High dose rate versus low dose rate brachytherapy in the treatment of stage IIIB cervical cancer, and the importance of brachytherapy timing

Purpose/Objective: To determine the efficacy of HDR versus LDR brachytherapy for Stage IIIB cervical cancer patients. Material and Methods: Forty-four HDR patients were retrospectively compared to 51 LDR patients treated at the same institution from 1977 to 1988 (LDR) and from 1989 to 1995 (HDR). A tumor burden score (TBS) of 2-9 was calculated for both groups of patients to assess volume of disease (2-4 low tumor burden, 5-9 high tumor burden). LDR and HDR patients received 60 Gy to the whole pelvis at 1.7 Gy/Fx. The majority of LDR patients were treated after completion of external beam radiation (EBR) with one 25 Gy implant to Point A (55 cGy/h). The HDR patients were treated with 4-5 HDR fractions of 3.7 Gy to 5.8 Gy/Fx for an LDR equivalence of 20-25 Gy (median dose/Fx 4.3 Gy, median insertion number 5). Clinical endpoints were calculated actuarially with significance determined by the log rank test and the relative risk (RR). Results: The median follow-up for the HDR and LDR groups was 1.8 and 5 years, respectively. Pelvic control and survival was better in the LDR group than the HDR group, 51%, 73%, 32%, 44% (p = 0.004, RR = 0.4), with grade III and above RTOG complications of 19% and 15%, respectively. The median age and performance status were similar between the two groups; however, a TBS score ≥7 was present in 23% of the HDR patients and in 9% of the LDR patients. Pelvic control in the HDR group was 58% with a TBS ≤4, and 17% with a TBS >4 (p = 0.01, RR = 0.4). The median EBR dose at the first HDR insertion was 31 Gy while all the LDR patients received 60 Gy before the insertion. Pelvic control rates in Table 1 indicate a trend towards improved outcome within the HDR group and same TBS if more external beam radiation was given prior to the first HDR insertion. Pelvic control was also higher within the HDR group when Point A received a BED Gy 10≥100 versus <100: 62%, 40%, respectively (RR 0.6). Conclusion: These retrospective results of HDR versus LDR brachytherapy for the treatment of Stage IIIB cervical cancer patients suggest lower survival and pelvic control for the HDR approach. Potential reasons for this include very high pelvic control rates in the LDR group, different patient cohorts with a higher TBS in the HDR group and performing the first HDR insertion before adequate tumor shrinkage. This trend became apparent over one year ago and dramatic changes in the HDR approach for Stage IIIB patients were implemented. These changes include performing the first insertion after 45 to 50 Gy of EBR, dose escalation to an LDR equivalent of 90 Gy and performing HDR fractionated interstitial brachytherapy in tumors that are poorly regressing. It appears that timing of the first HDR insertion with the EBR may be critical, and HDR brachytherapy should start only after adequate tumor shrinkage, possibly 45 Gy at a minimum. Finally, the literature at this point does not indicate that HDR is inferior to LDR in the treatment of Stage IIIB cervical cancer patients, and a high TBS at presentation may warrant more aggressive therapy