Adjuvant treatment of anaplastic oligodendrogliomas and oligoastrocytomas

  • Review
  • Intervention

Authors


Abstract

Background

Anaplastic oligodendrogliomas (AO) and anaplastic oligoastrocytomas (AOA) are known to be chemosensitive tumors. However, the impact of adding chemotherapy to surgery and radiotherapy has not been studied. Also, the value of chromosome 1p and 19q deletions as prognostic and predictive markers is only beginning to be defined.

Objectives

After surgery, to compare radiotherapy (RT) plus chemotherapy versus RT alone (standard of care) in adults with newly diagnosed AO or mixed AOA. To investigate the prognostic and predictive value of loss of heterozygosity of chromosomes 1p and 19q. Outcomes analyzed include overall survival (OS), progression-free survival (PFS), and treatment toxicity greater than or equal to grade 3.

Search methods

Cochrane Central Register for Controlled Trials (CENTRAL, Issue 4,2006), MEDLINE (1966 to 2006) and EMBASE (1988 to 2006) were searched. Reference lists from relevant studies were scanned for any additional relevant articles.

Selection criteria

RCTs of adults with AO or mixed AOA comparing surgery plus RT versus surgery plus RT plus chemotherapy were included. No specific chemotherapy regimens were excluded.

Data collection and analysis

Relevant studies were critically appraised and data was extracted. Based on the differences in patient selection with respect to the definition of AO (2 versus 3 high risk anaplastic features) and sequence of treatment (RT and chemotherapy), the results from the two RCTs were not able to be considered for meta-analysis.

Main results

Two RCTs have tested surgery plus RT plus early procarbazine, lomustine, and vincristine (PCV) chemotherapy versus surgery plus RT alone. Neither study observed a survival benefit with the addition of early PCV chemotherapy. However, both studies found a statistically significant increase in PFS associated with the administration of PCV chemotherapy before surgery or after surgery and RT, with the benefit ranging from 10 to 11 months. Co-deletion of chromosomes 1p and 19q identifies a favorable subgroup of tumors with better overall survival outcomes. The predictive value of 1p and 19q co-deletions is less clear with one study observing a longer PFS with chemotherapy, while the other study did not.

Authors' conclusions

Early PCV chemotherapy in addition to standard treatment of surgery and RT does not improve OS in patients with AO or AOA. However, it does improve PFS. It also is associated with significant toxicities. Tumors with 1p and 19q co-deletions are associated with better OS and may indicate a more chemo-responsive tumor.

摘要

背景

輔助性治療法治療未分化的寡樹突膠質細胞瘤(anaplastic oligodendroglioma)和星狀神經膠質細胞瘤(anaplastic oligoastrocytomas)

未分化的寡樹突膠質細胞瘤(AO)和星狀神經膠質細胞瘤(AOA)是已知對化療敏感的腫瘤(chemosensitive tumors),不過,至今仍未研究,手術和放射線療法加上化療對於病人的影響情形。此外,以染色體1p和19q缺失作為預後和預測性指標的才剛剛開始做評估。

目標

比較手術後,以放射線療法加上化療與單純放射線療法(標準照護)治療新近診斷為AO或混合型AOA的成人。研究調查染色體1p和19q異型(heterozygosity)缺失作為預後和預測性指標的價值性是需要的。結果分析包含了整體存活率(OS)、無惡化存活率(progressionfree survival, PFS) 和大於或相等於第3級的治療毒性。

搜尋策略

我們搜尋了Cochrane Central Register for Controlled Trials (CENTRAL, Issue 4, 2006) 、MEDLINE (1966年到2006年)和EMBASE (1988年到 2006年)等資料庫,也搜尋任何附加相關文獻中相關試驗的參考文獻。

選擇標準

我們只收納以「手術加上放射線療法」比較「手術加上放射線療法及化療」治療AO或混合型AOA成人的隨機對照試驗。沒有排除特定的化療方法。

資料收集與分析

從相關試驗中,嚴格地評估及數據摘錄。就AO(2與3高風險的未分化的特徵的定義)及後續的治療(放射線治療和化療)而言,以病人選擇作為差異的基準,有2份隨機對照試驗無法納入統合分析中。

主要結論

2份隨機對照試驗已經測試了,手術加上放射線治療及初期procarbazine、 lomustine和 vincristine (PCV) 化療藥物,與手術加上單純放射線治療,沒有任一試驗顯示附加初期PCV化療對病人存活的好處,不過,從2項試驗中發現到,在手術前或手術和放射線治療後,給予PCV化療,可以顯著地增加PFS,受益的範圍從10至11個月。共同缺失染色體1p和19q確定了對某些的腫瘤小組方面,是具有較佳的整體存活結果。在觀察到化療具有較長的PFS的1個試驗中,共同缺失1p和19q的預測價值並不顯著,另一個試驗則不然。

作者結論

除了標準的手術治療和RT之外,初期PCV化療不能改善AO或AOA病人的OS。不過,它卻可以改善PFS,但也產生明顯的毒性。在有較佳OS的1p and 19q共同缺失的腫瘤,可能顯示著更容易對化療有反應。

翻譯人

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

輔助性治療法治療未分化的寡樹突膠質細胞瘤(anaplastic oligodendroglioma)和星狀神經膠質細胞瘤(anaplastic oligoastrocytomas)

總結

AO和AOA都是屬於相對罕見的腦腫瘤,傳統上通常以在放射線治療後加上手術作為治療方法。從2份隨機對照試驗中顯示,雖然在標準療法加上Procarbazine、Iomustine 和PCV的化療,不能延長存活率,但是它確實能延遲這些腫瘤的惡化,不過,化學療法與很多嚴重的副作用是有關的。檢查這些腦瘤組織的病理樣品,特定染色體缺失可鑑定出,那些會有較佳存活結果的病人群組。

Plain language summary

Anaplastic oligodendrogliomas (AO) and anaplastic oligoastrocytomas (AOA) are relatively rare brain tumors. They have been traditionally treated with surgery followed by radiotherapy

Two randomized controlled trials (RCTs) have found that, although the addition of procarbazine, lomustine, and vincristine (PCV) chemotherapy to standard treatment does not prolong survival, it does delay progression of these tumors. However, this chemotherapy is associated with many serious side effects. Also, during pathologic examination of these brain tumor specimens, there are specific chromosome deletions which can identify a group of patients with better survival outcomes.