Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases a randomized clinical trial

Paul D. Brown, Kurt Jaeckle, Karla V. Ballman, Elana Farace, Jane H Cerhan, S. Keith Anderson, Xiomara W. Carrero, Fred G. Barker, Richard Deming, Stuart H. Burri, Cynthia Ménard, Caroline Chung, Volker W. Stieber, Bruce E. Pollock, Evanthia Galanis, Jan Craig Buckner, Anthony L. Asher

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353 Citations (Scopus)

Abstract

Importance Whole brain radiotherapy (WBRT) significantly improves tumor control in the brain after stereotactic radiosurgery (SRS), yet because of its association with cognitive decline, its role in the treatment of patients with brain metastases remains controversial. OBJECTIVE To determine whether there is less cognitive deterioration at 3 months after SRS alone vs SRS plus WBRT. DESIGN, SETTING, AND PARTICIPANTS At 34 institutions in North America, patients with 1 to 3 brain metastases were randomized to receive SRS or SRS plus WBRT between February 2002 and December 2013. INTERVENTIONS The WBRT dose schedule was 30 Gy in 12 fractions; the SRS dose was 18 to 22 Gy in the SRS plus WBRT group and 20 to 24 Gy for SRS alone. MAIN OUTCOMES AND MEASURES The primary end pointwas cognitive deterioration (decline >1 SD from baseline on at least 1 cognitive test at 3 months) in participants who completed the baseline and 3-month assessments. Secondary end points included time to intracranial failure, quality of life, functional independence, long-term cognitive status, and overall survival. RESULTS There were 213 randomized participants (SRS alone, n = 111; SRS plus WBRT, n = 102) with a mean age of 60.6 years (SD, 10.5 years); 103 (48%) were women. There was less cognitive deterioration at 3 months after SRS alone (40/63 patients [63.5%]) than when combined with WBRT (44/48 patients [91.7%]; difference,-28.2%; 90% CI,-41.9% to-14.4%; P <.001). Quality of life was higher at 3 months with SRS alone, including overall quality of life (mean change from baseline,-0.1 vs-12.0 points; mean difference, 11.9; 95%CI, 4.8-19.0 points; P =.001). Time to intracranial failure was significantly shorter for SRS alone compared with SRS plus WBRT (hazard ratio, 3.6; 95%CI, 2.2-5.9; P <.001). There was no significant difference in functional independence at 3 months between the treatment groups (mean change from baseline,-1.5 points for SRS alone vs-4.2 points for SRS plus WBRT; mean difference, 2.7 points; 95%CI,-2.0 to 7.4 points; P =.26). Median overall survival was 10.4 months for SRS alone and 7.4 months for SRS plus WBRT (hazard ratio, 1.02; 95%CI, 0.75-1.38; P =.92). For long-term survivors, the incidence of cognitive deterioration was less after SRS alone at 3 months (5/11 [45.5%] vs 16/17 [94.1%]; difference,-48.7%; 95%CI,-87.6%to-9.7%; P =.007) and at 12 months (6/10 [60%] vs 17/18 [94.4%]; difference,-34.4%; 95%CI,-74.4%to 5.5%; P =.04). CONCLUSIONS AND RELEVANCE Among patients with 1 to 3 brainmetastases, the use of SRS alone, compared with SRS combined withWBRT, resulted in less cognitive deterioration at 3 months. In the absence of a difference in overall survival, these findings suggest that for patients with 1 to 3 brainmetastases amenable to radiosurgery, SRS alonemay be a preferred strategy.

Original languageEnglish (US)
Pages (from-to)401-409
Number of pages9
JournalJAMA - Journal of the American Medical Association
Volume316
Issue number4
DOIs
StatePublished - Jul 26 2016

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Radiosurgery
Cognition
Radiotherapy
Randomized Controlled Trials
Neoplasm Metastasis
Brain
Quality of Life
Survival

ASJC Scopus subject areas

  • Medicine(all)

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Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases a randomized clinical trial. / Brown, Paul D.; Jaeckle, Kurt; Ballman, Karla V.; Farace, Elana; Cerhan, Jane H; Keith Anderson, S.; Carrero, Xiomara W.; Barker, Fred G.; Deming, Richard; Burri, Stuart H.; Ménard, Cynthia; Chung, Caroline; Stieber, Volker W.; Pollock, Bruce E.; Galanis, Evanthia; Buckner, Jan Craig; Asher, Anthony L.

In: JAMA - Journal of the American Medical Association, Vol. 316, No. 4, 26.07.2016, p. 401-409.

Research output: Contribution to journalArticle

Brown, PD, Jaeckle, K, Ballman, KV, Farace, E, Cerhan, JH, Keith Anderson, S, Carrero, XW, Barker, FG, Deming, R, Burri, SH, Ménard, C, Chung, C, Stieber, VW, Pollock, BE, Galanis, E, Buckner, JC & Asher, AL 2016, 'Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases a randomized clinical trial', JAMA - Journal of the American Medical Association, vol. 316, no. 4, pp. 401-409. https://doi.org/10.1001/jama.2016.9839
Brown, Paul D. ; Jaeckle, Kurt ; Ballman, Karla V. ; Farace, Elana ; Cerhan, Jane H ; Keith Anderson, S. ; Carrero, Xiomara W. ; Barker, Fred G. ; Deming, Richard ; Burri, Stuart H. ; Ménard, Cynthia ; Chung, Caroline ; Stieber, Volker W. ; Pollock, Bruce E. ; Galanis, Evanthia ; Buckner, Jan Craig ; Asher, Anthony L. / Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases a randomized clinical trial. In: JAMA - Journal of the American Medical Association. 2016 ; Vol. 316, No. 4. pp. 401-409.
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title = "Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases a randomized clinical trial",
abstract = "Importance Whole brain radiotherapy (WBRT) significantly improves tumor control in the brain after stereotactic radiosurgery (SRS), yet because of its association with cognitive decline, its role in the treatment of patients with brain metastases remains controversial. OBJECTIVE To determine whether there is less cognitive deterioration at 3 months after SRS alone vs SRS plus WBRT. DESIGN, SETTING, AND PARTICIPANTS At 34 institutions in North America, patients with 1 to 3 brain metastases were randomized to receive SRS or SRS plus WBRT between February 2002 and December 2013. INTERVENTIONS The WBRT dose schedule was 30 Gy in 12 fractions; the SRS dose was 18 to 22 Gy in the SRS plus WBRT group and 20 to 24 Gy for SRS alone. MAIN OUTCOMES AND MEASURES The primary end pointwas cognitive deterioration (decline >1 SD from baseline on at least 1 cognitive test at 3 months) in participants who completed the baseline and 3-month assessments. Secondary end points included time to intracranial failure, quality of life, functional independence, long-term cognitive status, and overall survival. RESULTS There were 213 randomized participants (SRS alone, n = 111; SRS plus WBRT, n = 102) with a mean age of 60.6 years (SD, 10.5 years); 103 (48{\%}) were women. There was less cognitive deterioration at 3 months after SRS alone (40/63 patients [63.5{\%}]) than when combined with WBRT (44/48 patients [91.7{\%}]; difference,-28.2{\%}; 90{\%} CI,-41.9{\%} to-14.4{\%}; P <.001). Quality of life was higher at 3 months with SRS alone, including overall quality of life (mean change from baseline,-0.1 vs-12.0 points; mean difference, 11.9; 95{\%}CI, 4.8-19.0 points; P =.001). Time to intracranial failure was significantly shorter for SRS alone compared with SRS plus WBRT (hazard ratio, 3.6; 95{\%}CI, 2.2-5.9; P <.001). There was no significant difference in functional independence at 3 months between the treatment groups (mean change from baseline,-1.5 points for SRS alone vs-4.2 points for SRS plus WBRT; mean difference, 2.7 points; 95{\%}CI,-2.0 to 7.4 points; P =.26). Median overall survival was 10.4 months for SRS alone and 7.4 months for SRS plus WBRT (hazard ratio, 1.02; 95{\%}CI, 0.75-1.38; P =.92). For long-term survivors, the incidence of cognitive deterioration was less after SRS alone at 3 months (5/11 [45.5{\%}] vs 16/17 [94.1{\%}]; difference,-48.7{\%}; 95{\%}CI,-87.6{\%}to-9.7{\%}; P =.007) and at 12 months (6/10 [60{\%}] vs 17/18 [94.4{\%}]; difference,-34.4{\%}; 95{\%}CI,-74.4{\%}to 5.5{\%}; P =.04). CONCLUSIONS AND RELEVANCE Among patients with 1 to 3 brainmetastases, the use of SRS alone, compared with SRS combined withWBRT, resulted in less cognitive deterioration at 3 months. In the absence of a difference in overall survival, these findings suggest that for patients with 1 to 3 brainmetastases amenable to radiosurgery, SRS alonemay be a preferred strategy.",
author = "Brown, {Paul D.} and Kurt Jaeckle and Ballman, {Karla V.} and Elana Farace and Cerhan, {Jane H} and {Keith Anderson}, S. and Carrero, {Xiomara W.} and Barker, {Fred G.} and Richard Deming and Burri, {Stuart H.} and Cynthia M{\'e}nard and Caroline Chung and Stieber, {Volker W.} and Pollock, {Bruce E.} and Evanthia Galanis and Buckner, {Jan Craig} and Asher, {Anthony L.}",
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doi = "10.1001/jama.2016.9839",
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T1 - Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases a randomized clinical trial

AU - Brown, Paul D.

AU - Jaeckle, Kurt

AU - Ballman, Karla V.

AU - Farace, Elana

AU - Cerhan, Jane H

AU - Keith Anderson, S.

AU - Carrero, Xiomara W.

AU - Barker, Fred G.

AU - Deming, Richard

AU - Burri, Stuart H.

AU - Ménard, Cynthia

AU - Chung, Caroline

AU - Stieber, Volker W.

AU - Pollock, Bruce E.

AU - Galanis, Evanthia

AU - Buckner, Jan Craig

AU - Asher, Anthony L.

PY - 2016/7/26

Y1 - 2016/7/26

N2 - Importance Whole brain radiotherapy (WBRT) significantly improves tumor control in the brain after stereotactic radiosurgery (SRS), yet because of its association with cognitive decline, its role in the treatment of patients with brain metastases remains controversial. OBJECTIVE To determine whether there is less cognitive deterioration at 3 months after SRS alone vs SRS plus WBRT. DESIGN, SETTING, AND PARTICIPANTS At 34 institutions in North America, patients with 1 to 3 brain metastases were randomized to receive SRS or SRS plus WBRT between February 2002 and December 2013. INTERVENTIONS The WBRT dose schedule was 30 Gy in 12 fractions; the SRS dose was 18 to 22 Gy in the SRS plus WBRT group and 20 to 24 Gy for SRS alone. MAIN OUTCOMES AND MEASURES The primary end pointwas cognitive deterioration (decline >1 SD from baseline on at least 1 cognitive test at 3 months) in participants who completed the baseline and 3-month assessments. Secondary end points included time to intracranial failure, quality of life, functional independence, long-term cognitive status, and overall survival. RESULTS There were 213 randomized participants (SRS alone, n = 111; SRS plus WBRT, n = 102) with a mean age of 60.6 years (SD, 10.5 years); 103 (48%) were women. There was less cognitive deterioration at 3 months after SRS alone (40/63 patients [63.5%]) than when combined with WBRT (44/48 patients [91.7%]; difference,-28.2%; 90% CI,-41.9% to-14.4%; P <.001). Quality of life was higher at 3 months with SRS alone, including overall quality of life (mean change from baseline,-0.1 vs-12.0 points; mean difference, 11.9; 95%CI, 4.8-19.0 points; P =.001). Time to intracranial failure was significantly shorter for SRS alone compared with SRS plus WBRT (hazard ratio, 3.6; 95%CI, 2.2-5.9; P <.001). There was no significant difference in functional independence at 3 months between the treatment groups (mean change from baseline,-1.5 points for SRS alone vs-4.2 points for SRS plus WBRT; mean difference, 2.7 points; 95%CI,-2.0 to 7.4 points; P =.26). Median overall survival was 10.4 months for SRS alone and 7.4 months for SRS plus WBRT (hazard ratio, 1.02; 95%CI, 0.75-1.38; P =.92). For long-term survivors, the incidence of cognitive deterioration was less after SRS alone at 3 months (5/11 [45.5%] vs 16/17 [94.1%]; difference,-48.7%; 95%CI,-87.6%to-9.7%; P =.007) and at 12 months (6/10 [60%] vs 17/18 [94.4%]; difference,-34.4%; 95%CI,-74.4%to 5.5%; P =.04). CONCLUSIONS AND RELEVANCE Among patients with 1 to 3 brainmetastases, the use of SRS alone, compared with SRS combined withWBRT, resulted in less cognitive deterioration at 3 months. In the absence of a difference in overall survival, these findings suggest that for patients with 1 to 3 brainmetastases amenable to radiosurgery, SRS alonemay be a preferred strategy.

AB - Importance Whole brain radiotherapy (WBRT) significantly improves tumor control in the brain after stereotactic radiosurgery (SRS), yet because of its association with cognitive decline, its role in the treatment of patients with brain metastases remains controversial. OBJECTIVE To determine whether there is less cognitive deterioration at 3 months after SRS alone vs SRS plus WBRT. DESIGN, SETTING, AND PARTICIPANTS At 34 institutions in North America, patients with 1 to 3 brain metastases were randomized to receive SRS or SRS plus WBRT between February 2002 and December 2013. INTERVENTIONS The WBRT dose schedule was 30 Gy in 12 fractions; the SRS dose was 18 to 22 Gy in the SRS plus WBRT group and 20 to 24 Gy for SRS alone. MAIN OUTCOMES AND MEASURES The primary end pointwas cognitive deterioration (decline >1 SD from baseline on at least 1 cognitive test at 3 months) in participants who completed the baseline and 3-month assessments. Secondary end points included time to intracranial failure, quality of life, functional independence, long-term cognitive status, and overall survival. RESULTS There were 213 randomized participants (SRS alone, n = 111; SRS plus WBRT, n = 102) with a mean age of 60.6 years (SD, 10.5 years); 103 (48%) were women. There was less cognitive deterioration at 3 months after SRS alone (40/63 patients [63.5%]) than when combined with WBRT (44/48 patients [91.7%]; difference,-28.2%; 90% CI,-41.9% to-14.4%; P <.001). Quality of life was higher at 3 months with SRS alone, including overall quality of life (mean change from baseline,-0.1 vs-12.0 points; mean difference, 11.9; 95%CI, 4.8-19.0 points; P =.001). Time to intracranial failure was significantly shorter for SRS alone compared with SRS plus WBRT (hazard ratio, 3.6; 95%CI, 2.2-5.9; P <.001). There was no significant difference in functional independence at 3 months between the treatment groups (mean change from baseline,-1.5 points for SRS alone vs-4.2 points for SRS plus WBRT; mean difference, 2.7 points; 95%CI,-2.0 to 7.4 points; P =.26). Median overall survival was 10.4 months for SRS alone and 7.4 months for SRS plus WBRT (hazard ratio, 1.02; 95%CI, 0.75-1.38; P =.92). For long-term survivors, the incidence of cognitive deterioration was less after SRS alone at 3 months (5/11 [45.5%] vs 16/17 [94.1%]; difference,-48.7%; 95%CI,-87.6%to-9.7%; P =.007) and at 12 months (6/10 [60%] vs 17/18 [94.4%]; difference,-34.4%; 95%CI,-74.4%to 5.5%; P =.04). CONCLUSIONS AND RELEVANCE Among patients with 1 to 3 brainmetastases, the use of SRS alone, compared with SRS combined withWBRT, resulted in less cognitive deterioration at 3 months. In the absence of a difference in overall survival, these findings suggest that for patients with 1 to 3 brainmetastases amenable to radiosurgery, SRS alonemay be a preferred strategy.

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