Does Molecular Genotype Provide Useful Information in the Management of Radioiodine Refractory Thyroid Cancers? Results of a Retrospective Study.
BACKGROUND
Whether mutation status should be used to guide therapy is an important issue in many cancers. We correlated mutation profile in radioiodine-refractory (RAIR) metastatic thyroid cancers (TCs) with patient outcome and response to tyrosine kinase inhibitors (TKIs), and discussed the results with other published data.


METHODS
Outcome in 82 consecutive patients with metastatic RAIR thyroid carcinoma prospectively tested for BRAF, RAS and PI3KCA mutations was retrospectively analyzed, including 55 patients treated with multikinase inhibitors.


RESULTS
Papillary thyroid carcinomas (PTCs) were the most frequent histological subtype (54.9 %), followed by poorly differentiated thyroid carcinoma [PDTC] (30.5 %) and follicular thyroid carcinoma [FTC] (14.6 %). A genetic mutation was identified in 23 patients (28 %) and BRAF was the most frequently mutated gene (23 %). Median progression-free survival (PFS) on first-line TKI treatment was 14.6 months (95% CI 9.9-18.4). BRAF mutation positively influenced median PFS, both in the entire TKI-treated cohort (median PFS 34.7 months versus 11.6 months; hazard ratio [HR] 0.29; 95% CI 0.09-0.98; p = 0.03) and in the TKI-treated PTC cohort (n = 22) [log-rank p = 0.086; HR 2.95; 95 % CI 0.81-10.70). However, in TKI-treated patients, PDTC histologic subtype was the only independent prognostic factor for PFS identified in the multivariate analysis (HR 2.36; 95% CI 1.01-5.54; p = 0.048).


CONCLUSIONS
Patients with BRAF-mutant PTC had a significantly longer PFS than BRAF wild-type when treated with TKIs. However, due to the small number of BRAF-mutant patients, further investigations are required, especially to understand the potential positive effect of BRAF mutations in RAIR TC patients while having a negative prognostic impact in RAI-sensitive PTC patients.
Medical Oncology Department, Centre Leon Berard, University Lyon I, 28 rue Laennec, 69003, Lyon, France. christelle.delafouchardiere@lyon.unicancer.fr.
Christelle
C
de la Fouchardiere
Department of Biostatistics, Centre Leon Berard, University Lyon I, Lyon, France.
Nadia
N
Oussaid
Medical Oncology Department, Centre Leon Berard, University Lyon I, 28 rue Laennec, 69003, Lyon, France.
Olfa
O
Derbel
Pathology Department, Hospital Lyon-Sud, University Lyon I, Pierre-Benite, France.
Myriam
M
Decaussin-Petrucci
Pathology Department, Centre Leon Berard, University Lyon I, Lyon, France.
Marie-Eve
ME
Fondrevelle
Molecular Biology Platform, Clinical Science Center, Centre Leon Berard, University Lyon I, Lyon, France.
Qing
Q
Wang
Department of Pathology, Edouard Herriot Hospital, University Lyon I, Lyon, France.
Pierre-Paul
PP
Bringuier
Department of Nuclear Medicine, Hospital Louis Pradel, University Lyon I, Bron, France.
Claire
C
Bournaud-Salinas
Department of General and Endocrine Surgery, Hospital Lyon-Sud, University Lyon I, Lyon, France.
Jean-Louis
JL
Peix
Department of General and Endocrine Surgery, Hospital Lyon-Sud, University Lyon I, Lyon, France.
Jean-Christophe
JC
Lifante
Department of Nuclear Medicine, Centre Leon Berard, University Lyon I, Lyon, France.
Anne-Laure
AL
Giraudet
Department of Biochemistry, Hospital Lyon-Sud, University Lyon I, Lyon, Pierre-Bénite, France.|Inserm UMR-S1052, CNRS UMR5286, Centre Leon Berard, University Lyon I, Lyon, France.
Jonathan
J
Lopez
Endocrinology Department-INSERM, UMR 1052, Hospital Louis Pradel, University Lyon I, Lyon, France.
Françoise
F
Borson-Chazot
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D019468:Disease Management; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007457:Iodine Radioisotopes / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D011836:Radiation Tolerance; D012189:Retrospective Studies; D015996:Survival Rate; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy
D014408:Biomarkers, Tumor; D007457:Iodine Radioisotopes