Clinical Behavior, Mutational Profile and T-Cell Repertoire of High-Grade Neuroendocrine Tumors of the Head and Neck

Author:

Cabezas-Camarero Santiago1,García-Barberán Vanesa2,Benítez-Fuentes Javier David1ORCID,Sotelo Miguel J.345,Plaza José Carlos6,Encinas-Bascones Alejandro7,De-la-Sen Óscar7,Falahat Farzin7,Gimeno-Hernández Jesús8,Gómez-Serrano Manuel8ORCID,Puebla-Díaz Fernando9,De-Pedro-Marina Manuel7,Iglesias-Moreno Maricruz7,Pérez-Segura Pedro1

Affiliation:

1. Medical Oncology Department, Hospital Clínico Universitario San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), 28040 Madrid, Spain

2. Molecular Oncology Laboratory, Hospital Clínico Universitario San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), 28040 Madrid, Spain

3. Medical Oncology Department, Aliada Cancer Center, Lima 15036, Peru

4. Medical Oncology Department, Clínica San Felipe, Lima 15072, Peru

5. Medical Oncology Department, Hospital María Auxiliadora, Lima 15801, Peru

6. Pathology Department, Hospital Clínico Universitario San Carlos, 28040 Madrid, Spain

7. Maxillofacial Surgery Department, Hospital Clínico Universitario San Carlos, 28040 Madrid, Spain

8. Otolaryngology-Head and Neck Surgery Department, Hospital Clínico Universitario San Carlos, 28040 Madrid, Spain

9. Radiation Oncology Department, Hospital Clínico Universitario San Carlos, 28040 Madrid, Spain

Abstract

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.

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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