학술논문
Clinical Behavior, Mutational Profile and T-Cell Repertoire of High-Grade Neuroendocrine Tumors of the Head and Neck.
Document Type
Article
Author
Cabezas-Camarero, Santiago; García-Barberán, Vanesa; Benítez-Fuentes, Javier David; Sotelo, Miguel J.; Plaza, José Carlos; Encinas-Bascones, Alejandro; De-la-Sen, Óscar; Falahat, Farzin; Gimeno-Hernández, Jesús; Gómez-Serrano, Manuel; Puebla-Díaz, Fernando; De-Pedro-Marina, Manuel; Iglesias-Moreno, Maricruz; Pérez-Segura, Pedro
Source
Subject
*HEAD & neck cancer treatment
*SEQUENCE analysis
*GENETIC mutation
*IMMUNOHISTOCHEMISTRY
*HEAD & neck cancer
*RETROSPECTIVE studies
*NEUROENDOCRINE tumors
*DESCRIPTIVE statistics
*T cells
*TUMOR markers
*COMBINED modality therapy
*TUMOR grading
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Language
ISSN
2072-6694
Abstract
Simple Summary: Among 1083 patients with HN cancer, 11 patients with neuroendocrine carcinomas (NECs) of the head and neck (HN) were identified. In our series, HN NECs diagnosed with localized or locally advanced disease achieved long-lasting survival with multimodality treatment. HN NECs harbored mutations in TP53, HFN1A and RB1, among others, had a median TMB of 6.72 muts/Mb and showed wide TCR repertoires. Among three patients with metastatic disease that received anti-PD1 therapy, there were two long-lasting responders. 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. [ABSTRACT FROM AUTHOR]