Adjuvant Whole-Brain Radiation Therapy Compared With Observation After Local Treatment of Melanoma Brain Metastases: A Multicenter, Randomized Phase III Trial

Angela M. Hong, Gerald B. Fogarty, Kari Dolven-Jacobsen, Bryan H. Burmeister, Serigne N. Lo, Lauren E. Haydu, Janette L. Vardy, Anna K. Nowak, Haryana M. Dhillon, Tasnia Ahmed, Brindha Shivalingam, Georgina V. Long, Alexander M. Menzies, George Hruby, Katharine J. Drummond, Catherine Mandel, Mark R. Middleton, Claudius H. Reisse, Elizabeth J. Paton, Victoria Steel & 4 others Narelle C. Williams, Richard A. Scolyer, Rachael L. Morton, John F. Thompson

Research output: Contribution to journalArticle

Abstract

PURPOSE: The brain is a common site of metastasis for patients with high-risk melanoma. Although surgery or stereotactic radiosurgery are highly effective local treatments for a small number of metastases, there is a high risk of developing additional brain metastases. The role of adjuvant whole-brain radiotherapy (WBRT) in reducing new metastases is controversial, with a lack of high-level evidence specifically for melanoma. METHODS: In this randomized phase III trial, patients who had local treatment of one to three melanoma brain metastases were randomly assigned to WBRT or observation. The primary end point was distant intracranial failure within 12 months, and secondary end points included time to intracranial failure, survival, and time to deterioration in performance status. RESULTS: Between April 2009 and September 2017, 215 patients were randomly assigned from 24 centers. Median follow-up was 48.1 months (range, 39.6 to 68 months). Forty-two percent of patients in the WBRT group and 50.5% of those in the observation developed distant intracranial failure within 12 months (odds ratio, 0.71; 95% CI, 0.41 to 1.23; P = .22) and the rates over the entire follow-up period were 52.0% and 57.9%, respectively (odds ratio, 0.79; 95% CI, 0.45 to 1.36; P = .39). Local failure rate was lower after WBRT (20.0% v 33.6%; P = .03). At 12 months, 41.5% of patients in the WBRT group and 51.4% of patients in the observation group had died (P = .28), with no difference in the rate of neurologic death. Median time to deterioration in performance status was 3.8 months after WBRT and 4.4 months with observation (P = .32). WBRT was associated with more grade 1 to 2 acute toxicity. CONCLUSION: After local treatment of one to three melanoma brain metastases, adjuvant WBRT does not provide clinical benefit in terms of distant intracranial control, survival, or preservation of performance status.

Original languageEnglish
Pages (from-to)3132-3141
Number of pages10
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology
Volume37
Issue number33
DOIs
Publication statusPublished - 20 Nov 2019

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Melanoma
Radiotherapy
Observation
Neoplasm Metastasis
Brain
Therapeutics
Odds Ratio
Survival
Radiosurgery
Nervous System
Mortality

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Hong, Angela M. ; Fogarty, Gerald B. ; Dolven-Jacobsen, Kari ; Burmeister, Bryan H. ; Lo, Serigne N. ; Haydu, Lauren E. ; Vardy, Janette L. ; Nowak, Anna K. ; Dhillon, Haryana M. ; Ahmed, Tasnia ; Shivalingam, Brindha ; Long, Georgina V. ; Menzies, Alexander M. ; Hruby, George ; Drummond, Katharine J. ; Mandel, Catherine ; Middleton, Mark R. ; Reisse, Claudius H. ; Paton, Elizabeth J. ; Steel, Victoria ; Williams, Narelle C. ; Scolyer, Richard A. ; Morton, Rachael L. ; Thompson, John F. / Adjuvant Whole-Brain Radiation Therapy Compared With Observation After Local Treatment of Melanoma Brain Metastases : A Multicenter, Randomized Phase III Trial. In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2019 ; Vol. 37, No. 33. pp. 3132-3141.
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title = "Adjuvant Whole-Brain Radiation Therapy Compared With Observation After Local Treatment of Melanoma Brain Metastases: A Multicenter, Randomized Phase III Trial",
abstract = "PURPOSE: The brain is a common site of metastasis for patients with high-risk melanoma. Although surgery or stereotactic radiosurgery are highly effective local treatments for a small number of metastases, there is a high risk of developing additional brain metastases. The role of adjuvant whole-brain radiotherapy (WBRT) in reducing new metastases is controversial, with a lack of high-level evidence specifically for melanoma. METHODS: In this randomized phase III trial, patients who had local treatment of one to three melanoma brain metastases were randomly assigned to WBRT or observation. The primary end point was distant intracranial failure within 12 months, and secondary end points included time to intracranial failure, survival, and time to deterioration in performance status. RESULTS: Between April 2009 and September 2017, 215 patients were randomly assigned from 24 centers. Median follow-up was 48.1 months (range, 39.6 to 68 months). Forty-two percent of patients in the WBRT group and 50.5{\%} of those in the observation developed distant intracranial failure within 12 months (odds ratio, 0.71; 95{\%} CI, 0.41 to 1.23; P = .22) and the rates over the entire follow-up period were 52.0{\%} and 57.9{\%}, respectively (odds ratio, 0.79; 95{\%} CI, 0.45 to 1.36; P = .39). Local failure rate was lower after WBRT (20.0{\%} v 33.6{\%}; P = .03). At 12 months, 41.5{\%} of patients in the WBRT group and 51.4{\%} of patients in the observation group had died (P = .28), with no difference in the rate of neurologic death. Median time to deterioration in performance status was 3.8 months after WBRT and 4.4 months with observation (P = .32). WBRT was associated with more grade 1 to 2 acute toxicity. CONCLUSION: After local treatment of one to three melanoma brain metastases, adjuvant WBRT does not provide clinical benefit in terms of distant intracranial control, survival, or preservation of performance status.",
author = "Hong, {Angela M.} and Fogarty, {Gerald B.} and Kari Dolven-Jacobsen and Burmeister, {Bryan H.} and Lo, {Serigne N.} and Haydu, {Lauren E.} and Vardy, {Janette L.} and Nowak, {Anna K.} and Dhillon, {Haryana M.} and Tasnia Ahmed and Brindha Shivalingam and Long, {Georgina V.} and Menzies, {Alexander M.} and George Hruby and Drummond, {Katharine J.} and Catherine Mandel and Middleton, {Mark R.} and Reisse, {Claudius H.} and Paton, {Elizabeth J.} and Victoria Steel and Williams, {Narelle C.} and Scolyer, {Richard A.} and Morton, {Rachael L.} and Thompson, {John F.}",
year = "2019",
month = "11",
day = "20",
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language = "English",
volume = "37",
pages = "3132--3141",
journal = "Journal of clinical oncology : official journal of the American Society of Clinical Oncology",
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Hong, AM, Fogarty, GB, Dolven-Jacobsen, K, Burmeister, BH, Lo, SN, Haydu, LE, Vardy, JL, Nowak, AK, Dhillon, HM, Ahmed, T, Shivalingam, B, Long, GV, Menzies, AM, Hruby, G, Drummond, KJ, Mandel, C, Middleton, MR, Reisse, CH, Paton, EJ, Steel, V, Williams, NC, Scolyer, RA, Morton, RL & Thompson, JF 2019, 'Adjuvant Whole-Brain Radiation Therapy Compared With Observation After Local Treatment of Melanoma Brain Metastases: A Multicenter, Randomized Phase III Trial' Journal of clinical oncology : official journal of the American Society of Clinical Oncology, vol. 37, no. 33, pp. 3132-3141. https://doi.org/10.1200/JCO.19.01414

Adjuvant Whole-Brain Radiation Therapy Compared With Observation After Local Treatment of Melanoma Brain Metastases : A Multicenter, Randomized Phase III Trial. / Hong, Angela M.; Fogarty, Gerald B.; Dolven-Jacobsen, Kari; Burmeister, Bryan H.; Lo, Serigne N.; Haydu, Lauren E.; Vardy, Janette L.; Nowak, Anna K.; Dhillon, Haryana M.; Ahmed, Tasnia; Shivalingam, Brindha; Long, Georgina V.; Menzies, Alexander M.; Hruby, George; Drummond, Katharine J.; Mandel, Catherine; Middleton, Mark R.; Reisse, Claudius H.; Paton, Elizabeth J.; Steel, Victoria; Williams, Narelle C.; Scolyer, Richard A.; Morton, Rachael L.; Thompson, John F.

In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Vol. 37, No. 33, 20.11.2019, p. 3132-3141.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Adjuvant Whole-Brain Radiation Therapy Compared With Observation After Local Treatment of Melanoma Brain Metastases

T2 - A Multicenter, Randomized Phase III Trial

AU - Hong, Angela M.

AU - Fogarty, Gerald B.

AU - Dolven-Jacobsen, Kari

AU - Burmeister, Bryan H.

AU - Lo, Serigne N.

AU - Haydu, Lauren E.

AU - Vardy, Janette L.

AU - Nowak, Anna K.

AU - Dhillon, Haryana M.

AU - Ahmed, Tasnia

AU - Shivalingam, Brindha

AU - Long, Georgina V.

AU - Menzies, Alexander M.

AU - Hruby, George

AU - Drummond, Katharine J.

AU - Mandel, Catherine

AU - Middleton, Mark R.

AU - Reisse, Claudius H.

AU - Paton, Elizabeth J.

AU - Steel, Victoria

AU - Williams, Narelle C.

AU - Scolyer, Richard A.

AU - Morton, Rachael L.

AU - Thompson, John F.

PY - 2019/11/20

Y1 - 2019/11/20

N2 - PURPOSE: The brain is a common site of metastasis for patients with high-risk melanoma. Although surgery or stereotactic radiosurgery are highly effective local treatments for a small number of metastases, there is a high risk of developing additional brain metastases. The role of adjuvant whole-brain radiotherapy (WBRT) in reducing new metastases is controversial, with a lack of high-level evidence specifically for melanoma. METHODS: In this randomized phase III trial, patients who had local treatment of one to three melanoma brain metastases were randomly assigned to WBRT or observation. The primary end point was distant intracranial failure within 12 months, and secondary end points included time to intracranial failure, survival, and time to deterioration in performance status. RESULTS: Between April 2009 and September 2017, 215 patients were randomly assigned from 24 centers. Median follow-up was 48.1 months (range, 39.6 to 68 months). Forty-two percent of patients in the WBRT group and 50.5% of those in the observation developed distant intracranial failure within 12 months (odds ratio, 0.71; 95% CI, 0.41 to 1.23; P = .22) and the rates over the entire follow-up period were 52.0% and 57.9%, respectively (odds ratio, 0.79; 95% CI, 0.45 to 1.36; P = .39). Local failure rate was lower after WBRT (20.0% v 33.6%; P = .03). At 12 months, 41.5% of patients in the WBRT group and 51.4% of patients in the observation group had died (P = .28), with no difference in the rate of neurologic death. Median time to deterioration in performance status was 3.8 months after WBRT and 4.4 months with observation (P = .32). WBRT was associated with more grade 1 to 2 acute toxicity. CONCLUSION: After local treatment of one to three melanoma brain metastases, adjuvant WBRT does not provide clinical benefit in terms of distant intracranial control, survival, or preservation of performance status.

AB - PURPOSE: The brain is a common site of metastasis for patients with high-risk melanoma. Although surgery or stereotactic radiosurgery are highly effective local treatments for a small number of metastases, there is a high risk of developing additional brain metastases. The role of adjuvant whole-brain radiotherapy (WBRT) in reducing new metastases is controversial, with a lack of high-level evidence specifically for melanoma. METHODS: In this randomized phase III trial, patients who had local treatment of one to three melanoma brain metastases were randomly assigned to WBRT or observation. The primary end point was distant intracranial failure within 12 months, and secondary end points included time to intracranial failure, survival, and time to deterioration in performance status. RESULTS: Between April 2009 and September 2017, 215 patients were randomly assigned from 24 centers. Median follow-up was 48.1 months (range, 39.6 to 68 months). Forty-two percent of patients in the WBRT group and 50.5% of those in the observation developed distant intracranial failure within 12 months (odds ratio, 0.71; 95% CI, 0.41 to 1.23; P = .22) and the rates over the entire follow-up period were 52.0% and 57.9%, respectively (odds ratio, 0.79; 95% CI, 0.45 to 1.36; P = .39). Local failure rate was lower after WBRT (20.0% v 33.6%; P = .03). At 12 months, 41.5% of patients in the WBRT group and 51.4% of patients in the observation group had died (P = .28), with no difference in the rate of neurologic death. Median time to deterioration in performance status was 3.8 months after WBRT and 4.4 months with observation (P = .32). WBRT was associated with more grade 1 to 2 acute toxicity. CONCLUSION: After local treatment of one to three melanoma brain metastases, adjuvant WBRT does not provide clinical benefit in terms of distant intracranial control, survival, or preservation of performance status.

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U2 - 10.1200/JCO.19.01414

DO - 10.1200/JCO.19.01414

M3 - Article

VL - 37

SP - 3132

EP - 3141

JO - Journal of clinical oncology : official journal of the American Society of Clinical Oncology

JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology

SN - 0732-183X

IS - 33

ER -