Multi-Institutional Prospective Study of Reirradiation with Proton Beam Radiotherapy for Locoregionally Recurrent Non-Small Cell Lung Cancer.
The management of recurrent NSCLC in the setting of prior radiation therapy is challenging. Proton radiotherapy (PRT) is ideally suited to minimize toxicity to previously irradiated organs. We report the safety/feasibility of PRT for NSCLC reirradiation in a prospective multi-institutional study.



Between October 2010 and December 2015, 57 patients with recurrent NSCLC in or near their prior radiation field were treated at three proton centers. Patients were classified by tumor volume, location, and clinical characteristics. Toxicities were scored using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Survival outcomes were estimated by using Kaplan-Meier analysis.



Fifty-two patients (93%) completed the reirradiation course. Their median age was 65 years (41-86). Patients with high tumor volume (clinical target volume-to-internal target volume ratio ≥250 cm3) were closed to enrollment owing to infeasibility in August 2012. Concurrent systemic therapy was delivered to 67% of patients. Fourteen patients (25%) had evidence of local (n = 9) or regional (n = 5) recurrence. Distant metastases after reirradiation developed in six patients (11%). The 1-year rates of overall and progression-free survival were 59% and 58%, respectively. In total, grade 3 or higher acute and/or late toxicity developed in 24 patients (42%), acute toxicity developed in 22 (39%), and late toxicity developed in seven (12%). Six grade 5 toxicities were observed. Increased overlap with the central airway region, mean esophagus and heart doses, and concurrent chemotherapy were associated with significantly higher rates of grade 3 or higher toxicity. Decreased overall survival was seen with increased mean esophagus dose (p = 0.007).



In this prospective study, PRT for recurrent NSCLC is feasible but can be associated with significant toxicity. Providers should remain cautious in reirradiating NSCLC, paying close consideration to tumor volume, location, and relevant dosimetric parameters. Further research is needed for optimal patient selection to improve overall outcomes.
Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania.
Hann-Hsiang
HH
Chao
Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania.
Abigail T
AT
Berman
Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania.
Charles B
CB
Simone
Division of Hematology/Oncology, University of Pennsylvania, Philadelphia, Pennsylvania.
Christine
C
Ciunci
Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania.
Peter
P
Gabriel
Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania.
Haibo
H
Lin
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
Stefan
S
Both
Division of Hematology/Oncology, University of Pennsylvania, Philadelphia, Pennsylvania.
Corey
C
Langer
Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania.
Kristi
K
Lelionis
Department of Radiation Oncology, University of Washington, Seattle, Washington.
Ramesh
R
Rengan
Division of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas.
Stephen M
SM
Hahn
Procure Proton Therapy Center, Oklahoma City, Oklahoma.
Kiran
K
Prabhu
Procure Proton Therapy Center, Oklahoma City, Oklahoma.
Marcio
M
Fagundes
Northwestern Medicine Chicago Proton Center, Warrenville, Illinois.
William
W
Hartsell
Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania.
Rosemarie
R
Mick
Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: plastaras@uphs.upenn.edu.
John P
JP
Plastaras
D000230:Adenocarcinoma / Q000473:pathology / Q000532:radiotherapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000532:radiotherapy*; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000532:radiotherapy*; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D061766:Proton Therapy; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted; D020266:Radiotherapy, Conformal; D000069475:Re-Irradiation; D015996:Survival Rate; D047368:Tumor Burden
Dosimetry; Non–small cell lung cancer; Proton; Reirradiation; Thoracic; Toxicity