Concomitant hyperthermia and radiation therapy for treating locally advanced rectal cancer
Editorial Group: Cochrane Colorectal Cancer Group
Published Online: 8 JUL 2009
Assessed as up-to-date: 29 APR 2009
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
How to Cite
De Haas-Kock DFM, Buijsen J, Pijls-Johannesma M, Lutgens L, Lammering G, Mastrigt GAPGV, De Ruysscher DKM, Lambin P, van der Zee J. Concomitant hyperthermia and radiation therapy for treating locally advanced rectal cancer. Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No.: CD006269. DOI: 10.1002/14651858.CD006269.pub2.
- Publication Status: New
- Published Online: 8 JUL 2009
Surgery has been the treatment of choice for patients with rectal cancer. For locally advanced cancer results were poor, with high rates of locoregional recurrences and poor overall survival data. Adding (chemo)radiotherapy upfront improved results mainly in locoregional control. Adding hyperthermia to radiotherapy preoperatively might have an equivalent beneficial effect.
To quantify the potential beneficial effect of thermo radiation compared to chemo-radiation with respect to pathological complete responses, overall survival and toxicity in rectal cancer therapy.
We identified the relevant phase II and III randomised controlled trials in any language trough electronic searches May 2007 of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2007), the Cochrane Colorectal Cancer Groups Specialised Register, MEDLINE (from 1966), EMBASE (from 1974), CINAHL (from 1982). Furthermore, various trial databases were searched for the identification of recent completed and ongoing trials (metaRegister of Controlled Trials, Cancer Research UK, Cancer.gov, The Eastern Cooperative Oncology Group Trials Database). All studies identified until May 2007 were considered for inclusion in the present study.
Only phase II and III randomised controlled clinical trials were included in the analysis.
Data collection and analysis
All identified studies were assessed by two independent reviewers. A weighted estimate of the treatment effect was computed for 2, 3, 4 and 5-year survival, for local tumour recurrence, severe acute and late toxicity and complete tumour response (CR). CR was defined either clinically by disappearance of all pretreatment signs of local tumour or pathologically by microscopically free margins. The risk ratio (RR) and hazard ratio (HR) were used. Analyses were performed with the Reference Manager (RevMan).
Six RCTs published between 1990 and 2007 were identified. A total number of 520 patients was treated, 258 in the radiotherapy only arm (RT) and 262 in the radiotherapy-hyperthermia arm (RHT).
Four studies (424 patients) reported overall survival (OS) rates. After 2 years, OS was significantly better in the RHT group (HR 2.06; 95% CI 1.33-3.17; p=.001), but this difference disappeared after a longer period (3, 4 and 5 year OS).
All but one studies reported CR rates. A significant higher CR rate was observed in the RHT group (RR 2.81; 95% CI 1.22-6.45; p=.01).
Only 2 studies reported on acute toxicity. In these 2 studies no significant differences were observed between the RT and the RHT group. Late toxicity data were not reported.
Further studies are needed to compare chemoradiation versus thermoradiation versus chemoradiation plus hyperthermia in well selected/conducted and quality controlled randomised trials.
Plain language summary
Hyperthermia seems to have an additional effect when added to radiotherapy in the treatment of advanced rectal cancer.
In the past decades, radiotherapy with or without chemotherapy followed by surgery has become standard treatment for advanced rectal cancer. Chemotherapy is often added, because it enhances the effect of radiotherapy. Another method to amplify radiotherapy is heating the tumor (hyperthermia). In larger tumours there are often regions with a low oxygen concentration. Low oxygen concentrations may hamper the effect of radiotherapy. Hyperthermia can overcome this problem and is able to improve the efficacy of radiotherapy. This systematic review of the literature was done to study the additional value of hyperthermia if added to radiotherapy in advanced rectal cancer,
Six studies were found in which 520 patients were included. Of them 258 patients were treated with radiotherapy only and 262 with the combination of chemotherapy and radiation. Four of the six studies containing 424 patients reported overall survival rates (i.e. also patients who died from other causes than cancer were reported). Overall survival after 2 years was significantly better in the group treated with the combination of hyperthermia and radiotherapy, but this difference disappeared after a longer period (3, 4 and 5 years). Five studies reported complete remission rates, i.e. a complete disappearance of the tumour. The chance to develop a complete remission was significantly higher in the combined treated patient group. Only 2 studies reported on acute toxicity (that is in general any adverse effect that develops within 3 months during and after treatment). In these 2 studies no significant differences were observed between both treatment groups. Late toxicity data (adverse effects that developed during the years following treatment) were not reported.
In conclusion hyperthermia seems to have an additional effect when added to radiotherapy in the treatment of advanced rectal cancer. It is not possible to say if this effect is as strong as the combination of chemotherapy and radiotherapy. More well conducted studies are needed to draw firm conclusions.
我們確定了第二期與三期的隨機對照試驗,在任何語言的電子搜尋上.2007年五月 Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2007)the Cochrane Colorectal Cancer Groups Specialised Register, MEDLINE (from 1966), EMBASE (from 1974), CINAHL (from 1982).搜查各試驗數據庫，以查明最近完成和正在進行的試驗.(metaRegister of Controlled Trials, Cancer Research UK, Cancer.gov, The Eastern Cooperative Oncology Group Trials Database)，直到2007年5月所有的研究確認被列入本研究.
所有確定的研究由兩個獨立審評評估,衡量估計局部腫瘤復發,嚴重急性晚期毒性和完全腫瘤反應(CR),治療效果計算了2，3，4和5年生存率，完全腫瘤反應被定義是所有局部腫瘤治療前的徵兆在臨床上消失或顯微鏡下的病理顯示free margins.使用風險率(RR)和風險比(HR)。進行分析使用Reference Manager (RevMan).
確立6個隨機對照試驗的發表1990年至2007年.總數為520個被治療的患者,258例使用放射線治療only arm (RT) 262例使用高熱放射線療法 arm (RHT).四個研究(424 患者)總體生存率(OS)報告.兩年後使用高熱放射線療法(RHT)的總體生存率(OS)較好.(HR 2.06; 95% CI 1.33−3.17; p = .001),但是，這種差異消失後一段較長的時間(3，4和5年總體生存率)。但所有的研究，其中一個報告完全腫瘤反應率.在高熱放射線療法組裡有顯著較高的完全腫瘤反應率被觀察(RR 2.81; 95% CI 1.22−6.45; p = .01).只有兩個研究,急性毒性被報告.在放射線治療組與高熱放射線治療組之間,這兩個研究觀察並沒有顯著的差異.晚期毒性數據並沒有被報告.
此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌
在過去的幾十年,手術之後放射線治療有或沒有化學治療,已成為治療晚期直腸癌標準,化療往往被加入，因為它提高放射治療的效果.另一種方法是放大放射線治療加熱腫瘤(高溫).在較大的腫瘤往往有氧氣濃度低的地區.低氧氣濃度可能妨礙放射線治療的效果.熱療可以解決這個問題，並能提高放射治療的療效.系統審查文獻完成了研究如果晚期直腸癌高溫加上放射線治療的更高價值,6項研究發現，其中包括520例。其中258例只接受放射治療和262結合化療和放療.六個研究其中有四個包含424個患者被報告總體生存率.(即使是癌症患者死於其他原因).結合高熱與放射線療法這組,兩年的總體生存率顯然較好.但是長期(3, 4 and 5 年)差異就消失了.五個研究報告完全緩解率,腫瘤完全消失.在合併治療的患者群組中,完全緩解發展的機會顯著的比較高.只有兩個研究,急性毒性被報告(即在治療後三個月內,發展全身不良的影響).這2個研究觀察出在這兩個治療組之間無顯著差異的研究。晚期毒性數據(在治療後數年間發展出不利的影響),並沒有被報告.最後,在治療晚期直腸癌我們把高溫加在放射線治療似乎有附加的效果.我們不能說效果像結合化學治療和放射治療一樣強. 同時需要進行更多的研究去確立結論.