小分子抑制剂治疗后伴有脑转移的晚期甲状腺癌的生存结果。

Survival Outcomes of Advanced Thyroid Cancer Enriched in Brain Metastases Following Treatment With Small Molecule Inhibitors.

机构信息

Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Palo Alto, California; Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio.

Department of Otolaryngology, Head and Neck Institute, Cleveland Clinic, Cleveland, Ohio.

出版信息

Endocr Pract. 2023 Nov;29(11):881-889. doi: 10.1016/j.eprac.2023.08.003. Epub 2023 Aug 18.

DOI:10.1016/j.eprac.2023.08.003

PMID:37597577

Abstract

OBJECTIVE

Small molecule inhibitors (SMIs) are targeted therapies increasingly used in advanced thyroid carcinomas. This study aimed to evaluate the survival outcomes of thyroid cancer on SMI treatment, including in patients with brain metastases.

METHODS

This retrospective study included patients with thyroid carcinomas who received at least one SMI between 2008 and 2022 at a tertiary level, academic institution. SMI included lenvatinib, sorafenib, dabrafenib-trametinib, selpercatinib, and cabozantinib. Patients were grouped by the presence of brain metastasis. Kaplan-Meier and log-rank tests modeled the overall survival (OS), defined from detection of first metastasis.

RESULTS

In total, 116 patients (49.1% female, median age 61.1 years [IQR, 51.1-71.0]) were included. Thyroid cancer subtypes were: 57 (49.6%) papillary, 23 (19.8%) anaplastic, 23 (19.8%) medullary, and 13 (11.2%) follicular. There were 18 (15.5%) patients with brain metastases, and 98 (84.5%) with visceral metastases. Age, sex, thyroid subtype, SMI, and time to recurrence were not different between cohorts. OS was shorter in the brain metastasis cohort (31.7 vs 42.2 months, P =.44) and was not different after excluding anaplastic thyroid cancer (29.1 vs 62.3 months, P =.21). In the case of papillary thyroid cancer, patients with brain metastases trended toward worse OS (22.0 vs 59.9 months, P =.13). Nonanaplastic histology, total thyroidectomy (OR, 40.0; P <.001), number of unique therapies (OR, 10.9; P =.047), and mutation-directed therapy (OR, 24.7; P =.003) were associated with improved OS.

CONCLUSION

This single-institutional analysis reports survival outcomes of 116 patients with advanced thyroid cancer on targeted therapies, including 18 patients with brain metastases. Mutation-directed therapy for BRAF mutations, RET mutations, RET fusions, and NTRK fusions had superior survival.

摘要

目的

小分子抑制剂（SMI）是越来越多地用于治疗晚期甲状腺癌的靶向治疗药物。本研究旨在评估甲状腺癌患者接受 SMI 治疗的生存结果，包括有脑转移的患者。

方法

本回顾性研究纳入了 2008 年至 2022 年期间在一家三级学术机构接受至少一种 SMI 治疗的甲状腺癌患者。SMI 包括仑伐替尼、索拉非尼、达拉非尼联合曲美替尼、塞尔帕替尼和卡博替尼。根据是否存在脑转移将患者分为两组。Kaplan-Meier 和对数秩检验用于建模总生存期（OS），OS 从首次转移检测开始计算。

结果

共纳入 116 例患者（49.1%为女性，中位年龄 61.1 岁[IQR，51.1-71.0]）。甲状腺癌亚型为：57 例（49.6%）为乳头状，23 例（19.8%）为间变性，23 例（19.8%）为髓样，13 例（11.2%）为滤泡状。有 18 例（15.5%）患者有脑转移，98 例（84.5%）有内脏转移。脑转移组和无脑转移组的年龄、性别、甲状腺亚型、SMI 和复发时间无差异。脑转移组的 OS 较短（31.7 与 42.2 个月，P=0.44），排除间变性甲状腺癌后无差异（29.1 与 62.3 个月，P=0.21）。在乳头状甲状腺癌患者中，有脑转移的患者 OS 趋势较差（22.0 与 59.9 个月，P=0.13）。非间变性组织学、甲状腺全切除术（OR，40.0；P<0.001）、独特治疗方案数量（OR，10.9；P=0.047）和针对突变的治疗（OR，24.7；P=0.003）与 OS 改善相关。