RT Journal Article
T1 Clinical Behavior, Mutational Profile and T-Cell Repertoire of High-Grade Neuroendocrine Tumors of the Head and Neck
A1 Cabezas Camarero, Santiago
A1 García Barberán, Vanesa
A1 Benítez Fuentes, Javier David
A1 Sotelo, Miguel J.
A1 Plaza, José Carlos
A1 Encinas Bascones, Alejandro
A1 De la Sen, Óscar
A1 Falahat Noushzady, Farzin
A1 Gimeno Hernández, Jesús
A1 Gómez Serrano, Manuel
A1 Puebla Díaz, Fernando
A1 De Pedro Marina, Manuel
A1 Iglesias Moreno, María Cruz
A1 Pérez Segura, Pedro
AB Neuroendocrine carcinomas (NECs) of the head and neck (HN) account for <1% of HN cancers (HNCs), with a 5-year overall survival (OS) <20%. This is a retrospective study of HN NECs diagnosed at our institution between 2005 and 2022. Immunohistochemistry and next-generation sequencing (NGS) were used to evaluate neuroendocrine markers, tumor mutational burden (TMB), mutational profiles and T-cell receptor repertoires. Eleven patients with high-grade HN NECs were identified (male:female ratio 6:5; median age 61 (Min-Max: 31-86)): nasoethmoidal (3), parotid gland (3), submaxillary gland (1), larynx (3) and base of tongue (1). Among n = 8 stage II/IVA/B, all received (chemo)radiotherapy with/without prior surgery or induction chemotherapy, with complete response in 7/8 (87.5%). Among n = 6 recurrent/metastatic patients, three received anti-PD1 (nivolumab (2), pembrolizumab (1)): two achieved partial responses lasting 24 and 10 months. After a median follow-up of 30 and 23.5 months since diagnosis and since recurrent/metastatic, median OS was not reached. Median TMB (n = 7) was 6.72 Mut/Mb. The most common pathogenic variants were TP53, HNF1A, SMARCB1, CDKN2A, PIK3CA, RB1 and MYC. There were 224 median TCR clones (n = 5 pts). In one patient, TCR clones increased from 59 to 1446 after nivolumab. HN NECs may achieve long-lasting survival with multimodality treatment. They harbor moderate-high TMBs and large TCR repertoires, which may explain responses to anti-PD1 agents in two patients and justify the study of immunotherapy in this disease.
PB MDPI
YR 2023
FD 2023-04-24
LK https://hdl.handle.net/20.500.14352/115328
UL https://hdl.handle.net/20.500.14352/115328
LA eng
NO Cabezas-Camarero, S., García-Barberán, V., Benítez-Fuentes, J. D., Sotelo, M. J., Plaza, J. C., Encinas-Bascones, A., De-la-Sen, Ó., Falahat, F., Gimeno-Hernández, J., Gómez-Serrano, M., Puebla-Díaz, F., De-Pedro-Marina, M., Iglesias-Moreno, M., & Pérez-Segura, P. (2023). Clinical Behavior, Mutational Profile and T-Cell Repertoire of High-Grade Neuroendocrine Tumors of the Head and Neck. Cancers, 15(9), 2431. https://doi.org/10.3390/cancers15092431
DS Docta Complutense
RD 10 abr 2025