Telemedicine-enabled biofeedback electropalatography rehabilitation (TEBER): A pilot study for patients treated with surgery for oral cavity carcinoma.

BACKGROUND: To address the rehabilitative barriers to frequency and precision of care, we conducted a pilot study of a biofeedback electropalatography (EPG) device paired with telemedicine for patients who underwent primary surgery +/- adjuvant radiation for oral cavity carcinoma. We hypothesized that lingual optimization followed by telemedicine-enabled biofeedback electropalatography rehabilitation (TEBER) would further improve speech and swallowing outcomes after "standard-of-care" SOC rehabilitation. METHOD: Pilot prospective 8-week (TEBER) program following 8 weeks of (SOC) rehabilitation. RESULTS: Twenty-seven patients were included and 11 completed the protocol. When examining the benefit of TEBER independent of standard of care, "range-of-liquids" improved by +0.36 [95% CI, 0.02-0.70, p = 0.05] and "range-of-solids" improved by +0.73 [95% CI, 0.12-1.34, p = 0.03]. There was a positive trend toward better oral cavity obliteration; residual volume decreased by -1.2 [95% CI, -2.45 to 0.053, p = 0.06], and "nutritional-mode" increased by +0.55 [95% CI, -0.15 to 1.24, p = 0.08]. CONCLUSION: This pilot suggests that TEBER bolsters oral rehabilitation after 8 weeks of SOC lingual range of motion.

The impact of surgical resection margins on outcomes for adults with head and neck osteosarcomas: A Canadian sarcoma research and Clinical Collaboration (CanSaRCC) study.

OBJECTIVE: The aim of the study is to describe the factors that influence outcome in adults with head and neck osteosarcoma (HNO) with a specific focus on the margin status. METHODS: Patients with a diagnosis of HNO between the years 1996-2021 were reviewed from the Canadian Sarcoma Research and Clinical Collaboration (CanSaRCC) Database. Baseline characteristics, pathology, treatment, and outcomes were analyzed. Univariable (UVA) and multivariable (MVA) Cox regression models were performed. 5-year locoregional control rate and overall survival (OS) were estimated using Kaplan-Meier method and Log-Rank test. RESULTS: Of 50 patients with a median age of 40 years (range 16-80), 27 (54%) were male. HNO commonly involved the mandible (n = 21, 42%) followed by maxilla (n = 15, 30%). Thirteen (33.3%) had low-intermediate grade and 26 (66.6%) had high grade tumors. Three patients (6%) had negative resection margins (>5 mm), 24 (48%) had close margins (1-5 mm), 15 (30%) had positive margins (<1mm) and 7 (16%) had unknown margin status. In total, 39 (78%) received chemotherapy - 22 (44%) received neoadjuvant chemotherapy while 17 (34%) received adjuvant chemotherapy. A total of 12 (24%) patients received radiotherapy, of whom 8 (16%) had adjuvant and 3 (6%) had neo-adjuvant. Median follow-up time was 6.3 years (range 0.26-24.9). Disease recurred in 21 patients (42%), of whom 15 (30%) had local recurrence only, 4 (8%) had distant metastasis, and 2 (4%) had both local and distant recurrence. 5-year locoregional control rate and OS was 62% and 79.2% respectively. Resection margins <3 mm was associated with lower 5 years OS and locoregional control rate (Log-Rank p = 0.02, p = 0.01 respectively). CONCLUSION: Osteosarcomas of the head and neck are rare and local recurrence remains a concern. Surgical resection with negative resection margins may improve survival, and a 3 mm resection margin threshold may optimize survival. Radiotherapy and/or chemotherapy should be considered in a multidisciplinary setting based on risk-features.

Glossectomy for the treatment of oral cavity carcinoma: Quantitative, functional and patient-reported quality of life outcomes differ by four glossectomy defects.

OBJECTIVE: The goal was to characterize four clinically distinct glossectomy defects to establish significant quantitative cut points using functional metrics, the MD Anderson Dysphagia Index (MDADI) and speech intelligibility. METHODS: Population included 101 patients treated with surgery, adjuvant radiation per NCCN guidelines, and ≥ 12 months follow-up. RESULTS: Defect groups: subtotal hemiglossectomy (1), hemiglossectomy (2), extended hemiglossectomy (3) and oral glossectomy (4) were compared: All outcomes supported a four defect model. Intergroup comparison of outcomes with subtotal hemiglossectomy as reference (p value): Tongue Protrusion <0.001,<0.001,<0.001; Elevation <0.001,<0.001,<0.001; Open Mouth Premaxillary Contact Elevation <0.001,<0.001,<0.001; Obliteration 0.6,<0.001,<0.001; Normalcy of Diet, <0.3,<0.001,<0.001; Nutritional Mode, <0.9,<0.8,<0.001; Range of Liquids, <0.4,<0.016,<0.02; Range of Solids, <0.5,<0.004,<0.001; Eating in Public, <0.2,<0.002,<0.03; Understandability of Speech, <0.9,<0.001,<0.001; Speaking in Public, <0.4,<0.03,<0.001; MDADI, <0.4,<0.005,<0.01; Single Word Intelligibility, <0.4,<0.1,<0.001; Sentence Intelligibility, <0.5,<0.08,<0.001; Words Per Minute Intelligibility, <0.6,<0.04,<0.001; Sentence Efficiency Ratio, <0.4,<0.03,<0.002. Proportion of patients by 4 defect groups who underwent: tissue transplantation, 51%,93.9%,100%,100%.Radiation,24%,67%,88%,80%.Between hemiglossectomy and extended hemiglossectomy, the defect extends into the contralateral floor of the mouth and/or the anterior tonsillar pillar; resection of these subunits limits tongue mobility with an impact on functional outcome and MDADI. Between extended hemiglossectomy and oral glossectomy, the defect extends to include the tip of the tongue and appears to impact functional outcome and MDADI. CONCLUSIONS: Subtotal hemiglossectomy, hemiglossectomy, extended glossectomy and oral glossectomy are associated with quantitative (elevation, protrusion, open mouth premaxillary contact and obliteration), qualitative (speech and swallowing) and MDADI differences, suggesting that these 4 ordinal defect groups are distinct.

Adult Head and Neck Rhabdomyosarcoma: Management, Outcomes, and the Effect of Intensity Modulated Radiation Therapy on Locoregional Control.

Purpose: Only 9% of adult rhabdomyosarcomas (RMS) present with primary disease in the head and neck (HNRMS). Management is often extrapolated from the pediatric experience in which prognosis is better but treatment imperatives differ. We report management and outcomes of adult HNRMS treated over 3 decades. Methods and Materials: Adult HNRMS treated from 1984 to 2017 were reviewed. HNRMS were categorized as embryonal/alveolar (E/A) or pleomorphic (P). Standard management was as follows: E/A-HNRMS were treated with neoadjuvant chemotherapy, definitive chemoradiotherapy (CRT), and then maintenance chemotherapy. P-HNRMS were generally treated with surgery +/- radiation. Intensity modulated radiation therapy (IMRT) was adopted from 2005 onward. Results: Fifty-eight patients were eligible; the median age was 32 years. Seventy-six percent of tumors (n = 45) were parameningeal and 45% (n = 26) were >5 cm. Of 45 patients with M0 HNRMS treated with curative intent, 33 (73%) were E/A-HNRMS and 12 (27%) P-HNRMS. Patients with E/A-HNRMS received definitive RT with 66 to 70 Gy in 2 Gy per fraction. Elective nodal RT was routinely delivered. In the pre-IMRT era (before 2005), 12 of 23 (52%) patients with M0 E/A-HNRMS experienced locoregional recurrences. In the IMRT era (2005 and onward), 1 of 10 patients (10%) with M0 disease recurred locally; this patient achieved a complete clinical response despite a 3-week interruption after 48 Gy because of local toxicity but experienced an in-field local recurrence 45 months later that resulted in death. Locoregional control was superior in the IMRT era vs pre-IMRT era (P = .049). Distant metastasis among patients with E/A-HNRMS was the predominant mode of treatment failure (n = 17 of 33, 52%). Conclusions: Our study shows a high rate of locoregional control for adult E/A-HNRMS following definitive CRT using IMRT, and CRT should be considered for the majority of patients in this population. In contrast, P-HNRMS is distinct and requires surgery +/- RT.

A Quantitative Analysis Examining Patients' Choice of Active Surveillance or Surgery for Managing Low-Risk Papillary Thyroid Cancer.

Background: It is important to understand patient preferences on managing low-risk papillary thyroid cancer (PTC). Methods: We prospectively followed patients with low-risk PTC <2 cm in maximal diameter, who were offered the choice of thyroidectomy or active surveillance (AS) at the University Health Network (UHN), in Toronto, Canada. The primary outcome was the frequency of AS choice (percentage with confidence interval [CI]). Univariate and multivariable analyses were performed to identify predictors of the choice of AS. Results: We enrolled 200 patients of median age 51 years (interquartile range 42-62). The primary tumor measured >1 cm in 55.5% (111/200) of participants. The AS was chosen by 77.5% [71.2-82.7%, 155/200] of participants. In a backwards conditional regression model, the clinical and demographic factors independently associated with choosing AS included: older age (compared with referent group <40 years)-age 40-64 years-odds ratio (OR) 2.78 [CI, 1.23-6.30, p = 0.014], age ≥65 years-OR 8.43 [2.13-33.37, p = 0.002], and education level of high school or lower-OR 4.41 [1.25-15.53, p = 0.021]; AS was inversely associated with the patient's surgeon of record being affiliated with the study hospital-OR 0.29 [0.11-0.76, p = 0.012]. In a separate backwards conditional logistic regression model examining associations with psychological characteristics, AS choice was independently associated with a fear of needing to take thyroid hormones after thyroidectomy-OR 1.24 [1.11-1.39, p < 0.001], but inversely associated with fear of PTC progression-OR 0.94 [0.90-0.98, p = 0.006] and an active coping mechanism ("doing something")-OR 0.43 [0.28-0.66, p < 0.001]. Conclusions: Approximately three-quarters of our participants chose AS over surgery. The factors associated with choosing AS included older age, lower education level, and having a surgeon outside the study institution. Patients' fears about either their PTC progressing or taking thyroid hormone replacement as well as the level of active coping style were associated with the decision. Our results inform the understanding of patients' decisions on managing low-risk PTC. Registration: Clinicaltrials.gov NCT03271892.

Evaluation of Sarcopenia in Older Patients Undergoing Head and Neck Cancer Surgery.

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 < .001). On univariate analysis, the presence and severity of sarcopenia was associated with the development of medical complications (P = .029), higher grade of complications (P = .032), LOS (P = .015), and overall survival (P = .001). On multivariate analysis, sarcopenia was associated with a longer LOS (ß = 0.32 [95% CI: 0.19-0.45], P < .001) and worse overall survival (HR = 2.21 [95% CI: 1.01-4.23], P = .017). CONCLUSIONS: Sarcopenia may aid in the prediction of prolonged hospital stay and death in patients who are candidates for major head and neck surgery. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:356-363, 2022.

Needs assessment for a decision support tool in oral cancer requiring major resection and reconstruction: a mixed-methods study protocol.

INTRODUCTION: Advanced 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 ANALYSIS: This 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 DISSEMINATION: This 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.

Tracheoesophageal voice prosthesis management in laryngectomy patients during the COVID-19 pandemic.

With the COVID-19 pandemic, there has been significant changes and challenges in the management of oncology patients. One of the major strategies to reduce transmission of the virus between patients and healthcare workers is deferral of follow-up visits. However, deferral may not be possible in total laryngectomy patients. Urgent procedures may be necessary to prevent complications related to ill-fitting tracheoesophageal puncture (TEP) voice prostheses, such as aspiration or loss of voicing. In this paper, we describe the Princess Margaret Cancer Center's approach to managing this unique patient population.

Development and validation of a Surgical Prioritization and Ranking Tool and Navigation Aid for Head and Neck Cancer (SPARTAN-HN) in a scarce resource setting: Response to the COVID-19 pandemic.

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.

A Prospective Mixed-Methods Study of Decision-Making on Surgery or Active Surveillance for Low-Risk Papillary Thyroid Cancer.

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 <2 cm in maximum diameter (NCT03271892). Patients were provided standardized medical information and were interviewed after making their decision (which dictated disease management). We evaluated patients' levels of decision-self efficacy (confidence in medical decision-making ability) at the time information was presented and their level of decision satisfaction after finalizing their decision (using standardized questionnaires). We asked patients to explain the reason for their choice and qualitatively analyzed the results. Results: We enrolled 74 women and 26 men of mean age 52.4 years, with a mean PTC size of 11.0 mm (interquartile range 9.0, 14.0 mm). Seventy-one patients (71.0% [95% confidence interval 60.9-79.4%]) chose AS over surgery. Ninety-four percent (94/100) of participants independently made their own disease management choice; the rest shared the decision with their physician. Participants had a high baseline level of decision self-efficacy (mean 94.3, standard deviation 9.6 on a 100-point scale). Almost all (98%, 98/100) participants reported high decision satisfaction. Factors reported by patients as influencing their decision included the following: perceived risk of thyroidectomy or the cancer, family considerations, treatment timing in the context of life circumstances, and trust in health care providers. Conclusions: In this Canadian study, ∼7 out of 10 patients with small, low-risk PTC, who were offered the choice of AS or surgery, chose AS. Personal perceptions about cancer or thyroidectomy, contextual factors, family considerations, and trust in health care providers strongly influenced patients' disease management choices.

A 4-gene signature from histologically normal surgical margins predicts local recurrence in patients with oral carcinoma: clinical validation.

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.

Frailty as a predictor of outcomes in patients undergoing head and neck cancer surgery.

OBJECTIVES: To evaluate whether frailty and functional measures are predictors of perioperative complications and length of hospital stay (LOS) in patients undergoing head and neck cancer surgery. STUDY DESIGN: Prospective study. METHODS: Patients 50 years and older undergoing major head and neck cancer surgery between 2011 and 2015 preoperatively completed Fried's Frailty Index, Barthel Index, Lawton-Brody questionnaire and Vulnerable Elders Survey-13. Primary outcome measures were postoperative complications and LOS, which were analyzed using multivariable logistic and linear regression models. RESULTS: There were 274 patients recruited (105 aged 50-64 and 169 aged 65 and older). Of these, 119, 132, and 23 were defined as non-frail, pre-frail, and frail, respectively. Frailty score and functional measures were not predictors of overall complications. In multivariable models, frailty score (odds ratio [OR] = 1.36; 95% confidence interval [CI], 1.04-1.78, P = .025) was a predictor of medical complications and Clavien-Dindo Grade III and higher complications independent of age and comorbidity. Higher frailty score (ß = 1.07; 95% CI, 1.02-1.12, P = .0025) and less independence on the Lawton Brody (ß = -0.08; 95% CI, -0.11 to -0.05, P < .001) and Barthel Index (ß = -0.12; 95% CI, -0.19 to -0.06, P < .001) were predictors of increased LOS. CONCLUSIONS: Frailty was a predictor of type and severity of complications. Both frailty and measures of independence in activities of daily living were independent predictors of LOS. Frailty and functional assessment can help surgeons identify patients at risk of adverse postoperative outcomes and thus aid in counselling patients as well as identifying patients that may benefit from comprehensive geriatric assessment and targeted interventions. LEVEL OF EVIDENCE: Prognosis study 2b Laryngoscope, 130:E340-E345, 2020.

Evaluation of Older Age and Frailty as Factors Associated With Depression and Postoperative Decision Regret in Patients Undergoing Major Head and Neck Surgery.

Importance: Clinicians should understand the prevalence of depression and decision regret in patients with head and neck cancer and whether these factors differ with age or frailty. Objectives: To assess whether age and frailty are associated with preoperative and/or worsening postoperative depression and postoperative decision regret in patients undergoing major head and neck surgery and to identify additional factors associated with depression and decision regret. Design, Setting, and Participants: This prospective cohort study was conducted at a single institution, with patients aged 50 years or older undergoing major head and neck surgery recruited from December 1, 2011, to April 30, 2014. Statistical analysis was performed from July 1, 2018, to June 30, 2019. Main Outcomes and Measures: Frailty, functional, and geriatric depression assessments were completed before surgery and 3, 6, and 12 months after surgery. Decision regret assessment was completed 6 months after surgery. The prevalence of depression and decision regret was determined by age group. Change in depression over time was compared between age groups using a linear-effects model. Variables potentially associated with moderate to severe depression and decision regret were analyzed using a logistic regression model. Results: The study included 274 patients (68 women and 206 men; mean [SD] age, 67.8 [9.5] years). Of these, 105 (38.3%) were 50 to 64 years of age and 169 (61.7%) were 65 years or older. The rate of preoperative moderate to severe depression was 9.6% (21 of 219), with no difference between younger and older adult cohorts. For both age groups, depression scores increased in the postoperative period from baseline to 6 months. At 12 months, there was a difference in depression scores between the younger and older adult cohort (4.8 [4.6] vs 3.1 [3.6]). A higher preoperative Fried Frailty Index score (odds ratio, 2.58 [95% CI, 1.63-4.06]) was associated with preoperative moderate to severe depression. For all patients, the mean Decision Regret Scale score was 18.2 (range, 0-95), and 26.7% of patients (48 of 180) had moderate to severe regret. There was no difference in Decision Regret Scale scores between younger and older patients. Preoperative depression but not frailty is associated with postoperative moderate to severe decision regret (odds ratio, 1.17 [95% CI, 1.06-1.28]). Conclusions and Relevance: In this cohort study, there was no difference based on age in the prevalence of moderate to severe depression or decision regret. A higher preoperative frailty score was associated with depression but not decision regret. Preoperative depression was the only factor associated with moderate to severe decision regret on multivariate analysis. Understanding the prevalence of and factors associated with moderate to severe depression and decision regret may aid in identifying patients who would benefit from more extensive preoperative counseling and preoperative and postoperative multispecialty assessment and treatment.

Postoperative wound infections, neutrophil-to-lymphocyte ratio, and cancer recurrence in patients with oral cavity cancer undergoing surgical resection.

BACKGROUND: It is unclear whether postoperative wound infections after head and neck cancer surgery are associated with cancer progression. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Hypoxia-induced pulmonary hypertension and chronic lung disease: caveolin-1 dysfunction an important underlying feature.

Caveolin-1 (cav-1) has been shown to play a significant role in the pathogenesis of pulmonary hypertension (PH). In the monocrotaline model of PH, the loss of endothelial cav-1 as well as reciprocal activation of proliferative and anti-apoptotic pathways initiate the disease process and facilitate its progression. In order to examine the role of cav-1 in hypoxia-induced PH, we exposed rats and neonatal calves to hypobaric hypoxia and obtained hemodynamic data and assessed the expression of cav-1 and related proteins eNOS, HSP90, PTEN, gp130, PY-STAT3, ß-catenin, and Glut1 in the lung tissue. Chronic hypoxic exposure in rats (48 h-4 weeks) and calves (two weeks) did not alter the expression of cav-1, HSP90, or eNOS. PTEN expression was significantly decreased accompanied by PY-STAT3 activation and increased expression of gp130, Glut1, and ß-catenin in hypoxic animals. We also examined cav-1 expression in the lung sections from steers with chronic hypoxic disease (Brisket disease) and from patients with chronic lung disease who underwent lung biopsy for medical reasons. There was no cav-1 loss in Brisket disease. In chronic lung disease cases, endothelial cav-1 expression was present, albeit with less intense staining in some cases. In conclusion, hypoxia did not alter the cav-1 expression in experimental models. The presence of cav-1, however, did not suppress hypoxia-induced activation of PY-STAT3 and ß catenin, increased gp130 and Glut1 expression, or prevent the PTEN loss, indicating cav-1 dysfunction in hypoxia-induced PH.

Prevalence, prognosis, and treatment implications of retropharyngeal nodes in unknown primary head and neck carcinoma.

OBJECTIVE: (1) To estimate the prevalence of radiographically positive Retro-Pharyngeal Lymph Nodes (RPLN) in unknown primary carcinoma of the head and neck and (2) to determine the prognostic implications of radiographically positive RPLN and other radiographic features (3) to identify patients at low risk for retropharyngeal metastasis. MATERIALS AND METHODS: The medical records of all 68 eligible patients treated at the Princess Margaret Cancer Centre between 2000 and 2014 were retrospectively reviewed for demographic, clinical, pathologic, and radiologic data. Radiologic data included: RPLN, extra capsular spread (ECS), neck staging and cystic/necrotic or matted neck nodes. LRR, DR, DFS and OS were estimated using the competing risk methods and the Kaplan-Meier method. RESULTS: Seven patients had concerning RPLN (10.3%). Forty-four patients were p16 positive (65%). RPLN status did not have any effect on LRR, DFS, DR and OS. Radiological ECS and p16 (neg.) status were found to be significant predictors of LRR (p = 0.023; p = 0.014). Matted nodes, radiological ECS and p16 (neg.) status were found to be significant predictors of DFS (p = 0.012; p < 0.001; p = 0.014). Matted nodes and radiological ECS were found to be significant predictors of OS (p = 0.017; p = 0.0036). Only radiological ECS was found to be a significant predictor of distant recurrence (p = 0.0066). CONCLUSIONS: 10% of CUP patients will harbor radiological positive RPLN. A large proportion of CUP patients are positive for p16. Radiologic features such as ECS and matted nodes can predict worse outcomes.

A protocol for a Canadian prospective observational study of decision-making on active surveillance or surgery for low-risk papillary thyroid cancer.

INTRODUCTION: Low-risk papillary thyroid cancer (PTC) is increasingly being diagnosed throughout the world; yet the mortality risk is low compared with other malignancies. Traditional management includes thyroid surgery, sometimes followed by radioactive iodine and thyroid hormone treatment. Active surveillance (AS) has been proposed as a means to reduce overtreatment of PTC. AS involves close disease follow-up, with the intention to intervene if the disease progresses, or on patient request. METHODS AND ANALYSIS: This is a multiphase prospective observational study. In the first phase of this study, consenting eligible adults with low-risk PTC, that is, <2 cm in maximal diameter, confined to the thyroid and not immediately adjacent to critical structures in the neck, are provided verbal and written information about PTC disease prognosis following surgery or AS. Questionnaires are administered at baseline and after the disease management decision on AS or surgery is finalised. Patients may choose either option (surgery or AS), and the primary outcome is the frequency with which either disease management option is chosen. Secondary outcomes include: rationale for the decision, role of the patient in decision-making and decision satisfaction. In the second phase of the study, consenting eligible adult patients who completed the first study phase may enrol in respective AS or surgery group follow-up studies. The following outcomes are examined 1 year after enrolment in the follow-up phase: decision regret about disease management choice (primary outcome), psychological distress, disease-specific quality of life, fear of disease progression, body image satisfaction, disease progression, crossover to surgery in the AS group, new chronic thyroid hormone use and healthcare resource utilisation. ETHICS AND DISSEMINATION: The University Health Network Research Ethics Board approved this study (ID 15-8942). The results will be published in an open access journal. TRIAL REGISTRATION NUMBER: NCT03271892; Pre-results.

Lymph node ratio relationship to regional failure and distant metastases in oral cavity cancer.

BACKGROUND: We aimed to investigate the impact of lymph node ratio (LNR, number of positive nodes/total number of excised nodes) on regional-only-failure, distant-only-failure and overall survival (OS) in oral squamous cell carcinoma (OSCC). METHODS: Retrospective review of pN0-2 OSCC-patients (1994-2012) treated with curative-surgery with neck dissection±postoperative radiotherapy (PORT)±concurrent chemotherapy. LNR was subjected to multivariable analysis (MVA) of regional-only-failure, distant-only-failure and OS. RESULTS: Overall 914 patients were identified; median follow-up: 51months (1-189); pN0: 482 (52.7%), pN1: 128 (14%), pN2a: 6 (0.7%); pN2b: 225 (24.6%); pN2c: 73 (8%); median number of dissected nodes: 36 (6-125); median number of pN+: 2 (1-49); median LNR for pN+ patients: 6%; extranodal extension: 187 (20.5%). Bilateral neck dissection: 368 (40.3%); PORT: 452 (49.5%); and concurrent chemotherapy: 80 (8.8%). High grade, lymphovascular invasion perineural invasion and pT3-4 were associated with high LNR. On MVA, LNR was associated with regional-only-failure (HR=1.06; 95%CI: 1.04-1.08; p<0.001), distant-only-failure (HR=1.03; 95%CI: 1.02-1.05; p=0.004) and lower OS (HR=1.03; 95%CI: 1.02-1.05; p<0.001). Similarly, in pN2-subgroup: LNR was associated with regional-only-failure (HR=1.04; 95%CI: 1.02-1.06; p<0.001), distant-only-failure (HR=1.03; 95%CI: 1.01-1.06; p=0.045) and lower OS (HR=1.03; 95%CI: 1.02-1.04; p<0.001). CONCLUSION: High LNR is associated with higher regional-only-failure/distant-only-failure and lower OS. LNR should be assessed in future prospective trials for selection of adjuvant therapy.

Hardware complications in oromandibular defects: Comparing scapular and fibular based free flap reconstructions.

BACKGROUND: Despite improvements in surgical technique and technology, hardware complications occur relatively frequently. This study analyzes hardware complications in patients undergoing oromandibular reconstruction using scapular (SFF) or fibular (FFF) free flaps. METHODS: Retrospective data for 178 patients was obtained (1999-2014) at University Hospital Network (Toronto, Canada). Univariable and multivariable analyses were performed to identify risk factors for hardware complications. RESULTS: Patients with FFF reconstruction (n=129) had significantly more hardware complications than those with SFF (n=49) (16% vs. 2%;p=0.01). Surgical site infection (SSI) (OR=7.05; p<0.01), defect type (OR=2.63; p<0.01) and flap (OR=0.12; p=0.01) were significant predictors of hardware complications on univariable analysis. Flap type (OR=0.12; p=0.04) was an independent predictor of plate complication after adjusting for SSI. A subgroup analysis suggested a trend towards fewer hardware complications with SFF stratified by mandibular defect type. CONCLUSIONS: Scapular free flaps are associated with a lower rate of hardware-related complications in oromandibular reconstruction.

Patterns of regional recurrence in papillary thyroid cancer patients with lateral neck metastases undergoing neck dissection.

BACKGROUND: Practice variability exists for the extent of neck dissection undertaken for papillary thyroid carcinoma (PTC) metastatic to the lateral neck nodes, with disagreement over routine level V dissection. METHODS: We performed a retrospective medical record review of PTC patients with lateral neck nodal metastases treated at University Health Network from 2000 to 2012. Predictive factors for regional neck recurrence, including extent of initial neck dissection, were analyzed using Cox regression. RESULTS: Out of 204 neck dissections in 178 patients, 110 (54%) underwent selective and 94 (46%) had comprehensive dissection including level Vb. Mean follow-up was 6.3 years (SD). Significant predictors of regional failure were the total number of suspicious nodes on preoperative imaging (p = 0.029), largest positive node on initial neck dissection (p < 0.01), and whether patients received adjuvant radiotherapy (p = 0.028). The 5-year ipsilateral regional recurrence rate was 8 and 9% with selective and comprehensive dissection, respectively (p = 0.89). CONCLUSION: The extent of neck dissection did not predict the probability of regional recurrence in PTC patients presenting with lateral neck metastases.