Citations

Background and purpose Radiation therapy is an important component of treatment in patients with malignancies of the head, neck, and spine. However, radiation to these regions has well-known potential side effects, many of which can be encountered on imaging. In this manuscript, we review selected radiographic manifestations of therapeutic radiation to the head, neck, and spine that may be encountered in the practice of radiology. Methods We conducted an extensive literature review of known complications of radiation therapy in the head, neck, and spine. We excluded intracranial and pulmonary radiation effects from our search. We selected complications that had salient, recognizable imaging findings. We searched our imaging database for illustrative examples of these complications. Results Based on our initial literature search and imaging database review, we selected cases of radiation-induced tumors, radiation tissue necrosis (osteoradionecrosis and soft tissue necrosis), carotid stenosis and blowout secondary to radiation, enlarging thyroglossal duct cysts, radiation myelopathy, and radiation-induced vertebral compression fractures. Conclusions We describe the clinical and imaging features of selected sequelae of radiation therapy to the head, neck, and spine, with a focus on those with characteristic imaging findings that can be instrumental in helping to make the diagnosis. Knowledge of these entities and their imaging findings is crucial for accurate diagnosis. Not only do radiologists play a key role in early detection of these entities, but many of these entities can be misinterpreted if one is not familiar with them.

Abstract Background and Aims Immunotherapy has emerged as an effective treatment for patients with advanced‐stage HCC. We aimed to investigate the efficacy of immunotherapy for advanced HCC in a nationwide cohort and racial and ethnic disparities in access to immunotherapy. Approach and Results We used the US National Cancer Database to identify patients with tumor‐node‐metastasis stage 3 or 4 HCC between 2017 and 2018. We performed multivariable Cox regression to identify factors associated with overall survival (OS) and logistic regression to identify factors associated with receipt of immunotherapy. Of the 3,990 patients treated for advanced HCC, 3,248 (81.4%) patients received chemotherapy and 742 (18.6%) patients received immunotherapy as a first‐line treatment. Immunotherapy was associated with improved OS compared with chemotherapy (adjusted HR: 0.76, 95% CI: 0.65–0.88) after adjusting for covariates. There were racial and ethnic disparities in access to immunotherapy, with Hispanic (adjusted OR [aOR]: 0.63, 95% CI: 0.46–0.83) and Black patients (aOR: 0.71, 95% CI: 0.54–0.89) less likely to receive immunotherapy compared with White patients. There was a significant interaction between race‐ethnicity and facility type, with higher disparity observed in nonacademic centers (interaction p = 0.004). Conclusions Immunotherapy was associated with improved OS compared with chemotherapy in advanced HCC. There are significant disparities in early access to immunotherapy, likely due to differential access to clinical trials and experimental therapies. A comprehensive approach to monitoring and eliminating racial‐ethnic disparities in the management of advanced HCC is urgently needed.

Abstract Outcomes for marginal zone lymphoma (MZL) and follicular lymphoma (FL) remain suboptimal, owing to the limited number of approved agents and the incurable nature of the diseases. BGB-3111-AU-003 was a phase 1/2, open-label, multicenter, single-agent study of the selective Bruton’s tyrosine kinase inhibitor zanubrutinib in 385 patients with B-cell malignancies. Here, we present safety and efficacy outcomes for the 53 enrolled patients with relapsed/refractory MZL (n = 20) and relapsed/refractory FL (n = 33), all of whom were enrolled during the part 2 dose expansion, and therefore received zanubrutinib at the recommended phase 2 dose. Treatment with zanubrutinib was generally well tolerated, with most adverse events being ≤ grade 2. Atrial fibrillation/flutter was not reported. Two patients required dose reduction, and 4 patients discontinued treatment because of adverse events. Response was assessed by an independent review committee for MZL and the investigators for FL, per Lugano 2014 classification for non-Hodgkin lymphoma. In patients with MZL, the overall response rate (ORR) was 80%, and the complete response (CR) rate was 20%. With median follow-up of 33.8 months, median progression-free survival (PFS) was not reached. In patients with FL, the ORR was 36.4%, and the CR rate was 18.2%. After a median follow-up of 33.9 months, median PFS was 10.4 months. In conclusion, the results of this study suggest a favorable benefit–risk profile and support zanubrutinib as a potentially meaningful addition to available therapies for patients with relapsed/refractory MZL and FL. This trial was registered at www.clinicaltrials.gov as #NCT02343120.

Abstract Inhibitory receptors have a critical role in the regulation of immunity. Siglecs are a family of primarily inhibitory receptors expressed by immune cells that recognize specific sialic acid modifications on cell surface glycans. Many tumors have increased sialic acid incorporation. Overexpression of the sialyltransferase ST8Sia6 on tumors led to altered immune responses and increased tumor growth. In this study, we examined the role of ST8Sia6 on immune cells in regulating antitumor immunity. ST8Sia6 knockout mice had an enhanced immune response to tumors. The loss of ST8Sia6 promoted an enhanced intratumoral activation of macrophages and dendritic cells, including upregulation of CD40. Intratumoral regulatory T cells exhibited a more inflammatory phenotype in ST8Sia6 knockout mice. Using adoptive transfer studies, the change in regulatory T cell phenotype was not cell intrinsic and depended on the loss of ST8Sia6 expression in APCs. Thus, ST8Sia6 generates ligands for Siglecs that dampen antitumor immunity.

Abstract Background The COVID-19 pandemic produced unprecedented demands and rapidly changing evidence and practices within critical care settings. The purpose of this study was to identify factors and strategies that hindered and facilitated effective implementation of new critical care practices and policies in response to the pandemic. Methods We used a cross-sectional, qualitative study design to conduct semi-structured in-depth interviews with critical care leaders across the United States. The interviews were audio-taped and professionally transcribed verbatim. Guided by the Consolidated Framework for Implementation Research (CFIR), three qualitative researchers used rapid analysis methods to develop relevant codes and identify salient themes. Results Among the 17 hospitals that agreed to participate in this study, 31 clinical leaders were interviewed. The CFIR-driven rapid analysis of the interview transcripts generated 12 major themes, which included six implementation facilitators (i.e., factors that promoted the implementation of new critical care practices) and six implementation barriers (i.e., factors that hindered the implementation of new critical care practices). These themes spanned the five CFIR domains (Intervention Characteristics, Outer Setting, Inner Setting, Characteristics of Individuals, and Process) and 11 distinct CFIR constructs. Salient facilitators to implementation efforts included staff resilience, commitment, and innovation, which were supported through collaborative feedback and decision-making mechanisms between leadership and frontline staff. Major identified barriers included lack of access to reliable and transferable information, available resources, uncollaborative leadership and communication styles. Conclusions Through applying the CFIR to organize and synthesize our qualitative data, this study revealed important insights into implementation determinants that influenced the uptake of new critical care practices during COVID-19. As the pandemic continues to burden critical care units, clinical leaders should consider emulating the effective change management strategies identified. The cultivation of streamlined, engaging, and collaborative leadership and communication mechanisms not only supported implementation of new care practices across sites, but it also helped reduce salient implementation barriers, particularly resource and staffing shortages. Future critical care implementation studies should seek to capitalize on identified facilitators and reduce barriers.

AbstractImmune checkpoint inhibitors (ICIs), as a novel class of anticancer therapy, can be more efficacious and less toxic than chemotherapy, but their clinical success is confined to certain tumor types. Elucidating their targets, mechanisms and scope of action, and potential synergism with chemotherapy and/or targeted therapies are critical to widen their clinical indications. Treatment response to an ICI targeting programmed death‐1 (anti‐PD‐1) is sought to be understood here by conducting a preplanned correlative analysis of a phase II clinical trial in patients with small bowel adenocarcinoma (SBA). The cytolytic capacity of circulating immune cells in cancer patients using a novel ex vivo cytotoxicity assay is evaluated, and the utility of circulating biomarkers is investigated to predict and monitor the treatment effect of anti‐PD‐1. Baseline expression of Bim and NKG7 and upregulation of CX3CR1 in circulating T cells are associated with the clinical benefit of anti‐PD‐1 in patients with SBA. Overall, these findings suggest that the frequency and cytolytic capacity of circulating, effector immune cells may differentiate clinical response to ICIs, providing a strong rationale to support immune monitoring using patient peripheral blood.

Background: Race-ethnic disparities in stroke care can contribute to inequality in stroke outcomes. We sought to determine the disparities in stroke performance metrics by race-ethnicity in a voluntary stroke registry of Florida and Puerto Rico Get With The Guidelines-Stroke (GWTG-S) data. Methods: Sixty-three sites who had enrolled in the FL-PR Stroke Registry (54 FL; 9 PR) recorded 38,684 ischemic stroke cases from 2010 to 2013. Generalized linear regression models were used to evaluate race-ethnic differences in 7 pre-defined acute stroke performance measures and defect-free care (IV tPA treatment, in-hospital antithrombotic therapy, DVT prophylaxis, antithrombotic therapy at discharge, anticoagulation therapy, statin medication at discharge, and smoking cessation counseling), adjusting for age and region (FL vs. PR). Results: Of acute ischemic stroke cases, 63% were non-Hispanic White (NHW), 18% NH-Black (NHB), and 17% Hispanic. The mean age was 71±14 years. NHW were older (73±14), followed by Hispanics (70±14), and NHB (63±14); p<0.0001. Defect-free care was better among NHB (78%) and NHW (76%) than in Hispanics (68%), p<0.0001. Defect-free care improved over time and the race-ethnic disparity decreased (2010: NHW 61%, NHB 64%, Hispanic 46%, p<0.0001; 2013: 91%, 91%, 86%, p=0.47 respectively). NHW were most likely to receive IV tPA treatment (arrived by 2 hours and treated by 3 hours; 88%) and early antithrombotic treatment (96%). Hispanics were least likely to receive DVT prophylaxis (76%), anticoagulation (92%), statins (89%), and smoking cessation counseling (93%). Conclusions: Race-ethnic disparities in acute stroke care are evident yet decreasing, coinciding with improvements in quality of care over time in Florida and Puerto Rico hospitals participating in GWTG-S. Special stroke quality improvement programs to target areas where performance is less than expected and minimize race-ethnic disparities are necessary to improve stroke care for all Americans.

Background: Higher prevalence of stroke in women and sex-specific disparities in stroke care are reported. We sought to determine sex-specific differences in stroke performance metrics in a large quality improvement registry of Florida and Puerto Rico based on Get With The Guidelines-Stroke (GWTG-S). Methods: 38,684 (49% women) acute ischemic stroke patients were included from 63 sites (54 FL; 9 PR) from 2010 to 2013. Logistic regression was used to evaluate sex-specific differences in defect-free care (IV tPA therapy, in-hospital antithrombotic therapy, DVT prophylaxis, antithrombotic therapy at discharge, anticoagulation therapy, statin medication at discharge, smoking cessation counseling) adjusting for age and race-ethnicity. Results: As compared to men, women were older (73±15 vs. 69±14 years; p<0.0001), less likely Hispanic (17% vs. 18%; p=0.0001), with lower age- and race-ethnic-adjusted rates of hypertension (34% vs. 37%; p=0.0009) and smoking (13% vs. 21%; p<0.0001), but higher rates of atrial fibrillation (18% vs. 16%; p=0.02). Overall, 9% of patients received thrombolysis. Women were less likely to receive thrombolysis (OR 0.92, 95% CI 0.86-0.99) and less likely to have door-to-needle time <1 hour (OR 0.84, 95% CI 0.73-0.97). Overall, defect-free care was 75% in women and 76% in men (lower early antithrombotic therapy [OR 0.86, 95% CI 0.77-0.96], less antithrombotic at discharge [OR 0.87, 95% CI 0.77-0.99], less statin therapy at discharge [OR 0.81, 95% CI 0.74-0.88] and less smoking cessation counseling [OR 0.74, 95% CI 0.56-0.98]). Defect- free care improved over the study period; it was significantly lower in women vs. men in 2010 (58.2% vs. 60.7%, p=0.005), but similar in 2013 (90.2% vs 90.0%; p=0.64). Conclusions: Women eligible to receive IV tPA for acute ischemic stroke were less likely to be treated and received less defect-free care compared to men, but these measures improved over time. These findings suggest that the adoption of GWTG-S quality improvement program helps reduce sex disparities in quality of care for acute ischemic stroke patients.

Background: Racial and ethnic disparities in stroke care are known to contribute to inequality in stroke outcomes. The goal of the FL-PR CReSD Study is to assess and evaluate Get With The Guidelines-Stroke (GWTG-S) quality improvement data collected among Florida and Puerto Rico hospitals to evaluate for race-ethnic, sex, and regional disparities in stroke performance metrics. We sought to analyze the temporal trends in stroke performance metrics among the 9 hospitals located in Puerto Rico from 2010 to 2013. Methods: Age-adjusted temporal trends were evaluated in the following GWTG-S pre-defined performance measures (IV tPA treatment within 3 hours among eligible patients arriving in 2 hours, in-hospital antithrombotic therapy, DVT prophylaxis, antithrombotic therapy at discharge, anticoagulation therapy, statin medication at discharge, and smoking cessation counseling) and defect-free care (compliance with all 7 performance measures). Results: The mean age of 3,094 registered stroke cases was 69.5 ± 14.0 years, 50% were men, and 2,184 (71%) were diagnosed as ischemic strokes. Defect-free care occurred in 60% of ischemic stroke patients. Lower performance metrics were found for IV tPA treatment (78%), DVT prophylaxis (64%), and statin medication at discharge (83%). An additional IV tPA measure of treatment by 4.5 hours when arriving by 3.5 hours was observed in 65% of patients. The performance metrics that significantly improved over time from 2010 to 2013 included: IV tPA treatment within 3 hours (64% to 87%, p=0.04), DVT prophylaxis (33% to 87%, p<0.0001), statin medication at discharge (78% to 87%, p=0.01), and defect-free care (37% to 79%, p<0.0001). Conclusions: In only four years, Puerto Rico hospitals participating in GWTG-S showed significant improvement across all pre-defined acute stroke performance measures. Wider implementation of quality improvement programs like GWTG-S among the 3.7 million inhabitants of Puerto Rico could further improve acute stroke care.