (4) criticallyassess the importance of an adaptive proton radiation therapy strategy in response to tumor and normaltissue responses to radiation therapy in one anatomic site, and (5) compare treatment-related morbidity withphotons and protons in these selected pediatric malignancies and in adult paranasal sinus tumors. Thephysical tools necessary to achieve these clinical goals will be investigated in Projects 3 and 4. The initialuse of many of these physical tools in Project 2 will be important for their later use in Project 1, Proton DoseEscalation and Proton vs. Photon Randomized Trials for Non-Small Cell Lung Cancer.
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