Citations

Abstract Surgery continues to be a mainstay of treatment for patients with symptomatic fibroids. Hysterectomy is an option for those desiring definitive treatment and myomectomy is preferred for those that have not yet completed childbearing or wish to retain their uterus. While open laparotomy remains a viable approach to both hysterectomy and myomectomy, minimally invasive techniques for the surgical management of symptomatic fibroids are preferred options for many due to improved patient outcomes. These include hysteroscopic myomectomy, laparoscopic and robotically assisted myomectomy, and vaginal, laparoscopic, and robotically assisted hysterectomy. Patients have a faster recovery and less postoperative pain compared to a laparotomic approach. More recently, uterine‐sparing outpatient modalities such as ultrasound‐guided radiofrequency ablation and high‐intensity focused ultrasound have emerged as promising alternatives for selected patients. Benefits include clinically significant reduction in fibroid size and menstrual bleeding with small or no abdominal incisions and an expedited convalescence. This article reviews preoperative evaluation and imaging for fibroids, as well as the techniques, approach, indications, patient selection, procedural management, and surgical and fertility outcomes for each surgical and procedural management of uterine fibroids.

ABSTRACT Apheresis medicine is a continually evolving field with numerous studies published each year. To help apheresis practitioners stay up to date with the current literature, members of the American Society for Apheresis (ASFA) Attending Physician Subcommittee identified and summarized 10 seminal articles published in 2025, from the field of apheresis medicine. PubMed was used to identify articles published in four topics including donor apheresis, therapeutic apheresis, apheresis education, and apheresis collection for cellular therapy. These articles met at least one of the following criteria: novel findings, practice‐altering outcomes, international in scope, randomized‐controlled trial, relevant to current clinical practice, and/or provide evidence for category III or IV indications based on the ASFA 9th Special Issue of the Guidelines on the Use of Therapeutic Apheresis in Clinical Practice‐Evidence‐Based Approach. Full length, peer‐reviewed manuscripts in English with data from human subjects were included while case reports, review articles, and meta‐analyses were excluded.

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.

Abstract Antidepressants are widely prescribed for major depressive disorder, yet only one-third of patients achieve remission after initial treatment. Previous genome-wide association studies (GWAS) of clinically assessed antidepressant response combined multiple antidepressant classes, potentially obscuring class-specific effects. This study focused on selective serotonin reuptake inhibitors (SSRIs), often first-line due to better tolerability. Data from 15 cohorts across four ancestries were integrated: European (N = 3887; 11 studies), East Asian (N = 1068; 4), African (N = 277; 1), and Admixed American (N = 250; 1). GWAS of non-remission and percentage improvement were conducted within cohorts, followed by ancestry-specific meta-analyses and trans-ancestry meta-regression. Single nucleotide polymorphism (SNP)-based heritability was estimated in European samples. Polygenic scores were used for leave-one-out prediction and to assess shared genetic architecture with psychiatric traits. Gene-level and gene-set enrichment analyses were also performed. No genome-wide significant variants were identified for either outcome in any ancestry-specific or trans-ancestry analyses. However, trans-ancestry meta-regression yielded eight independent loci with suggestive associations (p < 1 × 10 −5 ) for non-remission and 17 for percentage improvement. Gene-set analyses revealed nominal enrichment of the serotonergic synapse pathway for non-remission. SNP-based heritability estimates were not significantly different from zero for either outcome. Better SSRI response was nominally associated with lower genetic predisposition to major depressive disorder, post-traumatic stress disorder, and schizophrenia. This study represents the largest trans-ancestry GWAS of SSRI response, highlighting emerging biological signals. Limited power emphasises the need for larger and ancestrally diverse cohorts to better characterise the genetic architecture of antidepressant response.

Abstract Skull bone marrow (BM) is a recently identified site for immune activation responsive to CNS insults. The extent to which adaptive immunity is generated through skull BM is poorly understood. In this study, we evaluated how skull BM supports the early expansion of antiviral CD8 T cells during acute neurotropic virus infection. Virus antigen-specific CD8 T cells were rapidly identified in skull BM at a rate comparable to lymphoid compartments during acute Theiler’s murine encephalomyelitis viral (TMEV) infection. We therefore employed MHC class I conditional knockout mice and demonstrated the necessity of CD11c+ antigen-presenting cells (APCs) for the generation of various subsets of TMEV-specific CD8 T cells in skull BM. Importantly, the early expansion of skull BM-derived antiviral T cells was impeded by FTY720 treatment and restored upon shared circulation with a mouse exhibiting intact antigen presentation by CD11c+ APCs. Additionally, TMEV-specific CD8 T cells were retained in skull BM during both chronic CNS infection and long after infection has been resolved. Overall, we determined that skull BM responds to acute neurotropic viral infection through the rapid recruitment of virus-specific CD8 T cells primed in the periphery before serving as a reservoir for immunologic memory.

TPS6126 Background: Oral cavity cancers (OCC) are a rare subtype of head and neck cancer (HNC) with poor outcomes and limited second-line treatment options in the recurrent or metastatic (R/M) setting. Treatment-related morbidity and repeated local recurrences in OCC result in significant impairment of function and quality of life. Rural OCC patients comprise a sizable portion (50%) of our practice and are usually of lower socioeconomic status with lack of access to specialist care. They also have multiple barriers to treatment access and ancillary services, translating to poorer clinical outcomes. There is a critical need for effective and accessible therapies for R/M OCC in rural patients. Triple oral metronomic chemotherapy (TOMC) with Methotrexate, Erlotinib and Celecoxib (MEC) suppresses angiogenesis and activates antitumor microenvironment in HNC. Studies using TOMC in R/M OCC outside the US show reasonable efficacy (6-month OS 52.9%), better safety and lower cost compared to standard second line options. We hypothesize that a decentralized clinical trial with TOMC in R/M OCC is feasible, safe and effective in addition to being economical and accessible for rural patients. Methods: MC240701 is a single institution, open label, decentralized, single arm pilot study of MEC in patients with R/M OCC. Eligible pts must be ≥18 years old, have pathologically confirmed R/M OCC not amenable to curative-intent therapy, ECOG 0-2 and adequate organ function. At least 1 measurable lesion by RECIST 1.1 OR non-measurable disease (evident mucosal lesions, CNS/bone disease, lesions not meeting RECIST criteria) is permitted. Patients must have received standard first line immunotherapy with or without chemotherapy OR should be unable/unwilling to receive first line treatment. Key exclusion criteria include patients unable to take pills by mouth, serious medical co-morbidity or autoimmune disease, immunocompromised patients and other active malignancy. Primary endpoint is to demonstrate feasibility of decentralized clinical trials, secondary outcomes include overall response rate, progression free and overall survival and toxicity. Additional goals are to evaluate patient impact of decentralized treatment through surveys and interviews After initial screening and evaluation, patients are remotely consented and will receive study drugs by mail. All patients will receive the same treatment of Methotrexate 9mg/m 2 PO weekly, Erlotinib 150 mg PO daily, and Celecoxib 200 mg PO BID, each cycle will be 28 days. Treatment will continue until disease progression or treatment tolerance, study duration is for 2 years. All subsequent clinical and laboratory monitoring and response assessments (every 3 cycles) will be remotely performed or have an option for local testing. Enrollment began July 2025 and 4 out of planned 25 patients have been accrued. FDA IND:174540. Clinical trial information: NCT06997068 .

5069 Background: Inhibition of androgen receptor (AR)-signaling results in increases in double-strand DNA breaks and genomic instability. PARP inhibitors (PARPi) are a standard treatment option for patients (pts) with homologous recombination repair mutations (HRRm). Combinations of PARPi and AR pathway inhibitors (ARPI) are associated with synthetic lethality in multiple pre-clinical studies. Clinical trials have suggested potential benefits with co-targeting PARPi and ARPI in pts with and without HRRm. Methods: Alliance A031902 compared radiographic progression-free survival (rPFS) and overall survival (OS) as co-primary endpoints with enzalutamide and rucaparib (Enz/Ruca) versus enzalutamide plus placebo (Enz/Plac) for pts with metastatic castration resistant prostate cancer (mCRPC) regardless of BRCA/HRRm status. This trial was conducted by the Alliance for Clinical Trials in Oncology in 36 centers in the US. Target sample size was 1,002 patients. Eligibility required mCRPC with or without measurable metastatic disease and was agnostic regarding HRRm status. The trial was discontinued in 10/2023 due to changes in the treatment landscape for this pt population. Results: Between 10/21 and 4/23, 61 pts were randomized to Enz/Ruca (n=30) or Enz/Plac (n=31). Known BRCA1/2 or PALB2 mutations were present in 1 pt (3.3%) in the Enz/Ruca arm and 1 pt (3.2%) in the Enz/Plac arm; wildtype in 14 (46.7%) vs 15 (48.4%), and unknown in 15 (50%) vs 15 (48.4%), respectively. Three patients (11.5%) in the Enz/Ruca arm discontinued due to an adverse event (AE) vs 0 in the Enz/Plac arm. Among response-evaluable pts, 7/26 (27%) in the Enz/Ruca arm discontinued due to disease progression vs 10/31 (33%) in the Enz/Plac arm. Most common grade 3+ AEs were anemia (33% vs 3%) and hypertension (17% vs 10%) in the Enz/Ruca arm and Enz/Plac arm, respectively. All 61 pts were evaluable for response assessment. PSA declines ≥50% and ≥90% were observed in 79% vs 45% and 60% vs 43% of pts receiving Enz/Ruca versus Enz/Plac, respectively. Median PFS in the Enz/Ruca vs Enz/Plac arms was 17.1 vs 14.2 mos, respectively (HR 1.13 [95% CI: 0.42-3.01], p=0.81), median rPFS (inclusive of unequivocal clinical progression) was 17.1 vs 11.7 mos ( HR 0.72; 95% CI: 0.31-1.67, p = 0.44), and median OS was not reached vs 27.0 mos (HR 0.65; 95% CI: 0.29-1.45, p=0.29). Conclusions: In this prematurely terminated phase III study, Enz/Ruca was generally well tolerated, with the safety profile consistent with prior PARPi/ARPI combinations. Efficacy outcomes for rPFS and OS are inconclusive due to limited sample size. Definitive conclusions regarding the clinical benefit of this combination cannot be determined from this study. Clinical trial information: NCT04455750 .

3118 Background: Improved risk stratification is critically needed across multiple cancers to guide treatment decisions. This includes reducing overtreatment in Ductal Carcinoma in Situ (DCIS), addressing late recurrence risk in estrogen receptor-positive/lymph node-negative (ER+/LN-) breast cancer (BC), and refining prognosis in head & neck squamous cell carcinomas (HNSCC), and high-grade serous ovarian carcinoma (HGSOC). Tumor-infiltrating lymphocytes (TILs) reflect anti-tumor immunity, whereas tumor-associated macrophages (TAMs) polarize toward anti-tumor M1-like (CD68+) or immunosuppressive M2-like (CD163+) phenotypes. Integrating TILs with TAM polarization markers may better capture inflammatory balance and improve outcome prediction. We developed a hematoxylin and eosin (H&E)-only AI method (VAIP) to quantify TILs and virtual CD68/CD163 TAMs to develop multi-cancer based potential prognostic models. Methods: TILs were detected on H&E with HoVer-UNet, and virtual CD68 and CD163 macrophages were inferred with VISTA. In cancer regions, we computed cell densities and immune-balance ratios and trained cancer-specific Cox models with compact feature sets (DCIS 6; HGSOC 7; ER+ 4; HNSCC 4). Prognostic stratification used disease-free survival (DFS) for DCIS (N=273), HGSOC (training N=165, independent test N=220), and ER+ BC (training N=144, test N=622), and overall survival (OS) for HNSCC (N=77), reflecting clinical endpoints. Evaluation used cross-validation for cohorts without an external test set (DCIS, HNSCC) and independent training and testing when independent cohort was available (HGSOC, ER+). Results: Risk stratification performance across cancer types is in Table 1. The DCIS model used 6 features, largely TIL-macrophage contrast ratios (TIL/M2, TIL/M1). HGSOC used 7 features with a similar ratio-heavy immune-balance signature, plus macrophage-normalized density and polarization metrics (e.g., M1/N, M/N). In contrast, ER+ BC and HNSCC achieved best performance with 4 features dominated by macrophage measures, particularly M2 density and the M1/M2 ratio. Across sites, CD163-related macrophage metrics and immune-balance ratios were consistently informative. Conclusions: Integrating H&E-visible TILs with virtual CD68/CD163 TAMs enables fully automated, H&E-only prognostic biomarkers that stratify OS and DFS across multiple cancers, demonstrating consistent prognostic value in DCIS, ER+ BC, HGSOC, and HNSCC. These findings support further study of this histomorphometric risk classifier through broader external and prospective validation. Performance across cancer types. Cancer Type Cohort C-index HR [95% CI] p-value DCIS All 0.616 1.76 [1.20-2.59] <0.001 DCIS RT/No-treatment 0.624 1.94 [1.15-3.26] 0.003 HGSOC Test 0.553 1.38 [1.02-1.87] 0.030 ER+ BC Test 0.577 1.51 [1.00-2.28] 0.004 HNSCC All 0.603 1.92 [1.03-3.36] 0.012