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Importance Amyloid positron emission tomography (PET) is increasingly used in research and clinical settings to determine the etiology of cognitive decline and eligibility for amyloid-targeting therapies. To assist with amyloid PET evaluation and to guide clinical decision-making, images can be quantified in a standardized unit called Centiloid, the interpretation of which can vary according to the method and threshold used. Objective To collect Centiloid values from available studies and determine robust positivity cutoffs using data-driven methods and correspondence with visual reads. Data Sources PubMed search (October 2024) identified studies with Centiloid values. Corresponding authors were invited to share individual participant data. Additional data were obtained through access-controlled repositories and conference outreach (July 2024-July 2025). Study Selection Studies were included if they provided Centiloids, radiotracer, age, and sex. Data Extraction and Synthesis Each study was analyzed using a unified statistical pipeline; study estimates were pooled using random-effects meta-analysis. Main Outcomes and Measures Gaussian mixture models (GMMs) were fitted to Centiloid values for each study. In studies with a bimodal distribution (per integrated completed likelihood), single cutoffs for positivity were set as mean plus 2 SDs of the lower gaussian component. Using GMMs, a double-cutoff approach defined a lower certainty range using a 90% posterior probability cutoff for assignment to the low (amyloid-negative) vs high (amyloid-positive) component. An alternative Centiloid cutoff was derived from maximizing the correspondence (Cohen κ) with the binary visual reads when available. Results This meta-analysis included cross-sectional amyloid PET scans acquired with 5 radiotracers from 49 227 participants across 53 studies from 15 countries (mean age, 71 years; 54% female, 62% cognitively impaired). The data-driven GMM approach identified a bimodal distribution in 51 studies (n = 48 786), resulting in a single cutoff for positivity of 18 Centiloids (95% CI,16-19; I 2 = 97%). The double-cutoff approach revealed high confidence for interpreting scans as negative when Centiloid values were lower than 11 (95% CI, 9-13; I 2 = 95%) and interpreting scans as positive if Centiloid values were higher than 26 (95% CI, 24-28; I 2 = 95%). In analyses of correspondence with binary (positive or negative) visual reads of amyloid PET scans (n = 35 045; 36 studies), Centiloids were highly predictive of visual positivity (Cohen κ, 0.86; 95% CI, 0.83-0.89; I 2 = 96%) with a cutoff of 27 Centiloids (95% CI, 24-30; I 2 = 80%). Conclusions and Relevance In this individual participant data meta-analysis, positivity cutoffs converged around 18 Centiloids (data-driven) and 27 Centiloids (visual reads). Findings from a double-cutoff analysis suggest that scans in the 11 to 26 Centiloid range should be interpreted with caution depending on the context of use.

TPS160 Background: Up to 50% of patients with gastric cancer (GC) may develop peritoneal metastasis (PM) that is associated with resistance to systemic therapy and poor prognosis. Although cytoreductive surgery and intraperitoneal (IP) chemotherapy were shown to modestly improve the survival of patients with PM from gastric GC (PM-G), these clinical trials were performed in the pre-immunotherapy era. The significant heterogeneity in trial design and patient selection criteria further limit the applicability of these trial results to current clinical practice where anti-PD-1/L1 immunotherapy and/or targeted therapy in combination with chemotherapy have become a common, standard first-line therapy for the majority of patients with metastatic GC, raising the question of whether chemotherapy such as paclitaxel remains the most effective IP therapy. IP therapy using novel immunotherapy such as bispecific antibodies and chimeric antigen receptor T-cell therapy have demonstrated safety and promising antitumor activities in PM-G. We are conducting a phase 1b clinical trial that evaluates the efficacy of IP interleukin-2 (IL-2) in patients with PM-G with stable disease on first-line chemo-immunotherapy based on the hypothesis that IP IL-2 may synergize with intravenous (IV) chemo-immunotherapy to improve the treatment of PM-G. Multi-omics studies using patient blood, peritoneal fluid, and tissue specimens serially collected from this trial will be performed to characterize the changes in the tumor immune microenvironment of PM-G and identify new therapeutic targets. Methods: Patients with PM only from gastric adenocarcinoma are eligible for this phase 1b trial. All participants will continue IV fluorouracil-containing chemotherapy with nivolumab every 2 weeks and concurrently receive up to 16 doses of IP IL-2 (aldesleukin 6 × 10 5 IU/m2) weekly through an indwelling peritoneal catheter (Bard). Diagnostic laparoscopy (DL) will be performed before initiation of IP IL-2 and after 8 doses of IP therapy to assess treatment response based on the peritoneal cancer index (PCI), which is the primary endpoint of the trial. Patients with at least stable radiographic disease will continue to receive another 8 doses of IP IL-2 and undergo a third DL. Secondary endpoints include safety, peritoneal regression grading score, overall survival, and progression-free survival. Major inclusion criteria include mismatch repair-proficient or microsatellite-stable GC, PCI of 3-24, absence of distant metastasis other than PM, stable disease on first-line IV chemo-immunotherapy, tolerability of anti-PD-1 therapy, and adequate organ function. Enrollment began in 2024 and remains active. To date, seven of planned 15 patients have received study treatment without significant treatment-related adverse events and three of these patients underwent curative-intent cytoreductive surgery. Clinical trial information: NCT05802056 .

PURPOSE In large B-cell lymphoma (LBCL), use of high-dose methotrexate (HD-MTX) to prevent CNS relapse (so-called CNS prophylaxis) remains controversial. International guidelines continue to recommend HD-MTX in patients deemed ultra high risk (UHR) because of a lack of robust data specific to these subgroups. This study was designed to examine the impact of HD-MTX specifically in UHR patients. METHODS Data from two previous retrospective analyses were combined to produce a cohort of UHR patients (≥1 of the following criteria: CNS international prognostic index score 5-6; testicular, renal/adrenal, or breast involvement; ≥3 extranodal sites), treated with or without HD-MTX. The primary outcome was CNS relapse rate (isolated or concurrent with systemic relapse) measured from diagnosis with additional landmark analysis of all responding patients with no progression event at 6 months. RESULTS Analyses were performed on 1,923 patients meeting UHR criteria. No significant difference in 3-year CNS relapse rate was observed between no HD-MTX (n = 1,051) versus HD-MTX patients (n = 872), including in multivariable analyses adjusting for baseline characteristics (3-year rate, 9.3% v 8.1%; adjusted hazard ratio [HR], 1.13 [95% CI, 0.82 to 1.57]). Analyses restricted to isolated CNS relapse also confirmed no difference (5.9% v 5.7%; adjusted HR, 1.03 [95% CI, 0.69 to 1.53]). In the landmark analysis (no HD-MTX n = 782, HD-MTX n = 773), no difference in 3-year CNS relapse was observed (6.7% v 6.6%, adjusted HR, 0.95 [95% CI, 0.62 to 1.44]). CONCLUSION To our knowledge, this is the largest international comparative data set of patients with LBCL with UHR features showing no significant reduction in CNS relapse with HD-MTX in all UHR or in any individual subgroup. Despite inherent limitations of retrospective analyses, the data strongly support previous studies in suggesting HD-MTX prophylaxis has no meaningful benefit for most patients.

Recent advances in gastroesophageal cancer highlight the continued evolution of systemic therapy across disease stages, including refinements in perioperative strategies and expansion of biomarker‐directed treatment in advanced disease. Emerging therapeutic approaches, including next‐generation antibodies and combination strategies, are expected to further shape treatment selection and improve outcomes.

This multicenter, single-arm, phase 1/2 study evaluated the safety and efficacy of CD19-directed allogeneic chimeric-antigen-receptor (CAR) immunotherapy CTX110 in adult patients with relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (NHL). Patients received 1 or 2 treatment courses: standard lymphodepletion, followed by 1 CTX110 infusion at dose levels (DLs) 1-4 (3-60 × 107 CAR T-cells; dose escalation, N=32), or 2 infusions at DL4 on days 1 and 35 (cohort expansion, N=31). Primary endpoints in dose escalation and cohort expansion were incidence of dose-limiting toxicities and objective response rate, respectively. CTX110 was administered to 63 heavily pretreated patients: 59% primary refractory, 43% with ≥3 prior treatment lines. Among 57 patients whose first infusion was DL≥3, rates of objective and complete response (CR) were 65% and 39%, respectively. Among 22 patients achieving CR, 5 (23%) had ongoing CR at data cutoff, with 15-50 (median 34) months follow-up. The 2-infusion regimen appeared to prolong response duration compared to 1 infusion (hazard ratio 0.65). Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were reported in 54% and 13% of treated patients, respectively, including 2 grade ≥3 cases each. The most common grade ≥3 adverse events were neutropenia (59%), and anemia and thrombocytopenia (35% each). Serious adverse events occurred in 32% of treated patients, including CRS (14%), ICANS (8%), and febrile neutropenia (6%). In this r/r NHL population, CTX110 was well-tolerated, resulting in clinically meaningful responses at DL≥3, with a second infusion demonstrating evidence of further clinical benefit. This trial (NCT04035434) was registered at www.clinicaltrials.gov.

Abstract A short diagnosis-to-treatment interval independently predicts inferior outcomes in follicular lymphoma. Using international discovery and validation cohorts, we demonstrate its prognostic value beyond established prognostic indices, with implications for risk stratification, clinical trial design, and interpretation.

Abstract We evaluated outcomes by management type for patients with stage IA nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) in the Global NLPHL One Working Group retrospective database of 2243 patients with stages I to IV disease diagnosed from 1992 to 2021 at 38 international institutions. A total of 779 patients had stage IA disease with median age of 35 years (range, 3-89) and median follow-up of 6.1 years. The 6-year progression-free survival (PFS) and overall survival were 86.3% and 97.7%, respectively. Outcomes were analyzed for the 2 groups: complete resection and unresected disease. Patients with a complete resection and observation alone (n = 99) had a 6-year PFS of 65.5% vs 90.5% for those who received radiotherapy (RT) (n = 53). Patients with unresected disease (n = 627; 80.5%) had a 6-year PFS of 62.0% for rituximab alone (n = 31), 89.6% for RT alone (n = 325), 76.8% for ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) alone (n = 40), and 94.3% for ABVD plus RT (n = 130). A total of 127 patients relapsed (16.3%), of which 25 (19.7%) had transformation. Our analysis suggests the following: (1) RT improves the PFS in patients with completely resected disease; (2) rituximab or ABVD alone does not appear to achieve a durable response; and (3) chemotherapy was not observed to add additional PFS benefit when used in combination with RT. Thus, for stage IA NLPHL, RT alone is likely sufficient for definitive treatment.

Abstract Purpose Consensus recommendations and guidelines for reporting quantitative research in health professions education (HPE) research are lacking. This study synthesizes available quantitative reporting recommendations and guidelines to present a harmonized framework and derive quantitative standards for reporting HPE research. Method The authors identified existing standards, recommendations, and guidelines from peer-reviewed scientific journals in medicine, education, and social sciences by searching PubMed, Web of Science, and Google from August 2006 through April 2025. The authors also requested input from experts in HPE (scholars and journal editors) via electronic communication over 6 months (November 2024 to April 2025). The articles identified were then used to synthesize and generate an initial list of standards for reporting quantitative research in HPE. Two authors reviewed each article to rate its alignment with HPE research. All authors independently evaluated the full list of standards and discussed them as a group for their relevance and alignment for reporting in HPE; all authors also made recommendations for each standard (to report as is, report but modify, or drop). The group subsequently reviewed and collectively reached consensus on the final set of quantitative reporting standards. Results The authors reviewed a total of 34 articles, with 19 identified as having alignment with HPE quantitative research standards. Mean interrater agreement among author pairs was 98% (kappa = .96). Authors initially generated 40 reporting standards, of which 18 (45%) were modified and 1 (3%) was identified to be dropped. The final set of quantitative guidelines consisted of 39 standards, with each standard nested in one of 28 topic areas. Conclusions The quantitative reporting standards identified in this study provide guidance to ensure rigor in reporting expectations for HPE research. These standards may also facilitate critical appraisal of articles and enhance the quality and impact of quantitative HPE research.