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1. BRAF v600E–mutant cancers treated with vemurafenib alone or in combination with everolimus, sorafenib, or crizotinib or with paclitaxel and carboplatin (VEM-PLUS) study

Author

Nelson, Blessie Elizabeth, Roszik, Jason, Janku, Filip, Hong, David S., Kato, Shumei, Naing, Aung, Piha-Paul, Sarina, Fu, Siqing, Tsimberidou, Apostolia, Cabanillas, Maria, Busaidy, Naifa Lamki, Javle, Milind, Byers, Lauren Averett, Heymach, John V., Meric-Bernstam, Funda, and Subbiah, Vivek

Published
2023
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2. Atezolizumab plus taxane chemotherapy for the treatment of non-BRAF, non-RAS mutated anaplastic thyroid carcinoma: Final analysis.

Author

Hamidi, Sarah, primary, Dadu, Ramona, additional, Ferrarotto, Renata, additional, Gule-Monroe, Maria, additional, Liu, Suyu, additional, Fellman, Bryan M., additional, Williams, Michelle D., additional, Zafereo, Mark E., additional, Wang, Rui Jennifer, additional, Lu, Charles, additional, Ning, Matthew S., additional, McKinley, Brian, additional, Woodman, Scott Eric, additional, Duose, Dzifa Yawa, additional, Gunn, Gary Brandon, additional, Busaidy, Naifa Lamki, additional, and Cabanillas, Maria E., additional

Published
2024
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3. Anaplastic transformation in thyroid cancer revealed by single-cell transcriptomics

Author

Lu, Lina, Wang, Jennifer Rui, Henderson, Ying C., Bai, Shanshan, Yang, Jie, Hu, Min, Shiau, Cheng-Kai, Pan, Timothy, Yan, Yuanqing, Tran, Tuan M., Li, Jianzhuo, Kieser, Rachel, Zhao, Xiao, Wang, Jiping, Nurieva, Roza, Williams, Michelle D., Cabanillas, Maria E., Dadu, Ramona, Busaidy, Naifa Lamki, Zafereo, Mark, Navin, Nicholas, Lai, Stephen Y., and Gao, Ruli

Subjects
Thyroid cancer -- Development and progression -- Genetic aspects, Genetic transcription -- Health aspects, Cell transformation -- Genetic aspects -- Health aspects, Health care industry
Abstract

The deadliest anaplastic thyroid cancer (ATC) often transforms from indolent differentiated thyroid cancer (DTC); however, the complex intratumor transformation process is poorly understood. We investigated an anaplastic transformation model by dissecting both cell lineage and cell fate transitions using single-cell transcriptomic and genetic alteration data from patients with different subtypes of thyroid cancer. The resulting spectrum of ATC transformation included stress-responsive DTC cells, inflammatory ATC cells (iATCs), and mitotic-defective ATC cells and extended all the way to mesenchymal ATC cells (mATCs). Furthermore, our analysis identified 2 important milestones: (a) a diploid stage, in which iATC cells were diploids with inflammatory phenotypes and (b) an aneuploid stage, in which mATCs gained aneuploid genomes and mesenchymal phenotypes, producing excessive amounts of collagen and collagen-interacting receptors. In parallel, cancer- associated fibroblasts showed strong interactions among mesenchymal cell types, macrophages shifted from M1 to M2 states, and T cells reprogrammed from cytotoxic to exhausted states, highlighting new therapeutic opportunities for the treatment of ATC., Introduction Anaplastic thyroid cancer (ATC), characterized by an undifferentiated morphology, is arguably one of the most lethal malignancies. According to Surveillance, Epidemiology and End Results (SEER) data (released April 2021) [...]

Published
2023
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4. Anaplastic Thyroid Carcinoma, Version 2.2015.

Author

Haddad, Robert I, Lydiatt, William M, Ball, Douglas W, Busaidy, Naifa Lamki, Byrd, David, Callender, Glenda, Dickson, Paxton, Duh, Quan-Yang, Ehya, Hormoz, Haymart, Megan, Hoh, Carl, Hunt, Jason P, Iagaru, Andrei, Kandeel, Fouad, Kopp, Peter, Lamonica, Dominick M, McCaffrey, Judith C, Moley, Jeffrey F, Parks, Lee, Raeburn, Christopher D, Ridge, John A, Ringel, Matthew D, Scheri, Randall P, Shah, Jatin P, Smallridge, Robert C, Sturgeon, Cord, Wang, Thomas N, Wirth, Lori J, Hoffmann, Karin G, and Hughes, Miranda

Subjects
Rare Diseases, Cancer, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Antineoplastic Combined Chemotherapy Protocols, Carboplatin, Docetaxel, Doxorubicin, Humans, Paclitaxel, Radiotherapy, Intensity-Modulated, Taxoids, Thyroid Carcinoma, Anaplastic, Thyroid Neoplasms, Thyroidectomy, Oncology & Carcinogenesis
Abstract

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Thyroid Carcinoma focuses on anaplastic carcinoma because substantial changes were made to the systemic therapy recommendations for the 2015 update. Dosages and frequency of administration are now provided, docetaxel/doxorubicin regimens were added, and single-agent cisplatin was deleted because it is not recommended for patients with advanced or metastatic anaplastic thyroid cancer.

Published
2015

6. A phase 2 study of neoadjuvant lenvatinib in locally advanced invasive thyroid cancer.

Author

Abdelhamid Ahmed, Amr Hesham, primary, Russell, Marika D., additional, Kyriazidis, Natalia, additional, Silver Karcioglu, Amanda, additional, Sherman, Eric Jeffrey, additional, Ho, Alan Loh, additional, Fagin, James A, additional, Wong, Richard J., additional, Busaidy, Naifa Lamki, additional, Zafereo, Mark E., additional, Sadow, Peter, additional, Park, Jong Chul, additional, Wirth, Lori J., additional, and Randolph, Gregory W., additional

Published
2023
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7. Abstract 3131: Anaplastic transformation model in thyroid cancer revealed by single cell lineage and fate analysis

Author

Lu, Lina, primary, Wang, Jennifer Rui, additional, Henderson, Ying C., additional, Bai, Shanshan, additional, Yang, Jie, additional, Hu, Min, additional, Yan, Yuanqing, additional, Tran, Tuan M, additional, Li, Jianzhuo, additional, Shiau, Cheng-Kai, additional, Kieser, Rachel, additional, Zhao, Xiao, additional, Wang, Jiping, additional, Nurieva, Roza, additional, Williams, Michelle D., additional, Cabanillas, Maria E., additional, Dadu, Ramona, additional, Busaidy, Naifa Lamki, additional, Zafereo, Mark, additional, Navin, Nicholas, additional, Lai, Stephen Y., additional, and Gao, Ruli, additional

Published
2023
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8. Surgery After BRAF-Directed Therapy Is Associated with Improved Survival in BRAFV600E Mutant Anaplastic Thyroid Cancer: A Single-Center Retrospective Cohort Study

Author

Zhao, Xiao, primary, Wang, Jennifer Rui, additional, Dadu, Ramona, additional, Busaidy, Naifa Lamki, additional, Xu, Lei, additional, Learned, Kim O., additional, Chasen, Noah N., additional, Vu, Thinh, additional, Maniakas, Anastasios, additional, Eguia, Arturo A., additional, Diersing, Julia, additional, Gross, Neil D., additional, Goepfert, Ryan, additional, Lai, Stephen Y., additional, Hofmann, Marie-Claude, additional, Ferrarotto, Renata, additional, Lu, Charles, additional, Gunn, Gary Brandon, additional, Spiotto, Michael T., additional, Subbiah, Vivek, additional, Williams, Michelle D., additional, Cabanillas, Maria E., additional, and Zafereo, Mark E., additional

Published
2023
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10. Thyroid Carcinoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology

Author

Haddad, Robert I, primary, Bischoff, Lindsay, additional, Ball, Douglas, additional, Bernet, Victor, additional, Blomain, Erik, additional, Busaidy, Naifa Lamki, additional, Campbell, Michael, additional, Dickson, Paxton, additional, Duh, Quan-Yang, additional, Ehya, Hormoz, additional, Goldner, Whitney S., additional, Guo, Theresa, additional, Haymart, Megan, additional, Holt, Shelby, additional, Hunt, Jason P., additional, Iagaru, Andrei, additional, Kandeel, Fouad, additional, Lamonica, Dominick M., additional, Mandel, Susan, additional, Markovina, Stephanie, additional, McIver, Bryan, additional, Raeburn, Christopher D., additional, Rezaee, Rod, additional, Ridge, John A., additional, Roth, Mara Y., additional, Scheri, Randall P., additional, Shah, Jatin P., additional, Sipos, Jennifer A., additional, Sippel, Rebecca, additional, Sturgeon, Cord, additional, Wang, Thomas N., additional, Wirth, Lori J., additional, Wong, Richard J., additional, Yeh, Michael, additional, Cassara, Carly J., additional, and Darlow, Susan, additional

Published
2022
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11. Surgery After BRAF-Directed Therapy Is Associated with Improved Survival in BRAFV600E Mutant Anaplastic Thyroid Cancer: A Single-Center Retrospective Cohort Study.

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., and Subbiah, Vivek

Subjects
ANAPLASTIC thyroid cancer, NEOADJUVANT chemotherapy, COHORT analysis, SURGERY, PROGRESSION-free survival
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. [ABSTRACT FROM AUTHOR]

Published
2023
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12. Prognostic factors in RET dependent cancers treateded with RET inhibitors in early phase clinical trials.

Author

Gordon, Max, primary, Roszik, Jason, additional, Cabanillas, Maria E., additional, Hu, Mimi I-Nan, additional, Busaidy, Naifa Lamki, additional, Sherman, Steven I., additional, Dadu, Ramona, additional, Grubbs, Elizabeth Gardner, additional, Elamin, Yasir Y, additional, Cascone, Tina, additional, Byers, Lauren Averett, additional, Blumenschein, George R., additional, Fossella, Frank V., additional, Naing, Aung, additional, Hong, David S., additional, Heymach, John, additional, Meric-Bernstam, Funda, additional, and Subbiah, Vivek, additional

Published
2021
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14. Atezolizumab combinations with targeted therapy for anaplastic thyroid carcinoma (ATC).

Author

Cabanillas, Maria E., primary, Dadu, Ramona, additional, Ferrarotto, Renata, additional, Liu, Suyu, additional, Fellman, Bryan M., additional, Gross, Neil D., additional, Gule-Monroe, Maria, additional, Lu, Charles, additional, Grosu, Horiana, additional, Williams, Michelle D., additional, Duose, Dzifa Yawa, additional, Mallampati, Saradhi, additional, Dervin, Shannon, additional, Mckenna, Edward Francis, additional, Wang, Rui Jennifer, additional, Zafereo, Mark, additional, and Busaidy, Naifa Lamki, additional

Published
2020
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15. MON-491 TRK-Fusion Thyroid Cancer: A Clinical Overview in a Large Population at a Single Cancer Center

Author

Fazeli, Sasan, primary, Dadu, Ramona, primary, Waguespack, Steven G, primary, Sherman, Steven I, primary, Busaidy, Naifa Lamki, primary, Hu, Mimi I, primary, Jimenez, Camilo, primary, Habra, Mouhammed A, primary, Williams, Michelle, primary, Altameemi, Lina, primary, Poropatich, Kate, primary, Routbort, Mark J, primary, Luthra, Raja, primary, Patel, Keyur P, primary, and Cabanillas, Maria, primary

Published
2020
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17. High/low dose dexamethasone with physical activity for cancer-related fatigue in patients with advanced cancer: A phase II randomized double blind study.

Author

Yennu, Sriram, primary, Valero, Vicente, additional, Lim, Bora, additional, Booser, Daniel J., additional, Hernandez, Carolina Diaz, additional, Lu, Zhanni, additional, Liu, Diane D., additional, Busaidy, Naifa Lamki, additional, Reuben, James M., additional, Williams, Janet L., additional, Hess, Kenneth R., additional, Basen-Engquist, Karen, additional, and Bruera, Eduardo, additional

Published
2019
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18. Genomic landscape of FNAs positive for medullary thyroid cancer (MTC) and potential impact on systemic therapy.

Author

Wirth, Lori J., primary, Waguespack, Steven G., additional, Busaidy, Naifa Lamki, additional, Hu, Mimi I-Nan, additional, Grubbs, Elizabeth Gardner, additional, Weitzman, Steven P, additional, Zafereo, Mark, additional, Babiarz, Joshua, additional, Hao, Yangyang, additional, Huang, Jing, additional, Kennedy, Giulia, additional, Walsh, P. Sean, additional, and Kloos, Richard, additional

Published
2019
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19. NCCN Guidelines Insights: Thyroid Carcinoma, Version 2.2018

Author

Haddad, Robert I., primary, Nasr, Christian, additional, Bischoff, Lindsay, additional, Busaidy, Naifa Lamki, additional, Byrd, David, additional, Callender, Glenda, additional, Dickson, Paxton, additional, Duh, Quan-Yang, additional, Ehya, Hormoz, additional, Goldner, Whitney, additional, Haymart, Megan, additional, Hoh, Carl, additional, Hunt, Jason P., additional, Iagaru, Andrei, additional, Kandeel, Fouad, additional, Kopp, Peter, additional, Lamonica, Dominick M., additional, McIver, Bryan, additional, Raeburn, Christopher D., additional, Ridge, John A., additional, Ringel, Matthew D., additional, Scheri, Randall P., additional, Shah, Jatin P., additional, Sippel, Rebecca, additional, Smallridge, Robert C., additional, Sturgeon, Cord, additional, Wang, Thomas N., additional, Wirth, Lori J., additional, Wong, Richard J., additional, Johnson-Chilla, Alyse, additional, Hoffmann, Karin G., additional, and Gurski, Lisa A., additional

Published
2018
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20. Facilitating rapid precision oncology in anaplastic thyroid cancer: Clinical implications of next generation sequencing (NGS) mutation testing and impact on survival.

Author

Wang, Jennifer Rui, primary, Cote, Gilbert J, additional, Zafereo, Mark, additional, Iyer, Priyanka C., additional, Dadu, Ramona, additional, Busaidy, Naifa Lamki, additional, Gross, Neil D., additional, Sturgis, Erich M., additional, Ferrarotto, Renata, additional, Lu, Charles, additional, Gunn, Gary Brandon, additional, Myers, Jeffrey, additional, Lai, Stephen Yenzen, additional, Williams, Michelle D., additional, and Cabanillas, Maria E., additional

Published
2018
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21. Results of randomized phase II trial of dabrafenib versus dabrafenib plus trametinib in BRAF-mutated papillary thyroid carcinoma.

Author

Shah, Manisha H., primary, Wei, Lai, additional, Wirth, Lori J., additional, Daniels, Gregory A., additional, De Souza, Jonas A., additional, Timmers, Cynthia Dawn, additional, Sexton, Jennifer L., additional, Beshara, Mamdouh, additional, Nichols, Debra, additional, Snyder, Norka, additional, Devine, Catherine E, additional, Konda, Bhavana, additional, and Busaidy, Naifa Lamki, additional

Published
2017
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22. Comprehensive genomic sequencing (CGS) of 90 patient samples of anaplastic thyroid cancer (ATC).

Author

Khan, Saad A., primary, Ci, Bo, additional, Gerber, David E., additional, McFadden, David G, additional, Beg, Muhammad Shaalan, additional, Xie, Yang, additional, Kurian, Pamela, additional, Cabanillas, Maria E., additional, Busaidy, Naifa Lamki, additional, Sherman, Steven I., additional, Heilmann, Andreas, additional, Ross, Jeffrey S., additional, Bailey, Mark, additional, Burtness, Barbara, additional, and Ali, Siraj Mahamed, additional

Published
2016
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25. Accurate detection of circulating tumor cells (CTCs) in patients with metastatic papillary thyroid cancer (MPTC) via an interphase fluorescence in situ hybridization (IFISH) assay.

Author

Xu, Jian Yu, primary, Zaidi, Tanweer M, additional, Cote, Gilbert J, additional, Hu, Mimi I-Nan, additional, Waguespack, Steven G., additional, Cabanillas, Maria E., additional, Ying, Anita Kuo, additional, Busaidy, Naifa Lamki, additional, Habra, Mouhammed Amir, additional, Shanbhag, Namita, additional, Truong, Duy, additional, Yu, Robert K, additional, Shete, Sanjay, additional, Katz, Ruth L., additional, and Sherman, Steven I., additional

Published
2016
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26. Intrapatient comparative efficacy of selective RET inhibitors using growth modulation index in patients with RET aberrant cancers.

Author

Gouda, Mohamed Alaa, Ahmed, Jibran, Nelson, Blessie Elizabeth, Nardo, Mirella, Roszik, Jason, Cabanillas, Maria E., Hu, Mimi I-Nan, Busaidy, Naifa Lamki, Sherman, Steven I., Dadu, Ramona, Naing, Aung, Karp, Daniel D., Rodon Ahnert, Jordi, Hong, David S., Elamin, Yasir Y, Blumenschein, George R., Heymach, John, Meric-Bernstam, Funda, and Subbiah, Vivek

Published
2023
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27. Differentiated Thyroid Cancer: Management of Patients with Radioiodine Nonresponsive Disease

Author

Busaidy, Naifa Lamki and Cabanillas, Maria E.

Subjects
endocrine system, endocrine system diseases, Article Subject
Abstract

Differentiated thyroid carcinoma (papillary and follicular) has a favorable prognosis with an 85% 10-year survival. The patients that recur often require surgery and further radioactive iodine to render them disease-free. Five percent of thyroid cancer patients, however, will eventually succumb to their disease. Metastatic thyroid cancer is treated with radioactive iodine if the metastases are radioiodine avid. Cytotoxic chemotherapies for advanced or metastatic noniodine avid thyroid cancers show no prolonged responses and in general have fallen out of favor. Novel targeted therapies have recently been discovered that have given rise to clinical trials for thyroid cancer. Newer aberrations in molecular pathways and oncogenic mutations in thyroid cancer together with the role of angiogenesis in tumor growth have been central to these discoveries. This paper will focus on the management and treatment of metastatic differentiated thyroid cancers that do not take up radioactive iodine.

Published
2012
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28. Prospective evaluation of a 409-gene next generation sequencing platform to facilitate genotype-matched clinical trial enrollment.

Author

Kopetz, Scott, primary, Litzenburger, Beate, additional, Kinyua, Walter, additional, Sajan, Blessy, additional, Subbiah, Vivek, additional, Zinner, Ralph, additional, Wheler, Jennifer J., additional, Hong, David S., additional, Tsimberidou, Apostolia Maria, additional, Overman, Michael J., additional, Pagliaro, Lance C., additional, Busaidy, Naifa Lamki, additional, Westin, Shannon Neville, additional, Glisson, Bonnie S., additional, Heymach, John, additional, Meric-Bernstam, Funda, additional, Shaw, Kenna Rael, additional, Lee, J. Jack, additional, and Broaddus, Russell, additional

Published
2015
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29. Recurrent parathyroid carcinoma and the need for molecular profiling to aid in prognostication and therapeutics.

Author

Kwatampora, Lily, primary, Clarke, Callisia, additional, Silva, Angelica, additional, Zorba, Yildiz, additional, Williams, Michelle D., additional, Broaddus, Russell, additional, Clayman, Gary L., additional, El-Naggar, Adel K., additional, Gagel, Robert F., additional, Grubbs, Elizabeth Gardner, additional, Habra, Mouhammed Amir, additional, Hu, Mimi I-Nan, additional, Jimenez, Camilo, additional, Kopetz, Scott, additional, Lee, Jeffrey Edwin, additional, Sherman, Steven I., additional, Vassilopoulou-Sellin, Rena, additional, Waguespack, Steven, additional, Perrier, Nancy D, additional, and Busaidy, Naifa Lamki, additional

Published
2015
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31. Anaplastic transformation in thyroid cancer revealed by single-cell transcriptomics.

Author

Lina Lu, Rui Wang, Jennifer, Henderson, Ying C., Shanshan Bai, Jie Yang, Min Hu, Cheng-Kai Shiau, Pan, Timothy, Yuanqing Yan, Tran, Tuan M., Jianzhuo Li, Kieser, Rachel, Xiao Zhao, Jiping Wang, Nurieva, Roza, Williams, Michelle D., Cabanillas, Maria E., Dadu, Ramona, Busaidy, Naifa Lamki, and Zafereo, Mark

Abstract

The deadliest anaplastic thyroid cancer (ATC) often transforms from indolent differentiated thyroid cancer (DTC); however, the complex intratumor transformation process is poorly understood. We investigated an anaplastic transformation model by dissecting both cell lineage and cell fate transitions using single-cell transcriptomic and genetic alteration data from patients with different subtypes of thyroid cancer. The resulting spectrum of ATC transformation included stress-responsive DTC cells, inflammatory ATC cells (iATCs), and mitotic-defective ATC cells and extended all the way to mesenchymal ATC cells (mATCs). Furthermore, our analysis identified 2 important milestones: (a) a diploid stage, in which iATC cells were diploids with inflammatory phenotypes and (b) an aneuploid stage, in which mATCs gained aneuploid genomes and mesenchymal phenotypes, producing excessive amounts of collagen and collagen-interacting receptors. In parallel, cancer-associated fibroblasts showed strong interactions among mesenchymal cell types, macrophages shifted from M1 to M2 states, and T cells reprogrammed from cytotoxic to exhausted states, highlighting new therapeutic opportunities for the treatment of ATC. [ABSTRACT FROM AUTHOR]

Published
2023
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32. Surgery After BRAF-Directed Therapy Is Associated with Improved Survival in BRAF V600E Mutant Anaplastic Thyroid Cancer: A Single-Center Retrospective Cohort Study.

Author

Zhao X, Wang JR, Dadu R, Busaidy NL, Xu L, Learned KO, Chasen NN, Vu T, Maniakas A, Eguia AA, Diersing J, Gross ND, Goepfert R, Lai SY, Hofmann MC, Ferrarotto R, Lu C, Gunn GB, Spiotto MT, Subbiah V, Williams MD, Cabanillas ME, and Zafereo ME

Subjects
Humans, Proto-Oncogene Proteins B-raf genetics, Retrospective Studies, Prospective Studies, Thyroid Carcinoma, Anaplastic drug therapy, Thyroid Carcinoma, Anaplastic genetics, Thyroid Carcinoma, Anaplastic surgery, Thyroid Neoplasms drug therapy, Thyroid Neoplasms genetics, Thyroid Neoplasms surgery
Abstract

Background: The aim of this study was to describe the oncologic outcomes of patients with BRAF V600E -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 BRAF V600E -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.

Published
2023
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