Surgery After BRAF-Directed Therapy Is Associated with Improved Survival in BRAF^V600E Mutant Anaplastic Thyroid Cancer: A Single-Center Retrospective Cohort Study.

Content Provider	Europe PMC
Author	Zhao, Xiao Wang, Jennifer Rui Dadu, Ramona Busaidy, Naifa Lamki Xu, Lei Learned, Kim O. Chasen, Noah N. Vu, Thinh Maniakas, Anastasios Eguia, Arturo A. Diersing, Julia Gross, Neil D. Goepfert, Ryan Lai, Stephen Y. Hofmann, Marie-Claude Ferrarotto, Renata Lu, Charles Gunn, Gary Brandon Spiotto, Michael T. Subbiah, Vivek Williams, Michelle D. Cabanillas, Maria E. Zafereo, Mark E.
Copyright Year	2023
Abstract	Background: The aim of this study was to describe the oncologic outcomes of patients with BRAFV600E-mutated anaplastic thyroid cancer (ATC) who had neoadjuvant BRAF-directed therapy with subsequent surgery. For context, we also reviewed patients who received BRAF-directed therapy after surgery, and those who did not have surgery after BRAF-directed therapy. Methods: This was a single-center retrospective cohort study conducted at a tertiary care cancer center in Texas from 2017 to 2021. Fifty-seven consecutive patients with BRAFV600E-mutated ATC and at least 1 month of BRAF-directed therapy were included. Primary outcomes were overall survival (OS) and progression-free survival (PFS). Results: All patients had stage IVB (35%) or IVC (65%) ATC. Approximately 70% of patients treated with BRAF-directed therapy ultimately had surgical resection of residual disease. Patients who had neoadjuvant BRAF-directed therapy followed by surgery (n = 32) had 12-month OS of 93.6% [confidence interval (CI) 84.9–100] and PFS of 84.4% [CI 71.8–96.7]. Patients who had surgery before BRAF-directed therapy (n = 12) had 12-month OS of 74.1% [CI 48.7–99.5] and PFS of 50% [CI 21.7–78.3]. Finally, patients who did not receive surgery after BRAF-directed therapy (n = 13) had 12-month OS of 38.5% [CI 12.1–64.9] and PFS of 15.4% [CI 0–35.0]. Neoadjuvant BRAF-directed therapy reduced tumor size, extent of surgery, and surgical morbidity score. Subgroup analysis suggested that any residual ATC in the surgical specimen was associated with significantly worse 12-month OS and PFS (OS = 83.3% [CI 62.6–100], PFS = 61.5% [CI 35.1–88]) compared with patients with pathologic ATC complete response (OS = 100%, PFS = 100%). Conclusions: We observed that neoadjuvant BRAF-directed therapy reduced extent of surgery and surgical morbidity. While acknowledging potential selection bias, the 12-month OS rate appeared higher in patients who had BRAF-directed therapy followed by surgery as compared with BRAF-directed therapy without surgery; yet, it was not significantly different from surgery followed by BRAF-directed therapy. PFS appeared higher in patients treated with neoadjuvant BRAF-directed therapy relative to patients in the other groups. These promising results of neoadjuvant BRAF-directed therapy followed by surgery for BRAF-mutated ATC should be confirmed in prospective clinical trials.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC10122263&blobtype=pdf
Page Count	8
ISSN	10507256
Volume Number	33
DOI	10.1089/thy.2022.0504
PubMed Central reference number	PMC10122263
Issue Number	4
PubMed reference number	36762947
Journal	Thyroid
e-ISSN	15579077
Language	English
Publisher	Mary Ann Liebert, Inc., publishers
Publisher Date	2023-03-20
Publisher Place	USA
Access Restriction	Open
Rights License	This Open Access article is distributed under the terms of the Creative Commons License [CC-BY] (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © Xiao Zhao et al., 2023; Published by Mary Ann Liebert, Inc.
Subject Keyword	anaplastic thyroid cancer thyroid cancer BRAFV600E BRAF therapy neoadjuvant surgery
Content Type	Text
Resource Type	Article
Subject	Endocrinology, Diabetes and Metabolism Endocrinology