Akagi Y, Hirokawa Y, Kagemoto M, Matsuura K, Ito A, Fujita K, Kenjo M, Kiriu H, Ito K
Department of Radiology, Hiroshima University School of Medicine, Japan.
Int J Radiat Oncol Biol Phys. 1999 Feb 1;43(3):525-30. doi: 10.1016/s0360-3016(98)00433-7.
To establish the optimum fractionation for high-dose-rate (HDR) endoesophageal brachytherapy (EBT) for early stage esophageal cancer from retrospective data of patients treated with different HDR schedules following external beam irradiation (EBI).
The study population consisted of 35 consecutive early stage esophageal cancer patients who received EBI to the mediastinum, plus EBT, between May 1992 and November 1995 at the Hiroshima University Medical Center and Hiroshima City Hospital. All patients were treated with EBI, with doses ranging from 50 to 61 Gy. The spinal cord was spared after 44-45 Gy. HDR EBT was performed using a double-balloon applicator in conjunction with an Ir-192 remote afterloading system. One group of 10 patients was given a weekly endoesophageal boost of 4 or 5 Gy at a distance of 5 mm from the applicator surface over a period of 1-2 weeks. Another group of 25 patients was treated with 4 or 5 endoesophageal boosts with a fraction dose of either 2.5 or 2 Gy for 1 week. The linear quadratic (LQ) formula was used to calculate the biologically effective dose (BED) for tumor (Gy10) and esophageal mucosa (Gy3); Gy10 means alpha/beta equals 10 Gy, and Gy3 means alpha/beta equals 3 Gy. The Kaplan-Meier method was used to calculate the local control and late complication rates, while the Cox-Mantel test was used to evaluate statistical significance (p < 0.01).
Nine (26%) of the 35 patients recurred locally and 7 (20%) had late complications (esophageal ulcer grade by RTOG/EORTC criteria > 1). The 5-year overall survival, local control, and late complication rates were 38%, 57%, and 26%, respectively. The probability of local recurrence was not affected by the treatment parameters. Results from the LQ formula significantly correlate with data on late complications. A BED > 134 Gy3 and a fraction number = < 3 were associated with late complications (grade > 1). BED analysis showed that the fractionation dose should be decreased to 2.5 or 2.0 Gy at a distance of 5 mm from the applicator surface, and the number of doses increased to 4 or 5, respectively, to yield a satisfactory BED (< 134 Gy3).
A significant reduction in endoesophageal brachytherapy dose per fraction is necessary to reduce late complications. Our current treatment protocol for early-stage esophageal cancer consists of EBI of 60 Gy followed by 4 EBT doses at a fraction dose of 2.5 Gy applied over 1 week.
根据外照射（EBI）后采用不同高剂量率（HDR）方案治疗的患者回顾性数据，确定早期食管癌高剂量率腔内近距离放疗（EBT）的最佳分割方案。
研究人群包括1992年5月至1995年11月在广岛大学医学中心和广岛市立医院连续接受纵隔EBI加EBT的35例早期食管癌患者。所有患者均接受EBI治疗，剂量范围为50至61 Gy。脊髓在44 - 45 Gy后得到保护。使用双气囊施源器结合Ir - 192遥控后装系统进行HDR EBT。一组10例患者在距施源器表面5 mm处每周进行1 - 2周的腔内增量照射，每次4或5 Gy。另一组25例患者在1周内进行4或5次腔内增量照射，分次剂量为2.5或2 Gy。采用线性二次（LQ）公式计算肿瘤的生物等效剂量（BED，Gy10）和食管黏膜的生物等效剂量（BED，Gy3）；Gy10表示α/β等于10 Gy，Gy3表示α/β等于3 Gy。采用Kaplan - Meier法计算局部控制率和晚期并发症发生率，同时采用Cox - Mantel检验评估统计学意义（p < 0.01）。
35例患者中有9例（26%）出现局部复发，7例（20%）出现晚期并发症（按照RTOG/EORTC标准食管溃疡分级>1级）。5年总生存率、局部控制率和晚期并发症发生率分别为38%、57%和26%。局部复发概率不受治疗参数影响。LQ公式计算结果与晚期并发症数据显著相关。BED>134 Gy3且分次次数≤3次与晚期并发症（分级>1级）相关。BED分析表明，在距施源器表面5 mm处，分次剂量应降至2.5或2.0 Gy，分次次数分别增至4或5次，以获得满意的BED（<134 Gy3）。
为减少晚期并发症，必须显著降低腔内近距离放疗的每次分割剂量。我们目前早期食管癌的治疗方案包括60 Gy的EBI，随后在1周内进行4次EBT，分次剂量为2.5 Gy。
