Survival Outcomes of Thyroid Cancer Metastatic to Brain or Spinal Cord Following Treatment with Tyrosine Kinase Inhibitors

Presentation: S250
Topic: Immunotherapy / Systemic Therapy
Type: Oral
Date: Monday, July 10, 2023
Session: 2:00 PM - 3:30 PM Immunotherapy Session 2
Authors: Shannon S Wu1; Eric D Lamarre, MD2; Joseph Scharpf, MD2; Brian Burkey, MD3; Brandon Prendes, MD2; Jamie A Ku, MD2; Natalie Silver, MD2; Neil Woody, MD4; Shauna Campbell, MD4; Emrullah Yilmaz, MD, PhD5; Shlomo A Koyfman, MD4; Jessica L Geiger, MD5
Institution(s): 1Cleveland Clinic Lerner College of Medicine, Cleveland, OH; 2Department of Otolaryngology, Head and Neck Institute, Cleveland Clinic, Cleveland, OH; 3Department of Otolaryngology, Head and Neck Institute, Cleveland Clinic, Vero Beach, FL; 4Department of Radiation Oncology, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH; 5Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, OH

Background: Radioactive iodine (RAI) therapy is a successful targeted therapy in many patients with differentiated thyroid carcinoma; however, RAI-refractory disease carries a poorer prognosis relative to RAI sensitive disease. While metastasis to the brain or spinal cord in RAI-refractory thyroid cancer is relatively rare, such patients may carry a further worsened prognosis. With the emergence of tyrosine kinase inhibitors (TKI), we reviewed our institutional experience with survival outcomes of thyroid cancer patients receiving a TKI with and without brain and spinal cord metastases.

Methods: Patients with thyroid carcinoma treated at a tertiary-care, academic institution between 1/2005 and 10/2022 were queried from an IRB-approved database. Patients were included if they were diagnosed with any type of biopsy-proven thyroid carcinoma and received at least one TKI. Patients were grouped by presence or absence of metastasis to the central nervous system (CNS), as confirmed by radiographic imaging of metastasis to the brain or spinal cord. Kaplan-Meier method and log-rank test modeled overall survival (OS), defined from the time of detection of metastasis.

Results: In total, 117 patients (48.7% female, median age at diagnosis 61.2 years [IQR, 61.3-71.0], 47.0% current or former smokers) met inclusion criteria. Median follow-up time after initial thyroid cancer diagnosis was 6.0 years (IQR, 2.1-10.6). Thyroid cancer subtypes were as follows: 58 (49.6%) papillary, 23 (19.7%) anaplastic, 23 (19.7%) medullary, and 13 (11.1%) follicular. Thyroidectomy was performed in 96 (82.1%) patients, 67 (57.3%) patients received RAI, and 41 (35.0%) patients received definitive or postoperative radiation therapy. There were 32 (29.1%) tumors with lymphovascular invasion, 29 (24.8%) with extrathyroidal extension, and 8 (6.8%) with perineural invasion. There were 23 (19.7%) patients with CNS metastases, and 94 (80.3%) patients with non-CNS metastases, which were most commonly to lung, bone, or liver. Lenvatinib (n=62, 53.0%) was the most common TKI received, followed by sorafenib (n=26, 22.2%) dabrafenib/trametinib (n=23, 19.7%), selpercatinib (n=13, 11.1%), and cabozantinib (n=12, 10.3%). Median total duration on TKI was 6.5 months (IQR, 2.2-22.1), and median OS was 37.8 months (95% CI, 31.7-58.6). There were no significant differences in age, sex, thyroid subtype, TKI, duration of TKI, time to TKI initiation, or time to recurrence between CNS and non-CNS groups. Differences in OS did not achieve statistical significance when compared between CNS and non-CNS metastasis groups (median OS: 22.0 months [95% CI, 8.0-60.9] versus 42.2 months [95% CI, 33.0-62.3], respectively, p=0.131). OS outcomes were not significantly different after excluding ATC patients from the analysis (median OS: 50.0 months [95% CI, 7.4-91.9] versus 62.3 months [95% CI, 37.1-84.8] for CNS and non-CNS, respectively, p=0.366).

Conclusion: Patients with thyroid cancer metastatic to the brain or spinal cord had a median survival deficit of 20 months despite TKI treatment, compared to patients with non-CNS metastases. Although subgroup analyses stratified by thyroid carcinoma subtype were underpowered, CNS metastases trended towards worse OS. Future multi-institutional studies are needed to investigate TKI efficacy in patients with CNS-metastatic thyroid cancer.