High dose rate versus low dose rate intracavity brachytherapy for locally advanced uterine cervix cancer

Background

Radiotherapy has been successfully used to treat cervical cancer for nearly a century as cervical tissue is very sensitive to radiation. Improved survival and local control rates of the disease have made the combination of external beam radiotherapy (EBRT) and intracavity brachytherapy (ICBT) the standard treatment for locally advanced uterine cervix cancer. ICBT is divided into three modalities, low dose rate (LDR), high dose rate (HDR), and medium dose rate (MDR). Many studies have concluded that the LDR was superior to the HDR as the post-treatment repair of normal tissue was better. Nevertheless, due to some potential advantages of HDRs in modern afterloading ICBT, HDR ICBT has increasingly been used, instead of LDR ICBT, over the past 20 years.

Review question

Despite the practical advantages of HDR, controversy still persists regarding the efficacy and safety of HDR compared to LDR brachytherapy. We conducted this review to assess the efficacy and safety of HDR versus LDR ICBT for women with locally advanced uterine cervical cancer.

Main findings

Four studies involving 1265 women were included in our meta-analysis to compare HDR and LDR ICBT. The pooled results indicated there were no significant difference with regard to 3-, 5- and 10-year overall survival rates; 5- and 10-year disease-specific survival rates; 3- and 5-year relapse-free survival; 3- and 5-year local control rates; and local and distant recurrence. Only in respect to complications did HDR ICBTshow mildly increased numbers of small bowel complications. These results confirmed that there were no significant differences in the efficacy and safety of HDR versus LDR ICBT for women with locally advanced uterine cervical cancer.

Quality of the evidence

We included three randomised controlled trials and one quasi-randomised controlled trial. The way that randomisation was carried out was described in only two trials but they did not give details regarding allocation concealment and blinding. However, all trials had a low risk bias for incomplete outcome data (attrition bias) and selective reporting (reporting bias). The different methodological approaches used in the trials prevented any clear conclusion being reached regarding the quality of the evidence. According to GRADE, the quality of the evidence was low to moderate.

Authors' conclusions: 

Since the last version of this review, no new studies were identified for inclusion in this review to provide additional information. This review showed no significant differences between HDR and LDR ICBT when considering OS, DSS, RFS, local control rate, recurrence, metastasis and treatment related complications for women with cervical carcinoma. Due to some potential advantages of HDR ICBT (rigid immobilization, outpatient treatment, patient convenience, accuracy of source and applicator positioning, individualized treatment) we recommend the use of HDR ICBT for all clinical stages of cervix cancer. The overall risk of bias was high for the included studies as many of the items were either of high or unclear risk. The GRADE assessment of the quality of the evidence was low to moderate.

Read the full abstract...
Background: 

This is an updated version of the original Cochrane review published in 2010 (Issue 7).

Carcinoma of the uterine cervix is the second most common cancer and the third leading cause of cancer death among women. Radiotherapy has been used successfully to treat cervical cancer for nearly a century. The combination of external beam radiotherapy (EBRT) and intracavity brachytherapy (ICBT) has become a standard treatment for cervical cancer. Whether high dose rate (HDR) or low dose rate (LDR) brachytherapy improves outcomes in terms of local control rates, survival and complications for women with cervical cancer remains controversial.

Objectives: 

To assess the efficacy and safety of HDR versus LDR ICBT in combination with EBRT for women with uterine cervical cancer.

Search strategy: 

We searched the Cochrane Gynaecological Cancer Group Specialised Register and the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 1), MEDLINE (1966 to March 2014), EMBASE (1974 to March 2014), and the Chinese Biomedical Literature Database (CBM) (1978 to March 2014) for relevant original, published trials.

Selection criteria: 

Randomised controlled trials (RCTs) and quasi-RCTs that compared HDR with LDR ICBT, combined with EBRT, for women with locally advanced uterine cervical cancer.

Data collection and analysis: 

Two authors independently extracted the data using standardised forms. Primary outcome measures included overall survival (OS), relapse-free survival (RFS) and pelvic control rate, while secondary outcomes included rates of recurrence and complications.

Main results: 

Four studies involving 1265 women met the inclusion criteria. In our meta-analysis to compare HDR and LDR ICBT, the pooled risk ratios (RRs) were 0.95 (95% confidence interval (CI) 0.79 to 1.15), 0.93 (95% CI 0.84 to 1.04) and 0.79 (95% CI 0.52 to 1.20) for 3-, 5- and 10-year overall survival rates respectively; and 0.95 (95% CI 0.84 to 1.07) and 1.02 (0.88 to 1.19) for 5- and 10-year disease-specific survival (DSS) rates respectively. The RR for RFS was 1.04 (95% CI 0.71 to 1.52) and 0.96 (95% CI 0.81 to 1.14) at 3- and 5- years. For local control rates the RR was 0.95 (95% CI 0.86 to 1.05) and 0.95 (95% CI 0.87 to 1.05) at 3- and 5- years; with a RR of 1.09 (95% CI 0.83 to 1.43) for locoregional recurrence, 0.79 (95% CI 0.40 to 1.53) for local and distant recurrence, 2.23 (95% CI 0.78 to 6.34) for para-aortic lymph node metastasis, and 0.99 (95% CI 0.72 to 1.35) for distance metastasis. For bladder, rectosigmoid and small bowel complications, the RR was 1.33 (95% CI 0.53 to 3.34), 1.00 (95% CI 0.52 to 1.91) and 3.37 (95% CI 1.06 to 10.72) respectively. These results indicated that there were no significant differences except for increased small bowel complications with HDRs (P = 0.04).

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