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. 2025 Jan:202:110602.
doi: 10.1016/j.radonc.2024.110602. Epub 2024 Nov 1.

Patterns of loco-regional progression and patient outcomes after definitive-dose radiation therapy for anaplastic thyroid cancer

Julianna K Bronk  1 , Alexander Augustyn  2 , Abdallah S R Mohamed  1 , C David Fuller  1 , Adam S Garden  1 , Amy C Moreno  1 , Anna Lee  1 , William H Morrison  1 , Jack Phan  1 , Jay P Reddy  1 , David I Rosenthal  1 , Michael T Spiotto  1 , Steven J Frank  1 , Ramona Dadu  3 , Naifa Busaidy  3 , Mark Zafereo  4 , Jennifer R Wang  4 , Anastasios Maniakas  4 , Renata Ferrarotto  5 , Priyanka C Iyer  3 , Maria E Cabanillas  3 , G Brandon Gunn  6
Affiliations

Patterns of loco-regional progression and patient outcomes after definitive-dose radiation therapy for anaplastic thyroid cancer

Julianna K Bronk et al. Radiother Oncol. 2025 Jan.

Abstract

Background: The aim of this study is to characterize the patterns of loco-regional progression (LRP) and outcomes after definitive-dose intensity modulated radiation therapy (IMRT) for anaplastic thyroid cancer (ATC) with macroscopic neck disease at the time of IMRT.

Methods: Disease/treatment characteristics and outcomes for patients with unresected or incompletely resected ATC who received IMRT (≥45 Gy) were retrospectively reviewed. For those with LRP after IMRT, progressive/recurrent gross tumor volumes (rGTV) were contoured on diagnostic CTs and co-registered with initial planning CTs using deformable image registration. rGTVs were classified based on established spatial/dosimetric criteria.

Results: Forty patients treated between 2010-2020 formed the cohort. Median IMRT dose was 66 Gy (45-70 Gy); altered fractionation (AF) was used in 24 (60 %). All received concurrent chemotherapy. In addition to areas of gross disease, target volumes (TVs) commonly included: central compartment/upper mediastinum (levels VI/VII), neck levels II-V in an involved, and levels III-IV in an uninvolved lateral neck. Median overall survival was 7.1 m. Median progression free survival was 7.4 m for patients with locoregional disease and 1.8 m for patients with distant metastasis at the time of IMRT. Twenty-one patients (53 %) developed LRP at median of 10.9 m; freedom from LRP at 3 m and 12 m was 71 % (95 %CI 58-87 %) and 47 % (95 %CI 32-68 %). Forty-one individual rGTVs were identified and most occurred within the high dose (HD) TVs: Type A/central HD (n = 29, 71 %) and B/peripheral HD (n = 3, 7 %).

Conclusions: Despite an intensive treatment schedule, including AF and concurrent chemotherapy, classic radio-resistant and rapid Type A failures predominated; isolated extraneous dose failures were rare. While these findings support the IMRT and TV delineation strategies described herein, they highlight the importance of identifying novel strategies to further improve LRC for patients with unresectable disease without targetable mutations for contemporary neo-adjuvant strategies.

Keywords: Anaplastic thyroid cancer; Definitive intensity modulated radiation therapy; Patterns of failure.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MZ has grant funding from Eli Lilly and Merck to MD Anderson Cancer Center for ongoing phase II clinical trials. RF: Consulting/advisory role in the past 2 years:Coherus Bioscience, Eisai Medical Research, Elevar Therapeutics, Prelude Therapeutics, Regeneron Pharmaceuticals, Remix Therapeutics, Sanofi-aventis, Answers in CME, Labcorp Drug Development. Research funding (institution):ISA Therapeutics, Merck, Ayala Pharmaceuticals, Viracta, Gilead, Seagen, Prelude Therapeutics in the past 2 years. MEC: Advisory boards/consulting: Bayer, Exelixis, Lilly, Novartis. Clinical trial funding Merck, Genentech. CDF received/receives related funding and salary support from: National Institutes of Health (NIH) National Cancer Institute (NCI) and National Institute of Dental and Craniofacial Research (NIDCR) Administrative Supplements to Support Collaborations to Improve AIML-Readiness of NIH-Supported Data (R01CA257814-02S3; R01DE028290-04S2); NIH National Institute of Biomedical Imaging and Bioengineering (NIBIB) Research Education Programs for Residents and Clinical Fellows Grant (R25EB025787); NIH/NCI Cancer Center Support Grant (CCSG) (P30CA016672); Patient-Centered Outcomes Research Institute (PCS-1609-36195; sub-award from Princess Margaret Hospital). Dr. Fuller receives grant and infrastructure support from MD Anderson Cancer Center via the Charles and Daneen Stiefel Center for Head and Neck Cancer Oropharyngeal Cancer Research Program. Dr. Fuller has received NIH sub-award support from Oncospace, Inc. (R43CA254559, PI Lakshminarayanan) under a Small Business Innovation Research Grant Applications grant. Dr. Fuller has received direct industry grant/in-kind support, honoraria, and travel funding from Elekta AB. Dr. Fuller has served as a consulting capacity for Varian/Siemens Healthineers, Philips Medical Systems, and Oncospace, Inc. RD received research support from AstaZeneca, Merck, Eisai, Exellixis and serves in a cosulting role with Bayer, Novartis, Exelixis. NB: Honoraria: Eisai, Exelixis, Consulting or Advisory Role: Loxo, Eisai, Research Funding: GlaxoSmithKline/Novartis.

Figures

Fig. 1.
Fig. 1.
Workflow depicting identification and scoring of failures. A. Recurrent gross tumor volumes (rGTV, green) are contoured on diagnostic imaging, B. Deformable registration of original planning CT and diagnostic imaging is performed, C. rGTVs are co-registered to the original treatment plan allowing for spatial and dosimetric analysis at each location of recurrence (D). Red represents the original treatment plan high dose CTV, blue, intermediate dose CTV, and yellow, elective dose CTV. In this example, an illustration of a Type A, Type C, and Type E failure in the same patient is shown. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
Fig. 2.
Fig. 2.
Patient outcomes after IMRT for unresected or incompletely resected ATC. (A) Median OS from completion of radiation therapy was 7.1 months: 14.4 months for patients with Stage IVB disease at the time of IMRT, and 4.5 months for patients with Stage IVC disease at the time of IMRT (B, p = 0.01). Median time to any progression was 7.4 months for patients with Stage IVB disease and 1.8 months for patients with Stage IVC disease (C, p = 0.003). (D) In patients with Stage IVB disease, time to distant metastasis was 8.6 months. (E) Median FFLRP was 10.9 months. (F) In patients with Stage IVB disease, median OS was 10.9 months for patients with locoregional progression versus 45.6 months for patients with locoregional control (p = 0.20).
Fig. 3.
Fig. 3.
Recurrent gross tumor volumes (rGTV) categorized by spatial and dosimetric criteria. The majority of failures occurred in the high dose TV- Type A and B.
See this image and copyright information in PMC

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