Clinical Characteristics and Prognosis of Small Cell Carcinoma in the Nasopharynx: A Population-Based Study.

BACKGROUND: Nasopharyngeal small cell carcinoma (SmCC) is a rare histological type of nasopharyngeal cancer, and its prognosis remains poor. This study aimed to determine the clinical characteristics and survival prognostic factors of nasopharyngeal SmCC. METHODS: Detailed clinicopathologic and therapeutic characteristics of a patient diagnosed with nasopharyngeal SmCC were determined. Nasopharyngeal SmCC cases reported previously were reviewed and summarized. Furthermore, a retrospective analysis was performed on data from the Surveillance, Epidemiology, and End Results (SEER) Program database. Kaplan-Meier analysis was conducted to compare survival within groups. Univariate and multivariate analyses were performed to investigate prognostic factors. RESULTS: A nasopharyngeal SmCC patient treated with chemoradiotherapy who achieved 46 months long-term survival was reported. In reviewing 16 reported cases with epidemiologic and therapeutic details, we found most of nasopharyngeal SmCC patients were diagnosed with advanced grades and received chemoradiotherapy. In total, 13,993 cases of nasopharyngeal cancer were extracted from the SEER database, from which 57 nasopharyngeal SmCC cases were eventually screened out. The mean age of the patients was 55.70 years, and 64.9% of these cases were either grade III or IV; the median overall survival (OS) was 18 months. Statistically significant differences were observed in the OS values of groups categorized by age (P = .025) or radiotherapy (P = .037). Age (<70 years) and radiotherapy were identified as independent survival and prognostic factors. CONCLUSION: Patients with nasopharyngeal SmCC are usually diagnosed with advanced grades and have poor prognoses; nevertheless, they can benefit from radiotherapy with prolonged overall survival.

Combination of Tumor Mutational Burden and Specific Gene Mutations Stratifies Outcome to Immunotherapy Across Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma.

Purpose: To investigate the prognostic significance of tumor mutational burden (TMB) combined with specific prognosis-related gene mutations in immunotherapy for recurrent and metastatic head and neck squamous cell carcinoma (r/m HNSCC). Methods: One hundred thirty-two r/m HNSCC patients from the Morris and Allen cohorts had undergone immunotherapy. We constructed the immunotherapy-related gene prognostic index TP-PR combining TMB and PIK3CA, TP53, or ROS1 mutation. And we analyzed the differences in overall survival (OS) and immune cell infiltration between samples in different groups. The association of each signature's single-sample gene set enrichment analysis scores with TP-PR was tested using Spearman's correlation test. Results: The median OS of the patients with high TMB (TMB ≥10 mut/Mb) who received immunotherapy for r/m HNSCC was 2.5 times as long as that of the patients with low TMB (25 vs. 10 months). More importantly, the high TP-PR (TP-PR >0) group had better median OS (25 vs. 8 months) than the low TP-PR (TP-PR ≤0) group. CD8+ T cells and activated memory CD4+ T cells in the tissues of the patients with high TP-PR were higher than those in the patients with low TP-PR. Results showed that TP-PR stratification had a higher area under the curve (AUC) value (0.77, 95% CI 0.86-0.68) compared with TMB stratification (0.56, 95% CI 0.68-0.44). The differential gene expression in the high and low TP-PR groups mainly influenced metabolism-related signaling pathways. Conclusion: TP-PR was an effective predictor of immunotherapy outcome for r/m HNSCC, which might be better than TMB alone. Patients with high TP-PR had a better survival benefit than had the patients with low TP-PR.

Pathological and genomic phenotype of second neuroendocrine carcinoma during long-term follow-up after radical radiotherapy for nasopharyngeal carcinoma.

BACKGROUND: Second head and neck neuroendocrine carcinoma (NEC) after radical radiotherapy for nasopharyngeal carcinoma (NPC) treatment is rarely reported. The prognosis of second cancer is poor, and our research focuses on finding a breakthrough in the treatment. In this study, we aimed to investigate clinicopathological characteristics and to identify the genomic landscape of second head and neck NECs. METHODS: We collected five second head and neck NEC cases in the recent three years from our patient database. Clinicopathological data and images were obtained. Genomic analysis was performed using high-throughput second generation sequencing. KEGG pathway enrichment analyses between high-frequency mutations were performed using the STRING database. RESULTS: All patients had been diagnosed with second NEC, according to the pathological observations. The interval between diagnosis of NPC and NEC ranged from 10 to 18 years. Two patients had brain or liver metastasis at three and nine months, respectively, after the diagnosis of NEC. Three patients died of the disease with the overall survival time ranging from three to nine months. Commonly altered genes (50%) in second head and neck NECs included TP53, RB1, NOTCH2, PTEN, POLG, KMT2C, U2AF1, EPPK1, ELAC2, DAXX, COL22A1, and ABL1. Those genetic lesions might affect p53 signaling, MAPK signaling, PI3K-Akt signaling, sphingolipid signaling, and neurotrophin signaling pathways. CONCLUSIONS: Second head and neck NECs had poor prognosis. We revealed, for the first time, the mutational landscape, high-frequency somatic mutations, and potential signaling pathways of second head and neck NECs. Its optimal treatment model needs to be further studied in future clinical trials.