The overall goal of Project 1 is to determine, through a series of non-small cell lung cancer (NSCLC) clinicaltrials, whether proton therapy in its current state of the art or with the advances achieved through physicsresearch proposed in Projects 3 and 4 would lead to superior outcome compared to photon therapy. Despitethe apparent physical advantages of proton dose distributions, the answer to this question is not obviousbecause of the challenges of intra-fractional motion, inter-fractional anatomic changes (e.g., due to tumorshrinkage and weight loss), internal inhomogeneities, low density of lung tissue and other sources ofphysical and biological uncertainties. These factors affect the range of protons and cause the dosedistribution seen on a treatment plan to be different from the dose distribution actually received by thepatient. Initial trials will be conducted with the current state of the art of proton therapy. Physicsinvestigations proposed in Projects 3 and 4 will lead to improved accuracy and quality of proton dosedistributions. Additional clinical trials conducted with the advanced state of the art of proton therapy willallow the evaluation of the true potential of protons vs. photons.
The aims of this project are: 1) Stage II-IIIBRandomized Trial: a reduction in the rate of pneumonitis with equivalent tumor control may be realizedusing protons compared to photons in patients with stage II-IIIB NSCLC receiving concurrent chemotherapyand will be tested in a Bayesian adaptive randomized trial, 2) Stage II-IIIB Phase l/ll Dose Escalation Trial:local control can be improved in patients with stage II-IIIB as a result of higher fraction sizes and totalradiation doses to gross tumor volume delivered by simultaneous integrated proton boosts without increasingtoxicity when concurrent chemotherapy is used. 3) Stage l/ll Phase l/ll Trial: proton therapy with standardfractionation and higher BED may have a higher maximal tolerated dose (MTD) compared with conventionalphoton therapy, 4) Stage //// Randomized Trial: proton therapy (from Aim 3) compared to highest doseregimen safely achieved with photon therapy can lead to improved local control in centrally located stage IAor stage IB and selective stage II (T3NOMO) NSCLC, 5) Hypofractionated (-10 CGE per fraction orhigher) Stereotactic Body Proton Therapy (SBPT) of centrally located Stage I. The significance is thatthe results of our studies will allow us to determine which NSCLC patients are most likely to benefit fromproton therapy, and to set the stage for cooperative trials.
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