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

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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 Gy10 (range: 48–76.8 Gy10) for early disease, and 76.8 Gy10 (range: 38.4–86.4 Gy10) for advanced disease. Median cumulative BED at ICRU 38 reference points (EBRT + ICBT) was 97.7 Gy3 (range: 59.1–134.4 Gy3) at the rectum, 97.8 Gy3 (range: 54.6–130.4 Gy3) at the bladder, and 324 Gy3 (range: 185.5–618 Gy3) 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 Gy10 at point A suffered both proctitis and enterocolitis. Patients with cumulative BED at rectal point of ≥100 Gy3 had significantly higher incidence of proctitis (31% vs. 4%, p = 0.013).

Conclusions

In view of the therapeutic ratio, cumulative BED 70–80 Gy10 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 Gy3 to prevent late rectal complication.

Introduction

High-dose-rate intracavitary brachytherapy (HDR-ICBT) has been widely used in treatment of uterine cervical cancer in Asia and Europe 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12. Despite some criticism of HDR-ICBT (13), its application has been increasing in the United States 14, 15. However, a wide variation of dose and fractionation schedules exists for the combination of external beam radiotherapy (EBRT) and HDR-ICBT 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 15, 16, 17, 18. An optimum treatment schedule has not yet been clearly determined.

In this paper, we retrospectively analyzed the dose–response relationship for local control and late complication for uterine cervical cancer patients treated with a combination of EBRT and HDR-ICBT. The aim of this study was to determine an appropriate dose and fractionation schedule for EBRT and HDR-ICBT in the treatment of uterine cervical cancer.

Section snippets

Patients

Three hundred and twelve patients with uterine cervical cancer had been treated with radiotherapy at the University of the Ryukyus Hospital between August 1994 and December 1999. From these, 71 patients treated postoperatively, 65 patients treated with chemotherapy, 53 patients treated with palliative intent (i.e., Stage IVB, recurrence), 15 patients without pretreatment MRI, 10 patients with adenocarcinoma, 6 patients who underwent external beam radiotherapy at other institutions, and 4

Results

Median follow-up time for all 88 patients was 48 months (range: 8–88 months), and 58 months (range: 27–88 months) for the surviving 65 patients. No patients were lost to follow-up.

Discussion

An appropriate dose and schedule of radiotherapy have been determined mainly on the bases of retrospective dose–response analyses of local control and late complications for several malignant tumors. Dose–response analysis on local control has usually been performed as a function of tumor size and total dose delivered (23). However, there are some difficulties in retrospective evaluation of these two factors for uterine cervical cancer. Table 7 shows the data from previously published

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This study was supported by Grants-in-Aid for Cancer Research No. 14–6 from the Ministry of Health and Welfare, Japan.

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