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Whole brain radiation therapy (WBRT) alone versus WBRT and radiosurgery for the treatment of brain metastases

  • Review
  • Intervention




Historically, whole brain radiation therapy (WBRT) has been the main treatment for brain metastases. Stereotactic radiosurgery (SRS) delivers high-dose focused radiation and is being increasingly utilized to treat brain metastases. The benefit of adding SRS to WBRT is unclear. This is an updated version of the original Cochrane Review published in Issue 9, 2012.


To assess the efficacy of WBRT plus SRS versus WBRT alone in the treatment of adults with brain metastases.

Search methods

For the original review, in 2009 we searched the following electronic databases: CENTRAL, MEDLINE, Embase, and CancerLit in order to identify trials for inclusion in this review. For the first update the searches were updated in May 2012.

For this update, in May 2017 we searched CENTRAL, MEDLINE, and Embase in order to identify trials for inclusion in the review.

Selection criteria

We restricted the review to randomized controlled trials (RCTs) that compared use of WBRT plus SRS versus WBRT alone for upfront treatment of adults with newly diagnosed metastases (single or multiple) in the brain resulting from any primary, extracranial cancer.

Data collection and analysis

We used the generic inverse variance method, random-effects model in Review Manager 5 for the meta-analysis.

Main results

We identified three studies and one abstract for inclusion but we could only include two studies, with a total of 358 participants in a meta-analysis. This found no difference in overall survival (OS) between the WBRT plus SRS and WBRT alone groups (hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.65 to 1.02; 2 studies, 358 participants; moderate-quality evidence). For participants with one brain metastasis median survival was significantly longer in the WBRT plus SRS group (6.5 months) versus WBRT group (4.9 months; P = 0.04). Participants in the WBRT plus SRS group had decreased local failure compared to participants who received WBRT alone (HR 0.27, 95% CI 0.14 to 0.52; 2 studies, 129 participants; moderate-quality evidence). Furthermore, we observed an improvement in performance status scores and decrease in steroid use in the WBRT plus SRS group (risk ratio (RR) 0.64 CI 0.42 to 0.97; 1 study, 118 participants; low-quality evidence). Unchanged or improved Karnofsky Performance Scale (KPS) at six months was seen in 43% of participants in the combined therapy group versus only 28% in the WBRT-alone group (RR 0.78 CI 0.61 to 1.00; P value = 0.05; 1 study, 118 participants; low-quality evidence). Overall, risk of bias in the included studies was unclear.

Authors' conclusions

Since the last version of this review we have identified one new study that met the inclusion criteria. However, due to a lack of data from this study we were not able to include it in a meta-analysis. Given the unclear risk of bias in the included studies, the results of this analysis have to be interpreted with caution. In our analysis of all included participants, SRS plus WBRT did not show a survival benefit over WBRT alone. However, performance status and local control were significantly better in the SRS plus WBRT group. Furthermore, significantly longer OS was reported in the combined treatment group for recursive partitioning analysis (RPA) Class I patients as well as patients with single metastasis. Most of our outcomes of interest were graded as moderate-quality evidence according to the GRADE criteria and the risk of bias in the majority of included studies was mostly unclear.













メタ解析には、Review Manager 5を使用して、一般逆分散法、変量効果モデルにより解析を行った。


3件の試験および1件の抄録を特定したが、メタ解析に組み入れることができたのは2件の試験のみ、参加者合計358例であった。この解析からは、WBRTおよびSRSの併用療法群とWBRT単独療法群の間で、全生存期間(OS)に差は認められなかった[ハザード比(HR)0.82、95%信頼区間(CI)0.65~1.02、2試験、358例、エビデンスの質は中等度]。脳転移が単発の患者におけるOSの中央値は、WBRT群(4.9カ月)と比較してWBRTおよびSRSの併用療法群(6.5カ月)で有意な延長を認めた(p = 0.04)。WBRTおよびSRSの併用療法群では、WBRT単独療法群と比較して局所再発が減少した(HR 0.27、95%CI 0.14~0.52、2試験、129例、エビデンスの質は中等度)。さらに、WBRTおよびSRSの併用療法群では、全身状態のスコアの改善が認められ、ステロイドの使用も減少した[リスク比(RR)0.64、CI 0.42~0.97、1試験、118例、エビデンスの質は低い]。6カ月時点でカルノフスキー・パフォーマンス・スケール(KPS)に変化がない、または改善がみられたのは、併用療法群で43%であったのに対し、WBRT単独療法群では28%にとどまった(RR 0.78、CI 0.61~1.00、p = 0.05、1試験、118例、エビデンスの質は低い)。全体として、組み入れた試験のバイアスリスクは不明であった。


前回のレビュー以降、組み入れ基準を満たす試験を新たに1件特定した。しかし、この試験はデータが不足していたため、メタ解析に組み入れることができなかった。組み入れた試験のバイアスのリスクが不明であることを考慮すると、本解析の結果の解釈には注意が必要である。組み入れた全患者について解析したところ、SRSおよびWBRTの併用療法にはWBRT単独療法を上回る延命効果が認められなかった。しかし、全身状態および局所制御については、SRSおよびWBRT併用療法群の方が有意に良好であった。さらに、再帰分割分析(RPA)でClass Iの患者および単発転移の患者では、併用療法群の方がOSが有意に長かったことが報告されている。対象とした評価項目のエビデンスの質は、GRADE基準により大部分が中等度と格付けられた。また、組み入れた試験のバイアスのリスクは、ほとんどが不明であった。

Plain language summary

Is adding focused radiation (radiosurgery) to whole brain radiation therapy beneficial to people with brain metastases?

The issue
The benefit of adding stereotactic radiosurgery (SRS), which is non-surgical targeted radiation therapy, to whole brain radiation therapy (WBRT), where radiation is given to the whole brain when tumours cannot be removed by surgery, for people with brain metastases is unclear.

The aim of the review
We sought to determine whether adding SRS to WBRT is beneficial compared to WBRT alone in the treatment of brain metastases.

What are the main findings?
We identified three randomised controlled trials (RCTs), which are studies that randomly assign participants into different treatment groups, that looked at whether adding focused (targeted) radiation (radiosurgery) to WBRT is beneficial to people with brain metastases. Overall, participants who underwent WBRT and SRS did not survive longer than participants who were treated with WBRT alone. However, participants with high functional status to perform activities of daily life and those with a single metastasis did survive longer after SRS and WBRT. Participants treated with WBRT and SRS did experience improved local control and performance status, as well as decreased steroid use compared to participants treated with WBRT alone.

Quality of the evidence
The overall quality of the evidence was moderate based on the GRADE assessments for our outcomes of interest, and the overall risk of bias was unclear.

What are the conclusions?
Most of our conclusions are based on the results of one large trial with unclear risk of bias and therefore, we cautiously make the following remarks: we found that when radiosurgery was added to WBRT, there was no evidence to suggest that people lived any longer than if they had WBRT alone, except for people with only one brain metastasis (who may live longer if they receive the combination treatment). People having combination treatment also seemed to function better in daily life, their treated tumors were associated with having less chance of growing back, and they had to take less steroid medication. The side effects of combined therapy and WBRT alone were similar.

Ringkasan bahasa mudah

Adakah penambahan sinaran radiasi (radiosurgery) kepada terapi radiasi seluruh otak memberi manfaat kepada orang dengan metastasis otak?

Manfaat menambah radiosurgeri stereotaktik (SRS), merupakan terapi radiasi sasaran bukan pembedahan, kepada terapi radiasi seluruh otak (WBRT), di mana radiasi diberikan kepada seluruh otak apabila tumor tidak boleh dikeluarkan oleh pembedahan, untuk orang ynag mempunyai metastasis otak adalah tidak jelas.

Tujuan ulasan
Penyelidik cuba menentukan sama ada menambah SRS kepada WBRT adalah berfaedah berbanding dengan WBRT sahaja dalam rawatan metastasis otak.

Apakah penemuan utama?
Penyelidik mengenal pasti tiga kajian rawak terkawal (RCTs), yang merupakan kajian yang secara rawak memberikan peserta ke dalam kumpulan rawatan yang berbeza, yang menilai sama ada penambahan radiasi (sasaran radiasi) (radiosurgeri) kepada WBRT bermanfaat kepada orang dengan metastasis otak. Keseluruhannya, peserta yang menjalani WBRT dan SRS tidak dapat bertahan lebih lama daripada peserta yang dirawat dengan WBRT sahaja. Namun demikian, peserta yang mempunyai status fungsian yang tinggi untuk menjalankan aktiviti kehidupan seharian dan mereka yang mempunyai metastasis tunggal masih hidup lebih lama selepas SRS dan WBRT. Peserta yang dirawat dengan WBRT dan SRS mengalami pengalaman kawalan dan prestasi tempatan yang lebih baik, serta mengurangkan penggunaan steroid berbanding peserta yang dirawat dengan WBRT sahaja.

Kualiti bukti
Keseluruhan kualiti bukti adalah sederhana berdasarkan penilaian GRADE untuk hasil yang minat, dan keseluruhan risiko berat sebelah adalah tidak jelas.

Apakah kesimpulannya?
Kebanyakan kesimpulan penyelidik adalah berdasarkan kepada keputusan satu kajian besar dengan risiko berat sebelah yang tidak jelas dan oleh itu, penyelidik berhati-hati membuat kenyataan berikut: penyelidik mendapati bahawa apabila radiosurgeri telah ditambahkan kepada WBRT, tiada bukti untuk menunjukkan bahawa orang hidup lebih lama daripada jika mereka mempunyai WBRT sahaja, kecuali orang yang hanya mempunyai satu metastasis otak (yang boleh hidup lebih lama jika mereka menerima rawatan kombinasi). Orang yang mempunyai rawatan kombinasi juga seolah-olah berfungsi lebih baik dalam kehidupan seharian, tumor mereka yang dirawat dikaitkan dengan kurang peluang untuk tumbuh kembali, dan mereka perlu mengambil ubat steroid yang kurang. Kesan sampingan gabungan terapi dan WBRT sahaja adalah sama.

Catatan terjemahan

Diterjemahkan oleh Wong Chun Hoong (International Medical University). Disunting oleh Tuan Hairulnizam Tuan Kamauzaman (Universiti Sains Malaysia). Untuk sebarang pertanyaan berkaitan terjemahan ini sila hubungi









《実施組織》一般社団法人 日本癌医療翻訳アソシエイツ(JAMT:ジャムティ)『海外癌医療情報リファレンス』(成宮眞由美 翻訳、河村光栄(京都大学大学院、放射線腫瘍学・画像応用治療学) 監訳 [2018.01.13]《注意》この日本語訳は、臨床医、疫学研究者などによる翻訳のチェックを受けて公開していますが、訳語の間違いなどお気づきの点がございましたら、コクランジャパンまでご連絡ください。なお、2013年6月からコクラン・ライブラリーのNew review、Updated reviewとも日単位で更新されています。最新版の日本語訳を掲載するよう努めておりますが、タイム・ラグが生じている場合もあります。ご利用に際しては、最新版(英語版)の内容をご確認ください。《CD006121》