Citations

Abstract Secondary central nervous system (CNS) large B-cell lymphoma (SCNSL) occurs in the de novo setting, as a CNS-isolated relapse, or synchronous (concomitant CNS and systemic) relapse. SCNSL is a devastating event without therapeutic consensus. Thus, we aimed to evaluate treatment outcomes in an international cohort. Progression-free survival (PFS), overall survival (OS), and cumulative incidence of relapse (CIR, estimated using competing-risk models) were reported. Prognostic factors were identified in a 6-month landmark multivariate analysis. Outcomes after thiotepa autologous stem cell transplant (ASCT) and chimeric antigen receptor (CAR) T-cell therapy (CAR-T) delivered at relapse were compared after propensity score matching (PSM). A total of 1139 patients were included in the analysis (de novo: 537; relapsed SCNSL: 602). Two-year PFS estimates were 40.4%, 43.9%, and 16.2% for de novo SCNSL, CNS-isolated relapse, and synchronous relapse, respectively. Patients with CNS-isolated relapse demonstrated low rates of systemic recurrence (24-month CIR, 6%). Thiotepa-ASCT correlated with longer survival in de novo SCNSL (PFS: hazard ratio [HR], 0.57; P = .005; and OS: HR, 0.62; P = .023) and CNS-isolated relapses (PFS: HR, 0.55; P = .002; and OS: HR, 0.39; P< .0001). ASCT (thiotepa or no thiotepa) also associated with improved survival in synchronous relapses (PFS: HR, 0.57; P = .023; and OS: HR, 0.48; P = .019). Higher survival with thiotepa-ASCT than CAR-T was observed after PSM (PFS: HR, 0.45; P = .005 and OS: HR, 0.41; P = .014). These data support thiotepa-ASCT in eligible patients, particularly de novo disease and CNS-isolated relapses. CNS-isolated relapse was infrequently associated with systemic recurrence, supporting treatment regimens adopted from primary CNS lymphoma.

Background/Objectives: Surveillance for anal squamous cell carcinoma (ASCC) recurrence relies on clinical examination and imaging. Post-treatment edema, fibrosis, and inflammation can result in clinically indeterminate findings (CIFs) that delay diagnosis and increase patient and system burden. Circulating tumor tissue-modified viral (TTMV)-HPV DNA offers a biologically specific, noninvasive biomarker that may clarify equivocal assessments. Methods: In this multi-center retrospective study, 233 patients with HPV-associated ASCC were evaluated, including 185 with ≥1 post-treatment TTMV-HPV DNA test. CIFs were defined as exams or imaging results not definitively positive or negative for disease, and were paired with subsequent TTMV-HPV DNA tests. Concordance was defined by prespecified follow-up windows comparing TTMV-HPV DNA results with subsequent clinical outcomes. Results: Ninety patients (39%) experienced 214 CIFs, arising from exams (46%, 98) or imaging (54%, 116). Indeterminate rates by assessment were 7% for exams, 17% for imaging, and 1.3% for TTMV-HPV DNA testing. Overall, 52 CIF/TTMV-HPV DNA pairs were eligible for analysis, and TTMV-HPV DNA resolved disease status accurately for 48/52 (92%, 95% CI: 81.5–97.9). Negative tests predicted cancer-free status for 37/41 CIFs (90%), while 100% of positive tests (11/11) were concordant with clinically confirmed recurrence. In 73% of positive cases (8/11), TTMV-HPV DNA was the first indication of recurrence (median lead-time 29 days; IQR 25–147). Conclusions: TTMV-HPV DNA testing reliably clarifies clinically indeterminate findings during ASCC surveillance, demonstrating high accuracy (92%) and earlier detection of recurrence. These data support integration into post-treatment management to reduce diagnostic uncertainty and guide timely care.

Abstract Combination therapy incorporating programmed cell death protein 1 (PD-1) blockade results in unprecedented response rates in both frontline and relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL). Previous retrospective studies have suggested benefit for PD-1 blockade before autologous stem cell transplant (ASCT) but included few patients receiving PD-1 blockade with cytotoxic chemotherapy. To explore the impact of anti–PD-1 based salvage on outcomes for patients with R/R cHL, we retrospectively reviewed 1280 patients with R/R cHL who underwent ASCT from 2010 to 2022 at 6 transplant centers, none of whom received PD-1 blockade as part of frontline therapy. Overall, 25% received a PD-1 inhibitor at any point before ASCT (10% in conjunction with chemotherapy), 28% received salvage brentuximab vedotin (BV) without PD-1 blockade, and the rest received salvage chemotherapy alone. Patients who received PD-1 inhibitors at any point before ASCT had a significantly higher 2-year progression-free survival than those who received BV without PD-1 inhibitors or patients receiving chemotherapy alone (88.2%, 70.2%, and 67.4%, respectively; P< .0001). When restricted to patients in complete response before ASCT, the benefit of PD-1 blockade remained significant. PD-1 blockade before ASCT is independently associated with superior post-ASCT outcomes and patients proceeding to ASCT should be treated with PD-1–based salvage.

BACKGROUND: Increasing interest in neurosurgery residency has led to a growing number of unmatched applicants, who often struggle to find appropriate guidance for their next steps. The authors examined trends, opinions, and options available to unmatched neurosurgery residency reapplicants. STUDY DESIGN: Demographic data of US applicants from MD programs obtained from the National Resident Matching Program (2009 to 2024) were analyzed using 1-way ANOVA analysis of time-interval averages. Opinions about reapplicants were assessed via an online survey of national neurosurgery leaders, including residency program directors and chairpersons (N = 356). RESULTS: All application trends showed greater change over time; however, the rate of accepted reapplicants showed no significant change among early (2009 to 2013: 4.8 ± 1.8), mid (2014 to 2018: 7.6 ± 4.8), and recent periods (2019 to 2024: 9.8 ± 2.5; p = 0.068). The survey had a 23.0% response rate (82 of 356). Commonly indicated reasons for failure to match included poor interview skills, weak recommendation letters, and personality issues. Although most survey respondents supported candidates reapplying, dual applications (applying to more than 1 specialty) were not widely encouraged. For those reapplying, pursuing a preliminary general surgery or research fellowship, obtaining new letters of recommendation from new subinternships, and publishing higher-quality research were the most endorsed uses of time before reapplying. However, most programs reported interviewing reapplicants sometimes to rarely and matching a reapplicant rarely to never. CONCLUSIONS: The number of reapplicants successfully matching into neurosurgery has not changed significantly during the past 15 years. Surveys indicate that leaders view reapplicants unfavorably, despite reapplicants’ efforts to improve their applications. These results suggest that neurosurgery mentors may do a disservice to potential reapplicants based on how residency program leadership considers reapplications. Candid guidance is needed for reapplicants in the residency matching process.

PURPOSE To compare patient-reported and clinical outcomes between radical cystectomy (RC) and bladder-sparing therapy (BST) in patients with recurrent high-grade non–muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS This pragmatic, prospective observational cohort study was designed with patients, who selected and prioritized outcomes. Eligible adults were candidates for both RC or BST, had previous induction Bacillus Calmette-Guérin (BCG), and received their last treatment within 12 months. The primary outcome was the EORTC-QLQ-C30 physical function scale at 12 months. Secondary outcomes included other EORTC-QLQ-C30 scales, depression, anxiety, bladder cancer–specific quality of life (QOL), financial burden, and cancer-specific outcomes. Targeted maximum likelihood estimation (TMLE) was used to calculate average treatment effect (ATE) estimates between arms. Inverse probability weighted risk ratios (wRR) were calculated using quasi-Poisson regression. RESULTS Of 570 participants (mean age 71.4 years; 21% female), 371 selected BST and 199 selected RC. Physical function was significantly worse in the RC arm at 3 months; by 9 months, there was no difference between arms, and at 12 months, physical function did not differ (ATE, 0.9; 95% CI, –0.6 to 2.4; P = .22). RC was associated with better emotional function, generic health-related QOL, and financial burden, and lower depression and anxiety, while BST was associated with better bowel and sexual health. Cancer-specific survival was 99% for BST versus 96% for RC (wRR, 0.99; 95% CI, 0.97 to 1.01). RC was associated with a higher risk of adverse events and serious adverse events, including a 90-day mortality rate of 2.5%. CONCLUSION Most patient-prioritized outcomes were similar or better among participants who chose RC compared with BST. These findings support the continued role of RC in managing recurrent high-grade NMIBC.

ABSTRACT Objectives To critically evaluate clinical and voice‐related outcomes of in‐office serial intralesional steroid injection (SILSI) in adults diagnosed with idiopathic subglottic stenosis (iSGS). Data Sources MEDLINE, Embase, CINAHL Ultimate, CENTRAL, ClinicalTrials.gov . Review Methods A systematic search of databases was conducted from inception through April 5, 2025. Studies eligible for inclusion must have reported on adult SILSI recipients undergoing management of iSGS. Articles were independently screened and reviewed by two authors for treatment variables including steroid protocol, clinical outcomes, respiratory function, vocal outcomes, and complications. Results Of 383 studies identified, 14 met inclusion criteria ( n = 371). Triamcinolone was the most commonly used agent in 10 studies. Steroid dosage, number of treatment sessions, and injection interval varied widely across studies. Improvements in surgery‐free interval, peak expiratory flow, dyspnea index, degree of stenosis, and voice‐related outcomes were observed in several studies. No major complications were reported in the included studies. Conclusion Current evidence suggests SILSI represents a promising adjunctive therapy in the treatment of iSGS, with improvement noted across several measures. However, significant variability in steroid treatment regimens and inconsistent reporting of outcomes complicate interpretations of efficacy.

Abstract Wiskott-Aldrich syndrome (WAS), an X-linked disorder characterized by immunodeficiency, thrombocytopenia, autoimmunity, and malignancy, can be effectively treated with allogeneic hematopoietic cell transplantation (HCT). Older age at HCT and mismatched donors are known to affect overall survival (OS). However, the influence of specific clinical manifestations or WAS variant class on OS and factors associated with event-free survival (EFS) remain incompletely defined. We analyzed outcomes of 308 patients with WAS who underwent HCT at 37 institutions of the Primary Immune Deficiency Treatment Consortium from 1990 to 2018. With a median follow-up of 5.3 years, the 5-year OS and EFS were 87.2% and 79.7%, respectively. Age ≥5 years, donor type, and a pre-HCT history of severe infection had a negative impact on OS and EFS, whereas pre-HCT autoimmunity had no impact. Reduced-intensity regimens were associated with lower T-cell and myeloid donor chimerism, particularly when non–busulfan-based regimens were used. Low myeloid donor chimerism was associated with lower platelet counts. Mixed chimerism was not consistently associated with post-HCT autoimmunity. Patients with class I (exon 1-2 missense and intron 5 hot spot variants) and class II variants (all others) had similar pre-HCT clinical symptom severity and no difference in OS, EFS, or platelet recovery post-HCT. In conclusion, our study showed excellent long-term OS and EFS after HCT for WAS, highlighting the importance of early HCT, before the development of severe infections. We confirmed that HCT using busulfan-based conditioning was associated with improved donor chimerism and platelet recovery. This trial was registered at www.clinicaltrials.gov as NCT02064933.

Abstract Background Socioeconomic position (SEP) is a fundamental social determinant of health (SDoH) contributing to observed disparities in cancer and cardiovascular (CV) care among individuals with prostate cancer (PC). Understanding the influence of SEP on CV health is essential for addressing outcome inequities within this population. Methods We conducted a retrospective study utilizing Surveillance, Epidemiology, and End Results (SEER)-Medicare to evaluate CV outcomes in patients ≥65 years with PC from 2009 to 2017. We studied the impact of SEP on cardiovascular events (CVEs), cardiovascular mortality (CVm), PC-specific mortality (PCsm), and all-cause mortality. CVE, CVm, and PCsm were analyzed using competing risk models and all-cause mortality with Cox proportional hazards models. A subgroup analysis was performed in Non-Hispanic Black and Non-Hispanic White individuals. Results We included 141 242 patients of whom 76 844 were in high SEP areas (45.6%) and 64 398 in low SEP ones (54.4%). Both groups had a mean age of 72 years; patients in low SEP areas were 67.5% Non-Hispanic White, 34.4% having diabetes, 73.3% hypertension, and 67.7% dyslipidemia versus the high SEP group with 85.6% Non-Hispanic White, 30.4% diabetes, 69.9% hypertension, and 70.7% dyslipidemia. Patients in low SEP areas had higher risks of CVm (subdistribution hazard ratio [sHR] = 1.18, 95% CI = 1.12 to 1.25), PCsm (sHR = 1.12, 95% CI = 1.06 to 1.17), CVE (sHR = 1.07, 95% CI = 1.04 to 1.09), and all-cause mortality (HR 1.16, 95% CI = 1.13 to 1.20). Accentuated results were shown in the Non-Hispanic Black subgroup. Conclusion Adverse SEP plays a significant role in shaping outcomes among older patients with PC, contributing to elevated risks of adverse CV and survival outcomes.

Abstract Description Coccidiomycosis is an endemic fungal infection caused by Coccidioides spp., and diagnosis is often made with serology. Coccidiomycosis is especially problematic for immunocompromised patients, with greater risk for disseminated infection and mortality. This study evaluated current strategies for detecting antibodies to Coccidioides, including enzyme immunoassay (EIA), immunodiffusion (ID) and complement fixation (CF) and applied a new ID assay for improved sensitivity and specificity. Clinical sensitivity and specificity studies were done using 1544 unique serum specimens for which Coccidioides EIA testing was clinically requested. A full panel of EIA IgG, EIA IgM, ID and CF was performed on each, comparing our in-house immunodiffusion assay using reagents from Cactus Bio, LLC to our current reference laboratory. Full method validation was completed, as prescribed by CLIA. Using existing reference lab testing as the standard, a sensitivity of 96.9%, specificity 85.9%, PPV 54.9%, NPV 99.4% was achieved. Additional chart review demonstrated the in-house ID improved to 98.0% sensitivity, 94.6 specificity, 84.2% PPV, 99.4% NPV. Such high NPV supports using reflex testing, which allowed our lab to eliminate hundreds of unnecessary CF referrals each month, saving diagnostic time, financial waste and lab resources. A reflexive testing algorithm paired with this enhanced ID assay is especially useful for the immunosuppressed, for which Coccidioides infections carry a greater risk. Topic Categories Translational and Interventional Immunology (TI)