The protective role of postoperative radiation therapy in low and intermediate grade major salivary gland malignancies: A study of the Canadian Head and Neck Collaborative Research Initiative.

BACKGROUND: The objective of this study was to examine the utility of postoperative radiation for low and intermediate grade cancers of the parotid and submandibular glands. METHODS: The authors conducted a retrospective, Canadian-led, international, multi-institutional analysis of a patient cohort with low or intermediate grade salivary gland cancer of the parotid or submandibular gland who were treated from 2010 until 2020 with or without postoperative radiation therapy. A multivariable, marginal Cox proportional hazards regression analysis was performed to quantify the association between locoregional recurrence (LRR) and receipt of postoperative radiation therapy while accounting for patient-level factors and the clustering of patients by institution. RESULTS: In total, 621 patients across 14 tertiary care centers were included in the study; of these, 309 patients (49.8%) received postoperative radiation therapy. Tumor histologies included 182 (29.3%) acinic cell carcinomas, 312 (50.2%) mucoepidermoid carcinomas, and 137 (20.5%) other low or intermediate grade primary salivary gland carcinomas. Kaplan-Meier LRR-free survival at 10 years was 89.0% (95% confidence interval [CI], 84.9%-93.3%). In multivariable Cox regression analysis, postoperative radiation therapy was independently associated with a lower hazard of LRR (adjusted hazard ratio, 0.53; 95% CI, 0.29-0.97). The multivariable model estimated that the marginal probability of LRR within 10 years was 15.4% without radiation and 8.8% with radiation. The number needed to treat was 16 patients (95% CI, 14-18 patients). Radiation therapy had no benefit in patients who had early stage, low-grade salivary gland cancer without evidence of nodal disease and negative margins. CONCLUSIONS: Postoperative radiation therapy may reduce LLR in some low and intermediate grade salivary gland cancers with adverse features, but it had no benefit in patients who had early stage, low-grade salivary gland cancer with negative margins.

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.

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

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

Epidermal Carcinoma of the Conchal Bowl: Creation of a Multidisciplinary Pathway Approach.

BACKGROUND: Malignant neoplasms of the auricle make up 6% of all skin cancers. Management of cutaneous neoplasms of the conchal bowl presents a unique challenge in visualizing and defining margins that may extend into the external auditory canal (EAC). OBJECTIVES: The objective of this study was to create a multidisciplinary pathway for cutaneous carcinoma of the conchal bowl extending into the EAC. METHODS: We present a series of patients that were referred to dermatology or otolaryngology, with cutaneous neoplasms arising in the conchal bowl. A consensus approach from otolaryngology and dermatology, for evaluation and treatment, was created based on evaluation of these cases, and review of the otolaryngology and dermatology literature, in collaboration between the two specialties. RESULTS: Initial evaluation should be done by both dermatology and otolaryngology, with otomicroscopic evaluation of the canal. Imaging is recommended for lesions that approach the EAC, for bony and soft tissue spread. Excision of the tumor with Mohs micrographic surgery to achieve clearance in the conchal bowl should be performed initially. If extension into the external auditory meatus is present, otolaryngology would proceed with en bloc resection. Repair is dictated by the defect, with both specialties involved in follow-up. CONCLUSIONS: In collaboration between dermatology and otolaryngology, and following review of the literature, a pathway was created to manage skin cancer of the conchal bowl. This resulted in a stepwise approach for evaluation and management, ensuring that patients have a streamlined pathway for the treatment of these lesions.

The Association of Ethnicity and Oncologic Outcomes for Oral Cavity Squamous Cell Carcinoma (OSCC).

(1) Background: To compare oncologic outcomes of South Asian (SA) patients treated for oral squamous cell carcinoma (OSCC) to the general population. (2) Methods: Adult patients who underwent surgical resection of OSCC +/- adjuvant treatment between 2009 and 2022 (N = 697) at a regional cancer centre in Canada were included. SA patients, identified using a validated method, were compared to non-SA patients. Kaplan-Meier methods were used to compare the primary outcomes, disease-specific survival (DSS) and recurrence-free survival (RFS) across baseline univariate characteristics, including betel nut consumption. Median follow-up time was 36.4 months. Cox proportional hazard models were used to identify independent predictors of survival with significance set at p < 0.05. (3) Results: SA patients (9% of cohort, N = 64) were significantly younger and had lower rates of smoking and alcohol consumption compared to non-SA patients (p < 0.05). SA patients had a two-fold higher risk of recurrence and significantly worse disease-specific survival, even after adjusting for stage and high-risk features [RFS: HR 2.01 (1.28-3.14), DSS: HR 1.79 (1.12-2.88)]. The consumption of betel nut was not associated with outcomes. (4) Conclusions: SA patients had significantly worse oncologic outcomes, even after controlling for known predictors of poor prognosis. These findings are novel and can inform personalized treatment decisions and influence public health policies when managing patients with different ethnic backgrounds.

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.

Identifying Factors of Operative Efficiency in Head and Neck Free Flap Reconstruction.

Importance: Head and neck oncological resection and reconstruction is a complex process that requires multidisciplinary collaboration and prolonged operative time. Numerous factors are associated with operative time, including a surgeon's experience, team familiarity, and the use of new technologies. It is paramount to evaluate the contribution of these factors and modalities on operative time to facilitate broad adoption of the most effective modalities and reduce complications associated with prolonged operative time. Objective: To examine the association of head and neck cancer resection and reconstruction interventions with operative time. Design, Setting, and Participants: This large cohort study included all patients who underwent head and neck oncologic resection and free flap-based reconstruction in Calgary (Alberta, Canada) between January 1, 2007, and March 31, 2020. Data were analyzed between November 2021 and May2022. Interventions: The interventions that were implemented in the program were classified into team-based strategies and the introduction of new technology. Team-based strategies included introducing a standardized operative team, treatment centralization in a single institution, and introducing a microsurgery fellowship program. New technologies included use of venous coupler anastomosis and virtual surgical planning. Main Outcomes and Measures: The primary outcome was mean operative time difference before and after the implementation of each modality. Secondary outcomes included returns to the operating room within 30 days, reasons for reoperation, returns to the emergency department or readmissions to hospital within 30 days, and 2-year and 5-year disease-specific survival. Multivariate regression analyses were performed to examine the association of each modality with operative time. Results: A total of 578 patients (179 women [30.9%]; mean [SD] age, 60.8 [12.9] years) undergoing 590 procedures met inclusion criteria. During the study period, operative time progressively decreased and reached a 32% reduction during the final years of the study. A significant reduction was observed in mean operative time following the introduction of each intervention. However, a multivariate analysis revealed that team-based strategies, including the use of a standardized nursing team, treatment centralization, and a fellowship program, were significantly associated with a reduction in operative time. Conclusions: The results of this cohort study suggest that among patients with head and neck cancer, use of team-based strategies was associated with significant decreases in operative time without an increase in complications.

Spatial transcriptomics reveals distinct and conserved tumor core and edge architectures that predict survival and targeted therapy response.

The spatial organization of the tumor microenvironment has a profound impact on biology and therapy response. Here, we perform an integrative single-cell and spatial transcriptomic analysis on HPV-negative oral squamous cell carcinoma (OSCC) to comprehensively characterize malignant cells in tumor core (TC) and leading edge (LE) transcriptional architectures. We show that the TC and LE are characterized by unique transcriptional profiles, neighboring cellular compositions, and ligand-receptor interactions. We demonstrate that the gene expression profile associated with the LE is conserved across different cancers while the TC is tissue specific, highlighting common mechanisms underlying tumor progression and invasion. Additionally, we find our LE gene signature is associated with worse clinical outcomes while TC gene signature is associated with improved prognosis across multiple cancer types. Finally, using an in silico modeling approach, we describe spatially-regulated patterns of cell development in OSCC that are predictably associated with drug response. Our work provides pan-cancer insights into TC and LE biology and interactive spatial atlases ( http://www.pboselab.ca/spatial_OSCC/ ; http://www.pboselab.ca/dynamo_OSCC/ ) that can be foundational for developing novel targeted therapies.

Oncologic Significance of Therapeutic Delays in Patients With Oral Cavity Cancer.

Importance: Oral cavity cancer often requires multidisciplinary management, subjecting patients to complex therapeutic trajectories. Prolonged treatment intervals in oral cavity cancer have been associated with poor oncological outcomes, but there has yet to be a study investigating treatment times in Canada. Objective: To report treatment delays for patients with oral cavity cancer in Canada and evaluate the outcomes of treatment delays on overall survival. Design, Setting, and Participants: This multicenter cohort study was performed at 8 Canadian academic centers from 2005 to 2019. Participants were patients with oral cavity cancer who underwent surgery and adjuvant radiation therapy. Analysis was performed in January 2023. Main Outcomes and Measures: Treatment intervals evaluated were surgery to initiation of postoperative radiation therapy interval (S-PORT) and radiation therapy interval (RTI). The exposure variables were prolonged intervals, respectively defined as index S-PORT greater than 42 days and RTI greater than 46 days. Patient demographics, Charlson Comorbidity Index, smoking status, alcohol status, and cancer staging were also considered. Univariate (log rank and Kaplan-Meier) and multivariate (Cox regression) analyses were performed to determine associations with overall survival (OS). Results: Overall, 1368 patients were included; median (IQR) age at diagnosis was 61 (54-70) years, and 896 (65%) were men. Median (IQR) S-PORT was 56 (46-68) days, with 1093 (80%) patients waiting greater than 42 days, and median (IQR) RTI was 43 (41-47) days, with 353 (26%) patients having treatment time interval greater than 46 days. There were variations in treatment time intervals between institutions for S-PORT (institution with longest vs shortest median S-PORT, 64 days vs 48 days; η2 = 0.023) and RTI (institution with longest vs shortest median RTI, 44 days vs 40 days; η2 = 0.022). Median follow-up was 34 months. The 3-year OS was 68%. In univariate analysis, patients with prolonged S-PORT had worse survival at 3 years (66% vs 77%; odds ratio 1.75; 95% CI, 1.27-2.42), whereas prolonged RTI (67% vs 69%; odds ratio 1.06; 95% CI, 0.81-1.38) was not associated with OS. Other factors associated with OS were age, Charlson Comorbidity Index, alcohol status, T category, N category, and institution. In the multivariate model, prolonged S-PORT remained independently associated with OS (hazard ratio, 1.39; 95% CI, 1.07-1.80). Conclusions and Relevance: In this multicenter cohort study of patients with oral cavity cancer requiring multimodal therapy, initiation of radiation therapy within 42 days from surgery was associated with improved survival. However, in Canada, only a minority completed S-PORT within the recommended time, whereas most had an appropriate RTI. An interinstitution variation existed in terms of treatment time intervals. Institutions should aim to identify reasons for delays in their respective centers, and efforts and resources should be directed toward achieving timely completion of S-PORT.

Bax expression measured by AQUAnalysis is an independent prognostic marker in oral squamous cell carcinoma.

BACKGROUND: Resistance to apoptosis is a hallmark of cancer and proteins regulating apoptosis have been proposed as prognostic markers in several malignancies. However, the prognostic impact of apoptotic markers has not been consistently demonstrated in oral squamous cell carcinoma (OSCC). This inconsistency in reported associations between apoptotic proteins and prognosis can be partly attributed to the intrinsic low resolution and misclassification associated with manual, semi-quantitative methods of biomarker expression measurement. The aim of this study was to examine the association between apoptosis-regulating proteins and clinical outcomes in oral squamous cell carcinoma (OSCC) using the quantitative fluorescence immunohistochemistry (IHC) based AQUAnalysis technique. METHODS: Sixty-nine OSCC patients diagnosed between 1998-2005 in Calgary, Alberta, Canada were included in the study. Clinical data were obtained from the Alberta Cancer Registry and chart review. Tissue microarrays (TMAs) were assembled from triplicate cores of formalin-fixed paraffin embedded pre-treatment tumour tissue. Bax, Bcl-2 and Bcl-XL protein expression was quantified using fluorescent IHC and AQUA technology in normal oral cavity squamous epithelium (OCSE) and OSCC tumour samples. Survival was analyzed using Kaplan-Meier plots and the Cox proportional hazard model. RESULTS: Bax expression was predominantly nuclear in OCSE and almost exclusively cytoplasmic in OSCC. No similar differences in localization were observed for Bcl-2 or Bcl-XL. Only Bax expression associated with disease-specific survival (DSS), with 5-year survival estimates of 85.7% for high Bax versus 50.3% for low Bax (p = 0.006), in univariate analysis. High Bax expression was also significantly associated with elevated Ki67 expression, indicating that increased proliferation might lead to an improved response to radiotherapy in patients with elevated Bax expression. In multivariate analyses, Bax protein expression remained an independent predictor of DSS in OSCC [HR 0.241 (0.078-0.745), p = 0.013]. CONCLUSIONS: The AQUA technique used in our study eliminates observer bias and provides reliable and reproducible estimates for biomarker expression. AQUA also provides essential measures of quality control that cannot be achieved with manual biomarker scoring techniques. Our results support the use of Bax protein expression as a prognostic marker in conjunction with other clinico-pathological variables when designing personalized treatment strategies for OSCC patients.

The feasibility of patient-reported outcomes, physical function, and mobilization in the care pathway for head and neck cancer surgical patients.

BACKGROUND: Head and neck cancer (HNC) patients are an understudied population whose treatment often includes surgery, causing a wide range of side effects. Exercise prehabilitation is a promising tool to optimize patient outcomes and may confer additional benefits as a prehabilitation tool. The primary objective of this study was to assess the feasibility of measuring patient-reported outcomes (PROs), physical function, and in-hospital mobilization across the HNC surgical timeline in advance of a future prehabilitation trial. The secondary objective was to examine potential changes in these outcomes across the surgical timeline. METHODS: HNC patients scheduled to undergo oncologic resection with free-flap reconstruction completed assessments of PROs and physical function at three timepoints across the surgical timeline (baseline, in-hospital, and postsurgical/outpatient). Mobilization was measured during the in-hospital period. The feasibility of recruitment and measurement completion was tracked, as were changes in both PROs and physical function. RESULTS: Of 48 eligible patients, 16 enrolled (recruitment rate of 33%). The baseline and in-hospital PROs were completed by 88% of participants, while the outpatient assessments were completed by 81% of participants. The baseline and in-hospital assessment of physical function were completed by 56% of participants, and 38% completed the outpatient assessment. Measuring in-hospital mobilization was completed for 63% of participants. CONCLUSION: Measuring PROs and in-hospital mobilization is feasible across the surgical timeline in HNC; however, the in-person assessment of physical function prior to surgery was not feasible. A multidisciplinary collaboration between exercise specialists and clinicians supported the development of new clinical workflows in HNC surgical care that will aid in the implementation of a future prehabilitation trial for this patient population.

A Qualitative Study of Patient and Healthcare Provider Perspectives on Building Multiphasic Exercise Prehabilitation into the Surgical Care Pathway for Head and Neck Cancer.

Head and neck cancer (HNC) surgical patients experience a high symptom burden. Multiphasic exercise prehabilitation has the potential to improve patient outcomes, and to implement it into the care pathway, the perspectives of patients and healthcare providers (HCPs) must be considered. The purpose of this study was thus to gather feedback from HNC surgical patients and HCPs on building exercise into the standard HNC surgical care pathway. Methods: Semi-structured interviews were conducted with patients and HCPs as part of a feasibility study assessing patient-reported outcomes, physical function, and in-hospital mobilization. Interview questions included satisfaction with study recruitment, assessment completion, impact on clinical workflow (HCPs), and perceptions of a future multiphasic exercise prehabilitation program. This study followed an interpretive description methodology. Results: Ten patients and ten HCPs participated in this study. Four themes were identified: (1) acceptability and necessity of assessments, (2) the value of exercise, (3) the components of an ideal exercise program, and (4) factors to support implementation. Conclusion: These findings highlight the value of exercise across the HNC surgical timeline from both the patient and the HCP perspective. Results have informed the implementation of a multiphasic exercise prehabilitation trial in HNC surgical patients.

Clinical outcomes of head and neck cancer patients who refuse curative therapy in pursuit of alternative medicine.

BACKGROUND: We investigated the alarming trend of curable head and neck cancer (HNC) patients forgoing conventional treatment to pursue alternative medicine (AM). METHODS: A prospectively maintained database identified HNC patients with ≥12 weeks from diagnosis to treatment initiation between 2012 and 2017. Reasons for delay were categorized and clinical stages and outcomes of AM patients were assessed through chart review by December 2019. RESULTS: Among 1462 patients with primary HNC, 68 patients (4.7%) were confirmed to delay initiation of potentially curative treatment, and 19 of these patients (28%) delayed treatment to pursue AM. Eleven of 19 AM patients transitioned from curative intent to palliation while exploring AM. Continued treatment rejection was common and outcomes corresponded to patients' degree of treatment adherence. CONCLUSIONS: AM caused treatment delay and poor outcomes in potentially curable HNC. Improved knowledge among physicians regarding AM and complementary approaches is urgently needed to improve patient counseling. LEVEL OF EVIDENCE: Level 2c outcomes research.

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.

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.

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.

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.

Patient-Reported Outcomes after Fibula Free Flap Harvest: A Pilot Study.

SUMMARY: Patient-reported outcomes regarding donor-site morbidity and quality of life for the fibula free flap in head and neck reconstruction patients have not been studied. The authors reviewed and identified patients who had undergone head and neck reconstruction using a fibula free flap (2011 to 2016). Patients were assessed via physical examination and two patient-reported outcomes questionnaires: the Foot and Ankle Outcome Score (score range, 0 to 100) and the Pain Disability Questionnaire (score range, 0 to 100). Quantitative data were analyzed with appropriate statistical tests. Semistructured interviews exploring donor-site challenges were performed and analyzed using thematic analysis. Seventeen patients agreed to participate. Their mean age was 62 years (range, 41 to 81 years). Mean follow-up was 38 months (range, 12 to 65 years). Mean perceived level of function compared to baseline was 67 percent. Mean scores for the Foot and Ankle Outcome Score subscales were 84.6 (pain), 80.5 (symptoms), 86.7 (activities of daily living), 67.7 (sport), and 65.6 (quality of life). The mean Pain Disability Questionnaire score was 26.3 (mild/moderate perceived disability). Higher perceived level of function was associated with higher Foot and Ankle Outcome Score values (pain, symptoms, and activities of daily living, p < 0.05). Donor limbs had decreased range of motion and manual muscle testing scores compared with their contralateral limbs (p < 0.05). Lack of ankle support and balance, resulting in limitations and aversions to daily and sporting activities, were the most common themes regarding donor-site challenges. In conclusion, patients who have undergone fibula free flap harvest struggle with ankle support and balance and face functional difficulties that have an impact on their quality of life. Multidisciplinary approaches for targeted rehabilitation after fibula free flap harvest should be explored to determine the impact on patients' quality of life.

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.

Evaluating CNVII Recovery after Reconstruction with Vascularized Nerve Grafts: A Retrospective Case Series.

Few studies have evaluated vascularized nerve grafts (VNGs) for facial nerve (CNVII) reconstruction. We sought to evaluate long-term outcomes for CNVII recovery following reconstruction with VNGs. A retrospective review of all patients at a tertiary centre who underwent radical parotidectomy and immediate CNVII reconstruction with VNGs was performed (January 2009-December 2019). Preoperative demographics, perioperative factors (flap type, source of VNGs), and postoperative factors [complications, adjuvant therapy, revisionary procedures, length of follow-up, and CNVII function via the House-Brackmann scale (HB)] were collected. Data were summarized qualitatively. Twelve patients (Mage = 53 ± 18 years) with a mean follow-up of 33 (± 23) months were included. Six patients underwent reconstruction with a radial forearm flap and dorsal sensory branches of the radial nerve. Six patients underwent reconstruction with an anterolateral thigh flap and only deep motor branches of the femoral nerve to the vastus lateralis (n = 4) or combined with the lateral femoral cutaneous nerve (n = 2). Two patients regained nearly normal function (HB = 2). Eight patients regained at least resting symmetry (HB = 3 for n = 7; HB = 4 for n = 1). One patient regained a flicker of movement (HB = 5). One patient did not regain function (HB = 6). Six patients had static revision procedures to improve symmetry. Five patients had disease recurrence; 3 died from their disease. VNGs offer a practical and viable addition to the CNVII reconstruction strategy, and result in good functional recovery with acceptable donor site deficits. The associated adipofascial component of these flaps can also augment the soft tissue defect left after tumor ablation.