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Background: Active surveillance (AS) of small, low-risk papillary thyroid cancers (PTCs) is increasingly being considered. There is limited understanding of why individuals with low-risk PTC may choose AS over traditional surgical management. Methods: We present a mixed-methods analysis of a prospective observational real-life decision-making study regarding the choice of thyroidectomy or AS for management of localized, low-risk PTCs

At the request of the Head and Neck Cancers Advisory Committee of Ontario Health (Cancer Care Ontario), a working group and expert panel of clinicians with expertise in the management of head-and-neck cancer developed the present guideline. The purpose of the guideline is to provide advice about the organization and delivery of health care services for adult patients with head-and-neck cancer. This document updates the recommendations published in the Ontario Health (Cancer Care Ontario) 2009 organizational guideline The Management of Head and Neck Cancer in Ontario. The guideline development methods included an updated literature search, internal review by content and methodology experts, and external review by relevant health care providers and potential users. To ensure that all patients have access to the highest standard of care available in Ontario, the guideline establishes the minimum requirements to maintain a head-and-neck disease site program. Recommendations are made about the membership of core and extended provider teams, minimum skill sets and experience of practitioners, cancer centre&ndash, specific and practitioner-specific volumes, multidisciplinary care requirements, and unique infrastructure demands. The recommendations contained in this document offer guidance for clinicians and institutions providing care for patients with head-and-neck cancer in Ontario, and for policymakers and other stakeholders involved in the delivery of health care services for head-and-neck cancer.

Importance Skull base surgery requires precise preoperative assessment and intraoperative management of the patient. Surgical navigation is routinely used for complex skull base cases; however, the image guidance is commonly based on preoperative scans alone. Objective The primary objective of this study was to assess the image quality of intraoperative cone-beam computed tomography (CBCT) within anatomical landmarks used in sinus and skull base surgery. The secondary objective was to assess the registration error of a surgical navigation system based on intraoperative CBCT. Design Present study is a retrospective case series of image quality after intraoperative cone beam CT. Setting The study was conducted at Toronto General Hospital and Princess Margaret Cancer Centre, University Health Network, Toronto. Participants A total of 46 intraoperative scans (34 patients, 21 skull base, 13 head and neck) were studied. Main Outcome and Measures Thirty anatomical landmarks (vascular, soft tissue, and bony) within the sinuses and anterior skull base were evaluated for general image quality characteristics: (1) bony detail visualization; (2) soft-tissue visualization; (3) vascular visualization; and (4) freedom from artifacts (e.g., metal). Levels of intravenous (IV) contrast enhancement were quantified in Hounsfield's units (HU). Standard paired-point registration between imaging and tracker coordinates was performed using 6 to 8 skin fiducial markers and the corresponding fiducial registration error (FRE) was measured. Results Median score for bony detail on CBCT was 5, remaining at 5 after administration of IV contrast. Median soft-tissue score was 2 for both pre- and postcontrast. Median vascular score was 1 precontrast and 3 postcontrast. Median score for artifacts on CBCT were 2 for both pre-and postcontrast, and metal objects were noted to be the most significant source of artifact. Intraoperative CBCT allowed preresection images and immediate postresection images to be available to the skull base surgeon. There was a significant improvement in mean (standard deviation [SD]) CT intensity in the left carotid artery postcontrast 334 HU (67 HU) (p Conclusion Intraoperative CBCT in complex skull base procedures provides high-resolution bony detail allowing immediate assessment of complex resections. The use of IV contrast with CBCT improves the visualization of vasculature. Image-guidance based on CBCT yields registration errors consistent with standard techniques.

The incidence of differentiated thyroid cancer has increased significantly during the last several decades. Surgical resection is the primary treatment for thyroid cancer and is highly effective, resulting in 5-year survival rates greater than 98%. However, surgical resection can result in short- and long-term treatment-related morbidities. Additionally, as this malignancy often affects women less than 40 years of age, there is interest in more conservative treatment approaches and, an unmet need for therapeutic options that minimize the risk of surgery-related morbidities while simultaneously providing an effective cancer treatment. Photodynamic therapy (PDT) has the potential to reduce treatment-related side effects by decreasing invasiveness and limiting toxicity. Owing to multiple advantageous properties of the porphyrin-HDL nanoparticle (PLP) as a PDT agent, including preferential accumulation in tumor, biodegradability and unprecedented photosensitizer packing, we evaluate PLP-mediated PDT as a minimally invasive, tumor-specific treatment for thyroid cancer. On both a biologically relevant human papillary thyroid cancer (K1) mouse model and an anatomically relevant rabbit squamous carcinoma (VX2)-implanted rabbit thyroid model, the intrinsic fluorescence of PLP enabled tracking of tumor preferential accumulation and guided PDT. This resulted in significant and specific apoptosis in tumor tissue, but not surrounding normal tissues including trachea and recurrent laryngeal nerve (RLN). A long-term survival study further demonstrated that PLP-PDT enabled complete ablation of tumor tissue while sparing both the normal thyroid tissue and RLN from damage, thus providing a safe, minimally invasive, and effective alternative to thyroidectomy for thyroid cancer therapies.

Integration between a hand-held mass spectrometry desorption probe based on picosecond infrared laser technology (PIRL-MS) and an optical surgical tracking system demonstrates in situ tissue pathology from point-sampled mass spectrometry data. Spatially encoded pathology classifications are displayed at the site of laser sampling as color-coded pixels in an augmented reality video feed of the surgical field of view. This is enabled by two-way communication between surgical navigation and mass spectrometry data analysis platforms through a custom-built interface. Performance of the system was evaluated using murine models of human cancers sampled in situ in the presence of body fluids with a technical pixel error of 1.0 ± 0.2 mm, suggesting a 84% or 92% (excluding one outlier) cancer type classification rate across different molecular models that distinguish cell-lines of each class of breast, brain, head and neck murine models. Further, through end-point immunohistochemical staining for DNA damage, cell death and neuronal viability, spatially encoded PIRL-MS sampling is shown to produce classifiable mass spectral data from living murine brain tissue, with levels of neuronal damage that are comparable to those induced by a surgical scalpel. This highlights the potential of spatially encoded PIRL-MS analysis for in vivo use during neurosurgical applications of cancer type determination or point-sampling in vivo tissue during tumor bed examination to assess cancer removal. The interface developed herein for the analysis and the display of spatially encoded PIRL-MS data can be adapted to other hand-held mass spectrometry analysis probes currently available., Integration between a hand-held mass spectrometry desorption probe based on picosecond infrared laser technology (PIRL-MS) and an optical surgical tracking system demonstrates in situ tissue pathology from point-sampled mass spectrometry data.

To evaluate the diagnostic performance of radiologic extranodal extension (rENE) in predicting major (2 mm) and minor (≤2 mm) pathologic ENE (pENE).All oral cavity squamous cell carcinoma patients who underwent neck dissection with pathological nodal disease (pN+) between 2010 and 2015 were reviewed. Preoperative computed tomography and/or magnetic resonance imaging were reviewed by two head and neck neuroradiologists.Three hundred and thirty-four patients were included. The sensitivity and specificity of rENE were 37% [95% CI 29-44] and 98% [95% CI 96-100], respectively. Sensitivity for pENE improved in the subset of patients with major ENE (48% [95% CI 38-57]). The presence of rENE was associated with inferior 3-year overall survival: 26% [95% CI 17-41] versus 60% [95% CI 54-67].This large cohort study demonstrates high specificity, but low sensitivity for preoperative imaging in the detection of pENE in OCSCC. Patients with rENE demonstrated poor OS. pENE in the absence of rENE is still an adverse risk factor.

Intensity-modulated radiation therapy (IMRT) has enabled risk-tailored approach to elective mucosal and nodal clinical target volumes (CTVs) in treatment of head and neck carcinoma of unknown primary (HNCUP). This study report outcomes following such approach.HNCUP patients treated with definitive IMRT between 2005 and 2018 were reviewed. Local failure (LF), regional failure (RF), distant metastasis (DM), overall survival (OS) and grade ≥3 late toxicity (LT) were analyzed. Multivariable analysis (MVA) was used to identify OS predictors for entire cohort and cN2-3 subgroup.A total of 203 patients were eligible: cN1 (7%), cN2a (14%), cN2b (46%), cN2c (14%) and cN3 (19%). Among 118 patients with known HPV status (by p16 staining), 81 (68%) were positive. IMRT target volume spared contralateral tonsil (55%), bilateral or contralateral sides of hypopharynx (72%), nasopharynx (72%), larynx (87%) and contralateral uninvolved neck (21%). Median follow-up was 5 years. Five-year LF, RF, DM, OS, and LT were 3%, 14%, 10%, 79%, and 7% respectively. Four patients developed mucosal recurrence: 3 within and 1 at the margin of the elective mucosal CTV. None of ipsilateral neck irradiation patients failed in the contralateral uninvolved neck. MVA identified cN2c-N3, HPV-negative status and older age as predictors for inferior OS. Within cN2-3 subgroup (n = 189): cN2c-N3, HPV-negative status and older age predicted lower OS, while concurrent chemotherapy was associated with better OS.Definitive IMRT with risk-adaptive radiation volume de-escalation for HNCUP resulted in high probability of tumor control with acceptable rate of late toxicity.

Positive margins have been reported up to 80% in advanced maxillary cancers. Intraoperative navigation (IN) aims to improve margins, but provides a two-dimensional view of a registered instrument without anticipating any cutting directions, and the information is displayed in monitors outside surgical field. Augmented Reality (AR) can delineate margins while addressing the gaze-toggling drawback of IN. In a preclinical setting, we implemented preoperative-planned osteotomies needed for maxillectomies and projected this information on the surgical field using AR. We aimed to improve negative margin rates while retaining the benefits of AR.Five maxillary tumor models were built. Five fellowship-trained surgeons completed virtual unguided and AR-guided maxillectomies. Comparisons in terms of intratumoral cuts, close, adequate, and excessive distances from the tumor were performed. Differences between "ideal" cutting-plan and the AR-guided virtual osteotomies was obtained. Workload questionnaires to evaluate the technology were completed.115 virtual osteotomies were analyzed. Intra-tumoral and "close" margins were lower for the AR-assisted osteotomies (0.0% vs 1.9% p 0.0001 and 0.8% vs 7.9% p 0.0001). Proportion of "adequate" margins were higher in the AR simulations (25.3% vs 18.6%, p = 0.018). The AR osteotomies had high similarity with the pre-planned with interclass correlation index close to 1 in "adequate" margins 0.893 (95% CI: 0.804-0.949). Workload scores were better for AR-guided simulations for the domains of mental demand, performance, effort and frustration.The projector-based AR method improved margin delineation, and preoperative planning was accurately translated to the simulations. Clinical translation will aim to consolidate our preclinical findings to improve outcomes.

ImportanceThe impact of COVID-19 on the modality and timeliness of first-line cancer treatment is unclear yet critical to the planning of subsequent care.ObjectiveTo explore the association of the COVID-19 pandemic with modalities of and wait times for first cancer treatment.Design, Setting, and ParticipantsThis retrospective population-based cohort study using administrative data was conducted in Ontario, Canada, among adults newly diagnosed with cancer between January 3, 2016, and November 7, 2020. Participants were followed up from date of diagnosis for 1 year, until death, or until June 26, 2021, whichever occurred first, to ensure a minimum of 6-month follow-up time.ExposuresReceiving a cancer diagnosis in the pandemic vs prepandemic period, using March 15, 2020, the date when elective hospital procedures were halted.Main Outcomes and MeasuresThe main outcome was a time-to-event variable describing number of days from date of diagnosis to date of receiving first cancer treatment (surgery, chemotherapy, or radiation) or to being censored. For each treatment modality, a multivariable competing-risk regression model was used to assess the association between time to treatment and COVID-19 period. A secondary continuous outcome was defined for patients who were treated 6 months after diagnosis as the waiting time from date of diagnosis to date of treatment.ResultsAmong 313 499 patients, the mean (SD) age was 66.4 (14.1) years and 153 679 (49.0%) were male patients. Those who were diagnosed during the pandemic were less likely to receive surgery first (subdistribution hazard ratio [sHR], 0.97; 95% CI, 0.95-0.99) but were more likely to receive chemotherapy (sHR, 1.26; 95% CI, 1.23-1.30) or radiotherapy (sHR, 1.16; 95% CI, 1.13-1.20) first. Among patients who received treatment within 6 months from diagnosis (228 755 [73.0%]), their mean (SD) waiting time decreased from 35.1 (37.2) days to 29.5 (33.6) days for surgery, from 43.7 (34.1) days to 38.4 (30.6) days for chemotherapy, and from 55.8 (41.8) days to 49.0 (40.1) days for radiotherapy.Conclusions and RelevanceIn this cohort study, the pandemic was significantly associated with greater use of nonsurgical therapy as initial cancer treatment. Wait times were shorter in the pandemic period for those treated within 6 months of diagnosis. Future work needs to examine how these changes may have affected patient outcomes to inform future pandemic guideline development.

ImportanceWhile several studies have documented a link between socioeconomic status and survival in head and neck cancer, nearly all have used ecologic, community-based measures. Studies using more granular patient-level data are lacking.ObjectiveTo determine the association of baseline annual household income with financial toxicity, health utility, and survival.Design, Setting, and ParticipantsThis was a prospective cohort of adult patients with head and neck cancer treated at a tertiary cancer center in Toronto, Ontario, between September 17, 2015, and December 19, 2019. Data analysis was performed from April to December 2021.ExposuresAnnual household income at time of diagnosis.Main Outcome and MeasuresThe primary outcome of interest was disease-free survival. Secondary outcomes included subjective financial toxicity, measured using the Financial Index of Toxicity (FIT) tool, and health utility, measured using the Health Utilities Index Mark 3. Cox proportional hazards models were used to estimate the association between household income and survival. Income was regressed onto log-transformed FIT scores using linear models. The association between income and health utility was explored using generalized linear models. Generalized estimating equations were used to account for patient-level clustering.ResultsThere were 555 patients (mean [SD] age, 62.7 [10.7] years; 109 [20%] women and 446 [80%] men) included in this cohort. Two-year disease-free survival was worse for patients in the bottom income quartile (Conclusions and RelevanceIn this cohort study, patients with head and neck cancer with a household income less than CAD$30 000 experienced worse financial toxicity, health status, and disease-free survival. Significant disparities exist for Ontario’s patients with head and neck cancer.

Background Monitoring circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs), known as liquid biopsies, continue to be developed as diagnostic and prognostic markers for a wide variety of cancer indications, mainly due to their minimally invasive nature and ability to offer a wide range of phenotypic and genetic information. While liquid biopsies maintain significant promising benefits, there is still limited information regarding the kinetics of ctDNA and CTCs following radiation therapy which remains a vital treatment modality in head and neck cancers. This study aims to describe the kinetics of ctDNA and CTCs following radiation exposure in a preclinical rabbit model with VX2 induced buccal carcinoma. Methods Seven rabbits were inoculated with VX2 cells in the buccal mucosa and subjected to radiation. At selected time points, blood sampling was performed to monitor differing levels of ctDNA and CTC. Plasma ctDNA was measured with quantitative PCR for papillomavirus E6 while CTCs were quantified using an immunomagnetic nanoparticles within a microfluidic device. Comparisons of CTC detection with EpCAM compared to multiple surface markers (EGFR, HER2 and PSMA) was evaluated and correlated with the tumor size. Results Plasma ctDNA reflects the overall tumor burden within the animal model. Analysis of correlations between ctDNA with tumor and lymph node volumes showed a positive correlation (R = 0.452 and R = 0.433 [p Conclusion This study demonstrates the utility of ctDNA and CTCs detection in response to radiation treatment in a preclinical head and neck model, allowing for better understanding of liquid biopsy applications in both clinical practice and research development.

BackgroundSitravatinib, a tyrosine kinase inhibitor that targets TYRO3, AXL, MERTK and the VEGF receptor family, is predicted to increase the M1 to M2-polarized tumor-associated macrophages ratio in the tumor microenvironment and have synergistic antitumor activity in combination with anti-programmed death-1/ligand-1 agents. SNOW is a window-of-opportunity study designed to evaluate the immune and molecular effects of preoperative sitravatinib and nivolumab in patients with oral cavity squamous cell carcinoma.MethodsPatients with newly-diagnosed untreated T2-4a, N0-2 or T1 >1 cm-N2 oral cavity carcinomas were eligible. All patients received sitravatinib 120 mg daily from day 1 up to 48 hours pre-surgery and one dose of nivolumab 240 mg on day 15. Surgery was planned between day 23 and 30. Standard of care adjuvant radiotherapy was given based on clinical stage. Tumor photographs, fresh tumor biopsies and blood samples were collected at baseline, at day 15 after sitravatinib alone, and at surgery after sitravatinib–nivolumab combination. Tumor flow cytometry, multiplex immunofluorescence staining and single-cell RNA sequencing (scRNAseq) were performed on tumor biopsies to study changes in immune-cell populations. Tumor whole-exome sequencing and circulating tumor DNA and cell-free DNA were evaluated at each time point.ResultsTen patients were included. Grade 3 toxicity occurred in one patient (hypertension); one patient required sitravatinib dose reduction, and one patient required discontinuation and surgery delay due to G2 thrombocytopenia. Nine patients had clinical-to-pathological downstaging, with one complete response. Independent pathological treatment response (PTR) assessment confirmed a complete PTR and two major PTRs. With a median follow-up of 21 months, all patients are alive with no recurrence. Circulating tumor DNA and cell-free DNA dynamics correlated with clinical and pathological response and distinguished two patient groups with different tumor biological behavior after sitravatinib alone (1A) versus sitravatinib–nivolumab (1B). Tumor immunophenotyping and scRNAseq analyses revealed differential changes in the expression of immune cell populations and sitravatinib-targeted and hypoxia-related genes in group 1A vs 1B patients.ConclusionsThe SNOW study shows sitravatinib plus nivolumab is safe and leads to deep clinical and pathological responses in oral cavity carcinomas. Multi-omic biomarker analyses dissect the differential molecular effects of sitravatinib versus the sitravatinib–nivolumab and revealed patients with distinct tumor biology behavior.Trial registration numberNCT03575598.

Background: Resource restrictions were established in many jurisdictions to maintain health system capacity during the COVID-19 pandemic. Disrupted healthcare access likely impacted early cancer detection. The objective of this study was to assess the impact of the pandemic on weekly reported cancer incidence. Patients and Methods: This was a population-based study involving individuals diagnosed with cancer from September 25, 2016, to September 26, 2020, in Ontario, Canada. Weekly cancer incidence counts were examined using segmented negative binomial regression models. The weekly estimated backlog during the pandemic was calculated by subtracting the observed volume from the projected/expected volume in that week. Results: The cohort consisted of 358,487 adult patients with cancer. At the start of the pandemic, there was an immediate 34.3% decline in the estimated mean cancer incidence volume (relative rate, 0.66; 95% CI, 0.57–0.75), followed by a 1% increase in cancer incidence volume in each subsequent week (relative rate, 1.009; 95% CI, 1.001–1.017). Similar trends were found for both screening and nonscreening cancers. The largest immediate declines were seen for melanoma and cervical, endocrinologic, and prostate cancers. For hepatobiliary and lung cancers, there continued to be a weekly decline in incidence during the COVID-19 period. Between March 15 and September 26, 2020, 12,601 fewer individuals were diagnosed with cancer, with an estimated weekly backlog of 450. Conclusions: We estimate that there is a large volume of undetected cancer cases related to the COVID-19 pandemic. Incidence rates have not yet returned to prepandemic levels.

Objective Despite increasing recognition of the importance of functional outcomes for patients with head and neck cancer, post-treatment neck fibrosis remains poorly understood. We sought to develop and validate a patient reported outcome measure for head and neck cancer patients with neck fibrosis. Study design Prospective multiphase cross-sectional study. Methods To guide instrument development, we employed the World Health Organization International Classification of Functioning, Disability and Health as our conceptual framework. Items were generated using a composite strategy consisting of patient focus groups, literature review, and expert opinion from a multidisciplinary group. Candidate items were reduced through the item impact method. Preliminary psychometric properties of the finalized instrument were evaluated through measures of internal consistency, test-retest reliability, and construct validity. Results Four in person focus groups were held with 13 head and neck cancer patients. The process of item generation led to 221 relevant citations and 68 unique items. An additional 17 items were identified from review of existing neck disability questionnaires and expert opinion. A draft instrument with 25 candidate items was generated and reduced to its final 15-item scale using item impact method. Early psychometric testing revealed excellent internal consistency (Cronbach's alpha = 0.95) and test-retest reliability [ICC = 0.95]. Internal consistency at the item level was good (>0.7) for 11/15 individual items. Four separate constructs were evaluated. Three of the four constructs matched our a priori hypotheses. Conclusion The Neck Fibrosis Scale demonstrates preliminary reliability and validity for discriminate use. Further research is needed to confirm dimensionality and assess responsiveness. Level of evidence NA Laryngoscope, 2021.

OBJECTIVES/HYPOTHESIS Sarcopenia is a hallmark of aging and its identification may help predict adverse postoperative events in patients undergoing head and neck surgery. The study objective was to assess the relationship between sarcopenia and postoperative complications and length of stay in patients undergoing major head and neck cancer surgery. STUDY DESIGN Prospective cohort study. METHODS A prospective cohort study was performed of patients 50 years and older undergoing major head and neck surgery. Sarcopenia was defined as low muscle mass (determined by neck muscle cross-sectional imaging) with either low muscle strength (grip strength) or low muscle performance (timed walk test). Logistic regression was applied on binary outcomes, and linear regression was used for log-transformed length of hospital stay (LOS). Univariate and multivariate analyses were performed. RESULTS Of the 251 patients enrolled, pre-sarcopenia was present in 34.9% (n = 87) and sarcopenia in 15.6% (n = 39) of patients. Patients with sarcopenia were more likely to be older (P = .001), female (P = .001), have a lower body mass index (P = .001), and lower preoperative hemoglobin (P

OBJECTIVES/HYPOTHESIS Performance of thyroidectomy on an outpatient basis has gained popularity although many jurisdictions have not shifted their practice despite a strong safety profile. We sought to assess the uptake and safety of outpatient thyroidectomy in Ontario. STUDY DESIGN Retrospective cohort study. METHODS This was a population-based retrospecive cohort of adult patients undergoing hemithyroidectomy or total thyroidectomy between 1993 and 2017 in Ontario, Canada. Outpatient surgery was defined as discharge home on the same day of surgery. Outcomes of interest include 30-day all cause death, hematoma, emergency department use, and readmission. To adjust for confounding, propensity scores were calculated. Logistic regression models with inverse probability of treatment weighting (IPTW) were then used to estimate the exposure-outcome relationship. RESULTS The final cohort consisted of 81,199 patients: 8,442 underwent same day surgery and 72,757 were admitted. The proportion of patients undergoing outpatient thyroidectomy increased overtime (2.3% in 1993-1994 to 17.8% in 2016-2017). Factors associated with higher odds of outpatient thyroidectomy included: younger age, less material deprivation, less comorbidities, and higher surgeon volume. The absolute number of deaths (≤5) and hematomas (64, 0.8%) in the outpatient cohort was low. After IPTW adjustment, patients with outpatient management had lower odds of neck hematoma (OR 0.73[95CI% 0.58-0.93)], but higher odds of emergency department use (OR 1.67[95%CI 1.56-1.79]). CONCLUSIONS Outpatient thyroidectomy is not associated with an increased mortality risk. Less than one in five patients undergo outpatient thyroidectomy in Ontario, despite a well-established safety profile. LEVEL OF EVIDENCE 3 Laryngoscope, 131:2625-2633, 2021.

Background This American Head and Neck Society (AHNS) consensus statement focuses on evidence-based comprehensive pain management practices for thyroid and parathyroid surgery. Overutilization of opioids for postoperative pain management is a major contributing factor to the opioid addiction epidemic however evidence-based guidelines for pain management after routine head and neck endocrine procedures are lacking. Methods An expert panel was convened from the membership of the AHNS, its Endocrine Surgical Section, and ThyCa. An extensive literature review was performed, and recommendations addressing several pain management subtopics were constructed based on best available evidence. A modified Delphi survey was then utilized to evaluate group consensus of these statements. Conclusions This expert consensus provides evidence-based recommendations for effective postoperative pain management following head and neck endocrine procedures with a focus on limiting unnecessary use of opioid analgesics.

It is unclear whether postoperative wound infections after head and neck cancer surgery are associated with cancer progression.Patients undergoing surgery for oral cancer from 1998 to 2011 were reviewed. Univariable analyses and multivariable were performed. Propensity scores were used to create matched cohorts for infection and non-infection groups. Neutrophil-to-lymphocyte ratios (NLR) were determined prior to surgery and at the time of infection.Of 551 patients with oral cancer treated with surgery, 98 developed wound infections (18%). Tumor factors associated with wound infections included higher T and N category, extranodal extension, depth of invasion, lymphovascular and perineural invasion (p 0.02 for all). On univariable analysis, wound infection was a predictor for recurrence free survival (p 0.001), locoregional control (p = 0.01), and distant control (p 0.001). Wound infection was not a predictor of overall survival (p = 0.88), recurrence free survival (p = 0.17), locoregional control (p = 0.79) or distant control (p = 0.18) on multivariable analysis. Using a propensity score matched cohort of 83 patients with and without infection, wound infection was not associated with recurrence free survival (p = 0.21), overall survival (p = 0.71), and locoregional control (p = 0.84), although there was a trend towards increased distant metastases (p = 0.10). Patients with wound infection had a greater preoperative NLR as well as a greater rise in the NLR after surgery, but these were not associated with survival or recurrence.Patients with wound infections have more adverse pathologic features. However, wound infection was not associated with poorer cancer outcomes although a trend towards increased distant metastases should be investigated.

BACKGROUND The image-guided operating room (OR) is an emerging standard for dealing with complex cases in many surgical disciplines including neurosurgery, thoracic surgery, maxillofacial trauma, and orthopedic surgery. Its use in head and neck oncological surgery is not well established. The primary aim of this study was to assess the image quality of cone-beam CT (CBCT) under real clinical conditions. The secondary aim was to assess the effect on surgical performance and decision making. METHODS Intraoperative 3D imaging was performed using a CBCT capable C-Arm mounted on a multi-axis robot (Siemens Zeego) in the image-guided OR. All patients had immediate preoperative imaging taken with further intraoperative imaging performed as required. Ten initial patients, comprising 28 intraoperative scans, were used for questionnaire-based image reviews conducted with experienced head and neck clinicians. Scans were assessed for aspects of both image quality and clinical utility, on separate 5-point Likert scales (1-5). RESULTS The median rating for bony detail was 4 out of 5. Vascular detail was increased (P < 10-8 ) from 1 to 3 with the use of IV contrast (region of interest CT# was 284 HU [SD, 47 HU]). Images were rated as 4 for freedom from artifact. Soft tissue definition was 2, with no significant improvement (P = .2) with the addition of IV iodinated contrast. Surgeons rated the greatest clinical utility (4) for the CBCT when assessing postreconstruction imaging of a complex case. CONCLUSIONS The image quality of CBCT in the image-guided OR is good for bony detail and complex oncological reconstructions in the head and neck setting but probably has limited benefit for intraoperative soft tissue delineation. Future studies must also focus on clinical outcomes to help demonstrate the value of the image-guided OR.

Purpose Preoperative assessment of benign subglottic stenosis is usually performed by endoscopy and a computed tomography scan. Both diagnostic modalities have relevant limitations and sometimes an accurate assessment of the extent of disease is challenging. Description Based on computed tomography scans of benign glotto-subglottic stenosis and a control airway, color-coded three-dimensional (3D) models were produced using a commercially available 3D printer. The diagnostic relevance of 3D models was tested by means of a quiz. Evaluation 52 thoracic surgeons from 4 North American and 1 European institution with different levels of experience in airway surgery were invited to test the diagnostic accuracy of 3D models against endoscopy films and computed tomography scans. 3D models were found to be superior to the other two diagnostic tools in terms of grading the extent of the stenosis and selecting the correct surgical strategy. The group of residents benefited the most from the 3D models. Conclusions 3D models of complex glotto-subglottic airway stenosis are a useful supplement of the preoperative assessment. In addition, they can serve as a teaching tool for residents and fellows.

When deforming pathology limits intraoperative plating of the mandible, three-dimensional (3D) models can be generated by digitally replacing the deformed segment of bone with an inverted segment from the contralateral unaffected mandible to adapt a reconstruction plate. The purpose of this study was to use 3D conformance analysis to evaluate the degree of accuracy of this "segmental mirroring" technique.Using a pre-existing melanoma database (January 1, 2005-September 20, 2015), high-resolution computed tomography (CT) scans of the head and neck were obtained from patients without evidence of bony disease or defects involving the mandible. Using 3D software (Mimics, Materialise, Leuven, Belgium), each mandible was segmented based on four defect classes (Ic, II, IIc and III) of the Brown et al. (2016) classification system. An inverted, or "mirrored", image of each segment was digitally created and manually co-registered with the corresponding contralateral segment of the mandible. Conformance analysis was performed by calculating the root-mean-square (RMS) conformance distance and through evaluating 3D generated conformance maps. The primary outcome was degree of conformance. Data were analyzed using descriptive statistics and tests of statistical significance. The significance level was set at a p-value less than or equal to .05.A high degree of conformance (mean RMS 1 mm) was observed when comparing all classes of simulated reconstruction. The closest conformance was observed for class III simulated reconstructions (mean RMS: 0.4 ± 0.2 mm). Inclusion of the condyle resulted in a reduced mean RMS conformance (class II: 0.5 ± 0.3 mm vs class IIc: 0.7 ± 0.5 mm; p = 0.01). There was no significant difference between RMS conformance distances when comparing side of simulated reconstruction. Evaluation of 3D mapping demonstrated reduced conformance with simulated reconstruction of the condyle and coronoid process.The segmental mirroring technique can be used reliably to generate highly accurate three-dimensional models that may assist with mandibular reconstruction in circumstances where bony deformity limits intraoperative adaptation of a reconstruction plate. This technique is less accurate where pathology involves the mandibular condyle and, to a lesser degree, the coronoid process.

Background Care for patients with thyroid nodules is complex and multidisciplinary, and research demonstrates variation in care. The objective was to develop clinical guidelines and quality metrics to reduce unwarranted variation and improve quality. Methods Multidisciplinary expert consensus and modified Delphi approach. Source documents were workflow algorithms from Kaiser Permanente Northern California and Cancer Care of Ontario based on the 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer. Results A consensus-based, unified preoperative, perioperative, and postoperative workflow was developed for North American use. Twenty-one panelists achieved consensus on 16 statements about workflow-embedded process and outcomes metrics addressing safety, access, appropriateness, efficiency, effectiveness, and patient centeredness of care. Conclusion A panel of Canadian and United States experts achieved consensus on workflows and quality metric statements to help reduce unwarranted variation in care, improving overall quality of care for patients diagnosed with thyroid nodules.

Clinical trials with novel fluorescence contrast agents for head and neck cancer are driving new applications for fluorescence-guided surgery. Two-dimensional fluorescence imaging systems, however, provide limited in vivo assessment capabilities to determine tumor invasion depth below the mucosal surface. Here, we investigate the use of spatial frequency domain imaging (SFDI) methods for sub-surface fluorescence in tissue-simulating oral cancer phantoms. A two-step profile-correction approach for SFDI is under development to account for the complex surface topography of the oral cavity. First, for structured-illumination estimation of the surface profile, we are evaluating gray code and phase shift profilometry methods in agar-based oral cavity phantoms to maximize resolution and minimize sensitivity to surface discontinuities. Second, for profile-correction of the diffuse reflectance, global lighting effects within the oral cavity – analogous to an integrating sphere – are modeled using a multi-bounce numerical model. Subsurface fluorescence imaging is enabled based on the variations in optical sampling depth that result from changes in spatial frequency. An analytical depth recovery approach is based on a numerical diffusion theory model for semi-infinite fluorescence slabs of variable thickness. Depth estimation is evaluated in an agar-based phantom with fluorescence inclusions of thicknesses 1-5.5 mm originating from the top surface (“iceberg model”). Future clinical studies are necessary to assess in vivo performance and intraoperative workflow.

Purpose/objective(s) Local control (LC) of head and neck (HN) soft tissue sarcoma (STS) is generally lower than the > 90% rate expected in extremity STS. We report outcomes of high-risk adult HN STS [defined as requiring surgery and radiotherapy (RT) after joint in-person assessment by a HN surgeon and radiation oncologist with expertise in sarcoma management] using pre-operative (Pre-op) RT to reduce target volumes adjacent to optic or other vulnerable anatomy. Materials/methods A prospective series of newly diagnosed adult HN STS patients who underwent Pre-op RT between 1989-2019 was analyzed. Angiosarcoma, fibromatosis, and embryonal/alveolar rhabdomyosarcoma were not included due to natural history requiring different management paradigms; other histologies were excluded due to the anticipated favorable control rates in these subtypes (i.e., dermatofibrosarcoma protuberans, HN sinonasal solitary fibrous tumor/hemangiopericytoma). Actuarial rates of LC, distant control (DC), and overall survival (OS) were analyzed by resection margin status. Important wound complications, defined according to a published randomized trial evaluating Pre-op RT in extremity STS, were also reported. Results Eligibility comprised 59 cases arising from neck/supraclavicular (n = 23), sinonasal (n = 16), oral (n = 11), parapharyngeal (n = 7), and scalp (n = 2) regions. UICC/AJCC TNM-8 cT-categories were: T1 (n = 10), T2 (n = 20), T3 (n = 20), and T4 (n = 9). Neoadjuvant chemotherapy was given to 3 patients (2 rhabdomyosarcomas and 1 synovial sarcoma). Pre-op RT included: 50 Gy in 25 fractions over 5 weeks (n = 53) or 60 Gy in 30 fractions over 6 weeks (n = 6). Median interval from pre-op RT to surgery was 7.3 weeks (range: 2.9-19.6). Four patients (6.7%) had wound complications considered important according to the defined criteria. One healed following flap debridement and the remainder only required conservative management. Resection margins were grossly positive (gross+) in 4 (7%), microscopically positive (micro+) in 16 (27%), and negative in 39 (68%) patients. Six received a post-op boost of 10 Gy in 5 fractions (1 for micro+ and 5 for Conclusion HN STS patients requiring combined modality local management with moderate dose Pre-op RT in a sarcoma-focused multidisciplinary clinic setting have excellent LC and functional outcomes that parallel extremity cases, but with less wound complications. Micro+ margins without postop boost RT does not seem to compromise LC when managed within a collaborative environment.

Importance Although most thyroid nodules are benign, the potential for malignant neoplasms is associated with unnecessary workup in the form of imaging, fine-needle aspiration, and diagnostic surgery. The American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) is commonly used to assess the malignant neoplasm risk potential of thyroid nodules imaged by ultrasonography. However, standardized reporting of ACR TI-RADS descriptors is inconsistent. Objective To increase the documentation rate of ACR TI-RADS thyroid nodule characteristics to 80% in 18 months. Design, setting, and participants This prospective interrupted time series quality improvement study was conducted from December 1, 2018, to March 31, 2020, at a tertiary outpatient head and neck clinic among 229 patients who had at least 1 documented thyroid nodule identified on bedside clinic ultrasonography. Data analysis was performed throughout the entire study period because this was a quality improvement study with iterative small cycle changes; final analysis of the data was performed in April 2020. Main outcomes and measures The primary outcome was the documentation rates of 6 ACR TI-RADS ultrasonographic descriptors. Secondary outcomes included nodule fine-needle aspiration biopsy rate and physician-reported clinic flow efficiency. Results A total of 229 patients had at least 1 documented thyroid nodule and were included in the analysis. Size was the most frequently documented nodule characteristic (72 of 74 [97.3%]) at baseline, followed by echogenic foci (31 of 74 [41.9%]), composition (23 of 74 [31.1%]), echogenicity (17 of 74 [23.0%]), margin (6 of 74 [8.1%]), and shape (1 of 74 [1.4%]). After 3 Plan, Do, Study, Act (PDSA) cycles, the final intervention consisted of a standardized ultrasonography reporting form and educational initiatives for surgical trainees. After the third PDSA cycle (n = 36), reporting of nodule size, echogenic foci, and composition increased to 100%. Similarly, reporting of echogenicity (34 of 36 [94.4%]), shape (28 of 36 [77.8%]), and margin (25 of 36 [69.4%]) all increased. This represented a cumulative 90.3% documentation rate (195 of 216), a 56.5% increase from baseline (95% CI, 50.0%-61.9%). The standardized reporting form was used in 83.3% of eligible thyroid ultrasonography cases (30 of 36) after PDSA cycle 3, demonstrating good fidelity of implementation. There were no unintended consequences associated with clinic workflow, as a balancing measure, reported by staff surgeons. Conclusions and relevance This study suggests that implementation of an ACR TI-RADS-based reporting form in conjunction with educational initiatives improved documentation of ultrasonographic thyroid nodule characteristics, potentially allowing for improved bedside risk stratification and communication among clinicians.

This study aimed to assess whether surgical case volume for lateral neck dissection has an impact on the survival of patients who have well-differentiated thyroid cancer (WDTC) with lateral cervical node metastases. The authors used a population-based cohort study design.The study cohort consisted of WDTC patients in Ontario Canada who underwent thyroidectomy and lateral neck dissection. These patients were identified using both hospital- and surgeon-level administrative data between 1993 and 2017 (n = 1832). Surgeon and hospital volumes were calculated based on the number of cases managed in the year before the procedure by the physician and at the institution managing each case, respectively, and divided into tertiles. Multilevel Cox regression models were used to estimate the effect of volume on disease-free survival (DFS).A crude model without patient or treatment characteristics demonstrated that DFS was associated with both higher surgeon volume tertiles (p0.01) and higher hospital volume tertiles (p0.01). After control for clustering, patient/treatment covariates, and hospital volume, the lowest surgeon volume tertile (range, 0-20/year; mean, 6.5/year) remained an independent statistically significant negative predictor of DFS (hazard ratio, 1.71; 95 % confidence interval, 1.22-2.4; p0.01).Surgeon lateral neck dissection case volume is a predictor of better DFS for thyroid cancer patients, with the lowest surgeon volume tertile (20 neck dissections per year) demonstrating poorer DFS.

Purpose of review Image guided navigation has had significant impact in head and neck surgery, and has been most prolific in endonasal surgeries. Although conventional image guidance involves static computed tomography (CT) images attained in the preoperative setting, the continual evolution of surgical navigation technologies is fast expanding to incorporate both real-time data and bioinformation that allows for improved precision in surgical guidance. With the rapid advances in technologies, this article allows for a timely review of the current and developing techniques in surgical navigation for head and neck surgery. Recent findings Current advances for cross-sectional-based image-guided surgery include fusion of CT with other imaging modalities (e.g., magnetic resonance imaging and positron emission tomography) as well as the uptake in intraoperative real-time 'on the table' imaging (e.g., cone-beam CT). These advances, together with the integration of virtual/augmented reality, enable potential enhancements in surgical navigation. In addition to the advances in radiological imaging, the development of optical modalities such as fluorescence and spectroscopy techniques further allows the assimilation of biological data to improve navigation particularly for head and neck surgery. Summary The steady development of radiological and optical imaging techniques shows great promise in changing the paradigm of head and neck surgery.

Background Restoring anatomical contour and position of the malar eminence and orbital rim following ablative mid-face procedures is critical in maintaining facial contour and orbit position. Objective To report our reconstructive approach using the scapular tip free-flap (STFF) for orbito-zygomatic defects, evaluating contour and overall shape restoration. Methods The study included 2 series: a clinical cohort of 15 consecutive patients who underwent an orbito-zygomatic reconstruction with a STFF and a cohort of 10 patients who had CT scan imaging but did not have orbito-zygomatic surgical resection or reconstruction. Using a 3D software, overall conformance (OC) and contour conformance (CC) with respect to the mirrored contralateral (clinical cohort) or native zygoma (preclinical cohort) were analyzed. Postoperative orbital volumes were also measured in the clinical cohort. Mean, median, root-mean-square (RMS), minimum and maximum measurements were obtained both for OC and CC. Conformance values of clinical and preclinical cohort were compared to objectively evaluate the quality of reconstruction in terms of orbito-zygomatic framework restoration (Mann-Whitney test). Results All measurements for OC and CC between scapular tip and the zygoma showed no differences, both on the clinical (RMS: OC 3.29 mm vs CC 3.32 mm -p = NS-) and preclinical (RMS: OC 2.03 mm and CC 2.31 mm -p = NS-) cohorts. Moreover, there were no differences in post-operative orbital volumes in the clinical cohort. Clinical outcomes of the case-series are also reported. Conclusion The STFF is highly effective in restoring facial projection and orbital volume in orbito-zygomatic reconstruction.

An integrated augmented reality (AR) surgical navigation system that potentially improves intra-operative visualization of concealed anatomical structures. Integration of real-time tracking technology with a laser pico-projector allows the surgical surface to be augmented by projecting virtual images of lesions and critical structures created by multimodality imaging. We aim to quantitatively and qualitatively evaluate the performance of a prototype interactive AR surgical navigation system through a series of pre-clinical studies. Four pre-clinical animal studies using xenograft mouse models were conducted to investigate system performance. A combination of CT, PET, SPECT, and MRI images were used to augment the mouse body during image-guided procedures to assess feasibility. A phantom with machined features was employed to quantitatively estimate the system accuracy. All the image-guided procedures were successfully performed. The tracked pico-projector correctly and reliably depicted virtual images on the animal body, highlighting the location of tumour and anatomical structures. The phantom study demonstrates the system was accurate to 0.55 ± 0.33mm. This paper presents a prototype real-time tracking AR surgical navigation system that improves visualization of underlying critical structures by overlaying virtual images onto the surgical site. This proof-of-concept pre-clinical study demonstrated both the clinical applicability and high precision of the system which was noted to be accurate to

Made available in DSpace on 2020-12-12T01:55:37Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-12-01 Canada Foundation for Innovation Ontario Institute for Cancer Research Canada Research Chairs Prognostic biomarkers for recurrence of Oral Squamous Cell Carcinoma (OSCC) are urgently needed. We aimed to independently validate a 4-gene expression signature (MMP1, COL4A1, P4HA2, THBS2) predictive of OSCC recurrence risk. Gene expression was measured using Nanostring nCounter® in 245 histologically normal surgical resection margins from 62 patients. Association between risk scores for individual patients and recurrence was assessed by Kaplan-Meier analysis. Signature performance was quantified by concordance index (CI), hazard ratio (HR) and the area under receiver operating characteristics (AUC). Risk scores for recurrence were significantly higher than recurrence-free patients (p = 9.58e-7, Welch’s t-test). A solid performance of the 4-gene signature was determined: CI = 0.64, HR = 3.38 (p = 1.4E-4; log-rank test), AUC = 0.71. We showed that three margins per patient are sufficient to preserve predictive performance (CI = 0.65; HR = 2.92; p = 2.94e-3; AUC = 0.71). Association between the predicted risk scores and recurrence was assessed and showed HR = 2.44 (p = 9.6E-3; log-rank test, N = 62). Signature performance analysis was repeated using an optimized threshold (70th percentile of risks), resulting in HR = 3.38 (p = 1.4E-4; log-rank test, N = 62). The 4-gene signature was validated as predictive of recurrence risk in an independent cohort of patients with resected OSCC and histologically negative margins, and is potentially applicable for clinical decision making on adjuvant treatment and disease monitoring. São Paulo State University UNESP Faculty of Medicine Department of Surgery and Orthopedics Krembil Research Institute University Health Network Department of Clinical Pathology Sunnybrook Health Sciences Centre Princess Margaret Cancer Centre University Health Network Brazilian Institute for Cancer Control Department of Pathology Toronto General Hospital University Health Network Departments of Medical Biophysics University of Toronto Department of Computer Science University of Toronto Institute of Neuroimmunology Slovak Academy of Sciences Clinical Laboratory Genetics Genome Diagnostics University Health Network Department of Laboratory Medicine and Pathobiology The University of Toronto São Paulo State University UNESP Faculty of Medicine Department of Surgery and Orthopedics

Several technologies have been implemented in orthopedic surgery to improve surgical outcomes, usually focusing on more accurate execution of a surgical plan, but the development of the plan itself is also of great importance. The purpose of this study is to examine whether the use of preoperative computer planning platforms can improve the surgical plan?Eight surgeons created a preoperative surgical plan to resect a distal femur parosteal osteosarcoma in two settings: (1) Using a 2-D and 3-D CT scan only (current standard); and (2) using a computer-assisted planning platform. The plans were thereafter virtually executed using a novel surgical navigation system and a Sawbones model. This simulated model was derived from, and identical to, an actual patient scenario. The outcomes of interest were the number of positive margin cuts, and the volume of the resected specimen.Using the surgical plan developed with computer assistance, there were 4 positive margin cuts made by 2 surgeons. In comparison, using standard planning, there were 14 positive margin cuts made by all 8 surgeons (p = 0.02). The resection volume was larger in the computer-assisted plans (96 ± 10 mmComputer-assisted planning significantly decreased the risk of a positive margin resection in this Sawbones tumor model used to simulate resection of a primary bone sarcoma. This proof of concept study highlights the importance of advanced surgical planning and sets the ground for developing beneficial surgical planning systems.

IntroductionAdvanced oral cancer and its ensuing treatment engenders significant morbidity and mortality. Patients are often elderly with significant comorbidities. Toxicities associated with surgical resection can be devastating and they are often highlighted by patients as impactful. Given the potential for suboptimal oncological and functional outcomes in this vulnerable patient population, promotion and performance of shared decision making (SDM) is crucial.Decision aids (DAs) are useful instruments for facilitating the SDM process by presenting patients with up-to-date evidence regarding risks, benefits and the possible postoperative course. Importantly, DAs also help elicit and clarify patient values and preferences. The use of DAs in cancer treatment has been shown to reduce decisional conflict and increase SDM. No DAs for oral cavity cancer have yet been developed.This study endeavours to answer the question: Is there a patient or surgeon driven need for development and implementation of a DA for adult patients considering major surgery for oral cancer?Methods and analysisThis study is the first step in a multiphase investigation of SDM during major head and neck surgery. It is a multi-institutional convergent parallel mixed-methods needs assessment study. Patients and surgeon dyads will be recruited to complete questionnaires related to their perception of the SDM process (nine-item Shared Decision-Making Questionnaire, SDM-Q-9 and SDM-Q-Doc) and to take part in semistructured interviews. Patients will also complete questionnaires examining decisional self-efficacy (Ottawa Decision Self-Efficacy Scale) and decisional conflict (Decisional Conflict Scale). Questionnaires will be completed at time of recruitment and will be used to assess the current level of SDM, self-efficacy and conflict in this setting. Thematic analysis will be used to analyse transcripts of interviews. Quantitative and qualitative components of the study will be integrated through triangulation, with matrix developed to promote visualisation of the data.Ethics and DisseminationThis study has been approved by the research ethics boards of the Nova Scotia Health Authority (Halifax, Nova Scotia) and the University Health Network (Toronto, Ontario). Dissemination to clinicians will be through traditional approaches and creation of a head and neck cancer SDM website. Dissemination to patients will include a section within the website, patient advocacy groups and postings within clinical environments.

Objective The aim of this study is to determine if Hyams grade may help predict which patients with esthesioneuroblastoma (ENB) tumors are likely to develop regional recurrences, and to determine the impact of tumor extent on regional failure in ENB patients without evidence of nodal disease at presentation. Design The study was designed as a retrospective review for ENB patients. Settings The study was prepared at tertiary care academic center for ENB patients. Participants Patients with ENB were included in the study. Main Outcome Measures Oncologic outcomes (5-year regional and locoregional control (LRC) and overall survival) in patients with Hyams low grade versus high grade. Oncologic outcomes based on radiographic disease extent. Results A total of 43 patients were included. Total 25 patients (58%) had Hyams low-grade tumor, and 18 (42%) had high-grade tumor. Of the 34 patients without regional disease at presentation, 8 (24%) were treated with elective nodal radiation. There were no statistically significant differences in 5-year regional control in the Hyams low-grade versus high-grade groups (78 vs. 89%; p = 0.4). The 5-year LRC rates in patients with low grade versus high grade were 73 versus 89% (p = 0.6). The 5-year overall survival rates in patients with low-grade versus high-grade tumors were 86 versus 63% (p = 0.1). Radiographic extension of disease into the olfactory groove, olfactory nerve, dura, and periorbita were statistically associated with decreased 5-year overall survival (5-year OS 49 vs. 91% [p = 0.04], 49 vs. 91% [p = 0.04], 44 vs. 92% [p = 0.02], and 44 vs. 80% [p = 0.04], respectively). Conclusion ENBs are associated with a risk of regional failure. The current analysis suggests that Hyams low-grade and high-grade malignancies have comparable rates of early and delayed regional recurrences, although small sample size may limit our conclusions.

Background: Monitoring circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs), known as liquid biopsies, continue to be developed as diagnostic and prognostic markers for a wide variety of cancer indications, mainly due to their minimally invasive nature and ability to offer a wide range of phenotypic and genetic information. While liquid biopsies maintain significant promising benefits, there is still limited information regarding the kinetics of ctDNA and CTCs following radiation therapy which remains a vital treatment modality in head and neck cancers. This study aims to describe the kinetics of ctDNA and CTCs following radiation exposure in a preclinical rabbit model with VX2 induced buccal carcinoma. Methods: Seven rabbits were inoculated with VX2 cells in the buccal mucosa and subjected to radiation. At selected time points, blood sampling was performed to monitor differing levels of ctDNA and CTC. Plasma ctDNA was measured with quantitative PCR for papillomavirus E6 while CTCs were quantified using an immunomagnetic nanoparticles within a microfluidic device. Comparisons of CTC detection with EpCAM compared to multiple surface markers (EGFR, HER2 and PSMA) was evaluated and correlated with the tumor size.Results: Plasma ctDNA reflects the overall tumor burden within the animal model. Analysis of correlations between ctDNA with tumor and lymph node volumes showed a positive correlation (R= 0.452 and R = 0.433 [p Conclusion: This study demonstrates the utility of ctDNA and CTCs detection in response to radiation treatment in a preclinical head and neck model, allowing for better understanding of liquid biopsy applications in both clinical practice and research development.

Lateral craniofacial defects are particularly challenging to reconstruct due to the tissue variety and the complexity of the anatomical structures of the region. Technological advancements with the use of digital planning software have been increasingly utilized to assist the reconstructive surgeon to restore function and aesthetics in this location. The basic principle of “computer-assisted surgery” (CAS) relies in the ability to capture patients’ images and manipulate them to virtually reproduce the surgical ablation and create a plan for reconstruction. In addition, by three-dimensional (3D) printing it became possible to obtain products derived from virtual planning such as patient-specific protheses and cutting guides to assist during tumor resection and reconstruction. Virtual technology has also been utilized intraoperatively with promising results. Perhaps the most recent and substantial technological innovation has been the application of bioengineering to reconstructive surgery. Three-dimensionally printed biomaterials, also known as scaffolds, have been developed with the capacity of stimulate new tissue formation by incorporating stem cells, with infinite theoretical applications. In the current era of reconstructive surgery where better results are pursued, defects in the lateral craniofacial region have obligated researchers to create an operation of the future. The possibility of combining CAS with scaffolds, stem cells, and free tissue transfer might represent a forthcoming paradigm in reconstructive surgery.

This study evaluates a long-acting liposomal fluorescence / CT dual-modality contrast agent (CF800) in head and neck cancer to enhance intraoperative tumor demarcation with fluorescence imaging and cone-beam computed tomography (CBCT). CF800 was administered to 12 buccal cancer-bearing rabbits. Imaging was acquired at regular time points to quantify time-dependent contrast enhancement. Surgery was performed 5-7 days after, with intraoperative near-infrared fluorescence endoscopy and CBCT, followed by histological and ex-vivo fluorescence assessment. Tumor enhancement on CT was significant at 24, 96 and 120 hours. Volumetric analysis of tumor segmentation showed high correlation between CBCT and micro-CT. Fluorescence signal was apparent in both ex-vivo and in-vivo imaging. Histological correlation showed [100%] specificity for primary tumor. Sensitivity and specificity of CF800 in detecting nodal involvement require further investigation.CF800 is long acting and has dual function for CT and fluorescence contrast, making it an excellent candidate for image-guided surgery.

Background In the wake of the coronavirus disease 2019 (COVID‐19) pandemic, access to surgical care for patients with head and neck cancer (HNC) is limited and unpredictable. Determining which patients should be prioritized is inherently subjective and difficult to assess. The authors have proposed an algorithm to fairly and consistently triage patients and mitigate the risk of adverse outcomes. Methods Two separate expert panels, a consensus panel (11 participants) and a validation panel (15 participants), were constructed among international HNC surgeons. Using a modified Delphi process and RAND Corporation/University of California at Los Angeles methodology with 4 consensus rounds and 2 meetings, groupings of high‐priority, intermediate‐priority, and low‐priority indications for surgery were established and subdivided. A point‐based scoring algorithm was developed, the Surgical Prioritization and Ranking Tool and Navigation Aid for Head and Neck Cancer (SPARTAN‐HN). Agreement was measured during consensus and for algorithm scoring using the Krippendorff alpha. Rankings from the algorithm were compared with expert rankings of 12 case vignettes using the Spearman rank correlation coefficient. Results A total of 62 indications for surgical priority were rated. Weights for each indication ranged from −4 to +4 (scale range; −17 to 20). The response rate for the validation exercise was 100%. The SPARTAN‐HN demonstrated excellent agreement and correlation with expert rankings (Krippendorff alpha, .91 [95% CI, 0.88‐0.93]; and rho, 0.81 [95% CI, 0.45‐0.95]). Conclusions The SPARTAN‐HN surgical prioritization algorithm consistently stratifies patients requiring HNC surgical care in the COVID‐19 era. Formal evaluation and implementation are required. Lay Summary Many countries have enacted strict rules regarding the use of hospital resources during the coronavirus disease 2019 (COVID‐19) pandemic. Facing delays in surgery, patients may experience worse functional outcomes, stage migration, and eventual inoperability.Treatment prioritization tools have shown benefit in helping to triage patients equitably with minimal provider cognitive burden.The current study sought to develop what to the authors' knowledge is the first cancer–specific surgical prioritization tool for use in the COVID‐19 era, the Surgical Prioritization and Ranking Tool and Navigation Aid for Head and Neck Cancer (SPARTAN‐HN). This algorithm consistently stratifies patients requiring head and neck cancer surgery in the COVID‐19 era and provides evidence for the initial uptake of the SPARTAN‐HN., To the authors' knowledge, the Surgical Prioritization and Ranking Tool and Navigation Aid for Head and Neck Cancer (SPARTAN‐HN) is the first cancer surgery–specific prioritization tool for use during the coronavirus disease 2019 (COVID‐19) pandemic. The SPARTAN‐HN algorithm is reliable and valid for the stratification of patients with head and neck cancer who require urgent cancer care in resource‐restricted practice environments.

The purpose of this study was to determine which of the most commonly used flaps restore contour more accurately in mandibular body reconstructions using conformance analyses and virtual measurements.Using normal computed tomography (CT) scans and a 3D software, mandibular body defects were virtually created. "Single shot" and osteotomized fibula flaps (SS-FF and O-FF), iliac crest flaps (ICF) and scapular tip flaps (STF) were digitally harvested and coregistered to reconstruct those defects. Conformance analyses were performed by calculating the root mean square (RMS) for overall and contour conformance.Ten patients normal CT scans were included. The STF demonstrated improved overall conformance compared with the ICF, the SS-FF and the O-FF (RMS = 2.03 mm vs 4.53 mm vs 2.76 vs 2.37 mm, respectively; p.001). Similar trends were seen for contour conformance in STF compared with the ICF and the SS-FF (RMS = 2.48 mm vs 4.50 mm vs 3.28 mm, respectively), whereas the O-FF performed better than STF (RMS = 1.85 mm vs 2.48 mm; p.001).The osseous component of the STF resembles the mandibular body more accurately than the one in the ICF and FF without the need for an osteotomy. Future clinical studies can help to elucidate the clinical impact of these virtual findings.

Objective To identify predictors of unplanned hospitalization and emergency department (ED) use among head and neck oncology patients. Methods Peer reviewed publications were identified through a systematic search of MEDLINE, Embase and Cochrane CENTRAL. Studies describing a cohort of HNC patients that detailed predictors of unplanned hospitalization or ED use in risk-adjusted models were eligible for inclusion. The methodologic quality of included studies was assessed using the Quality In Prognostic Studies (QUIPS) tool and an adapted version of the GRADE framework. Results Of the 932 articles identified, 39 studies met our inclusion criteria with 31/39 describing predictors of surgical readmission and 10/39 describing predictors of ED use or unplanned hospitalization during radiation/chemoradiation treatment. Risk factors were classified into either ‘patient-related’, ‘cancer severity’ or ‘process’ factors. In the subset of studies looking at readmission following surgery wound complications (10/14 studies), presence of comorbidity (16/28 studies), low socioeconomic status (8/17 studies), cancer stage (9/14 studies), and prolonged hospital stay (7/18 studies) were the variables most frequently associated with readmission on multivariable analysis. Presence of comorbidity (6/10) and chemotherapy use (4/10) were more frequently associated with ED use and unplanned hospitalization. Conclusions Several consistent predictors have been identified across a variety of studies. This work is a critical first step towards the development of readmission and ED prediction models. It also enables meaningful comparison of hospital readmission rates with risk adjustment in HNC patients.

Background Current sentinel lymph node biopsy (SLNB) techniques, including use of radioisotopes, have disadvantages including the use of a radioactive tracer. Indocyanine green (ICG) based near-infrared (NIR) fluorescence imaging and cone beam CT (CBCT) have advantages for intraoperative use. However, limited literature exists regarding their use in head and neck cancer SLNB. Methods This was a prospective, non-randomized study using a rabbit oral cavity VX2 squamous cell carcinoma model (n = 10) which develops lymph node metastasis. Pre-operatively, images were acquired by MicroCT. During surgery, CBCT and NIR fluorescence imaging of ICG was used to map and guide the SLNB resection. Results Intraoperative use of ICG to guide fluorescence resection resulted in identification of all lymph nodes identified by pre-operative CT. CBCT was useful for near real time intraoperative imaging and 3D reconstruction. Conclusions This pre-clinical study further demonstrates the technical feasibility, limitations and advantages of intraoperative NIR-guided ICG imaging for SLN identification as a complementary method during head and neck surgery.

One of the largest geometric uncertainties in designing radiotherapy treatment plans for squamous cell cancers of the head and neck is contouring the gross tumor volume. We have previously described a method of projecting mucosal disease contours, visible on endoscopy, to volumetrically reconstructed planning computed tomography (CT) datasets, using electromagnetic (EM) tracking of a flexible endoscope, enabling rigid registration between endoscopic and CT images. However, to achieve better accuracy for radiotherapy planning, we propose refining this initial registration with image-based registration methods. In this paper, several types of cost functions are evaluated based on accuracy and robustness. Three phantoms and eight clinical cases are used to test each cost function, with initial registration of endoscopy to CT provided by the pose of the flexible endoscope recovered from EM tracking. Cost function classes include: cross correlation, mutual information and gradient methods. For each test case, a ground truth virtual camera pose was first defined by manual registration of anatomical features visible in both real and virtual endoscope images. A new set of evenly spaced fiducial points and a sample contour were created and projected onto the CT image to be used in assessing image registration quality. A new set of 5000 displaced poses was generated by random sampling displacements along each translational and rotational dimension. At each pose, fiducial and contour points in the real image were again projected on the CT image. The cost function, fiducial registration error and contouring error values were then calculated. While all cost functions performed well in select cases, only the normalized gradient field function consistently had registration errors less than 2 mm, which is the accuracy needed if this application of registering mucosal disease identified on optical image to CT images is to be used in the clinical practice of radiation treatment planning. (Registration: ClinicalTrials.gov NCT02704169)

The practices of head and neck surgical oncologists must evolve to meet the unprecedented needs placed on our health care system by the Coronavirus disease 2019 (COVID‐19) pandemic. Guidelines are emerging to help guide the provision of head and neck cancer care, though in practice, it can be challenging to operationalize such recommendations. Head and neck surgeons at Wuhan University faced significant challenges in providing care for their patients. Similar challenges were faced by the University of Toronto during the severe acute respiratory syndrome (SARS) pandemic in 2003. Herein, we outline our combined experience and key practical considerations for maintaining an oncology service in the midst of a pandemic.

Objectives To evaluate adjuvant chemoradiotherapy (CRT) for patients with oral cavity squamous cell carcinoma (OSCC) with minor or major extranodal extension (ENE). Materials and methods Surgically resected OSCC with pathologically involved lymph node(s) (pN+) between 2006 and 2017. Sections of pN+ were re-reviewed and classified as no, minor (≤2 mm), or major (>2 mm) ENE. Patterns of failure and survival were compared between the groups and stratified by adjuvant treatment. Multivariable (MVA) analysis assessed the value of adjuvant treatment for minor and major ENE. Results Total of 384 patients, 62 had minor and 114 had major ENE. Adjuvant CRT was delivered in 32(15%), 21(34%), and 45(39%) of patients with no, minor and major ENE, respectively. Patients with minor ENE had similar 5-year loco-regional control (LRC) and distant control (DC) but lower disease-free survival (DFS) (38% vs. 51%, p = 0·02) compared to patients with no ENE, while patients with major ENE had marginally lower LRC (59% vs 74%, p = 0·07), lower DC (58% vs 82%,p = 0·005) and DFS (13% vs. 38%, p=·001) compared to those with minor. On MVA, adjuvant chemotherapy was associated with improved DFS for major ENE (adjusted HR = 0·49; 95% CI 0·29-0·85, p = 0·01) but not for minor ENE after adjusting for age, ECOG status, T-, N-category, margin status, and radiotherapy. Conclusions Adjuvant chemoradiotherapy improves outcomes in patients with major ENE, but the benefit is unclear in patients with minor ENE. Future trials should focus on intensification of treatment for patients with major ENE and alternative adjuvant strategies for patients with minor ENE.