Citations

Abstract To investigate the cellular and molecular mechanisms associated with targeting CD30-expressing Hodgkin lymphoma (HL) and immune checkpoint modulation induced by combination therapies of CTLA4 and PD1, we leveraged Phase 1/2 multicenter open-label trial NCT01896999 that enrolled patients with refractory or relapsed HL (R/R HL). Using peripheral blood, we assessed soluble proteins, cell composition, T-cell clonality, and tumor antigen-specific antibodies in 54 patients enrolled in the phase 1 component of the trial. NCT01896999 reported high (>75%) overall objective response rates with brentuximab vedotin (BV) in combination with ipilimumab (I) and/or nivolumab (N) in patients with R/R HL. We observed a durable increase in soluble PD1 and plasmacytoid dendritic cells as well as decreases in plasma CCL17, ANGPT2, MMP12, IL13, and CXCL13 in N-containing regimens (BV + N and BV + I + N) compared with BV + I (P < 0.05). Nonresponders and patients with short progression-free survival showed elevated CXCL9, CXCL13, CD5, CCL17, adenosine–deaminase, and MUC16 at baseline or after one treatment cycle and a higher prevalence of NY-ESO-1-specific autoantibodies (P < 0.05). The results suggest a circulating tumor-immune-derived signature of BV ± I ± N treatment resistance that may be useful for patient stratification in combination checkpoint therapy. Significance: Identification of multi-omic immune markers from peripheral blood may help elucidate resistance mechanisms to checkpoint inhibitor and antibody–drug conjugate combinations with potential implications for treatment decisions in relapsed HL.

Spinal cord epidural electrical stimulation (EES) has been successfully employed to treat chronic pain and to restore lost functions after spinal cord injury. Yet, the efficacy of this approach is largely challenged by the suboptimal spatial distribution of the electrode contacts across anatomical targets, limiting the spatial selectivity of stimulation. In this study, we exploited different ESS paradigms, designed as either Spatial-Selective Stimulation (SSES) or Orientation-Selective Epidural Stimulation (OSES), and compared them to Conventional Monopolar Epidural Stimulation (CMES). SSES, OSES, and CMES were delivered with a 3- or 4-contact electrode array. Amplitudes and latencies of the Spinally Evoked Motor Potentials (SEMPs) were evaluated with different EES modalities. The results demonstrate that the amplitudes of SEMPs in hindlimb muscles depend on the orientation of the electrical field and vary between stimulation modalities. These findings show that the electric field applied with SSES or OSES provides more selective control of amplitudes of the SEMPs as compared to CMES. We demonstrate that spinal cord epidural stimulation applied with SSES or OSES paradigms in the rodent model could be tailored to the functional spinal cord neuroanatomy and can be tuned to specific target fibers and their orientation, optimizing the effect of neuromodulation.

Abstract Background Risk of bias (RoB) tools are critical in systematic reviews and affect subsequent decision‐making. RoB tools should have adequate interrater reliability and interconsensus agreement. We present an approach of post hoc evaluation of RoB tools using duplicated studies that overlap systematic reviews. Methods Using a back‐citation approach, we identified systematic reviews that used the Risk Of Bias In Nonrandomized Studies‐of Interventions (ROBINS‐I) tool and retrieved all the included primary studies. We selected studies that were appraised by more than one systematic review and calculated observed agreement and unweighted kappa comparing the different systematic reviews' assessments. Results We identified 903 systematic reviews that used the tool with 51,676 cited references, from which we eventually analyzed 171 duplicated studies assessed using ROBINS‐I by different systematic reviewers. The observed agreement on ROBINS‐I domains ranged from 54.9% (missing data domain) to 70.3% (deviations from intended interventions domain), and was 63.0% for overall RoB assessment of the study. Kappa coefficient ranged from 0.131 (measurement of outcome domain) to 0.396 (domains of confounding and deviations from intended interventions), and was 0.404 for overall RoB assessment of the study. Conclusion A post hoc evaluation of RoB tools is feasible by focusing on duplicated studies that overlap systematic review. ROBINS‐I assessments demonstrated considerable variation in interconsensus agreement among various systematic reviewes that assessed the same study and outcome, suggesting the need for more intensive upfront work to calibrate systematic reviewers on how to identify context‐specific information and agree on how to judge it.

Abstract Telemedicine has routinely been used in cancer care delivery for the past 3 years. The current state of digital health provides convenience and efficiency for both health-care professional and patient, but challenges exist in equitable access to virtual services. As increasingly newer technologies are added to telehealth platforms, it is essential to eliminate barriers to access through technical, procedural, and legislative improvements. Moving forward, implementation of new strategies can help eliminate disparities in virtual cancer care, facilitate delivery of treatment in the home, and improve real-time data collection for patient safety and clinical trial participation. The ultimate goal will be to extend high-quality survival for all patients with cancer through improved digital delivery of cancer care.

9022 Background: High quality education is crucial for hematology/oncology (H/O) training and lifelong learning. However, H/O has historically prioritized clinical and research careers over medical education careers. Consequently, few programs support H/O educators. A CoP is a group that shares “a concern or passion for something they do and learn how to do it better as they interact regularly.” We formed the ASCO Med Ed CoP in 2021 to provide a collaborative network and professional development venue for H/O educators. Methods: Following a published framework for developing a global health professions educator community (Establish-Grow-Sustain), we (ASCO Education Scholars Program graduates) developed CoP mission and vision statements and a leadership structure (Establish), formed committees and projects (Grow), and gathered at the ASCO Annual Meeting and via virtual Town Halls (Sustain). In 2023, we collected demographics and evaluated the CoP using a logic model focused on inputs, activities, outputs, and impact. Results: As of December 2023, the CoP includes 238 members from 143 institutions (38 [27%] non-U.S.): 207 (87%) ASCO members; 127 (53%) women, 106 (45%) men, 5 (2%) no response (NR); 111 (47%) White, 88 (37%) Asian/Pacific Islander, 27 (11%) Latinx/Hispanic, 12 (5%) Black/African-American, 8 (3%) Middle Eastern, 1 (0.4%) African, 16 (7%) NR; 146 (61%) hematologist/oncologists, 68 (29%) trainees, 6 (3%) radiation oncologists, 3 (1%) surgical oncologists, and 15 (6%) other professionals. The logic model is displayed (Table). Conclusions: The CoP has had an impact on its members, ASCO, and beyond and continues to grow and sustain itself by recruiting broadly, driving projects forward, and making structural adjustments for long-term sustainability. Upcoming projects include providing more educational resources and measuring outcomes such as changes in members’ knowledge, skills, and attitudes. Membership diversity continues to be a challenge and a priority. [Table: see text]

9018 Background: Comprehensive hematology education during fellowship is paramount for providing high-quality care, especially in busy practices. Variability in fellow educational experiences is expected. However, fellowship programs must ensure a well-rounded, equitable educational experience for all fellows to prepare them for practice and board exams in the increasingly dynamic field of hematology. Methods: We administered an e-mail survey to hematology/oncology fellows (n=30) at Mayo (Rochester) to explore inpatient hematology education experiences and the Fellow Hematology Curriculum (FHC) during 2021-2022. Based on results, we designed a fellow-led, consultant-supervised quality improvement (QI) initiative to improve FHC. Responses were in a five-point Likert scale and open-ended format. Results: Twenty fellows completed the survey (66% response rate). Respondents were well distributed (35% PGY4, 25% PGY5, 40% PGY6). Resources most used for self-education were ASH SAP (85%), UpToDate (80%), and NCCN guidelines (50%). 100% of respondents agreed/strongly agreed that the FHC could be improved. 95% agreed/strongly agreed that there is a high degree of variability among consultants regarding engagement in fellows’ education. 45% agreed that education is adequately paired with relevant clinical duties to reinforce key concepts. 25% agreed that FHC had well-defined structure and objectives. In the open-ended responses, a structured curriculum covering a set list of topics paired with the relevant rotation was the most common recommendation by the fellows for improving the FHC and the inpatient hematology educational experience. This prompted a QI initiative to implement a structured, evidence-based curriculum covering essential topics required for hematology practice. Each week of a four-week rotation has a relevant theme (eg, “Marrow Failure week” during the inpatient leukemia service). Fellows selected a topic of interest and created a lecture to be used by all faculty and learners during the relevant rotation (eg, “Aplastic Anemia” during the Marrow Failure). Consultants and pharmacists in respective disease groups reviewed the topics and presentations. These lectures are now provided to fellows and faculty via e-mail prior to relevant rotations. Conclusions: Our survey demonstrated that trainees’ individual educational experiences on inpatient hematology services are widely variable and largely unsatisfying without some form of structured, relevant learning. We identified the need for deliberate, coordinated education as a gap to bridge toward achieving the goal of equitable, comprehensive learning. We intend to perform a post-implementation survey after one year of practicing a structured, relevantly paired FHC. This assessment will be used to make improvements in subsequent iterations of the FHC using the Plan-Do-Study-Act methodology.

9011 Background: 'Gender disparities' is a familiar term in medicine. Only 35.2% of oncologists in the U.S. self-identified as women in 2021. Women in medicine are undercompensated and underpromoted. Little is known of the experiences of non-U.S. female physicians in the U.S. We created the first cross-sectional study to assess gender disparities in IMGs and Puerto Rican medical graduates (PRMGs) in oncology in the U.S. Methods: An anonymous online survey was created and distributed via Survey Monkey. Eligible participants were non-U.S. IMGs and PRMGs who trained and/or practiced independently in the U.S. Participants were recruited through email and social media from Sept-Dec 2023. Bivariate association analyses were performed using the two-sample Wilcoxon test for ordered categorical variables and Fisher’s exact test for nominal categorical variables. Results: 97 IMGs and PRMGs in oncology completed the survey. As shown in the table, women were more likely to move to the U.S. for family (22.4% vs 6.2%, p=0.040), whereas men did more for financial gains (20.8% vs 6.1%, p=0.040). culture, particularly to the traditions (65.3% vs 43.8%;p=0.042) and dress code (44.9% vs 20.8%, p=0.017). Women experienced higher rates of gender discrimination during training (53.2% vs 4.5%, p <0.001) and independent practice (57.6% vs 3.6%, p<0.001) than men. Women were also more likely than men to face ethnic/racial discrimination during training (69.6% vs 38.1%; p=0.005). Despite lack of statistical significance, higher trends of ethnic/racial discrimination during independent practice were reported by women (table). More women reported no plans on returning home (68.8% vs 38.3%), whereas more men planned to return home at some point (38.3% vs 16.7%). 18.8% of men vs 0% of women elected leadership opportunities as the reason for returning to their home country (p=0.001). Conclusions: Our study reveals the unfortunate reality that many IMG and PRMG women face in oncology in the U.S. Despite national efforts to reduce the gap in gender disparities, minority women continue to experience racial/ethnic and gender discrimination at higher rates than men. To overcome inequities and achieve gender equity pay transparency, diversity in selection committees is necessary. Further, efforts should be across all settings, academia, private practice, and industry. The time for gender equity in oncology is now. [Table: see text]