A Phase I/II Study of Hypofractionated Proton Therapy for Stage II-III Non-Small Cell Lung Cancer
Conventional fractionated photon-based radiotherapy to 60-63 Gy at 1.8-2 Gy/fraction with
concurrent chemotherapy remains the standard treatment practice in patients with stage III
non-small cell lung carcinoma (NSCLC) with local control rates of approximately 50% and a
median overall survival of just 18 months.Unfortunately, even the standard treatment has
significant toxicity with approximately 40% of patients developing grade 3 or higher acute
toxicities in the RTOG 9410 study.1 These outcomes are poor and more effective treatment
regimens are needed.
Higher doses of radiation have been hypothesized to improve local control in patients with
stage III NSCLC. This is expected to translate into better overall survival.Given the
significant improvements in outcome in patients receiving hypofractionation for stage I
NSCLC, perhaps similar gains could be achieved if hypofractionated radiotherapy could be
safely delivered to stage II-III NSCLC with concurrent chemotherapy. Hypofractionated
radiotherapy may offer improvement in local control compared with conventional fractionation
that may translate into improved overall survival. Furthermore, hypofractionation will
shorten the time interval during which patients are receiving less aggressive chemotherapy.
Proton therapy is a highly conformal radiotherapy technique that takes advantage of the
proton's characteristic Bragg Peak, resulting in significant reductions in the exit dose of
the treatment beam. Thus, proton therapy can substantially reduce the dose to critical
structures even compared with IMRT.
This study will investigate the safety and efficacy of delivering hypofractionated proton
therapy with concurrent chemotherapy in patients with stage II-III NSCLC
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Phase I: Establish the maximum tolerated dose of radiotherapy in terms of Gy (RBE)/fraction using hypofractionated proton therapy concurrently with chemotherapy.
This phase will have a minimum of 2 treated patients and we anticipate that the MTD will be located before a maximum of 28 patients are treated. The trial begins by treating 5 patients at 2.5 Gy (RBE)/fraction to a dose of 60 Gy (RBE).
Weekly until completion of radiation treatment
Brad Hoppe, MD
Proton Collaborative Group
United States: Institutional Review Board
|University of Florida Proton Therapy Institute||Jacksonville, Florida 32206|
|ProCure Proton Therapy Center||Warrenville, Illinois 60555|
|Princeton ProCure Management LLC||Somerset, New Jersey 08873|