Stereotactic radiosurgery for patients with multiple brain metastases: a case-matched study comparing treatment results for patients with 2-9 versus 10 or more tumors

Masaaki Yamamoto, Takuya Kawabe, Yasunori Sato, Yoshinori Higuchi, Tadashi Nariai, Shinya Watanabe, Hidetoshi Kasuya

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

OBJECT: Although stereotactic radiosurgery (SRS) alone is not a standard treatment for patients with 4-5 tumors or more, a recent trend has been for patients with 5 or more, or even 10 or more, tumors to undergo SRS alone. The aim of this study was to reappraise whether the treatment results for SRS alone for patients with 10 or more tumors differ from those for patients with 2-9 tumors.

METHODS: This was an institutional review board-approved, retrospective cohort study that gathered data from the Katsuta Hospital Mito GammaHouse prospectively accumulated database. Data were collected for 2553 patients who consecutively had undergone Gamma Knife SRS alone, without whole-brain radiotherapy (WBRT), for newly diagnosed (mostly) or recurrent (uncommonly) brain metastases during 1998-2011. Of these 2553 patients, 739 (28.9%) with a single tumor were excluded, leaving 1814 with multiple metastases in the study. These 1814 patients were divided into 2 groups: those with 2-9 tumors (Group A, 1254 patients) and those with 10 or more tumors (Group B, 560 patients). Because of considerable bias in pre-SRS clinical factors between groups A and B, a case-matched study, which used the propensity score matching method, was conducted for clinical factors (i.e., age, sex, primary tumor state, extracerebral metastases, Karnofsky Performance Status, neurological symptoms, prior procedures [surgery and WBRT], volume of the largest tumor, and peripheral doses). Ultimately, 720 patients (360 in each group) were selected. The standard Kaplan-Meier method was used to determine post-SRS survival times and post-SRS neurological death-free survival times. Competing risk analysis was applied to estimate cumulative incidence for local recurrence, repeat SRS for new lesions, neurological deterioration, and SRS-induced complications.

RESULTS: Post-SRS median survival times did not differ significantly between the 2 groups (6.8 months for Group A vs 6.0 months for Group B; hazard ratio [HR] 1.133, 95% CI 0.974-1.319, p = 0.10). Furthermore, rates of neurological death were very similar: 10.0% for group A and 9.4% for group B (p = 0.89); neurological death-free survival times did not differ significantly between the 2 groups (HR 1.073, 95% CI 0.649-1.771, p = 0.78). The cumulative incidence of local recurrence (HR 0.425, 95% CI 0.0.181-0.990, p = 0.04) and repeat SRS for new lesions (HR 0.732, 95% CI 0.554-0.870, p = 0.03) were significantly lower for Group B than for Group A patients. No significant differences between the groups were found for cumulative incidence for neurological deterioration (HR 0.994, 95% CI 0.607-1.469, p = 0.80) or SRS-related complications (HR 0.541, 95% CI 0.138-2.112, p = 0.38).

CONCLUSIONS: Post-SRS treatment results (i.e., median survival time; neurological death-free survival times; and cumulative incidence for local recurrence, repeat SRS for new lesions, neurological deterioration, and SRS-related complications) were not inferior (neither less effective nor less safe) for patients in Group B than for those in Group A. We conclude that carefully selected patients with 10 or more tumors are not unfavorable candidates for SRS alone. A randomized controlled trial should be conducted to test this hypothesis.

Original languageEnglish
Pages (from-to)16-25
Number of pages10
JournalJournal of neurosurgery
Volume121
DOIs
Publication statusPublished - 2014 Dec 1
Externally publishedYes

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Radiosurgery
Neoplasm Metastasis
Brain
Neoplasms
Therapeutics
Survival
Incidence
Recurrence
Radiotherapy
Karnofsky Performance Status
Propensity Score
Research Ethics Committees
Age Factors
Tumor Burden

Keywords

  • brain metastases
  • Gamma Knife
  • HR = hazard ratio
  • KPS = Karnofsky Performance Status
  • radiation therapy
  • radiosurgery
  • RPA = recursive partitioning analysis
  • SRS = stereotactic radiosurgery
  • stereotactic radiosurgery
  • tumor number
  • WBRT = whole-brain radiation therapy

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

Cite this

Stereotactic radiosurgery for patients with multiple brain metastases : a case-matched study comparing treatment results for patients with 2-9 versus 10 or more tumors. / Yamamoto, Masaaki; Kawabe, Takuya; Sato, Yasunori; Higuchi, Yoshinori; Nariai, Tadashi; Watanabe, Shinya; Kasuya, Hidetoshi.

In: Journal of neurosurgery, Vol. 121, 01.12.2014, p. 16-25.

Research output: Contribution to journalArticle

Yamamoto, Masaaki ; Kawabe, Takuya ; Sato, Yasunori ; Higuchi, Yoshinori ; Nariai, Tadashi ; Watanabe, Shinya ; Kasuya, Hidetoshi. / Stereotactic radiosurgery for patients with multiple brain metastases : a case-matched study comparing treatment results for patients with 2-9 versus 10 or more tumors. In: Journal of neurosurgery. 2014 ; Vol. 121. pp. 16-25.
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TY - JOUR

T1 - Stereotactic radiosurgery for patients with multiple brain metastases

T2 - a case-matched study comparing treatment results for patients with 2-9 versus 10 or more tumors

AU - Yamamoto, Masaaki

AU - Kawabe, Takuya

AU - Sato, Yasunori

AU - Higuchi, Yoshinori

AU - Nariai, Tadashi

AU - Watanabe, Shinya

AU - Kasuya, Hidetoshi

PY - 2014/12/1

Y1 - 2014/12/1

N2 - OBJECT: Although stereotactic radiosurgery (SRS) alone is not a standard treatment for patients with 4-5 tumors or more, a recent trend has been for patients with 5 or more, or even 10 or more, tumors to undergo SRS alone. The aim of this study was to reappraise whether the treatment results for SRS alone for patients with 10 or more tumors differ from those for patients with 2-9 tumors.METHODS: This was an institutional review board-approved, retrospective cohort study that gathered data from the Katsuta Hospital Mito GammaHouse prospectively accumulated database. Data were collected for 2553 patients who consecutively had undergone Gamma Knife SRS alone, without whole-brain radiotherapy (WBRT), for newly diagnosed (mostly) or recurrent (uncommonly) brain metastases during 1998-2011. Of these 2553 patients, 739 (28.9%) with a single tumor were excluded, leaving 1814 with multiple metastases in the study. These 1814 patients were divided into 2 groups: those with 2-9 tumors (Group A, 1254 patients) and those with 10 or more tumors (Group B, 560 patients). Because of considerable bias in pre-SRS clinical factors between groups A and B, a case-matched study, which used the propensity score matching method, was conducted for clinical factors (i.e., age, sex, primary tumor state, extracerebral metastases, Karnofsky Performance Status, neurological symptoms, prior procedures [surgery and WBRT], volume of the largest tumor, and peripheral doses). Ultimately, 720 patients (360 in each group) were selected. The standard Kaplan-Meier method was used to determine post-SRS survival times and post-SRS neurological death-free survival times. Competing risk analysis was applied to estimate cumulative incidence for local recurrence, repeat SRS for new lesions, neurological deterioration, and SRS-induced complications.RESULTS: Post-SRS median survival times did not differ significantly between the 2 groups (6.8 months for Group A vs 6.0 months for Group B; hazard ratio [HR] 1.133, 95% CI 0.974-1.319, p = 0.10). Furthermore, rates of neurological death were very similar: 10.0% for group A and 9.4% for group B (p = 0.89); neurological death-free survival times did not differ significantly between the 2 groups (HR 1.073, 95% CI 0.649-1.771, p = 0.78). The cumulative incidence of local recurrence (HR 0.425, 95% CI 0.0.181-0.990, p = 0.04) and repeat SRS for new lesions (HR 0.732, 95% CI 0.554-0.870, p = 0.03) were significantly lower for Group B than for Group A patients. No significant differences between the groups were found for cumulative incidence for neurological deterioration (HR 0.994, 95% CI 0.607-1.469, p = 0.80) or SRS-related complications (HR 0.541, 95% CI 0.138-2.112, p = 0.38).CONCLUSIONS: Post-SRS treatment results (i.e., median survival time; neurological death-free survival times; and cumulative incidence for local recurrence, repeat SRS for new lesions, neurological deterioration, and SRS-related complications) were not inferior (neither less effective nor less safe) for patients in Group B than for those in Group A. We conclude that carefully selected patients with 10 or more tumors are not unfavorable candidates for SRS alone. A randomized controlled trial should be conducted to test this hypothesis.

AB - OBJECT: Although stereotactic radiosurgery (SRS) alone is not a standard treatment for patients with 4-5 tumors or more, a recent trend has been for patients with 5 or more, or even 10 or more, tumors to undergo SRS alone. The aim of this study was to reappraise whether the treatment results for SRS alone for patients with 10 or more tumors differ from those for patients with 2-9 tumors.METHODS: This was an institutional review board-approved, retrospective cohort study that gathered data from the Katsuta Hospital Mito GammaHouse prospectively accumulated database. Data were collected for 2553 patients who consecutively had undergone Gamma Knife SRS alone, without whole-brain radiotherapy (WBRT), for newly diagnosed (mostly) or recurrent (uncommonly) brain metastases during 1998-2011. Of these 2553 patients, 739 (28.9%) with a single tumor were excluded, leaving 1814 with multiple metastases in the study. These 1814 patients were divided into 2 groups: those with 2-9 tumors (Group A, 1254 patients) and those with 10 or more tumors (Group B, 560 patients). Because of considerable bias in pre-SRS clinical factors between groups A and B, a case-matched study, which used the propensity score matching method, was conducted for clinical factors (i.e., age, sex, primary tumor state, extracerebral metastases, Karnofsky Performance Status, neurological symptoms, prior procedures [surgery and WBRT], volume of the largest tumor, and peripheral doses). Ultimately, 720 patients (360 in each group) were selected. The standard Kaplan-Meier method was used to determine post-SRS survival times and post-SRS neurological death-free survival times. Competing risk analysis was applied to estimate cumulative incidence for local recurrence, repeat SRS for new lesions, neurological deterioration, and SRS-induced complications.RESULTS: Post-SRS median survival times did not differ significantly between the 2 groups (6.8 months for Group A vs 6.0 months for Group B; hazard ratio [HR] 1.133, 95% CI 0.974-1.319, p = 0.10). Furthermore, rates of neurological death were very similar: 10.0% for group A and 9.4% for group B (p = 0.89); neurological death-free survival times did not differ significantly between the 2 groups (HR 1.073, 95% CI 0.649-1.771, p = 0.78). The cumulative incidence of local recurrence (HR 0.425, 95% CI 0.0.181-0.990, p = 0.04) and repeat SRS for new lesions (HR 0.732, 95% CI 0.554-0.870, p = 0.03) were significantly lower for Group B than for Group A patients. No significant differences between the groups were found for cumulative incidence for neurological deterioration (HR 0.994, 95% CI 0.607-1.469, p = 0.80) or SRS-related complications (HR 0.541, 95% CI 0.138-2.112, p = 0.38).CONCLUSIONS: Post-SRS treatment results (i.e., median survival time; neurological death-free survival times; and cumulative incidence for local recurrence, repeat SRS for new lesions, neurological deterioration, and SRS-related complications) were not inferior (neither less effective nor less safe) for patients in Group B than for those in Group A. We conclude that carefully selected patients with 10 or more tumors are not unfavorable candidates for SRS alone. A randomized controlled trial should be conducted to test this hypothesis.

KW - brain metastases

KW - Gamma Knife

KW - HR = hazard ratio

KW - KPS = Karnofsky Performance Status

KW - radiation therapy

KW - radiosurgery

KW - RPA = recursive partitioning analysis

KW - SRS = stereotactic radiosurgery

KW - stereotactic radiosurgery

KW - tumor number

KW - WBRT = whole-brain radiation therapy

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