Tumor volumes in T3 supraglottic cancers treated with radiotherapy in the modern era: A study of the Canadian Head & Neck Collaborative Research Initiative.

PURPOSE: To evaluate the association of primary tumor volume (TV) with overall survival (OS) and disease-free survival (DFS) in T3 N0-3M0 supraglottic cancers treated with intensity-modulated radiotherapy (IMRT). METHODS: This was a retrospective cohort study involving 239 patients diagnosed with T3 N0-3M0 supraglottic cancers between 2002 and 2018 from seven regional cancer centers in Canada. Clinical data were obtained from the patient records. Supraglottic TV was measured by neuroradiologists on diagnostic imaging. Kaplan-Meier method was used for survival probabilities, and a restricted cubic spline Cox proportional hazards regression analysis was used to analyze TV associations with OS and DFS. RESULTS: Mean (SD) of participants was 65.2 (9.4) years; 176 (73.6%) participants were male. 90 (38%) were N0, and 151 (64%) received concurrent systemic therapy. Mean TV (SD) was 11.37 (12.11) cm3 . With mean follow up (SD) of 3.28 (2.60) years, 2-year OS was 72.7% (95% CI 66.9%-78.9%) and DFS was 53.6% (47.4%-60.6%). Increasing TV was associated (per cm3 increase) with worse OS (HR, 1.01, 95% CI 1.00-1.02, p < 0.01) and DFS (HR, 1.01, 95% CI 1.00-1.02, p = 0.02). CONCLUSIONS: Increasing primary tumor volume is associated with worse OS and DFS in T3 supraglottic cancers treated with IMRT, with no clear threshold. The findings suggest that patients with larger tumors and poor baseline laryngeal function may benefit from upfront laryngectomy with adjuvant radiotherapy.

Multiphasic exercise prehabilitation for patients undergoing surgery for head and neck cancer: a hybrid effectiveness-implementation study protocol.

Head and neck cancer (HNC) treatment often consists of major surgery followed by adjuvant therapy, which can result in treatment-related side effects, decreased physical function, and diminished quality of life. Perioperative nutrition interventions and early mobilization improve recovery after HNC treatment. However, there are few studies on prehabilitation that include exercise within the HNC surgical care pathway. We have designed a multiphasic exercise prehabilitation intervention for HNC patients undergoing surgical resection with free flap reconstruction. We will use a hybrid effectiveness-implementation study design guided by the RE-AIM framework to address the following objectives: (1) to evaluate intervention benefits through physical function and patient-reported outcome assessments; (2) to determine the safety and feasibility of the prehabilitation intervention; (3) to evaluate the implementation of exercise within the HNC surgical care pathway; and (4) to establish a post-operative screening and referral pathway to exercise oncology resources. The results of this study will provide evidence for the benefits and costs of a multiphasic exercise prehabilitation intervention embedded within the HNC surgical care pathway. This paper describes the study protocol design, multiphasic exercise prehabilitation intervention, planned analyses, and dissemination of findings. Trial registration: https://clinicaltrials.gov/NCT04598087.

NCBP2 and TFRC are novel prognostic biomarkers in oral squamous cell carcinoma.

There are few prognostic biomarkers and targeted therapeutics currently in use for the clinical management of oral squamous cell carcinoma (OSCC) and patient outcomes remain poor in this disease. A majority of mutations in OSCC are loss-of-function events in tumour suppressor genes that are refractory to conventional modes of targeting. Interestingly, the chromosomal segment 3q22-3q29 is amplified in many epithelial cancers, including OSCC. We hypothesized that some of the 468 genes located on 3q22-3q29 might be drivers of oral carcinogenesis and could be exploited as potential prognostic biomarkers and therapeutic targets. Our integrative analysis of copy number variation (CNV), gene expression and clinical data from The Cancer Genome Atlas (TCGA), identified two candidate genes: NCBP2, TFRC, whose expression positively correlates with worse overall survival (OS) in HPV-negative OSCC patients. Expression of NCBP2 and TFRC is significantly higher in tumour cells compared to most normal human tissues. High NCBP2 and TFRC protein abundance is associated with worse overall, disease-specific survival, and progression-free interval in an in-house cohort of HPV-negative OSCC patients. Finally, due to a lack of evidence for the role of NCBP2 in carcinogenesis, we tested if modulating NCBP2 levels in human OSCC cell lines affected their carcinogenic behaviour. We found that NCBP2 depletion reduced OSCC cell proliferation, migration, and invasion. Differential expression analysis revealed the upregulation of several tumour-promoting genes in patients with high NCBP2 expression. We thus propose both NCBP2 and TFRC as novel prognostic and potentially therapeutic biomarkers for HPV-negative OSCC.

Association of Primary Tumor Volume With Survival in Patients With T3 Glottic Cancer Treated With Radiotherapy: A Study of the Canadian Head & Neck Collaborative Research Initiative.

Importance: The association of primary tumor volume with outcomes in T3 glottic cancers treated with radiotherapy with concurrent chemotherapy remains unclear, with some evidence suggesting worse locoregional control in larger tumors. Objective: To evaluate the association of primary tumor volume with oncologic outcomes in patients with T3 N0-N3 M0 glottic cancer treated with primary (chemo)radiotherapy in a large multi-institutional study. Design, Setting, and Participants: This multi-institutional retrospective cohort study involved 7 Canadian cancer centers from 2002 to 2018. Tumor volume was measured by expert neuroradiologists on diagnostic imaging. Clinical and outcome data were extracted from electronic medical records. Overall survival (OS) and disease-free survival (DFS) outcomes were assessed with marginal Cox regression. Laryngectomy-free survival (LFS) was modeled as a secondary analysis. Patients diagnosed with cT3 N0-N3 M0 glottic cancers from 2002 to 2018 and treated with curative intent intensity-modulated radiotherapy (IMRT) with or without chemotherapy. Overall, 319 patients met study inclusion criteria. Exposures: Tumor volume as measured on diagnostic imaging by expert neuroradiologists. Main Outcomes and Measures: Primary outcomes were OS and DFS; LFS was assessed as a secondary analysis, and late toxic effects as an exploratory analysis determined before start of the study. Results: The mean (SD) age of participants was 66 (12) years and 279 (88%) were men. Overall, 268 patients (84%) had N0 disease, and 150 (47%) received concurrent systemic therapy. The mean (SD) tumor volume was 4.04 (3.92) cm3. With a mean (SD) follow-up of 3.85 (3.04) years, there were 91 (29%) local, 35 (11%) regional, and 38 (12%) distant failures. Increasing tumor volume (per 1-cm3 increase) was associated with significantly worse adjusted OS (hazard ratio [HR], 1.07; 95% CI, 1.03-1.11) and DFS (HR, 1.04; 95% CI, 1.01-1.07). A total of 62 patients (19%) underwent laryngectomies with 54 (87%) of these within 800 days after treatment. Concurrent systemic therapy was associated with improved LFS (subdistribution HR, 0.63; 95% CI, 0.53-0.76). Conclusions and Relevance: Increasing tumor volumes in cT3 glottic cancers was associated with worse OS and DFS, and systemic therapy was associated with improved LFS. In absence of randomized clinical trial evidence, patients with poor pretreatment laryngeal function or those ineligible for systemic therapy may be considered for primary surgical resection with postoperative radiotherapy.

Validated algorithms for identifying timing of second event of oropharyngeal squamous cell carcinoma using real-world data.

BACKGROUND: Understanding occurrence and timing of second events (recurrence and second primary cancer) is essential for cancer specific survival analysis. However, this information is not readily available in administrative data. METHODS: Alberta Cancer Registry, physician claims, and other administrative data were used. Timing of second event was estimated based on our developed algorithm. For validation, the difference, in days between the algorithm estimated and the chart-reviewed timing of second event. Further, the result of Cox-regression modeling cancer-free survival was compared to chart review data. RESULTS: Majority (74.3%) of the patients had a difference between the chart-reviewed and algorithm-estimated timing of second event falling within the 0-60 days window. Kaplan-Meier curves generated from the estimated data and chart review data were comparable with a 5-year second-event-free survival rate of 75.4% versus 72.5%. CONCLUSION: The algorithm provided an estimated timing of second event similar to that of the chart review.

From Pathways to Practice: Impact of Implementing Mobilization Recommendations in Head and Neck Cancer Surgery with Free Flap Reconstruction.

One of the foundational elements of enhanced recovery after surgery (ERAS) guidelines is early postoperative mobilization. For patients undergoing head and neck cancer (HNC) surgery with free flap reconstruction, the ERAS guideline recommends patients be mobilized within 24 h postoperatively. The objective of this study was to evaluate compliance with the ERAS recommendation for early postoperative mobilization in 445 consecutive patients who underwent HNC surgery in the Calgary Head and Neck Enhanced Recovery Program. This retrospective analysis found that recommendation compliance increased by 10% despite a more aggressive target for mobilization (from 48 to 24 h). This resulted in a decrease in postoperative mobilization time and a stark increase in the proportion of patients mobilized within 24 h (from 10% to 64%). There was a significant relationship between compliance with recommended care and time to postoperative mobilization (Spearman's rho = -0.80; p < 0.001). Hospital length of stay was reduced by a median of 2 days, from 12 (1QR = 9-16) to 10 (1QR = 8-14) days (z = 3.82; p < 0.001) in patients who received guideline-concordant care. Engaging the clinical team and changing the order set to support clinical decision-making resulted in increased adherence to guideline-recommended care for patients undergoing major HNC surgery with free flap reconstruction.

Impact of Early Mobilization on Recovery after Major Head and Neck Surgery with Free Flap Reconstruction.

Surgery with free flap reconstruction is a standard treatment for head and neck cancer (HNC). Because of the complexity of HNC surgery, recovery can be challenging, and complications are common. One of the foundations of enhanced recovery after surgery (ERAS) is early postoperative mobilization. The ERAS guidelines for HNC surgery with free flap reconstruction recommend mobilization within 24 h. This is based mainly on evidence from other surgical disciplines, and the extent to which mobilization within 24 h improves recovery after HNC surgery has not been explored. This retrospective analysis included 445 patients from the Calgary Head and Neck Enhanced Recovery Program. Mobilization after 24 h was associated with more complications of any type (OR = 1.73, 95% CI [confidence interval] = 1.16-2.57) and more major complications (OR = 1.76; 95% CI = 1.00-3.16). When accounting for patient and clinical factors, mobilization after 48 h was a significant predictor of major complications (OR = 2.61; 95% CI = 1.10-6.21) and prolonged length of stay (>10 days; OR = 2.85, 95% CI = 1.41-5.76). This comprehensive analysis of the impact of early mobilization on postoperative complications and length of stay in a large HNC cohort provides novel evidence supporting adherence to the ERAS early mobilization recommendations. Early mobilization should be a priority for patients undergoing HNC surgery with free flap reconstruction.

Efficacy of Multimodal Analgesia for Postoperative Pain Management in Head and Neck Cancer Patients.

Postoperative opioid use has been linked to the subsequent development of opioid dependency. Multimodal analgesia (MMA) can reduce the use of opioids in the postoperative period, but MMA has not been well-studied after major head and neck surgery. Our goal is to explore the association between MMA and postoperative opioid use and pain control in patients undergoing major head and neck surgery. We performed a retrospective study in adult (age ≥ 18 years) patients undergoing primary head and neck cancer resection with free-flap reconstruction. All patients were treated using an established care pathway. The baseline group was treated between January 2015-December 2015 (n = 41), prior to the implementation of MMA, and were compared to an MMA-treated cohort treated between December 2017-June 2019 (n = 97). The primary outcome was the proportion of opioids prescribed and oral morphine equivalents (OMEs) consumed during the hospitalization. The secondary outcome was pain control. We found that the post-MMA group consumed fewer opioids in the postoperative period compared to the pre-MMA group. Prior to post-operative day (POD) 6, pain control was better in the post-MMA group; however, the pain control lines intersect on POD 6 and the pre-MMA group appeared to have better pain control from PODs 7-10. In conclusion, our data suggest MMA is an effective method of pain control and opioid reduction in patients undergoing surgery for head and neck cancer with free flap reconstruction. MMA use was associated with a significant decrease in the quantity of opioids consumed postoperatively. The MMA protocol was associated with improved pain management early in the postoperative course. Finally, the MMA protocol is a feasible method of pain control and may reduce the adverse side effects associated with opioid use.

Chronic opioid use following surgery for head and neck cancer patients undergoing free flap reconstruction.

BACKGROUND: Physician opioid-prescribing patterns have significant impacts on the current opioid crisis. Patients who use opioids in the postoperative period are at risk of developing chronic postoperative opioid use. This study determined the rate of chronic postoperative opioid use among head and neck cancer patients undergoing primary surgery with free-flap reconstruction. Additionally, this study identified major risk factors associated with the development of chronic postoperative opioid use. METHODS: A retrospective chart review was performed for all adults (age ≥ 18 years) undergoing primary head and neck surgical resection with free-flap reconstruction between January 2008 and December 2015. Patients were identified from a prospectively collected database, Otobase™. Data from the provincial drug insurance program were used to capture drug dispensing information to determine chronic opioid use at 3- and 12-months postoperatively. Data extracted from Otobase™ included patient demographics, social habits, clinical stage, pathological stage, type of surgery, and adjuvant treatment. RESULTS: The total cohort was comprised of 212 patients. Chronic opioid use at 3- and 12- months postoperatively was observed in 136 (64%) and 116 (55%) patients, respectively. Of the 212 patients, 85 patients (40%) were identified as preoperative opioid users and 127 were opioid naïve (60%). Of the 85 patients who were preoperative opioid users, 70 (82%) and 63 (77%) patients continued to use opioids 3- and 12-months postoperatively, respectively. The proportion of opioid-naïve patients who were using opioids at 3- and 12-months postoperatively was 52% (66 patients) and 42% (53 patients), respectively. Identified risk factors included preoperative opioid use, prior tobacco use, advanced pathologic T-stage, and adjuvant treatment. CONCLUSIONS: Among head and neck cancer patients that have undergone major resection with free-flap reconstruction, the prevalence of chronic postoperative opioid users was considerable. Identified risk factors included preoperative opioid use, prior tobacco use, tumor stage, and adjuvant treatment.

The impact of close surgical margins on recurrence in oral squamous cell carcinoma.

BACKGROUND: Close margins influence treatment and outcome in patients with oral squamous cell carcinoma (OSCC). This study evaluates 187 cases of surgically treated OSCC regarding the impact of close margins on recurrence-free survival (RFS) and disease-specific survival (DSS). METHODS: Predictors of worsened outcome were identified using Kaplan-Meier analysis and multivariate Cox regression analysis. RESULTS: Tumour size [HR:1.70(0.95-3.08)], nodal status [HR:2.15(1.00-4.64)], presence of extracapsular spread (ECS) [HR:6.36(2.41-16.74)] and smoking history [HR:2.87(1.19-6.86)] were associated with worsened RFS. Similar factors were associated with worsened DSS. Close margins did not influence RFS or DSS. CONCLUSIONS: While most conventional risk factors for OSCC conferred a worsened outcome, close margins did not. One explanation for this would be that close margins (< 5 mm) are equivalent to clear margins and the cutoff definition for a close margin should be re-evaluated. Lack of standardized pathology could also reduce accuracy of reporting of close surgical margins.

Designing and integrating a quality management program for patients undergoing head and neck resection with free-flap reconstruction.

BACKGROUND: Care pathways (CPs) offer a proven method of systematically improving patient care. CPs are particularly helpful in complex clinical conditions where variation in care is a problem such as patients undergoing major head and neck resection with free flap reconstruction. Although CPs have been used to manage this patient group, most CPs are implemented as part of relatively short-term quality improvement projects. This paper outlines a detailed methodology for designing and delivering a quality management program sustained for 9 years. METHODS: We describe a change management approach informed by Kotter's "8 Step Process" that provided a useful framework to guide program development and implementation. We then provide a detailed, step by step description of how such a program can be implemented as well as a detailed summary of time and costs for design, implementation and sustainability phases. An approach to design and delivery of a measurement, audit and feedback system is also provided. RESULTS: We present a summary of resources needed to design and implement a head and neck surgery quality management program. The primary result of this study is a design for a sustainable quality management program that can be used to guide and improve care for patients undergoing major head and neck resection with free flap reconstruction. CONCLUSIONS: A change management approach to design and delivery of a head and neck quality management program is practical and feasible.

The impact of a quality management program for patients undergoing head and neck resection with free-flap reconstruction: longitudinal study examining sustainability.

BACKGROUND: Care pathways (CPs) are helpful in reducing unwanted variation in clinical care. Most studies of CPs show they improve clinical outcomes but there is little known about the long-term impact of CPs as part of a sustained quality management program. Head and neck (HN) surgery with free flap reconstruction is complex, time-consuming and expensive. Complications are common and therefore CPs applied to this patient population are the focus of this paper. In this paper we report outcomes from a 9 year experience designing and using CPs in the management of patients undergoing major head and neck resection with free flap reconstruction. METHODS: The Calgary quality management program and CP design is described the accompanying article. Data from CP managed patients undergoing major HN surgery were prospectively collected and compared to a baseline cohort of patients managed with standard care. Data were retrospectively analyzed and intergroup comparisons were made. RESULTS: Mobilization, decannulation time and hospital length of stay were significantly improved in pathway-managed patients (p = 0.001). Trend analysis showed sustained improvement in key performance indicators including complications. Return to the OR, primarily to assess a compromised flap, is increasing. CONCLUSIONS: Care pathways when deployed as part of an ongoing quality management program are associated with improved clinical outcomes in this complex group of patients.

Correction to: Assessment of a virtual reality temporal bone surgical simulator: a national face and content validity study.

Following publication of the original article [1], the authors identified incorrect ordering and incorrect files being used for Figs. 1, 2 and 3.

Assessment of a virtual reality temporal bone surgical simulator: a national face and content validity study.

BACKGROUND: Trainees in Otolaryngology-Head and Neck Surgery must gain proficiency in a variety of challenging temporal bone surgical techniques. Traditional teaching has relied on the use of cadavers; however, this method is resource-intensive and does not allow for repeated practice. Virtual reality surgical training is a growing field that is increasingly being adopted in Otolaryngology. CardinalSim is a virtual reality temporal bone surgical simulator that offers a high-quality, inexpensive adjunct to traditional teaching methods. The objective of this study was to establish the face and content validity of CardinalSim through a national study. METHODS: Otolaryngologists and resident trainees from across Canada were recruited to evaluate CardinalSim. Ethics approval and informed consent was obtained. A face and content validity questionnaire with questions categorized into 13 domains was distributed to participants following simulator use. Descriptive statistics were used to describe questionnaire results, and either Chi-square or Fishers exact tests were used to compare responses between junior residents, senior residents, and practising surgeons. RESULTS: Sixty-two participants from thirteen different Otolaryngology-Head and Neck Surgery programs were included in the study (32 practicing surgeons; 30 resident trainees). Face validity was achieved for 5 out of 7 domains, while content validity was achieved for 5 out of 6 domains. Significant differences between groups (p-value of < 0.05) were found for one face validity domain (realistic ergonomics, p = 0.002) and two content validity domains (teaching drilling technique, p = 0.011 and overall teaching utility, p = 0.006). The assessment scores, global rating scores, and overall attitudes towards CardinalSim, were universally positive. Open-ended questions identified limitations of the simulator. CONCLUSION: CardinalSim met acceptable criteria for face and content validity. This temporal bone virtual reality surgical simulation platform may enhance surgical training and be suitable for patient-specific surgical rehearsal for practicing Otolaryngologists.

The Identification of Intraoperative Risk Factors Can Reduce, but Not Exclude, the Need for Completion Thyroidectomy in Low-Risk Papillary Thyroid Cancer Patients.

Background: The extent of initial surgical resection for low-risk papillary thyroid cancer (PTC) remains debatable. Since the 2015 American Thyroid Association (ATA) guidelines, several retrospective studies have reported that 40-60% of patients initially treated with lobectomy would require a completion thyroidectomy (CTx) due to high-risk pathological features (HRFs). These studies are limited by variable preoperative stratification and inability to quantify the value of intraoperative assessment. The study objectives were to determine whether diligent preoperative and intraoperative assessment improves the appropriateness of initial surgery for low-risk PTCs and whether varying the criteria for lobectomy reduces the need for CTx. Methods: A prospectively collected province-wide database was analyzed over a 10-year period (2008-2017) for patients who underwent a total thyroidectomy (TT) for PTC without preoperative HRFs. All patients had preoperative ultrasound and fine-needle aspirates. Unique to this database are mandatory synoptic operative fields that identify intraoperative risk factors such as positive lymph nodes and local invasion. Results: In total, 74% of patients (709/959) were deemed eligible for lobectomy. Of those eligible, 149 (21%) had intraoperative risk factors that would necessitate conversion to TT at the initial operation. A further 209 (30%) would require CTx due to HRFs on final pathology. Varying the preoperative criteria for lobectomy did not significantly affect intraoperative conversion or CTx rates. Conclusions: Although intraoperative assessment reduced the need for CTx in 21%, up to 30% of patients would still require a second operation. Altering the preoperative criteria does not influence this outcome. Patients deemed eligible for lobectomy should be informed that despite careful pre- and intraoperative assessment, there is up to a 30% risk of requiring CTx.

Prediction of survival of HPV16-negative, p16-negative oral cavity cancer patients using a 13-gene signature: A multicenter study using FFPE samples.

OBJECTIVES: To test the performance of an oral cancer prognostic 13-gene signature for the prediction of survival of patients diagnosed with HPV-negative and p16-negative oral cavity cancer. MATERIALS AND METHODS: Diagnostic formalin-fixed paraffin-embedded oral cavity cancer tumor samples were obtained from the Fred Hutchinson Cancer Research Center/University of Washington, University of Calgary, University of Michigan, University of Utah, and seven ARCAGE study centers coordinated by the International Agency of Research on Cancer. RNA from 638 Human Papillomavirus (HPV)-negative and p16-negative samples was analyzed for the 13 genes using a NanoString assay. Ridge-penalized Cox regressions were applied to samples randomly split into discovery and validation sets to build models and evaluate the performance of the 13-gene signature in predicting 2-year oral cavity cancer-specific survival overall and separately for patients with early and late stage disease. RESULTS: Among AJCC stage I/II patients, including the 13-gene signature in the model resulted in substantial improvement in the prediction of 2-year oral cavity cancer-specific survival. For models containing age and sex with and without the 13-gene signature score, the areas under the Receiver Operating Characteristic Curve (AUC) and partial AUC were 0.700 vs. 0.537 (p < 0.001), and 0.046 vs. 0.018 (p < 0.001), respectively. Improvement in predicting prognosis for AJCC stage III/IV disease also was observed, but to a lesser extent. CONCLUSIONS: If confirmed using tumor samples from a larger number of early stage oral cavity cancer patients, the 13-gene signature may inform personalized treatment of early stage HPV-negative and p16-negative oral cavity cancer patients.

Developing case-finding algorithms for second events of oropharyngeal cancer using administrative data: A population-based validation study.

BACKGROUND: Second event (recurrence or second primary cancer)-free survival is an important indicator for assessing treatment efficacy. However, second events are not explicitly documented in administrative data such as cancer registries. Thus, validated algorithms using administrative data are needed to identify second events of oropharyngeal cancers. METHODS: The algorithms were developed using classification and regression tree models. Data from chart review served as the reference standard. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. RESULTS: The high-sensitivity algorithm achieved 87.9% (95% confidence interval: 82.2%-93.6%) sensitivity, 84.5% (81.1%-87.8%) specificity, 61.2% (54.1%-68.4%) PPV, 96.2% (94.2%-98.1%) NPV, and 85.2% (82.3%-88.1%) accuracy. The high-PPV algorithm obtained 52.4% (43.6%-61.2%) sensitivity, 99.1% (98.2%-100.0%) specificity, 94.2% (88.7%-99.7%) PPV, 88.2% (85.3%-91.0%) NPV, and 88.9% (86.3%-91.5%) accuracy. CONCLUSION: The validity of the algorithms for identifying second events following primary treatment of oropharyngeal cancers was acceptable.

An evaluation of in-office flexible fiber-optic biopsies for laryngopharyngeal lesions.

BACKGROUND: Operative endoscopy and flexible fiber-optic in-office tissue biopsy are common techniques to assess suspicious laryngopharyngeal lesions. METHODS: The primary outcome was the delay to the initiation of treatment. Secondary outcomes were delay to biopsy, histopathological diagnosis, and assessment at a multidisciplinary oncology clinic. A retrospective analysis was performed to assess the relative delays between these approaches to biopsy of laryngopharyngeal lesions. RESULTS: There were 114 patients in the study cohort; 44 in-office and 70 operative endoscopic biopsies). The mean delay from consultation to biopsy was 17.4 days for the operative endoscopy group and 1.3 days for the in-office group. The mean delay from initial otolaryngology consultation to initiation of treatment was 51.7 days and 44.6 days for the operative endoscopy and in-office groups, respectively. CONCLUSION: In-office biopsy reduced the time from initial consultation to biopsy. The temporal gains via in-office biopsy did not translate into faster access to treatment. This outcome highlights the opportunity to improve access to treatment for patients with early diagnosis.

Efficacy of postoperative pain management in head and neck cancer patients.

BACKGROUND: Our study quantifies the effectiveness of perioperative pain control in a cohort of patients undergoing major head and neck surgery with free flap reconstruction. Our long-term goal is to improve pain control and thereby increase mobility, decrease postoperative complications and decrease hospital stay. METHODS: A retrospective analysis was performed at a tertiary, academic head and neck surgical oncology program in Calgary, Alberta, Canada from January 1, 2015 - December 31, 2015. Pain scores were recorded prospectively. Primary outcomes were frequency of postoperative pain assessments and pain intensity using the numeric rating scale. RESULTS: The cohort included 41 patients. Analysis was limited to pain scores recorded from postoperative days 1-14. There was an average of 7.3 pain measurements per day (SD 4.6, range 1-24) with the most frequent monitoring on postoperative days 1-4. Median pain scores ranged from 0 to 4.5 with the highest median score on postoperative day 6. The daily maximum pain scores recorded ranged from 8 to 10 with scores of 10 recorded on postoperative days 1, 2, 3, 5, 7, 8, and 10. Patients most frequently had inadequate pain control on postoperative days 1, 2, 4, and 5 with the majority occurring on postoperative day 1. CONCLUSIONS: Postoperative pain control could be improved at our centre. The frequency of pain assessments is also highly variable. Ongoing measurement, audit, and feedback of analgesic protocol effectiveness is an excellent first step in improving perioperative pain management in patients undergoing major head and neck cancer surgery with free flap reconstruction.

Assessing the performance of a Loop Mediated Isothermal Amplification (LAMP) assay for the detection and subtyping of high-risk suptypes of Human Papilloma Virus (HPV) for Oropharyngeal Squamous Cell Carcinoma (OPSCC) without DNA purification.

BACKGROUND: Oropharyngeal Squamous Cell Carcinoma (OPSCC) is increasing in incidence despite a decline in traditional risk factors. Human Papilloma Virus (HPV), specifically subtypes 16, 18, 31 and 35, has been implicated as the high-risk etiologic agent. HPV positive cancers have a significantly better prognosis than HPV negative cancers of comparable stage, and may benefit from different treatment regimens. Currently, HPV related carcinogenesis is established indirectly through Immunohistochemistry (IHC) staining for p16, a tumour suppressor gene, or polymerase chain reaction (PCR) that directly tests for HPV DNA in biopsied tissue. Loop mediated isothermal amplification (LAMP) is more accurate than IHC, more rapid than PCR and is significantly less costly. In previous work we showed that a subtype specific HPV LAMP assay performed similar to PCR on purified DNA. In this study we examined the performance of this LAMP assay without DNA purification. METHODS: We used LAMP assays using established primers for HPV 16 and 18, and new primers for HPV 31 and 35. LAMP reaction conditions were tested on serial dilutions of plasmid HPV DNA to confirm minimum viral copy number detection thresholds. LAMP was then performed directly on different human cell line samples without DNA purification. RESULTS: Our LAMP assays could detect 105, 103, 104, and 105 copies of plasmid DNA for HPV 16, 18, 31, and 35, respectively. All primer sets were subtype specific, with no cross-amplification. Our LAMP assays also reliably amplified subtype specific HPV DNA from samples without requiring DNA isolation and purification. CONCLUSIONS: The high risk OPSCC HPV subtype specific LAMP primer sets demonstrated, excellent clinically relevant, minimum copy number detection thresholds with an easy readout system. Amplification directly from samples without purification illustrated the robust nature of the assay, and the primers used. This lends further support HPV type specific LAMP assays, and these specific primer sets and assays can be further developed to test for HPV in OPSCC in resource and lab limited settings, or even bedside testing.