Citations

RET fusions appear in 1%-2% of non–small cell lung cancers (NSCLCs). The results from the ARROW study (ClinicalTrials.gov identifier: NCT03037385 ) supported US Food and Drug Administration approval of pralsetinib, an oral selective RET inhibitor, for metastatic RET -altered NSCLC and RET fusion–positive thyroid cancers. ARROW was a phase I/II open-label study of pralsetinib 400 mg once daily in RET fusion–positive NSCLCs. Coprimary end points were overall response rate (ORR) and safety. Key secondary end points included duration of response, progression-free survival, and overall survival (OS). At data lock (May 20, 2024), 281 patients initiated pralsetinib (median treatment duration, 15.0 months). ORR (measurable disease patients; n = 259) was 78% (95% CI, 69 to 86) for treatment-naïve patients and 63% (95% CI, 54 to 71) for prior platinum-based chemotherapy patients. Median OS was 44.3 months (95% CI, 30.9 to 53.1), 50.1 months (95% CI, 28.3 to not reached) in treatment-naïve patients, and 39.7 months (95% CI, 27.8 to 53.2) in prior platinum patients. Common grade ≥3 treatment-related adverse events were anemia (21%), hypertension (15%), and decreased neutrophils (13%). Three treatment-related deaths occurred (pneumonia, n = 2; interstitial lung disease and rhabdomyolysis, n = 1 each). Safety was consistent with previous ARROW reports; no hypersensitivity was reported in patients receiving prior immunotherapies. Pralsetinib produced robust, durable responses with manageable safety in treatment-naïve and previously treated patients with RET fusion–positive NSCLCs, confirming previous findings with longer follow-up.

PURPOSE Cancer recurrence is a critical outcome for patients and physicians. Retrospective cancer recurrence data can evaluate recurrence-directed treatment and generate novel interventions targeting recurrent cancers. However, large cancer databases do not provide recurrence-related information, stymying study at scale, and consequently require significant manual record review. Automated evaluation of records may allow for the rapid generation of easily analyzed data sets, accelerating the evaluation of recurrence altogether. METHODS Patients treated with radiation therapy at one tertiary referral center from 2010 to 2018 with a verified cancer status (cancer recurrence v no cancer recurrence) were identified. Patients with recurrent disease were initially identified through manual record review, and the associated pathology report was collected. Google Automated Machine Learning with Natural Language Processing (AutoNLP) and Google Gemini 1.5 Pro were used to generate a model for binary classification, with comparison to the gold-standard manually developed data set. RESULTS A total of 7,054 patients were identified. 3,431 (48.6%) were female, with a median age of 64 years. Head and neck (1,482, 21%), breast (1,480, 21%), upper GI (1,307, 18.5%), and lung/thorax (1,107, 15.7%) were the most common disease sites. Recurrence was verified for 1,546 patients (21.9%) using pathology reports, of which 1,249 positive cases were paired with 651 negative pathology reports for model development. Google Gemini 1.5 Pro consistently outperformed AutoNLP across all measurements of accuracy, generating a greater absolute difference in precision, recall, negative predictive value, and specificity, and a higher likelihood of correct classification at the individual level, rendering Gemini superior in recurrence status extraction. CONCLUSION AutoNLP and Google Gemini 1.5 Pro are promising tools for identifying recurrence from pathology reports, with the latter demonstrating superior overall performance, making it particularly suitable for clinical translation.

Background Kidney transplantation offers substantial clinical and economic benefits for patients with end-stage kidney disease (ESKD), yet organ shortages persist. Enhancing public awareness and health literacy regarding kidney donation is essential for effective donor recruitment. While online patient education materials are primary drivers of public perception, their readability, digital engagement, and accessibility remain underexplored barriers. Methods We analyzed the most prominent kidney donation websites identified through U.S.-based Google searches, including 11 primary organizations and 16 affiliated subdomains, for a total of 27 websites. Readability was benchmarked using Flesch-Kincaid, SMOG, and Gunning Fog indices. To assess qualitative metrics, we deployed a generative AI framework utilizing a Large Language Model (Claude) to conduct automated sentiment analysis and tone evaluation, validated by human review. We systematically mapped digital engagement features, including multimedia, interactive tools, and multilingual support, to determine content comprehensiveness. Results Websites consistently provided accurate information with a generally positive or neutral tone. Average readability exceeded recommended levels, with a combined mean grade of 12.3; 34% of websites were written at a college-level reading standard. Consensus across content was high. Multimedia elements were widely used, but engagement features were limited; only 30% of sites included extensive testimonials, and interactive tools were absent. AI-based analysis enabled standardized and reproducible evaluation, highlighting opportunities to improve accessibility, tone, and inclusivity. Conclusion Current U.S. kidney donation digital resources present a barrier to health equity due to excessive reading complexity and static engagement models. AI provides a scalable, reproducible framework to audit and optimize patient education materials. Future initiatives must leverage AI-guided content optimization to bridge the literacy gap, potentially increasing donor registration and access to transplantation.

Abstract Background & Aims Stricturing Crohn’s disease (CD) is a significant problem, and no selective anti-fibrotic therapies are available. Anti-inflammatory approaches are the mainstay of medical treatment. However, data on the efficacy of ustekinumab (USTE) in ileal stricturing CD are lacking. Our aim was to assess its efficacy in this setting. Methods We performed an international multicenter observational cohort study evaluating adult CD patients who received USTE within 6 months of imaging-confirmed symptomatic stricturing small bowel disease. Outcomes were rates of endoscopic balloon dilation (EBD), surgery, intervention (defined as the composite need for EBD or surgery), recurrent obstructive symptoms, and USTE persistence. Results Fifty-seven patients were included (51% female, median age 43 years). Median follow-up was 17 months. Intervention rates were 35%, 45%, and 69% of patients, at 12, 24, and 48 months, respectively. USTE persistence was 78%, 76%, and 52% at 12, 24, and 48 months. Estimated obstructive symptoms rates were 31% and 49% at 12 and 24 months, respectively. EBD within 6 months prior to starting USTE was associated with an increased risk of intervention. Increased bowel wall thickness on imaging, prior biologic use, and obstructive symptom duration were associated with USTE discontinuation. Occurrence of obstructive symptoms during treatment was associated with prior biologic use, EBD within 6 months of starting USTE, and a lower BMI. Conclusions USTE appears to be an appropriate medical option in biologic-experienced CD patients with ileal strictures. Further prospective data are needed to better define outcomes and predictors of response in this setting.

Abstract The rapid progress in tumour genome sequencing has created a need for bioinformatics tools to interpret the clinical significance of detected variants. VarStack² integrates information from several publicly available resources, including the Catalogue of Somatic Mutations in Cancer (COSMIC), ClinVar, cBioPortal, UCSC Genome Browser, and ClinicalTrials.gov, CIViC and presents it through a user-friendly interface. VarStack2 simplifies the process of retrieving data, saving users significant time compared to manually navigating each database individually. Users can input a variant by specifying a gene symbol, amino acid change, and coding sequence change, with the option to search tumour-specific studies in cBioPortal alongside their primary query. Results are organized into separate sections and can be exported in CSV format for further analysis. Additionally, VarStack2 offers a smart search feature that suggests variants for the gene of interest based on its database search results. These features make VarStack2 a useful tool for scientists and clinicians by enhancing the variant interpretation process and integrating somatic variant information into workflows. VarStack² is freely available at http://varstack.brown.edu/

Objective To validate International Bladder Cancer Group (IBCG) definitions of Bacillus Calmette‐Guérin (BCG)‐unresponsive and BCG‐exposed non‐muscle‐invasive bladder cancer (NMIBC) and assess prognostic heterogeneity across various BCG‐failure types. Patients and Methods From a multicentre international cohort of 3806 BCG‐treated patients, 591 who developed high‐grade NMIBC recurrence following BCG between 2003 and 2024 were included. Progression‐free survival (PFS) was the primary endpoint; cancer‐specific (CSM) and overall mortality (OM) were secondary endpoints. Cumulative incidence functions, competing‐risk models and multivariable Cox regression were used. Results Patients with BCG‐unresponsive and BCG‐exposed disease showed similar PFS, CSM, and OM (all P > 0.05). When stratified into five subgroups, prognosis varied: 5‐year progression rates were 29% for BCG‐unresponsive, 32.5% for late relapse (between 6 and 24 months) after adequate BCG, 30% for BCG‐exposed with inadequate BCG (<24 months from induction), 6.2% for BCG‐resistant, and 14% for very late relapse (>24 months since last BCG) ( P < 0.01). In multivariable analysis, BCG‐exposed after inadequate BCG (subdistribution hazard ratio [sHR] 3.42, 95% confidence interval [CI] 1.33–8.84), late relapse (sHR 3.74, 95% CI 1.59–8.78), and BCG‐unresponsive (sHR 2.34, 95% CI 1.00–5.44) were associated with higher progression risks compared to very late relapse. Limitations include retrospective design and treatment heterogeneity. Conclusions Under IBCG definitions, BCG‐unresponsive and BCG‐exposed NMIBC have similarly poor outcomes. A refined classification reveals prognostic heterogeneity, with late relapses after adequate BCG demonstrating outcomes comparable to BCG‐unresponsive, and very late relapses conferring better prognosis.

BACKGROUND Bertolotti syndrome is an underrecognized cause of chronic low back pain. Back pain generated from Bertolotti syndrome is believed to result from altered weight dissipation mechanics and/or instability of the pseudoarticulation, while local nerve root compression may result in radiculopathy. Here, the authors describe the findings of a patient with treatment-refractory low back pain found to have a cystic lesion arising from a Bertolotti joint causing L5 nerve root compression. To their knowledge, this has not been previously described in the literature. OBSERVATIONS Despite early recognition of Bertolotti syndrome, the patient’s back pain remained resistant to many years of both conservative and surgical management. The novel finding of a cyst arising from the pseudoarticulation complicated the management. The patient is scheduled to undergo further surgery this year. LESSONS This case highlights a pseudocyst associated with a Bertolotti joint. The cyst introduced additional clinical uncertainty to what is already an uncommon and difficult to treat condition. Resection of the Bertolotti joint failed to improve the patient’s symptoms. Postoperatively, a complex hemorrhagic pseudocyst was seen on imaging, possibly due to the pseudoarticulation with persistent motion. Ongoing efforts to characterize Bertolotti syndrome and its associated imaging findings are necessary to better optimize management strategies in these patients. https://thejns.org/doi/10.3171/CASE25948