钙电穿孔治疗皮肤转移瘤——一项非随机、Ⅱ期多中心临床试验。

Calcium electroporation in cutaneous metastases - A non-randomised phase II multicentre clinical trial.

机构信息

Center for Experimental Drug and Gene Electrotransfer (C∗EDGE), Department of Clinical Oncology and Palliative Care, Zealand University Hospital, Roskilde and Næstved, Ringstedgade 61, 4700, Næstved, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark.

Department of Gynaecology and Obstetrics, University Hospital Schleswig-Holstein, Campus Lübeck, Germany Ratzeburger Allee 160, 23562, Lübeck, Germany.

出版信息

Eur J Surg Oncol. 2023 Sep;49(9):106925. doi: 10.1016/j.ejso.2023.04.024. Epub 2023 May 11.

DOI:10.1016/j.ejso.2023.04.024

PMID:37268521

Abstract

BACKGROUND

Cutaneous metastases can cause distressing symptoms and be challenging to treat. Local therapies are essential in management. Calcium electroporation uses calcium and electrical pulses to selectively kill cancer cells. This multicentre study aimed to define response in cutaneous metastases across different cancer types.

METHODS

Patients with tumours ≤3 cm of any histology were included (stable or progressing on current therapy ≥2 months), at three centres. Tumours were treated with 220 mM calcium chloride injection and manual application of eight 0.1 ms pulses with 1 kV/cm and 1Hz with a handheld electrode, in local or general anaesthesia. Clinical response was evaluated after 1, 2, 3, 4, 5, 6, and 12 months. Primary endpoint was response at two months. The overall response rate (ORR) was partial- and complete responses of treated tumours. MR-imaging and qualitative interviews were performed in respective subsets.

RESULTS

Nineteen patients with disseminated cancer (breast n = 4, lung n = 5, pancreatic n = 1, colorectal n = 2, gastric n = 1, and endometrial cancer n = 1) were enrolled, and 58 metastases were treated (50 once, 8 retreated). The ORR was 36% (95% CI 22-53) after two months. Best ORR was 51% (CR 42%; PR 9%). Previous irradiation improved outcomes (p = 0.0004). Adverse events were minimal. Median pain score was reduced after two months (p = 0.017). Treatment may relieve symptoms according to qualitative interviews. MRI showed restriction in treated tissue.

CONCLUSION

The majority of tumours were treated only once with calcium electroporation, achieving an ORR of 36% after two months and best ORR of 51%. Efficacy, symptom-relief and safety support calcium electroporation as a palliative treatment option for cutaneous metastases.

摘要

背景

皮肤转移瘤可引起痛苦的症状，并难以治疗。局部治疗是管理的关键。钙电穿孔利用钙和电脉冲选择性地杀死癌细胞。这项多中心研究旨在定义不同癌症类型的皮肤转移瘤的反应。

方法

纳入任何组织学类型的肿瘤≤3cm（当前治疗进展或稳定≥2个月）的患者，在三个中心进行。肿瘤用 220mM 氯化钙注射液治疗，并在局部或全身麻醉下手动应用 8 个 0.1ms 脉冲，电压为 1kV/cm，频率为 1Hz，使用手持式电极。治疗后 1、2、3、4、5、6 和 12 个月评估临床反应。主要终点是两个月时的反应。总体反应率（ORR）为治疗肿瘤的部分和完全反应。磁共振成像和定性访谈分别在相应的亚组中进行。

结果

纳入 19 名患有播散性癌症（乳腺癌 n=4、肺癌 n=5、胰腺癌 n=1、结直肠癌 n=2、胃癌 n=1 和子宫内膜癌 n=1）的患者，共治疗 58 个转移瘤（50 个首次治疗，8 个再次治疗）。两个月时的 ORR 为 36%（95%CI 22-53）。最佳 ORR 为 51%（完全缓解 42%；部分缓解 9%）。之前的放疗改善了结果（p=0.0004）。不良反应最小。治疗后两个月疼痛评分中位数降低（p=0.017）。根据定性访谈，治疗可能缓解症状。磁共振成像显示治疗组织受限。