US Academic Research Articles

Mainstreamed genetic testing of breast cancer patients: experience from a single surgeon's practice in a large US Academic Center.

This study evaluated the impact of mainstreamed genetic testing (MGT) on the timing and uptake of testing in an academic breast surgeon's practice. Before September 2019 (pre-MGT phase), a breast surgery practice at Massachusetts General Hospital followed a traditional model of a pre-test consultation with a genetic counselor (GC) following a referral. After September 2019 (post-MGT phase), the same practice offered patients genetic testing in a single clinical encounter with a breast surgeon. We evaluated the waiting time between referral and GC visit in the pre-MGT phase and compared the uptake and positivity rates between both phases. In the pre-MGT phase (204 patients), the median waiting time for GC visit was seven days for patients with a newly diagnosed cancer, 211 days for patients with a personal history of cancer, and 224 days for non-cancer patients who had a family history. A total of 105 (51.5%) patients completed a GC appointment. In the post-MGT phase (202 patients), a significantly higher proportion of patients (88.1%, p < 0.001) consented to genetic testing, while the proportion of patients who tested positive was lower (pathogenic variant: 11.9% vs. 20.0%; variant of uncertain significance: 19.9% vs. 28.0%; p = 0.047). Implementing MGT can reduce the number of clinical visits, significantly shorten patients' wait time to test initiation, and increase the completion of genetic testing. Successful integration of this model relied on the genetic expertise of the breast surgeon involved and the support of the GC team.

Rank-Ordered List of Cost-effective Strategies for Preventing Prosthetic Joint Infection in Total Joint Arthroplasty in an Academic US Hospital.

Although the overall rate of prosthetic joint infection (PJI) is low, it remains a major complication associated with total joint arthroplasty (TJA). PJI represents a significant economic burden to the health care system that is projected to increase commensurate with increasing joint replacement volumes. This review provides a rank-ordered list of cost-effective strategies that are performable intraoperatively and have data supporting their efficacy at preventing PJI after TJA. This study may be helpful in assisting surgeons, ambulatory surgery center owners, and hospital acquisition committees to make reasonable and cost-conscious decisions in the face of changing reimbursement. [Orthopedics. 2023;46(6):327-332.].

Characterizing Clinical Trials in Plastic and Reconstructive Surgery: A Systematic Review of ClinicalTrials.gov From 2007 to 2020.

Clinical trials form the backbone of evidence-based medicine. ClinicalTrials.gov is the world's largest clinical trial registry, and the state of clinical trials in plastic and reconstructive surgery (PRS) within that database has not been comprehensively studied. To that end, we explored the distribution of therapeutic areas that are under investigation, impact of funding on study design and data reporting, and trends in research patterns of all PRS interventional clinical trials registered with ClinicalTrials.gov. Using the ClinicalTrials.gov database, we identified and extracted all clinical trials relevant to PRS that were submitted between 2007 and 2020. Studies were classified based on anatomic locations, therapeutic categories, and specialty topics. Cox proportional hazard was used to calculate adjusted hazard ratios (HRs) for early discontinuation and results reporting. A total of 3224 trials that included 372,095 participants were identified. The PRS trials grew at an annual rate of 7.9%. The therapeutic classes most represented were wound healing (41.3%) and cosmetics (18.1%). Funding for PRS clinical trials is largely provided through academic institutions (72.7%), while industry and US government constituted a minority. Industry-funded studies were more likely to be discontinued early than those funded by academics (HR, 1.89) or government (HR, 1.92) and to be nonblinded and nonrandomized. Academic-funded studies were the least likely to report results data within 3 years of trial completion (odds ratio, 0.87). A gulf exists in the representation of different PRS specialties among clinical trials. We highlight the role of funding source in trial design and data reporting to identify a potential source of financial waste and to stress the need for continued appropriate oversight.

Rolling Deck to Repository (R2R) - Challenges managing large data from the US Academic Research Fleet

Rolling Deck to Repository (R2R) - Challenges managing large data from the US Academic Research Fleet

Utilization and Factors Precluding Receipt of Checkpoint Inhibitor Consolidation for Stage III NSCLC in a Large US Academic Health System

ObjectivesWe sought to determine the proportion of patients with stage III non–small cell lung cancer (NSCLC) who initiate consolidation durvalumab or other immune checkpoint inhibitors (ICIs) after concurrent chemoradiotherapy (cCRT), as well as reasons for nonreceipt and prognostic implications. Materials and MethodsWe retrospectively identified consecutive patients with unresectable stage III NSCLC treated with definitive cCRT between October 2017 and December 2021 within a large US academic health system. Patients either received consolidation ICIs (ICI group) or did not (no-ICI group). Baseline characteristics and overall survival (OS) of the groups were assessed. Factors predictive of ICI nonreceipt were evaluated using logistic regression. ResultsOf 333 patients who completed cCRT, 229 (69%) initiated consolidation ICIs; 104 (31%) did not. Reasons for ICI nonreceipt included progressive disease post-cCRT (N = 31, 9%), comorbidity or intercurrent illness (N = 25, 8%), cCRT toxicity (N = 23, 7%; 19/23 pneumonitis), and EGFR/ALK alteration (N = 14, 4%). The no-ICI group had worse performance status and a higher rate of baseline pulmonary comorbidity. Larger planning target volume was associated with post-cCRT progressive disease, and higher lung radiation dose with cCRT toxicity. Median OS was 16 months in the no-ICI group and 34.4 months in the ICI group. In the no-ICI group, OS was superior among those with EGFR/ALK alterations (median 44.5 months) and worst among those with progressive disease (median 5.9 months, P < 0.001). Conclusion31% of patients who completed cCRT for stage III NSCLC did not receive consolidation ICIs. Survival amongst these patients is poor, especially for those with progressive disease post-cCRT.

Gender Discrepancies in Middle Author Publications in US Academic General Surgery

IntroductionTo explore gender discrepancies in publications at general surgery departments, we performed a cross-sectional comparing the number of women and men at each academic rank and their number of first author (FA), middle author (MA), last author (LA), and total publications. MethodsThirty academic general surgery departments were randomly selected. For each faculty, we tabulated: first, middle, last names, gender, academic rank, educational leadership, year of medical school graduation, and additional graduate degrees. Bibliography, H-index, and citations were downloaded from the Scopus database. ResultsOne thousand three hundred twenty-six faculty sampled, 881 (66.4%) men and 445 (33.5%) women. Men outnumbered women at all ranks, with increasing disparity at higher ranks. Men outnumbered women in all subspecialties—largest difference in transplant surgery (84.4% versus 15.6%, P < 0.001). Men at all ranks had more MA publications: assistant professor (rate ratio 1.20; 95% confidence interval, 1.01-1.43, P = 0.024), associate professor (1.65; 1.31-2.06, P < 0.001), and professor (1.50; 1.20-1.91, P = 0.008). Men associate professors had more LA publications (1.74; 1.34-2.37, P < 0.001). No differences found in FA publications at any rank, nor LA publications at assistant professor and professor ranks. At subspecialty level, men in surgical oncology (1.95; 1.55-2.45, P < 0.001) and transplant surgery (1.70; 1.09-2.66, P = 0.02) had more MA publications. ConclusionsWhile FA and LA publications did not differ significantly across genders, the largest difference lies in MA publications, beginning at junior ranks and persisting with seniority. Discrepancies in MA publications may reflect gender discrepancies in collaborative opportunities, hence total publications should be used cautiously when determining academic productivity.

The association of hemoglobin with postoperative delirium and atrial fibrillation after cardiac surgery: a retrospective sub-study

BackgroundMost cardiac surgery patients experience postoperative anemia. Delirium and Atrial Fibrillation (AF) are common and independent predictors of morbidity and mortality. Few reports examine their association with postoperative anemia. This study aims to quantify the association between anemia and these outcomes in patients undergoing cardiac surgery. MethodsThis post-hoc analysis of the DECADE randomized controlled trial ran at six academic US hospitals. Patients aged 18–85 years with heart rate > 50 bpm undergoing cardiac surgery who had daily hemoglobin measurements in the first 5 Postoperative Days (POD) were included. Delirium was assessed twice daily with the Confusion Assessment Method for the ICU (CAM – ICU), preceded by the Richmond Agitation and Sedation Scale, with patients excluded from assessment if sedated. Patients had daily hemoglobin measurements, continuous cardiac monitoring plus twice-daily 12-lead electrocardiograms, up to POD4. AF was diagnosed by clinicians blinded to hemoglobin levels. ResultsFive hundred and eighty-five patients were included. Mean postoperative hemoglobin Hazard Ratio (HR): 0.99 (95% CI 0.83, 1.19; p = 0.94) per 1 g.dL−1 hemoglobin decrease. 197 (34%) developed AF, mainly on POD = 2.3. Estimated HR = 1.04 (95% CI 0.93, 1.17; p = 0.51) per 1 g.dL−1 hemoglobin decrease. ConclusionsMost patients undergoing major cardiac surgery were anemic in the postoperative phase. AF and delirium occurred in 34% and 12% of patients, respectively, but neither were significantly correlated with postoperative hemoglobin.

Impact of COVID-19 Pandemic on Management and Outcomes of Acute Cholecystitis at US Academic Centers.

The COVID-19 pandemic has had wide-ranging effects on management of medical conditions. Many hospitals encountered staffing shortages, limited operating room availability, and shortage of hospital beds. There was increased psychological stress and fear of contracting COVID-19 infection, leading to delay in medical care for various disease processes. The objective of this study was to examine changes in management and outcomes attributed to the COVID-19 pandemic in patients presenting with acute calculus cholecystitis at US academic centers. Using the Vizient database, patients with the diagnosis of acute calculus cholecystitis who underwent intervention during the 15 months before the pandemic (prepandemic, October 2018 to December 2019) were compared with 15 months during the pandemic (pandemic, March 2020 to May 2021). Outcomes measures included demographics, characteristics, type of intervention, length of stay, in-hospital mortality, and direct cost. There were 146,459 patients with acute calculus cholecystitis identified (prepandemic: 74,605 vs pandemic: 71,854). Patients in the pandemic group were more likely to undergo medical management (29.4% vs 31.8%; p < 0.001) or percutaneous cholecystostomy tube placement (21.5% vs 18%; p < 0.001) and less likely to undergo laparoscopic cholecystectomy (69.8% vs 73.0%; p < 0.001). Patients in the pandemic group who underwent procedural intervention had longer length of stay (6.5 days vs 5.9 days; p < 0.001), higher in-hospital death (3.1% vs 2.3%; p < 0.001), and higher cost ($14,609 vs $12,570; p < 0.001). In this analysis of patients with acute calculus cholecystitis, there were distinct changes in the management and outcomes of patients due to the COVID-19 pandemic. Changes in the type of intervention and outcomes are likely related to delayed presentation with increases in the severity and complexity of the disease.

Separate But Not Equal? A Cross-Sectional Study of Segregation by Payor Mix in Academic Primary Care Clinics.

At some US Academic Health Centers (AHCs), patients with predominantly Medicaid insurance are seen in one clinic and patients with other insurance are seen in another. The extent of this practice and implications are unknown. To estimate the proportion of AHCs that have at least two primary care internal medicine clinics that differ substantially in proportion of patients with Medicaid and to compare patient demographic, staffing, and operational features. General internal medicine chiefs and clinic directors at 40 randomly selected US AHCs plus the top 10 AHCs in terms of NIH funding. An AHC was classified as maintaining clinics that differed substantially in the proportion of patients with Medicaid if any two differed by ≥ 40% (absolute). Other criteria were used for pre-specified secondary analyses (e.g., ≥ 30%). Thirty-nine of 50 AHCs (78%) participated. Four of 39 (10%; 95% CI, 3 to 24%) had two clinics differing by ≥ 40% in the proportion of patients with Medicaid, eight (21%; 95% CI, 9 to 36%) had clinics differing by ≥ 30%, and 15 (38%; 95% CI, 23 to 55%) had clinics differing by ≥ 20%. Clinics with more patients with Medicaid by any of the three criteria were more likely to employ resident physicians as providers of longitudinal care (with faculty supervision) and more likely to have patients who were Black or Hispanic. Some US AHCs maintain separate clinics defined by the proportion of patients with Medicaid. Clinics with a higher proportion of patients insured by Medicaid are more likely to employ residents (with faculty oversight), feature residents as providers of longitudinal care, and serve patients who are Black and Hispanic. Further research is needed to understand why some AHCs have primary care clinics distinguishable by insurance mix with the goal of ensuring that racism and discrimination are not root causes.

The Current State of Antiracism Curricula in Undergraduate and Graduate Medical Education: A Qualitative Study of US Academic Health Centers

We undertook a study to evaluate the current state of pedagogy on antiracism, including barriers to implementation and strengths of existing curricula, in undergraduate medical education (UME) and graduate medical education (GME) programs in US academic health centers. We conducted a cross-sectional study with an exploratory qualitative approach using semistructured interviews. Participants were leaders of UME and GME programs at 5 institutions participating in the Academic Units for Primary Care Training and Enhancement program and 6 affiliated sites from November 2021 to April 2022. A total of 29 program leaders from the 11 academic health centers participated in this study. Three participants from 2 institutions reported the implementation of robust, intentional, and longitudinal antiracism curricula. Nine participants from 7 institutions described race and antiracism-related topics integrated into health equity curricula. Only 9 participants reported having "adequately trained" faculty. Participants mentioned individual, systemic, and structural barriers to implementing antiracism-related training in medical education such as institutional inertia and insufficient resources. Fear related to introducing an antiracism curriculum and undervaluing of this curriculum relative to other content were identified. Through learners and faculty feedback, antiracism content was evaluated and included in UME and GME curricula. Most participants identified learners as a stronger voice for transformation than faculty; antiracism content was mainly included in health equity curricula. Inclusion of antiracism in medical education requires intentional training, focused institutional policies, enhanced foundational awareness of the impact of racism on patients and communities, and changes at the level of institutions and accreditation bodies.

Challenges and Solutions for Establishing Robust Diversity, Equity, and Inclusion Efforts in US Academic Radiation Oncology Departments

Challenges and Solutions for Establishing Robust Diversity, Equity, and Inclusion Efforts in US Academic Radiation Oncology Departments

Analysis of Diversity, Equity, and Inclusion Initiatives Presented Across US Academic Department of Surgery Websites in 2021.

Despite increased attention devoted to diversity, equity, and inclusion (DEI) within academic medicine, representation, lack of workforce and leadership diversity, and bias within medicine remain persistent problems. The purpose of the current study was to understand the current efforts and attention to DEI within academic departments of surgery in the United States. 251 department of surgery websites were reviewed, using a standardized data collection form and scoring procedure, accompanied by a 10 percent fidelity check by an independent reviewer. Only 16% of departments of surgery included DEI-specific information, such as a DEI mission statement or initiatives on their departmental sites, with less than seven percent of departments reporting a DEI committee. Such public information may have implications for recruitment and retention of diverse faculty and trainees, downstream effects for patient care, and could be critical to public accountability to improve diversity and create a culture of equity and inclusion.

Listening holistically: one village’s path to address child malnutrition in Mali

ABSTRACT This study chronicles a 14-year partnership between a Malian rural village and US academics to curb childhood malnutrition. Villagers described agricultural/nutritional traditions while expressing a desire for improved quality of life for the future. Through holistic observation and listening, student/faculty partners developed a trusting relationship, and documented the community’s fundamental knowledge-base. Collaborators studied children’s dietary intake to predict micronutrient deficiencies. Villagers ultimately chose to participate in the national lunch program and to additionally supplement children’s diets with eggs. The Expansive Collaborative Model described in this article, exemplifies a cross-cultural approach which could effectively mitigate malnutrition in remote African villages.

An Update on the Progress Toward Gender Equity in US Academic Pharmacy

Objective. To evaluate the status of gender equity in US pharmacy education since the two previous publications on the topic in 2004 and 2014.Methods. Data were gathered from existing national databases, internal American Association of Colleges of Pharmacy (AACP) databases, AACP meeting minutes, published reports, scholarly articles, pharmacy association websites, individual school websites, and LinkedIn profiles. Differences between men and women were evaluated on degree completion, discipline, rank, tenure status, research, leadership development, leadership positions, salaries, and professional awards. Comparisons were also made to academic medicine and dentistry.Results. Fifty-one percent of full-time faculty members across all academic pharmacy disciplines are women. The percentage of women at the rank of professor was 36.6%, compared to 25% in 2014. Of the 2992 tenured or tenure track pharmacy faculty, 39.2% were women. Out of 388 department chairs, 146 were women. Throughout 2014-2021, there were 121 chief executive officer (CEO) dean permanent appointments, with men holding 91 (75.2%) and women holding 30 (24.8%). Women received 29.7% of the National Institutes of Health grants awarded to pharmacy schools compared to men (70.3%), although women's funding amount was higher. In both the pharmacy practice discipline and all sciences disciplines, the total salary across all ranks and years in rank was significantly higher for men than women, even for department chairs, but there were no differences for CEO deans. To date, women have received 13% of four national pharmacy organizations' top 13 awards.Conclusion. Since 2014, some achievement gaps have narrowed, but areas of concern still exist and need continued attention and resources so inequities can be eliminated. Women in academic pharmacy need mentoring and support to extend throughout the trajectory of their careers in areas such as academic advancement, grant applications, salary negotiation, leadership pursuit, and award applications.

S17 Treatment Patterns Among Moderate-to-Severe Ulcerative Colitis Patients in TARGET-IBD

Background: The treatment paradigm for Ulcerative Colitis (UC) is becoming increasingly complex with more treatment options available. There is a growing need to discern patterns of UC treatments in real-world settings. The objectives of this study were to identify a real-world moderate-to-severe UC patient population and estimate the risk of treatment modification (i.e. drug switching, dose escalation, treatment augmentation) among patients initiating advanced or conventional therapies. Methods: TARGET-IBD, a non-interventional cohort of IBD patients enrolled from one of 34 participating academic and community-based gastroenterology US sites, was used to identify the study population. Enrolled patients consented to the collection of up to 3 years of retrospective and 5 years prospective data. Patients were considered moderate to severe if they were ever hospitalized due to UC, received advanced treatments (biologics or Janus kinase inhibitor [JAKi]), an immunomodulator (IMM), or took corticosteroids for >2 months of the year prior to enrollment. To assess treatment modification, patients had to initiate an advanced treatment, or conventional therapy (IMM and 5-aminosalicylic acids) 3 years prior to or after enrollment and have a follow-up duration of at least 1 day. The incidence proportion was defined as the number of patients that experienced a treatment modification in the study period divided by the number of patients at risk. Kaplan Meier curves and cumulative incidence functions were produced for both treatment classes. Fine Gray sub-distribution hazard regression models were used to estimate the unadjusted and multivariable-adjusted hazard rate ratios for treatment modification, with 95% confidence intervals. Results: Out of 1,854 adult UC patients enrolled in TARGET-IBD, 1,332 patients met criteria for moderate to severe UC, of which 1,096 (82%) used an advanced treatment by the date of enrollment. Compared to patients on conventional therapies, patients on advanced treatments were younger (39 vs 50 years old), less likely to be on Medicare (11.6% vs 18.6%), and disproportionately treated at academic sites (70% vs 56%). A total of 660 patients initiated advanced (n=366, 55.5%) or conventional (n=294, 44.5%) therapy during the observation periods and were evaluated for treatment modification. The incidence proportion of treatment modification was lower in patients with advanced treatment compared patients with conventional therapy [47.6% (95% CI = 41.3, 53.8) vs 64.8% (95% CI = 58.3, 71.2), respectively]. Kaplan Meier curve showed that the probability of treatment modification increased with time on treatment for both groups, but was significantly more likely for patients on conventional therapies (median survival = 11.3, 95% CI = 8.80, 13.19) compared to that of patients on advanced treatments (median survival = 13.0, 95% CI = 9.72, 16.90). Both univariate and multivariable models showed that use of an advanced treatment was associated with decreased likelihood of treatment modification (HR = 0.73, 95% CI = 0.56, 0.95). Conclusion(s): In this large, real-world cohort analysis, moderate-to-severe UC patients initiating advanced treatments were significantly less likely to experience treatment modifications than those receiving conventional therapies. This study highlights the importance of therapy selection for patients with moderate-to-severe UC and the need for additional, more efficacious, and durable treatments.

Analysis of Failure Rates for COVID-19 Entrance Screening at a US Academic Medical Center

This quality improvement study analyzes the rate of failures in entrance screening for COVID-19 among individuals entering a large academic medical center.

Cytokine Release Syndrome (CRS) Is Not Required for CAR-T Cell Efficacy in Aggressive Large B-NHL

BACKGROUND Chimeric antigen receptor (CAR) T-cell therapy for treatment of aggressive large B-cell non-Hodgkin lymphoma (B-NHL) has changed management and outcomes for this disease. Treatment with CAR T-cells is accompanied by a unique set of adverse effects, including development of cytokine release syndrome (CRS). Though rates of CRS varied in trials, the development of severe (Grade 3 or 4) CRS was rare and similar incidences have been noted in real world studies. Here, we addressed whether the development of CRS is associated with outcomes in patients with aggressive large B-NHL undergoing treatment with CAR T cells. METHODS Patients aged ≥18 years with aggressive large B-NHL who underwent apheresis between May 2018 and January 2021 for commercial CAR T-cell therapy at eight academic US medical centers were identified from the Cell Therapy Consortium (CTC) registry. Providers could prescribe either axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel). CRS was graded using ASTCT consensus criteria. Tumor response 90 days after CAR T-cell infusion was assessed per Lugano criteria by the treating clinician. Persistent cytopenias were defined as ANC<1000 and/or Plt<50 and evaluated at the following intervals post infusion: day 30, 3 months, 6 months, 9 months, and one year. Cox regression analysis and the Kaplan Meier method were used for survival outcomes. Logistic regression analysis was used to assess association with tumor response and persistent cytopenias. RESULTS This study included 351 patients who underwent apheresis for commercial CAR T cell therapy for aggressive large B-NHL (Table 1A). Of these, 262 (74.4%) developed CRS while 90 (25.5%) did not. The median age at apheresis was 61 (range 18-88) among patients who developed CRS and 65 (range 37-85) among those who did not (p=0.005). Of the patients included, 202 (57.6%) received axi-cel and 149 (42.5%) received tisa-cel. With median follow up of 21.6 months, there were no differences in progression free survival (PFS) or overall survival (OS) between patients who developed CRS and those who did not. Median PFS in patients who did not develop CRS was 5.99 months compared to 5.89 months (p=0.99) in those who did. Median OS in patients who did not develop CRS was 26.6 months compared to 17.5 months in patients who did (p=0.16). Exploratory analysis showed that CRS grade did not influence PFS or OS (Figure 1). Results of the multivariate analysis are summarized in Table 1. The development of CRS did not have a significant impact on PFS or OS. A peak ferritin level of greater than 5000 within 28-days following CAR T-cell infusion was associated with worse PFS (HR 2.61; CI: 1.71-3.98, p<0.001) and OS (HR 2.38; CI: 1.50-3.76, p<0.001). LDH greater than the upper limit of normal was associated with worse progression-free (HR 2.11; CI: 1.49-2.98, p<0.001) and OS (HR 2.34; CI: 1.55-3.53, p<0.001). The administration of steroids for treatment of CAR T-cell associated toxicities had no significant impact on PFS or OS. Presence of bulky disease (≥10 cm) had no impact on PFS but was associated with worse OS (HR 1.81; CI: 1.29-2.75, p=0.005). Receipt of bridging therapy was associated with worse PFS (HR 1.58; CI: 1.11-2.24, p=0.011), though not OS. At 30 days post-infusion, there was no difference in ORR (66% vs 52%, p=0.081) or CR rate (39% vs 27%, p=0.155) between patients who developed CRS and those who did not. The occurrence of CRS within 28 days of treatment was significantly associated with cytopenias at day 30 (p=0.001), but not at any other time point. Amongst patients with Grade ≥3, 63% had cytopenias at day 30, compared to 47% among patients who did not have CRS (p=0.142). Grade ≥3 CRS was not significantly associated with cytopenias beyond day 30. CONCLUSION Survival outcomes were similar in patients with aggressive large B-NHL treated with CAR T-cell therapy who did or did not develop CRS. Furthermore, the occurrence of CRS had no impact on ORRs or CR rates. Having CRS was associated with cytopenias at day 30 post infusion, though not at subsequent time points. These findings lend further support to the finding that development of CRS does not impact efficacy of CAR T-cell therapy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Predictors and Outcomes of Immune Effector Cell Associated Neurotoxicity Syndrome in Patients Receiving Chimeric Antigen Receptor T-Cell Therapy for Aggressive B-Cell Non-Hodgkin Lymphoma

BACKGROUND Chimeric antigen receptor (CAR) T-cell therapy has changed the treatment landscape for aggressive large B-cell non-Hodgkin lymphoma (B-NHL). Immune effector cell-associated neurotoxicity syndrome (ICANS) is recognized as an adverse event of special interest associated with CAR T-cell therapy. However, determinants of ICANS presentation and outcome remain poorly understood. In this multicenter retrospective study, we aimed to determine risk factors for ICANS and clinical outcomes in patients who develop ICANS. METHODS Patients aged ≥18 years with aggressive large B-NHL who underwent apheresis from May 2018 to January 2021 for commercial CAR T-cell therapy at eight academic US medical centers were identified from the Cell Therapy Consortium (CTC) registry. All centers were approved to administer axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) per provider discretion. ICANS and CRS were graded using ASTCT criteria and classified as severe if grade 3-5. Cox regression analysis and the Kaplan Meier method were used for survival outcomes. Laboratory values collected at lymphodepletion were used for the previously reported Endothelial Activation and Stress Index (EASIX) and modified EASIX (m-EASIX) score. Log transformation was applied to reduce skew. Predictors of severe ICANS were identified using logistic regression analysis. Best subset selection and receiver operating characteristic (ROC) analyses were applied to determine optimal predictors. RESULTS Baseline characteristics are summarized in Table 1. A total of 352 patients received axi-cel (n=203) and tisa-cel (n=149) with a median follow-up of 21.6 months. A total of 125 (35.5%) developed ICANS while 227 (69.8%) did not. Of those with ICANS, severe ICANS occurred in 75 (60%) and mild ICANS occurred in 50 (40%). The median age at apheresis was similar at 64 (range 22-89) compared to 62 (range 18-86) among patients with and without ICANS. The majority of patients who developed ICANS (87.2%) received axi-cel. CRS was more common in those with ICANS (94.4% vs. 63.3%). IPI grade 3 or higher was more common in patients who developed ICANS (59.9% vs. 47%). There were similar numbers of patients with bulky, primary refractory, and active CNS disease among patients with and without ICANS. Most patients with ICANS (82%) received steroids compared to those without ICANS (9.4%). Results of cox regression analyses are summarized in Table 2. The development of ICANS did not significantly impact PFS or OS nor did steroid administration. Exploratory analysis showed that severity of ICANS did not influence PFS or OS. Bulky disease (≥10 cm), LDH greater than the upper limit of normal, and peak ferritin greater than 5000 in the first 28-days post-infusion were associated with worse OS. There was a significant interaction term between ICANS and product for OS. We conducted an exploratory analysis stratified by product which showed that the development of ICANS with tisa-cel was associated with inferior OS (HR 3.65, CI: 1.35-9.91, p=0.011) but no difference in PFS. The development of ICANS with axi-cel had no impact on OS or PFS. Risk factors for ICANS evaluated as continuous variables at lymphodepletion included included ferritin (p=0.021), LDH (p=0.004), CRP (p<0.001), EASIX (p=0.004), and m-EASIX (p<0.001). Thrombocytopenia, neutropenia, and creatinine were not associated with severe ICANS. Best subset selection showed that higher CRP was the best model to predict severe ICANS. ROC comparison analysis showed no difference between CRP (AUC 0.64), EASIX (0.64), and m-EASIX (0.66). Post infusion, CRS (OR 2.27, CI: 1.46-3.08, p<0.001) and earlier onset of CRS (OR 0.83, CI: 0.71-0.94, p=0.005) were predictive of severe ICANS while time to steroid administration was not. CONCLUSION In this retrospective analysis, we showed that outcomes were similar in patients with aggressive large B-NHL treated with CAR T-cell therapy who did or did not develop ICANS regardless of severity. In stratified analysis, ICANS was associated with inferior OS in those who received tisa-cel but was limited by small sample size. Pre lymphodepletion CRP alone had the highest discriminatory ability to predict severe ICANS. After infusion, developing CRS and earlier onset of CRS were predictive of ICANS. Future studies should identify novel predictive scores for ICANS which may lead to strategies to prevent neurologic toxicity after CAR T-cell therapy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Proceedings From the ASCO/College of American Pathologists Immune Checkpoint Inhibitor Predictive Biomarker Summit.

Immune checkpoint inhibition (ICI) therapy represents one of the great advances in the field of oncology, highlighted by the Nobel Prize in 2018. Multiple predictive biomarkers for ICI benefit have been proposed. These include assessment of programmed death ligand-1 expression by immunohistochemistry, and determination of mutational genotype (microsatellite instability or mismatch repair deficiency or tumor mutational burden) as a reflection of neoantigen expression. However, deployment of these assays has been challenging for oncologists and pathologists alike. To address these issues, ASCO and the College of American Pathologists convened a virtual Predictive Factor Summit from September 14 to 15, 2021. Representatives from the academic community, US Food and Drug Administration, Centers for Medicare and Medicaid Services, National Institutes of Health, health insurance organizations, pharmaceutical companies, in vitro diagnostics manufacturers, and patient advocate organizations presented state-of-the-art predictive factors for ICI, associated problems, and possible solutions. The Summit provided an overview of the challenges and opportunities for improvement in assay execution, interpretation, and clinical applications of programmed death ligand-1, microsatellite instability-high or mismatch repair deficient, and tumor mutational burden-high for ICI therapies, as well as issues related to regulation, reimbursement, and next-generation ICI biomarker development. The Summit concluded with a plan to generate a joint ASCO/College of American Pathologists strategy for consideration of future research in each of these areas to improve tumor biomarker tests for ICI therapy.

The Current State of Departmental Diversity, Equity, and Inclusion Efforts Within US Academic Radiation Oncology Departments

Promoting a diverse workforce of healthcare professionals that delivers equitable patient care is an important goal in oncology, as in all of medicine. While most medical schools have a diversity office and associated initiatives, little is known about radiation oncology (RO) department-level efforts to promote diversity, equity, and inclusion (DEI). We describe the current state of DEI leadership and initiatives in RO departments in the US to guide future policies and programs. A total of 124 US RO departments affiliated with a medical school were contacted to identify departmental DEI leadership. Identified DEI leaders were asked to complete an anonymous survey assessing characteristics of their departmental DEI leadership, committee/organizational structure, activities, and perceived barriers to, and impact of, their work. Descriptive statistics are reported. Among 85 RO departments that responded (68.5% response rate), 48 (56.5%) reported having a departmental DEI leader. Thirty-four DEI leaders completed the survey (70.8%). Most DEI leaders were assistant or associate professors (n=28, 82.2%), women (n=25, 73.1%), and identified with at least one non-White race or Hispanic ethnicity (n=18, 53.6%). Nineteen (55.9%) had an associated departmental DEI committee; with 10 (52.6%) starting in 2020 or later. Few DEI leaders had administrative support (38.2%), funding (29.4%), protected time (23.5%), or increased compensation for added duties (23.5%). Seventeen (51.7%) believed their DEI-focused efforts were considered for promotion. The most reported initiatives included offering programming/education, supporting students from backgrounds underrepresented in medicine, improving recruitment practices/hiring, and implementing pipeline/pathway projects. The perceived impact of DEI initiatives included an increased culture of respect (89.7%), improved healthcare disparity awareness (75.9%), and improved systematic/structural racism awareness (79.3%). Departmental DEI efforts are increasingly common within RO, however, the structure, resources, and recognition associated with DEI work are variable. Additional dedicated resources and recognition for these efforts will help ensure a culture of inclusive excellence for the RO workforce and patients.