Citations

OBJECTIVE Wait-and-scan surveillance is now commonly employed for initial management of small- and medium-sized vestibular schwannomas. Although small differences in tumor size are unlikely to impact outcomes significantly, treatment with either radiosurgery or microsurgery is usually recommended following radiological detection of tumor growth. The objective of the current study was to identify potential inflection points in vestibular schwannoma tumor size, where the risks of treatment with single-fraction stereotactic radiosurgery (SRS) accelerate to inform timing of intervention. METHODS Adult (≥ 18 years old) patients with sporadic vestibular schwannoma who underwent SRS from 2000 through 2022 were included. RESULTS A total of 749 patients with a median age at SRS of 62 years were studied, the majority (n = 566 [76%]) of whom had tumors extending into the cerebellopontine angle (CPA) at SRS. The optimal tumor size cut point to predict SRS failure and need for salvage treatment was 4 mm or more of CPA extension (c-index 0.59, HR 3.60, p = 0.01). The optimal tumor size cut point to predict the outcome of facial nerve paresis was 13 mm or more of CPA extension, resulting in a c-index of 0.63 (HR 2.88, p = 0.01). Among patients with at least 3 months of surveillance before SRS, those with a tumor growth rate ≥ 2.5 mm/year were more likely to undergo salvage treatment than those with a growth rate < 2.5 mm/year, although this difference did not achieve statistical significance (HR 1.82, p = 0.18). CONCLUSIONS The risk of SRS failure requiring salvage treatment and the risk of post-SRS facial nerve paralysis increase at sizes of approximately 4 and 13 mm extension into the CPA, respectively, providing a size threshold anchor to help guide treatment decision-making regarding timing of SRS. Furthermore, rapid tumor growth during the initial wait-and-scan period may be associated with an increased risk of radiosurgical failure, which may influence choice of treatment.

BACKGROUND Ulnar neuropathy at Guyon’s canal is rare, but when it occurs, it is frequently due to underlying masses, including extraneural and intraneural ganglion cysts, as well as adventitial cysts. The pathogenesis of these cysts, especially at a rare site, remains controversial. The articular theory, which is gaining popularity, posits that a joint connection via a nerve (or vascular) branch to a neighboring joint represents the pathway for their formation and propagation. OBSERVATIONS A recently published case of a patient with an ulnar intraneural ganglion at the wrist with a series of postoperative cystic recurrences was reevaluated, as it challenged the articular theory. No discrete articular branch had been identified on imaging or at surgery. Serial MR images were reinterpreted, which revealed that the original intraneural cyst was treated; new sequential cysts—an adventitial cyst and then a soft tissue ganglion—developed, all arising from the same wrist joint. LESSONS This case strengthens the principles of the articular theory for intraneural ganglion, adventitial, and soft tissue ganglion cysts. A small wrist connection from the ulnar intraneural ganglion was unrecognized and untreated. Scarring disrupted the original nerve pathway and pressure dynamics. New cysts developed through neighboring joint capsular rents along different pathways into other “compartments” (vessel or soft tissues). https://thejns.org/doi/10.3171/CASE25618

Introduction Asthma is a multifactorial disease influenced by genetic and environmental factors, including diet. The gut microbiome contributes to airway inflammation via the gut-lung axis, partly through production of short chain fatty acids (SCFAs) from bacterial fermentation of dietary fiber. We hypothesized that dietary fiber supplementation could modulate the gut microbiome and increase SCFAs in children with asthma. Methods This is a double-blind, placebo-controlled trial of children who were randomized to consume 12 g of soluble corn fiber (SCF) as a supplement to their usual daily diet (50% the recommended daily fiber intake) or placebo for 4–6 weeks ( clinicaltrials.gov NCT03673618). Dietary surveys, asthma symptom questionnaires, fecal, blood and nasal samples were collected before and after the intervention period to quantify fiber intake, asthma control, nasal and gut microbiome, and serum short chain fatty acids (SCFAs). Results Of the 20 children enrolled, 15 completed the intervention with an average adherence rate of 83%. SCFA concentrations and gut microbiome changes varied by individual and treatment group. No significant differences in gut or nasal alpha or beta diversity were observed between groups post-intervention. However, differential abundance analysis showed a trend toward increased Bifidobacterium in the SCF group compared to placebo (ANCOM-BC p = 0.0004, FDR q = 0.073). Discussion Supplementation of 50% of recommended daily fiber intake had minimal impact on asthma symptoms, the microbiome, or SCFA levels. Future studies should consider higher fiber doses, different fiber types, or targeting individuals with low baseline fiber intake to account for observed variability in microbiome and SCFA responses. Clinical Trial Registration https://clinicaltrials.gov/study/NCT03673618 , identifier NCT03673618.

Abstract Background: As with most Sub-Saharan African countries, Nigeria has a rising incidence of cancer, with disproportionate mortality rates. The financial burden of cancer care often results in catastrophic healthcare spending, leading to treatment refusal, disruption, and discontinuation. This is particularly significant in Nigeria, where nearly all patients are uninsured, and out-of-pocket costs often exceed households’ ability to pay. Financial Navigation Programs (FNPs) have been shown to mitigate treatment-related financial toxicity in cancer care and reduce treatment abandonment, but there is a paucity of high-quality data on this intervention in resource-constrained settings. Here, we present a randomized controlled trial to evaluate the impact of a novel FNP in Nigeria. Methods: We designed the COST-FIN trial, a multi-site pragmatic single-blinded randomized controlled trial of newly diagnosed (<6 weeks from diagnosis) adults (≥18 years) with breast, colorectal, or prostate cancer at two tertiary cancer centers in Nigeria. Participants (n=200) will be randomized (1:1) to either the intervention (FNP) or the control arm and followed for 12 months. Data on key individual, treatment, and financial parameters will be collected via structured interviews and chart abstraction at baseline, 3, 6, and 12-month follow-up. In addition, participants randomized to the FNP will receive a tailored financial literacy assessment, financial planning support, and enhanced access to resources by trained financial navigators. Primary and secondary outcomes are Financial Catastrophe (FC) and Financial Distress (FD), respectively. Exploratory outcomes will include cost-related non-adherence and cost-effectiveness of the program. An interim analysis will be conducted when 50% of the estimated accruals reach 6 months of follow-up, with crossover if compelling evidence of benefit is demonstrated at that time point. All participants will be followed for 12 months from recruitment. Discussion: This first-of-its-kind study will provide evidence on the role of FNP in potentially eliminating financial barriers to cancer care in Nigeria. Given the country’s renewed interest in cancer control through the passage of the National Cancer Control Plan, findings from this study have the potential to influence policy reform and set the stage for further studies to evaluate the scalability and implementation of similar interventions in resource-limited settings. Trial registration : ClinicalTrials.gov NCT06630962. Oct 8, 2024 (https://clinicaltrials.gov/study/NCT06630962)

Abstract Neuroendocrine prostate cancer (NEPC) is an increasingly prevalent manifestation of acquired resistance to next generation AR signaling inhibitors (ARSI), that arises via transformation from advanced prostate adenocarcinoma (PRAD) through a mechanism called lineage plasticity. Through characterization of isogenic PRAD and NEPC mouse tumoroid models generated using human-relevant driver mutations (Pten-/-;Rb1-/-;Trp53-/-), we revealed an extensive epigenetic reprogramming in NEPC versus PRAD, particular at enhancers. CRISPR screens focused on TFs and coactivators revealed a NEPC lineage TF survival network comprised of ASCL1, NFIB, SOX1/11, FOXA1/2 and MYCL with exquisite dependency on the TIP60 acetyltransferase complex. During the PRAD-to-NEPC transition, FOXA1, NFIB and TIP60 chromatin binding redistributes to NEPC specific enhancers, resulting in expression of NEPC target genes in a coordinate fashion with ASCL1 functioning as master regulator, culminating in activation of MYCL. MYCL then directly recruits the TIP60 complex to target sites, where it acts as a requisite MYCL coactivator for target gene activation for NEPC growth/survival. The acetyltransferase activity of TIP60 and acetylation of its substrate H2A.Z are both required for NEPC survival, as well as two chromatin reader subunits of the TIP60 complex, BRD8 and YEATS4. Targeted chemical degradation of TIP60 revealed &gt;500-fold dependency in NEPC relative to normal prostate, credentialing the TIP60 complex as a potential therapeutic target in NEPC. Citation Format: Zhen Sun, Jimmy L. Zhao, Wazim M. Ismail, Zahra F. Khan, Teng Han, Subhiksha Nandakumar, Serina Young, Matthew Lange, Richard Koche, Alexandre Gaspar-Maia, Charles L. Sawyers. The TIP60 acetyltransferase complex is a critical dependency in neuroendocrine prostate cancer through its role as a critical coactivator of MYCL downstream of ASCL1 [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research and Treatment; 2026 Jan 20-22; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(2_Suppl):Abstract nr PR036.

Abstract Background Prostate cancer is a heterogeneous disease comprising diverse cell types within the tumor microenvironment that support cancer cell survival. Using single cell and spatial transcriptomics, we previously identified subpopulations of treatment-persistent cancer cells exhibiting regenerative properties and a distinct molecular signature. Herein, we aimed to characterize the locked ‘Persist’ signature (PS) and its association with outcomes in a large cohort of non-metastatic prostate cancer tumors. Methods Patients with non-metastatic prostate cancer that underwent Decipher prostate genomic classifier and whole-transcriptome profiling on biopsy (BX, n=146,941) and radical prostatectomy (RP, n=55,329) specimens between October 2016 and February 2024 were included (Veracyte Inc., San Diego, CA, USA). Baseline clinical and pathological data from deidentified patients as well as signature scores were retrieved from the Decipher Genomic Resource for Intelligent Discovery (GRID) registry (Clinical Trials identifier: NCT02609269). The PS score based on the expression of 17 genes was calculated for all samples. Results PS was significantly associated with adverse clinical and pathological variables. In biopsy sample, PS was higher in cases with worse T3/4 clinical stage, Grade group (GG4-5), and high/very high NCCN risk (p&lt;0.001 for all). In RP sample, PS was significantly higher in patients with GG4-5, extraprostatic extension, seminal vesicle invasion and lymph node involvement (p&lt;0.001 for all). PS was also higher in patients with very high Decipher (&gt;0.85) in both BX and RP (p&lt;0.001 for both). When evaluating the prognosis of PS in multiple retrospective cohorts, PS in biopsy was prognostic of adverse pathology features at RP. PS was also prognostic of distance metastasis (DM) in multiple RP cohorts with long-term follow up (META855). In the ARNEO trial testing apalutamide in addition to ADT as neo-adjuvant treatment prior RP, PS was prognostic of early recurrence. In the Stampede trial, PS was prognostic of progression free survival, PCSM and OS in both non-metastatic and metastatic disease. When associating PS with other GRID signatures, PS was higher in samples with homologous recombination deficiency, TP53 mutations, Luminal B and luminal proliferating subtypes. On the other hand, PS was lower in samples with low androgen receptor-activity, RB-loss and neuroendocrine-like tumors. Finally, PS was positively correlated with radiation sensitivity signatures. Conclusions Persist is a novel molecular signature associated with more aggressive tumor characteristics. Future studies aim to further examine beyond this signature potential to identify patients at risk of aggressive prostate cancer, and understand what the optimal treatments for those with treatment-persistent prostate cancer cells are. Citation Format: Francesco Ballesio, Sinja Taavitsainen, Mohammed Alshalalfa, Antti Kiviaho, Mazlina Ismail, Reetta Nätkin, Alexander Giesen, Thomas Munro, James A. Proudfoot, Hyunnam Ryu, Elai Davicioni, Matthew C. Cooperberg, R. Jeffrey. Karnes, Ruochen Jiang, Steven Joniau, Gerhardt Attard, Frank Claessens, Matti Nykter, Alfonso Urbanucci. Persist: a molecular signature for prostate cancer patients with preexisting treatment-persistent cells associated with aggressive disease [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research and Treatment; 2026 Jan 20-22; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(2_Suppl):Abstract nr B079.

Background: Circulating tumor DNA (ctDNA) is predictive of recurrence in resected stage III melanoma, yet its role in the neoadjuvant setting for clinical stage III (cSIII) is unclear. Objective: Assess the association between ctDNA and outcomes following neoadjuvant immunotherapy (IO) + targeted therapy (TT) in cSIII melanoma. Design: Patients in the NeoACTIVATE study were treated with neoadjuvant IO + TT, underwent lymphadenectomy, and received adjuvant immunotherapy. Methods: Patients with ctDNA testing performed at baseline, pre- and post-operation were analyzed. Baseline positron emission tomography–computed tomography volumetrics and surgical, major pathological responses (MPR) were assessed. Results: Thirteen patients had serial ctDNA, 10 (77%) were detectable at baseline, and 9/10 (90%) had ctDNA clearance. Seven (54%) achieved MPR, all with undetectable preoperative ctDNA, yet 3/7 (43%) had disease recurrence. Conclusion: ctDNA and MPR are poor predictors of recurrence following neoadjuvant IO + TT for cSIII melanoma patients. Further studies are warranted to define the role of ctDNA in this setting.

ABSTRACT Background VEXAS is a relatively newly described immunocompromising condition with hematopoietic stem cell transplant increasingly being used. Little is known regarding infections in this high‐risk population. Methods We conducted a retrospective review of ten adult patients diagnosed with VEXAS who underwent HSCT in the Mayo Clinic Rochester and the Arizona medical record system. Results Nine out of ten individuals developed bacterial infection with bacteremia found in eight individuals despite being on prophylaxis at the time of infection. Six of the ten individuals were found to have viral infection; there were no documented invasive fungal infections and only one individual had a parasitic infection. Conclusion Providers should have a high suspicion for infection, especially bacterial, in this patient population, regardless of prophylaxis use. Patients should also be educated on signs and symptoms of infection.

Background A substantial proportion of patients with chronic rhinosinusitis (CRS) remain partly controlled or uncontrolled despite endoscopic sinus surgery (ESS) and maximal medical therapy. For these difficult-to-treat cases, topical antibiotic irrigations have been proposed as an adjunctive therapy, particularly when delivered via large-volume, low-pressure systems that enhance sinus penetration post-ESS. Evidence on their efficacy and prescribing patterns in this population remains limited. Objective This study aims to evaluate the use and outcomes of topical antibiotic irrigations in patients with difficult-to-treat CRS. Methods A retrospective, multi-site cohort study was conducted across tertiary academic medical centers. Adult patients with persistent CRS symptoms despite bilateral full-house ESS and conventional postoperative medical management were included. Patients with cystic fibrosis or granulomatosis with polyangiitis were excluded. Demographic, clinical, and treatment data were collected. Primary outcomes were infection resolution at 8 weeks and changes in Sino-Nasal Outcome Test-22 (SNOT-22) scores. Results Sixty-seven patients met inclusion criteria. Mupirocin (41.8%), tobramycin (23.9%), and gentamicin (17.9%) were the most commonly prescribed agents. After 8 weeks, 62.7% of patients achieved infection clearance. Among 44 patients with SNOT-22 data, scores improved significantly from 34.8 ± 20.2 to 21.8 ± 14.7 ( P < .001). Improvement in SNOT-22 scores was more pronounced in patients who cleared the infection compared to those who did not. Conclusion Large-volume topical antibiotic irrigations were associated with high infection resolution rates and clinically meaningful SNOT-22 improvements in patients with difficult-to-treat CRS. These findings support their potential utility as an adjunctive therapy in select postsurgical patients and warrant further prospective investigation.

Objectives To comprehensively review the available literature on prehabilitation and rehabilitation exercise, nutrition, and psychological support interventions for patients with kidney cancer (KC), to summarise the clinically relevant efficacy and cost‐effectiveness of interventions, to expose key knowledge gaps, and to inform future investigations and initiatives. Methods This review was performed according to the per Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) Extension for Scoping Reviews Guidelines. We included randomised controlled trials (RCTs) assessing programmes of prehabilitation or rehabilitation, exercise, psychological support, or nutrition components in patients with KC or KC caregivers from January 2004 to March 2022. Statistically significant positive (SS+) and negative (SS−) results were summarised. Results The systematic search yielded 10 968 records including 18 RCTs, involving 2774 unique subjects, 706 of whom were KC patients/survivors. None included caregivers or assessed cost‐effectiveness. Two interventions were implemented before surgery, one was implemented prior to initiation of systemic therapy, eight were implemented during systemic or radiation therapy, three were implemented after treatment, while implementation time was not specified for four interventions. Conclusion Most (14/18) RCTs involving exercise, nutrition, psychological support, or prehabilitative or rehabilitative programmes for KC performed to date demonstrated SS+ results. The evidence was most robust regarding previously evaluated psychological support, especially mindfulness‐based interventions (9/10 studies demonstrating SS+ improvement in primary outcomes), followed by therapeutically valid exercise with/without psychological support (5/8 RCTs demonstrated efficacy), then nutrition or pharmacological interventions (2/5 demonstrated efficacy). Level 1 evidence supports counselling patients and referral to mindfulness‐based psychological therapy along with physical therapy or physical medicine and rehabilitation, as well as consideration of preoperative carbohydrate drinks. No studies have examined impact on caregivers, or cost‐effectiveness, which are both critical areas for future study.