Safety and efficacy of a five-fraction stereotactic body radiotherapy schedule for centrally located non–small-cell lung cancer: NRG Oncology/RTOG 0813 trial

Andrea Bezjak, Rebecca Paulus, Laurie E. Gaspar, Robert Timmerman, William L. Straube, William F. Ryan, Yolanda I. Garces, Anthony T. Pu, Anurag K. Singh, Gregory M. Videtic, Ronald C. McGarry, Puneeth Iyengar, Jason R. Pantarotto, James J. Urbanic, Alexander Y. Sun, Megan E. Daly, Inga S. Grills, Paul Sperduto, Daniel P. Normolle, Jeffrey D. BradleyHak Choy

Research output: Contribution to journalArticle

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Abstract

PURPOSE Patients with centrally located early-stage non–small-cell lung cancer (NSCLC) are at a higher risk of toxicity from high-dose ablative radiotherapy. NRG Oncology/RTOG 0813 was a phase I/II study designed to determine the maximum tolerated dose (MTD), efficacy, and toxicity of stereotactic body radiotherapy (SBRT) for centrally located NSCLC. MATERIALS AND METHODS Medically inoperable patients with biopsy-proven, positron emission tomography–staged T1 to 2 (# 5 cm) N0M0 centrally located NSCLC were accrued into a dose-escalating, five-fraction SBRT schedule that ranged from 10 to 12 Gy/fraction (fx) delivered over 1.5 to 2 weeks. Dose-limiting toxicity (DLT) was defined as any treatment-related grade 3 or worse predefined toxicity that occurred within the first year. MTD was defined as the SBRT dose at which the probability of DLT was closest to 20% without exceeding it. RESULTS One hundred twenty patients were accrued between February 2009 and September 2013. Patients were elderly, there were slightly more females, and the majority had a performance status of 0 to 1. Most cancers were T1 (65%) and squamous cell (45%). Organs closest to planning target volume/most at risk were the main bronchus and large vessels. Median follow-up was 37.9 months. Five patients experienced DLTs; MTD was 12.0 Gy/fx, which had a probability of a DLT of 7.2% (95% CI, 2.8% to 14.5%). Two-year rates for the 71 evaluable patients in the 11.5 and 12.0 Gy/fx cohorts were local control, 89.4% (90% CI, 81.6% to 97.4%) and 87.9% (90% CI, 78.8% to 97.0%); overall survival, 67.9% (95% CI, 50.4% to 80.3%) and 72.7% (95% CI, 54.1% to 84.8%); and progression-free survival, 52.2% (95% CI, 35.3% to 66.6%) and 54.5% (95% CI, 36.3% to 69.6%), respectively. CONCLUSION The MTD for this study was 12.0 Gy/fx; it was associated with 7.2% DLTs and high rates of tumor control. Outcomes in this medically inoperable group of mostly elderly patients with comorbidities were comparable with that of patients with peripheral early-stage tumors.

Original languageEnglish (US)
Pages (from-to)1316-1325
Number of pages10
JournalJournal of Clinical Oncology
Volume37
Issue number15
DOIs
StatePublished - May 20 2019

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Radiosurgery
Non-Small Cell Lung Carcinoma
Appointments and Schedules
Safety
Maximum Tolerated Dose
Neoplasms
Bronchi
Disease-Free Survival
Comorbidity
Radiotherapy
Epithelial Cells
Electrons
Biopsy
Survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Safety and efficacy of a five-fraction stereotactic body radiotherapy schedule for centrally located non–small-cell lung cancer : NRG Oncology/RTOG 0813 trial. / Bezjak, Andrea; Paulus, Rebecca; Gaspar, Laurie E.; Timmerman, Robert; Straube, William L.; Ryan, William F.; Garces, Yolanda I.; Pu, Anthony T.; Singh, Anurag K.; Videtic, Gregory M.; McGarry, Ronald C.; Iyengar, Puneeth; Pantarotto, Jason R.; Urbanic, James J.; Sun, Alexander Y.; Daly, Megan E.; Grills, Inga S.; Sperduto, Paul; Normolle, Daniel P.; Bradley, Jeffrey D.; Choy, Hak.

In: Journal of Clinical Oncology, Vol. 37, No. 15, 20.05.2019, p. 1316-1325.

Research output: Contribution to journalArticle

Bezjak, A, Paulus, R, Gaspar, LE, Timmerman, R, Straube, WL, Ryan, WF, Garces, YI, Pu, AT, Singh, AK, Videtic, GM, McGarry, RC, Iyengar, P, Pantarotto, JR, Urbanic, JJ, Sun, AY, Daly, ME, Grills, IS, Sperduto, P, Normolle, DP, Bradley, JD & Choy, H 2019, 'Safety and efficacy of a five-fraction stereotactic body radiotherapy schedule for centrally located non–small-cell lung cancer: NRG Oncology/RTOG 0813 trial', Journal of Clinical Oncology, vol. 37, no. 15, pp. 1316-1325. https://doi.org/10.1200/JCO.18.00622
Bezjak, Andrea ; Paulus, Rebecca ; Gaspar, Laurie E. ; Timmerman, Robert ; Straube, William L. ; Ryan, William F. ; Garces, Yolanda I. ; Pu, Anthony T. ; Singh, Anurag K. ; Videtic, Gregory M. ; McGarry, Ronald C. ; Iyengar, Puneeth ; Pantarotto, Jason R. ; Urbanic, James J. ; Sun, Alexander Y. ; Daly, Megan E. ; Grills, Inga S. ; Sperduto, Paul ; Normolle, Daniel P. ; Bradley, Jeffrey D. ; Choy, Hak. / Safety and efficacy of a five-fraction stereotactic body radiotherapy schedule for centrally located non–small-cell lung cancer : NRG Oncology/RTOG 0813 trial. In: Journal of Clinical Oncology. 2019 ; Vol. 37, No. 15. pp. 1316-1325.
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title = "Safety and efficacy of a five-fraction stereotactic body radiotherapy schedule for centrally located non–small-cell lung cancer: NRG Oncology/RTOG 0813 trial",
abstract = "PURPOSE Patients with centrally located early-stage non–small-cell lung cancer (NSCLC) are at a higher risk of toxicity from high-dose ablative radiotherapy. NRG Oncology/RTOG 0813 was a phase I/II study designed to determine the maximum tolerated dose (MTD), efficacy, and toxicity of stereotactic body radiotherapy (SBRT) for centrally located NSCLC. MATERIALS AND METHODS Medically inoperable patients with biopsy-proven, positron emission tomography–staged T1 to 2 (# 5 cm) N0M0 centrally located NSCLC were accrued into a dose-escalating, five-fraction SBRT schedule that ranged from 10 to 12 Gy/fraction (fx) delivered over 1.5 to 2 weeks. Dose-limiting toxicity (DLT) was defined as any treatment-related grade 3 or worse predefined toxicity that occurred within the first year. MTD was defined as the SBRT dose at which the probability of DLT was closest to 20{\%} without exceeding it. RESULTS One hundred twenty patients were accrued between February 2009 and September 2013. Patients were elderly, there were slightly more females, and the majority had a performance status of 0 to 1. Most cancers were T1 (65{\%}) and squamous cell (45{\%}). Organs closest to planning target volume/most at risk were the main bronchus and large vessels. Median follow-up was 37.9 months. Five patients experienced DLTs; MTD was 12.0 Gy/fx, which had a probability of a DLT of 7.2{\%} (95{\%} CI, 2.8{\%} to 14.5{\%}). Two-year rates for the 71 evaluable patients in the 11.5 and 12.0 Gy/fx cohorts were local control, 89.4{\%} (90{\%} CI, 81.6{\%} to 97.4{\%}) and 87.9{\%} (90{\%} CI, 78.8{\%} to 97.0{\%}); overall survival, 67.9{\%} (95{\%} CI, 50.4{\%} to 80.3{\%}) and 72.7{\%} (95{\%} CI, 54.1{\%} to 84.8{\%}); and progression-free survival, 52.2{\%} (95{\%} CI, 35.3{\%} to 66.6{\%}) and 54.5{\%} (95{\%} CI, 36.3{\%} to 69.6{\%}), respectively. CONCLUSION The MTD for this study was 12.0 Gy/fx; it was associated with 7.2{\%} DLTs and high rates of tumor control. Outcomes in this medically inoperable group of mostly elderly patients with comorbidities were comparable with that of patients with peripheral early-stage tumors.",
author = "Andrea Bezjak and Rebecca Paulus and Gaspar, {Laurie E.} and Robert Timmerman and Straube, {William L.} and Ryan, {William F.} and Garces, {Yolanda I.} and Pu, {Anthony T.} and Singh, {Anurag K.} and Videtic, {Gregory M.} and McGarry, {Ronald C.} and Puneeth Iyengar and Pantarotto, {Jason R.} and Urbanic, {James J.} and Sun, {Alexander Y.} and Daly, {Megan E.} and Grills, {Inga S.} and Paul Sperduto and Normolle, {Daniel P.} and Bradley, {Jeffrey D.} and Hak Choy",
year = "2019",
month = "5",
day = "20",
doi = "10.1200/JCO.18.00622",
language = "English (US)",
volume = "37",
pages = "1316--1325",
journal = "Journal of Clinical Oncology",
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TY - JOUR

T1 - Safety and efficacy of a five-fraction stereotactic body radiotherapy schedule for centrally located non–small-cell lung cancer

T2 - NRG Oncology/RTOG 0813 trial

AU - Bezjak, Andrea

AU - Paulus, Rebecca

AU - Gaspar, Laurie E.

AU - Timmerman, Robert

AU - Straube, William L.

AU - Ryan, William F.

AU - Garces, Yolanda I.

AU - Pu, Anthony T.

AU - Singh, Anurag K.

AU - Videtic, Gregory M.

AU - McGarry, Ronald C.

AU - Iyengar, Puneeth

AU - Pantarotto, Jason R.

AU - Urbanic, James J.

AU - Sun, Alexander Y.

AU - Daly, Megan E.

AU - Grills, Inga S.

AU - Sperduto, Paul

AU - Normolle, Daniel P.

AU - Bradley, Jeffrey D.

AU - Choy, Hak

PY - 2019/5/20

Y1 - 2019/5/20

N2 - PURPOSE Patients with centrally located early-stage non–small-cell lung cancer (NSCLC) are at a higher risk of toxicity from high-dose ablative radiotherapy. NRG Oncology/RTOG 0813 was a phase I/II study designed to determine the maximum tolerated dose (MTD), efficacy, and toxicity of stereotactic body radiotherapy (SBRT) for centrally located NSCLC. MATERIALS AND METHODS Medically inoperable patients with biopsy-proven, positron emission tomography–staged T1 to 2 (# 5 cm) N0M0 centrally located NSCLC were accrued into a dose-escalating, five-fraction SBRT schedule that ranged from 10 to 12 Gy/fraction (fx) delivered over 1.5 to 2 weeks. Dose-limiting toxicity (DLT) was defined as any treatment-related grade 3 or worse predefined toxicity that occurred within the first year. MTD was defined as the SBRT dose at which the probability of DLT was closest to 20% without exceeding it. RESULTS One hundred twenty patients were accrued between February 2009 and September 2013. Patients were elderly, there were slightly more females, and the majority had a performance status of 0 to 1. Most cancers were T1 (65%) and squamous cell (45%). Organs closest to planning target volume/most at risk were the main bronchus and large vessels. Median follow-up was 37.9 months. Five patients experienced DLTs; MTD was 12.0 Gy/fx, which had a probability of a DLT of 7.2% (95% CI, 2.8% to 14.5%). Two-year rates for the 71 evaluable patients in the 11.5 and 12.0 Gy/fx cohorts were local control, 89.4% (90% CI, 81.6% to 97.4%) and 87.9% (90% CI, 78.8% to 97.0%); overall survival, 67.9% (95% CI, 50.4% to 80.3%) and 72.7% (95% CI, 54.1% to 84.8%); and progression-free survival, 52.2% (95% CI, 35.3% to 66.6%) and 54.5% (95% CI, 36.3% to 69.6%), respectively. CONCLUSION The MTD for this study was 12.0 Gy/fx; it was associated with 7.2% DLTs and high rates of tumor control. Outcomes in this medically inoperable group of mostly elderly patients with comorbidities were comparable with that of patients with peripheral early-stage tumors.

AB - PURPOSE Patients with centrally located early-stage non–small-cell lung cancer (NSCLC) are at a higher risk of toxicity from high-dose ablative radiotherapy. NRG Oncology/RTOG 0813 was a phase I/II study designed to determine the maximum tolerated dose (MTD), efficacy, and toxicity of stereotactic body radiotherapy (SBRT) for centrally located NSCLC. MATERIALS AND METHODS Medically inoperable patients with biopsy-proven, positron emission tomography–staged T1 to 2 (# 5 cm) N0M0 centrally located NSCLC were accrued into a dose-escalating, five-fraction SBRT schedule that ranged from 10 to 12 Gy/fraction (fx) delivered over 1.5 to 2 weeks. Dose-limiting toxicity (DLT) was defined as any treatment-related grade 3 or worse predefined toxicity that occurred within the first year. MTD was defined as the SBRT dose at which the probability of DLT was closest to 20% without exceeding it. RESULTS One hundred twenty patients were accrued between February 2009 and September 2013. Patients were elderly, there were slightly more females, and the majority had a performance status of 0 to 1. Most cancers were T1 (65%) and squamous cell (45%). Organs closest to planning target volume/most at risk were the main bronchus and large vessels. Median follow-up was 37.9 months. Five patients experienced DLTs; MTD was 12.0 Gy/fx, which had a probability of a DLT of 7.2% (95% CI, 2.8% to 14.5%). Two-year rates for the 71 evaluable patients in the 11.5 and 12.0 Gy/fx cohorts were local control, 89.4% (90% CI, 81.6% to 97.4%) and 87.9% (90% CI, 78.8% to 97.0%); overall survival, 67.9% (95% CI, 50.4% to 80.3%) and 72.7% (95% CI, 54.1% to 84.8%); and progression-free survival, 52.2% (95% CI, 35.3% to 66.6%) and 54.5% (95% CI, 36.3% to 69.6%), respectively. CONCLUSION The MTD for this study was 12.0 Gy/fx; it was associated with 7.2% DLTs and high rates of tumor control. Outcomes in this medically inoperable group of mostly elderly patients with comorbidities were comparable with that of patients with peripheral early-stage tumors.

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