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

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.

Safety and Efficacy of Cetuximab-Based Salvage Chemotherapy After Checkpoint Inhibitors in Head and Neck Cancer.

BACKGROUND: There are still few data on the activity and safety of cetuximab-based salvage chemotherapy after immunotherapy (SCAI) in patients with squamous cell cancer of the head and neck (SCCHN). MATERIALS AND METHODS: This was a retrospective study of patients with SCCHN who received cetuximab-based SCAI after programmed cell death protein 1 or programmed cell death ligand 1(PD[L]1) inhibitors. Overall response rate (ORR) and disease control rate (DCR) with SCAI and with last chemotherapy before immunotherapy (LCBI) by RECIST 1.1, percentage change from baseline in target lesions (PCTL), progression-free survival (PFS), overall survival (OS), treatment compliance, and toxicity were evaluated. RESULTS: Between March 2016 and November 2019, 23 patients were identified. SCAI consisted of cetuximab-based combinations (3-weekly cisplatin-5FU-cetuximab [n = 2], weekly paclitaxel-cetuximab [n = 17], weekly cisplatin-cetuximab [n = 2], weekly carboplatin-paclitaxel-cetuximab [n = 2]). ORR was 56.5% (11 partial response, 2 complete response). DCR was 78.3%. Among 13 objective responders, median best PCTL was -53.5% (range, -30% to -100%). Median OS and PFS were 12 months and 6 months, respectively. In 10 patients receiving LCBI, ORR to LCBI was 40%, whereas ORR to SCAI achieved 60%. In LCBI-treated patients, median PFS with LCBI was 8 months and median PFS and OS with SCAI were 7 months and 12 months, respectively. Reduced dose intensity of the chemotherapy and cetuximab components occurred in 82.6% and 52.2% of the patients. Grade 1 or 2 adverse events (AEs) occurred in all patients. Grade 3 or 4 AEs developed in 65%, being grade 3 in all of them except in one patient (grade 4 neutropenia). There were no treatment-related deaths. CONCLUSION: Cetuximab-based salvage chemotherapy after PD(L)1 inhibitors associated with high response rates and deep tumor reductions with a manageable safety profile. Subsequent lines of therapy may explain the long survival achieved in our series. These results invite to design studies to elucidate the best therapeutic sequence in patients with SCCHN in the immunotherapy era. IMPLICATIONS FOR PRACTICE: Cetuximab-based salvage chemotherapy (SCAI) achieved high response rates in patients with recurrent/metastatic squamous cell cancer of the head and neck (SCCHN) after progression to PD-1/PD-L1 inhibitors. Objective response rate was higher than and progression-free survival was comparable to that of chemotherapy administered before immunotherapy (IO). In most patients, SCAI consisted of weekly, well-tolerated regimens. These observations have implications for current practice because of the limited evidence to date in SCCHN and the scant therapeutic options in this disease and invite to elucidate which may be the best treatment sequence for patients with head and neck cancer in the IO era.

Use of pectoralis major myofascial flap on the prevention of pharyngocutaneous fístula in salvage laryngectomy after chemoradiotherapy.

Background: Pharyngocutaneous fístula (PCF) is a major complication of salvage laryngectomies, mainly secondary to the effect of radiotherapy. Aims/objectives: Our main objective is to study the effect of pectoralis major myofascial flap (PMMF) on the prevention of PCF. Materials and methods: We studied all total laryngectomies (TL) performed between 2001 and 2018, noting the use of previous chemoradiation, the type of suture and the use of flaps. We recorded and compared the incidence of PCF in all groups. Results: A total of 146 patients were included, divided into a primary TL group (117 patients) and salvage TL (29 patients). PMMF was used in 62% of salvage TLs. The rates of PCF were 5.98% in primary TL and 17.2% in salvage procedures. Among the salvage TL group, in patients with pharyngeal closure alone, a PCF developed in 36.4% of cases, compared to 5.56% in the PMMF group. We found a similar rate of fistulae when comparing primary TL and salvage TL with PMMF, highlighting the protective effect of the flap. Conclusions and significance: The use of PMMF in salvage TL reduces the incidence of PCF, achieving a rate similar to that attained with primary TL.

Electrophysiological monitoring of hearing function during cochlear perilymphatic perfusions.

CONCLUSION: The cochlear perilymphatic perfusion produces, by itself, significant effects in the cochlear physiology that could be associated with the surgical procedure. These effects need to be well characterized to allow a reliable quantification of the effects of the experimental agent being tested. OBJECTIVES: The study focused on the accurate description of the electrophysiological effects on the cochlear potential recordings of perilymphatic perfusions. METHODS: Two successive cochlear perilymphatic perfusions were carried out. The first used artificial perilymph. The second used artificial perilymph alone or a kainic acid (KA) solution in artificial perilymph. The compound action potential of the auditory nerve (CAP-AN) was recorded: (1) before the first perfusion, (2) after the first perfusion and (3) after the second perfusion, and compared between groups. RESULTS: The first intracochlear perfusion with artificial perilymph produced significant effects in the CAP-AN that could be related to the surgical procedure. These effects were analysed separately from the effects produced by the KA. In particular, the KA administered intracochlearly produced a significant increase in the latency and a decrease in the amplitude of the CAP-AN N1 wave compared with the controls that were perfused twice with artificial perilymph.

The impact of comorbidity on the survival of patients with laryngeal squamous cell carcinoma.

UNLABELLED: Abstract Conclusions: In survival analysis, the combined Charlson comorbidity index (CCI) can be considered as a prognostic factor independent of the tumor node metastasis (TNM) classification, tumor stage, and tumor location. Severe comorbidity was the factor that had the greatest impact on prognosis in cases of initial tumor. OBJECTIVE: To study the influence of comorbidity on the survival of patients undergoing surgery for larynx cancer. METHODS: This was a retrospective study of the survival of 231 patients with laryngeal cancer who underwent surgery between 1995 and 2002. The CCI was used to assess comorbidity, the Kaplan-Meier method was used for survival analysis, and the Cox proportional risk regression model was used to identify independent prognostic factors. RESULTS: The multivariate analysis of specific mortality showed that patients classified as having severe comorbidity (CCI) were more likely to die (adjusted hazard ratio (adjHR) 1.85, 95% confidence interval (CI) 1.07-3.17). This difference was more important in patients with early tumor stages than in those with advanced stages.