Department of Radiation Oncology, Calvary Mater Newcastle, Waratah, NSW, Australia.
School of Medicine and Public Health, University of Newcastle, Callaghan, NSW, Australia.
Radiat Oncol. 2022 Sep 14;17(1):158. doi: 10.1186/s13014-022-02127-x.
Many patients with incurable esophageal cancer (ECa) present with dysphagia as their predominant symptom. Currently there is no consensus on how best to initially manage this scenario with multiple therapeutic options available. We aimed to assess the safety and efficacy of using hypofractionated radiotherapy given over a progressively shorter timeframe with concurrent carboplatin and paclitaxel in the management of patients with ECa and dysphagia.
In this phase I trial we enrolled patients with histologically proven squamous cell carcinoma or adenocarcinoma of the esophagus or the gastro-esophageal junction with symptomatic dysphagia from local disease and not for curative treatment. Patients needed to be 18 years or older, have an ECOG performance status of 0-2 and be suitable to receive carboplatin and paclitaxel chemotherapy. Patients were placed in four progressively shorter radiation schedules culminating in 30 Gy in 10 fractions in a step wise manner, all with concurrent carboplatin AUC 2 and paclitaxel 50 mg/m chemotherapy delivered weekly with the radiation therapy. The primary endpoint was the development of the dose limiting toxicities (DLTs) esophageal perforation or febrile neutropenia. Secondary endpoints were relief of dysphagia, time to improvement of dysphagia, dysphagia progression free survival and overall survival.
Eighteen patients were enrolled in the study between October 2014 and March 2019. There were no DLTs experienced during the trial. The most common grade 3 + acute toxicity experienced by patients were nausea and vomiting (both in 4/18 patients). The most common radiation specific acute toxicity experienced was esophagitis with 67% of patients experiencing grade 1-2 symptoms. All patients experienced improvement in dysphagia. The median time to dysphagia improvement was 3 weeks from the start of chemoradiotherapy (CTRT) (range 2-10 weeks). The median dysphagia free survival was 5.8 months with a median overall survival of 8.9 months.
Hypofractionated palliative CTRT with 30 Gy/10# of radiation therapy with concurrent weekly carboplatin and paclitaxel chemotherapy is well tolerated and provides a good response in improvement of dysphagia. Further studies need to be undertaken which provide both symptomatic improvement in the primary tumor but also control of the metastatic burden in these patients.
This trial was prospectively registered with www.anzctr.org.au Identifier: ACTRN12614000821695.
许多无法治愈的食管癌（ECa）患者以吞咽困难为主要症状。目前，对于多种治疗方法，如何最好地初始管理这种情况尚无共识。我们旨在评估短程分次放射治疗联合卡铂和紫杉醇在管理伴有吞咽困难的 ECa 患者中的安全性和疗效。
在这项 I 期试验中，我们招募了患有组织学证实的食管或胃食管交界处鳞状细胞癌或腺癌且因局部疾病出现症状性吞咽困难且不适合进行根治性治疗的患者。患者必须年满 18 岁，ECOG 体能状态为 0-2，适合接受卡铂和紫杉醇化疗。患者被分为四个逐渐缩短的放射治疗方案，最终以 30Gy 分 10 次完成，所有患者均同时接受卡铂 AUC2 和每周一次的紫杉醇 50mg/m 化疗。主要终点是出现剂量限制毒性（食管穿孔或发热性中性粒细胞减少症）。次要终点是吞咽困难的缓解、吞咽困难改善的时间、吞咽困难无进展生存期和总生存期。
2014 年 10 月至 2019 年 3 月期间，共有 18 名患者入组该研究。在试验过程中没有发生剂量限制毒性。患者最常见的 3 级+急性毒性是恶心和呕吐（均为 4/18 例）。最常见的放射治疗相关急性毒性是食管炎，67%的患者出现 1-2 级症状。所有患者的吞咽困难均有改善。从放化疗开始（CTRT）到吞咽困难改善的中位时间为 3 周（范围 2-10 周）。中位吞咽困难无进展生存期为 5.8 个月，中位总生存期为 8.9 个月。
短程姑息性 CTRT 采用 30Gy/10#放射治疗，同时每周给予卡铂和紫杉醇化疗，耐受性良好，并能很好地改善吞咽困难。需要进一步开展研究，为这些患者提供原发性肿瘤的症状改善，并控制转移灶的负担。
该试验在 www.anzctr.org.au 进行了前瞻性注册，标识符为 ACTRN12614000821695。
