Definitive Radiotherapy for Oligometastatic and Oligoprogressive Thyroid Cancer: A Potential Strategy for Systemic Therapy Deferral

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Stephanie O. Dudzinski Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

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Maria E. Cabanillas Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX

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Sarah Hamidi Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX

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Vicente R. Marczyk Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX

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Naifa L. Busaidy Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX

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Ramona Dadu Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX

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James Welsh Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

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Mimi I. Hu Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX

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G. Brandon Gunn Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

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Chenyang Wang Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

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Steven G. Waguespack Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX

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Jack Phan Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

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Thomas H. Beckham Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

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Joe Y. Chang Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

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Steven I. Sherman Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX

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Jay P. Reddy Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

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Anita K. Ying Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX

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Michael S. O’Reilly Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

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Aileen Chen Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

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Anna Lee Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

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Saumil J. Gandhi Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

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Zhongxing Liao Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

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Ethan B. Ludmir Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

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Quynh-Nhu Nguyen Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

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Steven H. Lin Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

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Mark E. Zafereo Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX

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Matthew S. Ning Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

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Background: Definitive radiotherapy (dRT) has been shown to be an effective option for patients with oligometastatic and oligoprogressive cancers; however, this approach has not been well-studied in metastatic thyroid cancer. Methods: This retrospective cohort included 119 patients with oligometastatic (34%) and oligoprogressive (66%) metastatic thyroid cancer treated from 2005 to 2024 with 207 dRT courses for 344 sites (50% thoracic, 37% bone, 7.5% brain, 4% abdominopelvic, and 1.5% neck/skull base). Histologies included 61% papillary, 15% poorly differentiated, 13% follicular, and 10% oncocytic, and 114 (96%) patients had radioiodine-refractory disease prior to dRT. Each course involved 1 to 5 sites, with prescriptions intended for definitive control (median BED10, 72 Gy), and palliative RT was excluded. Somatic mutation testing for oncologic drivers was performed in 103 (87%) patients. Results: Each patient had an average of 3 sites (range, 1–23) treated over 2 courses (range, 1–9). Follow-up from first dRT was a median 2.5 years, with overall survival at 3 and 5 years of 81.5% and 70%, respectively. Actuarial local control per site was 91% at 3 years. Median progression-free survival (PFS) after first course was 17 months (95% CI, 10–24 months), with poorly differentiated histology associated with worse outcomes (hazard ratio [HR], 2.20; 95% CI, 1.24–3.90; P=.007), BRAF mutation with improved PFS (HR, 0.59; 95% CI, 0.37–0.95; P=.029), and no significant findings with respect to systemic therapy. At initial dRT, 92 (77%) patients were not on systemic therapy; and after first dRT, freedom from systemic therapy escalation was a median 4.1 years (95% CI, 1.7–6.5 years), with 2- and 5-year continued deferral rates of 73% and 46%, respectively. Grade 3 toxicities were noted for 1.5% of courses, with no grade 4–5 events observed. Conclusions: This study underscores the potential of dRT as a feasible strategy for deferring systemic therapy escalation in patients with oligometastatic and oligoprogressive metastatic thyroid cancer, demonstrating that sequential dRT courses impart excellent local control and are safe to deliver repeatedly for multiple distant sites. Further studies are warranted to validate these findings and elucidate the full benefit of dRT as part of a multidisciplinary approach for metastatic thyroid cancer.

Submitted April 24, 2024; final revision received August 17, 2024; accepted for publication September 9, 2024. Published online December 11, 2024.

Author contributions: Data collection: Dudzinski, Ning. Writing—original draft: Dudzinski, Ning. Writing—review & editing: Cabanillas, Hamidi, Marczyk, Busaidy, Dadu, Welsh, Hu, Gunn, Wang, Waguespack, Phan, Beckham, Chang, Sherman, Reddy, Ying, O’Reilly, Chen, Lee, Gandhi, Liao, Ludmir, Nguyen, Lin, Zafereo.

Disclosures: Dr. Cabanillas has disclosed serving as a consultant for Novartis. Dr. Welsh has disclosed receiving grant/research support from Nanobiotix, Alkermes, Varian, ARTIDIS, Takeda, HotSpot Therapeutics, Gilead, Kiromic, Bayer Healthcare, Bristol Myers Squibb, AstraZeneca, Merck, SciClone Pharmaceuticals, Novocure, and Pebble Life Science; serving as a principal investigator for Nanobiotix, ARTIDIS, Alkermes, Takeda, Varian, HotSpot Therapeutics, Gilead Sciences, Kiromic, Bayer, Bristol Myers Squibb, SciClone Pharmaceuticals, Novocure, and Pebble Life Science; serving as a scientific advisor for Kezar Life Sciences, Nanobiotix, Novocure, and RefleXion Medical; serving as a consultant for Kezar Life Sciences, Nanobiotix, Nanorobotics, Novocure, and RefleXion Medical; and owning stock or having an ownership interest in Oligo Immune, Alpine Immune Sciences, Checkmate Pharmaceuticals, RefleXion Medical, OncoResponse, MolecularMatch, Nanorobotics, and Legion Healthcare Partners. Dr. Chang has disclosed receiving grant/research support from the Siemens-MDACC Alliance; serving as a consultant for Regeneron; and receiving honoraria from Varian and Ion Beam Applications. Dr. Lin has disclosed receiving grant/research support from STCube Pharmaceuticals, BeyondSpring Pharmaceuticals, and Nektar Therapeutics; serving as a scientific advisor for AstraZeneca and Creatv MicroTech; serving as a consultant for XRad Therapeutics; owning stock in and being a co-founder of Seek Diagnostics; and receiving royalties from STCube Pharmaceuticals. Dr. Zafereo has disclosed receiving grant/research support from Merck, Eli Lilly and Company, and Exelixis. The remaining authors have disclosed that they have not received any financial considerations from any person or organization to support the preparation, analysis, results, or discussion of this article.

Supplementary material: Supplementary material associated with this article is available online at https://doi.org/10.6004/jnccn.2024.7072. The supplementary material has been supplied by the author(s) and appears in its originally submitted form. It has not been edited or vetted by JNCCN. All contents and opinions are solely those of the author. Any comments or questions related to the supplementary materials should be directed to the corresponding author.

Correspondence: Matthew S. Ning, MD, MPH, Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Unit 0097, PO Box 301407, Houston, TX 77230-1407. Email: MSNing@mdanderson.org

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