Department of Radiotherapy, Leiden University Medical Center, Leiden, The Netherlands.
Department of Gastroenterology and Hepatology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Int J Radiat Oncol Biol Phys. 2017 Jul 15;98(4):908-917. doi: 10.1016/j.ijrobp.2017.01.033. Epub 2017 Jan 20.
To evaluate the toxicity and efficacy of the combination of external beam radiation therapy (EBRT) followed by high-dose-rate endorectal brachytherapy (HDREBT) boost in elderly and medically inoperable patients with rectal cancer.
A phase 1 dose-escalation study was performed. Treatment consisted of EBRT (13 × 3 Gy) followed by 3 weekly brachytherapy applications 6 weeks later. The HDREBT dose started at 5 Gy per fraction, increasing with 1 Gy per fraction if dose-limiting toxicity (DLT, defined as grade ≥3 proctitis <6 weeks after HDREBT) occurred in ≤2 patients per dose level. The primary endpoint was the maximum tolerated dose, defined as 1 dose level below the dose at which 3 patients experienced DLT. Secondary endpoints were toxicity, clinical tumor response, freedom from local progression, and local progression-free and overall survival (L-PFS and OS).
Thirty-eight patients with a median age of 83 years were included in the study. Thirty-two were evaluable for DLT and late toxicity and 33 for response evaluation. Maximum delivered dose was 8 Gy per fraction, resulting in a recommended dose of 7 Gy per fraction. Response occurred in 29 of 33 patients (87.9%), with 60.6% complete response (CR). The L-PFS and OS rates were 42% and 63%, respectively, at 2 years. Patients with CR showed a significantly improved L-PFS (60% at 2 years, P=.006) and a trend in improved OS (80% at 2 years, P=.11). Severe late toxicity occurred in 10 of 32 patients.
We found that HDREBT after EBRT results in a high overall response rate, with improved L-PFS for patients with a CR. The high observed rate of severe late toxicity requires further evaluation of the risks and benefits of an HDREBT boost.
评估在老年和医学上不可手术的直肠癌患者中，采用外照射放射治疗（EBRT）联合高剂量率腔内近距离放射治疗（HDREBT）加量的毒性和疗效。
进行了一项 1 期剂量递增研究。治疗包括 EBRT（13×3Gy），然后在 6 周后进行 3 次每周腔内近距离放射治疗。HDREBT 剂量从每分次 5Gy 开始，如果在每个剂量水平下有 2 名患者出现剂量限制毒性（DLT，定义为 HDREBT 后 <6 周时出现≥3 级直肠炎），则每分次增加 1Gy。主要终点是最大耐受剂量，定义为 3 名患者出现 DLT 的剂量水平低 1 个剂量水平。次要终点是毒性、临床肿瘤反应、无局部进展、局部无进展生存（L-PFS）和总生存（OS）。
共有 38 名中位年龄为 83 岁的患者入组该研究。32 名患者可评估 DLT 和晚期毒性，33 名患者可评估反应。最大递送达剂量为每分次 8Gy，导致推荐剂量为每分次 7Gy。33 名患者中有 29 名（87.9%）出现反应，60.6%为完全缓解（CR）。2 年时 L-PFS 和 OS 率分别为 42%和 63%。CR 患者的 L-PFS 明显改善（2 年时为 60%，P=.006），OS 也有改善趋势（2 年时为 80%，P=.11）。32 名患者中有 10 名发生严重晚期毒性。
我们发现，EBRT 后进行 HDREBT 可导致总反应率高，CR 患者的 L-PFS 改善。严重晚期毒性的高发生率需要进一步评估 HDREBT 加量的风险和益处。
