Phase 1 Study of Dose Escalation in Hypofractionated Proton Beam Therapy for Non-Small Cell Lung Cancer

Abstract

Summary Twenty five patients were treated with proton beam therapy to 45 Gy(RBE), 52.5 Gy(RBE), or 60 Gy(RBE) in 15 fractions using a 3+3 study design. Dose constraints were based on biologically equivalent doses to standard fractionated treatment. Two patients experienced high-grade toxicity, both possibly related to radiation therapy. We consider this approach to be a good option for patients who are not candidates for concurrent chemoradiation. Background Many patients with locally advanced non-small cell lung cancer (NSCLC) cannot undergo concurrent chemotherapy because of comorbidities or poor performance status. Hypofractionated radiation regimens, if tolerable, may provide an option to these patients for effective local control. Patients and Methods Twenty five patients were enrolled in a phase I dose-escalation trial of proton beam therapy (PBT) from September 2010 through July 2012. Eligible patients had histologically documented lung cancer, thymic tumors, carcinoid tumors, or metastatic thyroid tumors. Concurrent chemotherapy was not allowed, but concurrent treatment with biologic agents was. The dose-escalation schema comprised 15 fractions of 3 Gy(RBE)/fraction, 3.5 Gy(RBE)/fraction, or 4 Gy(RBE)/fraction. Dose constraints were derived from biologically equivalent doses of standard fractionated treatment. Results The median follow-up time for patients alive at the time of analysis was 13 months (range 8-28 months). Fifteen patients received treatment to hilar or mediastinal lymph nodes. Two patients experienced dose-limiting toxicity possibly related to treatment; one received 3.5-Gy(RBE) fractions and developed an in-field tracheoesophageal fistula 9 months after PBT and 1 month after bevacizumab. The other patient received 4-Gy(RBE) fractions and was hospitalized for bacterial pneumonia/radiation pneumonitis 4 months after PBT. Conclusion Hypofractionated PBT to the thorax delivered over 3 weeks was well tolerated even with significant doses to the lungs and mediastinal structures. Phase II/III trials are needed to compare the efficacy of this technique with standard treatment for locally advanced NSCLC.

Feasibility and efficacy of helical intensity-modulated radiotherapy for stage III non-small cell lung cancer in comparison with conventionally fractionated 3D-CRT

“…The incidences of acute RE ≥ grade 2 was significantly lower in the HT group than in the 3D-CRT group (P=0.027). Our results were in line with previous studies (26,27). Grade ≥2 esophagitis was seen in 40% of patients with NSCLC in a phase I dose escalation trial of proton beam therapy (27).…”

“…Our results were in line with previous studies (26,27). Grade ≥2 esophagitis was seen in 40% of patients with NSCLC in a phase I dose escalation trial of proton beam therapy (27). All patients were treated with hypofractionated (3-4 Gy/fraction) via proton beam therapy without concurrent chemotherapy.…”

Clinical Implementation of Intensity Modulated Proton Therapy in Thoracic Malignancies

“…Proton therapy for lung cancer may be better able to spare critical structures than intensity modulated photon radiation therapy (IMRT) (1)(2)(3)(4)(5)(6). Passive scattering proton therapy (PSPT), however, relies on 3-dimensional treatment planning (with its inherent limitations) and requires typically 0.5 to 1 cm smearing plus other uncertainty margins (7).…”

Proton radiotherapy for treating the most common carcinomas

“…High efficacy and tolerance was found by applying hypofractionation to proton radiotherapy when escalating the dose (50-70 Gy RBE in 10 fractions or 15 fractions of 45--60 Gy RBE ) in patients with early lung cancer [31,33,34,36,38,45]. Two-and 3-year overall survival (OS) rates ranged respectively 81-98% and 72-88% whilst for local control (LC) these were 80-97% and 74-96% respectively [33-36, 38, 39, 46].…”