The Journal of clinical endocrinology and metabolism · 2026
Molecular Profile of Advanced Radioiodine-refractory Thyroid Cancer and Response to Lenvatinib Treatment.
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Minaldi Elisa, Ramone Teresa, Ciampi Raffaele, Romei Cristina, Casalini Roberta, Gambale Carla, Prete Alessandro, Lorusso Loredana, Agate Laura, Torregrossa Liborio, Piaggi Paolo, Matrone Antonio, Elisei Rossella
Аннотация
CONTEXT: The predictive role of mutational status in the response to lenvatinib in advanced radioiodine-refractory thyroid cancer (RAIR-TC) is not yet defined.
OBJECTIVE: To identify a molecular signature of RAIR-TC treated with lenvatinib and its impact on clinical response to lenvatinib.
DESIGN: This is a retrospective study including 49 RAIR-TC patients treated with first-line lenvatinib and followed at least 1 year [median follow-up 9.2 years (interquartile range 6-14.1)]. Next-generation sequencing on tissues was used to detect genetic alterations.
SETTING: The study was performed in a referral center for the treatment of thyroid cancer.
RESULTS: Among 49 cases, BRAF (38.7%) and RAS (22.4%) were the most frequent driver mutations, while TERT and TP53 were mutated in 57.1% and 6.1%. No driver mutations were found in 34.6%. Driver mutations co-occurred with TERT or TP53 in 44.9%. In 10/49 (20.4%), no mutations were found. Cases with ≥1 mutation had longer progression-free survival (PFS) than cases negative for any mutation (P = .004). Both BRAF-mutated and RAS-mutated cases showed better PFS and overall survival (OS), although this was not statistically significant with respect to wild-type cases. Cases with a single driver mutation (group 1) showed longer PFS than cases without driver mutations (group 3) (P = .04) but no difference with cases with driver + TERT or TP53 (group 2) (P = .13). Group 1 showed longer OS than group 2 (P = .026) and group 3 (P = .034).
CONCLUSIONS: The RAIR-TC molecular profile is heterogeneous with TERT being the most frequent mutation. Cases negative for all mutations and cases presenting the coexistence of TERT + driver mutation had a worse response to lenvatinib. Conversely, the presence of 1 driver mutation correlated with a better response to lenvatinib.
OBJECTIVE: To identify a molecular signature of RAIR-TC treated with lenvatinib and its impact on clinical response to lenvatinib.
DESIGN: This is a retrospective study including 49 RAIR-TC patients treated with first-line lenvatinib and followed at least 1 year [median follow-up 9.2 years (interquartile range 6-14.1)]. Next-generation sequencing on tissues was used to detect genetic alterations.
SETTING: The study was performed in a referral center for the treatment of thyroid cancer.
RESULTS: Among 49 cases, BRAF (38.7%) and RAS (22.4%) were the most frequent driver mutations, while TERT and TP53 were mutated in 57.1% and 6.1%. No driver mutations were found in 34.6%. Driver mutations co-occurred with TERT or TP53 in 44.9%. In 10/49 (20.4%), no mutations were found. Cases with ≥1 mutation had longer progression-free survival (PFS) than cases negative for any mutation (P = .004). Both BRAF-mutated and RAS-mutated cases showed better PFS and overall survival (OS), although this was not statistically significant with respect to wild-type cases. Cases with a single driver mutation (group 1) showed longer PFS than cases without driver mutations (group 3) (P = .04) but no difference with cases with driver + TERT or TP53 (group 2) (P = .13). Group 1 showed longer OS than group 2 (P = .026) and group 3 (P = .034).
CONCLUSIONS: The RAIR-TC molecular profile is heterogeneous with TERT being the most frequent mutation. Cases negative for all mutations and cases presenting the coexistence of TERT + driver mutation had a worse response to lenvatinib. Conversely, the presence of 1 driver mutation correlated with a better response to lenvatinib.