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Bispecific antibodies have recently received approval for relapsed refractory B-cell lymphomas (r/r BCL). Little is known about the safety of radiation (RT) delivered with bispecific therapy (BT). We sought to assess the toxicity of combination therapy with BT and RT. We retrospectively identified patients (pts) at a single institution receiving BT and RT between 2018 and 2023. The temporal relationship of RT with respect to BT was defined as follows: "Pre-BT" RT 3 months (mo) prior to and up to the first dose of BT, "Peri-BT" 1 or more RT fractions between the first and last bispecific dose, "Post-BT" RT after the last BT dose through 3 mo post-BT. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded per ASTCT, and all other toxicities per CTCAE version 5. Nineteen patients underwent 20 courses of BT and received RT to 34 lesions. BT included mosunetuzumab (8), blinatumomab (7), epcoritamab (4), and glofitamab (1), with median BT treatment duration of one mo (0-6). Median follow up post RT and post BT was 2 mo (0-48) and 1 mo (0-48), respectively. Baseline characteristics were as follows: median age 61 (45-86), 25% female, 55% ECOG 0-1, histology DLBCL 65%, FL 25%, Grey zone 5%, Burkitt 5%, prior treatments 4.5 (1-12), 45% prior CAR T, 85% advanced stage, 80% extranodal, and 15% bulky disease (> 10 cm). Of the radiated lesions, 56% were Pre-BT (38% within 4 weeks of BT start), 21% Peri-BT, and 26% Post-BT. Sites treated included 29% spine/paraspinal, 21% abdomen/pelvis, 18% axilla, 15% head/neck, 6% skin/subcutaneous, 6% thorax, 6% CNS. Eighty-eight percent of lesions received RT with palliative intent. 16% of pts received comprehensive RT to all active lesions (5% bridging pre-BT, 11% salvage). Median CTV was 174 cc (10-4376). Median total dose was 20 Gy (4-45). Among DLBCL pts, the most common regimens included 20 Gy/5 fx (64%), 8 Gy/2 fx (16%), and 30 Gy/10 fx (12%). Common regimens among FL pts included 4 Gy/2 fx (50%), 8 Gy/2 fx (17%), and 30 Gy/10 fx (17%). CRS and ICANS events were infrequent, and all low grade (4 (20%) Gr 1-2; 3 (15%) Gr 1-2, respectively). Radiation-related toxicities were similarly all low grade. Of all lesions treated, 35% were associated with Gr 1 toxicities, and 24% with Gr 2. Toxicities included fatigue (29%), dermatitis (21%), nausea (9%), GI (15%), pain (3%) and dry mouth (3%). No patients were hospitalized for bispecific related toxicity. RT with BT appears safe, with acceptable rates of low grade, RT-related toxicity. CRS and ICANS events were infrequent and all low grade, suggesting no obvious exacerbation by RT. The safety and efficacy of combination RT and BT warrants further study in larger cohorts. [ABSTRACT FROM AUTHOR]

As a genomic resource provider, grappling with getting a handle on how your resource is utilized can be extremely challenging. At the same time, being able to thus document the plethora of use cases is vital to demonstrate sustainability. Herein, we describe a flexible workflow, built on readily available software, that the Human Disease Ontology (DO) project has utilized to transition to semi-automated methods to identify uses of the ontology in the published literature. The novel R package DO.utils (https://github.com/DiseaseOntology/DO.utils) has been devised with a small set of key functions to support our usage workflow in combination with Google Sheets. Use of this workflow has resulted in a 3-fold increase in the number of identified publications that use the DO and has provided novel usage insights that offer new research directions and reveal a clearer picture of the DO's use and scientific impact. The DO's resource use assessment workflow and the supporting software are designed to be useful to other resources, including databases, software tools, method providers and other web resources, to achieve similar results. Database URL: https://github.com/DiseaseOntology/DO.utils [ABSTRACT FROM AUTHOR]

Assess the value of 3rd trimester uterine artery (UtA) Doppler for predicting adverse outcomes in placental intrauterine growth restriction (IUGR). Results Of 1600 patients with EFW < 10th centile, 98 pregnancies met criteria for placental IUGR, 55 of which had abnormal UtA Doppler. [Extracted from the article]

Elevated LDH is associated with inferior outcomes for R/R BCL patients (pts) receiving chimeric antigen receptor T cells (CAR T). We assessed the proportion of pts who experience LDH normalization following bridging radiotherapy (BRT) and prognostic implications. We retrospectively analyzed 172 pts across 10 institutions who received BRT prior to CAR T from 2018-2020. LDH was collected both prior to leukapheresis (preBRT) and prior to CAR T infusion (postBRT) and classified as "Hi" or "Lo" based on institutional upper limits of normal. Pts were categorized into 4 groups: HiHi, HiLo, LoHi, and LoLo, based on their two respective LDH values. Progression-free survival (PFS) and overall survival (OS) were calculated from CAR T infusion using the Kaplan-Meier methods and modeled using Cox regression. Baseline characteristics were as follows: median age 62, 74% female, 71% diffuse large B cell lymphoma, 74% advanced stage, 39% bulky disease (≥10cm), 66% elevated preBRT LDH, 44% elevated postBRT LDH. 39% of pts received comprehensive BRT and 23% received systemic bridging. Of those with initially elevated LDH, 39% experienced normalization postBRT. Those with HiLo LDH had similar PFS and OS to those with LoLo LDH (p=0.42; p=0.64, respectively), and better PFS and OS compared to those with HiHi (p<0.001; p<0.001, respectively) and LoHi (p=0.002; p<0.001, respectively). Complete response (CR) rates differed between cohorts (p<0.001), with superior CR rates in HiLo and LoLo groups. Excluding pts who received systemic bridging, the PFS and OS differences across LDH subgroups were maintained (Table 1). Cytokine release syndrome grade 3+ events were low among all groups and neurotoxicity occurred less frequently among HiLo and LoLo cohorts (p=0.02). On multivariable analysis, pre-infusion normal LDH values (HR= 0.41, p<0.001) and comprehensive BRT (HR=0.42, p<0.001) maintained superior PFS. In pts with high preBRT LDH, those who achieved normalization were more likely to have received comprehensive BRT (p=0.002). Nearly 40% of pts with elevated pre-apheresis LDH experienced LDH normalization following BRT. These pts have superior clinical outcomes compared to those with persistently elevated LDH and comparable outcomes to those with persistently normal LDH. BRT may neutralize risk factors in at-risk pts with LDH response acting as a potential surrogate for treatment response. [ABSTRACT FROM AUTHOR]

Low-dose TSE can rapidly attain cutaneous control in MF/SS, though duration is limited. Hypofractionated (HF) TSE is gaining interest due to shorter treatment schedules and potential for decreased lymphotoxicity. However, the impact of standard fractionation (SF) or HF TSE on hematologic parameters is poorly characterized, and in advanced MF/SS cytopenias may preclude or delay initiation of critical systemic therapy. Here, we compare hematologic toxicities among SF and HF regimens. From 2015-2023, 111 patients (pts) underwent 121 courses of SF or HF TSE. SF was defined as 1 Gy/fraction totaling 12 Gy, and HF as 1.5-2 Gy/fraction totaling 12 Gy. Complete blood counts were recorded at the following intervals: 1 month (mo) pre-RT (3 mo pre-RT when 1 mo data were unavailable), -1 week through 1 mo post final RT fraction, >1-2 mo, and >2-3 mo. Toxicities were graded per CTCAEv5, with grade 1-2 categorized as low grade (LG) and 3-4 as high grade (HG). There were 104 SF and 17 HF courses of TSE, with median follow up of 21 mo (0-86). Cohorts were well balanced other than ECOG performance status (PS) 0-1 vs. 2-4, with poorer PS in the HF group (p = 0.03). At baseline, 16% had leukopenia (1% HG), 69% had anemia (all LG), 11% had thrombocytopenia (all LG), 45% had lymphopenia (17% HG), and 8% had neutropenia (1% HG). There were no significant differences in pre-TSE cytopenias between cohorts. Cytopenia rates post TSE did not differ between cohorts (see Table 1). HG lymphopenias were observed at all time points among the SF and HF cohorts: pre-TSE 16% vs 25%, -1 week-1mo 23% vs 33%, > 1 mo-2 mo 19% vs 29%, and > 2-3 mo 11% vs 20% (p > 0.05). Best cutaneous response rates did not significantly differ between SF and HF groups: CR 18% vs 18%, PR 73% vs 77%, SD 5% vs 0%, POD 1% vs 6%, unknown 3% vs 0%, respectively (p = 0.5). Median time to best response was 1.9 vs 2.8 months respectively (p = 0.2). Median time to disease progression was 5.8 vs 6.4 months, respectively (p = 0.8). MF/SS pts presenting for TSE have high rates of cytopenias at baseline which persist following TSE. Cytopenias following TSE and response rates did not differ between SF and HF regimens. Thus, TSE for cutaneous control using SF or HF appears unlikely to prevent subsequent initiation of systemic therapy due to hematologic toxicity. Table 1. Cytopenias following TSE by fractionation regimen. [ABSTRACT FROM AUTHOR]