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Characteristics and outcomes of RET-rearranged Korean non-small cell lung cancer patients in real-world practice.

真实世界实践中 RET 重排韩国非小细胞肺癌患者的特征和结局。

  • 影响因子:2.04
  • DOI:10.1093/jjco/hyaa019
  • 作者列表:"Lee J","Ku BM","Shim JH","La Choi Y","Sun JM","Lee SH","Ahn JS","Park K","Ahn MJ
  • 发表时间:2020-02-21
Abstract

OBJECTIVE:Since the first discovery of rearranged during transfection (RET) fusion in lung adenocarcinoma in 2011, two tyrosine kinase inhibitors, namely vandetanib and cabozantinib, are currently available. Despite favorable outcomes in systemic control, the intracranial therapeutic response remains insufficient. In this study, the clinical characteristics and outcomes of non-small cell lung cancer (NSCLC) patients with RET rearrangements were analyzed. METHODS:Patients with NSCLC harboring RET fusion who received treatment between January 2006 and January 2018 were analyzed. RET rearrangement was identified by FISH or NGS. RESULTS:A total of 59 patients were identified. About half of the patients were female (47.5%) and never smokers (50.9%). Most patients had adenocarcinoma (89.8%). A total of 17 patients (28.8%) had an intracranial lesion at the initial diagnosis of stage IV disease, and 11 additional patients (18.6%) developed intracranial metastases during follow-up. The median time to development of intracranial metastases was 19.0 months (95% CI: 9.6-28.5), resulting in a >60% cumulative incidence of brain metastasis at 24 months. The systemic efficacy of pemetrexed-based regimens was favorable with progression-free survival of 9.0 (95% CI: 6.9-11.2) and OS of 24.1 (95% CI: 15.2-33.0) months. The median progression-free survival for vandetanib and immunotherapy was 2.9 (95% CI: 2.0-3.8) and 2.1 (95% CI: 1.6-2.6) months, respectively. CONCLUSIONS:Given the likelihood of RET-rearranged NSCLC progressing to intracranial metastases and the absence of apparent clinical benefit of currently available targeted or immunotherapeutic agents, development of novel treatment with higher selectivity and better penetration of the blood-brain barrier remains a priority.

摘要

目的: 自 2011年首次在肺腺癌中发现转染期间重排 (RET) 融合以来,目前已有两种酪氨酸激酶抑制剂,即凡德他尼和卡博替尼。尽管全身控制结果良好,但颅内治疗反应仍然不足。本研究对 RET 重排的非小细胞肺癌 (NSCLC) 患者的临床特征和转归进行了分析。 方法: 分析 2006年1月至 2018年1月接受治疗的携带 RET 融合的 NSCLC 患者。RET 重排通过 FISH 或 NGS 鉴定。 结果: 共确定 59 例患者。大约一半的患者是女性 (47.5%) 和从不吸烟者 (50.9%)。大多数患者为腺癌 (89.8%)。共有 17 例患者 (28.8%) 在最初诊断为 IV 期疾病时出现颅内病变,另外 11 例患者 (18.6%) 在随访期间发生颅内转移。发生颅内转移的中位时间为 19.0 个月 (95% CI: 9.6-28.5),导致 24 个月时脑转移的累积发生率> 60%。基于培美曲塞的方案的全身疗效良好,无进展生存期为 9.0 (95% CI: 6.9-11.2),OS 为 24.1 (95% CI: 15.2-33.0) 个月。凡德他尼和免疫治疗的中位无进展生存期分别为 2.9 (95% CI: 2.0-3.8) 和 2.1 (95% CI: 1.6-2.6) 个月。 结论: 考虑到 RET 重排 NSCLC 进展为颅内转移的可能性,以及目前可用的靶向或免疫治疗药物缺乏明显的临床获益, 开发具有更高选择性和更好渗透血脑屏障的新型治疗仍然是一个优先事项。

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影响因子:1.84
发表时间:2020-01-01
来源期刊:Oncology letters
DOI:10.3892/ol.2019.11149
作者列表:["Das SK","Huang YY","Li B","Yu XX","Xiao RH","Yang HF"]

METHODS::The aim of the present study was to compare the safety and efficacy of cryoablation (CA) and microwave ablation (MWA) as treatments for non-small cell lung cancer (NSCLC). Patients with stage IIIB or IV NSCLC treated with CA (n=45) or MWA (n=56) were enrolled in the present study. The primary endpoint was progression-free survival (PFS); the secondary endpoints included overall survival (OS) time and adverse events (AEs). The median PFS times between the two groups were not significantly different (P=0.36): CA, 10 months [95% confidence interval (CI), 7.5-12.4] vs. MWA, 11 months (95% CI, 9.5-12.4). The OS times between the two groups were also not significantly different (P=0.07): CA, 27.5 months (95% CI, 22.8-31.2 months) vs. MWA, 18 months (95% CI, 12.5-23.5). For larger tumors (>3 cm), patients treated with MWA had significantly longer median PFS (P=0.04; MWA, 10.5 months vs. CA, 7.0 months) and OS times (P=0.04; MWA, 24.5 months vs. CA, 14.5 months) compared patients treated with CA. However, for smaller tumors (≤3 cm), median PFS (P=0.79; MWA, 11.0 months vs. CA, 13.0 months) and OS times (P=0.39; MWA, 30.0 months vs. CA, 26.5 months) between the two groups did not differ significantly. The incidence rates of AEs were similar in the two groups (P>0.05). The number of applicators, tumor size and length of the lung traversed by applicators were associated with a higher risk of pneumothorax and intra-pulmonary hemorrhage in the two groups. Treatment with CA resulted in significantly less intraprocedural pain compared with treatment with MWA (P=0.001). Overall, the present study demonstrated that CA and MWA were comparably safe and effective procedures for the treatment of small tumors. However, treatment with MWA was superior compared with CA for the treatment of large tumors.

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