American Brachytherapy Task Group Report: A pooled analysis of clinical outcomes for high-dose-rate brachytherapy for cervical cancer

Abstract

Purpose: Advanced imaging used in combination with brachytherapy (BT) has revolutionized the treatment of patients with cervical cancer. We present a comprehensive review of the literature for definitive radiation with high-dose-rate (HDR) BT. In addition, we investigate potential outcome improvement with image-based brachytherapy (IBBT) compared to studies using traditional Point A dosing. This review extensively investigates acute and late toxicities.

Methods and materials: This study reviews the literature from 2000 to 2015 with an emphasis on modern approaches including concurrent chemotherapy (chemoRT), radiation, and HDR BT and IBBT. Descriptive statistics and pelvic control (PC), disease-free survival (DFS), and overall survival (OS) outcomes were calculated using weighted means to report pooled analysis of outcomes.

Results: Literature search yielded 16 prospective, 51 retrospective studies that reported survival outcomes, and 13 retrospective studies that focused on acute and late toxicity outcomes regardless of applicator type. There are 57 studies that report Point A dose specification with 33 having chemoRT, and 10 studies that use IBBT, 8 with chemoRT. Patients receiving radiation and chemoRT with HDR BT in the prospective studies, with >24 months followup, rates of PC were: for RT: 73%, SD: 11; CRT: 82%, SD: 8; DFS-RT: 55%, SD: 10; CRT: 65%, SD: 7; OS-RT: 66%, SD: 7; CRT: 70%, SD: 11. In the retrospective studies, the PC rates (weighted means) for the radiation and chemoradiation outcomes are 75% vs. 80%, and for DFS, the values were 55% vs. 63%, respectively. Comparing patients receiving chemoRT and IBBT to traditional Point A dose specification, there is a significant improvement in PC (p < 0.01) and DFS (p < 0.01) with IBBT. The range of genitourinary late toxicity reported for radiation was Grade 3: 1-6% and for chemoRT 2-20%. The range of late gastrointestinal toxicity for radiation was Grade 3: 4-11% and for chemoRT, 1-11%. For the late gynecologic toxicity, only 1 of the 16 prospective trials report a Grade 1-2 of 17% for radiation and 9% for chemoRT effects.

Conclusions: We present concise outcomes of PC, DFS, OS, and toxicity for cervical cancer patients treated with chemoradiation and HDR BT. Our data suggest an improvement in outcomes with the use of IBBT compared with traditional Point A dose prescriptions. In conclusion, HDR BT is a safe, effective modality when combined with IBBT.

Keywords: Brachytherapy; Cervical cancer; HDR; Image guidance; Radiation.

Fig. 1

Search results. LDR = low-dose-rate; MDR = medium-dose-rate.

Fig. 2

Forest plot for the outcomes for the prospective studies. DFS = disease-free survival; OS = overall survival.

Fig. 3

Forest plot for the outcomes for the retrospective studies. DFS = disease-free survival; OS = overall survival.

Fig. 4

Forest plot comparison for the IBBT and non-IBBT studies. Comparison of chemoRT mean differences of the IBBT vs. Point A dosing studies for pelvic control (Study 1), DFS (Study 2), and OS (Study 3). IBBT = image-based brachytherapy; CI = confidence interval; DFS = disease-free survival; OS = overall survival; SMD = standardized mean difference.