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PD-L1 testing guides therapeutic decision-making for head and neck squamous cell carcinoma (HNSCC). We sought to understand whether chemoradiation therapy (CRT) influences the PD-L1 combined positive score (CPS) and other biomarkers of response to immunotherapy. PD-L1 expression was assessed using immunohistochemistry, and bulk RNA sequencing was performed on 146 HNSCC patients (65 primary sites, 50 paired local recurrences, and 31 paired regional recurrences). PD-L1 was scored using the CPS of ≥1, ≥20, and ≥50. Overall, 98 %, 54 %, and 17 % of HNSCCs had a CPS ≥1, ≥20, and ≥50, respectively. When using a cut-off of ≥1, CRT did not significantly change CPS at the locoregional recurrent site. However, there were significant changes when using CPS ≥20 or ≥50. The CPS changed for 32 % of patients when using a CPS ≥20 (p < 0.001). When using a CPS ≥50, there was a 20-23 % (p = 0.0058-0.00067) discordance rate at the site of locoregional recurrence. Oral cavity cancers had a significantly higher discordant rate than other primary sites for CPS ≥50, 44 % (8/18, p = 0.0058) and 58 % (7/12, p = 0.00067) discordance at the site of local and regional recurrence, respectively. When evaluating the 18 gene IFN-ɣ signature predictive of response to anti-PD-1 blockade, there was a statistically significant increase in the IFN-ɣ signature in recurrent larynx cancer (p = 0.02). Our study demonstrates that when using a higher cut-off of CPS ≥20 and ≥50, a repeat biopsy may be warranted after CRT for local and regional recurrent HNSCCs., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: S.I.P. has received consultancy payments from Abbvie, Astrazeneca/MedImmune, Cue Biopharma, Fusion Pharmaceuticals, MSD/Merck, Newlink Genetics, Oncolys Biopharma, Replimmune, Scopus Biopharma, and Sensei Bio. S.I.P. has received grants/research support from Abbvie, Astrazeneca/MedImmune, Cue Biopharma, Merck, and Tesaro. R.B.B. has received consultancy payments from Merck, Regeneron, Macrogenics, and Bristol Myers Squibb. R.B.B. has received institutional research grants from Bristol Myers Squibb. All other authors declare no potential conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: Understanding the role of transoral surgery in oropharyngeal cancer (OPC) requires prospective, randomized multi-institutional data. Meticulous evaluation of surgeon expertise and surgical quality assurance (QA) will be critical to the validity of such trials. We describe a novel surgeon credentialing and QA process developed to support the ECOG-ACRIN Cancer Research Group E3311 (E3311) and report outcomes related to QA., Patients and Methods: E3311 was a phase II randomized clinical trial of transoral surgery followed by low- or standard-dose, risk-adjusted post-operative therapy with stage III-IVa (AJCC 7th edition) HPV-associated OPC. In order to be credentialed to accrue to this trial, surgeons were required to demonstrate active hospital credentials and technique-specific surgical expertise with ≥20 cases of transoral resection for OPC. In addition, 10 paired operative and surgical pathology reports from the preceding 24 months were reviewed by an expert panel. Ongoing QA required <10% rate of positive margins, low oropharyngeal bleeding rates, and accrual of at least one patient per 12 months. Otherwise surgeons were placed on hold and not permitted to accrue until re-credentialed using a new series of transoral resections., Results: 120 surgeons trained in transoral minimally invasive surgery applied for credentialing for E3311 and after peer-review, 87 (73%) were approved from 59 centers. During QA on E3311, positive final pathologic margins were reported in 19 (3.8%) patients. Grade III/IV and grade V oropharyngeal bleeding was reported in 29 (5.9%) and 1 (0.2%) of patients., Conclusions: We provide proof of concept that a comprehensive credentialing process can support multicenter transoral head and neck surgical oncology trials, with low incidence of positive margins and *grade III/V oropharyngeal bleeding., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: In this study we determine the survival in patients with HPV-positive oropharyngeal carcinoma treated with transoral robotic surgery (TORS), neck dissection and risk-adapted adjuvant therapy., Methods: We retrospectively identified 122 patients with HPV-positive oropharyngeal carcinoma treated with TORS and neck dissection between 2011 and 2018. Survival probability was calculated. We determined the effect of the type of neck dissection performed (modified radical neck dissection-MRND vs. selective neck dissection - SND), extranodal extension (ENE), margin status, and presence of ≥ 5 metastatic nodes on survival., Results: Our patient population had a five-year overall survival of 91.0% (95% C.I. 85-97%). The five-year probability of recurrence or cancer-associated death was 0.0977 (95% C.I. 0.0927-0.1027). The five-year probability of cancer-associated death was 0.0528 (95% C.I. 0.048-0.0570). All patients who died of their disease had distant metastasis. Our PEG dependence rate was 0%. Patients with ENE and positive margins who underwent adjuvant chemoradiation did not have worse survival. Presence of ≥ 5 metastatic nodes portended worse survival after controlling for age, positive ENE and margins. Low yield (<18 nodes) on neck dissection worsened DFS on multivariable analysis. Furthermore, patients who underwent SND did not have worse OS than those who underwent MRND., Conclusion: Our study demonstrates that surgery could be simplified by performing TORS with SND rather than MRND. The one true poor prognostic factor in HPV-positive oropharyngeal carcinoma patients who undergo surgery is high nodal burden. Patients with high nodal burden are much more likely to die from their disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: Self-inflicted gunshot wounds (SIGSWs) to the craniomaxillofacial region are uncommon injuries but are associated with a high mortality rate. Therefore, treating these patients is a rare occurrence even in the largest trauma centers. As with many rare conditions, data specifically addressing this injury pattern are scarce. Because of the proximity of the blast, even low-velocity injuries can be associated with significant avulsion of tissue, comminution of structures, and tissue die back. Previous case reports have recommended the use of prophylactic antibiotics, but no study has specifically investigated the postinjury infection rate or microbial patterns in this patient population. The purpose of this study was to answer the following clinical question: "Among patients with SIGW to the maxillofacial region, what is the prevalence of postinjury infection, and are there any microbial patterns that can guide empiric antibiotic selection?", Study Design: We designed retrospective cohort study at a level I trauma center in Portland, Oregon. Data on 17 patients who had sustained a SIGSW involving the maxilla or the mandible and survived their initial injury were collected from 2010 to 2017., Results: Patients who had a culture-positive infection within 30 days of their injury were defined to have a postinjury infection. Six of the 17 patients (35%) developed a postinjury infection, with an average time to infection of 11 days from initial injury (range 3-19 days). Of the 17 subjects, 15 (88%) received a course of prophylactic antibiotics, on average, for 14 days (range 3-24 days). Of the 6 cases of postinjury infection, culture grew gram-negative bacteria in 4 cases-anaerobic bacteria in 2 and polymicrobial organisms in 2. There was no clear pattern or prevalence of any specific bacterium, but cultures notably included Staphylococcus aureus, Enterobacter species, Bacteroides species, and Escherichia coli., Conclusions: SIGSWs are associated with a high rate of postinjury infection (35%) despite prophylactic antibiotic usage in 88% of these cases. Given the antimicrobial patterns observed in this study, prophylactic antibiotics in this patient population should include empiric coverage for gram-negative and anaerobic bacteria., (Copyright © 2019 Elsevier Inc. All rights reserved.)

OX40 is a member of the tumor necrosis factor (TNF) receptor family and a potent co-stimulatory pathway that when triggered can enhance T-cell memory, proliferation and anti-tumor activity in patients with metastatic cancer. Ongoing investigations at our institution have demonstrated that OX40 expressing T cells are found in abundance in the tumors of patients with advanced stage head and neck squamous cell carcinoma (HNSCC). This has led to the initiation of human clinical trials investigating OX40-directed therapy for patients with HNSCC in both the metastatic and curative setting. The purpose of this review is to explore what is known about OX40 signaling and discuss how this pathway potentially can be modulated to improve outcome for patients with HNSCC., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: The outcomes of the reconstruction of post-ablative and post-traumatic orbital defects are often unpredictable when considering the restoration of the orbital dimensions. Intraoperative navigation offers the surgeon visualization of bony landmarks via comparison to preoperative computed tomography, aiding in bony reduction and implant placement. The purpose of this study was to assess whether intraoperative navigation-guided orbital reconstruction re-establishes orbital volume and globe projection in subjects with post-ablative and post-traumatic orbital defects., Material and Methods: The investigators initiated a retrospective cohort study and enrolled a sample of subjects that underwent primary or secondary reconstruction for unilateral orbital deformities secondary to traumatic injury or tumour surgery. Pre- and post-operative orbital volume and globe projection were measured using Analyze (Mayo Clinic Biomedical Imaging Resource, Rochester, MN, USA). A matched pairs t-test was used to assess the difference in pre- and post-operative orbital volume and globe projection., Results: Twenty-three subjects underwent intraoperative navigation-guided orbital reconstruction. The mean difference in orbital volume and globe projection between the non-operated orbit and operated orbit in the post-operative period was -1.3 cm(3) and 2.4mm respectively. Both final measurements were within the margin of error of clinically noticeable enophthalmos. The mean absolute difference in orbital volume and globe projection between the pre- and post-operative period was 5.1 cm(3) (p=<0.001) and 4.1mm (p=<0.001) respectively., Conclusion: The results of this study suggest that orbital reconstruction using intraoperative navigation is effective in establishing normal orbital volume and globe projection in post-traumatic and post-ablative defects, therefore restoring the orbit and globe to pre-traumatic and pre-ablative conditions., (Copyright © 2011 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)