Citations

Abstract Excessively restrictive inclusion and exclusion criteria in clinical trials are one of many barriers to clinical trial enrollment for patients with myelodysplastic syndromes/neoplasms (MDSs). Many organizations are developing efforts to increase clinical trial eligibility; yet, several recent publications focused on patients with MDS suggest that many patients with this disease may be excluded from clinical trials unnecessarily. Clinical trial eligibility should reflect the phase of the study and risks of the agent being studied. Phase 3 trials should be less restrictive than early-phase trials to represent the real-world population as closely as possible. We hypothesize that many clinical trials, particularly phase 3 trials, have unnecessarily restrictive eligibility criteria. This study aims to evaluate the most common eligibility criteria according to phase of trial and to determine whether criteria correspond with drug safety signals. We identified MDS clinical trials registered on ClinicalTrials.gov from 1 January 2000 to 1 September 2023 and analyzed the eligibility criteria of 191 therapeutic MDS trials. We found that categorical inclusion and exclusion criteria are remarkably similar in representation across trial phases. Additionally, only 13% of trials are concordant with drug safety signals, suggesting that the eligibility criteria are often arbitrary. On behalf of the icMDS (International Consortium for Myelodysplastic Syndromes), an association of international MDS experts, we provide a position statement on restrictive eligibility criteria for MDS clinical trials that should be avoided with the aim of removing barriers to clinical trial enrollment.

Background Flow-diverter stents (FDS) have become the standard of care for a wide range of intracranial aneurysms, but their efficacy/safety in the context of recurrent/recanalized aneurysms following stent-assisted coiling (SAC) is not well established. We evaluate the outcomes of FDS retreatment in a large multicenter cohort. Methods We retrospectively analyzed data from 118 patients across 22 institutions who underwent FDS retreatment for recurrent/persistent aneurysms after SAC (2008–22). The primary outcome was angiographic occlusion status at last follow-up, categorized as complete (100%), near-complete (90–99%), or incomplete (<90%) occlusion. Secondary outcomes included procedural complications and clinical outcomes measured by the modified Rankin Scale (mRS). Results A total of 118 patients (median age 57, 74.6% female) with median follow-up of 15.3 months were identified. Complete occlusion was achieved in 62.5% and near-complete occlusion in 25%. FDS deployment within the pre-existing stent was successful in 98.3% of cases. Major complications occurred in 3.4% of cases, including postoperative aneurysmal rupture with resultant mortality (1.6%) and thromboembolic events with long-term disability (1.6%). Favorable clinical outcomes (mRS 0–2) were observed in 95.1% of patients. Wider aneurysm neck diameter was a significant predictor of incomplete occlusion (adjusted OR (aOR) 1.23 per mm, P=0.044), with male sex trending towards association with non-occlusion (aOR 3.2, P=0.07), while baseline hypertension was associated with complete occlusion (aOR 0.32, P=0.048). Conclusions FDS treatment for recurrent/residual aneurysms after SAC represents a viable treatment option for these challenging cases with acceptable safety and reasonable occlusion rates, although lower than de novo FDS occlusion rates.

Objective The aim of the study was to assess the interrater reliability between seven individuals assessing quadriceps femoris cross-sectional area, echo intensity, and corrected echo intensity. Design A retrospective subanalysis of data collected in a randomized controlled clinical trial (IRB 19-008473. NCT ID NCT04302558). Patients aged 13–50 yrs with an anterior cruciate ligament tear requiring surgical reconstruction were assessed for cross-sectional area of the rectus femoris, vastus intermedius, vastus lateralis, vastus medialis, and vastus medialis obliquis, and echo intensity of the rectus femoris. Musculoskeletal ultrasound imaging of the quadriceps was performed by one physical therapist, and quantitative assessments were performed by four physicians and three physical therapists. Results Physicians and physical therapists had good reliability for cross-sectional area of the rectus femoris (median interclass correlation 0.86 doctor of medicine (MD) and 0.84 physical therapist), cross-sectional area of the vastus medialis obliquis (0.82 and 0.82), and echo intensity mean (0.92 and 0.92). Rectus femoris cross-sectional area had the smallest coefficient of variation (26.512.7%), whereas subcutaneous fat had the largest coefficient of variation (93.3% left, 86.4% middle, 86.1% right). Conclusions These findings demonstrate reliability between physicians and physical therapists in interpretation of ultrasound images of the quadriceps. The inconsistency demonstrates the need for a consistent training across disciplines to ensure accurate image interpretation.

Abstract Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for older adults with hematologic malignancies. Concerns on nonrelapse mortality (NRM) in older adults limit allo-HCT utilization. We executed a prospective, observational study BMT-CTN 1704 (Blood and Marrow Transplant Clinical Trials Network) enrolling allo-HCT recipients aged ≥60 years from 49 centers in the United States. We analyzed associations between 13 measurements of older adult health and NRM within 1 year to construct a comprehensive health assessment risk model (primary-CHARM) using multivariate Fine-Gray model and grouped penalized variable selection. Two machine learning (ML) models (Cox and pseudo-value boosting) were also explored. Models’ performances were compared using area under the curve (AUC), with bootstrap and cross-validation sampling to correct for optimism, decision curve analysis (DCA), calibration, and Brier scores. Among 1105 patients with median age of 67 (range, 60-82) years who received allo-HCT, NRM was 14.4% and overall survival (OS) 71.7% at 1 year. Factors statistically selected for inclusion in primary-CHARM were higher comorbidity burden, lower albumin, higher C-reactive protein, older age, higher weight-loss percentage, lower patient-reported performance score, and cognitive impairment. Primary-CHARM scores were independently associated with higher NRM (hazard ratio [HR], 2.72; P &lt; .0001) and worse OS (HR, 2.09; P &lt; .0001). Bootstrap bias–corrected AUC for primary-CHARM was 0.591. Comparing primary-CHARM with HCT-comorbidity index and 2 ML-CHARM models, calibration, Brier score, and DCA analysis favored primary-CHARM. Primary-CHARM, with mostly simple and readily available parameters, risk stratifies older adults for allo-HCT. Adopting primary-CHARM in practice may promote broader use of HCT by quantifying risk and enhance the design of strategies to improve outcomes. This trial was registered at www.ClinicalTrials.gov as #NCT03992352.

Background Data on the safety profiles and clinical outcomes of patients with solid tumors and cardiac metastasis treated with immune checkpoint inhibitors (ICIs) are limited. Methods This is an international multicenter retrospective study of patients with cancer and cardiac metastasis at baseline. Patients who had received ≥1 dose of ICI were included. Treatment-related adverse events (trAEs) were graded per Common Terminology Criteria for Adverse Event V.5.0. Objective response rates (ORR) were evaluated by Response Evaluation Criteria in Solid Tumors V.1.1 when available. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. Results Among 110 pts, median age at ICI initiation was 65 (IQR: 59–75). Median follow-up time since ICI initiation was 36 (95% CI: 26 to 51) months. Melanoma (38%, n=42) and non-small cell lung cancer (24%, n=26) were the most common. 68 (62%) patients received ICIs as first-line, and 29 (26%) patients were treated with combination anti-programmed death-1 and anti-cytotoxic T-lymphocyte antigen 4. The most common location of cardiac metastasis was in the atria (37%, n=41) and ventricles (35%, n=39). 15 patients (13.6%) had bilateral cardiac/pericardial metastasis, 44 (40%) had left-sided, and 43 (39.8%) had right-sided. At ICI initiation, 21% (n=23) had a cardiac thrombus. Cardiology referrals and cardiac MRIs at the time of cancer diagnosis were completed on 58 (53%) and 52 (47%) patients, respectively. Cardiac events occurred in 40 (36%) patients, including arrhythmias (n=14, 13%), arterial/venous emboli (n=4, 3.6%), and cardiac tamponade (n=3, 2.7%). 53 (47%) patients developed trAEs; most common were colitis/diarrhea (n=16, 15%), dermatitis (n=13, 12%), and hepatitis (n=9, 8.2%). ICI-related major cardiac trAEs occurred in 2 (1.8%) patients. 22 patients (20%) developed grade ≥3 trAE. Patients with multiple cardiac metastases had significantly lower responses to ICI-based regimens compared with patients with single cardiac metastasis (11% vs 63%, p=0.02). For melanoma, ORR, median PFS, and median OS were 38%, 9.0 months, and 28.9 months, respectively. 83% of patients with melanoma had concordant responses in overall disease burden and cardiac disease. 91 patients discontinued ICIs, and the main reason was progression or death in 55 (49%) patients. Conclusions Among patients with pre-existing cardiac metastasis, ICIs demonstrated meaningful clinical efficacy with no increase in safety signals. Most patients had concordant responses in the overall disease burden and cardiac mass. Multidisciplinary teams are crucial for the appropriate management of patients with cardiac metastasis.

686 Background: Blue-light cystoscopy (BLC) is an established procedure for use in the diagnosis and surveillance of patients with non-muscle-invasive bladder cancer (NMIBC). It is associated with improved detection rates compared to white light cystoscopy (WLC); however, limited data is available regarding its role in upstaging and/or upgrading when used alongside WLC. The aim of this study is to assess the incidence and features of patients undergoing upstaging and/or risk-group migration with the implementation of BLC. Methods: Using data from the prospective multi-institutional Cysview Registry (2014-2024), patients with NMIBC who underwent transurethral resection or biopsy of bladder tumors were identified. The patients in whom malignant lesions were exclusively detected by BLC, as well as those experiencing an upward change in risk category (as defined by the American Urological Association [AUA] classification) based on BLC findings, were documented. The clinical features of these patients were subsequently reviewed. Results: In this study, 2,854 patients were enrolled, who collectively underwent 4,158 resections and provided 6,432 separate pathology samples. A total of 201 (7%) patients had at least one malignant lesion detected exclusively by BLC while having negative WLC. These lesions (total 335) included carcinoma in-situ (CIS) in 145 (43%), low-grade Ta in 53 (16%), high-grade Ta in 95 (28%), high-grade T1 in 37 (11%), and high-grade T2 in 5 (1%). In patients with multifocal disease, BLC resulted in AUA risk-group upward migration in 66 (2.3%) patients.Theclinical features of these two groups are presented in the table. Taken together, the total rate of upgrading or upstaging using BLC was 9.3%, including migration to low-risk in 1.2%, intermediate-risk in 2.1%, and high-risk in 6%. Conclusions: Using BLC during transurethral resection or biopsy of bladder tumors results in risk group migration in over 9% of patients with NMIBC. This impacts patient management, including the administration of intravesical therapy when it was not initially planned, an extension in the duration of therapy, or the decision to proceed with radical cystectomy. Clinical features of patients with malignant lesions detected by BLC only (A) and those with risk group migration (B). Clinical features A B Age, median (IQR), year 71 (63-76) 71 (61-77) Gender, n (%) Male Female 140 (74)49 (26) 54 (82)12 (18) History of smoking, n (%) 117 (62) 40 (61) Primary occurrence, n (%) 65 (34) 14 (21) History on intravesical therapy, n (%) 92 (49) 40 (61) Urine cytology * , n (%) Positive Suspicious Atypical Negative/NA 33 (17)21 (10)41 (20)106 (53) 13 (20)7 (11)10 (15)36 (54) IQR: interquartile range; NA: not available. *Detected by either voided urine or bladder wash.

Objectives To evaluate the feasibility for use of electronic health record (EHR) data in conducting adverse event surveillance among women who received mid-urethral slings (MUS) to treat stress urinary incontinence (SUI) in five health systems. Design Retrospective observational study using EHR data from 2010 through 2021. Women with a history of MUS were identified using common data models; a common analytic code was executed at each site. A manual chart review was conducted in a per-site random patient subset to establish a reference standard. Automated text processing (Text Processed Integrated (TPI)) was developed and evaluated at each site to determine the surgical approach and synthetic mesh implantation. Patients were characterized and surgical outcomes were ascertained over 730 subsequent days. Setting Five large tertiary care academic medical centers. Participants Across five health systems, 9,906 eligible patients (mean age 57–60 per site) were identified. Main outcome measures Determination of surgical approach, synthetic mesh implantation, and assessment of the duration of surveillance for mortality and reoperation rates following MUS implantation. Results In the TPI cohort analysis, 3,331 patients were identified. Surgical approach per site was retropubic (42% to 77%), transobturator (6% to 44%), single incision (0% to 24%), and adjustable sling (0% to <4%). Concordance rates for TPI using chart review were 71%–90% at each site for the surgical approach and 28%–85% for synthetic mesh implantation. Patient follow-up observation rates for mortality and reoperation ranged from 22% to 36% at 90 days, 15% to 30% at 365 days, and 8% to 19% at 730 days. Conclusion Using EHR data alone, identification of medical devices and surgical approaches was feasible among women with MUS surgery for SUI, but long-term follow-up ascertainment rates were low. Medical device surveillance using EHR data should be evaluated in the context of the clinical use case, as applicability may vary.

OBJECTIVE The definitive influence of prestroke disability on outcomes in patients with a low Alberta Stroke Program Early CT Score (ASPECTS) treated with endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) due to large-vessel occlusion (LVO) remains unknown. This study aimed to investigate the impact of prestroke disability on outcomes in this specific population. METHODS Data from 32 international centers for AIS-LVO patients with a low ASPECTS who underwent EVT between January 2013 and December 2022 were analyzed retrospectively. Low ASPECTS and prestroke disability were defined as ASPECTS values of 2–5 and prestroke modified Rankin Scale (mRS) score ≥ 2. The primary outcome was a return to the prestroke mRS score at 90 days. Secondary outcomes were independent ambulation (mRS scores of 0–3) or a return to the prestroke mRS score at 90 days, good functional outcome (mRS scores of 0–2) or a return to the prestroke mRS score at 90 days, successful recanalization, and 90-day mortality. Safety outcomes were any intracranial hemorrhage or symptomatic intracranial hemorrhage. A symptomatic intracranial hemorrhage was defined as an intracranial hemorrhage with an associated worsening of ≥ 4 points in the National Institutes of Health Stroke Scale score. Outcomes were compared between patients with and without prestroke disability. RESULTS Of 293 patients, 50 (17.1%) had a prestroke disability. Of 50 patients, 20 (40.0%), 24 (48.0%), and 6 (12.0%) had prestroke mRS scores of 2, 3, and 4, respectively. The primary outcome showed no significant difference between the two groups. Compared with patients without prestroke disability, those with prestroke disability had a significantly smaller proportion of independent ambulation or return to prestroke mRS score (adjusted OR 0.13, 95% CI 0.03–0.53) and good functional outcome or return to prestroke mRS score (adjusted OR 0.21, 95% CI 0.05–0.91). Other secondary and safety outcomes showed no significant difference between the two groups. CONCLUSIONS The present study indicated that prestroke disability was not associated with a return to the prestroke mRS score at 90 days or intracranial hemorrhage. Physicians should not routinely exclude AIS-LVO patients with a low ASPECTS who have prestroke disability from EVT based on prestroke disability alone.