Citations

Purpose: To compare stone clearance, stone-free status, and complications between patients undergoing ureteroscopy for renal stones using either Flexible and Navigable Ureteral Access Sheath (FANS) or the CVAC 2.0 system. Materials and Methods: A prospective study was completed on patients undergoing flexible ureteroscopy for renal stones at a single institution from March 2024 to December 2024. Subject demographics, intra-op data, volumetric and single-dimension stone clearance on non-contrast CT, and complications were compared. Stone-free rates (SFRs) using standardized cutoffs were compared. Pearson correlation analysis was performed to assess the relationship between preoperative stone volume and postoperative stone burden. Subanalysis was performed for patients with preoperative stone burden >1.5 cm. Results: A total of 123 cases (CVAC 2.0-36, FANS-87) were included, with 64 eligible for volumetric analysis. Preoperative stone volume was larger in the CVAC group vs FANS (1075 mm 3 vs 397 mm 3 ; p < 0.001). Absolute stone clearance was greater in the CVAC group (1016 mm 3 vs 392 mm 3 ; p < 0.001), whereas residual stone volume (4.1 mm 3 vs 15.0 mm 3 ; p = 0.55) and SFRs (90% vs 81%; p = 0.48) were similar. In individuals with >1.5 cm preoperative stone burden, relative stone clearance was greater with CVAC 2.0 (98.9% vs 95.1%; p = 0.026). Pearson correlation analysis revealed positive linear relationship between preoperative stone volume and residual stone volume for FANS, but not for CVAC 2.0. Conclusions: In this comparative study of FANS and CVAC 2.0, over 95% stone clearance was observed in both groups despite large initial stone burdens. In contrast to FANS, residual stone volumes with CVAC 2.0 did not increase significantly with increasing preoperative stone volumes.

Abstract Our inability to obtain nerve samples from the vast majority of neuropathic pain patients impedes our ability to understand the disease, creates challenges in understanding mechanisms in specific patient populations, and limits our ability to make treatment decisions based on quantifiable molecular data. Fields like oncology have overcome these problems to take advantage of the insight that sequencing offers for understanding mechanisms of disease and have leveraged these molecular insights to dramatically change the treatment landscape in the past decade. Here we tested the hypothesis that skin biopsies could be used to gain insight into neuronal transcriptomic changes in patients with paclitaxel-induced peripheral neuropathy (PIPN). Our analysis reveals that hundreds of differentially expressed genes (DEGs) found through bulk RNA sequencing in these skin biopsies are likely contributed by dorsal root ganglion (DRG) neuronal axons and/or terminals. Up-regulated genes were representative of broad class of nociceptors whereas down-regulated genes were associated with putative injured DRG neurons expressing the PDIA2 gene. DEGs that could be confidently associated with specific subsets of skin cells were mostly expressed by keratinocytes supporting a growing literature tying keratinocyte-neuron communication abnormalities to pain in PIPN. We validated these findings by analyzing additional previously published datasets and through prospectively conducted spatial transcriptomics experiments on human skin biopsies. Our findings warrant further assessment of skin biopsies in additional neuropathic pain populations to gain insight into DRG neuron changes that have previously been thought to be inaccessible in routine clinical or scientific assessments in most patients.

Immune checkpoint inhibitors (ICIs) are an important class of cancer treatment. Endocrine immune-related adverse events (E-irAEs) account for a significant proportion of irAEs in ICI-treated patients. Diagnosing E-irAEs accurately and timely can be challenging in the absence of clear categorization and standardization across oncology, endocrinology and other specialties. While existing guidelines provide some broad directions to diagnosis and management, they lack clarity on irAE-specific symptom evaluation and work-up, as well as assessment of severity. These limitations can then impact triage, time-sensitive management and care escalation to specialists such as oncoendocrinologists. The objective of this study was to develop consensus-based statements on disease definitions for E-irAEs. A core working group of endocrinologists with expertise in the oncoendocrinology field drafted a survey with statements outlining the general approach to E-irAEs, disease definition and management approach of six specific diagnoses: ir-thyroiditis thyrotoxic phase, ir-thyroiditis hypothyroidism, ir-Graves’ disease, ir-hypophysitis, ir-adrenalitis and ir-type 1 diabetes mellitus. Severity grading tables were drafted for three disease categories—“thyroid”, “pituitary and adrenal”, and “diabetes mellitus”. A two-round modified Delphi process, using the RAND/University of California Los Angeles (RAND/UCLA) Appropriateness Method, was employed. In this process, a 25-member voting panel consisting of endocrinologists, oncologists and other specialists and healthcare providers with experience in management of ICI-treated patients and irAEs was recruited. The panel rated anonymously on usability, accuracy, appropriateness or agreement of 41 items on a 9-point scale in Survey 1, after which a meeting was convened. Statements were modified based on voting results from Survey 1 and Meeting 1, and the process was repeated in Survey 2 and Meeting 2. At the end of this process, consensus was achieved for all statements. Our study findings address the gap in standardized nomenclature, clinical, laboratory and radiological evaluations, and management principles of E-irAEs. With consensus achieved from a panel of experts from a variety of disciplines, we anticipate that the statements can form the basis for standardization of the diagnostic process and improvement of patient care.

AbstractAbstract Background Central nervous system (CNS) tumors are a significant cause of morbidity and mortality in Sub-Saharan Africa (SSA). This project aimed to assess and map out the current neuro-oncology capacity in SSA, brain tumor registries, and biobanks. Methods This cross-sectional study utilized an online survey to gather data from healthcare professionals involved in CNS tumor care across SSA through the Society for Neuro-Oncology SSA (SNOSSA). The survey captured information on the availability of neuro-oncology practitioners, neuropathology, molecular diagnostics, cancer registries, and biobanking. Results A total of 145 respondents representing 70 healthcare institutions across 22 countries participated. Of the 70 institutions, specialties included neurosurgery (89%, 62/70), anatomic pathology (74%, 52/70), and medical oncology (71%, 50/70). For radiologic evaluation, 64% (45/70) of responding institutions reported having both CT and MRI. Access to molecular testing through immunohistochemistry or next-generation sequencing was available in 46% (32/70) of responding institutions. Multidisciplinary tumor boards were available for CNS cases in 86% (60/70) of responding institutions. Brain tumor-specific registries were available in 29% (20/70) of responding institutions, and 10% (7/70) maintained brain tumor biorepositories. Conclusion This study demonstrates that SSA has substantial potential in neuro-oncology care practice capacity and facilities. The most significant gaps were in neuropathology and molecular testing, which makes widespread implementation of the WHO 2021 diagnosis challenging. Understanding the prevalence of CNS tumor subtypes in SSA is difficult due to the low number of brain tumor registries and biobanks.

PURPOSE This analysis aimed to contextualize the symptoms of peripheral neuropathy (PN) experienced by patients with triple-class refractory (TCR) multiple myeloma (MM) treated with elranatamab in the MagnetisMM-3 clinical trial with those experienced by patients with TCR MM receiving a new line of physician's choice of therapy in the real-world MagnetisMM-14 study. METHODS MagnetisMM-3 included 123 patients and MagnetisMM-14 included 35 who had TCR MM and were enrolled under the same eligibility criteria. Patient-reported symptoms of PN were collected monthly using the Chemotherapy-Induced Peripheral Neuropathy-20 item (CIPN20) questionnaire and compared for clinically meaningful differences across sensory, motor, and autonomic domains. Higher scores indicated worse patient-reported PN symptoms. RESULTS Baseline demographics and clinical characteristics for patients in MagnetisMM-3 and MagnetisMM-14 were generally similar. Patients in MagnetisMM-3 had a median of five ( v four in MagnetisMM-14) prior lines of therapy. In MagnetisMM-14, common index therapies included elotuzumab + pomalidomide (23%), carfilzomib + pomalidomide (19%), or carfilzomib + cyclophosphamide (19%), all with corticosteroids. Mean scores for sensory (15.8 v 14.8) and motor (14.4 v 12.2) domains of the CIPN20 were similar between MagnetisMM-3 and MagnetisMM-14 at baseline. Mean scores for the autonomic domain were 14.0 versus 21.3 at baseline, respectively. No clinically meaningful differences for any domain were found between month 6 scores or changes in scores from baseline to month 6 between MagnetisMM-3 and MagnetisMM-14 populations. CONCLUSION These findings suggest that elranatamab treatment was not associated with a worsening of patient-reported PN symptoms across the sensory, motor, and autonomic domains of the CIPN20. Moreover, PN symptoms reported with elranatamab treatment were similar to those reported with other common therapies used in real-world clinical practice for the management of MM. MagnetisMM-3 ClinicalTrials.gov identifier: NCT04649359 .

Abstract Aims To assess the potential for artificial intelligence-enabled electrocardiogram (AI-ECG) to serve as a long-term cardiac surveillance tool and predict left ventricular systolic dysfunction in childhood cancer patients. Methods and results We assessed performance of our previously established AI-ECG model to predict left ventricular ejection fraction (LVEF) ≤50% and ≤40% in patients with childhood cancer during internal testing (Boston Children’s Hospital) and external validation (Children’s Hospital of Philadelphia). The internal test cohort comprised 447 patients [57% male; age at cancer diagnosis 11.2 (5.4–15.7) years; 1553 ECG–echo pairs at median age 13.5 (IQR 7.7–17.9) years; 6.4% with LVEF ≤50%; 1.3% with LVEF ≤40%], 28% with leukaemia, 16% with lymphoma, 8% with neuroblastoma, 8% with sarcoma, 2% with gastrointestinal cancers, 3% with genitourinary cancers, 6% with central nervous system cancers, 11% with other/unspecified cancers, and 18% with missing/unknown cancer labels. Treatment strategies included anthracyclines (35%), bone marrow transplant (7%), and radiation (1%). The external test cohort comprised 2964 patients [55.4% male; 7054 ECG–echo pairs at median age 11.6 (IQR 6.8–15.1) years; 2.5% with LVEF ≤50%; 0.9% with LVEF ≤40%]. Similar AUROCs (0.80–0.85), sensitivities (0.75–0.82), NPVs (0.986–0.996), and percent predicted negative (51–65%) were obtained across institutions to predict LVEF ≤50%, outperforming a biomarker-based model benchmark. Patients with high AI-ECG risk scores for LVEF ≤50% had higher rates of mortality [hazard ratio 3.1 (95% CI 1.8–5.3), P &lt; 0.001] compared to patients with low AI-ECG risk scores. Conclusion AI-ECG shows promise as a digital biomarker for cardiac surveillance in the vulnerable childhood cancer survivor population.

Abstract BRCA-associated homologous recombination deficiency (HRD) is present in ~ 50% of high-grade serous carcinomas (HGSC) and predicts sensitivity to platinum-based therapy. However, there is little understanding of why some patients with BRCA-deficient tumors experience unexpectedly poor outcomes. We profiled 154 tumors, enriched for patients with BRCA-deficient tumors that experienced short overall survival (≤ 3 years, n = 42), using whole-genome, transcriptome, and methylation analyses. All but one BRCA-deficient tumor exceeded an accepted HRD genomic scarring threshold. However, patients with BRCA1-deficient HGSC with a more elevated HRD score survived significantly longer. Patients with BRCA2-deficient HGSC and loss of NF1 survived twice as long as those without NF1 loss, whereas PIK3CA or RAD21 amplification defined BRCA2-deficient HGSC with exceptionally short survival. BRCA1-deficient tumors in short survivors had evidence of immunosuppressive c-kit signaling and EMT. In a large HGSC cohort (n = 1,389) including 282 individuals with pathogenic germline BRCA variants (gBRCApv), the location of the mutation within functional domains stratified clinical outcomes. Notably, residual disease after primary surgery had limited prognostic effect in gBRCApv-carriers compared to non-carriers. Our findings indicate that tumor HR proficiency in the context of therapy response and survival is not a binary property, and highlight genomic and immune modifiers of outcomes in BRCA-deficient HGSC.