Toita Takafumi, Kakinohana Yasumasa, Ogawa Kazuhiko, Adachi Genki, Moromizato Hidehiko, Nagai Yutaka, Maehama Toshiyuki, Sakumoto Kaoru, Kanazawa Koji, Murayama Sadayuki
Department of Radiology, University of the Ryukyus School of Medicine, Okinawa, Japan.
Int J Radiat Oncol Biol Phys. 2003 Aug 1;56(5):1344-53. doi: 10.1016/s0360-3016(03)00288-8.
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.
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.
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 > or =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 > or =100 Gy(3) had significantly higher incidence of proctitis (31% vs. 4%, p = 0.013).
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.
确定外照射放疗（EBRT）与高剂量率腔内近距离放疗（HDR-ICBT）联合治疗子宫颈癌的合适剂量及分割方案。
分析88例接受EBRT和HDR-ICBT治疗的子宫颈鳞状细胞癌患者。根据美国近距离放疗协会的定义，25例患者被归类为早期疾病（非大块I/II期，直径小于4cm），63例患者为晚期疾病（直径大于4cm或IIIB期）。通过MRI测量肿瘤直径。在进行ICBT之前先给予盆腔EBRT。HDR-ICBT每周进行一次，A点分次剂量为6Gy。源加载符合子宫颈癌的曼彻斯特系统。未进行计划优化。大多使用Henschke型施源器（86%）。早期疾病患者A点（EBRT + ICBT）的中位累积生物等效剂量（BED）为64.8Gy(10)（范围：48 - 76.8Gy(10)），晚期疾病患者为76.8Gy(10)（范围：38.4 - 86.4Gy(10)）。ICRU 38参考点（EBRT + ICBT）处直肠的中位累积BED为97.7Gy(3)（范围：59.1 - 134.4Gy(3)），膀胱为97.8Gy(3)（范围：54.6 - 130.4Gy(3)），阴道为324Gy(3)（范围：185.5 - 618Gy(3)）。根据累积剂量和计算的BED分析精算盆腔控制率和晚期并发症发生率。
88例患者的3年精算盆腔控制率为82%：早期疾病患者为96%，晚期疾病患者为76%。对于盆腔控制，早期和晚期疾病患者的治疗方案及A点累积BED均未观察到显著的剂量 - 反应关系。3年精算晚期并发症发生率（≥1级）：直肠炎为12%，膀胱炎为11%，小肠结肠炎为14%。治疗方案和A点累积BED在直肠炎（p < 0.0001）和小肠结肠炎（p < 0.0001）的发生率上存在显著差异，但膀胱炎无差异。A点接受86.4Gy(10)治疗的所有4例患者均患有直肠炎和小肠结肠炎。直肠点累积BED≥100Gy(3)的患者直肠炎发生率显著更高（31%对4%，p = 0.013）。
鉴于治疗比，A点累积BED 70 - 80Gy(10)适用于接受EBRT和HDR-ICBT联合治疗的子宫颈癌患者。目前的结果和其他文献数据表明，直肠点累积BED应保持在100 - 120Gy(3)以下以预防晚期直肠并发症。
