Citations

Elevated intratumoral interstitial fluid pressure (IFP) can negatively impact the efficacy of neoadjuvant chemotherapy (NAC) of breast cancer. This study aims to predict breast cancer pathological complete response (pCR) to NAC based on IFP measures by 3-D subharmonic-aided pressure estimation (SHAPE). SHAPE uses the inverse linear relationship between hydrostatic pressure and subharmonic signal magnitude from intravascular ultrasound contrast agents. Thirty-eight breast cancer patients undergoing NAC from three clinical sites were enrolled for this study. SHAPE data were collected for each subject at 0%, 10%, and 30% of NAC completion using a Logiq E9 system (GE HeathCare) equipped with an RSP6-16D probe. The contrast agent used was Definity (Lantheus Medical Imaging). The subharmonic signal gradients between tumor and adjacent normal tissue were calculated and compared with patient pathological response outcome using t-test and receiver operating characteristic (ROC) curve analysis. Pressure gradients between pCR (15 patients) and non-pCR (23 patients) groups were significantly different at 0 (p = 0.02), 10 (p = 0.03), and 30% (p = 0.0003) completion of NAC. Area under the curve values of 0.69, 0.77, and 0.86 were achieved at 0%, 10%, and 30% of NAC completion, respectively. Overall, SHAPE pressure gradients may aid prediction of NAC pathological response in breast cancer patients.

Abstract Background Osteoarthritis is a leading cause of disability worldwide, and cell‐based treatments including adipose‐derived and bone marrow aspirate have been sought by the lay and medical community as treatment options. Objective To perform a scoping review of published literature on cell‐based injections allowed by the U.S. Food and Drug Administration for the treatment of osteoarthritis to synthesize existing evidence and identify research gaps for future evaluation. Methods A comprehensive search of five databases was executed from inception through January 2, 2025. Studies that met the inclusion criteria were original research studies written in English on Food and Drug Administration‐allowed cell‐based treatments in adults with osteoarthritis of any joint. Results The database search yielded 4257 unique records. After screening, 84 studies met the inclusion criteria, encompassing 9996 patients and a total of 10,508 procedures. The primary research study designs were cohort studies ( n = 62), focused on treatment of knee osteoarthritis ( n = 63), and described bone marrow aspirate ( n = 42) and adipose‐derived ( n = 42) treatments. Postprocedure monitoring ranged from 6 weeks to 5 years, with most studies ≤1 year ( n = 59). Patient‐reported outcomes were reported in 83 of 84 studies; few provided imaging outcomes including magnetic resonance imaging ( n = 9) or radiographs ( n = 2). Conclusion This review identified limited randomized controlled trials, limited studies outside the knee, limited description of cell‐based treatments, and treatment protocols, along with inconsistent patient‐reported outcomes limited to 1 year in most studies. We propose establishing reporting guidelines in research on cell‐based therapies.

Abstract Purpose: Circulating tumor fraction estimate (ctFE) is a machine learning–derived composite metric of circulating tumor DNA (ctDNA) burden. We hypothesized that pre-treatment and early on-treatment ctFE could robustly risk-stratify patients with locally advanced (LA) and oligometastatic non–small cell lung cancer (NSCLC) treated with radiotherapy (RT). Experimental Design: In a prospective phase II clinical trial (NCT03916419), 26 patients with unresectable stage IIB to IIIC NSCLC received magnetic resonance (MR)-guided hypofractionated chemoradiotherapy (chemoRT) followed by immunotherapy. Plasma ctDNA was profiled at baseline and mid-treatment (days 10–14) to derive ctFE and maximum variant allele frequency (Max VAF). A burden-based ctFE threshold derived from baseline samples was applied unchanged to mid-treatment samples and validated in two external cohorts: LA NSCLC treated with chemoRT (LA-RW; n = 94) and oligometastatic NSCLC treated with RT (OM-RW; n = 309). Results: Pre- and mid-treatment ctFE burden strongly stratified overall survival (OS) and progression-free survival (PFS), outperforming Max VAF and ctFE detectability. The baseline ctFE was prognostic for OS (HR 5.93, P = 0.005) and PFS (HR 11.08, P < 0.001) and remained significant at mid-treatment (OS: HR 7.08; PFS: HR 12.06; both P < 0.001). Early ctFE dynamics defined three molecular response groups with OS separation (median OS 60.8 vs. 13.0 vs. 2.9 months; P < 0.001). ctFE remained associated with survival in both validation cohorts. Conclusions: Early ctFE derived from a clinically available, tumor-naïve ctDNA assay enables noninvasive risk stratification in LA and oligometastatic NSCLC treated with RT, supporting its use as a practical biomarker for precision treatment adaptation.

Abstract Solitary bone plasmacytoma (SBP) and SBP with minimal marrow involvement (SBPmm) are treated similarly with definitive radiation therapy (RT) followed by observation. However, differences in the natural disease course after RT between the two, are not well described. We performed a multicenter study assessing outcomes after RT in 141 patients with SBP and 102 with SBPmm diagnosed between January 2010 and December 2024. About 92% of patients with SBPmm progressed to multiple myeloma (MM) vs 76% of those with SBP (P = .01). Among patients with SBP, 21% progressed with a second solitary bone lesion vs 4% with SBPmm (P< .01). Patients with longer time to progression (TTP) after initial RT could achieve durable responses with RT to a second solitary plasmacytoma in the absence of other myeloma-defining events (MDE). Multifocal lytic bone lesions were the most common MDE, occurring in 89% and 81% of patients with SBPmm and SBP, respectively. Patients with SBPmm had a median TTP of 15 months (95% confidence interval [CI], 14-21) compared to 43 months (95% CI, 34-55) for those with SBP (P< .0001); 67% with SBPmm progressed within 2 years of diagnosis. Del(17p) and 1q+ (gain or amplification) were associated with shorter TTP to MM in SBPmm, with 2-year progression rates of 100% and 82%, respectively. We report significant differences in risk and modes of progression between SBP and SBPmm. Patients with SBPmm are at particularly high risk for early progression to MM, with most developing bone disease as the MDE. These findings support prospective studies incorporating frontline systemic therapy for SBPmm.

Background: Previous studies suggest that internalized HIV stigma (IHS) results in HIV viral nonsuppression via directly increasing depression, which then reduces adherence leading to nonsuppression; however, the dynamics between IHS and mental health are likely more complex. We sought to better understand IHS-mental health dynamics using data from a longitudinal clinical cohort of people with HIV (PWH) receiving healthcare across 10 US primary care clinics. Methods: Among 8,506 PWH who had ≥2 timepoints in which IHS, depression, and anxiety were measured, we examined changes over time in both two-state (i.e., impact of IHS on depression or anxiety and vice versa) and four-state combinations of depression-IHS (i.e., no depression or IHS, depression/no IHS, no depression/IHS, both depression/IHS) and anxiety-IHS. Transition probabilities between states and factors influencing transitions were identified using multistate Markov models. Results: The impact of IHS on the transition rates of mental health measures (i.e., depression, anxiety) and vice versa were almost the same, suggesting that each influences the other. Over 50% of PWH remained in the same IHS-depression or IHS-anxiety state. PWH with IHS had almost twice the rate of transitioning from no depression/anxiety to having depression/anxiety compared to PWH without IHS; with similar results for the depression or anxiety with no IHS to reporting IHS transition. Conclusions: We demonstrate that IHS and mental health dynamics are more complex than previously suspected and that the associations are bidirectional, which has implications for both future analyses and optimal management of these conditions among PWH.

The classification and management of central nervous system (CNS) tumours have undergone substantial transformation over the past two decades, with the recognition of an expanding set of molecularly defined disease entities. Genome-wide DNA methylation profiling has emerged as an important complement to histopathology and targeted molecular testing, providing an epigenetic framework that captures tumour lineage, biological state and large-scale genomic alterations within a single assay. Accumulating evidence demonstrates that methylation-based approaches improve diagnostic precision, resolve biologically heterogeneous entities and support clinically meaningful risk stratification across a broad spectrum of CNS tumours. Methylation profiling has also increasingly been applied to outcome prediction, liquid biopsy-based analyses and the resolution of diagnostically challenging or misclassified cases. In addition, advances in multi-omic integration, computational inference from routinely acquired clinical data and evolving implementation frameworks are extending the clinical applicability of epigenetic profiling. This review synthesises the current state of DNA methylation profiling within the diagnostic and clinical framework of CNS tumours and considers how emerging technologies and practice models are shaping its ongoing integration into neuro-oncological care.

Objective Medium‐vessel vasculitis involving the visceral vasculature in adults is rare. Pancreatic ductal adenocarcinoma (PDAC) has been implicated in medium artery vascular thickening secondary to extravascular migratory metastasis with involvement of the celiac and superior mesenteric vessels. Methods Patients presenting to the rheumatology vasculitis subspecialty clinic were retrospectively identified using an electronic health record data exploration tool evaluating for diagnosis of pancreatic cancer, periaortitis, and vasculitis between January 2015 and December 2024. Results We retrospectively identified four patients with PDAC initially presenting with periarterial thickening of the celiac and superior celiac and superior mesenteric vessels (100% White, 50% male, median age 70.5 years). All four patients had abdominal pain with significant unintentional weight loss, with a median weight loss of 25 pounds (range 25–50 pounds). The median time to correct diagnosis was 221 days (range 162–340 days). All four patients had an elevated carbohydrate antigen 19‐9 level (range from 114 to 10,702, with a median of 341.5 U/mL). All four patients were diagnosed with endoscopic ultrasound–guided fine‐needle aspirations. The median number of biopsies required to make the diagnosis was three. Conclusion Isolated celiac and superior mesenteric periarterial thickening or “cuffing” is a vasculitis mimic that should prompt a comprehensive malignancy workup. Expedited referral to a tertiary center is essential given difficulty in tissue sampling with conventional methods and to avoid further delays in diagnosis.

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 Background Approximately 12 000 adolescents and young adults (ages 15-39, AYAs) are diagnosed with a primary central nervous system (CNS) tumor each year. DNA methylation profiling has transformed CNS tumor classification by refining diagnostic accuracy and identifying biologically distinct subtypes, but its application has not been systematically evaluated in the AYA population. In this study, we examined the spectrum of CNS tumor types across age groups, with a focus on the AYA population. Methods We assembled a large dataset of CNS tumor samples with age annotations and methylation profiles matching with high confidence to a CNS tumor type using the NCI/Bethesda classifier. Prevalence of tumor type, methylation class and DNA copy number aberrations were compared across age strata (pediatric, AYA, and adult). Results The cohort of 21 712 CNS tumors included 5351 tumors from AYAs (25%), which showed a mixed pattern, with tumors typical of childhood (eg, medulloblastoma) as well as those common in older adults (eg, glioblastoma). Several tumor types were specifically enriched in the AYA, including IDH-mutant astrocytoma, pleomorphic xanthoastrocytoma, posterior fossa group B ependymoma, and diffuse hemispheric glioma, H3 G34-mutant, among others. Distinct methylation subclasses of multiple tumor types were observed in the AYA, and patterns of genomic aberrations showed age-specific distributions. Conclusion Large-scale methylation profiling revealed unique classification patterns of CNS tumors in AYAs, with specific tumor types, subclasses, and genomic alterations enriched in this population. These data may serve as a valuable reference resource for better understanding the spectrum of CNS tumors affecting AYA patients.