Literature analysis of high dose rate brachytherapy fractionation schedules in the treatment of cervical cancer: is there an optimal fractionation schedule?

PURPOSE

A literature review and analysis was performed to determine whether or not efficacious high dose rate (HDR) brachytherapy fractionation schedules exist for the treatment of cervical cancer.

METHODS AND MATERIALS

English language publications from peer reviewed journals were assessed to calculate the total contribution of dose to Point A from both the external and intracavitary portions of radiation for each stage of cervical cancer. Using the linear quadratic formula, the biologically effective dose to the tumor, using an alpha/beta = 10, was calculated to Point A (Gy10) in order to determine a dose response relationship for local control and survival. Significant complications were assessed by calculating the dose to the late-responding tissues at Point A using an alpha/beta = 3 (Gy3) as a surrogate for normal tissue tolerance, since few publications list the actual bladder and rectal doses.

RESULTS

For all stages combined, the median external beam fractionation schedule to Point A was 40 Gy in 20 fractions, while the median HDR fractionation schedule was 28 Gy in 4 fractions. For stages IB, IIB, and IIIB the median biologically effective dose to Point A (Gy10) was 96, 96 and 100 Gy10s, respectively. No correlation was identified between Point A BED (Gy10s) to either survival or pelvic control. A dose response relationship could also not be identified when correlating Point A Gy3s to complications.

CONCLUSION

A dose response relationship could not be identified for either tumor control nor late tissue complications. These findings do not necessarily question the validity of the linear quadratic model, as much as they question the quality of the current HDR brachytherapy literature as it is currently presented and reported. Most of the HDR publications report inadequate details of the dose fractionation schedules. Only a minority of publications report significant complications using the actuarial method. In the future, all HDR publications for the treatment of cervical cancer should provide accurate fractionation details for each stage of disease, while reporting actuarial complication rates. The optimal fractionation schedule for treating cervical cancer using HDR brachytherapy is still unknown, and presently can be based only on single institutions with significant experience.