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Introduction: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has increased in recent decades, driven by infection with human papillomavirus (HPV). Transoral robotic surgery (TORS) and neck dissection (ND) has been employed as an alternative to radiotherapy/chemoradiotherapy. The current literature is lacking studies providing an exhaustive overview of recurrence characteristics and long-term outcomes in TORS-treated OPSCC-patients., Methods: All patients treated for OPSCC with primary TORS + ND in Eastern Denmark between 2013 and 2020 were included in the study. The aim was to explore overall survival (OS), recurrence-free survival (RFS), recurrence patterns, and ultimate failure rate (UFR). OS and RFS were examined using the Kaplan-Meier method. Cox proportional regression analyses were employed to examine effect of different variables on risk of death and recurrence., Results: The study included 153 patients of which 88.9 % (n = 136) were treated with TORS alone while 11.1 % (n = 17) received adjuvant therapy. The 1-, 3-, and 5-year OS were 97.4 %, 94.1 %, and 87.6 % while 1-, 3-, and 5-year RFS were 96.6 %, 87.8 %, and 84.9 %. The UFR was 6.5 % in the cohort. Patients with HPV+/p16 + OPSCC had a significantly better 5-year OS of 92.3 % than patients with discordant or double-negative HPV/p16 status (OS = 73.3 %). No differences in outcomes between patients treated with or without adjuvant therapy were found in regression analysis., Conclusion: Excellent survival and disease control was obtained with TORS + ND in this cohort, despite lesser application of adjuvant therapy than other TORS-centers, implying that TORS without adjuvant therapy can be successfully applied in treatment of early-stage OPSCC., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: The aim of this project is to create an interactive online patient decision aid (PDA) for oropharyngeal cancer (OPSCC) patients, eligible for transoral (robotic) surgery with an ultimate goal to assist both physicians and patients in making treatment choices., Materials and Methods: Following the International Patient Decision Aid Standards, a mixed-methods approach was employed. The study involved semi-structured in-depth interviews with patients and physicians, thinking-out-loud sessions, and study-specific questionnaires. Thematic coding and analysis were conducted on verbatim transcriptions of audio-recorded interviews., Results: The PDA drafts were evaluated by twenty OPSCC survivors and twenty multidisciplinary specialists. Significant revisions were made after phase 1 to enhance readability and reduce text, whilst incorporating videos and graphics. Following all phases, both patients and specialists rated the PDA as comprehensible, feasible, and a valuable addition to regular counseling., Conclusion: This study showcases the development of a PDA for early stage oropharyngeal cancer patients considering surgery and radiotherapy options. The decision aid emphasizes the disparities in short- and long-term side effects between the two treatments. Patients and physicians found the decision aid to be understandable, user-friendly, and helpful for future patients. The PDA is available on https://beslissamen.nl/., 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 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: To predict the necessity of enteral nutrition at 28 days after surgery in patients undergoing major head and neck oncologic procedures for oral and oropharyngeal cancers., Material and Methods: Data from 193 patients with oral cavity and oropharyngeal squamous cell carcinoma were retrospectively collected at two tertiary referral centers to train (n = 135) and validate (n = 58) six supervised machine learning (ML) models for binary prediction employing 29 clinical variables available pre-operatively., Results: The accuracy of the six ML models ranged between 0.74 and 0.88, while the measured area under the curve (AUC) between 0.75 and 0.87. The ML algorithms showed high specificity (range 0.87-0.96) and moderate sensitivity (range: 0.31-0.77) in detecting patients with ≥28 days feeding tube dependence. Negative predictive value was higher (range: 0.81-0.93) compared to positive predictive value (range: 0.40-0.71). Finally, the F1 score ranged between 0.35 and 0.74., Conclusions: Classification performance of the ML algorithms showed optimistic accuracy in the prediction of enteral nutrition at 28 days after surgery. Prospective studies are mandatory to define the clinical benefit of a ML-based pre-operative prediction of a personalized nutrition protocol., 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. Published by Elsevier Ltd.)

Background: Transoral robotic surgery (TORS) is increasingly employed in the management of oropharyngeal cancer without adjuvant treatment. Attaining safe surgical margins is paramount to preventing local recurrence (LR), but the necessary surgical margin dimension remains contentious., Methods: Systematic review and meta-analysis of studies reporting margin status and LR following TORS without adjuvant therapy for primary OPSCC., Results: The search identified 269 articles and 11 were selected for inclusion, with 406 patients included in the meta-analysis. Heterogeneity was noted in the definition of "close" margins. Random-effects pooled rate of positive margins was 7 % (95 % CI 0.04-0.12, I 2  = 54 %, p = 0.02) and close margins was 7 % (95 % CI 0.02-0.27, I 2  = 86 %, p=<0.01). The random-effects overall rate of LR was 6 % (95 % CI 0.04-0.10, I 2  = 11 %, p = 0.35), 13 % (95 % CI 0.02-0.620, I 2  = 0 %, p = 1.0) after a positive margin, and 3 % (95 % CI 0.03-0.24, I 2  = 23 %, p = 0.26) after a close margin. Odds ratio (OR) for LR indicated higher risk of LR for positive compared to close margins (7.5; 95 % CI 1.31-42.91, I 2  = 0 %, p = 0.51), and a slightly lower risk of LR between close and negative margins (2.22; 95 % CI 0.67-7.38, I 2  = 0 %, p = 0.8). A lack of frozen-section analysis (OR 2.91, p = 0.36) and HPV-negative disease (OR 1.68, p = 0.03) were associated with an elevated risk of LR., Conclusions: TORS as a standalone treatment is associated with low rates of LR; however, the literature is hampered by considerable heterogeneity in margin definitions. Larger multicentre studies are required to determine the precise margin cut-off required for oropharyngeal tumours managed with TORS alone., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Professor Vinidh Paleri is a proctor for Intuitive Medical Inc., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Transoral robotic surgery (TORS) has equivalent oncologic control to radiotherapy with potential for improved quality of life (QOL) and lower patient-reported decisional regret., Methods: Cross-sectional study between 2016 and 2021 of TORS patients with early-stage oropharyngeal squamous cell carcinoma who completed the Decision Regret Scale (DRS), M. D. Anderson Dysphagia Inventory (MDADI), and University of Washington Quality of Life (UW-QOL). The median time from treatment to questionnaire completion was 1.8 years (IQR 1.4-3.3, range 1.0-5.6)., Results: Of 65 patients, 84.6% expressed no or mild decisional regret. Regret was not associated with clinical parameters or adjuvant treatment but was correlated with MDADI (τ avg  = -0.23, p < 0.001) and UW-QOL (τ avg  = -0.27, p < 0.001). Worse MDADI was associated with older age and worse UW-QOL was associated with multi-site operation and shorter time to survey., Conclusions: Overall, the TORS cohort expressed very limited decisional regret. DRS scores were unaffected by clinicodemographics or additional adjuvant therapies, but decision regret was correlated with worse QOL and worse swallowing., 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: Transoral robotic surgery (TORS) has been used in the salvage setting for head and neck cancers both with and without reconstruction. The complications of salvage TORS and the effect of reconstruction on complications has not been studied., Objective: To study the complications of salvage TORS and examine the effect of reconstruction on complication rates., Method: An electronic search of the English- language literature using PubMed, Medline, and the Cochrane database was conducted and a systematic review performed in accordance with PRISMA guidelines (CRD42020181057)., Results: A total of 23 studies including 533 patients have been published on salvage TORS.The average patient age was 61.2 years.Prior treatment was described for 420 patients.205 (48.8%) underwent prior definitive radiotherapy (RT).160 (38.1%) underwent definitive chemoradiotherapy (CRT).Only 55 (13.1%) had prior surgery.Overall, there were 158 complications with a pooled rate of 33.6% (95%CI: 25.4-42.3%).77 were major complications requiring surgical intervention with a pooled rate of 18.9% (95% CI: 14.8-23.3%).The number of patients undergoing reconstruction among salvage cases in the literature is 59 (9.19%), with 24 local flaps and 25 microvascular free flaps.Reconstruction was associated with lower overall hemorrhage rates but had no impact on major hemorrhage rates., Conclusions: The pooled incidence rates of major complications, major POH and emergency tracheostomy following salvage TORS are 18.9%, 10.5%, and 4.4%.The rate of death following salvage TORS is 3.6%. Reconstruction was associated with lower overall hemorrhage rate after salvage TORS but had no impact on major postoperative hemorrhage rates., 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.)

Objectives: Our objective was to determine the negative predictive value (NPV) of preoperative FDG PET/CTfor detecting locoregional nodal disease. The aim was to help inform the decision-making process when identifying patients with early-stage OPSCC that would be suitable for transoral robotic surgery (TORS) as a single-modality treatment., Materials and Methods: A retrospective cohort study was conducted of adults with primary stage cT1-2 OPSCC with up to one metastatic neck lymph node (cN0-1) planned for TORS. Patients with a preoperative PET/CT and who had undergone staging neck dissection (ND) were included. Clinical and pathological nodal staging was established based on PET/CT and ND, respectively. The primary outcome was the frequency of occult (not seen on PET/CT) nodal disease on ND., Results: Eighty-eight patients were included (N = 88). The rate of occult nodal disease was 28.4 % (n = 25). The NPV of PET/CT in the clinically negative neck was 79 % and 66 % in cases with a single clinical node. Following staging ND, thetreatment plan changed in 27 % of cases overall, 7 % in cN0 and 36.7 % in cN1. Among these, 18 % met criteria for radiotherapy and 9 % for CRT. This represented a decrease in the number of ideal candidates for TORS as single-modality treatment from 88 to 64 (73 %)., Conclusions: PET/CT is a useful tool in the workup of patients for primary TORS. However, about one third of patients with early-stage OPSCC might benefit from adjuvant therapy not predicted by preoperative PET/CT. A staging ND helps confirm candidates for single-modality treatment with TORS., 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: This study assesses longitudinal epidemiologic trends in the oldest head and neck cancer (HNC) patients, comparing the oropharynx to other mucosal HNC sites., Materials and Methods: Using data from the Surveillance, Epidemiology, and End Results database, trends in incidence, two-year cancer specific mortality, and percent of cases recommended for and which received surgery from 2000 to 2018 in patients ages ≥85 years were assessed using Joinpoint analysis by HNC site. Trends were quantified as annual percentage change (APC) with 95% confidence intervals (CI)., Results: Among older adults, oropharyngeal cancer (OPC) incidence increased (APC = 1.80% [95% CI: 0.94-2.67]), while mortality decreased (APC = -2.01% [95% CI: -3.26--0.74]) from 2000 to 2018. At other mucosal HNC sites, incidence and mortality remained stable. Percentage of patients who received surgery significantly changed for oropharyngeal (APC = -15.34% from 2000 to 2005 [95% CI: -24.37 to -4.79]) and laryngeal (APC = -4.61% from 2000 to 2008 [95% CI -8.28 to -0.80]) cancers. Trends in recommendation for surgery varied by site with significant decreases at the larynx, oral cavity, and oropharynx., Conclusion: OPC incidence is increasing among the oldest HNC patients. An increasing proportion of HPV-associated tumors could account for associated mortality improvement. There has been a shift towards non-surgical therapy possibly due to known favorable response of HPV-associated OPC to radiation therapy and/or poor surgical candidacy in this age group. The evolving treatment approach has not been detrimental to population-level survival outcomes, but optimal treatment has yet to be established. Future studies with pathologically confirmed HPV status are needed to better understand older adult OPC burden., 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.)

Background and Aim: The aim of this study was to evaluate the long-term safety of the omission of immediate neck dissections (IND) in patients with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) achieving a less than complete nodal response on 12-week FDG PET-CT., Material and Methods: Patients with HPV-positive, node-positive HNSCC that were treated with radical (chemo) radiotherapy (RT) between January 2013 and September 2019 were identified. PET-CT responses were classified as complete (CR), incomplete (ICR) or equivocal (EQR) nodal responses. Clinical outcomes were obtained., Results: 347 patients were identified. Median follow-up was 43.9 (IQR, 30.8-61.2) months. 62.8% (218/347) achieved a CR, 23.4% (81/347) EQR and 13.8% (48/347) ICR nodal response. 70 of 81 (86.4%) patients with an EQR and 25 of 48 (52.1%) with an ICR had no residual disease during follow up (a pathologically negative ND if surgery undertaken or no subsequent neck or distant relapse clinically/radiologically). Median survival of the EQR and CR groups were not reached, and despite the omission of IND in 95% of the EQR group there was no statistically significant differences in overall survival (OS) between the groups, p = 1.0. Median survival of ICR was not reached. However, OS for ICR group was significantly worse than that of CR, and EQR, both p < 0.001., Conclusion: The omission of IND in those achieving an EQR nodal response does not compromise long-term survival. This supports the safety of extended surveillance in patients with HPV-positive disease and an EQR on 12-week FDG PET-CT., (Crown Copyright © 2022. Published by Elsevier Ltd. All rights reserved.)

Introduction/background: With the advent of TransOral Robotic Surgery (TORS) the ease of transoral procedures has been dramatically improved. TORS is already established for its feasibility, functional and oncological outcomes for selected lesions of oral cavity, oropharynx and laryngopharynx. This study reports on preliminary results with TransOral UltraSonic Surgery (TOUSS) for oncologic resections of oral cavity, oropharyngeal and supraglottic malignancies., Materials and Methods: Eighteen patients with malignancies of oral cavity, oropharynx and supraglottis underwent TOUSS with simultaneous neck dissection and adjuvant therapy as indicated, from January 2018 to April 2019. Essential equipment included the FK-retractor (Gyrus Medical, Tuttilngen, Germany) for TransOral exposure, the Olympus ENDOEYE Flex 5 mm 2D/10 mm 3D deflecting tip video laparoscopes, and 35 cm long ultrasonic harmonic scalpel (Thunderbeat). Parameters evaluated include tumor staging, mouth opening, TOUSS setup time, TOUSS primary removal time, surgical margins, blood transfusions, tracheostomy, postoperative complications, enteral feeding and resumption of oral diet, duration of hospital stay, and survival outcomes., Results: Eighteen patients underwent complete TransOral UltraSonic Surgery (TOUSS), with simultaneous unilateral or bilateral neck dissection. No procedure was abandoned intraoperatively due to difficulty in extirpation of the tumor. Margins were negative for ten patients (55.6%), close in five (27.8%), and positive in three patients (16.7%). Average TOUSS set-up time was 22.5 min (range, 10-30 min) and average TOUSS primary tumor removal time was 35.3 min (range, 15-60 min). Patients started tolerating oral feeds even in the second post op day (mean 6 days), and transitioning to complete oral feeds with removal of the nasogastric tube was achieved in all (mean, 16 days). The average hospital stay was 7.4 days (range 2-16 days). Secondary hemorrhage occurred in two cases and required an emergency tracheostomy and ligation of lingual artery. Minor cervicopharyngeal fistula occurred in four cases and settled in all with conservative non-surgical treatment. Overall survival at 3 years was 70.5%, and disease-specific survival was 94.4%., Conclusion: TransOral UltraSonic Surgery (TOUSS) is a safe and sound alternative method of endoscopic surgical treatment of oral cavity, oropharynx and supraglottic neoplasms. Advantages of this technique include faster resection time, intraoperative assistance from Narrow Band Imaging, easy affordability compared to TORS, and excellent functional outcomes., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: Many patients diagnosed with oropharyngeal squamous cell carcinoma (OPSCC) have the option of radiation- or surgery-based therapy, and would benefit from a treatment decision aid (DA) to make decisions congruent with their personal values. Our objective was to develop a patient-centered DA for patients with OPSCC that is comprehensible, usable, acceptable, and well-designed., Materials and Methods: Decisional needs from a pilot study of OPSCC survivors and treating physicians were used to inform a web-based prototype DA. A multidisciplinary steering group developed and iteratively revised the DA. Feasibility testing was conducted in two cycles to assess perspectives of stakeholders (medical, radiation and surgical oncologists, patient education experts, and OPSCC survivors). Survey data and open-ended responses were used to evaluate and refine the DA., Results: 16 physicians, 4 patient education experts, and 6 survivors of OPSCC evaluated a web-based DA prototype in two cycles of testing. Participant feedback was used to revise the DA content and design between cycles. The majority of participants across both cycles indicated that the DA was comprehensible (97%), usable (86%), acceptable (78%), and well-designed (93%). Approximately three quarters of respondents indicated that they would use or share the DA in clinical practice., Conclusion: We developed the first patient-centered treatment decision aid (DA) designed for patients with OPSCC, to our knowledge. The DA was perceived favorably by stakeholders, with more than three quarters of respondents indicating they would use it in clinical practice. This tool may improve clinical practice as an adjunct to shared decision-making for OPSCC., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: In this study, we aimed to analyze preoperative MRI images of oropharyngeal cancer patients who underwent surgical treatment, extracted radiomics features, and constructed a disease recurrence and death prediction model using radiomics features and machine-learning techniques., Materials and Methods: A total of 157 patients participated in this study, and 107 stable radiomics features were selected and used for constructing a predictive model., Results: The performance of the combined model (clinical and radiomics) yielded the following results: AUC of 0.786, accuracy of 0.854, precision of 0.429, recall of 0.500, and f1 score of 0.462. The combined model showed better performance than either the clinical and radiomics only models for predicting disease recurrence. For predicting death, the combined model performance has an AUC of 0.841, accuracy of 0.771, precision of 0.308, recall of 0.667, and f1 score of 0.421. The combined model showed superior performance over the predictive model using only clinical variables. A Cox proportional hazard model using the combined variables for predicting patient death yielded a c-index value that was significantly better than that of the model including only clinical variables., Conclusions: A predictive model using clinical variables and MRI radiomics features showed excellent performance in predicting disease recurrence and death in oropharyngeal cancer patients. In the future, a multicenter study is necessary to verify the model's performance and confirm its clinical usefulness., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: To assess the prognostic significance of oligometastatic versus polymetastatic disease in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC), and to evaluate the impact of definitive tumor directed therapy on the survival outcomes for patients with oligometastatic disease when compared to systemic therapy., Materials and Methods: This was a retrospective observational cohort study of patients with HPV-associated OPSCC who developed distant metachronous metastatic disease after undergoing initial primary surgical management from 2008 to 2017. We classified patients based on the extent of metastatic disease [Oligometastatic (≤5 metastases) and polymetastatic (>5 metastases)], and the initial treatment of metastatic disease [definitive tumor directed therapy (all metastases treated with surgery or radiotherapy) versus upfront systemic therapy]., Results: Among 676 patients undergoing primary surgical management for HPV-associated OPSCC, 39 patients (5.8%) developed metastases after a median follow-up of 29.6 months (range 4.5-127.0). Of the 34 metastatic patients who met study criteria, 26 (76.5%) were oligometastatic and 8 (23.5%) were polymetastatic. Oligometastatic patients had improved median overall survival (OS) compared to polymetastatic patients (47.9 vs. 22.7 months, p = 0.036). For oligometastatic patients, definitive tumor directed therapy was associated with an improved median progression free survival (not reached vs 6.13 months, p = 0.001) and median OS (not reached vs 40.7 months, p = 0.004)., Conclusion: In a cohort of patients surgically treated for HPV-associated OPSCC, metachronous metastatic disease was uncommon and, in most cases, considered oligometastatic. Oligometastasis portends a favorable prognosis and definitive tumor directed therapy may be associated with improved overall survival in these patients. Future multi-institutional efforts are warranted to further demonstrate the impact of definitive tumor directed therapy on disease outcomes., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: Analyze how otolaryngologists approach HPV-related oropharyngeal cancer in terms of patient selection for transoral surgery, perceptions of treatment related risks and benefits, and adjuvant treatment decisions., Materials and Methods: A survey on HPV-related cancer management was distributed to otolaryngologists in the US through RedCap. Differences in responses were analyzed using Pearson's chi-squared and Fisher's exact tests., Results: A total of 111 out of 143 (77.6%) otolaryngologists completed the survey. Overall, most prefer treating T1/T2 tumors using transoral robotic surgery (TORS) and T3 tumors through primary radiation therapy (RT), though there were significant differences between cohorts. Non-fellowship-trained surgeons and those in community practices favored RT for T1/T2 more than their fellowship-trained and academic counterparts, respectively. For adjuvant treatment, non-fellowship-trained surgeons favored adjuvant CRT, whereas fellowship-trained surgeons preferred only adjuvant RT, for patients with lymphovascular or perineural invasion, >1 lymph node involvement, or close deep margins. TORS was viewed as having less adverse sequelae (i.e. dysphagia, dysphonia, xerostomia). Though the two modalities had similar oncologic outcomes, TORS was perceived as providing better quality of life (QOL)., Conclusions: There are variations in HPV-related OPSCC management based on surgeon background and preferences across the US. TORS and primary RT are believed to offer similar oncologic control, but the former provides lesser adverse sequelae and better QOL. Additionally, surgeon demographics (i.e. fellowship status, practice type, and region) can affect management decisions, including patient selection for TORS and adjuvant therapy decisions. Further study is required to better understand and standardize appropriate HPV-positive OPSCC management., (Copyright © 2021. Published by Elsevier Ltd.)

Objectives: To determine whether up-front trans-oral robotic surgery (TORS) for clinically-staged locally-advanced human papillomavirus (HPV)-related oropharyngeal cancer is associated with oncologic and survival outcomes comparable to early-stage (cT1/T2) tumors., Materials and Methods: Retrospective cohort study of 628 patients with HPV-related oropharyngeal cancer who underwent up-front TORS from 2007 to 2017. Patients were stratified into two cohorts based on early-stage (cT1/2) versus locally-advanced (cT3/4) tumor at presentation., Results: We identified 589 patients who presented with early-stage tumors, and 39 patients with locally-advanced tumors. Of these, 73% of patients required adjuvant radiation, and 33% required adjuvant chemoradiation. There was no significant difference in the administration of adjuvant radiation or chemoradiation between the two cohorts. Patients in the locally-advanced disease cohort were significantly more likely to have Stage II/III disease by clinical and pathologic criteria by American Joint Committee on Cancer 8th edition criteria (p < 0.001). However, there was no significant difference in 5-year overall survival (OS) or recurrence-free survival (RFS) based on Kaplan-Meier survival estimates between the two cohorts (p = 0.75, 0.6, respectively), with estimated OS of 91% at 5 years, and estimated RFS of 86% at 5 years across the study population., Conclusions: Up-front TORS offers favorable survival outcomes for appropriately selected locally-advanced cases of HPV-related oropharyngeal cancer. Furthermore, up-front TORS is comparably effective in allowing avoidance of adjuvant therapy, particularly chemotherapy, in both cT1/T2 and locally-advanced HPV-positive oropharyngeal cancer. In the absence of clear technical contraindication to surgery, cT3/T4 classification should not be considered an absolute contraindication to surgery., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To investigate whether palatine tonsillectomy in youth influences the risk of oropharyngeal cancers (OPC) by assessing the association between history of tonsillectomy and risk of tonsillar, base of tongue (BOT) cancer, and other head and neck cancers (HNC)., Materials and Methods: RACKAM was a case-case study comparing frequency of tonsillectomy history in individuals diagnosed with HNC from 2013 to 2018 in 15 centers across France. History of tonsillectomy was defined using combined assessment of patients' recollections and surgeons' visualizations of tonsil area. OPC subsite-specific odds ratios (OR) of tonsillectomy were calculated using multinomial logistic regression with non-oropharyngeal HNC as reference., Results: 1045 patients were included in the study. Frequency of tonsillectomy was 19.5% in patients with tonsillar cancer (N = 85), 49.3% in BOT (N = 76), 33.8% in other oropharyngeal cancers (N = 202) and 38.0% in non-oropharyngeal HNC (N = 682). History of tonsillectomy was inversely associated with tonsillar cancer (adjusted OR 0.4; 95% CI 0.2-0.8), and positively associated with BOT cancer (adjusted OR 1.8; 95% CI 1.1-3.1), but was not associated with all OPC combined (adjusted OR 1.1; 95% CI 0.8-1.4). Sensitivity analyses considering only patients' or surgeons' assessments of tonsillectomy provided comparable results., Conclusion: We confirm the long-term protective effect of tonsillectomy performed in youth on future risk of tonsillar cancer, and our study is the second to report a concurrent increased risk of BOT cancer. Our data suggest that tonsillectomy in youth shifts the site of the first diagnosed oropharyngeal tumor and has a limited impact on overall risk of OPC., (Copyright © 2021. Published by Elsevier Ltd.)

Human papillomavirus is responsible of approximately 70% oropharyngeal tumours and is related with more favourable outcomes. It has led to an increasing interest for de-escalation treatment strategies such as Trans Oral Robotic Surgery (TORS). A literature review was performed searching for the role of TORS as de-escalation modality of treatment in patients with p16 positive oropharyngeal squamous cell carcinoma (OPSCC). Special attention was paid to the potential advantage offered by TORS in reducing adjuvant radiation therapy. Six questions were formulated. 67 studies were selected. Several trials analysing the role of upfront TORS to treat early stage p16+ OPSCC and the possibility of reducing the adjuvant radiotherapy were founded. A lot of studies based on the experience of single centres show promising results. Nevertheless to date no definitive data can be extrapolated. The continued investigation of this line of de-escalation therapy with randomized prospective clinical trials is needed., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Oropharyngeal squamous cell cancer (OPSCC) is now the most common site of head and neck squamous cell cancer. Despite the focus on treatment deintensification in clinical trials, little is known about the preferences, experiences and needs of patients with OPSCC when deciding between surgery and radiation therapy as primary treatment with curative intent. In this qualitative study, pre-treatment and post-treatment oropharyngeal cancer patients were recruited to take part in one-on-one interviews (n = 11 pre-treatment) and focus group discussions (n = 15 post-treatment) about treatment decision-making. Recordings were transcribed and assessed for emergent themes using framework analysis. From the one-on-one interviews and focus group discussions with OPSCC patients, fourteen themes were identified. Participants expressed alarm at diagnosis, decisional conflict, and a variety of roles in decision-making (physician-controlled, shared, and autonomous). Decisions were driven by the perceived recommendation of the treatment team, a desire for physical (surgical) tumor removal, fear of adverse effects of treatment, and patient-specific values. Although participants felt well-informed by their treating physicians, they identified a need for additional patient-centered information. Participants were critical of the poor quality of information available on the internet, and acknowledged the advantage of hearing the experiences of post-treatment patients. The experiences identified herein may be used to guide patient-centered communication during patient counseling and to inform interventions designed to support patients' needs at diagnosis, ultimately helping to implement high-quality, patient-centered care., (Copyright © 2020. Published by Elsevier Ltd.)

Introduction: Primary radiotherapy (RT) and transoral surgery (TOS) are effective local therapy treatments for oropharyngeal squamous cell carcinoma (OPSCC), but their cost profiles differ. We compared the one-year costs of these competing treatments using a large claims-based database., Methods: Eligible individuals were patients in the SEER-Medicare registry diagnosed with OPSCC between 2000 and 2011. Patients were categorized as receiving either primary RT +/- chemotherapy, or TOS +/- adjuvant RT or chemoradiotherapy (CRT), and all treatment costs from 1 month prior to diagnosis to 1 year after diagnosis were calculated. Univariable and multivariable linear regression models were used to determine predictors of payer expenditure. Patient-borne pharmacy costs were also analyzed., Results: The cohort included 3497 patients (73% RT, 27% TOS), of whom 73% were locally advanced. The mean total 13 month costs for RT alone, CRT, TOS alone, TOS + RT and TOS + CRT were $39,083, $63,537, $25,468, $36,592, and $99,919, respectively, for early-stage patients. For locally advanced individuals, the mean costs were $45,049, $68,099, $40,626, $53,729, and $71,397, respectively. On multivariable analysis, the adjusted increase in total costs versus RT alone were $21,844, -$5431, $7984, and $28,581 for CRT, TOS alone, TOS + RT, and TOS + CRT, respectively. The difference between CRT and TOS + RT became non-significant for TOS patients undergoing transoral surgery plus neck dissection. Cisplatin was associated with significant less cost than cetuximab and taxane-based chemotherapy., Conclusion: In this population of elderly patients, transoral surgery was generally associated with less expensive treatment, with the addition of chemotherapy serving as the main driver of increased cost., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: To determine if elderly patients (≥70 years) have differences in functional and survival outcomes compared to non-elderly patients (<70 years) following transoral robotic surgery., Materials and Methods: A retrospective cohort study was conducted on patients undergoing robotic surgery for head and neck cancer at a tertiary institution from 2011 to 2016. Functional status was evaluated with diet, enteric feeding status, Functional Oral Intake Scale (FOIS), tracheostomy tube placement, and unplanned readmission. Kaplan Meier method and Cox proportional hazard model were used to assess overall survival (OS) and disease-free survival (DFS) between elderly and non-elderly patients., Results: Two hundred and forty-six patients met inclusion criteria. The mean age of the cohort was 63.5 ± 9.74 years. There were 64 patients (26.0%) that were ≥70 years. Elderly patients were more likely to be discharged with enteric access (p < 0.002). As early as 3 months, there was no significant difference in need for enteric feeds, diet, or FOIS score. There was no difference in tracheostomy tube rates and unplanned readmission between both cohorts. There was no significant difference in OS and DFS between age groups when stratified by p16 status., Conclusions: Elderly patients are more likely to require perioperative enteric feeding, but 3-month, 1-year, and 2-year functional outcomes are comparable to younger patients. Survival outcomes are similar in both populations., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Robotic approaches and sentinel lymph node (SLN) biopsy are both strategies that evolved driven by the need to reduce impact of head and neck oncological surgery in terms of operative timing, morbidity, hospitalization time, and aesthetic results. A comprehensive review of the scientific literature was performed on PubMed, Embase, ResearchGate, Cochrane, and CENTRAL electronic databases with the aim to discuss the role that these two approaches can play together in the management of head and neck cancers (HNCs) of various sites. Dedicated publications on the combined robotics and SLN biopsy approaches resulted, up to now very limited, while their separated application in non-shared fields is gaining strength. However, the possibility to implement and combine technologies to minimize sequelae of head and neck surgery is an interesting and evolving topic., (Copyright © 2020 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.)

Objective: Prognostic factors specific to surgically managed human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (HPV(+)OPSCC) are not fully understood. Medical co-morbidities may have an impact on survival after surgical treatment. We aimed to identify co-morbidities associated with distant metastases-free survival (DMFS) and cancer-specific survival (CSS) in HPV(+)OPSCCs., Methods: This is a retrospective case series of HPV(+)OPSCC patients at a tertiary referral center from 2007 to 2016. All patients in the study underwent primary intent-to-cure transoral resection with concomitant neck dissection ± adjuvant radiation ± chemotherapy. Exclusion criteria included a history of previous head and neck cancer or distant metastases at diagnosis. Associations with DMFS and CSS were evaluated using univariable and multivariable Cox regression and summarized with hazard ratios (HRs)., Results: 406 patients were included in the cohort (100% HPV(+), 90% Male). All had tumors of the tonsil (62%) or base of tongue (38%). Median follow-up for the cohort was 4.0 years (IQR: 2.6-6.2). Higher tumor stage and a higher Adult Comorbidity Evaluation-27 score were significantly associated with worse DMFS and CSS (p < 0.02 for all). A history of diabetes mellitus (N = 36, 9%) was significantly associated with DMFS (HR 3.05 [95%CI 1.26-7.37], p = 0.014) and CSS (HR 4.82 [95%CI 1.84-12.61], p = 0.001). On multivariable analysis, after adjusting for tumor stage, diabetes remained significantly associated with worse DMFS (HR 2.58 [95%CI 1.06-6.26], p = 0.037)., Conclusion: Diabetes mellitus may be associated with worse DMFS and CSS in surgically managed HPV(+)OPSCC., Competing Interests: Declaration of Competing Interest The authors declared that there is no conflict of interest., (Copyright © 2020. Published by Elsevier Ltd.)

Objective: The incidence of oropharyngeal squamous cell carcinoma (OPSCC), especially human papillomavirus (HPV)-associated, is increasing worldwide. Immunotherapy become available for patients with carcinomas in the head and neck region, however without ideal biomarker. Markers like PD-L1 vary in the clone of the antibody used, and the method of evaluation. Adequate and reliable immune cells characterization and evaluation is still not found. Furthermore, studies analyzing representativeness of different tissue samples are scarce. We analyzed small biopsy, lymph node (LN) metastasis and resected OPSCC, in regards of tumor infiltrating lymphocyte (TIL) density, PD-L1 and p16 expression., Material and Methods: Patients with OPSCC diagnosed from 2000 to 2016, with small biopsy, resection specimen and LN metastasis samples were selected. We analyzed TILs on hematoxylin-eosin stain, and PD-L1 and p16 expression in tumor cells. Concordance between different tumor locations was evaluated., Results: 93 patients, with 65 small biopsies, 72 resection specimens, and 70 LN metastases were included. TILs, p16 and PD-L1 demonstrated very high concordance. Additionally, PD-L1 expression in the small biopsies was more representative of the PD-L1 expression in the resection specimens, than the LN samples., Conclusion: TILs density can be reliably assessed using hematoxylin-eosin stain with high concordance between the small biopsy, resection specimen and LN metastasis. Evaluation of concordance of p16 expression is very high, nevertheless some cases might be misdiagnosed on a small biopsy or lymph node metastasis. Evaluation of PD-L1 expression is very reliable on the biopsy specimen. Different PD-L1 clones and methods of evaluation still remain to be addressed., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The simultaneous use of two different free flaps, harvested from distinct donor sites, has demonstrated a reasonable degree of safety and success rates in head and neck composite defects reconstruction. Unfortunately, their relatively low frequent use, together with the lack of proper statistics on their management strategies, make their indications weak of robust conclusions to better define their role in common practice. The aim of the present study was to review the literature of the last 15 years regarding simultaneous free flap transposition, presenting advantages, disadvantages, and results of this technique, with the final purpose to propose an up-to-date panorama for the use of double free flap for complex head and neck defects reconstruction. Depending on which factors are present, surgeons may choose to select an approach that is theoretically safer, but yields less-than-ideal functional outcomes, such as local flap. Two free flaps may be necessary when the defect contains both a large, complex bony defect, large soft tissue needs, and proper surgical planning and meticulous monitoring continues to be the cornerstone of success., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To determine the effectiveness and outcomes of SND in the treatment of patients with squamous cell carcinoma of the head and neck (SCCHN) with clinically positive neck (cN+) at diagnosis., Material and Methods: We retrospectively reviewed 159 patients with SCCHN with cN+ at diagnosis, who underwent a SND with curative intent at a tertiary care academic teaching hospital in Spain. We registered patient and tumor characteristics, date and site of recurrences, together with the outcomes. Survival rates were calculated by the Kaplan-Meier method. The minimum follow-up was 18 months or till death., Results: A total of 28 neck recurrences were found in the whole series but only 10 neck recurrences occurred in absence of local recurrence. The regional control in the neck in absence of local recurrence was observed in 94% of patients. The neck recurrence rates did not correlated with the pN classification (P = 0.49), the administration of postoperative radiotherapy (P = 0.49) or extranodal extension (P = 0.43). The 5-year regional recurrence-free survival rate was 80% and 92% if only isolated neck recurrences are considered., Conclusions: SND offers an effective and oncologically safe surgical procedure in selected patients with clinically positive metastatic nodes in the neck. Our findings suggest that in cN1 and cN2 tumors, SND could replace the modified radical neck dissection without compromising oncologic efficacy., 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.)

Objectives: Contralateral lymph node (LN) involvement is a prognostic factor in clinical staging of oropharyngeal squamous cell carcinoma (OPSCC), while pathologic nodal staging in the AJCC 8th edition for human papillomavirus-mediated OPSCC (HPV + OPSCC) focuses exclusively on the number of involved LNs (pLN+). This study assessed if the presence of contralateral pLN+ adds prognostic importance to the number of pLN+., Materials and Methods: The National Cancer Database was queried for pLN+ HPV + OPSCC treated with surgery with 10 or more LN dissected. Data were evaluated with Cox regression, propensity score matching (PSM), and Kaplan-Meier overall survival (OS) analysis., Results: Of 3407 patients, 152 (4.5%) patients had contralateral pLN+. Subjects with contralateral pLN+ had higher pT/pN stage, more positive margins, extranodal extension (ENE), and lymphovascular invasion (LVI) (all p < 0.05). On univariate analysis, contralateral pLN+ trended toward worse OS (HR 1.58, 95% CI 0.98-2.55, p = 0.061). In the multivariable model (controlling for age, comorbidities, T-stage, N-stage, LN size, ENE, LVI, margin status and adjuvant therapy), LN laterality had no impact on OS (HR 0.87, 95% CI 0.52-1.45, p = 0.520). Further PSM analysis confirmed that contralateral pLN+ is not associated with OS in this population (HR 0.79, 95% CI 0.41-1.53, p = 0.494)., Conclusion: This study supports the AJCC 8th edition pathologic staging for HPV + OPSCC by observing that LN laterality is not associated with OS. ENE was associated with inferior OS and should be considered for future staging systems. Further study should be directed at the importance of nodal size in this population., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: The aim of the study is proposing a classification of different transoral lateral oropharyngectomy procedures in order to ensure better definitions of post-operative results., Methods: The classification resulted from the consensus of the different authors and was based on anatomical-surgical principles., Results: The classification comprises three types of lateral oropharyngectomy: type 1 is the resection of the palatine tonsil deep to the pharyngobasilar fascia; type 2 is performed by removing the entire palatine tonsil, the palatoglossus muscle, the palatopharyngeal muscle and the superior constrictor muscle; type 3 is performed by removing the entire palatine tonsil, the palatoglossus muscle, the palatopharyngeal muscle, the superior constrictor muscle, the buccopharyngeal fascia with extension to the pterygoid muscle and parapharyngeal space fat content. Based on the extension of the dissection we can use the suffix A (soft palate), B (posterior pharyngeal wall), C (base of tongue) and D (retromolar trigone)., Conclusion: The proposed classification introduces a simple and easy to use categorization of transoral lateral oropharyngectomies into three classes. Resection extensions are easily described using suffixes., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The objective of this study was to conduct a systematic review and meta-analysis of the incidence of positive surgical margins after transoral surgery for oropharyngeal carcinoma, as well as the factors associated with positive margins and their impact on local tumor control., Method: An electronic search of English-language literature databases was conducted, and a systematic review was performed in accordance with the PRISMA guidelines., Results: A total of 42 articles were included in the analysis. The overall rate of positive margins using transoral conventional surgery (CTS), transoral laser microsurgery (TLM), or transoral robotic surgery (TORS) was 7.8% in a cumulative total of 3619 patients. A positive margin status was associated with a reduction in local control. Assessment of intraoperative frozen sections was associated with a reduced risk of definitive positive margins, whereas a T4 classification was associated with an increased risk of definitive positive margins. Neither the primary site (the tonsillar fossa versus the base of the tongue), nor the HPV status, were associated with the margin status. The level of heterogeneity between the various studies was very high., Conclusion: The currently used transoral procedures are safe in regard to proper tumor resection and they should continue to be part of the armamentarium of surgical techniques used in head and neck surgery. The very high level of heterogeneity between studies calls for a definition consensus for margin status assessments in transoral surgery., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: To characterize temporal trends in treatment patterns for oropharyngeal carcinoma, and to evaluate the emerging role of surgical therapy in the era of transoral robotic surgery (TORS)., Methods: Patients with oropharynx cancer between 2004 and 2016 identified using the National Cancer Database. Demographics and primary treatment modalities were obtained. Treatment was classified as surgery alone, surgery with radiation/chemotherapy, or primary radiation/chemotherapy. Annual distribution of cases treated by the various modalities was tabulated by site and early (I/II) versus late (III/IV) stage disease (AJCC 7th edition). The "TORS era" was defined as beginning in 2010., Results: 149,534 patients were identified. The majority (56.8%) were treated with radiation ± chemotherapy. 53,069 patients had surgery as part of treatment, 72.6% (N = 38,533) of which received adjuvant therapy. 5293 TORS procedures were performed between 2010 and 2016 with trends away from open and other endoscopic procedures. Despite a 31.0% increase in the number of cases treated surgically from before TORS (2009) to 2016, the percentage of cases treated surgically decreased from 35.0% to 32.7%, with a 44.2% increase in non-surgical therapy. Increases in the percentage of patients treated surgically were observed for base of tongue tumors (24.3-25.2%) and early stage disease (59.9-62.2%)., Conclusion: Despite the increase in the overall number of patients with oropharynx cancer, the percentages of patients treated surgically remains relatively stable. Notable increases were observed for base of tongue tumors and early stage disease., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Knowledge of the rate of occult contralateral nodal disease for oropharynx cancers (OPSCC) in the era of Human Papillomavirus-dominated disease would inform practitioners as to who may be a candidate for unilateral neck management. The objective of this study was to determine the rate of pathologic contralateral positive nodes in patients in OPSCC patients with pT1 and pT2 disease treated with TORS and bilateral neck dissections (BND)., Methods: Retrospective review of medical records was performed at Princess Margaret Cancer Center, Toronto; Icahn School of Medicine at Mount Sinai, New York City; and Montefiore Medical Center, New York City. Patients with pT1-2 N0-3 (AJCC 8th Edition) OPSCC disease treated with TORS and BND were included., Results: Thirty-two patients met inclusion criteria. Twelve patients (37.5%) had a tonsil primary site, 19 (59.4%) patients had a base of tongue primary site, and 1 (3.1%) patient had a pharyngeal wall primary. Twenty-four (75%) patients were known to be p16+. Twenty-seven patients (84.4%) were radiographically negative in the contralateral neck preoperatively, and two of these patients had pathologic contralateral positive nodes. The occult pathologic contralateral nodal metastasis rate was 7.4% (2/27). The sensitivity, specificity, positive predictive value, and negative predictive value of suspicious contralateral nodes on preoperative imaging for pathologically positive nodes were 33.3%, 86.2%, 20% and 93% respectively. In the p16+ subgroup, the occult nodal positive rate in the contralateral neck was 5%., Conclusions: pT1-2 OPSCC patients undergoing TORS and elective contralateral neck dissection have a low rate of pathologic contralateral nodal positivity., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: To determine the comparative effectiveness of primary radiotherapy (RT) and primary surgery (PS) for locally advanced oropharyngeal squamous cell carcinoma (OPSCC)., Materials and Methods: Eligible individuals were patients in the SEER-Medicare registry diagnosed with locally advanced OPSCC between 2000 and 2011. Patients were categorized as receiving either primary RT ± chemotherapy, or PS ± adjuvant RT or chemoradiotherapy (CRT). Overall survival (OS) was analyzed using Cox multivariable analysis (MVA). Risks of gastrostomy dependence (GD), esophageal stricture (ES), and osteoradionecrosis (ORN) were analyzed using logistic regression., Results: A total of 2754 patients (69% RT, 31% PS) were included in this cohort, with a median age of 72 years. Patients treated with RT, CRT and PS experienced 3-year OS outcomes of 36.1%, 52.8%, and 54.9%, respectively (p < 0.001). Increasing age, unmarried status, increasing comorbidity, lower income, base of tongue (BOT) site, higher stage, no prior PET, and RT alone (but not CRT) were associated with inferior OS. Independent predictors of GD at 6 months included black race, BOT site, advanced stage, and CRT. The risks of ORN and stricture were not associated with treatment modality. Concurrent chemotherapy improved OS with definitive RT but had no impact in adjuvant RT. Only cisplatin- and taxane-containing regimens improved OS, but all concurrent agents, including cetuximab, significantly worsened GD., Conclusion: Local therapy decisions for locally advanced OPSCC must be individualized, with CRT increasing acute and chronic GD. The differential survival impact of concurrent chemotherapy in the definitive and adjuvant setting may be a consideration in decision-making., (Copyright © 2018. Published by Elsevier Ltd.)

Objectives: Delays in the initiation of postoperative radiation have been associated with worse outcomes; however, the effect of the overall treatment package time (interval from surgery through the completion of radiation) remains undefined. The purpose of this study was to determine the impact of package time on survival and to evaluate this effect among different subgroups of head and neck cancer patients., Patients and Methods: In this observational cohort study, the National Cancer Database was used to identify 35,167 patients with resected nonmetastatic head and neck cancer who underwent adjuvant radiation from 2004 to 2014. Kaplan-Meier survival estimates and multivariate Cox regression analyses were performed to determine the effect of treatment package time on overall survival., Results: Median package time was 96 days (interquartile range, 85-112 days). After adjusting for covariates, package times of 11 weeks or less were associated with improved survival (adjusted hazard ratio (aHR), 0.90; 95% confidence interval, 0.83-0.97) compared to an interval of 12-13 weeks, whereas package times of more than 14 weeks were associated with worse survival (aHR, 1.14, 1.14, and 1.22 for 14-15, 15-17, and >17 weeks, respectively). A significant interaction was identified between package time and disease site, nodal status, and stage. Specifically, patients with oropharyngeal tumors, advanced stage (III or IV) disease, or nodal involvement experienced more pronounced increases in mortality risk with delays in treatment time., Conclusions: Treatment package time independently impacts survival. This effect may be strongest for patients with oropharyngeal tumors or advanced stage disease., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Oropharyngeal tumor is traditionally resected from an open approach, often necessitating the need of a midline mandibulotomy in order to remove tumor safely with oncologic margins. The limitations imposed by a transoral route include poor visualization of the inferior extent of the oropharynx, rigid instrumentation, and inability to resect tumor that extends caudally into the supraglottis. While visualization with angled endoscopes, coupled with flexible laser development and microscopic magnification may overcome some of these limitations, this technique suffers from linear trajectory of the instruments which hampers expedient surgical resection in a 3-dimensional fashion. With development of the Da Vinci Surgical System, the safety and oncologic feasibility of removing oropharyngeal tumors are made possible because it provides a 3-dimensional magnification of the surgical field and wristed maneuverability of the surgical instruments which enable surgeons to operate around tight anatomical confines. Nevertheless, this first-generation robot is continually being modified with more flexibility and maneuverability through the development of robots like the FLEX Robotic System and more recently the Da Vinci Single Port System (SP). In this review, we will discuss the historic developments of robots for transoral applications, present the current approved robotic systems, and highlight the upcoming robots for transoral robotic surgery (TORS). Finally, we will also propose an ideal TORS surgical robot by highlighting the engineering technologies to accomplish these challenges., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: (1) Report the patterns of cervical node positivity for HPV + oropharyngeal squamous cell carcinoma (OPSCC) treated with transoral robotic surgery (TORS) and a unilateral level II-IV node dissection. (2) Investigate the regional failure rate following this operation. (3) Report the rate of pharyngocutaneous fistula (PCF) formation intraoperatively and postoperatively following TORS/neck dissection., Methods: Retrospective case series of 88 patients with HPV+ OPSCC treated with TORS and simultaneous neck dissection levels II-IV at the University of Washington from 2010 to 2016. Primary endpoints were PCF, regional recurrence, disease-free survival (DFS), and overall survival (OS)., Results: The overall frequency of cervical node positivity was 93%, with 84% in level IIa, 7% in IIb, 23% in III, and 13% in IV. Two patients developed PCF intraoperatively, repaired with a local digastric flap, and no postoperative PCF occurred. Sixteen patients (18%) received surgery alone, 49 patients (56%) received adjuvant radiation, and 23 patients (26%) underwent adjuvant chemoradiation. DFS at 2 years was 95% and OS at 2 years was 100%. No concerning level Ib nodes were identified preoperatively or during surgery, and no regional failures occurred in this location., Conclusion: Our data suggests, in TORS for HPV+ OPSCC, neck dissection of levels II-IV accurately stages the neck pathologically and prevents regional recurrences, with adjuvant therapy when indicated, and survival outcomes are excellent. Single-staged operations did not result in any postoperative PCF. Avoiding dissection of level Ib with TORS oropharyngectomy limits morbidity to the marginal mandibular nerve and salivary function, and resulted in no postoperative fistulas with minimal reconstruction interventions., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The 8th edition American Joint Committee on Cancer staging system for resected HPV-positive oropharynx carcinoma (HPV+ OPC) highlights high node number as a critical determinant of survival. We sought to characterize outcomes and patterns of failure in patients with high pathologically involved node number oropharynx cancer., Methods: We retrospectively identified 116 HPV+ OPC patients sequentially treated with neck dissection and either resection or intraoperative brachytherapy of the primary tumor between 2010 and 2016. External beam radiation was given based on the pathologic findings. Cox proportional hazards regression was used for multivariate analysis., Results: With a median follow-up of 27 months, the 3-year overall survival and progression free survival (PFS) were 89% and 81%, respectively. On multivariate analysis, ≥5 involved lymph nodes was significantly associated with worse PFS (hazard ratio 4.3, 95% confidence interval (CI) 1.5-12.0, P = 0.001). Rates of 3-year locoregional recurrence (LRR) in patients with ≤4 vs ≥5 were 6% and 22% (log-rank P = 0.12). Rates of 3-year distant metastases (DM) were 12% and 53% between ≤4 and ≥5 (log-rank P < 0.001)., Conclusion: Our findings confirm that patients with 5 or more involved lymph nodes appear to have substantially worsened rates of disease recurrence. While these patients appear to be at high risk of both LRR and DM, the predominant mechanism of failure is distant, and the rate of DM in this group was over 50%. Dedicated clinical trials in this patient population are warranted with a focus on mitigating the high DM rate., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: The National Comprehensive Cancer Network (NCCN) guidelines state that surgical patients with advanced-stage head and neck cancer (HNC) and risk factors other than extranodal extension (ENE) or positive margins should consider post-operative chemoradiation (POCRT). The goal of our study was to determine if POCRT is associated with overall survival (OS) compared with post-operative radiation therapy (PORT) and whether this varies with patient age., Material and Methods: We conducted a retrospective study of 5319 adult patients with stage III-IV HNC who received primary surgical treatment with POCRT or PORT in the National Cancer Database (2010-2013). Patients with distant metastases, ENE, and positive margins were excluded. Intermediate risk features included pT3-T4, pN2-N3 disease, and lymphovascular invasion. Our main outcome was overall survival (OS). Statistical analysis included chi-squared tests and Cox proportional hazards regressions., Results: On multivariable analysis for non-oropharyngeal cancer patients <70 years, POCRT was associated with improved OS for T1-4N2-3 disease (hazard ratio [HR], 0.73, 95% confidence interval [CI]; 0.58-0.93) but was not associated with OS for T3-4N0-1 disease (HR, 0.92; 95% CI, 0.71-1.19). For patients ≥70 years, POCRT was not associated with improved OS for patients with T1-4N2-3 disease (HR, 1.21; 95% CI, 0.79-1.86) or T3-4N0-1 disease (HR, 1.08; 95% CI, 0.71-1.65). For oropharyngeal cancer patients with HPV-positive disease, POCRT was associated with decreased OS (HR, 9.52; 95% CI, 2.38-38.08)., Conclusion: Chemoradiation may offer a survival benefit for non-oropharyngeal intermediate-risk advanced-stage HNC patients <70 years of age with T1-4N2-3 disease, but may not benefit those ≥70 years of age or those with T3-4N0-1 disease., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Importance: The American Joint Committee on Cancer, 8th edition (AJCC-8) contains a new staging system for human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC). Our study aim was to evaluate the effectiveness of the AJCC-8 relative to the AJCC 7th edition (AJCC-7)., Materials and Methods: A retrospective chart review was performed on a multi-institutional, prospectively collected dataset from two tertiary referral centers. All patients had HPV+ OPSCC treated primarily with surgery. The prognostic value of AJCC-7 and AJCC-8 were compared for 5-year overall survival (OS) and disease-specific survival (DFS)., Results: AJCC-8 pathological staging effectively risk stratified patients, creating a Cox model with a better fit (lower Akaike's Information Criterion, p < 0.0001) when compared to AJCC-7 pathological stages for both OS and DFS. The AJCC-8 pathologic staging did not produce a better fit than the AJCC-8 clinical staging (p = 0.15) for OS, however, AJCC-8 pathologic was more effective than AJCC-8 clinical for DFS (p < 0.0001). 76% of patients did not change their stage between clinical and pathologic AJCC-8 staging; 14% were upstaged by 1, <1% were upstaged by 2, 7% were downstaged by 1, and 3% downstaged by 2., Conclusions and Relevance: The new AJCC-8 staging system represents a significant improvement over AJCC-7 for risk stratification into groups that predict overall survival and disease-specific survival of surgically treated HPV+ OPSCC patients. The AJCC- 8 pathologic staging system was not significantly better than the AJCC-8 clinical staging system for overall survival, however, the pathologic staging system was better than the clinical for disease free survival., (Published by Elsevier Ltd.)

Introduction: Extracapsular extension (ECE) in regional lymph nodes and positive surgical margins (PSM) are considered high-risk adverse pathologic features in patients with oropharyngeal squamous cell carcinoma (OPSCC) that each constitute an indication for postoperative adjuvant chemoradiation. We identify pre-operative clinical factors that can predict post-operative ECE and/or PSM and create a nomogram to help clinical decision making., Methods: Adult patients with non-metastatic OPSCC with initial surgical treatment and confirmed HPV status diagnosed between 2010 and 2014 were selected from the National Cancer Database. Clinical staging was modified to American Joint Committee on Cancer 8th edition parameters. Logistic regression was used for multivariate analysis to identify predictors of pathologic ECE and/or PSM., Results: 5065 patients were included. 47.5% of the 3336 HPV-positive (HPV+) patients had ECE/PSM. 40.4% of the 1729 HPV-negative (HPV-) patients with had ECE/PSM. A model was built that included age, clinical ECE, tumor grade, and clinical T and N staging for HPV+ patients. Increasing N-classification was highly predictive of pathologic ECE and/or PSM (N1 OR = 3.6, N2 OR = 7.0, N3 OR = 11.2, p < 0.01). Clinical ECE (OR = 4.1, p < 0.01), tumor grade (ORs 2.2-4.4 with p < 0.05), and increasing clinical T-classification (ORs 1.2-1.8, p < 0.05) were also associated with ECE and/or PSM. A similar model was built for HPV- with similar predictive capability. Two internally validated nomograms were designed that demonstrated good discrimination (HPV+ AUC = 0.66, 95% CI: 0.64-0.68, and HPV- AUC = 0.70, 95% CI: 0.67-0.72) and good calibration (goodness-of-fit statistic of HPV+ 6.32, p = 0.61 and HPV- 11.66, p = 0.17)., Conclusions: These are the first nomograms designed to help predict ECE or PSM for both HPV+ and HPV- OPSCC. The nomograms can facilitate shared decision-making between clinicians and patients as they consider upfront treatment selection for OPSCC., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: To determine the outcomes and toxicities of minimally-invasive surgery with adjuvant intensity-modulated radiotherapy +/- chemotherapy (AT) compared to definitive surgical therapy (ST) in a contemporary cohort of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC)., Methods: From 2005 to 2013, a consecutive cohort of 190 HPV-positive OPSCC patients was retrospectively reviewed from multi-institutional databases maintained by the Departments of Otorhinolaryngology and Radiation Oncology. A total of 116 AT patients and 42 ST patients with intermediate or high risk pathologic features were included in the final analysis. All patients received minimally invasive surgery. Time to recurrence and time to death from the onset of surgery were evaluated. Toxicity data collected included dysphagia or xerostomia requiring feeding tube placement >6 months, or mandibular osteonecrosis requiring surgery or hyperbaric oxygen., Results: All AT patients received IMRT to a median dose of 60 Gy. Chemotherapy delivered to 67.2% of AT patients. AT group included more high-risk patients given higher nodal classification (p = 0.005) and extracapsular extension (p = 0.0005). AT improved disease-free survival (HR 2.77, CI 1.22-6.28; p = 0.02) and local-regional control (HR 14.83, CI 3.240-67.839; p = 0.001). Disease-free survival with AT and tumor extracapsular extension was improved when compared to ST (HR of 4.34, CI 1.540-12.213; p = 0.006). Dysphagia or mandibular osteonecrosis toxicity after AT vs. ST of 19.0% vs. 2.4%., Conclusions: AT improved local-regional control and disease-free survival but was associated with greater toxicity. The recurrence benefit was most pronounced in tumors with extracapsular extension., (Copyright © 2018 Elsevier Ltd. All rights reserved.)