A comparison between full-length 16S rRNA Oxford nanopore sequencing and Illumina V3-V4 16S rRNA sequencing in head and neck cancer tissues.

Describing the microbial community within the tumour has been a key aspect in understanding the pathophysiology of the tumour microenvironment. In head and neck cancer (HNC), most studies on tissue samples have only performed 16S rRNA short-read sequencing (SRS) on V3-V5 region. SRS is mostly limited to genus level identification. In this study, we compared full-length 16S rRNA long-read sequencing (FL-ONT) from Oxford Nanopore Technology (ONT) to V3-V4 Illumina SRS (V3V4-Illumina) in 26 HNC tumour tissues. Further validation was also performed using culture-based methods in 16 bacterial isolates obtained from 4 patients using MALDI-TOF MS. We observed similar alpha diversity indexes between FL-ONT and V3V4-Illumina. However, beta-diversity was significantly different between techniques (PERMANOVA - R2 = 0.131, p < 0.0001). At higher taxonomic levels (Phylum to Family), all metrics were more similar among sequencing techniques, while lower taxonomy displayed more discrepancies. At higher taxonomic levels, correlation in relative abundance from FL-ONT and V3V4-Illumina were higher, while this correlation decreased at lower levels. Finally, FL-ONT was able to identify more isolates at the species level that were identified using MALDI-TOF MS (75% vs. 18.8%). FL-ONT was able to identify lower taxonomic levels at a better resolution as compared to V3V4-Illumina 16S rRNA sequencing.

Customised acoustic therapy delivered through a web-based platform-An innovative approach to tinnitus treatment.

OBJECTIVES: Customised acoustic therapy aims to moderate the neural pathways implicated in the pathophysiology of tinnitus. This study aimed to assess the efficacy of customised acoustic therapy administered via a web-based treatment platform. DESIGN: Clinical trial with prospective recruitment. Fifty-eight participants underwent 6 weeks of customised acoustic therapy. SETTING: Treatment was delivered for 2 h each day using a smartphone, tablet or computer. Treatment was integrated into usual daily activities. PARTICIPANTS: Participants with subjective tinnitus were recruited through public and private otolaryngology clinics and electronic and print media. MAIN OUTCOMES MEASURED: FiveQ, a novel 5 question tinnitus questionnaire, was measured at baseline and each week of treatment. Statistical analyses, including Wilcoxon, Mann-Whitney and mixed linear regression, were used to assess treatment efficacy and identify factors associated with treatment response. RESULTS: 39/58 participants (67.2%) had an improvement in symptom severity scores, 4 had no change (6.9%) and 15 had a decline from baseline (25.9%). Mean FiveQ scores improved by 22.9% from 40.8 (SD = 21.4) at baseline to 31.5 (SD = 21.3) following 6 weeks of treatment (p < 0.001). With the exception of the slight tinnitus group, all other groups (from mild to catastrophic) demonstrated a treatment response. Participants with low frequency tinnitus (<2000 Hz) had a significantly greater treatment response (p < 0.001). CONCLUSION: Customised acoustic therapy administered via a web-based platform demonstrated encouraging efficacy. At least mild symptoms at baseline and low frequency tinnitus were associated with a greater treatment response. Customised acoustic therapy offers accessible and efficacious tinnitus treatment, however longer term clinical studies are required to confirm the observed initial benefit is maintained.

Preclinical feasibility of robot-assisted sentinel lymph node biopsy using multi-modality magnetic and fluorescence guidance in the head and neck.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is a staging procedure dependent on accurate mapping of draining lymphatics via tracers. Robot-assisted SLNB enables access to multiple neck levels with a single incision and intraoperative fluorescence guidance to the SLN. METHODS: Lymphatic mapping in swine was done using a magnetic tracer and fluorescent dye, injected into the tongue. MRI preoperatively mapped lymphatic spread of the magnetic tracer. Dissection was performed using a da Vinci Xi robot guided by fluorescence-imaging of the dye. RESULTS: Robot-assisted SLNB was successfully performed in all animals (n = 5). A novel MRI protocol differentiated SLNs (n = 6) from lower echelon nodes (n = 11) based on flow progression. Fluorescence imaging provided valuable intraoperative guidance and correlated with magnetic-positive nodes. CONCLUSIONS: This study demonstrates preclinical feasibility of a robot-assisted approach to SLNB using magnetic and fluorescent tracers in the head and neck, enabling both preoperative mapping and intraoperative guidance.

Correlation between radiologic and pathologic extranodal extension in HPV-associated oropharyngeal cancer: Systematic review.

Pretreatment determination of extranodal extension (ENE) has significant clinical implications in human papillomavirus positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC). Unfortunately there is no gold-standard imaging modality for radiological assessment of ENE in HPV+ OPSCC, leading to subjective assessments and complex decision making concerning ENE. A systematic review of diagnostic test accuracy was therefore undertaken, with five databases systemically searched to evaluate the diagnostic performance of an imaging modality for detection of ENE in HPV+ OPSCC. A meta-analysis was conducted on four CT studies using a random-effects model. While a narrative synthesis was provided for the studies using PET/CT and "CT and MRI." Out of 1772 hits, six studies were included in the review. Meta-analysis on four CT studies showed CT had an overall sensitivity of 77% and specificity of 60%. PET/CT had a sensitivity of 37.5% and specificity of 97%. "CT and MRI" had a sensitivity of 62% and specificity of 78%. Further diagnostic studies involving CT, PET/CT and MRI are ultimately required.

FiveQ: A new easy-to-use validated clinical instrument for tinnitus severity.

OBJECTIVES: Tinnitus is a complex and debilitating phenomenon with potentially significant implications on quality of life. New presentations can be resource and time intensive for clinicians. Validated comprehensive tinnitus questionnaires may lack practical utility in the high-volume clinical setting. Concise, targeted questionnaires may offer an efficient alternative. This study aimed to assess the validity of the FiveQ, a novel five question construct designed to measure tinnitus severity. Convergent validity was assessed through correlating FiveQ against two comprehensive validated questionnaires, the Tinnitus Handicap Questionnaire (THQ) and Tinnitus Handicap Inventory (THI). DESIGN: Cross-sectional study with prospective recruitment. The 117 voluntarily recruited participants completed the FiveQ, THI and THQ questionnaires. Results were comparatively analysed. SETTING: Recruitment was via electronic and print media, audiology clinics and public and private otolaryngology outpatient clinics. Surveys were completed electronically. PARTICIPANTS: Members of the public aged over 18 with subjective tinnitus were invited to participate. MAIN OUTCOME MEASURED: Analyses for establishing the content validity, construct validity, internal consistency, explorary factor analysis, and responsiveness of FiveQ was performed. RESULTS: FiveQ demonstrated a high positive correlation with both the THI (r = 0.773, p < .001) and THQ (r = 0.808, p < .001). Internal consistency for FiveQ reached an acceptable threshold (Cronbach's alpha 0.86). Exploratory factor analysis demonstrated that one latent factor underlies the five items of the FiveQ. FiveQ demonstrated better responsiveness than both the THI and THQ after a 6 week interval repeat measurement. CONCLUSION: FiveQ demonstrated high-positive correlations with existing validated tinnitus questionnaires as well as acceptable internal consistency and factor analysis. The concise construct of FiveQ allows clinicians to efficiently estimate tinnitus severity, target treatment towards dominant symptoms and establish a reliable estimation of treatment response following interventions.

Assessment of Toxic Effects and Survival in Treatment Deescalation With Radiotherapy vs Transoral Surgery for HPV-Associated Oropharyngeal Squamous Cell Carcinoma: The ORATOR2 Phase 2 Randomized Clinical Trial.

Importance: The optimal approach for treatment deescalation in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCCs) is unknown. Objective: To assess a primary radiotherapy (RT) approach vs a primary transoral surgical (TOS) approach in treatment deescalation for HPV-related OPSCC. Design, Setting, and Participants: This international, multicenter, open-label parallel-group phase 2 randomized clinical trial was conducted at 9 tertiary academic cancer centers in Canada and Australia and enrolled patients with T1-T2N0-2 p16-positive OPSCC between February 13, 2018, and November 17, 2020. Patients had up to 3 years of follow-up. Interventions: Primary RT (consisting of 60 Gy of RT with concurrent weekly cisplatin in node-positive patients) vs TOS and neck dissection (ND) (with adjuvant reduced-dose RT depending on pathologic findings). Main Outcomes and Measures: The primary end point was overall survival (OS) compared with a historical control. Secondary end points included progression-free survival (PFS), quality of life, and toxic effects. Results: Overall, 61 patients were randomized (30 [49.2%] in the RT arm and 31 [50.8%] in the TOS and ND arm; median [IQR] age, 61.9 [57.2-67.9] years; 8 women [13.6%] and 51 men [86.4%]; 31 [50.8%] never smoked). The trial began in February 2018, and accrual was halted in November 2020 because of excessive toxic effects in the TOS and ND arm. Median follow-up was 17 months (IQR, 15-20 months). For the OS end point, there were 3 death events, all in the TOS and ND arm, including the 2 treatment-related deaths (0.7 and 4.3 months after randomization, respectively) and 1 of myocardial infarction at 8.5 months. There were 4 events for the PFS end point, also all in the TOS and ND arm, which included the 3 mortality events and 1 local recurrence. Thus, the OS and PFS data remained immature. Grade 2 to 5 toxic effects occurred in 20 patients (67%) in the RT arm and 22 (71%) in the TOS and ND arm. Mean (SD) MD Anderson Dysphagia Inventory scores at 1 year were similar between arms (85.7 [15.6] and 84.7 [14.5], respectively). Conclusions and Relevance: In this randomized clinical trial, TOS was associated with an unacceptable risk of grade 5 toxic effects, but patients in both trial arms achieved good swallowing outcomes at 1 year. Long-term follow-up is required to assess OS and PFS outcomes. Trial Registration: Clinicaltrials.gov Identifier: NCT03210103.

Preclinical evaluation of a mannose-labeled magnetic tracer for enhanced sentinel lymph node retention in the head and neck.

Sentinel lymph node biopsy in cancers of the head and neck offers demonstrated clinical and diagnostic value, but adoption is limited by concerns about the detrimental consequence to survival of false negative results in a highly curable setting. The aim of this study was to demonstrate potential to overcome this via application of a novel mannose-labeled magnetic iron oxide tracer. In a large animal model, preoperative imaging and intraoperative magnetometer detection were used to identify magnetic lymph nodes. Iron quantification mapped the distribution of tracer within lymphatic levels. Over a 4-week test period, uptake of magnetic tracer in lymph nodes increased in a linear-like fashion, with a substantial percentage of accumulated iron (83%) being retained in the sentinel node. This result indicates a high affinity of mannose-labeled particles to the sentinel node, while providing a means for the magnetometer probe to indicate node status based on intraoperative signal.

Randomized Trial of Radiotherapy Versus Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma: Long-Term Results of the ORATOR Trial.

PURPOSE: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has risen rapidly, because of an epidemic of human papillomavirus infection. The optimal management of early-stage OPSCC with surgery or radiation continues to be a clinical controversy. Long-term randomized data comparing these paradigms are lacking. METHODS: We randomly assigned patients with T1-T2, N0-2 (≤ 4 cm) OPSCC to radiotherapy (RT) (with chemotherapy if N1-2) versus transoral robotic surgery plus neck dissection (TORS + ND) (with or without adjuvant therapy). The primary end point was swallowing quality of life (QOL) at 1-year using the MD Anderson Dysphagia Inventory. Secondary end points included adverse events, other QOL outcomes, overall survival, and progression-free survival. All analyses were intention-to-treat. Herein, we present long-term outcomes from the trial. RESULTS: Sixty-eight patients were randomly assigned (n = 34 per arm) between August 10, 2012, and June 9, 2017. Median follow-up was 45 months. Longitudinal MD Anderson Dysphagia Inventory analyses demonstrated statistical superiority of RT arm over time (P = .049), although the differences beyond 1 year were of smaller magnitude than at the 1-year timepoint (year 2: 86.0 ± 13.5 in the RT arm v 84.8 ± 12.5 in the TORS + ND arm, P = .74; year 3: 88.9 ± 11.3 v 83.3 ± 13.9, P = .12). These differences did not meet the threshold to qualify as a clinically meaningful change at any timepoint. Certain differences in QOL concerns including more pain and dental concerns in the TORS + ND arm seen at 1 year resolved at 2 and 3 years; however, TORS patients started to use more nutritional supplements at 3 years (P = .015). Dry mouth scores were higher in RT patients over time (P = .041). CONCLUSION: On longitudinal analysis, the swallowing QOL difference between primary RT and TORS + ND approaches persists but decreases over time. Patients with OPSCC should be informed about the pros and cons of both treatment options (ClinicalTrials.gov identifier: NCT01590355).

Trans-oral robotic surgery for head and neck cancers using the Medrobotics Flex® system: the Adelaide cohort.

Trans-oral robotic surgery for head and neck cancers can be performed using rigid, multi-port robots with linear access but the Medrobotics Flex® system offers an alternative as it is endo-luminal, single-port, and uses flexible instruments. To assess the utility of the Medrobotics Flex® system for head and neck cancer (HNC) resections. A retrospective review of all HNC resections done over a 2.5-year period (Jan 2017-July 2019) at the Memorial Hospital, using the Flex® system. Data collected include patient demographics, tumour site, tumour stage, p16 status, smoking history, surgery performed, histologic margins, complications, overall survival, recurrence, and adjuvant treatments received. There were 49 head and neck cancer cases in total done using the Medrobotics Flex® system. Median age 60 years, with M:F ratio 3.5:1. Outcomes: oropharyngeal cancers (82%), p16 positive (89%), overall survival (94%), local recurrence (6%), and adjuvant treatment (84%). Cancer procedures done included lateral oropharyngectomy (43%), tongue base mucosectomy (27%), tongue base resection (18%), and others (12%) which include a single case each of supraglottic laryngectomy, hypopharyngeal tumour resection, partial pharyngectomy, partial glossectomy, and vocal cord tumour resection. Clear margins were related to tumour T stage and achieved for T1 tonsil cancer (75%), T2 tonsil cancer (70%), T3 tonsil cancer (50%), T1 tongue base cancer (80%), and T2 tongue base cancer (66.7%). Median operating time with neck dissection was 2 h 40 min, whilst median length of hospital stay was 1 day (IQR 1-7 days). Complications included a single case each of secondary haemorrhage (managed conservatively), oro-cervical fistula, wound infection, tongue numbness, and a medical event. There was no primary haemorrhage and no mortality. The Medrobotics Flex® system is a safe and reliable tool for head and neck cancer surgery.

Comparison of different guidelines for oral cancer.

BACKGROUND: Guidelines should provide accessible and reliable information for decision-making. Also, they should be translatable to multiple settings, allowing their use in diverse situations. METHODS: We searched in GOOGLE, PUBMED, SCIELO, and SCOPUS for guidelines on oral squamous cell carcinoma. They were evaluated using the AGREE II protocol. RESULTS: We identified 16 guidelines that fulfilled inclusion criteria. The mean score and range for each AGREE II domain were: "scope and purpose" 74.1% (6-100.0%); "stakeholder" 78.6% (0-100.0%); "rigor of development" 71.4% (0-100.0%); "clarity of presentation" 71.4% (6-100.0%); "applicability" 50.0% (0-85.7%); "editorial independence" 57.1% (14.3-85.7%) and "overall assessment" 57.1% (14.3-100.0%). CONCLUSION: Guidelines for oral cancer present variable quality. Among those available, only four surpassed the 70% AGREE II score threshold.

National Surgical Quality Improvement Program risk calculator validity in South Australian laryngectomy patients.

BACKGROUND: Assessing an individual patient's post-operative risk profile prior to laryngectomy for cancer is difficult. The American College of Surgeons' National Surgical Quality Improvement Program (ACS-NSQIP) risk calculator was developed to better inform preoperative decision-making. The calculator uses patient-specific characteristics to estimate the risk of experiencing post-operative complications within 30 days of surgery. We investigated the ACS-NSQIP risk calculator's performance for Australian laryngectomy patients. METHODS: The ACS-NSQIP risk calculator was used to retrospectively calculate the 30-day post-operative predicted outcomes in patients who underwent laryngectomy for laryngeal, hypopharyngeal and thyroid cancers (with laryngeal involvement) in two institutions in South Australia. These data were compared against the actual mortality, morbidity, complications and length of stay (LOS) collected from a retrospective chart review. RESULTS: A total of 144 patients underwent surgical intervention for malignancies with laryngeal involvement. The median LOS was 25 days (range 13-197) compared to the predicted LOS of 6.5 days (range 3.5-12.5). Overall mortality was 2.78% with post-operative complications occurring in 63% of patients. The most common complication was wound infection, occurring in 33% of patients. Hosmer-Lemeshow plots demonstrated good agreement between predicted and observed rates for complications. CONCLUSION: The ACS-NSQIP risk calculator effectively predicted post-operative complication rates in South Australian laryngeal cancer patients undergoing laryngectomy. However, differences in predicted and actual LOS may limit the usefulness of the calculator's LOS predictions for Australian patients.

Treatment de-escalation for HPV-associated oropharyngeal squamous cell carcinoma with radiotherapy vs. trans-oral surgery (ORATOR2): study protocol for a randomized phase II trial.

BACKGROUND: Patients with human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPC) have substantially better treatment response and overall survival (OS) than patients with HPV-negative disease. Treatment options for HPV+ OPC can involve either a primary radiotherapy (RT) approach (± concomitant chemotherapy) or a primary surgical approach (± adjuvant radiation) with transoral surgery (TOS). These two treatment paradigms have different spectrums of toxicity. The goals of this study are to assess the OS of two de-escalation approaches (primary radiotherapy and primary TOS) compared to historical control, and to compare survival, toxicity and quality of life (QOL) profiles between the two approaches. METHODS: This is a multicenter phase II study randomizing one hundred and forty patients with T1-2 N0-2 HPV+ OPC in a 1:1 ratio between de-escalated primary radiotherapy (60 Gy) ± concomitant chemotherapy and TOS ± de-escalated adjuvant radiotherapy (50-60 Gy based on risk factors). Patients will be stratified based on smoking status (< 10 vs. ≥ 10 pack-years). The primary endpoint is OS of each arm compared to historical control; we hypothesize that a 2-year OS of 85% or greater will be achieved. Secondary endpoints include progression free survival, QOL and toxicity. DISCUSSION: This study will provide an assessment of two de-escalation approaches to the treatment of HPV+ OPC on oncologic outcomes, QOL and toxicity. Results will inform the design of future definitive phase III trials. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03210103. Date of registration: July 6, 2017, Current version: 1.3 on March 15, 2019.

Transoral robotic narrow field oropharyngectomy for tumours of the parapharyngeal space.

The advent of transoral robotic surgery (TORS) has allowed transoral approaches for parapharyngeal space (PPS) tumours to be re-evaluated. It provides enhanced visualisation and instrument access for appropriate tumours. We describe a specific technique, TORS narrow-field oropharyngectomy, that is ideal for benign PPS tumours which have been violated by intra-oral biopsy or incision and drainage. This allows the contaminated, overlying oropharyngeal mucosa to be resected en-bloc with the PPS tumour, reducing the risk of local recurrence. This technique provides a window into the PPS, improving visualisation of underlying neurovascular structures as well as the tumour. This reduces the risk of tumour spillage and leads to superior vascular access and haemorrhage control. This technique is only applicable to PPS tumours that are appropriate for transoral approaches and is specifically designed for those selected patients that have been placed at risk of seeding or local scarring by intra-oral procedures prior to definitive resection. We present two such cases: a 38-year-old male with a PPS inflammatory cyst and a 66-year-old female with a PSS pre-styloid Schwannoma.

How I do it: transnasal retraction during transoral robotic oropharyngeal resection.

Collapse of the resection plane presents a frustrating problem during transoral robotic resection, in a situation already typified by limited vision and access for instruments. We present a quick and cost-effective retraction technique to effectively mitigate this issue and increase the ease and reliability of robotic oropharyngeal resection. This technique utilises a simple transnasal apparatus to create greater exposure of the resection plane. A Y-suction catheter is inserted into the oropharynx via the nasal cavity. A silk suture is then used to attach it to the oropharyngeal resection specimen. When pulled from the nasal cavity, this apparatus adds a non-intrusive, tremor-free fixation point that pulls the resected specimen along a unique cephalo-posterior vector. This significantly improves access and vision of the desired dissection plane. The entire process takes approximately 1-2 min per side to properly execute. It can be adapted for various pathologies and subsites of the oropharynx. This transnasal technique is a simple, minimally invasive, and inexpensive method for improving wound tension during transoral oropharyngeal resection.

Transoral robotic surgery using the Medrobotic Flex® system: the Adelaide experience.

Transoral robotic surgery (TORS) has become an accepted treatment option for a variety of benign and malignant pathologies of the head and neck. The Medrobotics Flex® system is a novel single port platform available as an alternative tool to current multiport robotic technology. We present the Adelaide experience with this system thus far. The Medrobotics Flex® system was introduced in Adelaide in January 2017. Patient demographics, pathology, indication for surgery and complications are prospectively recorded for all cases. The first 20 patients are presented in this case series. 11/20 underwent surgery for malignant disease. Of these nine were diagnosed with oropharyngeal squamous cell carcinoma (OPSCC). Histopathology revealed clear margins of primary tumour excision in 8/9 patients. There were no intraoperative complications. In terms of secondary complications, one patient undergoing tonsillectomy for recurrent tonsillitis experienced a secondary haemorrhage at day 13 following operation and one patient undergoing lateral oropharyngectomy for pT3N2b tonsillar SCC sustained an oro-cervical fistula, which settled with conservative management. We have found the Medrobotic Flex® system to be a safe, reliable tool for managing transoral surgery. The range of pathology managed with this platform, as well as the histologic outcomes presented, demonstrates efficacy in the oropharynx and posterior oral cavity for both benign and malignant disease.

Prognosis of oral squamous cell carcinoma with perineural invasion: A comparative study of classification types.

OBJECTIVE: To investigate the histological location and extent of perineural invasion (PNI) as prognostic factors. DESIGN: Retrospective review of medical records and histological analysis of 116 patients with oral squamous cell carcinoma (OSCC). SETTING: Two major public tertiary hospitals treating head and neck cancer, Royal Adelaide Hospital and Flinders Medical Centre, in South Australia. PARTICIPANTS: Patients diagnosed with OSCC who underwent primary surgical treatment with curative intent at these two centres from January 1, 2005 through December 31, 2015. MAIN OUTCOME MEASURES: The primary end points were disease-free survival (DFS) and disease-specific survival (DSS). RESULTS: The presence of PNI as a binary factor alone did not significantly influence the clinical outcomes. Extratumoural (ET) PNI as measured from the tumour edge was associated with worse DFS on multivariate analyses. Multifocal PNI was associated with worse DFS and DSS. DFS in multifocal PNI was worse irrespective of whether adjuvant therapy was administered. CONCLUSIONS: The presence of multifocal and ET PNI in OSCC is associated with poor clinical outcomes. Patients with multifocal PNI were associated with worse DFS even with adjuvant therapy.

Radiotherapy versus transoral robotic surgery and neck dissection for oropharyngeal squamous cell carcinoma (ORATOR): an open-label, phase 2, randomised trial.

BACKGROUND: Transoral robotic surgery (TORS) with concurrent neck dissection has supplanted radiotherapy in the USA as the most common treatment for oropharyngeal squamous cell carcinoma (OPSCC), yet no randomised trials have compared these modalities. We aimed to evaluate differences in quality of life (QOL) 1 year after treatment. METHODS: The ORATOR trial was an investigator-initiated, multicentre, international, open-label, parallel-group, phase 2, randomised study. Patients were enrolled at six hospitals in Canada and Australia. We randomly assigned (1:1) patients aged 18 years or older, with Eastern Cooperative Oncology Group scores of 0-2, and with T1-T2, N0-2 (≤4 cm) OPSCC tumour types to radiotherapy (70 Gy, with chemotherapy if N1-2) or TORS plus neck dissection (with or without adjuvant chemoradiotherapy, based on pathology). Following stratification by p16 status, patients were randomly assigned using a computer-generated randomisation list with permuted blocks of four. The primary endpoint was swallowing-related QOL at 1 year as established using the MD Anderson Dysphagia Inventory (MDADI) score, powered to detect a 10-point improvement (a clinically meaningful change) in the TORS plus neck dissection group. All analyses were done by intention to treat. This study is registered with ClinicalTrials.gov (NCT01590355) and is active, but not currently recruiting. FINDINGS: 68 patients were randomly assigned (34 per group) between Aug 10, 2012, and June 9, 2017. Median follow-up was 25 months (IQR 20-33) for the radiotherapy group and 29 months (23-43) for the TORS plus neck dissection group. MDADI total scores at 1 year were mean 86·9 (SD 11·4) in the radiotherapy group versus 80·1 (13·0) in the TORS plus neck dissection group (p=0·042). There were more cases of neutropenia (six [18%] of 34 patients vs none of 34), hearing loss (13 [38%] vs five [15%]), and tinnitus (12 [35%] vs two [6%]) reported in the radiotherapy group than in the TORS plus neck dissection group, and more cases of trismus in the TORS plus neck dissection group (nine [26%] vs one [3%]). The most common adverse events in the radiotherapy group were dysphagia (n=6), hearing loss (n=6), and mucositis (n=4), all grade 3, and in the TORS plus neck dissection group, dysphagia (n=9, all grade 3) and there was one death caused by bleeding after TORS. INTERPRETATION: Patients treated with radiotherapy showed superior swallowing-related QOL scores 1 year after treatment, although the difference did not represent a clinically meaningful change. Toxicity patterns differed between the groups. Patients with OPSCC should be informed about both treatment options. FUNDING: Canadian Cancer Society Research Institute Grant (#701842), Ontario Institute for Cancer Research Clinician-Scientist research grant, and the Wolfe Surgical Research Professorship in the Biology of Head and Neck Cancers grant.

Predictive value of computed tomography in identifying extracapsular spread of cervical lymph node metastases in p16 positive oropharyngeal squamous cell carcinoma.

BACKGROUND: Extracapsular spread (ECS) of lymph node metastases is associated with poor prognosis and is an indication for adjuvant chemoradiotherapy. Accurately identifying ECS using imaging may allow us to recommend primary chemoradiotherapy to avoid trimodality treatment. We investigated the accuracy of staging CT in diagnosing ECS in P16 + oropharyngeal squamous cell carcinoma (OPSCC). METHODS: Patients with pathologically determined cervical nodal metastases from P16 + OPSCC were included. Two blinded radiologists scored images to predict the presence of ECS in comparison to histopathology. RESULTS: Eighty patients with a total of 91 specimens were evaluated. Pathologic ECS was identified in 53.8% of the patients. Sensitivity and specificity of CT for the two observers were 56.5% and 60.9%, and 73.3% and 66.7%, respectively. The presence of perinodal stranding was found to be significantly associated with pathological ECS. CONCLUSION: Computed tomography displays consistently high specificity, which may be used to rule out the presence of extracapsular spread in cervical nodal metastases of P16 + oropharyngeal squamous cell carcinoma.