Randomized Phase II Study Comparing Prophylactic Cranial Irradiation Alone to Prophylactic Cranial Irradiation and Consolidative Extracranial Irradiation for Extensive-Disease Small Cell Lung Cancer (ED SCLC)

NRG Oncology RTOG 0937

Elizabeth M. Gore, Chen Hu, Alexander Y. Sun, Daniel F. Grimm, Suresh S. Ramalingam, Neal E. Dunlap, Kristin A. Higgins, Maria Werner-Wasik, Aaron M. Allen, Puneeth Iyengar, Gregory M.M. Videtic, Russell K. Hales, Ronald C. McGarry, James J. Urbanic, Anthony T. Pu, Candice A. Johnstone, Volker W. Stieber, Rebecca Paulus, Jeffrey D. Bradley

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Introduction: NRG Oncology RTOG 0937 is a randomized phase II trial evaluating 1-year overall survival (OS) with prophylactic cranial irradiation (PCI) or PCI plus consolidative radiation therapy (PCI+cRT) to intrathoracic disease and extracranial metastases for extensive-disease SCLC. Methods: Patients with one to four extracranial metastases were eligible after a complete response or partial response to chemotherapy. Randomization was to PCI or PCI+cRT to the thorax and metastases. Original stratification included partial response versus complete response after chemotherapy and one versus two to four metastases; age younger than 65 years versus 65 years or older was added after an observed imbalance. PCI consisted of 25 Gy in 10 fractions. cRT consisted of 45 Gy in 15 fractions. To detect an improvement in OS from 30% to 45% with a 34% hazard reduction (hazard ratio = 0.66) under a 0.1 type 1 error (one sided) and 80% power, 154 patients were required. Results: A total of 97 patients were randomized between March 2010 and February 2015. Eleven patients were ineligible (nine in the PCI group and two in the PCI+cRT group), leaving 42 randomized to receive PCI and 44 to receive PCI+cRT. At planned interim analysis, the study crossed the futility boundary for OS and was closed before meeting the accrual target. Median follow-up was 9 months. The 1-year OS was not different between the groups: 60.1% (95% confidence interval [CI]: 41.2-74.7) for PCI and 50.8% (95% CI: 34.0-65.3) for PCI+cRT (p = 0.21). The 3- and 12-month rates of progression were 53.3% and 79.6% for PCI and 14.5% and 75% for PCI+cRT, respectively. Time to progression favored PCI+cRT (hazard ratio = 0.53, 95% CI: 0.32-0.87, p = 0.01). One patient in each arm had grade 4 therapy-related toxicity and one had grade 5 therapy-related pneumonitis with PCI+cRT. Conclusions: OS exceeded predictions for both arms. cRT delayed progression but did not improve 1-year OS.

Original languageEnglish (US)
JournalJournal of Thoracic Oncology
DOIs
StateAccepted/In press - 2017

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Cranial Irradiation
Small Cell Lung Carcinoma
Survival
Neoplasm Metastasis
Confidence Intervals
Medical Futility
Drug Therapy

Keywords

  • Extensive disease
  • Oligometastases
  • PCI
  • Small cell lung cancer
  • Thoracic radiation therapy

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Randomized Phase II Study Comparing Prophylactic Cranial Irradiation Alone to Prophylactic Cranial Irradiation and Consolidative Extracranial Irradiation for Extensive-Disease Small Cell Lung Cancer (ED SCLC) : NRG Oncology RTOG 0937. / Gore, Elizabeth M.; Hu, Chen; Sun, Alexander Y.; Grimm, Daniel F.; Ramalingam, Suresh S.; Dunlap, Neal E.; Higgins, Kristin A.; Werner-Wasik, Maria; Allen, Aaron M.; Iyengar, Puneeth; Videtic, Gregory M.M.; Hales, Russell K.; McGarry, Ronald C.; Urbanic, James J.; Pu, Anthony T.; Johnstone, Candice A.; Stieber, Volker W.; Paulus, Rebecca; Bradley, Jeffrey D.

In: Journal of Thoracic Oncology, 2017.

Research output: Contribution to journalArticle

Gore, EM, Hu, C, Sun, AY, Grimm, DF, Ramalingam, SS, Dunlap, NE, Higgins, KA, Werner-Wasik, M, Allen, AM, Iyengar, P, Videtic, GMM, Hales, RK, McGarry, RC, Urbanic, JJ, Pu, AT, Johnstone, CA, Stieber, VW, Paulus, R & Bradley, JD 2017, 'Randomized Phase II Study Comparing Prophylactic Cranial Irradiation Alone to Prophylactic Cranial Irradiation and Consolidative Extracranial Irradiation for Extensive-Disease Small Cell Lung Cancer (ED SCLC): NRG Oncology RTOG 0937', Journal of Thoracic Oncology. https://doi.org/10.1016/j.jtho.2017.06.015
Gore, Elizabeth M. ; Hu, Chen ; Sun, Alexander Y. ; Grimm, Daniel F. ; Ramalingam, Suresh S. ; Dunlap, Neal E. ; Higgins, Kristin A. ; Werner-Wasik, Maria ; Allen, Aaron M. ; Iyengar, Puneeth ; Videtic, Gregory M.M. ; Hales, Russell K. ; McGarry, Ronald C. ; Urbanic, James J. ; Pu, Anthony T. ; Johnstone, Candice A. ; Stieber, Volker W. ; Paulus, Rebecca ; Bradley, Jeffrey D. / Randomized Phase II Study Comparing Prophylactic Cranial Irradiation Alone to Prophylactic Cranial Irradiation and Consolidative Extracranial Irradiation for Extensive-Disease Small Cell Lung Cancer (ED SCLC) : NRG Oncology RTOG 0937. In: Journal of Thoracic Oncology. 2017.
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title = "Randomized Phase II Study Comparing Prophylactic Cranial Irradiation Alone to Prophylactic Cranial Irradiation and Consolidative Extracranial Irradiation for Extensive-Disease Small Cell Lung Cancer (ED SCLC): NRG Oncology RTOG 0937",
abstract = "Introduction: NRG Oncology RTOG 0937 is a randomized phase II trial evaluating 1-year overall survival (OS) with prophylactic cranial irradiation (PCI) or PCI plus consolidative radiation therapy (PCI+cRT) to intrathoracic disease and extracranial metastases for extensive-disease SCLC. Methods: Patients with one to four extracranial metastases were eligible after a complete response or partial response to chemotherapy. Randomization was to PCI or PCI+cRT to the thorax and metastases. Original stratification included partial response versus complete response after chemotherapy and one versus two to four metastases; age younger than 65 years versus 65 years or older was added after an observed imbalance. PCI consisted of 25 Gy in 10 fractions. cRT consisted of 45 Gy in 15 fractions. To detect an improvement in OS from 30{\%} to 45{\%} with a 34{\%} hazard reduction (hazard ratio = 0.66) under a 0.1 type 1 error (one sided) and 80{\%} power, 154 patients were required. Results: A total of 97 patients were randomized between March 2010 and February 2015. Eleven patients were ineligible (nine in the PCI group and two in the PCI+cRT group), leaving 42 randomized to receive PCI and 44 to receive PCI+cRT. At planned interim analysis, the study crossed the futility boundary for OS and was closed before meeting the accrual target. Median follow-up was 9 months. The 1-year OS was not different between the groups: 60.1{\%} (95{\%} confidence interval [CI]: 41.2-74.7) for PCI and 50.8{\%} (95{\%} CI: 34.0-65.3) for PCI+cRT (p = 0.21). The 3- and 12-month rates of progression were 53.3{\%} and 79.6{\%} for PCI and 14.5{\%} and 75{\%} for PCI+cRT, respectively. Time to progression favored PCI+cRT (hazard ratio = 0.53, 95{\%} CI: 0.32-0.87, p = 0.01). One patient in each arm had grade 4 therapy-related toxicity and one had grade 5 therapy-related pneumonitis with PCI+cRT. Conclusions: OS exceeded predictions for both arms. cRT delayed progression but did not improve 1-year OS.",
keywords = "Extensive disease, Oligometastases, PCI, Small cell lung cancer, Thoracic radiation therapy",
author = "Gore, {Elizabeth M.} and Chen Hu and Sun, {Alexander Y.} and Grimm, {Daniel F.} and Ramalingam, {Suresh S.} and Dunlap, {Neal E.} and Higgins, {Kristin A.} and Maria Werner-Wasik and Allen, {Aaron M.} and Puneeth Iyengar and Videtic, {Gregory M.M.} and Hales, {Russell K.} and McGarry, {Ronald C.} and Urbanic, {James J.} and Pu, {Anthony T.} and Johnstone, {Candice A.} and Stieber, {Volker W.} and Rebecca Paulus and Bradley, {Jeffrey D.}",
year = "2017",
doi = "10.1016/j.jtho.2017.06.015",
language = "English (US)",
journal = "Journal of Thoracic Oncology",
issn = "1556-0864",
publisher = "International Association for the Study of Lung Cancer",

}

TY - JOUR

T1 - Randomized Phase II Study Comparing Prophylactic Cranial Irradiation Alone to Prophylactic Cranial Irradiation and Consolidative Extracranial Irradiation for Extensive-Disease Small Cell Lung Cancer (ED SCLC)

T2 - NRG Oncology RTOG 0937

AU - Gore, Elizabeth M.

AU - Hu, Chen

AU - Sun, Alexander Y.

AU - Grimm, Daniel F.

AU - Ramalingam, Suresh S.

AU - Dunlap, Neal E.

AU - Higgins, Kristin A.

AU - Werner-Wasik, Maria

AU - Allen, Aaron M.

AU - Iyengar, Puneeth

AU - Videtic, Gregory M.M.

AU - Hales, Russell K.

AU - McGarry, Ronald C.

AU - Urbanic, James J.

AU - Pu, Anthony T.

AU - Johnstone, Candice A.

AU - Stieber, Volker W.

AU - Paulus, Rebecca

AU - Bradley, Jeffrey D.

PY - 2017

Y1 - 2017

N2 - Introduction: NRG Oncology RTOG 0937 is a randomized phase II trial evaluating 1-year overall survival (OS) with prophylactic cranial irradiation (PCI) or PCI plus consolidative radiation therapy (PCI+cRT) to intrathoracic disease and extracranial metastases for extensive-disease SCLC. Methods: Patients with one to four extracranial metastases were eligible after a complete response or partial response to chemotherapy. Randomization was to PCI or PCI+cRT to the thorax and metastases. Original stratification included partial response versus complete response after chemotherapy and one versus two to four metastases; age younger than 65 years versus 65 years or older was added after an observed imbalance. PCI consisted of 25 Gy in 10 fractions. cRT consisted of 45 Gy in 15 fractions. To detect an improvement in OS from 30% to 45% with a 34% hazard reduction (hazard ratio = 0.66) under a 0.1 type 1 error (one sided) and 80% power, 154 patients were required. Results: A total of 97 patients were randomized between March 2010 and February 2015. Eleven patients were ineligible (nine in the PCI group and two in the PCI+cRT group), leaving 42 randomized to receive PCI and 44 to receive PCI+cRT. At planned interim analysis, the study crossed the futility boundary for OS and was closed before meeting the accrual target. Median follow-up was 9 months. The 1-year OS was not different between the groups: 60.1% (95% confidence interval [CI]: 41.2-74.7) for PCI and 50.8% (95% CI: 34.0-65.3) for PCI+cRT (p = 0.21). The 3- and 12-month rates of progression were 53.3% and 79.6% for PCI and 14.5% and 75% for PCI+cRT, respectively. Time to progression favored PCI+cRT (hazard ratio = 0.53, 95% CI: 0.32-0.87, p = 0.01). One patient in each arm had grade 4 therapy-related toxicity and one had grade 5 therapy-related pneumonitis with PCI+cRT. Conclusions: OS exceeded predictions for both arms. cRT delayed progression but did not improve 1-year OS.

AB - Introduction: NRG Oncology RTOG 0937 is a randomized phase II trial evaluating 1-year overall survival (OS) with prophylactic cranial irradiation (PCI) or PCI plus consolidative radiation therapy (PCI+cRT) to intrathoracic disease and extracranial metastases for extensive-disease SCLC. Methods: Patients with one to four extracranial metastases were eligible after a complete response or partial response to chemotherapy. Randomization was to PCI or PCI+cRT to the thorax and metastases. Original stratification included partial response versus complete response after chemotherapy and one versus two to four metastases; age younger than 65 years versus 65 years or older was added after an observed imbalance. PCI consisted of 25 Gy in 10 fractions. cRT consisted of 45 Gy in 15 fractions. To detect an improvement in OS from 30% to 45% with a 34% hazard reduction (hazard ratio = 0.66) under a 0.1 type 1 error (one sided) and 80% power, 154 patients were required. Results: A total of 97 patients were randomized between March 2010 and February 2015. Eleven patients were ineligible (nine in the PCI group and two in the PCI+cRT group), leaving 42 randomized to receive PCI and 44 to receive PCI+cRT. At planned interim analysis, the study crossed the futility boundary for OS and was closed before meeting the accrual target. Median follow-up was 9 months. The 1-year OS was not different between the groups: 60.1% (95% confidence interval [CI]: 41.2-74.7) for PCI and 50.8% (95% CI: 34.0-65.3) for PCI+cRT (p = 0.21). The 3- and 12-month rates of progression were 53.3% and 79.6% for PCI and 14.5% and 75% for PCI+cRT, respectively. Time to progression favored PCI+cRT (hazard ratio = 0.53, 95% CI: 0.32-0.87, p = 0.01). One patient in each arm had grade 4 therapy-related toxicity and one had grade 5 therapy-related pneumonitis with PCI+cRT. Conclusions: OS exceeded predictions for both arms. cRT delayed progression but did not improve 1-year OS.

KW - Extensive disease

KW - Oligometastases

KW - PCI

KW - Small cell lung cancer

KW - Thoracic radiation therapy

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U2 - 10.1016/j.jtho.2017.06.015

DO - 10.1016/j.jtho.2017.06.015

M3 - Article

JO - Journal of Thoracic Oncology

JF - Journal of Thoracic Oncology

SN - 1556-0864

ER -