Palliation of metastatic bone pain: single fraction versus multifraction radiotherapy

 

Abstract

Background

Recent randomised studies reported that single fraction radiotherapy was as effective as multifraction radiotherapy in relieving pain due to bone metastasis. However, there are concerns about the higher retreatment rates and the efficacy of preventing future complications such as pathological fracture and spinal cord compression by single fraction radiotherapy.

Objectives

To undertake a systematic review and meta-analysis of single fraction radiotherapy versus multifraction radiotherapy for metastatic bone pain relief and prevention of bone complications.

Search methods

Trials were identified through MEDLINE, EMBASE, Cancerlit, reference lists of relevant articles and conference proceedings. Relevant data was extracted.

Selection criteria

Randomised studies comparing single fraction radiotherapy with multifraction radiotherapy on metastatic bone pain

Data collection and analysis

The analyses were performed using intention-to-treat principle. The results were pooled using meta-analysis to estimate the effect of treatment on pain response, re-treatment rate, pathological fracture rate and spinal cord compression rate.

Main results

Eleven trials that involved 3435 patients were identified. Of 3435 patients, 52 patients were randomised more than once for different painful bone metastasis sites. Altogether, 3487 painful sites were randomised. The trials included patients with painful bone metastases of any primary sites, but were mainly prostate, breast and lung. The overall pain response rates for single fraction radiotherapy and multifraction radiotherapy were 60% (1059/1779) and 59% (1038/1769) respectively, giving an odds ratio of 1.03 (95% confidence interval [CI], 0.89 to 1.19) indicating no difference between the two radiotherapy schedules. There was also no difference in complete pain response rates for single fraction radiotherapy (34% [497/1441]) and multifraction radiotherapy (32% [463/1435]) with an odds ratio of 1.11 (95% CI 0.94 to 1.30). Patients treated by single fraction radiotherapy had a higher re-treatment rate with 21.5% (267/1240) requiring re-treatment compared to 7.4% (91/1236) of patients in the multifraction radiotherapy arm (odds ratio 3.44 [95% CI 2.67 to 4.43]). The pathological fracture rate was also higher in single fraction radiotherapy arm patients. Three percent (37/1240) of patients treated by single fraction radiotherapy developed pathological fracture compared to 1.6% (20/1236) for those treated by multifraction radiotherapy (odds ratio 1.82 [95% CI 1.06 to 3.11]). The spinal cord compression rates were similar for both arms (odds ratio 1.41 [95% CI 0.72 to 2.75]). Repeated analyses excluding dropout patients gave similar results.

Authors' conclusions

Single fraction radiotherapy was as effective as multifraction radiotherapy in relieving metastatic bone pain. However, the retreatment rate and pathological fracture rates were higher after single fraction radiotherapy. Studies with quality of life and health economic end points are warranted to find out the optimal treatment option.

 

Plain language summary

Easing of bone pain caused by metastatic cancer: single versus multifraction radiotherapy

The spread of tumour to the bone (metastasis) is a common characteristic of many malignancies including cancers of the prostate, breast and lung. This may be associated with pain, compression of the spinal cord and the potential for bone fracture. Radiotherapy is used to treat bone metastases, however, the optimum treatment schedule is unclear. This review compares whether a single fraction of radiotherapy is better than multifractions of radiotherapy for alleviating the symptoms associated with tumours that have spread to the bone. Eleven randomised trials were identified in the published literature that compared single versus multifraction radiotherapy for bone metastases. Pooled analysis of these trials suggested that single fraction radiotherapy was as effective as multifraction radiotherapy in controlling bone pain. However, there were more bone fractures in patients treated by single fraction radiotherapy, and they received further treatment sessions more often than those receiving multifraction radiotherapy.

 

摘要

背景

緩解骨轉移疼痛：單一與多次放射治療的比較

最近的隨機研究報告認為，單一次與多次放射治療對於緩解骨轉移所造成的疼痛一樣有效。但是，單一次放射治療是否會造成較高的再治療率，以及其預防骨轉移之後的併發症，如病理性骨折和脊髓壓迫的效果卻仍有疑慮。

目標

對於單一次與多次放射治療對於緩解骨轉移所造成的疼痛，以及預防骨轉移造成的併發症的效果，進行有系統的回顧 和統合分析 (metaanalysis)。

搜尋策略

從MEDLINE、EMBASE、Cancerlit、相關文章的參考文獻，以及會議紀錄中找出相關的試驗(trials)，相關的資料將被選出用以分析。

選擇標準

收錄比較單一次與多次放射治療，對於緩解骨轉移疼痛的隨機研究。

資料收集與分析

資料分析均使用治療意向 (intentiontotreat) 為原則。使用統合分析 (metaanalysis) 的方法將各試驗的結果匯集起來，以分析治療對於疼痛的緩解、再治療率、病理性骨折和脊髓壓迫的發生率。

主要結論

一共收錄11個試驗，共包含3,435個病人。在這些病例中，52例患者由於不同的骨轉移部位，而被隨機分配一次以上。因此，共有3,487個骨轉移疼痛部位被隨機分配在兩組。這些試驗包括任何原發癌症的骨轉移，但主要是前列腺癌，乳癌和肺癌。單一次與多次放射治療的疼痛緩解率為分別為60% (1,059/1,779) 和59％ (1,038/1,769)，odds ratio為1.03 (95% CI為0.89−1.19)，顯示兩者無顯著性差異。此外，單一次與多次放射治療的疼痛完全緩解率分別為34%(497/1,441)以及32% (463/1,435)，odds ratio為1.11 (95% CI為0.94−1.30)，兩組亦無差別。然而，單一放射治療有較高的再治療率為21.5% (267/1,240)，相較於多次放射治療只有7.4% (91/1,236)，odds ratio為3.44 (95% CI為2.67−4.43)。單一放射治療亦有較高的病理性骨折發生率為3% (37/1,240)，相較於多次放射治療只有1.6% (20/1,236)，odds ratio為1.82 (95% CI為1.06−3.11)。兩組脊髓壓迫的發生率則差不多，odds ratio為1.41 (95% CI為0.72−2.75)。若排除中途放棄治療的病人，分析仍有類似的結果。

作者結論

單一次與多次放射治療對於緩解骨轉移所造成的疼痛一樣有效。但是，單一次放射治療會造成較高的再治療率，以及較高的病理性骨折發生率。要找出最佳的治療選擇，仍然需要有比較生活品質和健康經濟學的研究。

翻譯人

本摘要由臺灣大學附設醫院何承勳翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

骨頭轉移是許多惡性腫瘤的一個共同特點，包括前列腺癌，乳癌和肺癌。並可能與疼痛，脊髓壓迫和骨折有關。放射治療可以用於治療骨轉移，不過，治療的最佳時程設計目前還不清楚。本回顧比較單一次放射治療對於緩解骨轉移造成的相關症狀是否優於多次放射治療。在發表的文獻中，一共有11個隨機試驗，比較單一次與多次放射治療對於骨轉移的效果。整體分析這些試驗，發現單一次放射治療，在控制骨頭疼痛與多次放射治療一樣有效。然而，接受單一放射治療的病人有更多的骨折以及較高的再治療率。