◥Purpose: Pembrolizumab improved survival in patients with recurrent or metastatic head and neck squamous-cell carcinoma (HNSCC). The aims of this study were to determine if pembrolizumab would be safe, result in pathologic tumor response (pTR), and lower the relapse rate in patients with resectable human papillomavirus (HPV)-unrelated HNSCC.Patients and Methods: Neoadjuvant pembrolizumab (200 mg) was administered and followed 2 to 3 weeks later by surgical tumor ablation. Postoperative (chemo)radiation was planned. Patients with high-risk pathology (positive margins and/or extranodal extension) received adjuvant pembrolizumab. pTR was quantified as the proportion of the resection bed with tumor necrosis, keratinous debris, and giant cells/histiocytes: pTR-0 (<10%), pTR-1 (10%-49%), and pTR-2 (≥50%). Coprimary endpoints were pTR-2 among all patients and 1-year relapse rate in patients with high-risk pathology (historical: 35%). Correlations of baseline PD-L1 and T-cell infiltration with pTR were assessed. Tumor clonal dynamics were evaluated (Clin-icalTrials.gov NCT02296684).Results: Thirty-six patients enrolled. After neoadjuvant pembrolizumab, serious (grades 3-4) adverse events and unexpected surgical delays/complications did not occur. pTR-2 occurred in eight patients (22%), and pTR-1 in eight other patients (22%). One-year relapse rate among 18 patients with high-risk pathology was 16.7% (95% confidence interval, 3.6%-41.4%). pTR ≥10% correlated with baseline tumor PD-L1, immune infiltrate, and IFNg activity. Matched samples showed upregulation of inhibitory checkpoints in patients with pTR-0 and confirmed clonal loss in some patients.Conclusions: Among patients with locally advanced, HPVunrelated HNSCC, pembrolizumab was safe, and any pathologic response was observed in 44% of patients with 0% pathologic complete responses. The 1-year relapse rate in patients with high-risk pathology was lower than historical.

Objective To comprehensively examine the prognostic significance of extranodal extension (ENE) in human papillomavirus–positive oropharyngeal squamous cell carcinoma (HPV‐positive OPSCC). Methods Retrospective cohort of cases diagnosed with HPV‐positive OPSCC from 2010 to 2015 in the National Cancer Database. Inclusion of all OPSCC HPV‐positive cases with appropriate International Classification of Diseases‐0‐3 codes that received surgery with a neck dissection. Univariate and multivariable analyses were conducted. Hazard ratios (HR) for the independent effects of ENE and N stage on overall survival were estimated by Cox proportional hazards regression. Results Cases that were ENE‐negative had the highest 5‐year survival (92.6%; 95% confidence interval [CI]: 90.5%–94.7%). ENE‐positive cases had the lowest 5‐year survival (84.0%; 95% CI: 80.7%−87.4%). After adjusting for confounding variables, ENE‐positivity was associated with almost twice the hazard of death (HR = 1.90; 95% CI: 1.35–2.67) compared to ENE‐negative cases. Nodal (N) category 1, ENE‐positive status was associated with an increased risk of death (HR = 1.88; 95% CI: 1.26–2.80) compared with N1, ENE‐negative status. Compared to N1/ENE‐negative cases, N2/ENE‐positive cases had the poorest survival (HR: 2.93; 95% CI: 1.94–4.43). Both microscopic and macroscopic ENE were associated with worse outcomes compared to node‐positive/ENE‐negative status. Conclusion The implementation of the American Joint Committee on Cancer 8th edition staging system provides a much‐improved framework to develop and discuss treatment plans for HPV‐positive OPSCC. We feel that careful consideration should be given to the importance of ENE in patients with HPV‐positive OPSCC. Level of Evidence 4 Laryngoscope, 130:939–945, 2020

Otolaryngologists should offer injection laryngoplasty to patients with a diagnosis of UVFP within 6 months of diagnosis (recommendation based on grade C evidence with a preponderance of benefit over harm). Laryngoscope, 128:935-940, 2018.

Objective:To test the hypothesis that there is shared regional or global functional connectivity dysfunction in a large cohort with isolated focal dystonia affecting different body regions compared to control participants. In this case-control study we obtained resting-state MRI scans (3-4 7.3 minute runs) with eyes closed in participants with focal dystonia (cranial [17], cervical [13], laryngeal [18], limb [10]) and age- and sex-matched controls.Methods:Rigorous preprocessing for all analyses was performed to minimize effect of head motion during scan acquisition (dystonia N=58, control N=47 analyzed). We assessed regional functional connectivity by computing a seed-correlation map between putamen, pallidum, and sensorimotor cortex and all brain voxels. We assessed significant group differences on a cluster-wise basis. In a separate analysis, we applied 300 seed regions across the cortex, cerebellum, basal ganglia and thalamus to comprehensively sample the whole brain. We obtained participant whole-brain correlation matrices by computing the correlation between seed average time courses for each seed pair. Weighted object-oriented data analysis assessed group-level whole-brain differences.Results:Participants with focal dystonia had decreased functional connectivity at the regional level, within the striatum and between lateral primary sensorimotor cortex and ventral intraparietal area, whereas whole-brain correlation matrices did not differ between focal dystonia and control groups. Rigorous quality control measures eliminated spurious large-scale functional connectivity differences between groups.Conclusion:Regional functional connectivity differences, not global network level dysfunction, contributes to common pathophysiological mechanisms in isolated focal dystonia. Rigorous quality control eliminated spurious large-scale network differences between focal dystonia and control participants.

No abstract