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Purpose Fibula free flaps (FFF) are the gold standard tissue for reconstruction of segmental mandibular defects. A comparison of mini-plate (MP) and reconstruction bar (RB)-based fixation of FFFs has been previously described in a systematic review. Long-term studies comparing the two plating methods are lacking. The authors aim to examine the complication profile between MPs and RBs at a single tertiary cancer center. We hypothesized that increased components and a lack of rigid fixation inherent to MPs would lead to higher rates of hardware exposure/failure. Methods A retrospective review was performed from a prospectively maintained database at Memorial Sloan Kettering Cancer Center. Patients who underwent FFF-based reconstruction of mandibular defects between 2015-2021 were included. Data on patient demographics, risk factors, operative indications, and chemoradiation was collected. Primary outcomes of interest were perioperative flap-related complications, union rates, osteoradionecrosis (ORN), return to the operating room (OR), and hardware exposure/failure. Recipient site complications were stratified into two groups: early (90 days). Results 96 patients met inclusion criteria (RB=63, MP=33). Patients in were similar with respect to age, comorbidities, smoking history, and operative characteristics. The mean follow-up period was 17.24 months. There were no differences in rates of hardware failure overall; however, in patients with an initial complication after 90 days, MPs had significantly higher rates of hardware exposure (3 vs. 0, p=0.046). Conclusions MPs were found to have a higher risk of exposed hardware in patients with a late initial recipient site complication. It is possible that improved fixation with highly adaptive RBs designed by computer-aided design/manufacturing (CAD/CAM) technology explains these results. Future studies are needed to assess the effects of rigid mandibular fixation on patient reported outcome measures in this unique population.

Supplementary Figure 1 Legend from Effects of Tobacco Smoke on Gene Expression and Cellular Pathways in a Cellular Model of Oral Leukoplakia

Perspective on this Article from Effects of Cigarette Smoke on the Human Oral Mucosal Transcriptome

Use of tobacco is responsible for ∼30% of all cancer-related deaths in the United States, including cancers of the upper aerodigestive tract. In the current study, 40 current and 40 age- and gender-matched never smokers underwent buccal biopsies to evaluate the effects of smoking on the transcriptome. Microarray analyses were carried out using Affymetrix HGU133 Plus 2 arrays. Smoking altered the expression of numerous genes: 32 genes showed increased expression and 9 genes showed reduced expression in the oral mucosa of smokers versus never smokers. Increases were found in genes involved in xenobiotic metabolism, oxidant stress, eicosanoid synthesis, nicotine signaling, and cell adhesion. Increased numbers of Langerhans cells were found in the oral mucosa of smokers. Interestingly, smoking caused greater induction of aldo-keto reductases, enzymes linked to polycyclic aromatic hydrocarbon–induced genotoxicity, in the oral mucosa of women than men. Striking similarities in expression changes were found in oral compared with the bronchial mucosa. The observed changes in gene expression were compared with known chemical signatures using the Connectivity Map database and suggested that geldanamycin, a heat shock protein 90 inhibitor, might be an antimimetic of tobacco smoke. Consistent with this prediction, geldanamycin caused dose-dependent suppression of tobacco smoke extract–mediated induction of CYP1A1 and CYP1B1 in vitro. Collectively, these results provide new insights into the carcinogenic effects of tobacco smoke, support the potential use of oral epithelium as a surrogate tissue in future lung cancer chemoprevention trials, and illustrate the potential of computational biology to identify chemopreventive agents. Cancer Prev Res; 3(3); 266–78

Supplementary Figure 1 from Effects of Tobacco Smoke on Gene Expression and Cellular Pathways in a Cellular Model of Oral Leukoplakia

Perspective from Effects of Tobacco Smoke on Gene Expression and Cellular Pathways in a Cellular Model of Oral Leukoplakia

Supplementary Methods, Tables 1-5 from Effects of Cigarette Smoke on the Human Oral Mucosal Transcriptome

El presente estudio tuvo como objetivo describir patrones de activación cerebral mediante una técnica de Imagen por resonancia magnética funcional -fMRI- (abreviatura en inglés de Functional Magnetic Resonance Imaging) en una muestra de niños con Trastorno de estrés postraumático (TEPT) y compararlos con un grupo de controles. Estudio cuasi-experimental en el que se tomó un grupo de 15 niños con TEPT y se comparó con un grupo de 7 niños sin TEPT. Se emplearon dos tareas experimentales: una prueba de caras y una versión del Stroop emocional. Los resultados preliminares, señalan diferencias en el procesamiento de estímulos, principalmente de carácter negativo en los niños con TEPT y cambios en los patrones de activación a nivel de estructuras frontales. Se concluye que el trauma a edad temprana afecta el curso normal del desarrollo cerebral y se evidencia la importancia de abordar los aspectos explícitos e implícitos asociados a la experiencia traumática como parte de la intervención.

The past two years have witnessed a significant increase in the endorsement of conspiracy theories especially due to the emerging uncertainty caused by the pandemic. The prevalence of conspiracy beliefs could have negative social, health, and civic outcomes, thus it is important to understand the formalization and maintenance mechanism of conspiracy beliefs. The aim of this study is to examine the relationship between the deficit in learning and recognizing the probabilistic patterns of the environment while making decisions in an uncertain and unstable environment and the general tendency to engage with conspiracy theories. The Generic Conspiracist’s Belief Scale (GCBS) is used to estimate conspiracy theory beliefs and a web-based aversive learning task consisting of two blocks, i.e. stable and volatile, is designed to objectively assess individuals' ability to adapt their learning to changes in environmental volatility. Participants were recruited on social media and 69 participated in the experiment, 39 of which completed the whole experiment online. Our results suggest conspiracy belief is correlated with a deficit in the perception of the higher-order statistics about the causal structure of an aversive environment to guide decision-making (r(37) = -0.48, P = 0.002). People with high conspiracy beliefs are less able to update their learning rates to adapt to the changes in environmental volatility.

Background The presentation of frail older adults to the Emergency Department (ED) may be complicated by swallowing and/or communication impairment. Adults with communication impairment may experience difficulty accessing healthcare. Dysphagia is associated with frailty irrespective of age and/or number of chronic diseases [1]. This study aims to determine the prevalence and characteristics of swallowing and/or communication impairments among frail older adults attending the ED. Methods A retrospective cohort study of consecutive ED attendees aged ≥ 75 years assessed by an interdisciplinary Gerontological ED team between October 2021 – February 2022 was conducted. A swallow/communication screening tool determined requirement for Speech and Language Therapy (SLT) referral. Data related to demographics and SLT interventions was extracted. Data analysis was completed using STATA Version 12. Ethical approval was obtained. Results Among 518 patients, 118 (23%) (mean age 82.4 (+/-6.4) years, 54% male) required SLT assessment. These patients had high rates of frailty (Median CFS= 6 (IQR 5-7), suspected delirium (4AT ≥ 4 in 45%), suspected malnutrition (MNA score 0-11 in 75%), and probable sarcopenia (SARC-F= ≥ 4 in 75%). Therapy Outcome Measurement Scales and the Functional Oral Intake Scale were used in this first episode of SLT care. Oropharyngeal dysphagia was identified for 43% (27% mild, 10% moderate, 3% moderate-severe, 3% severe), with 6% presenting with signs/symptoms of oesophageal dysphagia. Changes in baseline communication was identified for 57%; cognitive communication difficulties (38%), dysarthria (11%), dysphonia (8%). SLT intervention and management approaches were initiated in the ED. Conclusion Findings indicate a high prevalence of swallowing/communication impairment in frail older adults attending the ED. Future research should explore SLT outcomes at point of discharge to refine these swallowing/communication presentations. Reference 1. Bahat G et al. Association between dysphagia and frailty in community-dwelling older adults. The Journal of Nutrition, Health & Ageing. 2019:23, 571–577.

Importance This study reports the impact of laser surgery on quality of life in patients with oral cavity lesions. Objective To compare postoperative pain and quality of life in patients treated with flexible fiberoptic CO2 laser vs electrocautery in patients with oral cavity precancerous lesions and early stage cancers. Design Randomized controlled trial. Setting Single center. Participants Patients with premalignant oral cavity lesions and early stage oral cancer. Intervention Patients were randomized to have surgical resection using either flexible fiber carbon dioxide laser (Laser) or electrocautery (EC). The patients were then followed over a period of 28 days to assess for outcomes including pain, quality of life, performance status, return to work, and return to diet. Quality of life was measured by the University of Washington Quality of Life (UWQOL) questionnaire and the performance status score (PSS). Main outcome measure The primary endpoint for this study was the numerical pain rating on postoperative day (POD) 7. Results Sixty‐two patients were randomized (32 laser and 30 electrocautery). Lesions excised were carcinoma in 30(48%), dysplasia in 31(50%) and benign in 1(2%). There was no difference in the location of lesion, size of lesion, defect size, type of closure, resection time, and blood loss between Laser and EC arms. Patients who had Laser had less pain compared to EC (mean pain score on POD 7 L = 2.84 vs EC = 3.83, P = 0.11). better UW QOL scores and PSS scores, quicker return to normal diet (median days L = 26.0 vs EC = 28.5, P = 0.17) and faster return to work (median days L = 13.0 vs EC = 16.5, P = 0.14). However, these results were not statistically significant. Conclusion There was a trend for patients treated with laser to have less pain and better quality of life scores but these result were not statistically significant. Based on the actual observed difference, a large multicenter RCT with 90 patients in each arm is required to determine the clinical relevance of our results.

The most common cancer caused by human papillomavirus (HPV) infection in the United States is oropharyngeal cancer (OPC), and its incidence has been rising since the turn of the century. Because of substantial long-term morbidities with chemoradiation and the favorable prognosis of HPV-positive OPC, identifying the optimal deintensification strategy for this group has been a keystone of academic head-and-neck surgery, radiation oncology, and medical oncology for over the past decade. However, the first generation of randomized chemotherapy deintensification trials failed to change the standard of care, triggering concern over the feasibility of de-escalation. National database studies estimate that up to one third of patients receive nonstandard de-escalated treatments, which have subspecialty-specific nuances. A synthesis of the multidisciplinary deintensification data and current treatment standards is important for the oncology community to reinforce best practices and ensure optimal patient outcomes. In this review, the authors present a summary and comparison of prospective HPV-positive OPC de-escalation trials. Chemotherapy attenuation compromises outcomes without reducing toxicity. Limited data comparing transoral robotic surgery (TORS) with radiation raise concern over toxicity and outcomes with TORS. There are promising data to support de-escalating adjuvant therapy after TORS, but consensus on treatment indications is needed. Encouraging radiation deintensification strategies have been reported (upfront dose reduction and induction chemotherapy-based patient selection), but level I evidence is years away. Ultimately, stage and HPV status may be insufficient to guide de-escalation. The future of deintensification may lie in incorporating intratreatment response assessments to harness the powers of personalized medicine and integrate real-time surveillance.

This paper critically examines the evolving state of sport governance with an applied examination of the Gaelic Athletic Association (GAA) in Ireland. The challenge, which this article considers, is how this transformation becomes realised in an organisation, like the GAA, whilst remaining broadly aligned to an amateur and volunteer-led ethos, still representative of its membership at large and continuing to be broadly equitable in its funding and other fiscal policies. At a governance level it raises specific questions about the role of elected boards, their backgrounds, competencies, scope, and purpose as this strategic ‘step change’ becomes embedded and, inevitably, poses many challenging questions. Put simply, if the direction of an organisation changes, requiring new and different attributes on behalf of those governing it, what is the most effective way to ensure this happens within specific cultural constraints and what are the associated challenges if it does not achieve this outcome? Refereed/Peer-reviewed

High-dose (HD) cisplatin remains the standard of care with chemoradiation for locally advanced oropharyngeal cancer (OPC). Cooperative group trials mandate bolus-HD (100 mg/m2 × 1 day, every 3 weeks) cisplatin administration at the beginning of the week to optimize radiosensitization-a requirement which may be unnecessary. This analysis evaluates the impact of chemotherapy administration day of week (DOW) on outcomes. We also report our institutional experience with an alternate dosing schedule, split-HD (50 mg/m2 × 2 days, every 3 weeks). We retrospectively reviewed 435 definitive chemoradiation OPC patients from 10 December 2001 to 23 December 2014. Those receiving non-HD cisplatin regimens or induction chemotherapy were excluded. Data collected included DOW, dosing schedule (bolus-HD vs split-HD), smoking, total cumulative dose (TCD), stage, Karnofsky Performance Status, human papillomavirus status and creatinine (baseline, peak and posttreatment baseline). Local failure (LF), regional failure (RF), locoregional failure (LRF), distant metastasis (DM), any failure (AF, either LRF or DM) and overall survival (OS) were calculated from radiation therapy start. Median follow-up was 8.0 years (1.8 months-17.0 years). DOW, dosing schedule and TCD were not associated with any outcomes in univariable or multivariable regression models. There was no statistically significant difference in creatinine or association with TCD in split-HD vs bolus-HD. There was no statistically significant association between DOW and outcomes, suggesting that cisplatin could be administered any day. Split-HD had no observed differences in outcomes, renal toxicity or TCD compared to bolus-HD cisplatin. Our data suggest that there is some flexibility of when and how to give HD cisplatin compared to clinical trial mandates.

Background Proton beam radiation therapy (PBRT) has dosimetric advantages compared to photon radiation therapy for the treatment of major salivary gland tumors (MSGTs). Methods Patients with non-metastatic MSGTs treated at a single proton therapy center from October 2013 to October 2018 were retrospectively reviewed. Results Sixty-eight patients with MSGTs were included and the most common site and histology were the parotid gland (75.0%) and adenoid cystic carcinoma (22.1%), respectively. The 3-year rates of locoregional control, progression-free survival, and overall survival were 95.1% (95% CI: 89.9%-100.0%), 80.7% (70.2%-92.7%), and 96.1% (95% CI: 90.9%-100.0%), respectively. Conclusion In a large cohort of MSGTs treated with PBRT, the rates of locoregional control were high in short-term follow-up and treatment was well tolerated.

Background Patients with human papillomavirus–related oropharyngeal cancers have excellent outcomes but experience clinically significant toxicities when treated with standard chemoradiotherapy (70 Gy). We hypothesized that functional imaging could identify patients who could be safely deescalated to 30 Gy of radiotherapy. Methods In 19 patients, pre- and intratreatment dynamic fluorine-18-labeled fluoromisonidazole positron emission tomography (PET) was used to assess tumor hypoxia. Patients without hypoxia at baseline or intratreatment received 30 Gy; patients with persistent hypoxia received 70 Gy. Neck dissection was performed at 4 months in deescalated patients to assess pathologic response. Magnetic resonance imaging (weekly), circulating plasma cell-free DNA, RNA-sequencing, and whole-genome sequencing (WGS) were performed to identify potential molecular determinants of response. Samples from an independent prospective study were obtained to reproduce molecular findings. All statistical tests were 2-sided. Results Fifteen of 19 patients had no hypoxia on baseline PET or resolution on intratreatment PET and were deescalated to 30 Gy. Of these 15 patients, 11 had a pathologic complete response. Two-year locoregional control and overall survival were 94.4% (95% confidence interval = 84.4% to 100%) and 94.7% (95% confidence interval = 85.2% to 100%), respectively. No acute grade 3 radiation–related toxicities were observed. Microenvironmental features on serial imaging correlated better with pathologic response than tumor burden metrics or circulating plasma cell-free DNA. A WGS-based DNA repair defect was associated with response (P = .02) and was reproduced in an independent cohort (P = .03). Conclusions Deescalation of radiotherapy to 30 Gy on the basis of intratreatment hypoxia imaging was feasible, safe, and associated with minimal toxicity. A DNA repair defect identified by WGS was predictive of response. Intratherapy personalization of chemoradiotherapy may facilitate marked deescalation of radiotherapy.

This study aimed to describe the cerebral activation patterns using fMRI (Functional Magnetic Resonance Imaging) technology in a sample of 15 children with Posttraumatic Stress Disorder (PTSD) and 7 with no PTSD. The study used a Quasi-experimental methodology where two experimental tasks were applied: an emotional face task and a version of an emotional Stroop task. The results point out differences in the group of PTSD on the processing of negative stimuli and changes in their frontal lobe activation. These preliminary results suggest that early traumatic experiences affect typical brain development patterns. And explicit and implicit variables involved in the traumatic experiences are discussed as a part of any intervention process. Resumen El presente estudio tuvo como objetivo describir patrones de activación cerebral mediante una técnica de Imagen por resonancia magnética funcional -fMRI- (abreviatura en inglés de Functional Magnetic Resonance Imaging) en una muestra de niños con Trastorno de estrés postraumático (TEPT) y compararlos con un grupo de controles. Estudio cuasi-experimental en el que se tomó un grupo de 15 niños con TEPT y se comparó con un grupo de 7 niños sin TEPT. Se emplearon dos tareas experimentales: una prueba de caras y una versión del Stroop emocional. Los resultados preliminares, señalan diferencias en el procesamiento de estímulos, principalmente de carácter negativo en los niños con TEPT y cambios en los patrones de activación a nivel de estructuras frontales. Se concluye que el trauma a edad temprana afecta el curso normal del desarrollo cerebral y se evidencia la importancia de abordar los aspectos explícitos e implícitos asociados a la experiencia traumática como parte de la intervención.

Because of the national emergency triggered by the coronavirus disease 2019 (COVID‐19) pandemic, government‐mandated public health directives have drastically changed not only social norms but also the practice of oncologic medicine. Timely head and neck cancer (HNC) treatment must be prioritized, even during emergencies. Because severe acute respiratory syndrome coronavirus 2 predominantly resides in the sinonasal/oral/oropharyngeal tracts, nonessential mucosal procedures are restricted, and HNCs are being triaged toward nonsurgical treatments when cures are comparable. Consequently, radiation utilization will likely increase during this pandemic. Even in radiation oncology, standard in‐person and endoscopic evaluations are being restrained to limit exposure risks and preserve personal protective equipment for other frontline workers. The authors have implemented telemedicine and multidisciplinary conferences to continue to offer standard‐of‐care HNC treatments during this uniquely challenging time. Because of the lack of feasibility data on telemedicine for HNC, they report their early experience at a high‐volume cancer center at the domestic epicenter of the COVID‐19 crisis., Cancer care is undeniably affected by the coronavirus disease 2019 (COVID‐19) public health emergency, but quality cancer care must persist. A high‐volume cancer center from the domestic epicenter of the COVID‐19 crisis shares its multidisciplinary approach to integrating current public health restrictions and adopting telemedicine to optimize the care of patients with head and neck cancer; it is hoped that this center's experience will provide helpful insights to oncology colleagues.

Purpose To demonstrate temporal lobe necrosis (TLN) rate and clinical/dose-volume factors associated with TLN in radiation-naïve patients with head and neck cancer treated with proton therapy where the field of radiation involved the skull base. Materials and Methods Medical records and dosimetric data for radiation-naïve patients with head and neck cancer receiving proton therapy to the skull base were retrospectively reviewed. Patients with Results Between 2013 and 2019, 234 patients were included. The median follow-up time was 22.5 months (range = 3.2–69.3). Overall TLN rates of any grade, ≥ grade 2, and ≥ grade 3 were 5.6% (N = 13), 2.1%, and 0.9%, respectively. The estimated 2-year TLN rate was 4.6%, and the 2-year rate of any brain necrosis was 6.8%. The median time to TLN was 20.9 months from proton completion. Absolute volume receiving 40, 50, 60, and 70 GyRBE (absolute volume [aV]); mean and maximum dose received by the temporal lobe; and dose to the 0.5, 1, and 2 cm3 volume receiving the maximum dose (D0.5cm3, D1cm3, and D2cm3, respectively) of the temporal lobe were associated with greater TLN risk while clinical parameters showed no correlation. Among volume parameters, aV50 gave maximum AUC (0.921), and D2cm3 gave the highest AUC (0.935) among dose parameters. The 11-cm3 cutoff value for aV50 and 62 GyRBE for D2cm3 showed maximum specificity and sensitivity. Conclusion The estimated 2-year TLN rate was 4.6% with a low rate of toxicities ≥grade 3; aV50 ≤11 cm3, D2cm3 ≤62 GyRBE and other cutoff values are suggested as constraints in proton therapy planning to minimize the risk of any grade TLN. Patients whose temporal lobe(s) unavoidably receive higher doses than these thresholds should be carefully followed with MRI after proton therapy.

BACKGROUND Proton therapy (PT) improves outcomes in patients with nasal cavity (NC) and paranasal sinus (PNS) cancers. Herein, the authors have reported to their knowledge the largest series to date using intensity-modulated proton therapy (IMPT) in the treatment of these patients. METHODS Between 2013 and 2018, a total of 86 consecutive patients (68 of whom were radiation-naive and 18 of whom were reirradiated) received PT to median doses of 70 grays and 67 grays relative biological effectiveness, respectively. Approximately 53% received IMPT. RESULTS The median follow-up was 23.4 months (range, 1.7-69.3 months) for all patients and 28.1 months (range, 2.3-69.3 months) for surviving patients. The 2-year local control (LC), distant control, disease-free survival, and overall survival rates were 83%, 84%, 74%, and 81%, respectively, for radiation-naive patients and 77%, 80%, 54%, and 66%, respectively for reirradiated patients. Among radiation-naive patients, when compared with 3-dimensional conformal proton technique, IMPT significantly improved LC (91% vs 72%; P

ImportanceUse of proton therapy reirradiation (PT-ReRT) for head and neck cancer is increasing; however, reports are heterogenous and outcomes can be difficult to interpret.ObjectiveTo evaluate outcomes and toxic effects following PT-ReRT in a uniform and consecutive cohort of patients with head and neck squamous cell carcinoma.Design, Setting, and ParticipantsThis retrospective cohort study included patients with recurrent primary head and neck squamous cell carcinoma who were treated with PT-ReRT from January 1, 2013, to December 31, 2020, at a single institution. Patient, clinical, and treatment characteristics were obtained, and multidisciplinary review was performed to record and grade early and late toxic effects.ExposuresProton therapy reirradiation.Main Outcomes and MeasuresFollow-up was defined from the start of PT-ReRT. The Kaplan-Meier method was used for outcomes of interest, including local control (LC), locoregional control, distant metastatic control, progression-free survival, and overall survival (OS). Cox proportional hazards regression modeling was used to assess associations of covariates with OS.ResultsA total of 242 patients (median [range] age, 63 [21-96] years; 183 [75.6%] male) were included. Of these patients, 231 (95.9%) had a Karnofsky performance status score of 70 or higher, and 145 (59.9%) had at least a 10–pack-year smoking history. Median (range) follow-up was 12.0 (5.8-26.0) months for all patients and 24.5 (13.8-37.8) months for living patients. A total of 206 patients (85.1%) had recurrent disease vs second primary or residual disease. The median (range) interval between radiation courses was 22 (1-669) months. Median PT-ReRT dose was 70 cobalt gray equivalents (CGE) for the fractionated cohort and 44.4 CGE for the quad shot cohort. For the fractionated cohort, the 1-year LC was 71.8% (95% CI, 62.8%-79.0%) and the 1-year OS was 66.6% (95% CI, 58.1%-73.8%). For the quad shot cohort, the 1-year LC was 61.6% (95% CI, 46.4%-73.6%) and the 1-year OS was 28.5% (95% CI, 19.4%-38.3%). Higher Karnofsky performance status scores (hazard ratio [HR], 0.50; 95% CI, 0.25-0.99; P = .046) and receipt of salvage surgery prior to PT-ReRT (HR, 0.57; 95% CI, 0.39-0.84; P = .005) were associated with improved OS, whereas receipt of quad shot (HR, 1.97; 95% CI, 1.36-2.86; P Conclusions and RelevanceThe findings of this cohort study suggest that, compared with previous reports with photon-based reirradiation, patients are living longer with aggressive PT-ReRT; however, surviving patients remain at risk of early and late complications.

Background Numerous studies and guidelines suggest an outcome detriment from radiation treatment breaks (rTBs) and the need for compensatory dosing in patients with head and neck cancer. Methods In a consecutive cohort of 521 patients with oropharyngeal squamous cell carcinoma (OPSCC), we investigated the impact of rTBs and prolongation of overall treatment time (OTT) on OS, DFS, LRC, and cancer recurrence using competing risk and multivariate analyses. Results Neither OTT prolongation by ≤2 days nor rTBs of ≤3 days were associated with detriments to clinical outcomes. Consecutive breaks of ≥3 days were also not significantly associated with detriment to clinical outcomes. There was significantly increased competing mortality in those with longer breaks. Conclusions In OPSCC patients treated with definitive concurrent chemoradiotherapy, there is no significant association between disease failure and total rTBs of ≤3 consecutive or scattered days. Further investigation is needed for longer breaks.

Treatment of oropharyngeal cancer (OPC) has undergone considerable evolution since the discovery of human papillomavirus (HPV)-associated OPC. It is widely understood that HPV OPC affects a younger population and standard treatment offers improved oncologic outcomes compared with non-HPV OPC but can cause significant toxicities and long-term side effects. Surgery for treatment de-escalation is an active area of research. The purpose of this review is to explore surgery as it relates to the treatment of HPV OPC with a focus on the evolution of treatment, rationale for surgery, surgical techniques, outcomes, and the role of surgery in de-escalation of treatment.

ImportancePatients with oropharyngeal carcinoma (OPC) treated with radiotherapy often experience substantial toxic effects, even with modern techniques such as intensity-modulated radiation therapy (IMRT). Intensity-modulated proton therapy (IMPT) has a potential advantage over IMRT due to reduced dose to the surrounding organs at risk; however, data are scarce given the limited availability and use of IMPT.ObjectiveTo compare toxic effects and oncologic outcomes among patients with newly diagnosed nonmetastatic OPC treated with IMPT vs IMRT with or without chemotherapy.Design, Setting, and ParticipantsThis retrospective cohort study included patients aged 18 years or older with newly diagnosed nonmetastatic OPC who received curative-intent radiotherapy with IMPT or IMRT at a single-institution tertiary academic cancer center from January 1, 2018, to December 31, 2021, with follow-up through December 31, 2021.ExposuresIMPT or IMRT with or without chemotherapy.Main Outcomes and MeasuresThe main outcomes were the incidence of acute and chronic (present after ≥6 months) treatment-related adverse events (AEs) and oncologic outcomes, including locoregional recurrence (LRR), progression-free survival (PFS), and overall survival (OS). Fisher exact tests and χ2 tests were used to evaluate associations between toxic effects and treatment modality (IMPT vs IMRT), and the Kaplan-Meier method was used to compare LRR, PFS, and OS between the 2 groups.ResultsThe study included 292 patients with OPC (272 [93%] with human papillomavirus [HPV]-p16–positive tumors); 254 (87%) were men, 38 (13%) were women, and the median age was 64 years (IQR, 58-71 years). Fifty-eight patients (20%) were treated with IMPT, and 234 (80%) were treated with IMRT. Median follow-up was 26 months (IQR, 17-36 months). Most patients (283 [97%]) received a dose to the primary tumor of 70 Gy. Fifty-seven of the patients treated with IMPT (98%) and 215 of those treated with IMRT (92%) had HPV-p16–positive disease. There were no significant differences in 3-year OS (97% IMPT vs 91% IMRT; P = .18), PFS (82% IMPT vs 85% IMRT; P = .62), or LRR (5% IMPT vs 4% IMRT; P = .59). The incidence of acute toxic effects was significantly higher for IMRT compared with IMPT for oral pain of grade 2 or greater (42 [72%] IMPT vs 217 [93%] IMRT; P P P P P = .003), nausea of grade 2 or greater (0 [0%] IMPT vs 18 [8%] IMRT; P = .04), and weight loss of grade 2 or greater (22 [37%] IMPT vs 138 [59%] IMRT; P Conclusions and RelevanceIn this study, curative-intent radiotherapy with IMPT for nonmetastatic OPC was associated with a significantly reduced acute toxicity burden compared with IMRT, with few chronic toxic effects and favorable oncologic outcomes, including locoregional recurrence of only 5% at 2 years. Prospective randomized clinical trials comparing these 2 technologies and of patient-reported outcomes are warranted.

PURPOSE Telomerase reverse transcriptase ( TERT) promoter mutations are prognostic in many cancers and have been observed in human papillomavirus (HPV)–negative head and neck squamous cell carcinomas (HNSCCs). However, the role of TERT promoter mutations in HPV-negative HNSCCs remains poorly understood in these cancers, which have increased risk for locoregional failure (LRF). PATIENTS AND METHODS We retrospectively identified patients who were diagnosed with HNSCC between July 1, 2004, and October 12, 2017, at Memorial Sloan Kettering Cancer Center and whose tumors underwent next-generation sequencing using the MSK-IMPACT panel. Patients with HPV-positive oropharyngeal squamous cell carcinoma (SCC) were excluded. Cumulative incidence of LRF, patterns of failure, and overall survival were measured. RESULTS We identified 117 patients with SCC of the oral cavity (OSCC), larynx, hypopharynx, or HPV-negative oropharynx whose tumors underwent next-generation sequencing. Sequencing was performed on 95 tumors that were obtained after recurrence and 22 that were obtained before recurrence. TERT promoter mutations were enriched in OSCC compared with laryngopharyngeal cancers (81.1% v 7.0%; P < .001), which was the largest genetic difference between these anatomic disease subsites. TERT promoter mutations were associated with LRF in OSCCs (Gray's test, P < .001) and in the overall cohort (Gray's test, P < .001). On multivariate analysis, TERT promoter mutations were associated with an increased risk for LRF (subdistribution hazard ratio, 2.82; 95% CI, 1.47 to 5.42; P = .0019), independent of oral cavity primary site and TP53 mutation status. CONCLUSION TERT promoter status is associated with the cumulative incidence of LRF and patterns of failure. TERT promoter mutations may define a subset of OSCCs with unique pathogenesis that is associated with an increased risk of LRF. Validation in prospective cohorts is warranted.

Objectives/hypothesis We used the National Cancer Database to identify the patterns of care and prognostic factors in adult patients with head and neck soft-tissue sarcoma (HNSTS). Study design Retrospective cohort analysis. Methods Using the National Cancer Database, we identified patients age ≥ 18 years who were diagnosed with HNSTS between 2004 and 2013. Both χ2 and multivariate logistic regression were used to identify factors associated with radiation therapy (RT) utilization. Kaplan-Meier methods were used to estimate overall survival (OS) and Cox proportional regression was used to determine significant contributors to OS. Results Our final cohort included 1,282 patients (682 treated with surgery only, 199 treated with RT only, and 401 treated with surgery and RT). Patients with younger age, poor tumor grade, rhabdomyosarcoma histology, and chemotherapy treatment were more likely to receive RT alone without surgery. Among the 1,083 surgical patients, RT utilization was associated with positive margins (odds ratio [OR]: 2.18, 95% confidence interval [CI]: 1.36-3.48), poor grade (OR: 2.92, 95% CI: 1.95-4.38), and chemotherapy use (OR: 1.78, 95% CI: 1.15-2.76). Radiotherapy utilization among surgical patients was not affected by demographic factors (age, sex, or ethnicity) or treatment institution (academic or community). For surgical patients, poor grade, large tumor size, and rhabdomyosarcoma histology were associated with worse OS on multivariate analysis. Conclusions In this analysis of HNSTS, younger patients with poor tumor grade and rhabdomyosarcoma histology were more likely to receive RT without surgery. Among surgical patients, adjuvant RT was more likely to be used for positive margins and poor grade, with no demographic disparities identified. Poor grade and rhabdomyosarcoma histology were negative prognostic factors for surgical patients. Level of evidence NA Laryngoscope, 130:120-127, 2020.