Citations

ObjectivePatients with myelin oligodendrocyte glycoprotein antibody (MOG‐IgG)‐associated disease (MOGAD) suffer from severe optic neuritis (ON) leading to retinal neuro‐axonal loss, which can be quantified by optical coherence tomography (OCT). We assessed whether ON‐independent retinal atrophy can be detected in MOGAD.MethodsEighty patients with MOGAD and 139 healthy controls (HCs) were included. OCT data was acquired with (1) Spectralis spectral domain OCT (MOGAD: N = 66 and HCs: N = 103) and (2) Cirrus high‐definition OCT (MOGAD: N = 14 and HCs: N = 36). Macular combined ganglion cell and inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (pRNFL) were quantified.ResultsAt baseline, GCIPL and pRNFL were lower in MOGAD eyes with a history of ON (MOGAD‐ON) compared with MOGAD eyes without a history of ON (MOGAD‐NON) and HCs (p < 0.001). MOGAD‐NON eyes had lower GCIPL volume compared to HCs (p < 0.001) in the Spectralis, but not in the Cirrus cohort. Longitudinally (follow‐up up to 3 years), MOGAD‐ON with ON within the last 6–12 months before baseline exhibited greater pRNFL thinning than MOGAD‐ON with an ON greater than 12 months ago (p < 0.001). The overall MOGAD cohort did not exhibit faster GCIPL thinning compared with the HC cohort.InterpretationOur study suggests the absence of attack‐independent retinal damage in patients with MOGAD. Yet, ongoing neuroaxonal damage or edema resolution seems to occur for up to 12 months after ON, which is longer than what has been reported with other ON forms. These findings support that the pathomechanisms underlying optic nerve involvement and the evolution of OCT retinal changes after ON is distinct in patients with MOGAD. ANN NEUROL 2022;92:476–485

Background: As the incidence of shoulder arthroplasty rises at exponential rates, race is an important consideration, as racial disparities have been reported in lower-extremity arthroplasty in the United States. Our study sought to examine these disparities. Methods: Using the National Inpatient Sample (NIS) database, all anatomic total shoulder arthroplasty (aTSA) and reverse total shoulder arthroplasty (RSA) procedures from 2011 to 2017 were analyzed. The patients were divided into the Black, Hispanic, and White groups. Results: Overall, 91.4% of the patients undergoing any shoulder arthroplasty procedure were White, 4.75% were Black, and 3.85% were Hispanic. Age and sex-standardized RSA utilization rates (per 100,000) in White patients increased by 139% from 6.94 in 2011 to 16.60 in 2017. The disparity for Black patients, compared with White patients, was 118% in 2011 and 124% in 2017; the disparity for Hispanic patients was 112% in 2011 and 103% in 2017. Similar disparities in aTSA utilization rates were seen; when compared with White patients, there was a 150% disparity in 2011 and a 197% disparity in 2017 for Black patients, and a 169% disparity in 2011 and a 262% disparity in 2017 for Hispanic patients. Finally, Blacks had a higher rate of non-home discharge, longer length of stay, and higher overall costs, while Hispanics had a longer length of stay and higher cost than Whites. Conclusions: Despite many efforts to reduce racial disparities in health-care utilization, the chasm in shoulder arthroplasty in the United States appears to be large and widening further. The exponential increase in utilization of shoulder arthroplasty has not been shared equally among races, and the disparities are larger than those reported in lower-extremity arthroplasty.

Abstract In 1997, the American Institute for Cancer Research (AICR) published 14 recommendations related to diet for individuals to reduce cancer incidence on a global basis; smoking was also discouraged. We operationalized these into nine recommendations that are particularly relevant to western populations in a cohort of 29,564 women ages 55 to 69 years at baseline in 1986 who had no history of cancer or heart disease. The cohort was followed through 1998 for cancer incidence (n = 4,379), cancer mortality (n = 1,434), cardiovascular disease (CVD) mortality (n = 1,124), and total mortality (n = 3,398). The median number (range) of recommendations followed was 4 (0-8), and 33% of the cohort had ever smoked. Women who followed no or one recommendation compared with six to nine recommendations were at an increased risk of cancer incidence [relative risk (RR) 1.35, 95% confidence interval (CI) 1.15-1.58] and cancer mortality (RR 1.43, 95% CI 1.11-1.85), but there was no association with CVD mortality (RR 1.06, 95% CI 0.78-1.43). We calculated the population attributable risk (PAR) to estimate the proportion of cancer incidence, cancer mortality, and CVD mortality that theoretically would have been avoidable if the entire cohort had never smoked, had followed six to nine recommendations, or had done both. The PARs for smoking were 11% (95% CI 10-13) for cancer incidence, 21% (95% CI 17-24) for cancer mortality, and 20% (95% CI 16-23) for CVD mortality. The PARs for not following six to nine recommendations were 22% (95% CI 12-30) for cancer incidence, 11% (95% CI −5 to 24) for cancer mortality, and 4% (95% CI −20 to 19) for CVD mortality. When smoking and the operationalized AICR recommendations were combined together, the PARs were 31% (95% CI 19-37) for cancer incidence, 30% (95% CI 15-40) for cancer mortality, and 22% (95% CI 4-36) for CVD mortality. These data suggest that the adherence to the AICR recommendations, independently and in conjunction with not smoking, is likely to have a substantial public health impact on reducing cancer incidence and, to a lesser degree, cancer mortality at the population level.

Abstract Pain is common in chronic pancreatitis (CP) and profoundly reduces quality of life (QoL). Multiple underlying mechanisms contribute to a heterogenous pain experience and reduce efficacy of pain management. This study was designed to characterize the distribution of mechanism-based pain phenotypes in painful CP. The data analyzed were collected as part of the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies, an NCI/NIDDK-funded longitudinal study of the natural history of CP. The PROspective Evaluation of Chronic pancreatitis for EpidEmiologic and translational stuDies includes patient-reported outcome (PRO) measures of pain, medication use, global health, and QoL. Of subjects (N = 681) with CP, 80% experienced abdominal pain within the year before enrollment. Subjects who experienced pain in the week before enrollment (N = 391) completed PROMIS Neuropathic and Nociceptive Pain Quality instruments which were then used to classify them by pain type: 40% had nociceptive, 5% had neuropathic-like, and 32% had both types of pain. The prevalence of having both types of pain was higher among women and subjects with diabetes mellitus, whereas nociceptive-only pain was more prevalent among men and those with pancreatic duct stricture. Other factors, including pain medication use and healthcare utilization, did not differ between groups based on pain type. Subjects in the Both group had significantly worse health and QoL scores relative to those with nociceptive-only pain, suggesting that using psychosocial pain surveys may be useful for understanding pain subtypes in patients with CP. Additional research is needed to identify biochemical and biophysical signatures that may associate with and predict responses to mechanism-specific interventions.

11039 Background: Participation in mentorship programs for early career physicians may be crucial to developing key skills and professional networks to navigate racial, ethnic and gender leadership disparities in medicine. A 6-month virtual facilitated peer mentorship program was developed and piloted through the Society for Neuro-Oncology (SNO) Women & Diversity Committee. The evaluation of the program’s feasibility to positively impact early career physicians, investigators and trainees is presented here. Methods: We designed and conducted a virtual mentoring program pilot open to SNO’s multidisciplinary members in residency, fellowship, or early career phase, leveraging peer-mentoring sessions with mid-to late-career physician mentors. A curriculum with online resources was provided recommending groups meet for 6 sessions: 3 involving the mentor and 3 dedicated to peer-mentoring. Group assignments were based on time-zones and interests. Pre- and post-participation surveys assessed mentee experience. Descriptive statistics were used to assess participant demographics and survey results. Results: Our call for participation was broad; all 20 mentee applicants participated in 5 groups. Mentees were 90% women and 60% were from diverse racial and ethnic backgrounds. Most were aged 31-40 (75%) and junior faculty (50%) in neuro-oncology (65%). The 5 senior mentors (3 men and 3 of diverse race and ethnic backgrounds) practiced either neuro-oncology (3), neurosurgery (1) or radiation oncology (1). The proportion who reporting having a signature lecture increased from 15% to 62% during the pilot. A large majority reported their participation was worthwhile (85%), that they would participate again (92%) and would recommend it to others (92%). Feedback themes included positive personal growth, peer support, networking and job opportunities, access to CV reviews, lack of and desire for late career female mentors, and virtual scheduling constraints. While the pilot was limited by several variables, it was timely to connect participants in Q3 of 2020 early in the COVID-19 global pandemic. The virtual meeting environment created a venue to share and discuss topics such as work-life balance, burnout, leading through change and social connection. Despite not achieving 100% professional concordance, participants found the experience worthwhile. The tools and curriculum of topics provided was implemented differently across groups, leading to varied experiences. Finally, we did not have 100% post pilot follow up despite multiple attempts limiting our complete understanding of the pilot. Conclusions: This virtual mentorship pilot program proved feasible and of value in development of early career women and diverse individuals. A resource toolkit has been designed to scale and diffuse.

6530 Background: Only a small fraction of patients with cancer participate in treatment trials. Patients identifying as members of racial and ethnic minority groups are consistently underrepresented in these trials. A recent systematic review reported that patients, regardless of race and ethnicity, are willing to enroll in trials if asked to participate by their treating clinician. Prospective and longitudinal data and metrics at the site- and clinician-level are necessary to understand whether patients are equitably considered for clinical trials. Methods: ASCO and Association of Community Cancer Centers (ACCC) developed a self-assessment for trial sites to record and gauge the number of patients across races and ethnicities screened, offered, and enrolled into clinical trials. Research sites, from across the US, were recruited through an open call to apply to participate in the ASCO-ACCC Pilot Project. There were 65 sites assigned to this pilot study, which tested the feasibility and utility of the site assessment. Sites were asked to enter 2019 and 2020 aggregate data for each step along the clinical trial enrollment continuum by select races and ethnicities (Black, Hispanic/Latinx, White) and overall. Results: 62 of 65 sites completed the study and represented a range of settings and practice types (61% academic, 26% hospital/health system, 13% independent). Only 2 sites (3%) were able to provide the data requested at each enrollment step in the assessment (table). Sites that collected the data did not do so routinely (table) and most had to compile data through multiple sources and/or manual extraction (40-100% across enrollment steps). Sites with missing data reported they did not collect data at all (36-64% across enrollment steps), did not collect data in a systematic way (0-29% across enrollment steps), or stated it would be too burdensome to manually review charts to extract data (12-29% across enrollment steps). Conclusions: Data collection and routine evaluation of participation metrics, by race and ethnicity, are necessary to assess and monitor equity and diversity in clinical trials. Most sites in this study did not collect, or routinely collect, data for screening, offering, and consenting patients to clinical trials. Without these data, sites are unable to evaluate and monitor whether their patients have equitable access to clinical trials or establish strategies to address any inequities. ASCO and ACCC will continue to partner with sites to better understand their processes and the feasibility of collecting such data in a systematic and automated way, such as through electronic health record systems. [Table: see text]

5553 Background: In patients with high-grade ovarian cancer in first-line setting, predictive factors of bevacizumab efficacy are needed, for selecting patients. In ICON-7 trial, a poor tumor intrisic chemosensitivity (defined by unfavorable modeled CA-125 kinetic ELIMination rate constant KELIM) was a predictive biomarker. Among patients with high-risk diseases, only those with unfavorable KELIM had survival benefit from bevacizumab (mOS: 29.7 vs 20.6 months, HR = 0.78)(Colomban. JNCI CS 2020). The objective was to perform an external validation in GOG-0218 trial (NCT00262847). Methods: In GOG-0218, 1,873 patients were treated with carboplatin-paclitaxel +/- concurrent bevacizumab/placebo followed by a 15 month maintenance. Patient KELIM values were estimated with longitudinal CA-125 kinetics during the first 100 chemotherapy days. The association between KELIM score (categorized as favorable ≥ 1, or unfavorable < 1) and efficacy of bevacizumab (bevacizumab-concurrent + maintenance, vs placebo) for PFS and OS was assessed using univariate/multivariate analyses, in a Training set with 2/3 patients managed the investigators, and then a Validation set with all patients, managed by NGR-GOG. Results: KELIM was assessable in 1,662 patients with ≥ 3 CA-125 available values. In both sets, the patients with unfavorable KELIM derived benefit from bevacizumab compared to placebo (Training: PFS, HR = 0.65 [0.54-0.80]; OS, HR = 0.80 [0.65-0.99]; Validation: PFS, HR = 0.69 [0.59-0.82]; OS, HR = 0.87 [0.73-1.03]), whilst those with favorable KELIM had no benefit from bevacizumab (Training: PFS, HR = 0.96 [0.75-1.23]; OS, HR = 1.05 [0.80-1.37]; Validation, PFS, HR = 0.96 [0.79-1.17]; OS HR = 1.11 [0.89-1.84]). The highest benefit was observed in patients with high-risk diseases (stage IV or sub-optimally resected stage III) characterized by unfavorable KELIM, for PFS (Learning (n = 276): mPFS: 9.0 vs 5.2 months, HR = 0.61 [0.48-0.78]; Validation (n = 433): mPFS: 9.1 vs 5.6 months, HR = 0.64 [0.53-0.78]), and for OS (Learning (n = 278): mOS: 38.9 vs 27.9 months, HR = 0.72 [0.56-0.93], Validation set (n = 438): mOS: 35.1 vs 29.1 months, HR = 0.79 [0.65-0.97]). Conclusions: This validation analysis of GOG-0218 trial confirms the outcomes of ICON-7 trial about the association between poor tumor chemosensitivity and benefit from concurrent + maintenance bevacizumab, suggesting that bevacizumab is mainly effective in patients with poorly chemosensitive diseases. No benefit was found in patients with favorable KELIM. The patients who derived the highest benefit from bevacizumab in PFS and OS (OS absolute benefit ̃ 6 to 9 months) were those with high-risk diseases (stage IV, or incompletely resected stage III) associated with an unfavorable KELIM score (calculator on https://www.biomarker-kinetics.org/CA-125).

5091 Background: Controversy surrounding prostate-specific antigen (PSA) based screening for prostate cancer (PCa) highlights the need for non-invasive assays that better discriminate patients with and without clinically significant prostate cancer (csPCa). Such distinction avoids overtreatment in patients with absent or indolent disease while capturing pathology that would derive benefit from intervention. We analyzed the presence of specific methylated DNA markers (MDMs) within urine samples of patients with biopsy proven PCa and assessed the ability to discriminate these patients from healthy controls with no clinical suspicion for PCa. Methods: 24 healthy volunteers with no clinical suspicion for PCa were age-matched to 24 patients with biopsy-confirmed disease across all Gleason scores. Urine collected from subjects was centrifuged with the cell-free supernatant analyzed in a blinded fashion for methylation signal within specific DNA sequences across 14 genes ( HES5, ZNF655, ITPRIPL1, MAX.chr3.193, SLCO3A1, CHST11, SERPINB9, WNT3A, KCNB2, GAS6, AKR1B1, MAX.chr3.727, GRASP, ST6GALNAC2) by target enrichment long-probe quantitative-amplified signal assays. A patient was considered to have a positive MDM panel if any individual marker exceeded the corresponding100% specificity cut-off value (overall MDM panel specificity of 100%). MDM panel positivity was used to evaluate the sensitivity for distinguishing patients with PCa (any Gleason score) from controls as well as discriminate csPCa cancers from PCa Gleason 6. Results: Median age of healthy controls and PCa patients was 70 years (IQR 67-72) and 65 years (IQR 61-71), respectively. Median PSA was 6.4 (IQR 4.9-9.0) among PCa patients, including median PSA of 5 (IQR 4.0-6.1) for Gleason 6, and 7.8 (IQR 5.1-9.2) for Gleason ≥7 disease. Gleason 6, Gleason 7, and Gleason 8+ cancer was noted in 8, 10, and 6 patients, respectively. Utilizing an overall specificity cut-off of 100% for discriminating normal controls from PCa cases across the MDM panel revealed an overall sensitivity of 83% (95% CI: 63-95%) for detection of PCa (6 of 8 Gleason 6, 9 of 10 Gleason 7, 5 of 6 Gleason 8+) and 88% (95% CI: 62-98%) for csPCa (Gleason ≥ 7). When considering a 100% specificity threshold for controls and Gleason 6 patients, the sensitivity the MDM panel was 69% (95% CI: 41-89%) for csPCa (6 of 10 Gleason 7, 5 of 6 Gleason 8+). Conclusions: We describe a panel of 14 MDMs within urine that offer high specificity and sensitivity for detection of prostate cancers as well as selective identification of clinically significant disease states. Prospective comparison between urine MDMs and PSA blood testing is necessary to discern the differential clinical impact of each screening methodology.

e15567 Background: Radiographic surveillance of colorectal cancer (CRC) after therapy is costly and insensitive. We have reported high cross-sectional performance of methylated DNA markers (MDMs) for detection of primary CRC and metastatic recurrence. This study evaluated MDMs to detect recurrence and measure response to anti-cancer therapy in a longitudinal cohort. Methods: This was a nested case-control study drawn from a prospective cohort of adult patients with CRC who completed definitive treatment and followed forward from the start of surveillance by cross-sectional imaging (CT or MRI) and carcinoembryonic antigen (CEA), collected every 3-6 months under routine care. Blood was collected in LBgard® tubes (Biomatrica, San Diego CA). Cases had recurrent CRC (defined by RECIST v1.1 or radiographic findings that justify re-initiation of anti-cancer therapy as determined by treating clinicians). Controls remained NED (no radiographic recurrence and off therapy for ≥4 surveillance visits). From 6mL of plasma, MDMs ( CNNM1, ANKRD13B, FER1L4, ZNF568, CHST2, ZNF671, VAV3, QKI, GRIN2D, DTX1, PDGFD, SFMBT2, JAM3) were measured by target enrichment long-probe quantitative-amplified signal assays, normalized to B3GALT6, in blinded fashion. Previously published random forest models of MDMs +/- CEA, developed on independent patients with intact primary tumors, were used to develop a summary score. Results: With a median follow-up of 276 days (IQR 187-343) and 3 visits per patient (54 visits total), 18 patients had recurrence after start of surveillance. Another 18 patients remained NED after median 555 days (IRQ 469-662) and 4 surveillance visits per patient (76 visits total). Using a 90th %-ile cut-off summary score from 60 NED patients in a prior cross-sectional measurement, the MDM panel was positive in 15 of 18 patients who recurred and only 2 of the 18 NED patients (Table). Of the 76 patient visits for NED patients, 67 (88%) were below the threshold. The MDM panel score crossed the positivity threshold by a median of 127 days (IRQ 0-233) preceding clinical or radiographic documentation of recurrence. A random forest model with CEA was more sensitive but less specific (Table). In patients who resumed therapy, the MDM panel scores correlated closely with subsequent RECIST scores (not shown). Conclusions: Plasma MDMs rise in anticipation of recurrent CRC prior to radiographic detection and remain low in patients without radiographic disease over serial measurements, warranting further development of this tumor-agnostic liquid biopsy approach as a cost-effective tool to assist cancer surveillance.[Table: see text]