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Proton Beam Radiotherapy and Concurrent Chemotherapy for Unresectable Stage III Non-Small Cell Lung Cancer: Final Results of a Phase 2 Study.
JAMA Oncol 2017; 3(8):e172032JO

Abstract

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.

Authors+Show Affiliations

Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston.Department of Radiation Oncology, University of Nebraska Medical Center, Omaha.Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston.Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston.Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston.Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston.Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston.Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston.Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston.Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston.Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston.Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston.Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston.Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston.Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston.Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston.Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston.Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston.Thoracic/Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston.Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston.Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston.

Pub Type(s)

Clinical Trial, Phase II
Journal Article

Language

eng

PubMed ID

28727865

Citation

Chang, Joe Y., et al. "Proton Beam Radiotherapy and Concurrent Chemotherapy for Unresectable Stage III Non-Small Cell Lung Cancer: Final Results of a Phase 2 Study." JAMA Oncology, vol. 3, no. 8, 2017, pp. e172032.
Chang JY, Verma V, Li M, et al. Proton Beam Radiotherapy and Concurrent Chemotherapy for Unresectable Stage III Non-Small Cell Lung Cancer: Final Results of a Phase 2 Study. JAMA Oncol. 2017;3(8):e172032.
Chang, J. Y., Verma, V., Li, M., Zhang, W., Komaki, R., Lu, C., ... Cox, J. D. (2017). Proton Beam Radiotherapy and Concurrent Chemotherapy for Unresectable Stage III Non-Small Cell Lung Cancer: Final Results of a Phase 2 Study. JAMA Oncology, 3(8), pp. e172032. doi:10.1001/jamaoncol.2017.2032.
Chang JY, et al. Proton Beam Radiotherapy and Concurrent Chemotherapy for Unresectable Stage III Non-Small Cell Lung Cancer: Final Results of a Phase 2 Study. JAMA Oncol. 2017 08 10;3(8):e172032. PubMed PMID: 28727865.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Proton Beam Radiotherapy and Concurrent Chemotherapy for Unresectable Stage III Non-Small Cell Lung Cancer: 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, Y1 - 2017/08/10/ PY - 2017/7/21/pubmed PY - 2017/9/7/medline PY - 2017/7/21/entrez SP - e172032 EP - e172032 JF - JAMA oncology JO - JAMA Oncol VL - 3 IS - 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. SN - 2374-2445 UR - https://www.unboundmedicine.com/medline/citation/28727865/Proton_Beam_Radiotherapy_and_Concurrent_Chemotherapy_for_Unresectable_Stage_III_Non_Small_Cell_Lung_Cancer:_Final_Results_of_a_Phase_2_Study_ L2 - https://jamanetwork.com/journals/jamaoncology/fullarticle/10.1001/jamaoncol.2017.2032 DB - PRIME DP - Unbound Medicine ER -