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LBA5012 Background: There is a critical evidence gap on the relative benefits and harms of proton therapy (PT) compared with photon-based intensity-modulated radiation therapy (IMRT) in prostate cancer. Herein we report early results from COMPPARE, a non-randomized comparative study of outcomes with PT and IMRT in prostate cancer. Methods: Between 2018-2022, 2524 patients from 51 facilities (28 PT and 23 IMRT) enrolled in COMPPARE, including 1501 treated with PT and 1023 treated with IMRT, and were followed prospectively. Treatment naïve patients with localized prostate cancer except those with very high-risk disease were eligible. Treatment was pragmatic with daily standard fractionation (1.8-2.1 Gy) and moderate hypofractionation (2.4-3.1 Gy) permitted. Use of rectal spacers and androgen deprivation were at physician discretion. Patient-reported quality of life data and treatment team-reported toxicity and disease control outcomes were collected at baseline and pre-specified time intervals via VisionTreeOptimalCare; treatment planning and delivery data were collected via the Advanced Treatment Consortium. We analyzed 1404 PT patients and 939 IMRT patients. We report the early primary endpoint of the study, a comparison of patient reported bowel urgency and bowel frequency at 2-years using the EPIC tool, and the secondary endpoints of 2-year CTCAE v5 ≥ grade 2 gastrointestinal toxicity outcomes and 3-year freedom from biochemical progression (FFBP) results reported by the study teams. Results: Study sample size was targeted at 1,500 PT patients and 1,000 IMRT patients, and median follow-up time was 4.0 years. The primary endpoint and secondary toxicity 2-year endpoints focused on the alternative hypothesis of PT superiority. All results include inverse probability of treatment weighting. Using generalized linear mixed effects models, we found there to be no significant difference in EPIC bowel urgency scores (p = 0.324) or bowel frequency scores (p = 0.514) between PT and IMRT cohorts over time up to the 2-year endpoint. For grade 2 gastrointestinal toxicity, the 2-year cumulative incidence was 5.2% for PT and 5.6% for IMRT. Gray’s Test for competing risks showed a hazard ratio (HR) of 0.91 [95% confidence interval (CI): 0.65-1.28, p = 0.6] for PT versus IMRT. The exploratory non-inferiority endpoint of 3-year FFBP was 98.0% for PT and 97.9% for IMRT, and Gray’s Test showed a HR of 0.95 (95% CI: 0.52-1.71, p = 0.90). Conclusions: Analysis of early results of COMPPARE show no significant differences between PT and IMRT in patient reported bowel frequency and urgency, grade ≥2 gastrointestinal toxicity, or FFBP. Assessment of long-term disease control, late toxicity and secondary malignancy will require longer follow-up. Clinical trial information: NCT03561220 .

Due to increasingly nuanced Crohn disease therapy selection and disease evaluation, radiologic assessment of transmural healing, although aspirational, may be more complete than endoscopic assessment of mucosal healing, which is the current treatment target.

7546 Background: MRD assessment informs relapse risk in MM but is typically bone marrow-based and invasive. We therefore compared two minimally invasive MRD assays: BM-informed cfDNA whole-genome sequencing (cfWGS) and plasma proteomic MRD (EasyM). Methods: 71 longitudinal plasma samples (22 diagnosis, 49 follow-up) from 22 newly diagnosed MM patients across 8 Canadian sites (TFRIM4) had paired cfWGS and EasyM (Rapid Novor Inc). cfWGS MRD used patient-specific mutation lists from diagnostic BM WGS (Abelman et al., medRxiv 2025). EasyM used mass spectrometry to quantify residual M-protein from baseline. The primary endpoint was progression-free survival (PFS). Results: Among 22 MM patients (8 male, 14 female; median age at diagnosis 62 years), 8 progressed at a median follow-up of 52.6 months (range: 10-79 months). At 1-year maintenance (n = 18 available), cfWGS MRD+ (6/18) predicted inferior PFS (HR 20.12, 95% CI 2.23-181.60, p = 0.007). EasyM any-detect positivity was frequent (16/18, reflecting delayed clearance) and not prognostic (p = 0.99), with poor agreement vs cfWGS (44.4%, κ = 0.118). An exploratory EasyM clearance threshold of 0.93% (hypothesis-generating) classified 5/18 patients as MRD+ and stratified PFS (HR 8.78, 95% CI 1.55-49.82, p = 0.004), improving agreement with cfWGS (17/18, 94.4%, κ = 0.870). Progression clustered in cfWGS+/EasyM-high patients (EasyM >0.93%; 4/5; median 11.9 months post-collection [1.9–22.8]) and occurred once in cfWGS−/EasyM-low patients (1/12, 27.6 months). The only discordant case (cfWGS+/EasyM−) progressed 8.7 months after collection. Higher quantitative MRD burden was associated with inferior PFS (cfWGS: HR 2.92 per 1 SD, 95% CI 1.29-6.59, p = 0.01; EasyM: HR 5.48 per 1 SD, 95% CI 0.79-37.90, p = 0.085). At ~100 days post-autologous stem cell transplantation (ASCT; n = 16 available), EasyM was uniformly MRD+ (16/16) while cfWGS was MRD+ in 7/16 patients. Applying an EasyM clearance threshold (2.13%; 9 cleared vs 7 residual) improved agreement with cfWGS (14/16; 87.5%; κ = 0.746). Of two discordant cases, one cfWGS+/EasyM-cleared patient relapsed 38.6 months post-collection and one cfWGS−/EasyM-residual patient remained progression-free at last follow-up. At post-ASCT, both assays showed consistent but underpowered associations with PFS (cfWGS HR 6.32, 95% CI 0.70–56.76, p = 0.100; EasyM-clearance HR 2.36, 95% CI 0.39–14.18, p = 0.335). Across all post-treatment samples (n = 49), continuous cfWGS burden correlated with EasyM residual M-protein (rho = 0.535, p < 0.001). Conclusions: BM-informed cfWGS MRD strongly stratified PFS, whereas EasyM required a clearance definition due to near-universal early positivity. Concordant plasma burdens support complementary MRD information. Future work will validate these findings in larger cohorts and quantify the incremental value of combined cfWGS and proteomic MRD for early relapse prediction.

7029 Background: Mosun, a CD20xCD3 T-cell engaging bispecific antibody, is approved for relapsed/refractory follicular lymphoma after ≥2 prior lines of therapy. We report an interim analysis and PROs with Mosun SC in elderly/unfit patients with previously untreated DLBCL. Methods: MorningSun (NCT05207670) is a Phase 2, basket study of Mosun SC in patients with B-cell non-Hodgkin lymphoma. In the DLBCL cohort, eligible patients (aged ≥80 years, or 65–79 years and ineligible for chemoimmunotherapy) received outpatient Mosun SC: Day (D) 1 (5 mg), D8 (45 mg) and D15 (45 mg) of Cycle (C) 1, then 45 mg on D1 for up to 17 21-day cycles. Primary endpoint was progression-free survival (PFS) rate at 24 months. Other endpoints included overall survival (OS), objective response rate (ORR), complete response (CR) rate, change from baseline (CfB) in lymphoma symptoms as assessed by the Functional Assessment of Cancer Therapy-Lymphoma subscale (FACT-Lym LYMS; higher scores indicate improvement, a ≥3-point increase is considered clinically meaningful) and safety. Results: Forty-nine patients were enrolled, primarily from community sites (n=34). Median age was 83 years (range: 71–101). International Prognostic Index was 3–5 in 53.1% patients and 18.4% of patients had bulky disease. As of February 10, 2025, the median duration of follow-up was 12.5 months (range: 1.4–30.8). PFS and OS rates at 12 months were 71.3% (95% confidence interval [CI]: 54.8–82.7) and 74.7% (95% CI: 58.5–85.4), respectively. ORR was 73.5% and CR rate was 59.2%. Completion rates for FACT-Lym LYMS were ≥95% at baseline and remained ≥87% at each subsequent timepoint. Patients reported improvement in health-related quality of life (HRQoL) over time, demonstrated by increased mean CfB (standard deviation [SD]) in FACT-Lym LYMS scores: C4D1, 5.1 (9.8); C9D1, 5.6 (11.8); C17D1, 9.8 (11.4). Clinically meaningful improvements in lymphoma symptoms were observed in 53.1% (95% CI: 38.3–67.5) of patients. The most common any-grade adverse event (AE) was injection site reaction (53.1%; all Grade [Gr] 1/2). Gr 3/4 AEs were reported in 65.3% of patients and 8.2% experienced a Gr 5 AE (no Gr 5 AEs were Mosun related, per investigator assessment). Serious AEs occurred in 42.9% of patients. Infection AEs occurred in 49.0% of patients (Gr 1: 4.1%; Gr 2: 28.6%; Gr 3: 16.3%) and resolved in 91.7%. Cytokine release syndrome occurred in 12.2% of patients (Gr 1: 10.2%; Gr 2: 2.0%; all resolved). Updated data with around one additional year of follow-up will be presented. Conclusions: Mosun SC showed promising efficacy with manageable safety in elderly/unfit patients with previously untreated DLBCL in an outpatient setting. Clinically meaningful improvements in lymphoma symptoms suggest that Mosun SC improves aspects of HRQoL in this population. Clinical trial information: NCT05207670 .

Abstract Background Meningiomas exhibit clinical heterogeneity. Radiotherapy (RT) remains the only adjuvant therapy, but tumor-control is variable, and biomarkers are limited. NRG/RTOG-0539 is the first prospective phase 2 trial to stratify meningioma patients for adjuvant RT based on clinical risk. Here, we apply modern molecular tools to this cohort and identify correlates of RT response. Methods Tumor tissue from 100 RTOG-0539 patients was profiled using DNA methylation arrays, RNA sequencing, and whole-exome sequencing. Recurrence scores, Molecular Groups, gene expression, and copy number alterations were compared across clinical groups and between RT responders and non-responders; non-response was defined as progression or death within 3 years. Results Modern grading criteria, including brain invasion, TERT mutation, CDKN2A/B deletion, and 1p/1q status, would reclassify 10% of tumors and alter treatment group assignment in 7%. Non-responders to RT exhibited more frequent 1p and 14q loss, and more copy number alterations. Transcriptomic and epigenetic profiling revealed immune-related signatures in responders and cell cycle–related pathways in non-responders, several of which overlapped with targets of vorinostat, a histone deacetylase inhibitor previously validated in aggressive meningioma models. The Proliferative Molecular Group was an independent predictor of post-RT recurrence in multivariable analysis, outperforming WHO grade. Conclusion Multi-omic analysis of the NRG/RTOG-0539 cohort shows that updated WHO grading criteria, incorporating molecular and cytogenetic features, improve risk stratification. However, molecular classification, particularly the Proliferative group, remains an independent and stronger predictor of RT response. These findings support integrating molecular biomarkers alongside modern grading frameworks to guide treatment and trial design in meningioma. Clinical Trial Information NCT00895622.

The NCCN Guidelines for Prostate Cancer include recommendations for staging and risk assessment after a prostate cancer diagnosis and for the care of patients with localized, regional, recurrent, and metastatic disease. These NCCN Guidelines Insights summarize the panel’s discussions on select 2026 updates to the guidelines regarding nonmetastatic disease: the elimination of the very-low-risk group, updates to the Principles of Active Surveillance, and caution in the use of focal therapy in newly diagnosed patients.

Color Doppler twinkling is associated with rough-surfaced objects like kidney stones, some clinical breast biopsy markers, and polymethyl methacrylate (PMMA) bone cement. Microbubbles are theorized as the predominant source of twinkling, supported by decreased twinkling under increased pressure. PMMA, metallic breast markers, a low-twinkling PMMA sample, and a non-twinkling metal rod were scanned in a pressure chamber up to 1000 psi using a General Electric Logiq E9 system and C1-6 probe (1.7–3.6 MHz Doppler transmit frequency). Clinical markers maintained distinct twinkling up to 250 psi. PMMA often twinkled at higher pressures, sometimes up to 1000 psi. The controls showed no twinkling. To understand physical structure associations with twinkling, the samples were scanned in a micro-CT system with a pixel resolution of 2 μm. Analysis of PMMA and Cork internal voids showed no correlation with twinkling. However, a correlation between Sa (average difference between the mean surface profile and actual surface profile) values and twinkling was found. This indicates that internal structure is not important for twinkling, and certain surface roughness is critical, possibly providing sites for surface microbubbles to oscillate from incident ultrasound waves.

Abstract Context Prior reports of plasma estradiol concentrations and their reference ranges in postmenopausal women identified marked variation, in part due to assay method and body mass index (BMI). Objective To develop an international reference range for plasma estradiol in postmenopausal women, support accurate assessment of concentrations during systemic and local (eg, vaginal) estradiol therapy, and improve risk prediction for diseases, including osteoporosis, breast, and endometrial cancers. Methodology Estradiol concentrations were measured using primarily liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays in 5 international cohorts of community-dwelling, postmenopausal women of primarily European ancestry aged 38-100 years who were not using exogenous estrogens (n = 7206). Measurements were harmonized to the Centers for Disease Control and Prevention (CDC) reference measurement procedure (RMP) by re-assaying a subset of samples for each cohort and generating recalibration equations. Reference intervals were determined for all women, non-obese women, and specific BMI categories. Results Estradiol concentrations from separate LC-MS/MS assays correlated closely with the CDC RMP, and harmonization minimized inter-assay variability. Estradiol concentrations correlated with BMI but not with chronological age. The reference range (2.5th-97.5th percentile) was 1.1-18.2 pg/mL (4.0-66.8 pmol/L) with median of 4.9 pg/mL (18.0 pmol/L) for all postmenopausal women and 1.1-12.5 pg/mL (4.0-45.9 pmol/L) with median of 4.1 pg/mL (15.1 pmol/L) for non-obese women (BMI &lt; 30). Reference ranges increased progressively with higher BMI categories. Conclusion Cross-calibration of estradiol measurements with the CDC RP enabled the development of harmonized plasma estradiol reference ranges for postmenopausal women who were not using exogenous estrogens, suitable for future studies to establish clinical utility. Increasing obesity in postmenopausal women was associated with increasing estradiol concentration and BMI category-specific reference ranges.

Abstract Introduction As targeted treatments for narcolepsy type 1 (NT1) emerge, timely diagnosis and care planning are essential to optimize outcomes. This ongoing initiative aims to identify and address barriers to NT1 recognition and treatment to support practice improvements and patient-centered care. Methods Patient surveys (N=38) were collected in August 2025 through collaboration with the Hypersomnia Foundation to inform an ongoing initiative at five US sleep centers. Results from patient surveys are reviewed at expert-led clinic-based sessions to identify patient needs in care, and case-based discussions challenge participants to apply the latest evidence into practice scenarios. Pre- and post-session surveys are designed to measure the impact on knowledge, confidence, and self-reported performance. Additionally, clinicians will develop strategies for care improvement. Results The top patient-reported barriers to NT1 diagnosis were finding a provider familiar with sleep disorders (42%) and limited appointments/referrals (26%). Ninety-five percent waited over 1 year for formal diagnosis (1-5 years, 71%; 5-10 years, 19%; &gt;10 years, 5%). Narcolepsy symptoms had a significant impact on daily living (82%; 4 or 5 on a 5-point Likert scale), with many patients reporting fatigue (63%), excessive daytime sleepiness (58%), disrupted nighttime sleep (53%), sleep paralysis (50%), and cataplexy (37%) despite treatment. Patients’ top treatment goals were finding a treatment that is effective for their symptoms/type of narcolepsy (61%) and that improves daily functioning/quality of life (55%). However, 19% (1, 2, or 3 on a 5-point Likert scale) reported their care team had not discussed treatment options and 37% (1, 2, or 3 on a 5-point Likert scale) were not routinely asked about treatment goals. Patients were interested in discussing the cause of narcolepsy (63%) and their preferences for treatment (61%). Preliminary findings from the clinic-based sessions have generated practical strategies to address identified gaps in NT1 care. Conclusion Patient surveys uncovered persistent challenges in NT1 diagnosis, communication, and treatment planning. Incorporating these perspectives and case-based scenarios into clinic-based sessions have the potential to improve focused approaches to care and can provide a foundation for integrating evidence into practice as the NT1 landscape evolves. Support (if any) This program was supported by an educational grant from Takeda Pharmaceuticals U.S.A., Inc.