Department of Radiation Oncology (MAASTRO Clinic), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
Eur J Cancer. 2012 Oct;48(15):2339-46. doi: 10.1016/j.ejca.2012.04.014. Epub 2012 May 18.
Sequential chemotherapy and individualised accelerated radiotherapy (INDAR) has been shown to be effective in non-small cell lung cancer (NSCLC), allowing delivering of high biological doses. We therefore performed a phase II trial (clinicaltrials.gov; NCT00572325) investigating the same strategy in concurrent chemo-radiation in stage III NSCLC.
137 stage III patients fit for concurrent chemo-radiation (PS 0-2; FEV(1) and DLCO ≥ 30%) were included from April 2006 till December 2009. An individualised prescribed dose based on normal tissue dose constraints was applied: mean lung dose (MLD) 19 Gy, spinal cord 54 Gy, brachial plexus 66 Gy, central structures 74 Gy. A total dose between 51 and 69 Gy was delivered in 1.5 Gy BID up to 45 Gy, followed by 2 Gy QD. Radiotherapy was started at the 2nd or 3rd course of chemotherapy. Primary end-point was overall survival (OS) and secondary end-point toxicity common terminology criteria for adverse events v3.0 (CTCAEv3.0).
The median tumour volume was 76.4 ± 94.1 cc; 49.6% of patients had N2 and 32.1% N3 disease. The median dose was 65.0 ± 6.0 Gy delivered in 35 ± 5.7 days. Six patients (4.4%) did not complete radiotherapy. With a median follow-up of 30.9 months, the median OS was 25.0 months (2-year OS 52.4%). Severe acute toxicity (≥ G3, 35.8%) consisted mainly of G3 dysphagia during radiotherapy (25.5%). Severe late toxicity (≥ G3) was observed in 10 patients (7.3%).
INDAR in concurrent chemo-radiation based on normal tissue constraints is feasible, even in patients with large tumour volumes and multi-level N2-3 disease, with acceptable severe late toxicity and promising 2-year survival.
序贯化疗和个体化加速放疗（INDAR）已被证明在非小细胞肺癌（NSCLC）中有效，能够提供高生物学剂量。因此，我们开展了一项 II 期临床试验（clinicaltrials.gov；NCT00572325），研究在 III 期 NSCLC 中同步放化疗中采用相同策略的效果。
2006 年 4 月至 2009 年 12 月，共纳入 137 例适合同步放化疗（PS 0-2；FEV1 和 DLCO≥30%）的 III 期患者。采用基于正常组织剂量限制的个体化规定剂量：平均肺剂量（MLD）19 Gy，脊髓 54 Gy，臂丛神经 66 Gy，中央结构 74 Gy。在 45 Gy 前，以 1.5 Gy BID 给予 51-69 Gy 总剂量，然后是 2 Gy QD。放疗在第 2 或第 3 个化疗疗程开始。主要终点是总生存（OS），次要终点是毒性（常见不良事件术语标准 3.0 版，CTCAEv3.0）。
肿瘤体积中位数为 76.4±94.1 cc；49.6%的患者有 N2 疾病，32.1%有 N3 疾病。中位剂量为 65.0±6.0 Gy，在 35±5.7 天内完成。有 6 例（4.4%）患者未完成放疗。中位随访 30.9 个月，中位 OS 为 25.0 个月（2 年 OS 为 52.4%）。严重急性毒性（≥G3）主要为放疗期间的 G3 吞咽困难（25.5%）。10 例（7.3%）患者出现严重迟发性毒性。
基于正常组织限制的同步放化疗中 INDAR 是可行的，即使在肿瘤体积较大和多水平 N2-3 疾病的患者中，也具有可接受的严重迟发性毒性和有前途的 2 年生存率。
