Combination external beam radiotherapy and high-dose-rate intracavitary brachytherapy for uterine cervical cancer: Analysis of dose and fractionation schedule

Abstract

Purpose To determine an appropriate dose and fractionation schedule for a combination of external beam radiotherapy (EBRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT) for uterine cervical cancer. Methods Eighty-eight patients with uterine cervical squamous cell carcinoma treated with EBRT and HDR-ICBT were analyzed. Twenty-five patients were classified as early disease (nonbulky Stage I/II, less than 4-cm diameter) and 63 patients as advanced disease (greater than 4 cm diameter or Stage IIIB) according to the American Brachytherapy Society definition. Tumor diameter was measured by MRI. Pelvic EBRT was delivered before applications of ICBT. HDR-ICBT was performed once a week, with a fraction point A dose of 6 Gy. Source loadings corresponded to the Manchester System for uterine cervical cancer. No planned optimization was done. A Henschke-type applicator was mostly used (86%). Median cumulative biologic effective dose (BED) at point A (EBRT + ICBT) was 64.8 Gy 10 (range: 48–76.8 Gy 10) for early disease, and 76.8 Gy 10 (range: 38.4–86.4 Gy 10) for advanced disease. Median cumulative BED at ICRU 38 reference points (EBRT + ICBT) was 97.7 Gy 3 (range: 59.1–134.4 Gy 3) at the rectum, 97.8 Gy 3 (range: 54.6–130.4 Gy 3) at the bladder, and 324 Gy 3 (range: 185.5–618 Gy 3) at the vagina. Actuarial pelvic control rate and late complication rate were analyzed according to cumulative dose and calculated BED. Results The 3-year actuarial pelvic control rate was 82% for all 88 patients: 96% for those with early disease, and 76% for advanced disease. For pelvic control, no significant dose–response relationship was observed by treatment schedules and cumulative BED at point A for both early and advanced disease. The 3-year actuarial late complication rates (Grade ≥1) were 12% for proctitis, 11% for cystitis, and 14% for enterocolitis. There were significant differences on the incidence of proctitis ( p < 0.0001) and enterocolitis ( p < 0.0001), but not for cystitis by the treatment schedules and cumulative point A BED. All 4 patients treated with 86.4 Gy 10 at point A suffered both proctitis and enterocolitis. Patients with cumulative BED at rectal point of ≥100 Gy 3 had significantly higher incidence of proctitis (31% vs. 4%, p = 0.013). Conclusions In view of the therapeutic ratio, cumulative BED 70–80 Gy 10 at point A is appropriate for uterine cervical cancer patients treated with a combination of EBRT and HDR-ICBT. Present results and data from other literatures suggested that cumulative BED at the rectal point should be kept below 100–120 Gy 3 to prevent late rectal complication.