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3026 citation(s) found for "Ha, Kevin".

Mechanical Thrombectomy for Intermediate- and High-Risk Pulmonary Embolism: A Retrospective Observational Cohort Study
Merren, Michael P. , Feller, David, Lange, Sawyer B., Ahmad, Sumera , Buda, Kevin , Kor, Nathan T , Motiei, Arashk, Ursoleo, Jacopo D’Andria , Nabzdyk, Christoph G., Caples, Sean M., Elmadhoun, Omar, Nabzdyk, Christoph S. , Ahmad, Sumera R , Buda, Kevin G , D'Andria Ursoleo, Jacopo , Nabzdyk, Christoph , Lange, Sawyer, Takahashi, Edwin A. , Caples, Sean M., Elmadhoun, Omar

Journal of Intensive Care Medicine | May 28, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.1177/08850666261452151 | PMID 42206966 Get It

Pulmonary embolism (PE) is a leading cause of cardiovascular morbidity and mortality. Systemic thrombolysis is recommended for high-risk PE, but risk of major bleeding limits its use despite its efficacy. While mechanical thrombectomy (MT) has emerged as an alternative reperfusion strategy, real-world safety data remains limited. The objective of this single-center retrospective observational cohort study was to characterize the safety profile and procedural complications of MT. Methods Adult patients with intermediate-risk and high-risk PE who underwent MT at a quaternary academic medical center between January 1, 2017, and December 31, 2024, were included. Demographic, clinical, laboratory, imaging, procedural, outcome, and mortality data were collected. Major adverse events and bleeding were defined according to established criteria. Results From a total of 103 screened patients, 65 were included. Of these, 22 (34%) were classified as high-risk and 43 (66%) as intermediate-risk. Baseline demographics were similar between groups. High-risk patients demonstrated greater clinical disease severity, with higher mean Pulmonary Embolism Severity Index (PESI) scores (188.5 vs 122.4). Clinical deterioration prior to MT occurred in 35% of intermediate-risk patients. Extracorporeal membrane oxygenation (ECMO) consultation rate (32% vs 7%), peri-procedural ECMO use (18% vs 2.3%), major bleeding (27% vs 4.7%), and in-hospital mortality (36% vs 11.6%) were higher in the high-risk group. Thrombus removal was achieved in 77% and 88% of high- and intermediate-risk patients, respectively. High-risk patients had longer ICU (mean 4 vs 1.3 days) and hospital stays (mean 21.5 vs 6.4 days), higher thirty-day mortality (36% vs 14%), and lower 90-day survival (59% vs 79%). Conclusions MT achieved high rates of thrombus removal in both groups. In this retrospective cohort, high-risk patients had greater baseline clinical severity and was associated with higher bleeding rates, greater resource utilization, including ECMO consultation and peri-procedural use, prolonged ICU and hospital stays, as well as increased mortality.
IDE892 as monotherapy and in combination with IDE397 in patients with 5-methylthioadenosine phosphorylase-deleted ( MTAP -Del) advanced solid tumors (IDE892001): Phase 1 trial.
Garmezy, Benjamin, Herzberg, Benjamin, Devarakonda, Siddhartha, Parikh, K, Zarrabi, Kevin , Song, Michael M., Xiong, Henry Q., Sahebjam, Solmaz , Graef, Thorsten, Sachdev, Jasgit C. , Beaupre, Darrin M., Ahnert, Jordi Rodon, Herzberg, Benjamin, Devarakonda, Siddhartha, Salkeni, Mohamad Adham , Segar, Jennifer , Liu, Emily L. , Graef, Thorsten

Journal of Clinical Oncology | May 28, 2026 | Volume: 44 | Issue: 16_suppl | Pages: No page available

10.1200/jco.2026.44.16_suppl.tps3182 Get It

TPS3182 Background: MTAP deletion in solid tumors causes intracellular accumulation of methylthioadenosine (MTA) which partially inhibits activity of the key methylating enzyme, protein arginine methyltransferase 5 (PRMT5) and creates synthetic lethal dependencies on PRMT5 and methionine adenosyltransferase 2A (MAT2A), the rate limiting step in the synthesis of PRMT5 substrate, S-adenosyl methionine. PRMT5 and MAT2A are essential to transcription modulation, gene splicing, and DNA damage response. IDE892 is an MTA-cooperative PRMT5 inhibitor designed to exploit this vulnerability in MTAPdel tumors. Preclinical studies report robust antitumor activity with IDE892 monotherapy in MTAPdel xenograft models and an enhanced response when combined with IDE397 (an allosteric MAT2A inhibitor). IDE892-001 is a Phase 1 study evaluating safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity of IDE892 alone and in combination with IDE397. Methods: IDE892-001 is an ongoing, open-label, multicenter four-part study: IDE892 monotherapy dose escalation (Part 1), monotherapy dose expansion in MTAPdel NSCLC (Part 2), IDE892 + IDE397 dose escalation (Part 3), and combination expansion in MTAPdel NSCLC (Part 4). Adults with advanced or metastatic MTAPdel solid tumors including lung, urothelial, gastrointestinal cancers (including pancreatic and biliary tract cancers) and mesothelioma are eligible following disease progression on standard therapies. Key exclusion criteria include symptomatic brain metastases, cardiac disease, active severe infection, and prior treatment with a PRMT5 or MAT2A inhibitor. Part 1 uses a Bayesian optimal interval design to determine maximum tolerated dose (MTD) and recommended doses for expansion (RDE). Part 3 uses a modified toxicity probability interval design to evaluate escalating combinations of IDE892 and IDE397. Oral treatment is given QD in 21-day cycles until progression or unacceptable toxicity. Serial blood samples are collected for PD analyses. Imaging will be performed every 6 weeks through week 24, then every 9–12 weeks. Efficacy endpoints will be assessed by RECIST v1.1. Primary objectives for dose-escalation cohorts (Parts 1 and 3) are safety and tolerability, including determination of MTD/RDE. In expansion cohorts (Parts 2 and 4), co-primary objectives include safety and preliminary antitumor activity (objective response rate and duration of response). Secondary endpoints for all parts include PK of IDE892 alone and in combination with IDE397. Exploratory assessments include progression free survival, changes in circulating and tumor-based markers of PRMT5 pathway modulation, molecular predictors of response, exposure–response relationships, and metabolite characterization. Clinical trial information: NCT07277413 .
Clinical characteristics and survival outcomes of early-onset renal cell carcinoma by metastatic status: A National Cancer Database study.
Du, Simo , Li, W, Esagian, Stepan M., Dimitrios, Makrakis, Zhang, Xiaoyi, Peng, Jiahao , Ezhilarasu, Preetham, Han, Kevin, Wang, Yuqing , Chang, Victor Tsu-Shih, Zhang, Tiantian , Esagian, Stepan M. , Makrakis, Dimitrios , Liu, Bolun , Ezhilarasu, Preetham, Han, Kevin

Journal of Clinical Oncology | May 28, 2026 | Volume: 44 | Issue: 16_suppl | Pages: No page available

10.1200/jco.2026.44.16_suppl.e16510 Get It

e16510 Background: Early-onset RCC may reflect distinct biology and hereditary predisposition, yet data on stage-specific clinical features and outcomes remain limited. We comprehensively evaluated age-stratified, stage-specific clinical features and survival outcomes using the National Cancer Database. Methods: Adults with histologically confirmed RCC diagnosed between 2004 and 2022 were analyzed. Patients were categorized into three groups by age at diagnosis: early-onset ( < 40 years), middle-aged (40–50 years), and late-onset ( > = 50 years). The sociodemographic and clinical characteristics, comorbidities, histology, and treatment patterns were compared using descriptive statistics. Overall survival (OS) was evaluated using Cox proportional hazards models, adjusting for the aforementioned variables. Stage-specific analyses were conducted, including a metastatic disease cohort. Results: Among 742,114 patients, 4.3% were classified as early-onset, 10.9% as middle-aged, and 84.8% as late-onset. Overall, 12.6% presented with metastatic disease. Compared with late-onset, early-onset patients were more likely to be from racial minority populations (non-White: 16.9 % vs. 20.2 % in late-onset), uninsured, and had fewer comorbidities (Charlson–Deyo score 0: 85.2% vs. 65.2%). Early-onset RCC was characterized by a lower proportion of papillary RCC (8.9% vs. 12.5%) and higher proportions of clear cell (54.9% vs. 50.8%) and chromophobe RCC (9.3% vs. 4.5%) than late-onset RCC and more likely to undergo partial nephrectomy (50.4% vs. 30.2%). They also presented with earlier-stage disease, with lower rates of stage III (7.4% vs. 10.2% vs. 13.4%) and stage IV disease (5.4% vs. 8.9% vs. 13.5%) compared with middle-aged and late-onset groups. Among patients with metastatic disease, early-onset RCC demonstrated higher minority representation (30.8% vs. 14.1%) and a higher prevalence of non-clear cell histology (70.6% vs. 58.1%). In multivariable analysis, compared with early-onset RCC, middle-aged (HR 1.44, 95% CI 1.39–1.50; P < 0.001) and late-onset patients (HR 2.83, 95% CI 2.74–2.93; P < 0.001) experienced significantly worse OS. However, among metastatic disease, this survival advantage was attenuated. Early-onset patients had similar OS to middle-aged patients (HR 0.99, 95% CI 0.93–1.05, p = 0.69) and late-onset patients only had a modestly worse OS than the early-onset group (HR 1.09, 95% CI 1.03–1.15 p = 0.003). Conclusions: Early-onset RCC was associated with more favorable baseline characteristics, earlier stage at diagnosis, and higher utilization of nephron-sparing nephrectomy, corresponding to improved OS. However, this survival advantage diminishes in metastatic disease despite better baseline health, highlighting stage-dependent differences in outcomes and suggesting distinct histologic patterns in advanced early-onset RCC.
Incidence, severity, and management of severe adverse events in first-line (1L) treatments for metastatic pancreatic ductal adenocarcinoma (mPDAC): A retrospective observational study.
Almudallal, Omar, Meloni, Seema, Rangarajan, Nivedita , Laursen, Ashley Ann, Perrot, Valérie , Chacko, Kevin, Sobiesk, Matthew, Bekaii-Saab, Tanios S., McWilliams, Robert R. , Meloni, Seema , Sobiesk, Matthew, Bekaii‐Saab, Tanios

Journal of Clinical Oncology | May 28, 2026 | Volume: 44 | Issue: 16_suppl | Pages: No page available

10.1200/jco.2026.44.16_suppl.e16377 Get It

e16377 Background: 1L systemic treatment of mPDAC can lead to severe adverse events (AEs). To contextualize the safety profile of irinotecan-based regimens, real-world data were used to characterize AEs and their management in patients receiving 1L mPDAC treatment with FOLFIRINOX (FFX) or gemcitabine+Nab-paclitaxel (Gem+NabP). Methods: De-identified data from Mayo Clinic electronic health records (all sites; records collected 2010–2023) were used. Natural language processing was leveraged to confirm staging and metastatic classification and to extract treatment data. Adults with mPDAC with stage IV and/or TNM staging of M1 who received ≥ 1 dose of FFX or Gem+NabP were included. Primary endpoint: proportion of patients with AEs of interest (diarrhea, nausea, vomiting, neuropathy, and neutropenia) following initiation of 1L treatment. Secondary endpoints: proportion of patients who received treatment for each AE of interest, median time to resolution and treatment of each AE of interest, and proportion of patients who switched mPDAC treatment or had dose reductions due to AEs. Results: In total, 405 patients (FFX, 197; Gem+NabP, 208) were identified. The proportions of patients who experienced and were treated for any-grade AEs of interest are reported in the Table. Of the AEs of interest, neutropenia resolved most quickly (median time from onset to resolution, FFX: 9.5 days; Gem+NabP: 12.5 days); neuropathy took the longest time to resolve (FFX: 44.0 days; Gem+NabP: 74.0 days). Median time to AE treatment was shortest for nausea and vomiting (both 0.0 days for FFX and for Gem+NabP). Time to treatment was longest for neuropathy (FFX: 158.5 days; Gem+NabP: 70.0 days). Only 5.1% of patients on FFX and 13.4% on Gem+NabP received treatment for neuropathy. Of patients in the FFX group who switched/reduced treatment (n=140), 58.6% received a dose reduction and 7.1% switched to Gem+NabP due to AEs. Conclusions: At the Mayo Clinic sites, incidence of any-grade AEs associated with 1L mPDAC treatment were similar or higher than rates of any-grade or ≥ 2/3–4 grade AEs reported in the literature. Nausea, vomiting and diarrhea were the most commonly treated AEs for both irinotecan-based (FFX) and non-irinotecan-based (Gem+NabP) 1L regimens; neutropenia and neuropathy were less commonly treated. FFX dose reductions were commonly attempted before switching regimens. Proportion experiencing any-grade AE (AE incidence in the literature) Proportion experiencing AE treated for an AE FFX Gem+NabP FFX Gem+NabP Diarrhea 74.6% (50–80%, any grade) 43.8% (< 5%, any grade) 92.5% 56.0% Nausea 81.7% (45%, any grade) 72.1% (20%, grade ≥ 2) 98.8% 96.7% Vomiting 54.8% (10%, any grade) 42.8% (20%, grade ≥ 2) 98.1% 98.9% Neutropenia 58.9% (45%, grade 3–4) 48.1% (12–21%, grade 3–4) 62.1% 46.0% Neuropathy 59.9% (25%, grade 3–4) 32.2% (30%, grade 3–4) 5.1% 13.4%
cfDNA WGS vs plasma proteomics for minimally invasive MRD assessment in multiple myeloma.
Abelman, Dor, Wong, Aimee, Eagles, Jenna , Shah, Saumil , Bruce, Jeff, Campos, Cecília Bonolo de , White, Darrell, Song, Kevin , Braggio, Esteban, Murugesan, Alli , Stewart, Keith, Reiman, Tony, Trudel, Suzanne, Abelman, Dor , Wong, Aimee, Bruce, Jeffrey, Pedersen, Stephanie , Scott, David S. , Chow, Signy , White, Darrell , Sandhu, Irwindeep , Braggio, Esteban , Trudel, Suzanne , Pugh, Trevor J.

Journal of Clinical Oncology | May 28, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 7546-7546

10.1200/jco.2026.44.16_suppl.7546 Get It

7546 Background: MRD assessment informs relapse risk in MM but is typically bone marrow-based and invasive. We therefore compared two minimally invasive MRD assays: BM-informed cfDNA whole-genome sequencing (cfWGS) and plasma proteomic MRD (EasyM). Methods: 71 longitudinal plasma samples (22 diagnosis, 49 follow-up) from 22 newly diagnosed MM patients across 8 Canadian sites (TFRIM4) had paired cfWGS and EasyM (Rapid Novor Inc). cfWGS MRD used patient-specific mutation lists from diagnostic BM WGS (Abelman et al., medRxiv 2025). EasyM used mass spectrometry to quantify residual M-protein from baseline. The primary endpoint was progression-free survival (PFS). Results: Among 22 MM patients (8 male, 14 female; median age at diagnosis 62 years), 8 progressed at a median follow-up of 52.6 months (range: 10-79 months). At 1-year maintenance (n = 18 available), cfWGS MRD+ (6/18) predicted inferior PFS (HR 20.12, 95% CI 2.23-181.60, p = 0.007). EasyM any-detect positivity was frequent (16/18, reflecting delayed clearance) and not prognostic (p = 0.99), with poor agreement vs cfWGS (44.4%, κ = 0.118). An exploratory EasyM clearance threshold of 0.93% (hypothesis-generating) classified 5/18 patients as MRD+ and stratified PFS (HR 8.78, 95% CI 1.55-49.82, p = 0.004), improving agreement with cfWGS (17/18, 94.4%, κ = 0.870). Progression clustered in cfWGS+/EasyM-high patients (EasyM >0.93%; 4/5; median 11.9 months post-collection [1.9–22.8]) and occurred once in cfWGS−/EasyM-low patients (1/12, 27.6 months). The only discordant case (cfWGS+/EasyM−) progressed 8.7 months after collection. Higher quantitative MRD burden was associated with inferior PFS (cfWGS: HR 2.92 per 1 SD, 95% CI 1.29-6.59, p = 0.01; EasyM: HR 5.48 per 1 SD, 95% CI 0.79-37.90, p = 0.085). At ~100 days post-autologous stem cell transplantation (ASCT; n = 16 available), EasyM was uniformly MRD+ (16/16) while cfWGS was MRD+ in 7/16 patients. Applying an EasyM clearance threshold (2.13%; 9 cleared vs 7 residual) improved agreement with cfWGS (14/16; 87.5%; κ = 0.746). Of two discordant cases, one cfWGS+/EasyM-cleared patient relapsed 38.6 months post-collection and one cfWGS−/EasyM-residual patient remained progression-free at last follow-up. At post-ASCT, both assays showed consistent but underpowered associations with PFS (cfWGS HR 6.32, 95% CI 0.70–56.76, p = 0.100; EasyM-clearance HR 2.36, 95% CI 0.39–14.18, p = 0.335). Across all post-treatment samples (n = 49), continuous cfWGS burden correlated with EasyM residual M-protein (rho = 0.535, p < 0.001). Conclusions: BM-informed cfWGS MRD strongly stratified PFS, whereas EasyM required a clearance definition due to near-universal early positivity. Concordant plasma burdens support complementary MRD information. Future work will validate these findings in larger cohorts and quantify the incremental value of combined cfWGS and proteomic MRD for early relapse prediction.
Real-world clinical outcomes by HER2 expression in locally advanced/metastatic urothelial carcinoma (la/mUC): Results from the global SGNDV-003 retrospective study.
Koshkin, Vadim S. , Jaillon, Christine Abraham, Mar, Nataliya, Maillet, Denis, Shariat, Shahrokh F., Singh, Parminder, Drakaki, Alexandra, Graham, Laura, Merseburger, Axel S. , Huang, Jiaoti, Galsky, Matthew D., Sokolowski, Kevin M. , Jiang, Dingfeng, Lonning, Shaparak, Yu, Hong, Burgess, Earle F., Mar, Nataliya , Maillet, Denis , Shariat, Shahrokh F. , Singh, Parminder Pal , Khaki, Ali Raza , Drakaki, Alexandra , Galsky, Matthew D. , Yin, Lei , Zhang, Wei , Burgess, Earle F.

Journal of Clinical Oncology | May 27, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 4562-4562

10.1200/jco.2026.44.16_suppl.4562 Get It

4562 Background: Approximately 50-80% of patients (pts) with la/mUC have tumors with HER2 protein expression. As HER2-directed therapies enter development, a robust understanding of HER2 prevalence and real-world outcomes with standard-of-care (SOC) therapies across HER2 expression subgroups is needed. SGNDV-003 (NCT05902494) is a global retrospective chart review study in which HER2 status was assessed via central lab testing and outcomes were analyzed by HER2 status in pts with la/mUC. Methods: SGNDV-003, conducted 6/2023-7/2025, included pts with la/mUC who received ≥1 prior treatment (tx) (incl. 1 line of platinum-based chemotherapy [chemo]). HER2 status was centrally tested using a UC-specific investigational immunohistochemistry [IHC] and in situ hybridization (ISH) assays. HER2 status was defined as: HER2-positive (IHC3+ or IHC2+/ISH+), HER2-low (IHC2+/ISH- or IHC1+), HER2-expressing (IHC3+, 2+, 1+), and HER2-zero (IHC0). Index line of therapy (LOT) was defined as the first LOT received after platinum-based chemo. Outcomes included real-world objective response rate (rwORR) (per RECIST 1.1 or physician-assessed response) to index LOT, real-world progression-free survival (rwPFS), and overall survival (OS) from start of index LOT. Data was analyzed via descriptive statistics. Results: A total of 353 pts with la/mUC and available HER2 status were analyzed (male, 76%; median age, 70 years). 70% of pts were HER2 expressing (19% HER2-positive, 51% HER2-low); 30% were HER2-zero. Disease characteristics were well balanced by HER2 status. Index LOT tx and real-world outcomes are shown in the Table. Immuno-oncology therapies (IO) and enfortumab vedotin (EV) were the most common index LOTs. For IO, rwORRs were 21% for HER2-expressing and 17% for HER2-zero. For EV mono, rwORRs were 36% (HER2-expressing) and 38% (HER2-zero), respectively. Conclusions: This global study provides a robust estimate of HER2 distribution in la/mUC based on standardized central lab testing, showing high prevalence of HER2 expression. Real-world outcomes with current SOC therapies were broadly consistent across HER2 subgroups, establishing an important benchmark for the clinical development of HER2-directed therapies in this setting. HER2-positive (n=67) HER2-low (n=181) HER2-expressing (n=248) HER2-zero (n=105) Total (n=353) Real-world Outcomes rwORR, n (%)[95% CI] 17 (25.4)[15.5, 37.5] 50 (27.6)[21.3, 34.7] 67 (27.0)[21.6, 33.0] 22 (21.0)[13.6, 30.0] 89 (25.2)[20.8, 30.1] Median rwPFS (95% CI), mo 2.8(2.0, 4.1) 3.7(2.7, 5.1) 3.0(2.7, 4.5) 2.6(2.1, 3.4) 2.9 (2.6, 3.5) Median OS(95% CI), mo 12.2(9.3, 16.5) 11.5(9.5, 13.5) 11.9(10.3, 13.4) 7.7(5.9, 9.9) 10.8(9.1, 12.3) Index LOT, n% IO EV monoChemoOther tx 37 (55)17 (25)10 (15)3 (5) 94 (52)51 (28)24 (13)14 (8) 131 (53)68 (27)34 (14)17 (7) 65 (62)21 (20)12 (11)7 (7) 196 (56)89 (25)46 (13)24 (7)
First-in-human phase 1/2 study of ETX-19477, an oral, potent, and selective PARG inhibitor, in patients with advanced solid tumors (ERADIC8).
Rosen, Ezra, Advani, Pooja , Banda, Kalyan , Chan, Nancy, McKean, William Bennion , Spira, A, Yap, Timothy A., Zarrabi, Kevin , Trehan, Sanjay K., McCormick, Daniel, Holleran, John P., Stansfield, Ryan, Santini, Angelina M., Veal, James M., Stafford, Jeffrey, Penson, Richard T. , Batalini, Felipe , Cecchini, Michael , Chan, Nancy, Spira, Alexander I. , Yadav, Siddhartha , Yap, Timothy Anthony , Bain, Gretchen , Stansfield, Ryan K., Stafford, Jeffrey A.

Journal of Clinical Oncology | May 27, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 3109-3109

10.1200/jco.2026.44.16_suppl.3109 Get It

3109 Background: Poly(ADP-ribose) glycohydrolase (PARG) is an enzyme that catalyzes the removal of poly-ADP-ribose (PAR) chains from proteins during DNA damage repair. PARG inhibition leads to selective cell death in tumors with underlying replication fork defects, including BRCAm tumors, through a mechanism distinct from PARP inhibition. ETX-19477 is an oral, potent, and selective PARG inhibitor that shows robust preclinical activity in mouse models of ovarian, breast, and gastric cancers. Methods: ERADIC8 is an open-label, multicenter, Phase 1/2 study, consisting of two parts, dose escalation and dose expansion. A Bayesian Optimal Interval Design was used to enroll patients (pts) into dose escalation cohorts, with enrichment for pts with BRCAm high grade serous ovarian (HGSOC) and breast cancers. The primary objective is to assess safety/tolerability of ETX-19477 and define the maximum tolerated dose (MTD) and recommended Phase 2 dose(s). Secondary and exploratory objectives include pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity per RECIST v1.1. ETX-19477 is given orally once or twice daily in 21-day cycles. Results: As of Jan 6 2026, 45 pts were enrolled into the study across 11 dose levels (range: 80-750 mg QD, 190-350 mg BID). Tumor types included ovarian (n=24, BRCAm: 18), breast (n=8, BRCAm: 7), endometrial (n=6, BRCAm: 0), colorectal (CRC, n=3, BRCAm: 1), and other (n=4, BRCAm: 0) cancers. Treatment-related AEs (TRAEs; any grade) occurring in >20% of pts were nausea (53%), vomiting (38%), and fatigue (24%). The only Gr3 TRAE occurring in >5% of pts was neutropenia (16%). There was one Gr4 TRAE of neutropenia in 1 pt (2%) and no Gr5 TRAEs. ETX-19477 exposure is dose proportional, and the BID regimen achieves >85% PARG inhibition throughout the dosing interval in a blood-based PAR accumulation pharmacodynamic assay. As of the data cutoff, dose escalation is ongoing at 350 mg BID (MTD has not been defined) and dose expansion is ongoing at 200-300 mg BID. Among BRCAm, HGSOC pts enrolled at BID dose levels, there were 7 evaluable pts with a median of 4 prior lines of therapy (range 2–11): 2 pts achieved a partial response (PR, 29%) and 3 pts achieved stable disease (SD, 43%). Both pts with PRs were platinum-resistant and received prior PARP inhibitor treatment. 1 pt with BRCAm CRC remains on active therapy (250 mg BID) with SD for 7 months. Conclusions: ETX-19477 was well tolerated and showed anti-tumor activity in heavily pretreated pts with BRCAm, platinum-resistant HGSOC during dose escalation. These findings provide the first clinical proof-of-concept of PARG inhibition in HGSOC. ETX-19477 is being further evaluated in the dose expansion phase of the study. Clinical trial information: NCT06395519 .
Continued CNS-penetrant TKI therapy with or without local CNS therapy after brain metastasis diagnosis in NSCLC.
Dhamelia, Parth , Ammakola, Yagnapriya, Batra, Nitya, Pustake, M, Ganiyani, Mohammad Arfat, Zhu, Kevin, Ahluwalia, M., Khosla, Atulya Aman , Ammakola, Yagnapriya, Pustake, Manas Vaibhav , Jatwani, Karan , Singh, Rohit , Ahluwalia, Manmeet S.

Journal of Clinical Oncology | May 27, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 2036-2036

10.1200/jco.2026.44.16_suppl.2036 Get It

2036 Background: Patients with oncogene-driven metastatic non–small cell lung cancer (NSCLC) treated with CNS-penetrant tyrosine kinase inhibitors (TKIs) frequently develop brain metastases (BM) while continuing targeted therapy, and outcomes of adding local CNS-directed therapy in this setting are not well defined. We evaluated outcomes associated with local CNS therapy after post-TKI BM diagnosis. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network. Adults with NSCLC treated with osimertinib or lorlatinib who subsequently had a coded diagnosis of BM (ICD-10 C79.31) at least 1 month after TKI initiation and evidence of continued TKI use were included. Patients were stratified by receipt of CNS-directed local therapy (SRS/SBRT or neurosurgery) within 3 months of the index BM diagnosis versus no local therapy. The primary outcome was all-cause mortality within 180 days of the index event. Secondary outcomes included hospitalization and systemic corticosteroid use. Cohorts were balanced using 1:1 propensity score matching on demographics, comorbidities, extracranial disease, laboratory values, and TKI exposure. Survival analyses were performed, and proportional hazards assumptions were validated using Schoenfeld residuals (p>0.05). Results: Among 1,157 eligible patients, 1,053 matched pairs were generated. Within 180 days of the index brain metastasis diagnosis, mortality was lower among patients who received local CNS therapy compared with those who did not (10.9% vs 18.1%), corresponding to a hazard ratio (HR) for death of 0.54 (95% CI 0.43–0.68; p<0.001). Survival probabilities at 180 days were 88.7% in the local therapy cohort and 80.2% in the no local therapy cohort. Hospitalization within 180 days occurred in 20.3% of patients receiving local therapy and 22.4% of those without local therapy (p=0.24), with a nonsignificant trend toward delayed hospitalization (HR 0.84, 95% CI 0.69–1.01). Systemic corticosteroid use was common and similar between groups (61.3% vs 59.4%; p=0.40), with no significant difference in time to steroid initiation. In an osimertinib-only sensitivity analysis, 180-day mortality was 10.5% among patients receiving local CNS therapy compared with 19.4% among those without local therapy (HR 0.48, 95% CI 0.37–0.61; p<0.001). Conclusions: In this multi-institutional real-world cohort of patients with NSCLC receiving osimertinib or lorlatinib who developed BM, receipt of local CNS-directed therapy within 3 months was associated with lower 6-month mortality compared with continuation of targeted therapy alone, with consistent findings in an osimertinib-only sensitivity analysis. These results suggest a potential survival benefit of local CNS intervention in selected patients, while acknowledging residual confounding related to intracranial disease burden and clinical indication.
Burnout in Urology is a Quality of Care Problem, and Joy in Work is the Solution
Bowman, Max , Lam, John S. , Koo, Kevin , Kraft, Kate H. , Harris, A O , North, Amanda , Harris, Andrew , Harris, Andrew , North, Amanda C.

Urology Practice | May 27, 2026 | Volume: 13 | Issue: 5 | Pages: 464-467

10.1097/upj.0000000000001027 | PMID 42201807 Get It

Frailty and postoperative outcomes following craniopharyngioma resection: a multicenter Registry for Adenomas of the Pituitary and Related Disorders analysis
Chen, Anthony Yulin, Feng, Rui, Collopy, Calen, Rennert, Robert C., Couldwell, William T., Kshettry, Varun R., Gardner, Paul, Silverstein, Julie M., Kim, Albert H., Barkhoudarian, Garni, Kelly, Daniel, Pacione, Donato , Suryadevara, Carter M. , Kim, Won, Bergsneider, Marvin, Zada, Gabriel, Wu, Kyle C., Prevedello, Daniel M., BENJAMIN, CAROLINA, Catalino, Michael P., Mamelak, Adam, Cheok, Stephanie K., Zwagerman, Nathan T., Gompel, Jamie J. Van, Fernandez-Miranda, Juan C., Yuen, Kevin C. J., Little, Andrew S., Karsy, Michael, Evans, James J., Karsy, Michael , Barkhoudarian, Garni , Palit, Sandhya R. , Karsy, Michael , Kelleher, Sean T., Rennert, Robert C , Couldwell, William T. , Kshettry, Varun R. , Silverstein, Julie , Kim, Albert H , Kelly, Daniel, Bergsneider, Marvin , Chicoine, Michael , Zada, Gabriel , Prevedello, Daniel M. , Catalino, Michael Paul, Mamelak, Adam N. , Cheok, Stephanie , Zwagerman, Nathan T. , Gompel, Jamie J. Van , Fernandez‐Miranda, Juan C. , Yuen, Kevin C.J. , Little, Andrew S. , Evans, James J.

Neurosurgical Focus | May 27, 2026 | Volume: 60 | Issue: 6 | Pages: E7

10.3171/2026.2.focus251160 | PMID 42224740 Get It

OBJECTIVE Frailty is a known predictor of adverse outcomes in pituitary surgery, yet its impact regarding craniopharyngioma remains unclear. The authors assessed preoperative frailty, measured by the 11-factor modified frailty index (mFI-11), and its association with perioperative morbidity among adult patients undergoing craniopharyngioma surgery. METHODS Using the Registry for Adenomas of the Pituitary and Related Disorders (RAPID) database, the authors performed a retrospective cohort study of the records of patients ≥ 18 years of age who underwent craniopharyngioma surgery between June 2007 and November 2024. Patients were stratified into the following categories according to their numeric mFI-11 score: fit (scores 0 and 1), managing well (scores 2 and 3), and mildly frail (scores 4–6). Primary outcomes included hospital length of stay (LOS) and discharge disposition. Secondary outcomes included 90-day readmission, surgical outcomes, and complications. Multivariable analyses were performed to identify independent predictors of hospital LOS and non-home discharge, adjusting for age, surgeon experience, American Society of Anesthesiologists class, complications, and surgical approach. RESULTS Among 278 patients (221 fit, 43 managing well, 14 mildly frail), higher-frailty patients were older (mean age 47.8 ± 16.1 years in fit vs 60.1 ± 12.5 years in managing well vs 67.6 ± 8 years in mildly frail, p < 0.001) and more likely to present urgently (24.2% vs 36.4% vs 78.6%, p = 0.001). Gross-total resection was achieved less frequently in frail patients (44.8% vs 24.3% vs 23.1%, p = 0.030). Overall complication rates were similar; however, increasing frailty was associated with higher rates of postoperative mortality (0% vs 2.8% [1/36] vs 7.7% [1/13], p = 0.018), pneumonia (0.5% [1/195] vs 2.8% [1/36] vs 15.4% [2/13], p = 0.006), and reintubation (2.6% [5/195] vs 2.8% [1/36] vs 30.8% [4/13], p = 0.002). Higher frailty was associated with a stepwise rise in median [IQR] LOS (5 [3–8] days vs 7 [4–12] days vs 13 [6.5–21.8] days, p < 0.001) and remained an independent predictor of extended LOS on multivariable analysis (β = 1.729 per point, p = 0.006). Rates of non-home discharge showed a similar pattern (9.2% vs 30.0% vs 64.3%, p < 0.001), with frailty independently predicting non-home discharge (OR 2.352, 95% CI 1.527–3.822). Unplanned 90-day readmission rates were significantly higher in the mildly frail cohorts (22.5% vs 45.7% vs 53.8%, p = 0.002). CONCLUSIONS The mFI-11 scores independently predicted perioperative morbidity following craniopharyngioma resection. Incorporating frailty screening into preoperative screening may improve risk stratification, family and patient counseling, and discharge planning.