Citations

AbstractObjectiveInternal nasal valve dysfunction is a prevalent cause of nasal obstruction. This systematic review, along with a Meta‐analysis, evaluated the efficacy of temperature‐controlled radiofrequency device (RFD) treatment in alleviating nasal obstruction by rectifying nasal valve collapse.Data SourcesA comprehensive review of studies retrieved from PubMed, SCOPUS, Embase, Web of Science, and Cochrane databases (up to December 2022) was conducted.Review MethodsWe included studies that evaluated the quality of life and nasal obstruction scores before and after RFD treatment. In addition, sham‐controlled studies were analyzed.ResultsIn total, 451 patients across 8 studies were included in the analysis. Patients who underwent RFD treatment reported a significantly enhanced quality of life 24 months after treatment compared to pretreatment scores. The rates of clinically improved states and positive responses regarding quality of life after treatment were 82% and 91%, respectively. Moreover, the disease‐specific quality of life, as assessed by the Nasal Obstruction Symptom Evaluation score, significantly improved.ConclusionRFD may help improve nasal obstruction symptoms. Further randomized clinical studies on larger cohorts are essential to substantiate its efficacy in enhancing nasal valve function.

Abstract Background Sinonasal neoplasms, whether benign and malignant, pose a significant challenge to clinicians and represent a model area for multidisciplinary collaboration in order to optimize patient care. The International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors (ICSNT) aims to summarize the best available evidence and presents 48 thematic and histopathology‐based topics spanning the field. Methods In accordance with prior International Consensus Statement on Allergy and Rhinology documents, ICSNT assigned each topic as an Evidence‐Based Review with Recommendations, Evidence‐Based Review, and Literature Review based on the level of evidence. An international group of multidisciplinary author teams were assembled for the topic reviews using the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses format, and completed sections underwent a thorough and iterative consensus‐building process. The final document underwent rigorous synthesis and review prior to publication. Results The ICSNT document consists of four major sections: general principles, benign neoplasms and lesions, malignant neoplasms, and quality of life and surveillance. It covers 48 conceptual and/or histopathology‐based topics relevant to sinonasal neoplasms and masses. Topics with a high level of evidence provided specific recommendations, while other areas summarized the current state of evidence. A final section highlights research opportunities and future directions, contributing to advancing knowledge and community intervention. Conclusion As an embodiment of the multidisciplinary and collaborative model of care in sinonasal neoplasms and masses, ICSNT was designed as a comprehensive, international, and multidisciplinary collaborative endeavor. Its primary objective is to summarize the existing evidence in the field of sinonasal neoplasms and masses.

AbstractBackgroundThe impact of sinonasal malignancies (SNMs) on quality of life (QOL) at presentation is poorly understood. The Sinonasal Outcome Test (SNOT‐22) and University of Washington Quality of Life (UWQOL) are validated QOL instruments with distinctive subdomains. This study aims to identify factors impacting pretreatment QOL in SNM patients to personalize multidisciplinary management and counseling.MethodsPatients with previously untreated SNMs were prospectively enrolled (2015–2022) in a multicenter observational study. Baseline pretreatment QOL instruments (SNOT‐22, UWQOL) were obtained along with demographics, comorbidities, histopathology/staging, tumor involvement, and symptoms. Multivariable regression models identified factors associated with reduced baseline QOL.ResultsAmong 204 patients, presenting baseline QOL was significantly reduced. Multivariable regression showed worse total SNOT‐22 QOL in patients with skull base erosion (p = 0.02). SNOT‐rhinologic QOL was worse in women (p = 0.009), patients with epistaxis (p = 0.036), and industrial exposure (p = 0.005). SNOT extranasal QOL was worse in patients with industrial exposure (p = 0.016); worse SNOT ear/facial QOL if perineural invasion (PNI) (p = 0.027). Squamous cell carcinoma pathology (p = 0.037), palate involvement (p = 0.012), and pain (p = 0.017) were associated with worse SNOT sleep QOL scores. SNOT psychological subdomain scores were significantly worse in patients with palate lesions (p = 0.022), skull base erosion (p = 0.025), and T1 staging (p = 0.023). Low QOL was more likely in the presence of PNI on UW health (p = 0.019) and orbital erosion on UW overall (p = 0.03). UW social QOL was worse if palatal involvement (p = 0.023) or PNI (p = 0.005).ConclusionsOur findings demonstrate a negative impact on baseline QOL in patients with SNMs and suggest sex‐specific and symptom‐related lower QOL scores, with minimal histopathology association. Anatomical tumor involvement may be more reflective of QOL than T‐staging, as orbital and skull base erosion, PNI, and palate lesions are significantly associated with reduced baseline QOL.

Abstract In the pivotal study ECHELON-1, brentuximab vedotin (BV), doxorubicin, vinblastine, and dacarbazine (A + AVD) demonstrated superior efficacy compared with bleomycin + AVD for the treatment of advanced-stage classic Hodgkin lymphoma (cHL). However, there are minimal available data regarding the frequency of dose reductions or omission of BV during curative therapy and the potential impact on patient outcomes. In a real-world analysis, we retrospectively reviewed the characteristics and outcomes of 179 patients with stage III or IV cHL treated with frontline A + AVD from January 2010 to April 2022. Treatment consisted of up to 1.2 mg/kg of BV and standard dose AVD IV on days 1 and 15 of each 28-day cycle for up to 6 cycles. At the time of treatment, the median patient age was 37 years, and a high-risk International Prognostic Score was observed in 46% of patients. Overall, 91% of patients received 6 cycles of AVD; 55% of patients did not receive the intended cumulative dose of BV (CDB); 28% of patients received two-thirds or less than the planned CDB. At a median follow-up time of 27.4 months (95% confidence interval [CI], 24.8-29), the median progression-free survival (PFS) was not reached, and the 12-month PFS was 90.3% (95% CI, 85.9-95.0). The impact of CDB on PFS was not significant (P = .15), nor was high CDB significantly associated with increased adverse events. In real-world experience, A + AVD is a highly effective treatment for patients with advanced-stage cHL, including for patients with prominent dose reductions of BV.

ImportanceSystematic data on the association between anticancer therapies and thromboembolic events (TEEs) in patients with COVID-19 are lacking.ObjectiveTo assess the association between anticancer therapy exposure within 3 months prior to COVID-19 and TEEs following COVID-19 diagnosis in patients with cancer.Design, Setting, and ParticipantsThis registry-based retrospective cohort study included patients who were hospitalized and had active cancer and laboratory-confirmed SARS-CoV-2 infection. Data were accrued from March 2020 to December 2021 and analyzed from December 2021 to October 2022.ExposureTreatments of interest (TOIs) (endocrine therapy, vascular endothelial growth factor inhibitors/tyrosine kinase inhibitors [VEGFis/TKIs], immunomodulators [IMiDs], immune checkpoint inhibitors [ICIs], chemotherapy) vs reference (no systemic therapy) in 3 months prior to COVID-19.Main Outcomes and MeasuresMain outcomes were (1) venous thromboembolism (VTE) and (2) arterial thromboembolism (ATE). Secondary outcome was severity of COVID-19 (rates of intensive care unit admission, mechanical ventilation, 30-day all-cause mortality following TEEs in TOI vs reference group) at 30-day follow-up.ResultsOf 4988 hospitalized patients with cancer (median [IQR] age, 69 [59-78] years; 2608 [52%] male), 1869 had received 1 or more TOIs. Incidence of VTE was higher in all TOI groups: endocrine therapy, 7%; VEGFis/TKIs, 10%; IMiDs, 8%; ICIs, 12%; and chemotherapy, 10%, compared with patients not receiving systemic therapies (6%). In multivariable log-binomial regression analyses, relative risk of VTE (adjusted risk ratio [aRR], 1.33; 95% CI, 1.04-1.69) but not ATE (aRR, 0.81; 95% CI, 0.56-1.16) was significantly higher in those exposed to all TOIs pooled together vs those with no exposure. Among individual drugs, ICIs were significantly associated with VTE (aRR, 1.45; 95% CI, 1.01-2.07). Also noted were significant associations between VTE and active and progressing cancer (aRR, 1.43; 95% CI, 1.01-2.03), history of VTE (aRR, 3.10; 95% CI, 2.38-4.04), and high-risk site of cancer (aRR, 1.42; 95% CI, 1.14-1.75). Black patients had a higher risk of TEEs (aRR, 1.24; 95% CI, 1.03-1.50) than White patients. Patients with TEEs had high intensive care unit admission (46%) and mechanical ventilation (31%) rates. Relative risk of death in patients with TEEs was higher in those exposed to TOIs vs not (aRR, 1.12; 95% CI, 0.91-1.38) and was significantly associated with poor performance status (aRR, 1.77; 95% CI, 1.30-2.40) and active/progressing cancer (aRR, 1.55; 95% CI, 1.13-2.13).Conclusions and RelevanceIn this cohort study, relative risk of developing VTE was high among patients receiving TOIs and varied by the type of therapy, underlying risk factors, and demographics, such as race and ethnicity. These findings highlight the need for close monitoring and perhaps personalized thromboprophylaxis to prevent morbidity and mortality associated with COVID-19–related thromboembolism in patients with cancer.

ImportanceCurrent olfactory neuroblastoma (ONB) staging systems inadequately delineate locally advanced tumors, do not incorporate tumor grade, and poorly estimate survival and recurrence.ObjectiveThe primary aims of this study were to (1) examine the clinical covariates associated with survival and recurrence of ONB in a modern-era multicenter cohort and (2) incorporate Hyams tumor grade into existing staging systems to assess its ability to estimate survival and recurrence.Design, Setting, and ParticipantsThis retrospective, multicenter, case-control study included patients with ONB who underwent treatment between January 1, 2005, and December 31, 2021, at 9 North American academic medical centers.InterventionStandard-of-care ONB treatment.Main Outcome and MeasuresThe main outcomes were overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) as C statistics for model prediction.ResultsA total of 256 patients with ONB (mean [SD] age, 52.0 [15.6] years; 115 female [44.9%]; 141 male [55.1%]) were included. The 5-year rate for OS was 83.5% (95% CI, 78.3%-89.1%); for DFS, 70.8% (95% CI, 64.3%-78.0%); and for DSS, 94.1% (95% CI, 90.5%-97.8%). On multivariable analysis, age, American Joint Committee on Cancer (AJCC) stage, involvement of bilateral maxillary sinuses, and positive margins were associated with OS. Only AJCC stage was associated with DFS. Only N stage was associated with DSS. When assessing the ability of staging systems to estimate OS, the best-performing model was the novel modification of the Dulguerov system (C statistic, 0.66; 95% CI, 0.59-0.76), and the Kadish system performed most poorly (C statistic, 0.57; 95% CI, 0.50-0.63). Regarding estimation of DFS, the modified Kadish system performed most poorly (C statistic, 0.55; 95% CI, 0.51-0.66), while the novel modification of the AJCC system performed the best (C statistic, 0.70; 95% CI, 0.66-0.80). Regarding estimation of DSS, the modified Kadish system was the best-performing model (C statistic, 0.79; 95% CI, 0.70-0.94), and the unmodified Kadish performed the worst (C statistic, 0.56; 95% CI, 0.51-0.68). The ability for novel ONB staging systems to estimate disease progression across stages was also assessed. In the novel Kadish staging system, patients with stage VI disease were approximately 7 times as likely to experience disease progression as patients with stage I disease (hazard ratio [HR], 6.84; 95% CI, 1.60-29.20). Results were similar for the novel modified Kadish system (HR, 8.99; 95% CI, 1.62-49.85) and the novel Dulguerov system (HR, 6.86; 95% CI, 2.74-17.18).Conclusions and RelevanceThe study findings indicate that 5-year OS for ONB is favorable and that incorporation of Hyams grade into traditional ONB staging systems is associated with improved estimation of disease progression.

Background: Most strokes and cardiovascular diseases (CVDs) are potentially preventable if their risk factors are identified and well controlled. Digital platforms, such as the PreventS-MD web app (PreventS-MD) may aid health care professionals (HCPs) in assessing and managing risk factors and promoting lifestyle changes for their patients. Methods: This is a mixed-methods cross-sectional two-phase survey using a largely positivist (quantitative and qualitative) framework. During Phase 1, a prototype of PreventS-MD was tested internationally by 59 of 69 consenting HCPs of different backgrounds, age, sex, working experience, and specialties using hypothetical data. Collected comments/suggestions from the study HCPs in Phase 1 were reviewed and implemented. In Phase 2, a near-final version of PreventS-MD was developed and tested by 58 of 72 consenting HCPs using both hypothetical and real patient (n = 10) data. Qualitative semi-structured interviews with real patients (n = 10) were conducted, and 1 month adherence to the preventive recommendations was assessed by self-reporting. The four System Usability Scale (SUS) groups of scores (0–50 unacceptable; 51–68 poor; 68–80.3 good; >80.3 excellent) were used to determine usability of PreventS-MD. Findings: Ninety-nine HCPs from 27 countries (45% from low- to middle-income countries) participated in the study, and out of them, 10 HCPs were involved in the development of PreventS before the study, and therefore were not involved in the survey. Of the remaining 89 HCPs, 69 consented to the first phase of the survey, and 59 of them completed the first phase of the survey (response rate 86%), and 58 completed the second phase of the survey (response rate 84%). The SUS scores supported good usability of the prototype (mean score = 80.2; 95% CI [77.0–84.0]) and excellent usability of the final version of PreventS-MD (mean score = 81.7; 95% CI [79.1–84.3]) in the field. Scores were not affected by the age, sex, working experience, or specialty of the HCPs. One-month follow-up of the patients confirmed the high level of satisfaction/acceptability of PreventS-MD and (100%) adherence to the recommendations. Interpretation: The PreventS-MD web app has a high level of usability, feasibility, and satisfaction by HCPs and individuals at risk of stroke/CVD. Individuals at risk of stroke/CVD demonstrated a high level of confidence and motivation in following and adhering to preventive recommendations generated by PreventS-MD.

AbstractBackgroundPrimary cutaneous B‐cell lymphoma (PCBCL) is a group of B‐cell lymphomas of the skin containing primary cutaneous follicle centre lymphoma (PCFCL) and marginal zone B‐cell lymphoma/lymphoproliferative disorder (PCMZL), which are indolent, and diffuse large B‐cell lymphoma, leg type (PCDLBCL‐LT), which is aggressive.ObjectivesTo evaluate treatment outcomes between PCBCL subtypes after treatment with rituximab and to compare the efficacy of intralesional against systemic rituximab in indolent subtypes.MethodsA search for patients diagnosed with PCBCL and treated with rituximab (systemic or intralesional) across all Mayo Clinic sites was performed, yielding 39 patients.ResultsEight patients had PCFCL (six treated intralesionally and two systemically), 11 had PCMZL (four intralesional, eight systemic with one dual‐treated) and 20 had PCDLBCL‐LT (all systemic). The average age at diagnosis was 62.1 years (SD = 15.1), with average follow‐up of 1852.6 days (SD = 1473.2). 69.2% of all patients treated with any form of rituximab experienced a complete response (100% PCFCL, 81.8% PCMZL and 50% PCDLBCL‐LT). When comparing all three subtypes, a significant difference was seen in overall treatment response (p = 0.022), and progressive disease rates (p = 0.015), but not in retreatment with rituximab (p = 0.440), time to retreatment (p = 0.757), recurrence (p = 0.907) or survival (p = 0.093). In the indolent subtypes, no difference in overall treatment response (p = 1.000), progressive disease rates (p = 1.000), recurrence (p = 0.650), rituximab retreatment (p = 0.650) or time to retreatment (p = 0.724) was observed.ConclusionsThis study suggests that rituximab, as systemic therapy and intralesional therapy, is effective in the management of PCBCL, and that intralesional therapy should be considered before more aggressive therapy in indolent disease.

Abstract Differences in clonality, genomic and epigenetic alterations are known to occur between primary Glioblastoma (pGBM) and recurrent (rGBM), but this has been insufficient to yield a promising therapeutic approach. Recent studies show that the GBM tumor microenvironment (TME), composed of reactive glial cells, microglial subtypes, neuronal activity, myeloid cells, lymphocytes, etc., plays a crucial role in the invasiveness and evolution of the glioma cells. Nevertheless, how the spatial architecture and interplay among these cells facilitates GBM resurgence is largely unknown. To this point, we developed a pipeline for characterizing the TME changes using single nucleus and spatial transcriptomics (ST). We retrospectively collected matched, fresh-frozen, IDH-wildtype pGBM and rGBM samples (n=14, 7 patients) from the Mayo Clinic Neuroscience Biobank. Single nucleus RNA sequencing was performed using the 10x Chromium platform. Matched FFPE blocks from 8 samples were collected from the Mayo Clinic pathology department for 4 of the 7 patients. A region of interest was identified from the corresponding histopathology slide by a pathologist, avoiding areas of necrosis and hemorrhage. The region was collected from the block using a 5mm biopsy punch. The tissue was re-paraffinized, and a 5µm thick section was used to perform ST with the 10x Visium for FFPE platform. We performed transcriptomic and image texture-based clustering of capture dots along with differential gene expression analysis. Based on gene expression, we identified and characterized conserved regions across samples. We used single nucleus data to infer cell composition. Spatial correlation and autocorrelation statistics were calculated on features, such as gene expression, gene set scores, cell type prediction, and antibody capture. The features’ relative spatial changes were compared between pGBM and rGBM. Our analyses showed high heterogeneity within and across samples, but we found higher molecular and textural heterogeneity in rGBM samples compared to pGBM. We found higher androgen response activity (p < 0.001) presents diffusely (I: 0.09) throughout rGBM tissue but localized to mesenchymal-like regions in pGBM (I: 0.15). KRAS signaling signature was decreased in pGBM (p < 0.01) and increased in rGBM (p < 0.01). This increase was significantly overexpressed in cluster 0 for rGBM (p=0.02), which is an area characterized by neural progenitor signature. No significant difference in KRAS or EGFR magnitude or distribution of expression was present for either GBM type, indicating an independent mechanism for pGBM. We established a pipeline for assessing the spatio-temporal changes of the GBM TME. We found evidence indicating differences in the type of growth signaling, the cells bing targeted, and their distribution across the TME between pGBM and rGBM. Our work suggests how ST can help us better understand the intricate dynamics of GBM. Citation Format: Jean R. Clemenceau, Paola Suarez Meade, Mark E. Jentoft, Alfredo Quiñones-Hinojosa, Tae Hyun Hwang. Spatial transcriptomic landscape of the primary and recurrent glioblastoma tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 144.