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Foundation OneTM Genomic Interrogation of Thyroid Cancers in Patients with Metastatic Disease Requiring Systemic Therapy.

CONTEXT
Clinical applications of genomic assessment of thyroid cancers are rapidly evolving.


OBJECTIVES, DESIGN AND SETTING
We studied tumor samples from patients with imminently threatening and rare thyroid cancers to identify genomic alterations that might correlate with outcomes and/or be productively therapeutically targetable.


PATIENT CONTEXT
Progressive and metastatic, and/or rare, thyroid cancers, 2012-2016, Mayo Clinic sites.


INTERVENTION
Foundation One TM tumor interrogation.


MAIN OUTCOME MEASURES
Genomic alterations, patient characteristics, overall survival.


RESULTS
Samples from 55 patients were evaluated: 20 ATCs (36%), 25 radioactive iodine refractory DTC/PDTCs (45%; 14 PTC, 6 PDTC, 5 HCC), 8 MTCs (15%) and 2 "others" (SETTLE and a primary thyroid sarcoma). Overall, 72% of DTCs, 79% of ATCs and 75% of MTCs were deemed to have potentially productively targetable alterations. The most commonly encountered mutation was of TERT promoter (56% of DTCs, 68% of ATCs) - but this is not presently targetable. Targetable BRAFV600E mutations were found in 40% of DTC/PDTCs (83% of PTCs) and 32% of ATCs; of MTCs, 75% had targetable RET mutations, 25% HRAS mutations.  Of patient tumors with non-mutated BRAFV600E, 53% of DTC/PDTCs and 69% of ATCs had other potentially productively targetable mutations.  Genomic alterations in our series of poor prognosis metastatic DTC/PDTCs also closely resembled those seen in ATC.


CONCLUSIONS
Whereas genomic interrogation of favorable prognosis thyroid cancer seems ill advised, potentially productively targetable mutations were demonstrated in the majority of tumors from patients with metastatic thyroid cancers requiring systemic therapy, suggesting a rationale for the selective application of this technology.