TY - JOUR
T1 - Proton beam radiotherapy and concurrent chemotherapy for unresectable stage III non–small cell lung cancer
T2 - Final results of a phase 2 study
AU - Chang, Joe Y.
AU - Verma, Vivek
AU - Li, Ming
AU - Zhang, Wencheng
AU - Komaki, Ritsuko
AU - Lu, Charles
AU - Allen, Pamela K.
AU - Liao, Zhongxing
AU - Welsh, James
AU - Lin, Steven H.
AU - Gomez, Daniel
AU - Jeter, Melenda
AU - O'Reilly, Michael
AU - Zhu, Ronald X.
AU - Zhang, Xiaodong
AU - Li, Heng
AU - Mohan, Radhe
AU - Heymach, John V.
AU - Vaporciyan, Ara A.
AU - Hahn, Stephen
AU - Cox, James D
N1 - Publisher Copyright:
© 2017 American Medical Association. All rights reserved.
PY - 2017/8
Y1 - 2017/8
N2 - IMPORTANCE: Proton beam radiotherapy (PBT) has the potential to reduce toxic effects in the definitive management of locally advanced non–small cell lung cancer (NSCLC), but long-term prospective data are lacking. OBJECTIVE: To report the final (5-year) results of a prospective study evaluating concurrent chemotherapy and high-dose PBT to treat unresectable stage III NSCLC. DESIGN, SETTING, AND PARTICIPANTS: In this open-label, single-group assignment study, with median follow-up of 27.3 months for all patients and 79.6 months for survivors, 64 patients were enrolled and analyzed; inclusion criteria were unresectable IIIA/IIIB histologically confirmed NSCLC, Karnofsky performance status 70 to 100, and 6-month prediagnosis weight loss of no more than 10%. Staging used positron emission tomography and/or computed tomography. Induction chemotherapy was allowed. INTERVENTIONS: Concurrent chemotherapy (carboplatin-paclitaxel) and passively scattered PBT (74-Gy relative biological effectiveness) in all patients. MAIN OUTCOMES AND MEASURES: Kaplan-Meier analysis of overall survival (OS), progression-free survival (PFS), actuarial distant metastasis, and locoregional recurrence. Patterns of treatment failure were categorized as local/regional or distant. Acute and late toxic effects were prospectively assigned using Common Terminology Criteria for Adverse Events, v3.0. RESULTS: Of 64 patients (22 [34%] female; median [range] age, 70 [37-78] years; stage IIIA, 30 [47%]; IIIB, 34 [53%]), 17 (27%) were alive at last follow-up. Median OS was 26.5 months (5-year OS, 29%; 95% CI, 18%-41%). Five-year PFS was 22% (95% CI, 12%-32%); 5-year actuarial distant metastasis and locoregional recurrence were 54% (n = 36) and 28% (n = 22), respectively. Treatment failures were largely (31 [48%] patients) distant, with low rates of crude local (10 [16%]) and regional (9 [14%]) recurrences. Rates of grade 2 and 3 acute esophagitis were 18 (28%) and 5 (8%), respectively. Acute grade 2 pneumonitis occurred in 1 (2%) patient. Late toxic effects were uncommon: 1 (2%) patient developed an esophageal stricture (grade 2) and 1 (2%) grade 4 esophagitis. Late grades 2 and 3 pneumonitis occurred in 10 (16%) and 8 (12%), respectively. Two (3%) patients developed a bronchial stricture (grade 2), and 1 (2%) a grade 4 bronchial fistula. There were no acute or late grade 5 toxic effects. CONCLUSIONS AND RELEVANCE: Concurrent chemotherapy and PBT to treat unresectable NSCLC afford promising clinical outcomes and rates of toxic effects compared with historical photon therapy data. Further optimization of proton therapy, particularly intensity-modulated proton therapy, is still needed.
AB - IMPORTANCE: Proton beam radiotherapy (PBT) has the potential to reduce toxic effects in the definitive management of locally advanced non–small cell lung cancer (NSCLC), but long-term prospective data are lacking. OBJECTIVE: To report the final (5-year) results of a prospective study evaluating concurrent chemotherapy and high-dose PBT to treat unresectable stage III NSCLC. DESIGN, SETTING, AND PARTICIPANTS: In this open-label, single-group assignment study, with median follow-up of 27.3 months for all patients and 79.6 months for survivors, 64 patients were enrolled and analyzed; inclusion criteria were unresectable IIIA/IIIB histologically confirmed NSCLC, Karnofsky performance status 70 to 100, and 6-month prediagnosis weight loss of no more than 10%. Staging used positron emission tomography and/or computed tomography. Induction chemotherapy was allowed. INTERVENTIONS: Concurrent chemotherapy (carboplatin-paclitaxel) and passively scattered PBT (74-Gy relative biological effectiveness) in all patients. MAIN OUTCOMES AND MEASURES: Kaplan-Meier analysis of overall survival (OS), progression-free survival (PFS), actuarial distant metastasis, and locoregional recurrence. Patterns of treatment failure were categorized as local/regional or distant. Acute and late toxic effects were prospectively assigned using Common Terminology Criteria for Adverse Events, v3.0. RESULTS: Of 64 patients (22 [34%] female; median [range] age, 70 [37-78] years; stage IIIA, 30 [47%]; IIIB, 34 [53%]), 17 (27%) were alive at last follow-up. Median OS was 26.5 months (5-year OS, 29%; 95% CI, 18%-41%). Five-year PFS was 22% (95% CI, 12%-32%); 5-year actuarial distant metastasis and locoregional recurrence were 54% (n = 36) and 28% (n = 22), respectively. Treatment failures were largely (31 [48%] patients) distant, with low rates of crude local (10 [16%]) and regional (9 [14%]) recurrences. Rates of grade 2 and 3 acute esophagitis were 18 (28%) and 5 (8%), respectively. Acute grade 2 pneumonitis occurred in 1 (2%) patient. Late toxic effects were uncommon: 1 (2%) patient developed an esophageal stricture (grade 2) and 1 (2%) grade 4 esophagitis. Late grades 2 and 3 pneumonitis occurred in 10 (16%) and 8 (12%), respectively. Two (3%) patients developed a bronchial stricture (grade 2), and 1 (2%) a grade 4 bronchial fistula. There were no acute or late grade 5 toxic effects. CONCLUSIONS AND RELEVANCE: Concurrent chemotherapy and PBT to treat unresectable NSCLC afford promising clinical outcomes and rates of toxic effects compared with historical photon therapy data. Further optimization of proton therapy, particularly intensity-modulated proton therapy, is still needed.
UR - http://www.scopus.com/inward/record.url?scp=85028816742&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85028816742&partnerID=8YFLogxK
U2 - 10.1001/jamaoncol.2017.2032
DO - 10.1001/jamaoncol.2017.2032
M3 - Article
C2 - 28727865
AN - SCOPUS:85028816742
SN - 2374-2437
VL - 3
JO - JAMA Oncology
JF - JAMA Oncology
IS - 8
M1 - e172032
ER -