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.

Authors' conclusions: 

Further studies are needed to compare chemoradiation versus thermoradiation versus chemoradiation plus hyperthermia in well selected/conducted and quality controlled randomised trials.

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Background: 

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.

Objectives: 

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.

Search strategy: 

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.

Selection criteria: 

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).

Main results: 

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.

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