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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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., (© 2023. The Author(s).)

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., (© 2022 Wiley Periodicals LLC.)

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.

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.

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 10 5 , 10 3 , 10 4 , and 10 5 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.

Background: Long operating time and high blood loss contribute to post-surgical morbidity. Therefore, strategies to reduce these factors should to be tested using robust methods. The purpose of this study was to evaluate the impact of using the harmonic scalpel on operating time and blood loss in patients undergoing resection for advanced oral cancer (OSCC)., Methods: Thirty-six adult head and neck cancer patients with advanced OSCC requiring primary tumor resection with uni- or bi- lateral selective neck dissection from July 2012 to September 2014 were randomized to either the control group (traditional surgery) or the experimental group (harmonic surgery). Patients older than 18 years who were able to provide informed consent were eligible. Primary outcomes of interest were: intraoperative blood loss (mL) and operative time (minutes) for the ablative part of the surgery., Results: Mean blood loss in the experimental group was 260 mL versus 403 mL in the control group (p = 0.08). Mean operative time was 140 min in the experimental group and 159 min in the control group (p = 0.2)., Conclusions: In this randomized controlled trial, use of the harmonic scalpel did not effect intraoperative blood loss or OR time in patients undergoing surgery for advanced OSCC., Trial Registration: ClinicalTrials.gov, NCT02017834 .

Background: The purposes of this study were to explore the association of a postoperative clinical care pathway for patients undergoing major head and neck surgery with microvascular reconstruction on postdischarge health care utilization and cost and to compares a nonpathway group (n = 60) to a prospective, pathway-managed group (n = 54). Our primary purpose was to understand whether pathway-managed patients used postdischarge health care resources differently than patients managed without a care pathway., Methods: Health care utilization data (counts and costs) were collected for the 3 months after discharge. Differences in utilization were compared using Poisson regression. The null hypothesis was that there were no differences in utilization between the pathway and nonpathway groups., Results: Pathway patients had fewer postdischarge encounters in 2 of 4 sectors. Readmission costs were significantly less in the pathway group only., Conclusion: A postoperative inpatient clinical care pathway in patients with head and neck cancer is associated with decreased health care utilization and inpatient costs in the 3 months after discharge. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1216-E1220, 2016., (© 2015 Wiley Periodicals, Inc.)

Background: Pulmonary complications are common after major head and neck oncologic surgery with microsurgical reconstruction and are associated with increased mortality and morbidity. Clinical care pathways are evidence-based tools that reduce unnecessary practice variation and ultimately improve patient outcomes. In this study, the authors evaluate the effectiveness of a comprehensive care pathway on reducing postoperative pulmonary complications and hospital length of stay in patients undergoing major head and neck carcinoma resection with free flap reconstruction., Methods: Fifty-five consecutive patients treated according to a prescribed postoperative clinical care pathway were compared to a historical cohort of patients treated before the implementation of the pathway. The incidence of pulmonary complications, hospital length of stay, and free flap survival were compared between the control and intervention groups., Results: Patients on the clinical care pathway had 32.5 percent fewer pulmonary complications (p < 0.0001) and 7.4 days' shorter hospital length of stay (p = 0.0007) than patients not on the postoperative pathway. There was no significant difference in the rate of flap reoperation., Conclusions: A multidisciplinary, comprehensive, clinical care pathway for patients undergoing major head and neck surgery with microsurgical reconstruction is effective in reducing postoperative pulmonary complications and hospital length of stay. The postoperative pathway is safe in this patient population and should be considered for adoption into clinical practice., Clinical Question/level of Evidence: Therapeutic, III.

Background: The objective of this study is to evaluate the cost-effectiveness of a postoperative clinical care pathway for patients undergoing major head and neck oncologic surgery with microvascular reconstruction., Methods: This is a comparative trial of a prospective treatment group managed on a postoperative clinical care pathway and a historical group managed prior to pathway implementation. Effectiveness outcomes evaluated were total hospital days, return to OR, readmission to ICU and rate of pulmonary complications. Costing perspective was from the government payer., Results: 118 patients were included in the study. All outcomes demonstrated that the postoperative pathway group was both more effective and less costly, and is therefore a dominant clinical intervention. The overall mean pre- and post-pathway costs are $22,733 and $16,564 per patient, respectively. The incremental cost reduction associated with the postoperative pathway was $6,169 per patient., Conclusion: Implementing the postoperative clinical care pathway in patients undergoing head and neck oncologic surgery with reconstruction resulted in improved clinical outcomes and reduced costs.

Objective: Patients with head and neck cancer frequently present to academic tertiary referral centers with imaging studies that have been performed and interpreted elsewhere. At our institution, these outside head and neck imaging studies undergo formal second opinion reporting by a fellowship-trained academic neuroradiologist with expertise in head and neck imaging. The purpose of this study was to determine the impact of this practice on cancer staging and patient management., Methods: Our institutional review board approved the retrospective review of randomized original and second opinion reports for 94 consecutive cases of biopsy proven or clinically suspected head and neck cancer in calendar year 2010. Discrepancy rates for staging and recommended patient management were calculated and, for the 32% (30/94) of cases that subsequently went to surgery, the accuracies of the reports were determined relative to the pathologic staging gold standard., Results: Following neuroradiologist second opinion review, the cancer stage changed in 56% (53/94) of cases and the recommended management changed in 38% (36/94) of patients with head and neck cancer. When compared to the pathologic staging gold standard, the second opinion was correct 93% (28/30) of the time., Conclusion: In a majority of patients with head and neck cancer, neuroradiologist second opinion review of their outside imaging studies resulted in an accurate change in their cancer stage and this frequently led to a change in their management plan.

Background: Prolonged procedure time in head and neck cancer ablation and free flap reconstruction cases has been shown to significantly increase perioperative complications. The authors' objective was to evaluate the effectiveness of a standardized surgical nursing team for head and neck cancer ablation and free flap reconstruction operations for reducing procedure time., Methods: A retrospective cohort analysis of consecutive patients presenting for head and neck cancer ablation and free flap reconstruction between January 1, 2007, and September 1, 2010, was performed. A standardized head and neck surgical nursing team was introduced on May 1, 2009, at our center. Procedure time and case time were measured before and after the introduction of the team. Univariable analyses were performed to evaluate the difference in procedure and case time between the two cohorts. A multivariable linear regression model was developed to control for confounding variables., Results: There were 52 cases before the team was introduced and 49 cases after. Mean procedure time was reduced by 47.1 minutes (p = 0.04) and mean case time was reduced by 68.9 minutes (p = 0.01) after team introduction. The multivariable linear regression analysis demonstrated a significant reduction in operative time after team introduction, controlling for confounding variables., Conclusions: The introduction of a standardized surgical nursing team led to a significant reduction in procedure and case time. A standardized team approach improves operating room efficiency in complex cases such as free flap reconstruction following tumor ablation., Clinical Question/level of Evidence: Therapeutic, III.

Objectives: To determine the impact of the harmonic scalpel on intraoperative blood loss and operative time in selective neck dissection (SND) (levels I-IV) for head and neck squamous cell carcinoma (HNSCC)., Study Design: Prospective randomized controlled trial., Setting: A single, tertiary care institution (Foothills Medical Centre) in Calgary, Alberta, Canada., Subjects: A total of 31 patients (36 neck dissections) were prospectively enrolled between January 2009 and March 2010., Methods: Patients were randomized to receive a neck dissection with either the harmonic scalpel or the traditional technique of using electrocautery and sharp dissection. The study included adult patients older than age 18 years diagnosed with HNSCC and who required an SND (levels I-IV). Study exclusion criteria included previous treatment for head and neck cancer and all patients unwilling or unable to provide informed consent. Primary clinical outcomes were intraoperative blood loss and operative time. Secondary outcomes included intraoperative complications and surgical drain output., Results: Intraoperative blood loss was significantly lower in the harmonic scalpel group compared to the traditional group (158 vs 61 mL, P = .02). There was no difference in operative time (81 minutes harmonic vs 85 minutes traditional) or total drain output (at both 48 hours and 1 week) between the groups. There were no intraoperative complications reported in either group., Conclusions: Results from this study suggest that the harmonic scalpel can reduce blood loss during SND for HNSCC. The harmonic scalpel had no impact on operative time, postoperative drain output, or complication rate.