Department of Pulmonary Diseases, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.
Eur J Cardiothorac Surg. 2009 Dec;36(6):1052-7. doi: 10.1016/j.ejcts.2009.05.025. Epub 2009 Jul 17.
Concurrent chemoradiotherapy is standard of care in stage III non-small-cell lung cancer, although surgery may be beneficial in selected patients in whom induction therapy has achieved 'down-staging' of mediastinal nodal disease. Previous studies incorporated treatment 'splits' for re-evaluation, and such gaps lead to poorer survival in patients undergoing chemoradiotherapy. We describe the outcome of a treatment strategy to limit the duration of treatment splits.
A prospective database (2003-2007) of stage III non-small-cell lung cancer patients treated with concurrent chemoradiotherapy outwith clinical trials at our centre was reviewed. Preoperative chemoradiotherapy consisted of one induction course of cisplatin-gemcitabine, followed by two courses of cisplatin-etoposide with once-daily thoracic radiotherapy using four-dimensional involved-field treatment planning. After a dose of 46-50 Gy, potentially resectable patients without disease progression underwent immediate planned mediastinal re-staging and patients with persistent N2 disease or who were unfit for surgery continued to full-dose radiotherapy. Effort was made to shorten the treatment split by substituting mediastinoscopy for endoscopic procedures (transbronchial and -oesophageal).
A total of 34 patients had potentially resectable disease at the start of treatment. Toxicity of chemoradiotherapy was predominantly leucocytopaenia grade III/IV in 38% of courses and grade III oesophagitis in five patients (15%), but was manageable and reversible. After re-staging, 24 patients (71%) proceeded to surgery. A radical resection was achieved in 23 patients; nine had a complete pathological response. Re-staging was accurate with only one false-negative mediastinoscopy. One patient died 10 days after surgery. Median time from end of induction treatment to re-staging or surgery was 12 (range: 0-51 days) and 35 days (range: 18-63 days), respectively. Median survival for resected patients was not reached. Six patients had persisting N2 disease, of which two continued radiotherapy after a split of 3 and 4 days.
Image-guided, involved-field preoperative chemoradiotherapy can be performed with acceptable toxicity, and the present strategy achieves the goal of limiting splits in treatment delivery that may adversely affect survival in patients who do not undergo down-staging with induction therapy.
在 III 期非小细胞肺癌中，同步放化疗是标准治疗方法，尽管对于诱导治疗使纵隔淋巴结疾病降期的某些患者，手术可能有益。先前的研究纳入了治疗“分割”进行重新评估，而这种间断会导致接受放化疗的患者生存状况较差。我们描述了一种限制治疗分割持续时间的治疗策略的结果。
回顾了我们中心在临床试验之外用同步放化疗治疗 III 期非小细胞肺癌患者的前瞻性数据库（2003-2007 年）。术前放化疗包括顺铂-吉西他滨的一个诱导疗程，随后是两个顺铂-依托泊苷疗程，同时使用四维适形靶区治疗计划进行每日一次胸部放射治疗。在 46-50Gy 剂量后，没有疾病进展的潜在可切除患者立即进行计划的纵隔重新分期，如果存在持续性 N2 疾病或不适合手术的患者继续进行全剂量放疗。通过纵隔镜检查替代内镜（经支气管和经食管）来缩短治疗分割。
共有 34 名患者在治疗开始时具有潜在的可切除疾病。放化疗的毒性主要是白细胞减少症 III/IV 级，占 38%，有 5 例（15%）患者为 III 级食管炎，但可管理和逆转。重新分期后，24 名患者（71%）进行了手术。23 名患者实现了根治性切除，9 名患者获得了完全病理缓解。重新分期准确，只有 1 例纵隔镜检查假阴性。1 例患者术后 10 天死亡。从诱导治疗结束到重新分期或手术的中位时间分别为 12 天（范围：0-51 天）和 35 天（范围：18-63 天）。接受手术切除的患者中位生存期未达到。6 名患者存在持续性 N2 疾病，其中 2 名患者在分割 3 天和 4 天后继续放疗。
在可接受的毒性下，可进行图像引导的、适形靶区的术前放化疗，并且目前的策略实现了限制治疗交付分割的目标，这可能会影响接受诱导治疗而未降期的患者的生存。
