Improving Operating Room Efficiency in Otolaryngology-Head and Neck Surgery: A Scoping Review.

OBJECTIVE: One minute of operating room (OR) time costs $36 to 37. However, ORs are notoriously inefficient. There is growing literature on improving OR efficiency, but no formal review of this topic within otolaryngology has been performed. This study reviews and synthesizes the current literature on improving OR efficiency within otolaryngology. DATA SOURCES: MEDLINE, EMBASE, Web of Science, CINAHL, Cochrane Library, preprints.org, and medRxiv were searched on November 4, 2022. REVIEW METHODS: Published English studies were included if they reported on metrics for improving OR efficiency within otolaryngology. There were no publication date restrictions. Articles were screened by 2 reviewers. Preferred Reporting Items for Systematic Reviews and Meta-analysis reporting for scoping reviews was followed. RESULTS: The search yielded 9316 no-duplicate articles; 129 articles were included. Most of the studies reported on head and neck procedures (n = 52/129). The main tactics included surgical considerations: hemostatic devices, techniques, and team/simultaneous approaches; anesthetic considerations: local anesthetic and laryngeal mask airways; procedure location considerations: procedures outside of the OR and remote technologies; standardization: equipment, checklists, and personnel; scheduling considerations: use of machine learning for booking, considering patient/surgeon factors, and utilizing dedicated OR time/multidisciplinary teams for on-call cases. CONCLUSION: The current literature brings to attention numerous strategies for improving OR efficiency within otolaryngology. Applying these strategies and implementing novel techniques to manage surgical cases may assist in offloading overloaded health care systems and improving access to care while facilitating patient safety and outcomes. Anticipated barriers to implementation include resistance to change, funding, and the current strain on health care systems and providers.

Outcomes for potentially Resectable patients undergoing primary chemoradiation treatment for T1-T2 HPV Negative oropharyngeal squamous cell carcinoma.

BACKGROUND: Transoral surgical resectability (TOS) is a prognostic factor for patients with HPV+ T1-2 oropharyngeal squamous cell carcinoma (OPSCC) disease undergoing radiotherapy (RT), but it is unclear whether this holds for HPV-negative (HPV-) patients. We aimed to compare outcomes of potential TOS-candidates vs. non-TOS candidates, among patients who underwent RT/CRT for early T-stage HPV- OPSCC. METHODS: For patients treated with RT/CRT for early T-stage HPV-negative OPSCC between 2014 and 2021, pretreatment imaging was reviewed by four head-and-neck surgeons, masked to clinical outcomes, to assess primary-site suitability for TOS. Extracapsular extension (ECE) was assessed by a head-and-neck neuroradiologist. We compared outcomes based on surgical resectability relating to: (1) the primary site tumor alone, and (2) the primary site plus the absence/presence of ECE (overall assessment). Kaplan-Meier curves for overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS) were compared using the log-rank test. RESULTS: Seventy patients were included in the analysis. The primary site was TOS-favorable in 46/70 (66%). Based on the overall assessment, 41/70 (58.6%) were TOS-favorable. The 3-year OS, DSS and PFS for primary site TOS-favorable versus unfavorable were OS: 76.9% versus 37.4%; DSS: 78.1% versus 46.2%, PFS: 69.9% versus 41.3%, (log-rank test = 0.01, 0.03, 0.04; respectively). Additionally, patients with an overall assessment of TOS favorability demonstrated better survival outcomes compared with TOS-unfavorable patients (OS: 77.3% vs. 46.2%; DSS: 78.2% vs. 56.5%, PFS: 72.3% vs. 42.1%, log-rank test = 0.01, 0.04, 0.01; respectively). CONCLUSION: Patients with TOS-favorable HPV-negative early T-stage OPSCC have superior survival outcomes than TOS-unfavorable patients.

Metabolic pathway-based subtypes associate glycan biosynthesis and treatment response in head and neck cancer.

Head and Neck Squamous Cell Carcinoma (HNSCC) is a heterogeneous malignancy that remains a significant challenge in clinical management due to frequent treatment failures and pronounced therapy resistance. While metabolic dysregulation appears to be a critical factor in this scenario, comprehensive analyses of the metabolic HNSCC landscape and its impact on clinical outcomes are lacking. This study utilized transcriptomic data from four independent clinical cohorts to investigate metabolic heterogeneity in HNSCC and define metabolic pathway-based subtypes (MPS). In HPV-negative HNSCCs, MPS1 and MPS2 were identified, while MPS3 was enriched in HPV-positive cases. MPS classification was associated with clinical outcome post adjuvant radio(chemo)therapy, with MPS1 consistently exhibiting the highest risk of therapeutic failure. MPS1 was uniquely characterized by upregulation of glycan (particularly chondroitin/dermatan sulfate) metabolism genes. Immunohistochemistry and pilot mass spectrometry imaging analyses confirmed this at metabolite level. The histological context and single-cell RNA sequencing data identified the malignant cells as key contributors. Globally, MPS1 was distinguished by a unique transcriptomic landscape associated with increased disease aggressiveness, featuring motifs related to epithelial-mesenchymal transition, immune signaling, cancer stemness, tumor microenvironment assembly, and oncogenic signaling. This translated into a distinct histological appearance marked by extensive extracellular matrix remodeling, abundant spindle-shaped cancer-associated fibroblasts, and intimately intertwined populations of malignant and stromal cells. Proof-of-concept data from orthotopic xenotransplants replicated the MPS phenotypes on the histological and transcriptome levels. In summary, this study introduces a metabolic pathway-based classification of HNSCC, pinpointing glycan metabolism-enriched MPS1 as the most challenging subgroup that necessitates alternative therapeutic strategies.

Personalized Treatment of Recurrent, Metastatic Head and Neck Cancer Guided by Patient-Derived Xenograft Models.

Recurrent or metastatic head and neck squamous cell carcinoma (RMHNSCC) is associated with a poor prognosis and short survival duration. There is an urgent need to identify personalized predictors of drug response to guide the selection of the most effective therapy for each individual recurrence. We tested the feasibility of patient-derived xenografts (PDX) for guiding their RMHNSCC salvage treatment. Fresh tumor samples from eligible, consented patients were implanted into mice. Established tumors were expanded in mouse PDX cohorts to identify responses to candidate salvage drug treatments in parallel testing. Patients alive and suitable for chemotherapy were treated based on responses determined by PDX testing. Nine patient tumors were successfully engrafted in mice with an average time of 89.2±41.7 days. Four patients' PDX models underwent parallel drug testing. Two patients received PDX-guided therapy. In one of these patients, single agents of cetuximab and paclitaxel demonstrated the best responses in the PDX model, and this patient exhibited sequential partial responses to each drug, including a 17-month clinical response to cetuximab. The main limitation of PDX testing for RMHNSCC was the time delay in obtaining testing results. Despite this, parallel PDX testing may be feasible for a subset of patients and appears to correlate with clinical benefit.

A comparison of timing and patterns of treatment failure, and survival outcomes after progression between HPV+ and HPV- patients undergoing chemoradiation for oropharyngeal squamous cell carcinomas.

BACKGROUND: We aimed to analyze and compare the timing and patterns of treatment failure, and survival after progression between HPV-positive (HPV+) and HPV-negative (HPV-) patients undergoing chemoradiation for oropharyngeal squamous cell carcinomas (OPSCC). METHODS: A retrospective review was performed of all patients undergoing primary chemoradiation for OPSCC between 2008 and 2021. Demographic and clinical data were collected. Kaplan-Meier estimates for overall survival (OS), and time to recurrence/metastases (TTR) were compared using the log-rank test, with Cox regression used for multivariable modeling comparing HPV+ and HPV- patients. RESULTS: HPV- patients developed recurrence or metastases at earlier time points than HPV+ patients (8.8 vs. 15.2 months, p < 0.05), due to earlier local/locoregional recurrence and distant metastases, but not isolated regional recurrences. HPV- distant metastases exclusively occurred in a single organ, most commonly the lungs or bone, while HPV+ metastases frequently had multi-organ involvement in a wide variety of locations (p < 0.05). Once progression (recurrence/metastases) was diagnosed, HPV+ patients experienced superior survival to HPV- patients on univariate and multivariate analysis, largely due to improved outcomes after treatment of local/locoregional recurrences (p < 0.05). There were no differences in survival after isolated regional recurrences or distant metastases. CONCLUSION: HPV+ OPSCC patients relapse later compared to HPV- patients in local/locoregional and distant sites. HPV+ patients with local/locoregional recurrence experience superior survival after recurrence, which does not hold true for isolated regional recurrences or distant metastases. These data can be useful to inform prognosis and guide treatment decisions in patients with recurrent OPSCC.

Predicting the need for a replan in oropharyngeal cancer: A radiomic, clinical, and dosimetric model.

BACKGROUND: Patients with oropharyngeal cancer (OPC) treated with chemoradiation can experience weight loss and tumor shrinkage, altering the prescribed treatment. Treatment replanning ensures patients do not receive excessive doses to normal tissue. However, it is a time- and resource-intensive process, as it takes 1 to 2 weeks to acquire a new treatment plan, and during this time, overtreatment of normal tissues could lead to increased toxicities. Currently, there are limited prognostic factors to determine which patients will require a replan. There remains an unmet need for predictive models to assist in identifying patients who could benefit from the knowledge of a replan prior to treatment. PURPOSE: We aimed to develop and evaluate a CT-based radiomic model, integrating clinical and dosimetric information, to predict the need for a replan prior to treatment. METHODS: A dataset of patients (n = 315) with OPC treated with chemoradiation was used for this study. The dataset was split into independent training (n = 220) and testing (n = 95) datasets. Tumor volumes and organs at risk (OARs) were contoured on planning CT images. PyRadiomics was used to compute radiomic image features (n = 1218) on the original and filtered images from each of the primary tumor, nodal volumes, and ipsilateral and contralateral parotid glands. Nine clinical features and nine dose features extracted from the OARs were collected and those significantly (p < 0.05) associated with the need for a replan in the training dataset were used in a baseline model. Random forest feature selection was applied to select the optimal radiomic features to predict replanning. Logistic regression, Naïve Bayes, support vector machine, and random forest classifiers were built using the non-correlated selected radiomic, clinical, and dose features on the training dataset and performance was assessed in the testing dataset. The area under the curve (AUC) was used to assess the prognostic value. RESULTS: A total of 78 patients (25%) required a replan. Smoking status, nodal stage, base of tongue subsite, and larynx mean dose were found to be significantly associated with the need for a replan in the training dataset and incorporated into the baseline model, as well as into the combined models. Five predictive radiomic features were selected (one nodal volume, one primary tumor, two ipsilateral and one contralateral parotid gland). The baseline model comprised of clinical and dose features alone achieved an AUC of 0.66 [95% CI: 0.51-0.79] in the testing dataset. The random forest classifier was the top-performing radiomics model and achieved an AUC of 0.82 [0.75-0.89] in the training dataset and an AUC of 0.78 [0.68-0.87] in the testing dataset, which significantly outperformed the baseline model (p = 0.023, testing dataset). CONCLUSIONS: This is the first study to use radiomics from the primary tumor, nodal volumes, and parotid glands for the prediction of replanning for patients with OPC. Radiomic features augmented clinical and dose features for predicting the need for a replan in our testing dataset. Once validated, this model has the potential to assist physicians in identifying patients that may benefit from a replan, allowing for better resource allocation and reduced toxicities.

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.

HPV16 Intratypic Variants in Head and Neck Cancers: A North American Perspective.

Human papillomavirus (HPV) is the major causative agent for cervical and many head and neck cancers (HNCs). HPVs randomly acquire single nucleotide polymorphisms (SNPs) that may become established via positive selection. Within an HPV type, viral isolates differing by <2% in the L1 region are termed "variants" and classified based on combinations of SNPs. Studies in cervical cancer demonstrate clear differences between HPV16 intratypic variants in terms of persistence of infection, tumor histology, cancer risk, and death. Much less is known about the frequency of HPV16 variants in HNC, and their effects on clinical outcomes. We combined HPV16 positive (HPV16+) HNC samples from a local Southwestern Ontario, Canada cohort with those from the Cancer Genome Atlas to create a larger North American cohort of 149 cases with clinical data and determined the distribution of intratypic variants and their impact on clinical outcomes. Most isolates were lineage A, sublineage A1, or A2, with roughly half exhibiting the T350G polymorphism in E6. Univariable analysis identified significant differences between 350T and 350G intratypic variants in clinical T, N, and O staging, as well as disease-free survival. Multivariable analysis failed to identify any clinical factor as a statistically significant covariate for disease-free survival differences between 350T and 350G. Significant differences in several measures of B-cell mediated immune response were also observed between 350T and 350G intratypic variants. We suggest that HPV genetic variation may be associated with HNC clinical characteristics and may have prognostic value.