Efficacy
The evidence supporting this protocol is provided by two meta analyses and a phase III multicentre international randomised trial.rrr
The 2014 Cochrane review by Liu et al. of 4 studies involving 1265 patients compared high dose rate (HDR) brachytherapy with low dose rate (LDR) intracavity brachytherapy (ICBT) in patients with locally advanced uterine cervix cancer (stage I-III).r They reported the 5- and 10-year pooled results for overall survival (OS) relative risk (RR) as 0.93 (95% CI 0.84 to 1.04) and 0.79 (95% CI 0.52 to 1.20), respectively. The disease specific survival (DSS) rates were 0.95 (95% CI 0.84 to 1.07) and 1.02 (95% CI 0.88 to 1.19) for 5 and 10 years, respectively. At 5 years, local control RR was 0.95 (95% CI 0.87 to 1.05) and RR 1.09 (95% CI 0.83 to 1.43) for locoregional recurrence. Both treatments were found to be equally efficacious in terms of OS, DSS, recurrence free survival (RFS), local control rates, recurrence and metastasis. For HDR treatment there was an increase in small bowel complications RR 3.37 (95% CI 1.06-10.72, p=0.04). HDR ICBT is recommended over LDR ICBT for all clinical stages of cervix cancer due to the potential advantages in the form of rigid immobilisation, outpatient treatment, patient convenience, accuracy of source and applicator positioning and individualised treatment.rrr
External beam radiation therapy (EBRT) and ICBT versus EBRT alone
ICBT is an integral component in radical radiation therapy for cervical cancer. There is a higher incidence of local failure if EBRT alone is used. Lanciano et al. analysed the pre-treatment and treatment factors which improved outcomes in the 1973 and 1978 patterns of care studies and found that the only treatment factor that had an impact on pelvic control rates was the use of ICBT.r
© IJRBP 1991.r
Han et al. reviewed the SEER database containing 7359 patients treated for stage IB2-IVA cervical cancer between 1988 and 2009.r Comparing those who received EBRT and brachytherapy vs EBRT alone, four-year cancer specific survival (CSS) was 64.3% vs 51.5% (p<0.001) and OS was 58.2% vs 46.2% (P<0.001), respectively. Despite the higher CSS and OS, a decline in the use of brachytherapy was seen from 83% in 1988 to 58% in 2009 (p<0.001).
Robin et al. reviewed the National Cancer Database (NCDB) containing 15194 patients treated for locally advanced cervical cancer between 2004 and 2012.r They reported that 49.5% of patients received EBRT and brachytherapy and overall survival was significantly higher than those who received EBRT alone (HR 0.554, p <0.001).
Figure 1. Kaplan-Meier survival curves comparing patients that received EBRT alone versus patients that received EBRT and brachytherapy.
Gynecol Oncol 2016r
Figure 2. Kaplan-Meier survival curves comparing patients that received EBRT alone versus patients that received EBRT with chemo versus patients that received EBRT and brachytherapy without chemotherapy versus patients that received standard of care (SOC) including EBRT with chemotherapy as well as a brachytherapy boost.
Gynecol Oncol 2016r
Alternative boost modalities
Gill et al. examined the NCDB containing 7654 patients with stage IIB-IVA cervical cancer treated with EBRT + brachytherapy boost, or EBRT + IMRT or SBRT boost from 2004-2011. They reported a decrease in the use of brachytherapy from 2004 to 2011 (96.7% to 86.1%) and a similar increase in SBRT and IMRT use (3.35% to 13.9%; p<0.01).r It was found that IMRT or SBRT boost resulted in inferior overall survival (HR 1.86; 95 CI 1.35-2.55, p<0.01) and increased toxicity when compared to brachytherapy.