Department of Radiation Oncology, San Raffaele Scientific Institute, Milan, Italy.
Int J Radiat Oncol Biol Phys. 2013 Sep 1;87(1):67-72. doi: 10.1016/j.ijrobp.2013.05.004. Epub 2013 Jun 19.
To investigate the feasibility of preoperative adaptive radiochemotherapy by delivering a concomitant boost to the residual tumor during the last 6 fractions of treatment.
Twenty-five patients with T3/T4N0 or N+ rectal cancer were enrolled. Concomitant chemotherapy consisted of oxaliplatin 100 mg/m(2) on days -14, 0, and +14, and 5-fluorouracil 200 mg/m(2)/d from day -14 to the end of radiation therapy (day 0 is the start of radiation therapy). Radiation therapy consisted of 41.4 Gy in 18 fractions (2.3 Gy per fraction) with Tomotherapy to the tumor and regional lymph nodes (planning target volume, PTV) defined on simulation CT and MRI. After 9 fractions simulation CT and MRI were repeated for the planning of the adaptive phase: PTVadapt was generated by adding a 5-mm margin to the residual tumor. In the last 6 fractions a boost of 3.0 Gy per fraction (in total 45.6 Gy in 18 fractions) was delivered to PTVadapt while concomitantly delivering 2.3 Gy per fraction to PTV outside PTVadapt.
Three patients experienced grade 3 gastrointestinal toxicity; 2 of 3 showed toxicity before the adaptive phase. Full dose of radiation therapy, oxaliplatin, and 5-fluorouracil was delivered in 96%, 96%, and 88% of patients, respectively. Two patients with clinical complete response (cCR) refused surgery and were still cCR at 17 and 29 months. For the remaining 23 resected patients, 15 of 23 (65%) showed tumor regression grade 3 response, and 7 of 23 (30%) had pathologic complete response; 8 (35%) and 12 (52%) tumor regression grade 3 patients had ≤5% and 10% residual viable cells, respectively.
An adaptive boost strategy is feasible, with an acceptable grade 3 gastrointestinal toxicity rate and a very encouraging tumor response rate. The results suggest that there should still be room for further dose escalation of the residual tumor with the aim of increasing pathologic complete response and/or cCR rates.
研究在治疗的最后 6 个分数期间对残留肿瘤进行同步推量放疗的可行性。
25 例 T3/T4N0 或 N+直肠腺癌患者入组。同步化疗包括奥沙利铂 100mg/m²（第-14、0 和+14 天）和 5-氟尿嘧啶 200mg/m²/天（第-14 天至放疗结束）。放疗采用 Tomotherapy 进行，照射肿瘤和区域淋巴结（定义在模拟 CT 和 MRI 上的计划靶区[PTV]），总剂量为 41.4Gy，共 18 次，每次 2.3Gy。在 9 个分数后重复模拟 CT 和 MRI 以规划适应性阶段：通过向残留肿瘤添加 5mm 边界生成 PTVadapt。在最后 6 个分数中，对 PTVadapt 给予 3.0Gy/次的推量（总剂量为 18 次 45.6Gy），同时对 PTVadapt 外的 PTV 给予 2.3Gy/次。
3 例患者出现 3 级胃肠道毒性；其中 2 例在适应性阶段前出现毒性。96%、96%和 88%的患者分别接受了全剂量放疗、奥沙利铂和 5-氟尿嘧啶。2 例临床完全缓解（cCR）的患者拒绝手术，在 17 个月和 29 个月时仍为 cCR。对于其余 23 例接受手术的患者，23 例中有 15 例（65%）的肿瘤退缩分级为 3 级，7 例（30%）为病理完全缓解；肿瘤退缩分级为 3 级的 8 例（35%）和 12 例（52%）患者的肿瘤中残留活细胞分别为≤5%和 10%。
适应性推量策略是可行的，具有可接受的 3 级胃肠道毒性发生率和非常令人鼓舞的肿瘤反应率。结果表明，仍有进一步提高残留肿瘤剂量的空间，以提高病理完全缓解率和/或 cCR 率。
