Hypofractionated Proton Therapy with Concurrent Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer: A Phase 1 Trial from the University of Florida and Proton Collaborative Group
JournalInternational Journal of Radiation Oncology Biology Physics
MetadataShow full item record
AbstractPurpose: We report the safety data from the first multicenter phase 1 trial investigating the use of hypofractionated proton therapy with concurrent chemotherapy for patients with stage II or III non-small cell lung cancer. Methods and Materials: From 2013 through 2018, patients with newly diagnosed stage II or III non-small cell lung cancer were enrolled in a multicenter phase 1 clinical trial evaluating concurrent chemotherapy with increasing dose-per-fraction proton therapy. This was a stepwise 5 + 2 dose-intensification protocol with the following dose arms: (1) 2.5 GyRBE per fraction to 60 GyRBE; (2) 3.0 GyRBE per fraction to 60 GyRBE; (3) 3.53 GyRBE per fraction to 60.01 GyRBE; and (4) 4.0 GyRBE per fraction to 60 GyRBE. A dose arm was considered tolerable if no radiation therapy-attributable severe adverse event (SAE) occurred within 90 days of treatment among 5 patients enrolled on the arm or if 1 SAE occurred among 7 patients enrolled. Dose constraints to the heart, brachial plexus, and spinal cord were more conservative at higher doses per fraction. Results: The study closed early because of slow accrual and competing enrollment in NRG 1308 before accrual was met, with no maximum tolerated dose identified. Eighteen patients were treated, including 5 patients on arms 1 and 2, 7 patients on arm 3, and 1 patient on arm 4. Two SAEs occurred among 7 patients treated at 3.53 GyRBE per fraction; however, per outside expert review, both were attributed to chemotherapy and unrelated to radiation therapy. Conclusions: Hypofractionated proton therapy delivered at 2.5 to 3.53 GyRBE per fraction to a dose of 60 GyRBE with concurrent chemotherapy has an acceptable toxicity profile. Further exploration of this regimen is warranted on a phase 2 clinical trial. 2020 The Author(s)
SponsorsThis research was made possible through the support of the James E. Lockwood, Jr. Professorship.
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85084234539&doi=10.1016%2fj.ijrobp.2020.03.015&partnerID=40&md5=3a2c404f3ad49e7c313ce598d57ddddb; http://hdl.handle.net/10713/12767
- Accelerated hypofractionated three-dimensional conformal radiation therapy (3 Gy/fraction) combined with concurrent chemotherapy for patients with unresectable stage III non-small cell lung cancer: preliminary results of an early terminated phase II trial.
- Authors: Ren XC, Wang QY, Zhang R, Chen XJ, Wang N, Liu YE, Zong J, Guo ZJ, Wang DY, Lin Q
- Issue date: 2016 Apr 23
- Dose escalation of accelerated hypofractionated three-dimensional conformal radiotherapy (at 3 Gy/fraction) with concurrent vinorelbine and carboplatin chemotherapy in unresectable stage III non-small-cell lung cancer: a phase I trial.
- Authors: Lin Q, Liu YE, Ren XC, Wang N, Chen XJ, Wang DY, Zong J, Peng Y, Guo ZJ, Hu J
- Issue date: 2013 Aug 17
- A Phase 2 Trial of Concurrent Chemotherapy and Proton Therapy for Stage III Non-Small Cell Lung Cancer: Results and Reflections Following Early Closure of a Single-Institution Study.
- Authors: Hoppe BS, Henderson R, Pham D, Cury JD, Bajwa A, Morris CG, D'Agostino H Jr, Flampouri S, Huh S, Li Z, McCook B, Nichols RC Jr
- Issue date: 2016 May 1
- High-dose accelerated hypofractionated three-dimensional conformal radiotherapy (at 3 Gy/fraction) with concurrent vinorelbine and carboplatin chemotherapy in locally advanced non-small-cell lung cancer: a feasibility study.
- Authors: Liu YE, Lin Q, Meng FJ, Chen XJ, Ren XC, Cao B, Wang N, Zong J, Peng Y, Ku YJ, Chen Y
- Issue date: 2013 Aug 11
- Phase 1 trial of preoperative image guided intensity modulated proton radiation therapy with simultaneously integrated boost to the high risk margin for retroperitoneal sarcomas.
- Authors: DeLaney TF, Chen YL, Baldini EH, Wang D, Adams J, Hickey SB, Yeap BY, Hahn SM, De Amorim Bernstein K, Nielsen GP, Choy E, Mullen JT, Yoon SS
- Issue date: 2017 Jan-Mar