427PD - Pediatric, adolescent and young adult (PAYA) thyroid carcinoma harbors frequent and diverse targetable genomic alterations including kinase fusions
|Date||10 October 2016|
|Event||ESMO 2016 Congress|
|Session||Endocrine and neuroendocrine tumours|
|Topics|| Cancer in Adolescents
Cancer in Young Adults
|Presenter||Pierre Vanden Borre|
|Citation||Annals of Oncology (2016) 27 (6): 136-148. 10.1093/annonc/mdw369|
P. Vanden Borre1, A.B. Schrock2, P. Anderson3, A.M. Heilmann4, O. Holmes4, K. Wang5, S. Khan6, J.C. Morris7, S.I. Ou8, S. Waguespack9, P. Stephens10, R.L. Erlich4, V. Miller11, J.S. Ross12, S. Ali12
Thyroid carcinoma in children and young adults is rare but carries the potential for morbidity and mortality. A series of advanced pediatric, adolescent and young adult (PAYA) thyroid carcinoma cases were assayed in the course of clinical care to identify genomic alterations (GAs) linked to potential benefit from targeted therapy.
Hybrid-capture based comprehensive genomic profiling (CGP) was performed prospectively on 58 consecutively submitted PAYA thyroid carcinomas.
All patients were 39 years old or younger including 41 patients with papillary thyroid carcinoma (PTC) (median age: 26 years, range: 7-39 years), 3 with anaplastic thyroid carcinoma (ATC) (median age: 33 years, range 25-33 years), and 14 with medullary thyroid carcinoma (MTC) (median age: 33 years, range 15-39). 64% (37/58) of the patients were female. GAs were detected in 93% (54/58) of cases, with a mean of 1.4 GAs per case. Clinically relevant GAs, defined as GAs associated with at least one actively recruiting clinical trial or an FDA-approved therapy, were identified in 91% (53/58) of cases. BRAF V600E was present in 46% (19/41) of PTCs and in 1/3 ATCs. Oncogenic fusions were identified in 37% (15/41) and 33% (1/3) of PTC and ATC cases, respectively. In addition to fusions previously observed in PAYA thyroid carcinoma involving RET, NTRK1, and NTRK3, 3 ALK fusions (EML4-ALK, STRN-ALK, and GTF2IRD1-ALK) were detected in pediatric patients with PTC. In PAYA patients with MTC, RET mutation occurred in 93% (13/14) of cases, including the predominant RET M918T mutation and 3 insertion/deletions in exons 6 and 11. Two patients with MTC harboring in-frame deletions in RET exons 6 and 11 experienced clinical benefit from vandetanib treatment.
CGP identified diverse targetable genomic alterations in PAYA patients with thyroid carcinoma. 83% of PTC cases harbored either activating kinase mutations or rearrangements, including three cases with ALK fusions. Genomic alteration data and our clinical observations suggest that young patients with advanced thyroid carcinoma can often benefit from CGP to identify matched targeted therapies.
Clinical trial identification
Legal entity responsible for the study
P. Vanden Borre, A.B. Schrock, A.M. Heilmann, O. Holmes, K. Wang, P. Stephens, R.L. Erlich, V. Miller, J.S. Ross, S. Ali: Employee and has stock ownership in Foundation Medicine.
All other authors have declared no conflicts of interest.