Cranial irradiation for preventing brain metastases of small cell lung cancer in patients in complete remission

 

Abstract

Background

Prophylactic cranial irradiation halves the rate of brain metastases in patients with small cell lung cancer. Individual randomized trials conducted on patients in complete remission were unable to clarify whether this treatment improves survival.

Objectives

This study aims to test whether prophylactic cranial irradiation prolongs survival of patients with small cell lung cancer in complete remission.

Search methods

Published and unpublished trials were eligible. Electronic databases (Medline, Cancerlit, Excerpta Medica, Biosis from 1965 to 1998), reference lists of trial publications, review articles and relevant books were used to identify potentially eligible trials. The search was also guided by discussions with investigators and experts, and the examination of meeting proceedings and of the Physician Data Query clinical trial registry.

Selection criteria

Randomized trials comparing prophylactic cranial irradiation with no prophylactic cranial irradiation in patients with small cell lung cancer in complete remission.

Data collection and analysis

Meta-analysis based on updated individual data. The main endpoint was survival.

Main results

Seven trials with a total of 987 participants were included. The relative risk of death in the treatment group compared to the control group was 0.84 (95% confidence interval=0.73 to 0.97, P=0.01), corresponding to a 5.4 percent increase in the 3-year survival rate (from 15.3 percent in the control group to 20.7 percent in the treatment group). Prophylactic cranial irradiation also increased disease-free survival (relative risk=0.75, 95% confidence interval=0.65 to 0.86, P<0.001) and decreased the risk of brain metastases (relative risk=0.46, 95% confidence interval=0.38 to 0.57, P<0.001). Increasing doses of irradiation decreased the risk of brain metastases when four groups (8 Gy, 24-25 Gy, 30 Gy, 36-40 Gy) were analyzed [trend test, P=0.02], but the effect on survival did not differ significantly according to the dose. We found a trend (P=0.01) for a decrease in the brain metastasis risk in favour of earlier administration of cranial irradiation after the initiation of induction treatment.

Authors' conclusions

Prophylactic cranial irradiation significantly improves survival and disease-free survival for patients with small cell lung cancer in complete remission. Further clinical trials are needed to confirm the potential greater benefit on brain metastasis rate suggested when cranial irradiation is given earlier or at higher doses.

 

Plain language summary

Prophylactic cranial irradiation improves survival rate of patients with small-cell lung cancer in complete remission

Small-cell lung cancer accounts for 20-25% of lung cancer. Treatment with chemotherapy and thoracic radiotherapy yields complete response rates of 50-85%. But, due to relapses, only 15% of patients who achieved complete response survived at 3 years since treatment. Tumour spread to brain (metastasis) is one of the main types of relapse, occurring in more than 50% of patients. Several clinical trials showed that prophylactic cranial irradiation (X-ray treatment of the brain for preventing brain metastasis) halves the rate of brain metastasis but they did not show whether this treatment can help people to live longer. This review found that prophylactic cranial irradiation given to patients in complete remission after initial treatment improves survival. At 3 years since treatment 20.7% of patients who received prophylactic cranial irradiation survived, compared to 15.3% for those who did not received this irradiation. Prophylactic cranial irradiation should now be considered part of the standard treatment of patients with small-cell lung cancer in complete remission.

 

摘要

背景

預防腦部轉移之腦部放射線治療在小細胞肺癌達到完全緩解病人的地位

預防性的腦部放射線治療使小細胞肺癌病人的腦部轉移發生率減半。在完全緩解的病人身上進行的個別隨機試驗無法澄清這治療是否提高生存。

目標

這個研究的目的在評估預防性腦部放射線治療是否能延長小細胞肺癌達到完全緩解病人的存活

搜尋策略

公開以及未公開的臨床試驗都符合資格。電子資料庫(Medline, Cancerlit, Excerpta Medica, Biosis from 1965 to 1998)、公開試驗的參考名單、回顧性的文章以及相關書籍都被用來辨識可能符合資格的試驗。同時，藉由與研究員和專家討論、檢驗研討會手冊和Physician Data Query臨床試驗名冊表來引導搜尋。

選擇標準

用隨機試驗來比較有無預防性的腦部放射線治療在小細胞肺癌完全緩解的病人的效力。

資料收集與分析

以最新的個別資料做統合分析。最主要的結果是存活率。

主要結論

收入7個試驗，總共有987個病人。治療組別和對照組別比較的相對死亡風險是0.84(95%的CI是0.73到0.97，P值是0.01)，並且相對應的在3年存活率上增加了5.4%。預防性腦部放射線治療也增加無病存活率(是0.75，95%的CI是0.65到0.86，P值＜0.001)和減少腦部轉移的風險(是0.46，95%的CI是0.38到0.57，P值＜0.001)。比較4個組別(8 Gy, 24 – 25 Gy, 30 Gy, 36 – 40 Gy)，增加放射線治療的劑量會減少腦部轉移的風險，但是對於存活的影響沒有顯著的差異。我們發現在開始給予誘導治療後盡早給予腦部放射線治療有降低腦部轉移的趨勢(P = 0.01。

作者結論

在小細胞肺癌達到完全緩解病人的身上，預防性的腦部放射線治療顯著的改善存活和無病的存活。將來需要更多的臨床試驗來確定何時給予或者是給予高劑量的腦部放射線治療對於腦部轉疑率有更多幫助。

翻譯人

本摘要由臺北榮民總醫院葉尚倫翻譯。

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

總結

預防性的腦部放射線治療改善了小細胞肺癌病人存活率並達到完全緩解。 小細胞肺癌佔了20 – 25%的肺癌，化學治療和胸部放射線治療達到的完全緩解率是50 – 85%。但是因為復發，只有13%的病人能從開始治療達到3年的完全緩解。腦部轉移是復發主要一種，發生在超過50%的病人。數個臨床試驗發現預防性腦部放射線治療使腦部轉移機率減半，但是並沒有有發現是否能延長存活。這篇回顧發現預防性腦部放射線治療改善了一開始治療達到緩解的病人的存活。開始治療後的三年，接受預防性腦部放射線治療的病人有20.7%存活；而沒接受預防性腦部放射線治療的病人有15.3%存活。現在必須把預防性腦部放射線治療考慮為小細胞肺癌達到完全緩解的病人的標準治療的一部份。