A Multi-institutional Prospective Observational Study of Stereotactic Radiosurgery for Patients With Multiple Brain Metastases (JLGK0901 Study Update): Irradiation-related Complications and Long-term Maintenance of Mini-Mental State Examination Scores

Masaaki Yamamoto, Toru Serizawa, Yoshinori Higuchi, Yasunori Sato, Jun Kawagishi, Kazuhiro Yamanaka, Takashi Shuto, Atsuya Akabane, Hidefumi Jokura, Shoji Yomo, Osamu Nagano, Hidefumi Aoyama

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Purpose The JLGK0901 study showed the noninferiority of stereotactic radiosurgery (SRS) alone as initial treatment of 5 to 10 brain metastases (BMs) compared with 2 to 4 BMs in terms of overall survival and most secondary endpoints (Lancet Oncol 2014;15:387-95). However, observation periods were not long enough to allow confirmation of the long-term safety of SRS alone in patients with 5 to 10 BMs. Methods and Materials This was a prospective observational study of Gamma Knife SRS-treated patients with 1 to 10 newly diagnosed BMs enrolled at 23 facilities between March 1, 2009, and February 15, 2012. Results The 1194 eligible patients were categorized into the following groups: group A, 1 tumor (n=455); group B, 2 to 4 tumors (n=531); and group C, 5 to 10 tumors (n=208). Cumulative rates of Mini-Mental State Examination (MMSE) score maintenance (MMSE score decrease <3 from baseline) determined with a competing risk analysis of groups A, B, and C were 93%, 91%, and 92%, respectively, at the 12th month after SRS; 91%, 89%, and 91%, respectively, at the 24th month; 89%, 88%, and 89%, respectively, at the 36th month; and 87%, 86%, and 89%, respectively, at the 48th month (hazard ratio [HR] of group A vs group B, 0.719; 95% confidence interval [CI], 0.437-1.172; P=.18; HR of group B vs group C, 1.280; 95% CI, 0.696-2.508; P=.43). During observations ranging from 0.3 to 67.5 months (median, 12.0 months; interquartile range, 5.8-26.5 months), as of December 2014, 145 patients (12.1%) had SRS-induced complications. Cumulative complication incidences by competing risk analysis for groups A, B, and C were 7%, 8%, and 6%, respectively, at the 12th month after SRS; 10%, 11%, and 11%, respectively, at the 24th month; 11%, 11%, and 12%, respectively, at the 36th month; and 12%, 12%, and 13%, respectively, at the 48th month (HR of group A vs group B, 0.850; 95% CI, 0.592-1.220; P=.38; HR of group B vs group C, 1.052; 95% CI, 0.666-1.662, P=.83). Leukoencephalopathy occurred in 12 of the 1074 patients (1.1%) with follow-up magnetic resonance imaging and was detected after salvage whole-brain radiation therapy in 11 of these 12 patients. In these 11 patients, leukoencephalopathy was detected by magnetic resonance imaging 5.2 to 21.2 months (median, 11.0 months; interquartile range, 7.0-14.4 months) after whole-brain radiation therapy. Conclusions Neither MMSE score maintenance nor post-SRS complication incidence differed among groups A, B, and C. This longer-term follow-up study further supports the already-reported noninferiority hypothesis of SRS alone for patients with 5 to 10 BMs versus 2 to 4 BMs.

Original languageEnglish
Pages (from-to)31-40
Number of pages10
JournalInternational Journal of Radiation Oncology Biology Physics
Volume99
Issue number1
DOIs
Publication statusPublished - 2017 Sep 1
Externally publishedYes

Fingerprint

Radiosurgery
metastasis
maintenance
brain
Observational Studies
examination
Prospective Studies
Neoplasm Metastasis
irradiation
Brain
Confidence Intervals
Leukoencephalopathies
hazards
confidence
intervals
Radiotherapy
Maintenance
Magnetic Resonance Imaging
tumors
Neoplasms

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

A Multi-institutional Prospective Observational Study of Stereotactic Radiosurgery for Patients With Multiple Brain Metastases (JLGK0901 Study Update) : Irradiation-related Complications and Long-term Maintenance of Mini-Mental State Examination Scores. / Yamamoto, Masaaki; Serizawa, Toru; Higuchi, Yoshinori; Sato, Yasunori; Kawagishi, Jun; Yamanaka, Kazuhiro; Shuto, Takashi; Akabane, Atsuya; Jokura, Hidefumi; Yomo, Shoji; Nagano, Osamu; Aoyama, Hidefumi.

In: International Journal of Radiation Oncology Biology Physics, Vol. 99, No. 1, 01.09.2017, p. 31-40.

Research output: Contribution to journalArticle

Yamamoto, Masaaki ; Serizawa, Toru ; Higuchi, Yoshinori ; Sato, Yasunori ; Kawagishi, Jun ; Yamanaka, Kazuhiro ; Shuto, Takashi ; Akabane, Atsuya ; Jokura, Hidefumi ; Yomo, Shoji ; Nagano, Osamu ; Aoyama, Hidefumi. / A Multi-institutional Prospective Observational Study of Stereotactic Radiosurgery for Patients With Multiple Brain Metastases (JLGK0901 Study Update) : Irradiation-related Complications and Long-term Maintenance of Mini-Mental State Examination Scores. In: International Journal of Radiation Oncology Biology Physics. 2017 ; Vol. 99, No. 1. pp. 31-40.
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abstract = "Purpose The JLGK0901 study showed the noninferiority of stereotactic radiosurgery (SRS) alone as initial treatment of 5 to 10 brain metastases (BMs) compared with 2 to 4 BMs in terms of overall survival and most secondary endpoints (Lancet Oncol 2014;15:387-95). However, observation periods were not long enough to allow confirmation of the long-term safety of SRS alone in patients with 5 to 10 BMs. Methods and Materials This was a prospective observational study of Gamma Knife SRS-treated patients with 1 to 10 newly diagnosed BMs enrolled at 23 facilities between March 1, 2009, and February 15, 2012. Results The 1194 eligible patients were categorized into the following groups: group A, 1 tumor (n=455); group B, 2 to 4 tumors (n=531); and group C, 5 to 10 tumors (n=208). Cumulative rates of Mini-Mental State Examination (MMSE) score maintenance (MMSE score decrease <3 from baseline) determined with a competing risk analysis of groups A, B, and C were 93{\%}, 91{\%}, and 92{\%}, respectively, at the 12th month after SRS; 91{\%}, 89{\%}, and 91{\%}, respectively, at the 24th month; 89{\%}, 88{\%}, and 89{\%}, respectively, at the 36th month; and 87{\%}, 86{\%}, and 89{\%}, respectively, at the 48th month (hazard ratio [HR] of group A vs group B, 0.719; 95{\%} confidence interval [CI], 0.437-1.172; P=.18; HR of group B vs group C, 1.280; 95{\%} CI, 0.696-2.508; P=.43). During observations ranging from 0.3 to 67.5 months (median, 12.0 months; interquartile range, 5.8-26.5 months), as of December 2014, 145 patients (12.1{\%}) had SRS-induced complications. Cumulative complication incidences by competing risk analysis for groups A, B, and C were 7{\%}, 8{\%}, and 6{\%}, respectively, at the 12th month after SRS; 10{\%}, 11{\%}, and 11{\%}, respectively, at the 24th month; 11{\%}, 11{\%}, and 12{\%}, respectively, at the 36th month; and 12{\%}, 12{\%}, and 13{\%}, respectively, at the 48th month (HR of group A vs group B, 0.850; 95{\%} CI, 0.592-1.220; P=.38; HR of group B vs group C, 1.052; 95{\%} CI, 0.666-1.662, P=.83). Leukoencephalopathy occurred in 12 of the 1074 patients (1.1{\%}) with follow-up magnetic resonance imaging and was detected after salvage whole-brain radiation therapy in 11 of these 12 patients. In these 11 patients, leukoencephalopathy was detected by magnetic resonance imaging 5.2 to 21.2 months (median, 11.0 months; interquartile range, 7.0-14.4 months) after whole-brain radiation therapy. Conclusions Neither MMSE score maintenance nor post-SRS complication incidence differed among groups A, B, and C. This longer-term follow-up study further supports the already-reported noninferiority hypothesis of SRS alone for patients with 5 to 10 BMs versus 2 to 4 BMs.",
author = "Masaaki Yamamoto and Toru Serizawa and Yoshinori Higuchi and Yasunori Sato and Jun Kawagishi and Kazuhiro Yamanaka and Takashi Shuto and Atsuya Akabane and Hidefumi Jokura and Shoji Yomo and Osamu Nagano and Hidefumi Aoyama",
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TY - JOUR

T1 - A Multi-institutional Prospective Observational Study of Stereotactic Radiosurgery for Patients With Multiple Brain Metastases (JLGK0901 Study Update)

T2 - Irradiation-related Complications and Long-term Maintenance of Mini-Mental State Examination Scores

AU - Yamamoto, Masaaki

AU - Serizawa, Toru

AU - Higuchi, Yoshinori

AU - Sato, Yasunori

AU - Kawagishi, Jun

AU - Yamanaka, Kazuhiro

AU - Shuto, Takashi

AU - Akabane, Atsuya

AU - Jokura, Hidefumi

AU - Yomo, Shoji

AU - Nagano, Osamu

AU - Aoyama, Hidefumi

PY - 2017/9/1

Y1 - 2017/9/1

N2 - Purpose The JLGK0901 study showed the noninferiority of stereotactic radiosurgery (SRS) alone as initial treatment of 5 to 10 brain metastases (BMs) compared with 2 to 4 BMs in terms of overall survival and most secondary endpoints (Lancet Oncol 2014;15:387-95). However, observation periods were not long enough to allow confirmation of the long-term safety of SRS alone in patients with 5 to 10 BMs. Methods and Materials This was a prospective observational study of Gamma Knife SRS-treated patients with 1 to 10 newly diagnosed BMs enrolled at 23 facilities between March 1, 2009, and February 15, 2012. Results The 1194 eligible patients were categorized into the following groups: group A, 1 tumor (n=455); group B, 2 to 4 tumors (n=531); and group C, 5 to 10 tumors (n=208). Cumulative rates of Mini-Mental State Examination (MMSE) score maintenance (MMSE score decrease <3 from baseline) determined with a competing risk analysis of groups A, B, and C were 93%, 91%, and 92%, respectively, at the 12th month after SRS; 91%, 89%, and 91%, respectively, at the 24th month; 89%, 88%, and 89%, respectively, at the 36th month; and 87%, 86%, and 89%, respectively, at the 48th month (hazard ratio [HR] of group A vs group B, 0.719; 95% confidence interval [CI], 0.437-1.172; P=.18; HR of group B vs group C, 1.280; 95% CI, 0.696-2.508; P=.43). During observations ranging from 0.3 to 67.5 months (median, 12.0 months; interquartile range, 5.8-26.5 months), as of December 2014, 145 patients (12.1%) had SRS-induced complications. Cumulative complication incidences by competing risk analysis for groups A, B, and C were 7%, 8%, and 6%, respectively, at the 12th month after SRS; 10%, 11%, and 11%, respectively, at the 24th month; 11%, 11%, and 12%, respectively, at the 36th month; and 12%, 12%, and 13%, respectively, at the 48th month (HR of group A vs group B, 0.850; 95% CI, 0.592-1.220; P=.38; HR of group B vs group C, 1.052; 95% CI, 0.666-1.662, P=.83). Leukoencephalopathy occurred in 12 of the 1074 patients (1.1%) with follow-up magnetic resonance imaging and was detected after salvage whole-brain radiation therapy in 11 of these 12 patients. In these 11 patients, leukoencephalopathy was detected by magnetic resonance imaging 5.2 to 21.2 months (median, 11.0 months; interquartile range, 7.0-14.4 months) after whole-brain radiation therapy. Conclusions Neither MMSE score maintenance nor post-SRS complication incidence differed among groups A, B, and C. This longer-term follow-up study further supports the already-reported noninferiority hypothesis of SRS alone for patients with 5 to 10 BMs versus 2 to 4 BMs.

AB - Purpose The JLGK0901 study showed the noninferiority of stereotactic radiosurgery (SRS) alone as initial treatment of 5 to 10 brain metastases (BMs) compared with 2 to 4 BMs in terms of overall survival and most secondary endpoints (Lancet Oncol 2014;15:387-95). However, observation periods were not long enough to allow confirmation of the long-term safety of SRS alone in patients with 5 to 10 BMs. Methods and Materials This was a prospective observational study of Gamma Knife SRS-treated patients with 1 to 10 newly diagnosed BMs enrolled at 23 facilities between March 1, 2009, and February 15, 2012. Results The 1194 eligible patients were categorized into the following groups: group A, 1 tumor (n=455); group B, 2 to 4 tumors (n=531); and group C, 5 to 10 tumors (n=208). Cumulative rates of Mini-Mental State Examination (MMSE) score maintenance (MMSE score decrease <3 from baseline) determined with a competing risk analysis of groups A, B, and C were 93%, 91%, and 92%, respectively, at the 12th month after SRS; 91%, 89%, and 91%, respectively, at the 24th month; 89%, 88%, and 89%, respectively, at the 36th month; and 87%, 86%, and 89%, respectively, at the 48th month (hazard ratio [HR] of group A vs group B, 0.719; 95% confidence interval [CI], 0.437-1.172; P=.18; HR of group B vs group C, 1.280; 95% CI, 0.696-2.508; P=.43). During observations ranging from 0.3 to 67.5 months (median, 12.0 months; interquartile range, 5.8-26.5 months), as of December 2014, 145 patients (12.1%) had SRS-induced complications. Cumulative complication incidences by competing risk analysis for groups A, B, and C were 7%, 8%, and 6%, respectively, at the 12th month after SRS; 10%, 11%, and 11%, respectively, at the 24th month; 11%, 11%, and 12%, respectively, at the 36th month; and 12%, 12%, and 13%, respectively, at the 48th month (HR of group A vs group B, 0.850; 95% CI, 0.592-1.220; P=.38; HR of group B vs group C, 1.052; 95% CI, 0.666-1.662, P=.83). Leukoencephalopathy occurred in 12 of the 1074 patients (1.1%) with follow-up magnetic resonance imaging and was detected after salvage whole-brain radiation therapy in 11 of these 12 patients. In these 11 patients, leukoencephalopathy was detected by magnetic resonance imaging 5.2 to 21.2 months (median, 11.0 months; interquartile range, 7.0-14.4 months) after whole-brain radiation therapy. Conclusions Neither MMSE score maintenance nor post-SRS complication incidence differed among groups A, B, and C. This longer-term follow-up study further supports the already-reported noninferiority hypothesis of SRS alone for patients with 5 to 10 BMs versus 2 to 4 BMs.

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