The role of external beam radiation therapy in thyroid cancer management: A Scoping Review

Abstract

Background: This scoping review aimed to evaluate the role of external beam radiation therapy (EBRT) in the management of thyroid cancers, a heterogeneous disease encompassing multiple histological subtypes, and to clarify its integration with emerging targeted therapies.

Methods: Following PRISMA-ScR guidelines, a systematic search of PubMed and BioMed Central from 2012 to 2024 identified 91 studies from an initial pool of 2,309 records. Of these, 36 (39.5%) addressed anaplastic thyroid carcinoma (ATC), 31 (34%) differentiated thyroid carcinoma (DTC), 6 (6.5%) medullary thyroid cancer (MTC), 12 (13.5%) rare subtypes, and 6 (6.5%) focused on metastasis-directed EBRT. EBRT was analyzed as definitive treatment, postoperative EBRT (poRT), or in combination with systemic therapies.

Results: Definitive EBRT remains a key option for patients with inoperable, locally advanced ATC, particularly when vital structures such as the trachea or esophagus are involved. Although the studies included in this review did not allow conclusions regarding whether targeted therapies have modified EBRT indications in ATC, recent guidelines increasingly recommend systemic therapies-particularly BRAF/MEK inhibitors-as first-line treatment in unresectable disease, with EBRT considered following re-evaluation. In DTC, poRT combined with radioactive iodine (RAI) reduced the 5-year locoregional recurrence rate by up to 30% in high-risk patients (extrathyroidal extension, incomplete resection, or nodal metastases). While a consistent overall survival (OS) benefit was not observed, improved local control may help reduce recurrence-related morbidity. IMRT improved locoregional failure-free survival (LFFS) compared to 3D-CRT, and proton therapy showed favorable toxicity profiles in small cohorts. In MTC, poRT was associated with reduced locoregional recurrence in patients with extracapsular extension or nodal metastases, but similar to DTC, its impact on OS remains unclear. For primary thyroid lymphoma, EBRT achieved high local control but is generally reserved for refractory or chemotherapy-ineligible patients.

Conclusion: EBRT remains an important modality for locoregional control in thyroid cancers, especially in high-risk or inoperable cases. While OS benefit has not been consistently demonstrated across histologies, local control may improve patient outcomes by reducing the burden of recurrence or prolonging survival in selected situations. The integration of EBRT with evolving systemic therapies warrants further prospective investigation.

Keywords: Anaplastic Thyroid Carcinoma; Differentiated Thyroid Carcinoma; Medullary Thyroid Carcinoma; Radiotherapy; Thyroid Neoplasms.