Combined use of hyperthermia and radiation therapy for treating locally advanced cervix carcinoma

Cure of cervix carcinomas can be achieved by complete surgical removal of the tumour or destruction of the tumour or by means of radiation. If the tumour has grown beyond the boundaries of the cervix or has reached a size larger than 4 cm in diameter it is designated as locally advanced cervix carcinoma. For such tumours surgery alone is considered insufficient and radiotherapy will be chosen instead. However, the larger the tumour, the smaller the chance that radiotherapy alone will be able to cure the tumour. In several clinical studies it was found that the respons of these tumours to radiotherapy was improved by adding hyperthermia. Hyperthermia is a type of cancer treatment in which body tissue is exposed to high temperatures (i.e. around 42 to 43 degrees Celcius during one hour) to damage and kill cancer cells.. This temperature is in itself able to kill tumour cells under certain conditions and also increases the lethal effect of radiation on tumour cells. can However, the results observed with this treatment were not consistent in subsequent clinical studies. Therefore we analysed the results of all clinical studies published so far comparing the treatment results of radiotherapy alone with the results of combined radiotherapy and hyperthermia in patients with locally advanced cervix carcinoma. The results do suggest a better outcome for patients treated with the combination of radiotherapy with hyperthermia. Thus following treatment a complete disappearance of the tumour was observed more regularly, regrowth of the tumour at the site of origin during follow up was observed less frequently and more patients were still alive at last follow-up. Treatment related side effects were not increased by the addition of hyperthermia to standard radiotherapy. However, the number of patients included in the clinical studies analysed is limited as the majority of patients had stage IIIB disease. The authors therefore conclude that hyperthermia may provide a clinically relevant improvement in treatment outcome for patients with locally advanced cervix carcinoma, in particular patients with stage IIIB disease. Additional clinical data are needed to warrant its use for all patients with locally advanced cervix carcinoma.

Authors' conclusions: 

The limited number of patients available for analysis, methodological flaws and a significant over-representation of patients with FIGO stage IIIB prohibit drawing definite conclusions regarding the impact of adding hyperthermia to standard radiotherapy. However, available data do suggest that the addition of hyperthermia improves local tumour control and overall survival in patients with locally advanced cervix carcinoma without affecting treatment related grade 3 to 4 acute or late toxicity.

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Background: 

Hyperthermia is a type of cancer treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells. It was introduced into clinical oncology practice several decades ago. Positive clinical results, mostly obtained in single institutions, resulted in clinical implementation albeit in a limited number of cancer centres worldwide. Because large scale randomised clinical trials (RCTs) are lacking, firm conclusions cannot be drawn regarding its definitive role as an adjunct to radiotherapy in the treatment of locally advanced cervix carcinoma (LACC).

Objectives: 

To assess whether adding hyperthermia to standard radiotherapy for LACC has an impact on (1) local tumour control, (2) survival and (3) treatment related morbidity.

Search strategy: 

The electronic databases of the Cochrane Central Register of Controlled Trials (CENTRAL), (Issue 1, 2009) and Cochrane Gynaecological Cancer Groups Specialised Register, MEDLINE, EMBASE, online databases for trial registration, handsearching of journals and conference abstracts, reviews, reference lists, and contacts with experts were used to identify potentially eligible trials, published and unpublished until January 2009.

Selection criteria: 

RCTs comparing radiotherapy alone (RT) versus combined hyperthermia and radiotherapy (RHT) in patients with LACC.

Data collection and analysis: 

Between 1987 and 2009 the results of six RCTs were published, these were used for the current analysis.

Main results: 

74% of patients had FIGO stage IIIB LACC. Treatment outcome was significantly better for patients receiving the combined treatment (Figures 4 to 6). The pooled data analysis yielded a significantly higher complete response rate (relative risk (RR) 0.56; 95% confidence interval (CI) 0.39 to 0.79; p < 0.001), a significantly reduced local recurrence rate (hazard ratio (HR) 0.48; 95% CI 0.37 to 0.63; p < 0.001) and a significantly better overall survival (OS) following the combined treatment with RHT(HR 0.67; 95% CI 0.45 to 0.99; p = 0.05). No significant difference was observed in treatment related acute (RR 0.99; 95% CI 0.30 to 3.31; p = 0.99) or late grade 3 to 4 toxicity (RR 1.01; CI 95% 0.44 to 2.30; p = 0.96) between both treatments.

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