Extricating human tumour immune alterations from tissue inflammation.

Immunotherapies have achieved remarkable successes in the treatment of cancer, but major challenges remain1,2. An inherent weakness of current treatment approaches is that therapeutically targeted pathways are not restricted to tumours, but are also found in other tissue microenvironments, complicating treatment3,4. Despite great efforts to define inflammatory processes in the tumour microenvironment, the understanding of tumour-unique immune alterations is limited by a knowledge gap regarding the immune cell populations in inflamed human tissues. Here, in an effort to identify such tumour-enriched immune alterations, we used complementary single-cell analysis approaches to interrogate the immune infiltrate in human head and neck squamous cell carcinomas and site-matched non-malignant, inflamed tissues. Our analysis revealed a large overlap in the composition and phenotype of immune cells in tumour and inflamed tissues. Computational analysis identified tumour-enriched immune cell interactions, one of which yields a large population of regulatory T (Treg) cells that is highly enriched in the tumour and uniquely identified among all haematopoietically-derived cells in blood and tissue by co-expression of ICOS and IL-1 receptor type 1 (IL1R1). We provide evidence that these intratumoural IL1R1+ Treg cells had responded to antigen recently and demonstrate that they are clonally expanded with superior suppressive function compared with IL1R1- Treg cells. In addition to identifying extensive immunological congruence between inflamed tissues and tumours as well as tumour-specific changes with direct disease relevance, our work also provides a blueprint for extricating disease-specific changes from general inflammation-associated patterns.

Effect of the intratumoral microbiota on spatial and cellular heterogeneity in cancer.

The tumour-associated microbiota is an intrinsic component of the tumour microenvironment across human cancer types1,2. Intratumoral host-microbiota studies have so far largely relied on bulk tissue analysis1-3, which obscures the spatial distribution and localized effect of the microbiota within tumours. Here, by applying in situ spatial-profiling technologies4 and single-cell RNA sequencing5 to oral squamous cell carcinoma and colorectal cancer, we reveal spatial, cellular and molecular host-microbe interactions. We adapted 10x Visium spatial transcriptomics to determine the identity and in situ location of intratumoral microbial communities within patient tissues. Using GeoMx digital spatial profiling6, we show that bacterial communities populate microniches that are less vascularized, highly immuno­suppressive and associated with malignant cells with lower levels of Ki-67 as compared to bacteria-negative tumour regions. We developed a single-cell RNA-sequencing method that we name INVADEseq (invasion-adhesion-directed expression sequencing) and, by applying this to patient tumours, identify cell-associated bacteria and the host cells with which they interact, as well as uncovering alterations in transcriptional pathways that are involved in inflammation, metastasis, cell dormancy and DNA repair. Through functional studies, we show that cancer cells that are infected with bacteria invade their surrounding environment as single cells and recruit myeloid cells to bacterial regions. Collectively, our data reveal that the distribution of the microbiota within a tumour is not random; instead, it is highly organized in microniches with immune and epithelial cell functions that promote cancer progression.

Towards developing an intervention to support periodic health checks for adults with intellectual and developmental disabilities: Striving for health equity.

BACKGROUND: Although the Canadian Consensus Guidelines for Primary Care of Adults with Intellectual and Developmental Disabilities recommends conducting periodic health checks in primary care, uptake is lacking. This study seeks to understand factors influencing the conduct of periodic health checks and identify what needs to change to increase them. METHOD: Qualitative data from five stakeholder groups (adults with intellectual and developmental disabilities, primary care providers, administrative staff, family, disability support workers) was guided by the Behaviour Change Wheel and the Theoretical Domains Framework to identify barriers and 'what needs to change' to support periodic health checks. RESULTS: Stakeholders (n = 41) voiced multiple barriers. A total of 31 common and 2 unique themes were identified plus 33 items 'needing to change'. CONCLUSION: Despite barriers, stakeholders saw merit in periodic health checks as a preventative and equitable healthcare offering for adults with intellectual and developmental disabilities. Results will inform future intervention development steps.

Taking action towards climate-resilient, low-carbon, health systems: Perspectives from Canadian health leaders and healthcare professionals.

Climate change poses significant public health and health system challenges including increased demand for health services due to chronic and acute health impacts from vector-borne diseases, heat-related illness, and injury from severe weather. As climate change worsens, so do its effects on health systems such as increasing severity of weather extremes causing damage to healthcare infrastructure and interference with supply chains. Ironically, health sectors globally are significant contributors to climate change, generating an estimated 5% of global emissions. Achieving "net zero" health systems require large-scale change with shared decision-making to coordinate a pan-Canadian approach to creating climate-resilient and low-carbon healthcare. In this article, we discuss healthcare professionals' and health leaders' perceptions of responsibility for practicing and advocating for climate-resilient and low-carbon healthcare in Canada.

A case of endocrine mucin-producing sweat gland carcinoma with distant metastasis.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare cutaneous adnexal neoplasm typically arising on the face of older individuals, most commonly around the eyelids. Histopathologic features include a circumscribed proliferation of low-grade epithelioid cells with areas of cystic and cribriform growth, foci of intracytoplasmic and extracellular mucin, and coexpression of endocrine, neuroendocrine, and cytokeratin markers by immunohistochemistry. Given histopathologic and immunohistochemical similarities, EMPSGC is often likened to solid papillary carcinoma of the breast and endocrine ductal carcinoma in situ, and is thought by many to represent a forme fruste of mucinous carcinoma of the skin. To date, the vast majority of reported cases of EMPSGC have been described as having indolent behavior, with no cases of distant metastasis yet reported. Here we report a unique case of EMPSGC that recurred over several years following standard surgical excision and Mohs micrographic surgery, with subsequent metastasis to the parotid gland and axial skeleton.

An exploration of Canadian transitional care programs for older adults.

Transitional care programs are effective for improving patient outcomes upon discharge from acute care services and reducing the burden of healthcare costs; however, little is known about the types of transitional care programs for older adults across Canada. This exploratory study gathered an in-depth understanding of Canadian transitional care programs and described how each program functions to support older adults and family/friend caregivers. Nine key informants were interviewed about the development of transitional care programs within four Canadian provincial regions including Atlantic, Central, Prairie, and West Coast. Key facilitators and barriers influencing the development and long-term success of transitional care programs included program scope, program structure, continuity of care, funding, and health system infrastructure. Future research is required to identify how a broad range of transitional care programs operate and to disseminate knowledge with health leaders and decision-makers to ensure transitional care programs are embedded as essential health system services.

2b or not 2b? Shoulder function after level 2b neck dissection: A double-blind randomized controlled clinical trial.

BACKGROUND: Selective neck dissection (SND) is a mainstay of head and neck cancer treatment. A common sequela is shoulder syndrome from spinal accessory nerve (SAN) trauma. Extensive dissection in neck levels 2 and 5 leads to SAN dysfunction. However, it is not known whether limited level 2 dissection reduces SAN injury. The purpose of this double-blind randomized controlled trial was to determine whether omitting level 2b dissection would improve shoulder-related quality of life and function. METHODS: Patients with head and neck cancers undergoing surgery were randomized 1:1 to SND without level 2b dissection (group 1) or with it (group 2) on their dominant-hand side. Patients, caregivers, and assessors were blinded. The primary outcome was the change in the Neck Dissection Impairment Index (NDII) score after 6 months. An a priori calculation of the minimally important clinical difference in the NDII score was determined to establish a sample size of 15 patients per group (power = 0.8). Secondary outcomes included shoulder strength and range of motion (ROM) and SAN nerve conduction. The trial was registered at ClinicalTrials.gov (NCT00765791). RESULTS: Forty patients were enrolled, and 30 were included (15 per group). Six months after the surgery, group 2 demonstrated a significant median decrease in the NDII from the baseline (30 points) and in comparison with group 1, whose NDII dropped 17.5 points (P = .02). Shoulder ROM and SAN conduction demonstrated significant declines in group 2 (P ≤ .05). No adverse events occurred. CONCLUSIONS: Level 2b should be omitted in SND when this is oncologically safe and feasible. This allows for an optimal balance between function and cancer cure.

Surgical Options for Locally Advanced Oropharyngeal Cancer.

OPINION STATEMENT: Oropharyngeal squamous cell carcinoma (OPSCC) incidence rates have been steadily increasing over the past several decades, and this has been largely attributed to human papillomavirus (HPV)-related OPSCC. The rise of HPV-related OPSCC and the observed distinct survival advantage it offers compared to HPV-unrelated OPSCC have resulted in the development of a new staging system specifically for OPSCC in the eighth edition of the AJCC Staging Manual for head and neck cancer. The observations on HPV-related OPSCC and its prognostic implications have coincided with increasing utilization of transoral surgical approaches to oropharyngeal tumors, such as transoral laser microsurgery (TLM) and transoral robotic surgery (TORS). These approaches were once thought to only be applicable to patients with low T-stage OPSCC tumors; however, they are being increasingly utilized in locally advanced OPSCC cases as several studies have shown that both of these transoral approaches are oncologically sound alternatives to concurrent chemoradiation therapy (CCRT), which was previously the standard-of-choice treatment in patients with locally advanced disease. Moreover, these transoral approaches have displayed better long-term swallowing outcomes compared to CCRT, as severe dysphagia is often the most bothersome functional impairment to OPSCC survivors who have undergone CCRT. While open surgical approaches were previously not utilized in the locally advanced OPSCC setting due to the risk of severe surgical complications compared to the potential benefits of organ preservation with CCRT and comparable survival rates after either treatment regimen, these approaches are still reasonable options for select patients in the salvage surgery setting, as they allow for maximum exposure to the deep oropharyngeal anatomy. Data from multiple clinical trials evaluating the potential for TORS to de-escalate radiation dose or CCRT regimen in certain settings will inform clinical decision-making for OPSCC patients for the next decade and allow for more personalized treatments tailored to an individual patient's disease burden.

Transitional care programs for older adults moving from hospital to home in Canada: A systematic review of text and opinion.

BACKGROUND: Investing in transitional care programs is critical for ensuring continuity of health and coordinated care for older adults transitioning across health settings. However, literature delineating the scope of transitional care programs across Canada is limited. The aim of this systematic review of text and opinion is to characterize Canadian transitional care programs for older adults transitioning from hospital to home. METHODS: Following JBI guidelines for systematic review of text and opinion, we conducted a search of Canadian grey literature sources published online between 2016 to 2023. A 3-phase search was undertaken for: 1) Canadian databases and organizational websites; 2) advanced Google search of national sources and news media reports; and 3) advanced Google search of provincial/territorial sources. Two reviewers independently screened sources for eligibility against inclusion criteria. Data were extracted by one reviewer and verified by a second. Textual data were extracted from multiple sources to characterize each transitional care program. RESULTS: Grey literature search produced a total of 17,092 text and opinion sources, identifying 119 transitional care programs in Canada. Model of care was a key characteristic defining the design and delivery of transitional care programs within community (n = 42), hospital (n = 45), and facility-based (n = 32) settings. Programs were characterized by goal, population and eligibility, setting and length of program, intervention and services, and healthcare team members. Patient, caregiver, and health system outcomes were reported for 18 programs. The province of Ontario has the most transitional care programs (n = 84) and reported outcomes, followed by British Columbia (n = 10). CONCLUSIONS: Characterizing transitional care programs is important for informing health services planning and scaling up of transitional care program models across Canada. Recognizing transitional care programs as a core health service is critical to meet the health care needs of older adults at the right time and place. TRIAL REGISTRATION: PROSPERO ID 298821.

Cueing and gait improvement among people with Parkinson's disease: a meta-analysis.

OBJECTIVE: To compare the relative efficacy of visual versus auditory cueing on gait among individuals with Parkinson's disease (PD). DATA SOURCES: A systematic search was completed up to September 2011, using the following databases: EMBASE, Scopus, Medline, CINAHL, and PubMed. STUDY SELECTION: Four authors searched the databases using the following terms: Parkinson's disease (including abbreviations), gait, cadence, step, pace, cueing, cues, and prompt. All studies that evaluated the effect of cueing on gait in PD were selected by consensus of 2 pairs of authors who reviewed the titles and abstracts. Each pair of authors then applied the inclusion and exclusion criteria to each study, and 25 articles were chosen. Inclusion criteria were cueing studies that reported pre- and postoutcome measures of gait parameters. Exclusion criteria were lack of data and studies that evaluated gait aids. DATA EXTRACTION: Gait measures of cadence, stride length, and velocity, before and after cueing, were collected from each study. If data were represented in graphs, a pair of authors extracted the data points individually, then compared and averaged values. DATA SYNTHESIS: The data were synthesized using a meta-analysis based on cue type. Auditory cueing demonstrated significant improvement of cadence (Hedge g=.556; 95% confidence interval [CI], .291-.893), stride length (Hedge g=.497; 95% CI, .289-.696), and velocity (Hedge g=.544; 95% CI, .294-.795). In contrast, visual cueing significantly improved stride length only (Hedge g=.554; 95% CI, .072-1.036). CONCLUSIONS: The findings suggest that auditory cueing is more effective for treating gait disorders in PD. Further research is needed to determine the optimum auditory cueing strategy for gait improvements.

Transitional care programs in Canada for older adults transitioning from hospital to home: protocol for a systematic review of text and opinion.

OBJECTIVE: The objective of this systematic review is to identify what transitional care programs exist across Canada, including the characteristics and outcomes of these programs. INTRODUCTION: There is growing evidence of the benefits of transitional care programs to support older adults moving from hospital to home. However, there is limited literature identifying the types of transitional care programs that exist internationally and little evidence available within Canada. INCLUSION CRITERIA: Sources of gray literature published from 2016 that focus on older adults receiving services from transitional care programs to move from hospital to home in Canada will be considered for inclusion. Sources of gray literature will be excluded if interventions are targeted at adults younger than 65 years, Indigenous adults younger than 55 years, or if the primary discharge destination is not an independent community dwelling. Interventions designed for older adults waiting in hospital for long-term care placement will also be excluded from this review. METHODS: An initial limited search of Canadian national gray literature resources will be undertaken, followed by an advanced Google search of Canadian resources and news media reports. Lastly, an advanced search of Google for all 10 provinces and 3 territories will be undertaken to target examples of local transitional care programs that may not be found through a national search, such as local pilot projects, health region-specific programs, and provincial organizations. All identified sources will be retrieved and full text review of selected citations assessed in detail by 2 independent reviewers. Data about the characteristics and outcomes of transitional care programs and results will be extracted and synthesized, with a meta-aggregation approach for grading according to JBI ConQual method. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42022298821.

Integrating health geography and behavioral economic principles to strengthen context-specific behavior change interventions.

The long-term economic viability of modern health care systems is uncertain, in part due to costs of health care at the end of life and increasing health care utilization associated with an increasing population prevalence of multiple chronic diseases. Control of health care spending and sustaining delivery of health care services will require strategic investments in prevention to reduce the risk of disease and its complications over an individual's life course. Behavior change interventions aimed at reducing a range of harmful and risky health-related behaviors including smoking, physical inactivity, excess alcohol consumption, and excess weight, are one approach that has proven effective at reducing risk and preventing chronic disease. However, large-scale efforts to reduce population-level chronic diseases are challenging and have not been very successful at reducing the burden of chronic diseases. A new approach is required to identify when, where, and how to intervene to disrupt patterns of behavior associated with high-risk factors using context-specific interventions that can be scaled. This paper introduces the need to integrate theoretical and methodological principles of health geography and behavioral economics as opportunities to strengthen behavior change interventions for the prevention of chronic diseases. We discuss how health geography and behavioral economics can be applied to expand existing behavior change frameworks and how behavior change interventions can be strengthened by characterizing contexts of time and activity space.

Behavior change interventions are challenged by lack of information about the contexts influencing decisions patients make as part of their daily routine such as when, where, and how health behaviors occur. A new approach is required to strengthen behavior change interventions by integrating contexts of time and activity space so that strategies can be scaled across populations to influence how individuals make decisions about improving their health behaviors. Incorporating ideas from health geography and behavioral economics into the design of behavior change interventions provides an opportunity to collect and investigate individual-level health information characterizing contexts of individuals' activities across space, connections to place, time management, and patterns in behavior over time. By visualizing and characterizing key spatiotemporal contexts about an individual's day-to-day routine, insight can be gained about where and for how long activities occur and what opportunities exist for adapting day-to-day routines. This paper will discuss how theory from health geography could be applied to understand contexts influencing behaviors and how spatiotemporal information could be applied for the purpose of tailoring behavioral economic strategies to strengthen the design of behavior change interventions.

Neutrophil to lymphocyte ratio and peripheral blood biomarkers correlate with survival outcomes but not response among head and neck and salivary cancer treated with pembrolizumab and vorinostat.

BACKGROUND: Associations between peripheral blood biomarkers and oncologic outcomes were explored in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HN) and salivary gland cancer (SGC) treated with pembrolizumab and vorinostat on a phase II trial (NCT02538510). EXPERIMENTAL DESIGN: Twenty-five HN and 25 SGCs were treated with pembrolizumab and vorinostat. Baseline peripheral blood was available in 21 HN and 20 SGCs and evaluated for associations with grade ≥3 adverse events (G ≥ 3AE) by CTCAEv4, objective response rate (ORR), overall survival (OS), and progression-free survival (PFS). RESULTS: Higher pretreatment neutrophil-to-lymphocyte ratio (NLR) and neutrophils, as well as lower pretreatment lymphocytes and T helper cells correlated with worse OS and PFS. Higher NLR further predicted increased rates of G ≥ 3AEs. No correlations with ORR were observed. CONCLUSIONS: In a prospectively evaluated cohort of HN and SGCs treated with pembrolizumab and vorinostat, we observed novel associations between peripheral blood biomarkers and oncologic outcomes and toxicities.

Peripheral lymphocytes and lactate dehydrogenase correlate with response and survival in head and neck cancers treated with immune checkpoint inhibitors.

BACKGROUND: Little is known regarding associations between peripheral blood biomarkers (PBBMs) and survival, response, and toxicity in recurrent/metastatic head and neck squamous cell carcinomas (R/M HNSCC) treated with immune checkpoint inhibitors (ICIs). METHODS: In this single-institution retrospective cohort study, a dataset of patients with R/M HNSCC treated with ICIs between 08/2012-03/2021 was established, including demographic and clinicopathologic characteristics. Pretreatment PBBMs were collected and evaluated for associations with grade ≥3 adverse events (G ≥ 3AE) by CTCAEv5, objective response (ORR) by RECIST 1.1, overall survival (OS), and progression-free survival (PFS). Multivariable models for each outcome were created using elastic net variable selection. RESULTS: Our study included 186 patients, with 51 (27%) demonstrating complete or partial response to immunotherapy. Multivariable models adjusted for ECOG performance status (PS), p16, and smoking demonstrated that pretreatment higher LDH and absolute neutrophils, as well as lower percent lymphocytes correlated with worse OS and PFS. Higher LDH and lower % lymphocytes also correlated with worse ORR. CONCLUSIONS: In the largest study to date examining PBBMs in ICI-treated R/M HNSCCs, our variable selection method revealed PBBMs prognostic for survival and response to immunotherapy. These biomarkers warrant further investigation in a prospective study along with validation with CPS biomarker.

Radiation therapy for low- and high-risk perineural invasion in head and neck cutaneous squamous cell carcinoma: Clinical outcomes and patterns of failure.

BACKGROUND: Perineural invasion (PNI) in head and neck squamous cell carcinoma (HNSCC) portends poor prognosis. Extent of treatment of nerve pathways with varying degrees of PNI and patterns of failure following elective neural radiotherapy (RT) remain unclear. METHODS: Retrospective review of HNSCC patients with high-risk (clinical/gross, large-nerve, extensive) or low-risk (microscopic/focal) PNI who underwent curative-intent treatment from 2010 to 2021. RESULTS: Forty-four patients (mean follow-up 22 months; 59% high-risk, 41% low-risk PNI) were included. Recurrence following definitive treatment occurred in 31% high-risk and 17% low-risk PNI patients. Among high-risk patients, 69% underwent surgery with post-operative RT and 46% underwent elective neural RT. Local control (83% low-risk vs. 75% high-risk), disease-free, and overall survival did not differ between groups. CONCLUSIONS: High local control rates were achieved in high-risk PNI patients treated with adjuvant or primary RT, including treatment of both involved and uninvolved, communicating cranial nerves, with few failures in electively treated regions.

E-prescribing and medication safety in community settings: A rapid scoping review.

Background: Medication prescribing is essential for the treatment, curing, maintenance, and/or prevention of an illness and disease, however, medication errors remain common. Common errors including prescribing and administration, pose significant risk to patients. Electronic prescribing (e-prescribing) is one intervention used to enhance the safety and quality of prescribing by decreasing medication errors and reducing harm. E-prescribing in community-based settings has not been extensively examined. Objective: To map and characterize the current evidence on e-prescribing and medication safety in community pharmacy settings. Methods: We conducted a rapid scoping review of quantitative, qualitative, and mixed methods studies reporting on e-prescribing and medication safety. MEDLINE All (OVID), Embase (Elsevier), CINAHL Full Text (EBSCOHost), and Scopus (Elsevier) databases were searched December 2022 using keywords and MeSH terms related to e-prescribing, medication safety, efficiency, and uptake. Articles were imported to Covidence and screened by two reviewers. Data were extracted by a single reviewer and verified by a second reviewer using a standardized data extraction form. Findings are reported in accordance with JBI Manual for Evidence Synthesis following thematic analysis to narratively describe results. Results: Thirty-five studies were included in this review. Most studies were quantitative (n = 22), non-experimental study designs (n = 16) and were conducted in the United States (n = 18). Half of included studies reported physicians as the prescriber (n = 18), while the remaining reported a mix of nurse practitioners, pharmacists, and physician assistants (n = 6). Studies reported on types of errors, including prescription errors (n = 20), medication safety errors (n = 9), dispensing errors (n = 2), and administration errors (n = 1). Few studies examined patient health outcomes, such as adverse drug events (n = 5). Conclusions: Findings indicate that most research is descriptive in nature and focused primarily on rates of prescription errors. Further research, such as experimental, implementation, and evaluation mixed-methods research, is needed to investigate the effects of e-prescribing on reducing error rates and improving patient and health system outcomes.

Hospital to Home: Supporting the Transition From Hospital to Home for Older Adults.

BACKGROUND: An increasing proportion of older adults experience avoidable hospitalizations, and some are potentially entering long-term care homes earlier and often unnecessarily. Older adults often lack adequate support to transition from hospital to home, without access to appropriate health services when they are needed in the community and resources to live safely at home. PURPOSE: This study collaborated with an existing enhanced home care program called Home Again in Nova Scotia, to identify factors that contribute to older adult patients being assessed as requiring long-term care when they could potentially return home with enhanced supports. METHODS: Using a case study design, this study examined in-depth experiences of multiple stakeholders, from December 2019 to February 2020, through analysis of nine interviews for three focal patient cases including older adult patients, their family or friend caregivers, and healthcare professionals. RESULTS: Findings indicate home care services for older adults are being sought too late, after hospital readmission, or a rapid decline in health status when family caregivers are already experiencing caregiver burnout. Limitations in home care services led to barriers preventing family caregivers from continuing to care for older adults at home. CONCLUSIONS: This study contributes knowledge about gaps within home care and transitional care services, highlighting the importance of investing in additional home care services for rehabilitation and prevention of rapidly deteriorating health.

Factors Associated with Falls in Canadian Long Term Care Homes: a Retrospective Cohort Study.

Background: Half of Canadians living in long-term care (LTC) homes will fall each year resulting in consequences to independence, quality of life, and health. The objective in this study was to analyze factors that contribute to, or are protective against, falls in Canadian LTC homes. Methods: We analyzed of a retrospective cohort of a stratified random sample of Canadian LTC homes in Western Canada from 2011-2017. We accessed variables from the RAI-MDS 2.0 to assess the association of the dependent variable "fall within the last 31-180 days" with multiple independent factors, using generalized estimating equation models. Results: A total of 28,878 LTC residents were analyzed. Factors found to increase the odds of falling were other fractures (OR 3.64 [95% confidence interval; CI 3.27, 4.05]), hip fractures (OR 3.58 [3.27, 3.93]), moderately impaired cognitive skills (OR 2.45 [2.28, 2.64]), partial support to balance standing (OR 2.44 [2.30, 2.57]), wandering (OR 2.31 [2.18, 2.44]). Conclusion: A range of factors identified were associated with falls for people living in LTC homes. Individual physical ability represented the largest group of independent factors contributing to falls. Residents who experience any fracture or an acute change in behaviour, mobility, or activities of daily living (ADL) should be considered at increased risk of falls.

Oncologic outcomes of salvage surgery and immune checkpoint inhibitor therapy in recurrent head and neck squamous cell carcinoma: A single-institution retrospective study.

BACKGROUND: Survival outcomes in recurrent head and neck squamous cell carcinoma (HNSCC) are poor. This study aimed to compare survival outcomes between salvage surgery and immunotherapy in patients with recurrent advanced HNSCC. METHODS: Patients with advanced stage (stage III or IV) recurrent HNSCC following treatment with platinum-based chemotherapy were included. Survival was estimated using the Kaplan-Meier method, and Cox regression was used for multivariate logistic regression. RESULTS: Two-year overall survival after salvage surgery was 68.6% and after immunotherapy patients was 24.6%. Multivariate logistic regression showed that salvage surgery was associated with improved survival without statistical significance (hazard ratio [HR] 0.12, p = 0.25). Subgroup analysis of patients with oral cavity/oropharyngeal cancer noted improved survival with salvage surgery over immunotherapy (HR 0.006, p = 0.01) and decreased survival with neutrophil-to-lymphocyte ratio (NLR) > 5 (HR 6.4, p = 0.02). CONCLUSION: Our retrospective single-institutional data suggest that resectable advanced stage recurrent HNSCC may have improved survival with salvage surgery in appropriately selected patients, but larger prospective studies are required.

Trends in Positive Surgical Margins in cT1-T2 Oral Cavity Squamous Cell Carcinoma.

OBJECTIVES/HYPOTHESIS: To evaluate trends in contemporary positive surgical margin incidence in cT1-T2 oral cavity squamous cell carcinoma and to evaluate factors associated with surgical margin status. STUDY DESIGN: Retrospective analysis of large dataset. METHODS: Retrospective analysis of the National Cancer Database. RESULTS: Between 2004 and 2016, 39,818 patients with cT1 or cT2 oral cavity squamous cell carcinoma received primary curative-intent surgery. Positive surgical margins were present in 7.95% of patients, and univariable adjusted probability of positive surgical margins over the study period declined by 1% per year (odds ratio [OR], 0.99; 95% confidence interval [CI], 0.98-1.0; P = .049). Multivariable regression revealed the annual rate of positive surgical margins declined significantly (OR, 0.95 per year; 95% CI, 0.92-0.97; P < .001). Factors associated with increased odds of positive surgical margins included cT2 disease, subsite, understaged disease, lymphovascular invasion, tumor grade, and positive lymph nodes. Race and socioeconomic status were not associated with surgical margin status. Treatment at an academic center was associated with increased time to definitive surgery (median 35 days IQR 22-50 vs. median 27 days IQR 14-42; P < .001) and a 20% reduction in positive surgical margin rate (OR, 0.80; 95% CI, 0.71-0.90; P < .001). Treatment at high-volume centers was less likely to be associated with positive surgical margins (OR, 0.85; 95% CI, 0.74-0.98; P = .02). CONCLUSION: Surgical subsite, clinical T and N category, presence of lymphovascular invasion, and histologic grade were independent predictors of positive surgical margins. Patients are increasingly being treated at high-volume and academic centers. Overall, the rate of positive surgical margins in cT1-T2 oral cavity squamous cell carcinoma is decreasing. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:1962-1970, 2022.