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Carlos Suárez,1,2 Fernando López,1– 3 William M Mendenhall,4 Simon Andreasen5– 7†, Lauge Hjorth Mikkelsen,7 Johannes A Langendijk,8 Stefano Bondi,9 Juan P Rodrigo,1– 3 Leif Bäck,10 Antti A Mäkitie,10– 12 Verónica Fernández-Alvarez,13 Andrés Coca-Pelaz,1– 3 Robert Smee,14 Alessandra Rinaldo,15 Alfio Ferlito16 1Instituto de Investigación Sanitaria del Principado de Asturias and CIBERONC, ISCIII, Oviedo, Spain; 2Instituto Universitario de Oncología del Principado de Asturias, Universidad of Oviedo, Oviedo, Spain; 3Department of Otorhinolaryngology, Hospital Universitario Central de Asturias, Oviedo, Spain; 4Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL, USA; 5Department of Otorhinolaryngology Head and Neck Surgery and Audiology, Rigshospitalet, Copenhagen, Denmark; 6Department of Otorhinolaryngology and Maxillofacial Surgery, Zealand University Hospital, Køge, Denmark; 7Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; 8Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; 9Department of Otorhinolaryngology-Head and Neck Surgery, San Raffaele Hospital, Vita-Salute University, Milan, Italy; 10Department of Otorhinolaryngology - Head and Neck Surgery, University of Helsinki, Helsinki University Hospital, Helsinki, Finland; 11Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki, Finland; 12Division of Ear, Nose and Throat Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden; 13Vascular Surgery Department, Hospital Universitario Central de Asturias, Oviedo, Spain; 14Department of Radiation Oncology, The Prince of Wales Cancer Centre, Sydney, NSW, Australia; 15University of Udine School of Medicine, Udine, Italy; 16International Head and Neck Scientific Group, Padua, Italy†Simon Andreasen passed away on February 28, 2020Correspondence: Carlos SuárezInstituto de Investigación Sanitaria del Principado de Asturias and CIBERONC, ISCIII, Avenida de Roma s/n, Oviedo 33011, SpainEmail csuareznieto@gmail.comFernando LópezDepartment of Otorhinolaryngology, Hospital Universitario Central de Asturias, Avenida de Roma s/n, Oviedo 33011, SpainEmail flopez_1981@yahoo.esAbstract: The aim of this review is to analyze the latest trends in the management of non-vestibular skull base and intracranial schwannomas in order to optimize tumor control and quality of life. Non-vestibular cranial nerve schwannomas are rare lesions, representing 5– 10% of cranial nerve schwannomas. Management decisions should be individualized depending on tumor size, location and associated functional deficits. Generally, large sized schwannomas exerting significant mass effect with increased intracranial pressure are treated surgically. In some cases, even after optimal skull base resection, it is not possible to achieve a gross total resection because tumor location and extent and/or to reduce morbidity. Thus, subtotal resection followed by stereotactic radiosurgery or fractioned radiotherapy offers an alternative approach. In certain cases, stereotactic radiosurgery or radiotherapy alone achieves good tumor control rates and less morbidity to gross total resection. Finally, given the slow growth rate of most of these tumors, observation with periodic radiographic follow-up approach is also a reasonable alternative for small tumors with few, if any, symptoms.Keywords: schwannoma, head and neck, cranial nerves, non-vestibular, skull base

Carlos Suárez,1,2,* Verónica Fernández-Alvarez,3,* Marc Hamoir,4 William M Mendenhall,5 Primoz Strojan,6 Miquel Quer,7 Carl E Silver,8 Juan P Rodrigo,1,2,9 Alessandra Rinaldo,10 Alfio Ferlito11 1Head & Neck Cancer Laboratory, Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain; 2Head & Neck Cancer Laboratory, Instituto Universitario de Oncología del Principado de Asturias, CIBERONC, University of Oviedo, Oviedo, Spain; 3Department of Vascular Surgery, Hospital Universitario de Cabueñes, Gijón, Spain; 4Department of Head and Neck Surgery, Head and Neck Oncology Program, King Albert II Cancer Institute, St Luc University Hospital, Brussels, Belgium; 5Department of Radiation Oncology, University of Florida, Gainesville, FL, USA; 6Department of Radiation Oncology, Institute of Oncology, Ljubljana, Slovenia; 7Department of Otolaryngology, Hospital Santa Creu i Sant Pau, Barcelona, Spain; 8Department of Surgery, University of Arizona, Phoenix, AZ, USA; 9Department of Otolaryngology, Hospital Universitario Central de Asturias, Oviedo, Spain; 10University of Udine School of Medicine, Udine, Italy; 11International Head and Neck Scientific Group Padua, Italy *These authors contributed equally to this work Abstract: Carotid blowout syndrome (CBS) refers to rupture of the carotid artery and is an uncommon complication of head and neck cancer that can be rapidly fatal without prompt diagnosis and intervention. CBS develops when a damaged arterial wall cannot sustain its integrity against the patient’s blood pressure, mainly in patients who have undergone surgical procedures and radiotherapy due to cancer of the head and neck, or have been reirradiated for a recurrent or second primary tumor in the neck. Among patients irradiated prior to surgery, CBS is usually a result of wound breakdown, pharyngocutaneous fistula and infection. This complication has often been fatal in the past, but at the present time, early diagnosis and modern technology applied to its management have decreased morbidity and mortality rates. In addition to analysis of the causes and consequences of CBS, the purpose of this paper is to critically review methods for early diagnosis of this complication and establish individualized treatment based on endovascular procedures for each patient. Keywords: carotid blowout, head and neck cancer, reirradiation, surgery, covered stents, embolization

R Michael Baskin,1 Brian J Boyce,1,2 Robert Amdur,2,3 William M Mendenhall,2,3 Kathryn Hitchcock,2,3 Natalie Silver,1,2 Peter T Dziegielewski1,2 1Department of Otolaryngology, University of Florida, Gainesville, FL, USA; 2University of Florida Health Cancer Center, Gainesville, FL, USA; 3Department of Radiation Oncology, University of Florida, Gainesville, FL, USA Abstract: The increasing incidence of oropharyngeal squamous cell carcinoma (OPSCC) emphasizes the importance of optimizing treatment for the disease. Historical protocol has utilized definitive radiation and invasive open procedures; these techniques expose the patient to significant risks and morbidity. Transoral robotic surgery (TORS) has emerged as a therapeutic modality with promise. Here, the literature regarding proper patient selection and other considerations for this procedure was reviewed. Multiple patient and tumor-related factors were found to be relevant for successful use of this treatment strategy. Outcomes regarding early and advanced-stage OPSCC were analyzed. Finally, the literature regarding use of TORS in three distinct patient populations, individuals with primary OPSCC, carcinoma of unknown primary and those with recurrent OPSCC, was examined. Keywords: oropharyngeal cancer, TORS, robotic surgery, carcinoma of unknown primary

Aims: Smoking and human papillomavirus (HPV) are both distinct risk factors for head and neck cancer, but the nature of interaction between these 2 risk factors in the development of head and neck cancer remains unclear. The purpose of this review is to determine the potential effect of smoking in causation of HPV-related head and neck carcinoma.Method: A literature search was carried out using the keywords human papillomavirus, head and neck cancer, smoking, tobacco, and cervical cancer. The English-language articles, references, and other relevant studies evaluating the association of smoking, HPV, and risk of head and neck cancer were collected and analyzed.Conclusion: Overall, our review points to smoking tobacco posing an additional risk for development of head and neck cancer in the presence of HPV infection. This is consistent with available laboratory data that show evidence of biological plausibility for interaction between smoking and progression of HPV infection to carcinogenesis. It is therefore important that cessation of smoking is promoted in smokers with HPV infection. [ABSTRACT FROM AUTHOR]

Locally recurrent nasopharyngeal carcinoma (NPC) presents substantial challenges in clinical management. Although postoperative re-irradiation (re-RT) has been acknowledged as a potential treatment option, standardized guidelines and consensus regarding the use of re-RT in this context are lacking. This article provides a comprehensive review and summary of international recommendations on postoperative management for potentially resectable locally recurrent NPC, with a special focus on postoperative re-RT. A thorough search was conducted to identify relevant studies on postoperative re-RT for locally recurrent NPC. Controversial issues, including resectability criteria, margin assessment, indications for postoperative re-RT, and the optimal dose and method of re-RT, were addressed through a Delphi consensus process. The consensus recommendations emphasize the need for a clearer and broader definition of resectability, highlighting the importance of achieving clear surgical margins, preferably through an en bloc approach with frozen section margin assessment. Furthermore, these guidelines suggest considering re-RT for patients with positive or close margins. Optimal postoperative re-RT doses typically range around 60 Gy, and hyperfractionation has shown promise in reducing toxicity. These guidelines aim to assist clinicians in making evidence-based decisions and improving patient outcomes in the management of potentially resectable locally recurrent NPC. By addressing key areas of controversy and providing recommendations on resectability, margin assessment, and re-RT parameters, these guidelines serve as a valuable resource for clinical experts involved in the treatment of locally recurrent NPC., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: There is an inverse relationship between cancer cure and overall treatment time (OTT) in patients treated with surgical resection and radiotherapy (RT)., Methods: OTT was evaluated based on the reconstruction procedure in 420 patients with oral cavity and larynx cancers treated with surgery and RT between 1991 and 2020., Results: With OTT >85 days, the difference between no versus yes flap reconstruction was ~20 percentage points and significant for all comparisons: primary closure (+/- skin graft), 49%, vs. rotation or free flap, 71% ( P <0.0001); primary closure (+/- skin graft), 49%, versus free flap without bone, 66% ( P =0.0358); and primary closure (+/- skin graft), 49%, versus free flap with bone, 82% ( P <0.0001)., Conclusions: The use of flap reconstructions results in substantial increases in OTT. Findings suggest a need to reevaluate current policies regarding the choice of reconstruction and starting RT sooner after surgery., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Radiotherapy is one of the mainstay treatment modalities for the management of non-metastatic head and neck cancer (HNC). Notable improvements in treatment outcomes have been observed in the recent decades. Modern radiotherapy techniques, such as intensity-modulated radiotherapy and charged particle therapy, have significantly improved tumor target conformity and enabled better preservation of normal structures. However, because of the intricate anatomy of the head and neck region, multiple critical neurological structures such as the brain, brainstem, spinal cord, cranial nerves, nerve plexuses, autonomic pathways, brain vasculature, and neurosensory organs, are variably irradiated during treatment, particularly when tumor targets are in close proximity. Consequently, a diverse spectrum of late neurological sequelae may manifest in HNC survivors. These neurological complications commonly result in irreversible symptoms, impair patients' quality of life, and contribute to a substantial proportion of non-cancer deaths. Although the relationship between radiation dose and toxicity has not been fully elucidated for all complications, appropriate application of dosimetric constraints during radiotherapy planning may reduce their incidence. Vigilant surveillance during the course of survivorship also enables early detection and intervention. This article endeavors to provide a comprehensive review of the various neurological complications of modern radiotherapy for HNC, summarize the current incidence data, discuss methods to minimize their risks during radiotherapy planning, and highlight potential strategies for managing these debilitating toxicities., 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 © 2024 Elsevier B.V. All rights reserved.)

Purpose: Adenoid cystic carcinoma (ACC) is a rare malignancy accounting for 1% of all head and neck cancers. Treatment for ACC has its challenges and risks, yet few outcomes studies exist. We present long-term outcomes of patients with ACC of the head and neck treated with proton therapy (PT)., Materials and Methods: Under an institutional review board-approved, single-institutional prospective outcomes registry, we reviewed the records of 56 patients with de novo, nonmetastatic ACC of the head and neck treated with PT with definitive ( n  = 9) or adjuvant PT ( n  = 47) from June 2007 to December 2021. The median dose to the primary site was 72.6 gray relative biological equivalent (range, 64-74.4) delivered as either once ( n  = 19) or twice ( n  = 37) daily treatments. Thirty patients received concurrent chemotherapy. Thirty-one patients received nodal radiation, 30 electively and 1 for nodal involvement., Results: With a median follow-up of 6.2 years (range, 0.9-14.7), the 5-year local-regional control (LRC), disease-free survival, cause-specific survival, and overall survival rates were 88%, 85%, 89%, and 89%, respectively. Intracranial extension ( P  = .003) and gross residual tumor ( P  = .0388) were factors associated with LRC rates. While the LRC rate for those with a gross total resection was 96%, those with subtotal resection or biopsy alone were 81% and 76%, respectively. The 5-year cumulative incidence of clinically significant grade ≥3 toxicity was 15%, and the crude incidence at the most recent follow-up was 23% ( n  = 13)., Conclusion: This is the largest sample size with the longest median follow-up to date of patients with ACC treated with PT. PT can provide excellent disease control for ACC of the head and neck with acceptable toxicity. T4 disease, intracranial involvement, and gross residual disease at the time of PT following either biopsy or subtotal resection were significant prognostic features for worse outcomes.

Background: Patients with head and neck cancer (HNC) may experience substantial anatomical changes during the course of radiotherapy treatment. The implementation of adaptive radiotherapy (ART) proves effective in managing the consequent impact on the planned dose distribution., Methods: This narrative literature review comprehensively discusses the diverse strategies of ART in HNC and the documented dosimetric and clinical advantages associated with these approaches, while also addressing the current challenges for integration of ART into clinical practice., Results and Conclusion: Although based on mainly non-randomized and retrospective trials, there is accumulating evidence that ART has the potential to reduce toxicity and improve quality of life and tumor control in HNC patients treated with RT. However, several questions remain regarding accurate patient selection, the ideal frequency and timing of replanning, and the appropriate way for image registration and dose calculation. Well-designed randomized prospective trials, with a predetermined protocol for both image registration and dose summation, are urgently needed to further investigate the dosimetric and clinical benefits of ART., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Sinonasal neoplasms, whether benign and malignant, pose a significant challenge to clinicians and represent a model area for multidisciplinary collaboration in order to optimize patient care. The International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors (ICSNT) aims to summarize the best available evidence and presents 48 thematic and histopathology-based topics spanning the field., Methods: In accordance with prior International Consensus Statement on Allergy and Rhinology documents, ICSNT assigned each topic as an Evidence-Based Review with Recommendations, Evidence-Based Review, and Literature Review based on the level of evidence. An international group of multidisciplinary author teams were assembled for the topic reviews using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses format, and completed sections underwent a thorough and iterative consensus-building process. The final document underwent rigorous synthesis and review prior to publication., Results: The ICSNT document consists of four major sections: general principles, benign neoplasms and lesions, malignant neoplasms, and quality of life and surveillance. It covers 48 conceptual and/or histopathology-based topics relevant to sinonasal neoplasms and masses. Topics with a high level of evidence provided specific recommendations, while other areas summarized the current state of evidence. A final section highlights research opportunities and future directions, contributing to advancing knowledge and community intervention., Conclusion: As an embodiment of the multidisciplinary and collaborative model of care in sinonasal neoplasms and masses, ICSNT was designed as a comprehensive, international, and multidisciplinary collaborative endeavor. Its primary objective is to summarize the existing evidence in the field of sinonasal neoplasms and masses., (© 2023 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Background: Pediatric esthesioneuroblastoma (EN) can infiltrate skull base anatomy, presenting challenges due to high radiation doses and pediatric tissue sensitivity. This study reports outcomes of pediatric EN treated with proton radiotherapy (PT)., Procedure: Using an IRB-approved prospective outcomes registry, we evaluated patient, tumor, and treatment-related variables impacting disease control and toxicity in pediatric nonmetastatic EN treated with modern multimodality therapy, including PT., Results: Fifteen consecutive patients (median age 16) comprising Kadish stage B (n = 2), C (n = 9), and D (n = 4) tumors were assessed, including six with intracranial involvement, four with cranial nerve deficits, and four with cervical lymphadenopathy. Before radiation, two had subtotal and 13 had gross total resections (endoscopic or craniofacial). Two underwent neck dissection. Eleven received chemotherapy before radiation (n = 5), concurrent with radiation (n = 4), or both (n = 2). Median total radiation dose (primary site) was 66 Gy/CGE for gross disease and 54 Gy/CGE (cobalt Gray equivalent) for microscopic disease. Median follow-up was 4.8 years. No patients were lost to follow-up. Five-year disease-free and overall survival rates were 86% (no local or regional recurrences). Two patients developed vertebral metastases and died. Two required a temporary feeding tube for oral mucositis/dysphagia. Late toxicities included symptomatic retinopathy, major reconstructive surgery, cataracts, chronic otitis media, chronic keratoconjunctivitis, hypothyroidism, and in-field basal cell skin cancer., Conclusions: A multimodality approach for pediatric EN results in excellent local control. Despite the moderate-dose PT, serious radiation toxicity was observed; further dose and target volume reductions may benefit select patients. Longer follow-up and comparative data from modern photon series are necessary to fully characterize any relative PT advantage., (© 2023 Wiley Periodicals LLC.)

Purpose: Obtaining prior authorization (PA) before treatment is becoming increasingly burdensome in oncology, especially in radiation oncology. Here, we describe the impact of a strategic novel operational PA redesign to shorten authorization time and to improve patient access to cancer care at a large United States academic proton therapy center. We ask whether such a redesign may be replicable and adoptable across oncology centers., Materials and Methods: Our PA redesign strategy was based on a 3-tiered approach. Specifically, we (1) held payors accountable to legally backed timelines, (2) leveraged expertise on insurance policies and practices, and (3) updated the submission, appeal writing, and planning procedures for PA. Metrics were compared at the following 3 time points: 6 months before, at phase-in, and at 6 months after intervention., Results: In analyzing the impact of improving PA access to care, the percentage of approvals for commercial proton beam therapy improved by an absolute 30.6% postintervention ( P < .001). The proportion of commercially insured patients treated with proton beam therapy also increased by 6.2%, and the number of new starts rose by 11.7 patients/mo. Overall patient census increased by 13 patients/d. Median authorization time was 1 week, and 90% of surveyed providers reported reduced PA burden and improved patient care., Conclusion: This is the first validated, comprehensive operational strategy to improve access to cancer therapy while reducing the burden of PA. This novel approach may be helpful for addressing barriers to PA in medical and surgical oncology because the redesign is predicated on laws that regulate PA across disciplines., Competing Interests: Conflict of Interest: Nancy P. Mendenhall is the Editor-in-Chief of International Journal of Particle Therapy. All other authors declare no conflict of interest., (©Copyright 2023 The Author(s).)

Background: Prescription drug monitoring programs (PDMPs) have proliferated due to increasing opioid-related deaths. We evaluated acute opioid use changes for 64 patients treated with highly conformal radiotherapy (RT) following a state-mandated PDMP., Methods: Patients receiving proton therapy (PT) (n=40), intensity-modulated RT (IMRT) (n=14), or both (n=10) were divided into preintervention (n=26) and postintervention cohorts (n=38); records were reviewed retrospectively under an institutional review board (IRB)-approved tracking protocol. Dosages prescribed during acute therapy (during RT-3 months post-RT) and patient-reported pain (Defense and Veterans Pain Rating Scale) were endpoints. Dosages were treated as responses in Chi-square tests (three-level ordinal response)., Results: Overall, 72% (n=46) received opioids; of which 22% (n=10) of all patients and 10% (n=2) of opioid-naive patients continued analgesic management 3 months post-RT. Median total doses were 975 and 1,025 morphine milligram equivalents (MME) in pre- and postintervention groups, with no significant differences in MME prescribed (P=0.8) or uncontrolled pain (P=0.3). Statistically significant factors were tonsil primaries (P<0.01) and alcohol use (P=0.02). Uncontrolled pain episodes during and post-RT did not vary per cohort (P=0.19)., Conclusions: PDMP use was not associated with management changes in patient-reported acute pain during RT (IMRT or PT). Following highly conformal RT, few patients remained on narcotics 3 months post-RT.

Background: Locally recurrent prostate cancer following primary external beam radiotherapy without distant metastasis is a challenging problem, with no current consensus on the optimal management of these patients. Traditional whole-gland salvage treatments offered up to a 50% 5-year disease-free survival rate but with troubling levels of risk for significant complications. Recent progress in advanced imaging techniques has allowed a more accurate selection of patients with local-only recurrence and a selection of patients that may be suitable for newer partial-gland salvage treatments that may reduce late complications., Methods: This article reviews advances in patient selection and provides an overview of whole- and partial-gland salvage results from selected recent meta-analyses, multi-institutional series, and studies from centers of excellence for these treatment approaches., Results: Salvage radical prostatectomy produces 5-year relapse-free survival (RFS) rates in the 50%-60% range with severe gastrointestinal (GI) toxicity in < 2% but severe genitourinary (GU) toxicity in 15%-23% of patients. The whole-gland options of high and low dose rate brachytherapy and stereotactic body radiation therapy appear to offer similar 5-year control rates, with low severe GU and GI toxicity rates of 4%-8% and <2%, respectively. Cryotherapy and high-intensity focused ultrasound (HIFU) offer similar 5-year RFS rates but carry significant risks for severe GU and GI toxicity in the range of 10%-27% and <2%, respectively. Early results of partial-gland salvage techniques in selected patients appear promising, with 3-year RFS rates of 48%-72% and rare grade 3 toxicity., Conclusion: It is important to understand the relative effectiveness and risks of the various treatment options to effectively counsel patients who face this distressing clinical situation. Whole-gland salvage options offer the possibility of long-term control but with significant risks of severe toxicity. Emerging data for the partial-gland salvage options in appropriately selected patients may offer hope of reasonable control rates with reduced severe toxicity., (© 2023 Wiley Periodicals LLC.)

Proton therapy (PT) is a form of highly conformal external-beam radiotherapy used to mitigate acute and late effects following radiotherapy. Indications for treatment include both benign and malignant skull-base and central nervous system pathologies. Studies have demonstrated that PT shows promising results in minimizing neurocognitive decline and reducing second malignancies with low rates of central nervous system necrosis. Future directions and advances in biologic optimization may provide additional benefits beyond the physical properties of particle dosimetry., Competing Interests: Conflicts of Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To evaluate lymphovascular invasion as an independent predictor for overall survival in patients with oral cavity squamous cell carcinoma., Study Design: Retrospective cohort study., Setting: Multi-center, population-based facilities reporting to the National Cancer Database registry., Methods: The database was accessed to collect data on patients with oral cavity squamous cell carcinoma. A multivariate cox proportional hazards model was used to analyze the association between presence of lymphovascular invasion and overall survival., Results: 16,992 patients met inclusion criteria. 3,457 patients had lymphovascular invasion. The mean follow-up was 32 ± 19 months. Lymphovascular invasion predicted reduced 2-year overall survival (relative hazard 1.29, 95% CI: 1.20, 1.38, p < 0.001) and 5-year overall survival (relative hazard 1.30, 95% CI: 1.23, 1.39, p < 0.001). LVI reduced overall survival in patients with squamous cell carcinoma of the oral tongue (HR: 1.27, 95% CI: 1.17, 1.39, p < 0.001), floor of mouth (HR: 1.33, 95% CI: 1.17, 1.52, p < 0.001) and buccal mucosa (HR: 1.44, 95% CI: 1.15, 1.81, p = 0.001). Patients with lymphovascular invasion treated with surgery plus post-operative radiotherapy had significantly improved survival compared to those who underwent surgery alone (relative hazard 1.79, 95% CI: 1.58, 2.03, p < 0.001), and patients treated with surgery + post-operative chemoradiotherapy had improved survival compared to those treated with surgery alone (relative hazard 2.0, 95% CI: 2.26, 1.79, p < 0.001)., Conclusion: Lymphovascular invasion is an important independent risk factor for decreased overall survival in oral cavity squamous cell carcinoma involving the oral tongue, floor of mouth and buccal mucosa subsites., 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 © 2023 Elsevier Ltd. All rights reserved.)

Background: To evaluate disease control, toxicities, and variables associated with clinical outcomes for patients with head and neck squamous cell carcinoma and clinical N3 disease (HNSCC N3) treated with definitive chemoradiation therapy., Methods: We performed a retrospective review of patients with HNSCC N3 treated at two high-volume academic centers between 1996 and 2019., Results: We identified 85 patients with a median follow-up of 2.8 years. Five-year overall survival, regional control, and freedom from distant metastases rates were 38%, 80%, and 80%, respectively. Severe complications were identified in 19% of patients., Conclusions: Favorable regional control is achievable with definitive chemoradiation therapy for patients with HNSCC N3 disease. Distant metastases are a common pattern of failure and should be a focus of prospective study., (© 2023 Wiley Periodicals LLC.)

Purpose: To discuss the role of proton beam therapy (PBT) in the treatment of patients with oropharyngeal squamous cell carcinoma (OPSCC)., Materials and Methods: A review of the pertinent literature., Results: Proton beam therapy likely results in reduced acute and late toxicity as compared with intensity-modulated radiation therapy (IMRT). The extent of the reduced toxicity, which may be modest, depends on the endpoint and technical factors such as pencil beam versus passive scattered PBT and adaptive replanning. The disease control rates after PBT are likely similar to those after IMRT., Conclusion: Proton beam therapy is an attractive option to treat patients with OPSCC. Whether it becomes widely available depends on access., Competing Interests: Conflicts of Interest: William M. Mendenhall, MD, is the Advisory Editor of the International Journal of Particle Therapy. The authors have no additional relevant conflicts of interest to disclose., (©Copyright 2023 The Author(s).)