Washington University School of Medicine Saint Louis, MO
S. Kuchipudi1, Y. Huang1, T. Brown2, D. Adkins3, P. Oppelt3, N. Rammohan1, A. J. Apicelli III4, P. W. Grigsby1, and S. Markovina1; 1Washington University School of Medicine in St. Louis, Department of Radiation Oncology, St. Louis, MO, 2Washington University School of Medicine in St. Louis, Department of Surgery, St. Louis, MO, 3Department of Medicine, Division of Oncology, Washington University School of Medicine in St. Louis, St. Louis, MO, 4VA St. Louis Health Care System, Saint Louis, MO
Purpose/Objective(s): Anaplastic thyroid carcinoma (ATC) is rare and extremely aggressive. Survival has historically been poor with many patients presenting with distant metastases (DM), rapid progression of unresected disease, and recurrence after initial response to radiation therapy (RT). Recently, targeted therapies including kinase and immune checkpoint inhibitors have demonstrated efficacy in ATC. The optimal timing and integration with surgery, RT and chemotherapy remains unknown. The objective of this single-institution retrospective study is to report overall survival (OS) of patients with ATC during implementation of mutation analysis and targeted therapy. Materials/
Methods: Patient and tumor parameters for patients diagnosed with ATC were obtained from the medical record. OS was calculated from the date of diagnosis. Molecular analysis including BRAF IHC and/or targeted genetic sequencing was determined by commercial FDA-approved test. OS was compared between tumors with or without BRAF mutation, and between patients receiving targeted therapy or not using Kaplan Meier curves and Cox Proportional Hazard method with log-rank statistic. Results: A total of 111 patients were identified with ATC diagnosis from 1966 to 2022. Median follow-up was 5.6 months for the whole cohort, and 25.9 months for those alive at last follow-up. The median age at diagnosis was 65, and 51% of the patients were female. DM were present at diagnosis in 31.5% of patients. 41 patients (36.9%) underwent a total thyroidectomy (TT) and adjuvant external beam radiation therapy (EBRT), while 33.3% of the total cohort had tumor molecular analysis (n=37), beginning in 2014. OS was 30% at 24 months and 18% at 48 months. For patients receiving TT and EBRT, OS was 32% at 24 months and 23% at 48 months. For patients with available molecular tumor analysis, more common after 2019, OS 46% at 24 months and 32% at 48 months. Tumor BRAF status was known for 34 patients and those with BRAF mutation had worse OS compared to those with BRAF wild type tumor (p = 0.046). Patients who received targeted therapy (kinase or immune checkpoint inhibitors, n=14) had OS of 86% at 12 months, 78% at 24 months, compared to 26% at both time points for patients with tumor mutational analysis but did not receive targeted therapy (p = 0.0092). Median OS for patients presenting with DM who received targeted therapy was 24.2 months versus 25.9 months for those presenting without DM. Patients with p53 mutant tumors had worse median OS than those without (4.9 versus 13.9 months), though OS was similar for those who received targeted therapy (21.2 versus 27.6 months). In all cases targeted therapy was administered after primary surgery and/or RT. Conclusion: OS is improved in the molecular era for patients with ATC. BRAF and TP53 mutations are associated with worse OS. Without accounting for patient selection bias, those who received targeted therapy have favorable OS when administered in the adjuvant setting.
