Consensus Statement: Recommendations on Actionable Biomarker Testing for Thyroid Cancer Management

Abstract

Thyroid cancer management is rapidly changing. The identification of actionable biomarkers through both germline and somatic testing are now an integral part of directing patient management. However, deficiencies and disparities within existing thyroid cancer biomarker test approaches are resulting in inconsistent application for patient care. An expert panel was convened to create consensus biomarker testing algorithms and recommendations on actionable biomarker testing for patients diagnosed with medullary thyroid cancer, non-anaplastic follicular cell-derived thyroid cancer, or anaplastic follicular cell-derived thyroid cancer who may benefit from targeted therapies. A review of international guidelines was performed to determine the current state, and a literature review was carried out to further evaluate the evidence supporting the use of actionable biomarkers in patients diagnosed with thyroid cancer. Thyroid biomarker-related gaps impacting patient care were also discussed, with an emphasis on the importance of a multidisciplinary team approach for optimal patient care. The recommendations are presented with the aim to help physicians navigate the current thyroid cancer biomarker testing landscape with its many challenges, balancing aspirational care with what is practical and feasible in terms of economic realities and jurisdictional constraints. By remaining therapy-agnostic, these algorithms and recommendations are broadly applicable.

Keywords: ALK; BRAF; NTRK; RAS; RET; Algorithms; Biomarkers; Cancer management; Familial thyroid carcinoma; Genetic testing; IHC; Immunohistochemistry; Medullary thyroid carcinoma; Microsatellite instability; Mismatch repair; Molecular testing; NGS; Next-generation sequencing; PD-L1; Predictive; Targeted therapy; Thyroid cancer; Tumor mutational burden.

Fig. 1

Actionable biomarker testing to aid in the management of patients diagnosed with medullary thyroid cancer (MTC). White/clear shading represents the patient’s clinical diagnosis/stage; orange shading represents molecular test results. Dark blue shading conveys a necessary action for molecular testing or clinical provision, while light blue shading conveys a recommended action. Solid black arrows indicate a necessary pathway; dashed black shading represents “if/when” pathways. Abbreviations: P/LP, pathogenic/Likely pathogenic; VUS, variant of unknown significance

Fig. 2

Constitutional (germline) testing in patients diagnosed with non-anaplastic follicular cell-derived thyroid cancer. White/clear shading represents the patient’s clinical diagnosis/stage; orange shading represents molecular test results. Dark blue shading conveys a necessary action for molecular testing or clinical provision, green shading represents an action to be considered for clinical provision, and grey shading represents no further action needs to be taken. Solid black arrows indicate a necessary pathway, a solid grey arrow indicates no further action, and a dashed grey arrow indicates a pathway to be considered. Abbreviations: P/LP, pathogenic/likely pathogenic; VUS, variant of unknown significance

Fig. 3

Tumor testing of actionable biomarkers in patients diagnosed with non-anaplastic follicular cell-derived thyroid cancer. White/clear shading represents the patient’s clinical diagnosis/stage; orange shading represents molecular test results. Dark blue shading conveys a necessary action for molecular testing or clinical provision; green shading represents an action to be considered for clinical provision. Solid black arrows indicate a necessary pathway, and a dashed grey arrow indicates a pathway to be considered. Abbreviations: VUS, variant of unknown significance

Fig. 4

Tumor testing of actionable biomarkers in patients diagnosed with anaplastic follicular cell-derived thyroid carcinoma. White/clear shading represents the patient’s clinical diagnosis/stage, dark blue shading conveys a necessary action for molecular testing or clinical provision, red shading indicates a priority action, and light blue shading represents a recommended action. Solid black arrows indicate a necessary pathway