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

Shannon S Wu; Eric D Lamarre; Joseph Scharpf; Brandon Prendes; Jamie A Ku; Natalie Silver; Brian Burkey; Neil Woody; Shauna R Campbell; Emrullah Yilmaz; Shlomo A Koyfman; Jessica Geiger

doi:10.1016/j.eprac.2023.08.003

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

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

Authors

Affiliations

¹ Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Palo Alto, California; Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio.
² Department of Otolaryngology, Head and Neck Institute, Cleveland Clinic, Cleveland, Ohio.
³ Department of Otolaryngology, Head and Neck Institute, Cleveland Clinic, Vero Beach, Florida.
⁴ Department of Radiation Oncology, Taussig Cancer Center, Cleveland Clinic, Cleveland, Ohio.
⁵ Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, Ohio.
⁶ Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, Ohio. Electronic address: geigerj@ccf.org.

PMID: 37597577
DOI: 10.1016/j.eprac.2023.08.003

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^V600E mutations, RET mutations, RET fusions, and NTRK fusions had superior survival.

Keywords: brain metastasis; papillary thyroid cancer; survival outcomes; thyroid cancer; tyrosine kinase inhibitors.

MeSH terms

Brain Neoplasms* / drug therapy
Female
Humans
Male
Middle Aged
Mutation
Proto-Oncogene Proteins B-raf / genetics
Retrospective Studies
Thyroid Cancer, Papillary
Thyroid Neoplasms* / pathology

Substances

Proto-Oncogene Proteins B-raf