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Objectives: In an evolving era of immunotherapeutic options for persistent or recurrent laryngeal squamous cell carcinoma (LSCC), there is a need for improved biomarkers of treatment response and survival to inform optimal treatment selection and prognostication. Herein, our primary objective was to explore correlations between tumor infiltrating lymphocytes (TILs) and PD-L1 Combined Positive Score (CPS). Secondarily, we sought to explore their combined association with survival outcomes in patients with persistent or recurrent LSCC treated with salvage surgery., Materials and Methods: This was a retrospective cohort study at a single academic medical center. Immunohistochemistry staining for TILs and PD-L1 was performed on a tissue microarray of persistent or recurrent LSCC pathologic specimens. Correlations between TIL subsets and PD-L1 CPS were examined using Pearson's correlation coefficient and survival outcomes were analyzed with the Kaplan-Meier method and log-rank tests., Results: Only CD103 + TILs showed a statistically significant, weakly-positive correlation with PD-L1 CPS (r 2  = 0.264, p < 0.015). No other TIL subsets correlated with PD-L1 CPS in our cohort. The most favorable survival outcomes were seen in patients with pathologic N0 tumors showing high CD103 + TILs and/or high PD-L1 CPS staining., Conclusion: Among patients with persistent or recurrent LSCC, CD103 + TILs only modestly correlated with PD-L1 CPS. A combined biomarker score incorporating CD103 + TILs and PD-L1 CPS greatly enhanced survival discrimination. This model may have additional utility in predicting the clinical benefit of immunotherapies in persistent or recurrent LSCC in the future., 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 © 2022 Elsevier Ltd. All rights reserved.)

Objective: Trust is crucial to the success of any personal or professional relationship. Literature on trust in the surgeon-patient relationship has been largely explored through quantitative methodologies, primarily examining why trust may or may not exist. We aimed to qualitatively elucidate the mechanisms of how trust develops between otolaryngologists and their patients., Methods: Patients were recruited by surgery scheduling staff following an outpatient visit where a decision had been made to proceed with surgery at a tertiary academic medical center. We used qualitative realist thematic analysis of phone interviews to explore participants' (n = 17) perceptions and conceptualization of trust formation within the surgeon-patient relationship., Results: Thematic analysis revealed three themes regarding trust formation in the surgeon-patient relationship: 1) Trust Across Various Contexts; 2) Impact of Prior Knowledge; and 3) Interpersonal Connection during the Clinical Encounter., Conclusion: An interpersonal surgeon-patient connection is crucial to the formation of trust. Trust is also influenced by surgeon and institutional reputation and witnessed surgeon interactions with the healthcare team., Practice Implications: Patients perceive trust in a surgeon as carrying unique importance. To optimize conditions for trust development in this context, surgical care paradigms should promote meaningful preoperative interpersonal surgeon-patient relationships and positive surgeon and institutional reputations., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Trust is an essential element of an effective physician-patient relationship. There is limited literature examining trust between trainees and patients in the surgical setting. The goal of this study was to investigate how otolaryngology patients perceive trust in trainees during delivery of surgical care., Design: We extracted trainee-specific data from a larger, qualitative interview study examining trust in the surgeon-patient relationship. We then used realist thematic analysis to explore preoperative otolaryngology patients' perceptions of trust in trainees during delivery of surgical care., Setting: Department of Otolaryngology-Head and Neck Surgery at Michigan Medicine in Ann Arbor, MI, a tertiary academic medical center., Participants: Using convenience sampling, adults 18 years or older scheduled to undergo elective otolaryngologic surgery between February and June 2019 were invited, and 12 agreed to participate in the study., Results: All participants (n = 12) self-identified as White/Caucasian with a mean age of 60 years (range, 28-82). Participants were 50% (n = 6) female and 50% (n = 6) male. Thematic analysis of participants' perspectives about trust in trainees during delivery of surgical care revealed 3 themes. Trust in trainees is conditional based on (i) level of trainee involvement; (ii) trust in the attending surgeon; and, (iii) trust in the institution., Conclusion: Trust in trainees during delivery of surgical care is conditional on types of tasks trainees perform, bounded by trust in their attending surgeon, and positively influenced by institutional trust. Trainees and surgical educators must look to innovative methods to engender trust more efficiently in the clinic and immediate pre-operative setting. Such approaches can have a positive impact on patient outcomes, facilitate stronger trainee-attending interpersonal relationships, and empower surgeons to practice the professional values integral to surgical care., (Copyright © 2020 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

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.

Objectives: Financial toxicity (FT) is a significant barrier to high-quality cancer care, and patients with head and neck cancer (HNCA) are particularly vulnerable given their need for intensive support, daily radiotherapy (RT), and management of long-term physical, functional, and psychosocial morbidities following treatment. We aim to identify predictors of FT and adverse consequences in HNCA following RT., Materials and Methods: We performed a prospective survey study of patients with HNCA seen in follow-up at an academic comprehensive cancer center (CCC) or Veterans Affairs hospital between 05/2016 and 06/2018. Surveys included validated patient-reported functional outcomes and the COST measure, a validated instrument for measuring FT., Results: The response rate was 86% (n = 63). Younger age and lower median household income by county were associated with lower COST scores (i.e., worse FT) on multivariable analysis (p = .045 and p = .016, respectively). Patients with worse FT were more likely to skip clinic visits (RR (95% CI) 2.13 (1.23-3.67), p = .007), be noncompliant with recommended supplements or medications (1.24 (1.03-1.48), p = .02), and require supportive infusions (1.10 (1.02-1.20), p = .02). At the CCC, patients with worse FT were more likely to require feeding tubes (1.62 (1.14-2.31), p = .007). Overall, 36% reported that costs were higher than expected, 48% were worried about paying for treatment, and 33% reported at least a moderate financial burden from treatment., Conclusion: HNCA patients experience substantial FT from their diagnosis and/or therapy, with potential implications for medical compliance, QOL, and survivorship care., (Published by Elsevier Ltd.)

Objectives: We sought to describe the genetic complexity of 14 UM-SCC oral cavity cancer cell lines that have remained uncharacterized despite being used as model systems for decades., Materials and Methods: We performed exome sequencing on 14 oral cavity UM-SCC cell lines and denote the mutational profile of each line. We used a SNP array to profile the multiple copy number variations of each cell line and use immunoblotting to compare alterations to protein expression of commonly amplified genes (EGFR, PIK3CA, etc.). RNA sequencing was performed to characterize the expression of genes with copy number alterations., Results: The cell lines displayed a highly complex network of genetic aberrations that was consistent with alterations identified in the HNSCC TCGA project including PIK3CA amplification, CDKN2A deletion, as well as TP53 and CASP8 mutations, enabling genetic stratification of each cell line in the panel. Copy number FISH and spectral karyotyping analysis demonstrate that cell lines retain chromosomal heterogeneity., Conclusions: Collectively, we developed an important resource for future oral cavity HNSCC cell line studies and highlight the complexity of genomic aberrations in cell lines., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Well-differentiated thyroid carcinoma has seen a tremendous rise in global incidence over the past three decades, largely owing to widespread screening and identification of small, incidentally detected tumors. With this increased incidence has emerged a movement questioning whether all cases of thyroid cancer merit a treatment approach focused on oncologic completeness. Such trends towards thoughtful, evidence-based treatment de-escalation paradigms reflect better risk stratification of thyroid cancers, and recognition that not all detected disease poses a threat to health or survival. Thus, national and professional guidelines are evolving to incorporate higher thresholds for surgery, acceptance of less than total thyroidectomy in specific circumstances, higher thresholds for adjuvant therapy, and introduction of the role of active surveillance for selected cases of low risk disease. Despite these common themes, there are significant differences among guidelines. This lack of consensus in guidelines persists due to variation in clinical practice patterns, differences in consideration and interpretation of existing evidence, cultural and geographical considerations, and resources available for both diagnosis and treatment., (Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Tumor infiltrating lymphocytes (TILs) have been shown to be an important prognostic factor in patients with previously untreated head and neck cancer. After organ preservation therapy for laryngeal cancer and subsequent persistence/recurrence, the prognostic value of TILs is unknown. Our goal was to determine if TILs have value as a prognostic biomarker in patients with surgically salvageable persistent/recurrent laryngeal squamous cell carcinoma. Levels of TILs were quantified on tissue microarrays from 183 patients undergoing salvage total laryngectomy for persistent/recurrent laryngeal cancer after radiation or chemoradiation between 1997 and 2014. Demographic and clinical data were abstracted. Immunohistology evaluation included CD4, CD8, PDL-1, p16, CD31, Vimentin, EGFR, and p53. Elevated levels of either CD8 or CD4 positive TILs were associated with improved disease specific survival (CD8: HR 0.46, 95% CI 0.24-0.88, CD4: HR 0.43; 95% CI 0.21-0.89) and disease free survival (CD8: HR 0.53, 95% CI 0.29-0.94, CD4: HR 0.52; 95% CI 0.27-0.99). Levels of CD8 (HR 0.74; 95% CI 0.47-1.17) or CD4 (HR 0.66; 95% CI 0.40-1.08) TILs were not significantly associated with overall survival. In bivariate analysis, patients with elevated CD4 and/or CD8 TILs had significantly improved disease specific survival (HR 0.42; 95% CI 0.21-0.83) and disease free survival (HR 0.45; 95% CI 0.24-0.84) compared to patients with low levels of CD4 and CD8. PDL-1, p16, CD31, Vimentin, EGFR, and p53 were not significant prognostic factors. On multivariate analysis, elevated CD8 TILs were associated with improved disease specific survival (HR 0.35; 95% CI 0.14-0.88, p = .02) and disease free survival (HR 0.41; 95% CI 0.17-0.96, p = .04). CD8, and possibly CD4, positive TILs are associated with favorable disease free and disease specific survival for recurrent/persistent laryngeal cancer., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Optimal management of oral cancer relies upon accurate and individualized risk prediction of relevant clinical outcomes. Individualized prognostic calculators have been developed to guide patient-physician communication and treatment-related decision-making. However it is critical to scrutinize their accuracy prior to integrating into clinical care., Aim: To compare and evaluate oral cavity cancer prognostic calculators using an independent dataset., Methods: Five prognostic calculators incorporating patient and tumor characteristics were identified that evaluated five-year overall survival. A total of 505 patients with previously untreated oral cancer diagnosed between 2003 and 2014 were analyzed. Calculators were applied to each patient to generate individual predicted survival probabilities. Predictions were compared among prognostic tools and with observed outcomes using Kaplan-Meier plots, ROC curves and calibration plots., Results: Correlation between the five calculators varied from 0.59 to 0.86. There were considerable differences between individual predictions from pairs of calculators, with as many as 64% of patients having predictions that differed by more than 10%. Four of five calculators were well calibrated. For all calculators the predictions were associated with survival outcomes. The area under the ROC curve ranged from 0.65 to 0.71, with C-indices ranging from 0.63 to 0.67. An average of the 5 predictions had slightly better performance than any individual calculator., Conclusion: Five prognostic calculators designed to predict individual outcomes of oral cancer differed significantly in their assessments of risk. Most were well calibrated and had modest discriminatory ability. Given the increasing importance of individualized risk prediction, more robust models are needed., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: To identify predictive factors of severe long-term toxicity after re-irradiation of recurrent/persistent or second-primary head and neck cancer., Methods: Outcomes and treatment plans of patients who underwent modern IMRT based re-irradiation to the head and neck from 2008-2015 were reviewed. Co-variables including demographic, clinical and oncologic factors, as well as interval to re-irradiation and re-irradiated planning tumor volume (PTV) were analyzed as predictors of developing severe (CTCAE grade⩾3) long-term toxicity with death as a competing risk., Results: A total of 66 patients who met inclusion criteria were eligible for analysis. A median re-irradiation dose of 70Gy was delivered at a median of 37.5months after initial radiotherapy. Re-irradiation followed surgical resection in 25 (38%) patients, and concurrent chemotherapy was delivered to 41 (62%) patients. Median follow-up after re-irradiation was 23months and median overall survival was 22months (predicted 2year overall survival 49%). Of the 60 patients who survived longer than 3months after re-irradiation, 16 (25%) patients experienced severe long-term toxicity, with the majority (12 of 16) being feeding tube -dependent dysphagia. In multivariable analysis, shorter intervals to re-irradiation (<20months) and larger re-irradiated PTVs (>100cm(3)) were independent predictors of developing severe long-term toxicity. Patients with longer disease-free intervals and smaller PTVs had a 94% probability of being free of severe toxicity at two years., Conclusion: Selection of patients with longer re-irradiation intervals and requiring smaller re-irradiated PTVs can independently predict avoidance of severe long-term toxicity., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: Surgical margin status frequently affects decisions regarding adjuvant treatment; however, reporting and interpretation of surgical margins is subject to considerable subjectivity because of many factors including the adequacy of resection. We developed a novel measure of the adequacy of surgical resection, the tumor: specimen index (TSI), and tested its utility at predicting clinical outcomes in a retrospective cohort study., Patients and Methods: An institutional database was queried to identify previously untreated patients with T1 and T2 oral tongue cancer who underwent surgery during 1985-2009 (n=433). The TSI, a geometric mean representing the percentage of the surgical specimen that is occupied by the tumor in average single dimension, was calculated from the largest measured lengths, widths, and heights of the tumor in relation to the entire surgical specimen. Multivariate analyses of locoregional recurrence-free probability (LRRFP) and disease-specific survival (DSS) were performed with commonly accepted prognosticators in addition to TSI and surgical margins status., Results: The mean TSI was 41 (range 11-90; SD 14). Surgical margin status was associated with TSI; margins were negative in 84% of patients with TSI<45 and in 63% of patients with TSI⩾45 (p<0.001). TSI⩾45 was associated with worse LRRFP (57% vs. 76%, p<0.001) and worse DSS (68% vs. 85%, p<0.001). In a multivariate analysis that did not include TSI, surgical margin status independently predicted LRRFP (p=0.014) but not DSS. When TSI was included, only TSI, and not surgical margin status, was an independent predictor of both LRRFP (p=0.002) and DSS (p=0.011)., Conclusion: The tumor: specimen index is an easily-calculated metric for estimating the adequacy of 3-dimensional resection in T1 and T2 oral tongue cancer that independently predicts oncologic outcomes., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: To describe an institutional experience conducting an annual free head and neck (H&N) cancer screening clinic. Specific aims included: (1) identifying factors predicting which individuals will have findings suspicious for malignancy; and (2) evaluating potential barriers to subsequent follow-up among patients with suspicious findings., Materials and Methods: This retrospective cohort study involved individuals presenting to an annual H&N cancer screening clinic (2001-2012). Original screening clinic data and electronic medical records were reviewed. Descriptive and comparative statistics were utilized in order to address the study aims., Results: Of 1573 participants, 325 (21%) had abnormal findings on screening, of which 183 (12%) had findings suspicious for cancer. No demographic factors predicted a suspicion for cancer. The presence of patient-reported symptoms (16% vs. 8%; p<0.001) were significantly associated with a suspicion for cancer. Only 20% of individuals with a suspicion for cancer returned to our institution for recommended follow-up. Patients who did not complain of symptoms were less likely to return for follow-up (2% vs. 36%; p<0.001). Of the patients who returned for follow-up evaluation, malignancies were diagnosed in three patients., Conclusion: Few individuals presenting to a H&N cancer screening clinic will have a malignancy detected, and barriers may influence patients' likelihood to present for subsequent evaluation. Due to self-selection among patients presenting for screening, traditional risk factors may not be associated with the likelihood of detecting a suspicion for H&N cancer. Head and neck cancer screening clinics should thus target patients at high risk, and attempt to ensure appropriate follow-up thereafter., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: The ethical principle of autonomy is explored as it applies to situations in which patients' capacities to make decisions are questionable., Case Report: A 40-year-old man presented to the Emergency Department with an epidural hematoma, and refused to undergo emergent surgical treatment. Considering the acutely life-threatening nature of his problem and the inability to confirm the patient's capacity in the presence of a traumatic brain injury, the decision was made to proceed with emergent surgical treatment without consent., Discussion: The concept of conditional autonomy is introduced, defined, and employed to defend the process whereby a select group of patients may be treated without full knowledge of their wishes., (Copyright © 2011 Elsevier Inc. All rights reserved.)