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Optimizing Plasma p-tau217 Thresholds for Detection of Preclinical Alzheimer’s Disease Across Different Racial and Ethnic Backgrounds (P10-13.011)
Piura, Yoav, Lachner, Christian, Algeciras-Schimnich, Alicia, Figdore, Daniel, Petersen, Ronald, Jack, Clifford, Aduen, Paula, Schecter, Leah, Graff-Radford, Neill, Day, Gregory, Piura, Yoav , Lachner, Christian , Algeciras‐Schimnich, Alicia , Figdore, Daniel J. , Bornhorst, Joshua , Petersen, Ronald, Jack, Clifford, Aduen, Paula, Graff‐Radford, Neill R.

Neurology | June 10, 2026 | Volume: 106 | Issue: 11_Supplement_1 | Pages: No page available

10.1212/wnl.0000000000215003 Get It

Efficacy and safety profile of volume-staged stereotactic radiosurgery for ruptured, large pediatric arteriovenous malformations: a multicenter cohort analysis
Tos, Salem M., Hajikarimloo, Bardia, Chan, Jason W., Sneed, Penny K. , McDermott, Michael W. , Seymour, Zachary , Grills, Inga, Reda, Wael A., Tawadros, Sameh R., Eldin, Reem Emad, Lunsford, L Dade, Niranjan, Ajay, Samanci, Yavuz, Lee, Cheng-chia, Yang, Huai-che, Sheehan, Darrah, Sheehan, Kimball, Liscak, Roman, Chytka, Tomáš , Alzate, Juan, Kondziolka, Douglas, Moreno, Nuria Martínez , Martínez‐Álvarez, Roberto , Hallan, David R , Fritch, Chanju, Jareczek, Francis, Sciscent, Bao Y., Mathieu, D, Carrier, Louis, Abdelsalam, Ahmed, Starke, Robert M., BENJAMIN, CAROLINA, Almeida, Timoteo, Singh, S.P., Lazo, Erwin, Chen, Ching-Jen, Esquenazi, Y., Becerril-Gaitan, Andrea, Blanco, Angel I., Palmer, Joshua D., Picozzi, Piero, Lanterna, Luigi Alberto Andrea, Bowden, Greg N., Peterson, Jennifer L., Chiang, Veronica , Pikis, Stylianos , Xu, Zhiyuan, Sheehan, Jason P., Shinya, Yuki , Tos, Salem M , Hajikarimloo, Bardia , Mantziaris, Georgios , Chan, Jason , Nabeel, Ahmed M. , Reda, Wael A. , Tawadros, Sameh R. , Abdelkarim, Khaled , El-Shehaby, Amr M. N. , Eldin, Reem M. Emad, Bin-Alamer, Othman , Lunsford, L. Dade , Niranjan, Ajay , Peker, Selçuk , Samancı, Yavuz , Lee, Cheng-chia, Yang, Huai‐Che , Sheehan, Darrah, Sheehan, Kimball , Liščák, Roman , Alzate, Juan Diego , Meng, Ying , Martinez-Álvarez, Roberto, Fritch, Chanju , Jareczek, Francis J. , Sciscent, Bao Y. , Mathieu, David , Abdelsalam, Ahmed , Starke, Robert M., Almeida, Timóteo , Tripathi, Manjul , Speckter, Herwin , Lazo, Erwin , Esquenazi, Yoshua , Becerril‐Gaitan, Andrea , Amsbaugh, Mark J. , Upadhyay, Rituraj , Palmer, Joshua D. , Franzini, Andrea , Picozzi, Piero , Lanterna, Andrea Luigi, Bowden, Greg , Sheehan, Jason P.

Journal of Neurosurgery: Pediatrics | June 10, 2026 | Volume: No volume available | Issue: No issue available | Pages: 1-10

10.3171/2026.1.peds25593 | PMID 42284606 Get It

OBJECTIVE Ruptured, large pediatric arteriovenous malformations (AVMs) pose a significant management challenge due to high rerupture risk and the morbidity of conventional treatments. Volume-staged stereotactic radiosurgery (VS-SRS) has emerged as an alternative; however, evidence for its use in this specific population is limited. This study aimed to evaluate the long-term efficacy and safety of VS-SRS for ruptured, large AVMs in a dedicated pediatric cohort. METHODS This international, multicenter, retrospective cohort study from 21 centers analyzed outcomes for 42 pediatric patients (age < 18 years) with previously ruptured, large AVMs treated with VS-SRS. The primary outcome was complete AVM obliteration, and secondary outcomes included post-SRS hemorrhage, radiation-induced changes (RICs), and favorable outcome. Favorable outcome in this study was defined as obliteration without post-SRS hemorrhage or permanent RIC. RESULTS At the initial SRS, the median patient age was 14.5 years, and the median AVM volume was 15.0 cm 3 ; most AVMs were high grade (Spetzler-Martin grades IV and V). With a median follow-up of 41.5 months, complete AVM obliteration was achieved in 21 patients (50.0%). The cumulative obliteration rate was 37% at 5 years and 56% at 10 years. Patients with a nidus volume of ≤ 10 cm 3 had significantly higher cumulative obliteration rates than those with a nidus volume > 10 cm 3 (log-rank test, p = 0.021). Similarly, patients treated with a prescription dose > 17 Gy showed significantly higher cumulative obliteration rates compared to those treated with a dose ≤ 17 Gy (log-rank test, p = 0.012). The cumulative 5-year incidences of hemorrhage and RICs following VS-SRS were 19% and 7%, respectively. In multivariable analysis, only larger total AVM volume was an independent predictor of a lower likelihood of favorable outcome (hazard ratio 0.89, 95% CI 0.80–0.99; p = 0.036). CONCLUSIONS In this multicenter pediatric cohort, VS-SRS for ruptured, large AVMs provides a reasonable chance of long-term obliteration, but generally acceptable risks of post-SRS hemorrhage and RICs exist. VS-SRS should be considered as an option for pediatric patients with large, ruptured AVMs.
Associations Between Cumulative Head Trauma and Self‐Reported Parkinsonism and Parkinson's Disease in Former Soccer Players
Miner, Annalise E., Kmiecik, Matthew J., Dunckley, Nathaniel, Adler, Charles H., Driver‐Dunckley, Erika , Nowinski, Christopher J. , Gottesman, Joshua , Tripodis, Yorghos, Stern, Robert A., McKee, Ann C., Stein, Thor D., Alosco, Michael L., Driver-Dunckley, Erika D., Miner, Annalise E., Kmiecik, Matthew J. , Namburi, Niharika , Dunckley, Nathaniel, Adler, Charles H. , Tripodis, Yorghos , McKee, Ann C. , Stein, Thor D. , Mez, Jesse , Briggs, Farren , Alosco, Michael L.

Movement Disorders | June 8, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.1002/mds.70380 | PMID 42252813 Get It

Abstract Background Cumulative head trauma, encompassing repetitive head impacts (RHI) and traumatic brain injury (TBI), has been associated with later‐life neurodegenerative disease. Studies on parkinsonism/Parkinson's disease (PD) have evaluated RHI and TBI in isolation, yielding mixed results. Cumulative head trauma may better predict PD risk. Objective To examine independent and cumulative effects of RHI through soccer participation and TBI history on PD diagnosis and age at diagnosis. Methods We used a cross‐sectional cohort design with data from the Fox Insight study. Participants completed self‐report questionnaires on PD diagnosis, TBI (no TBI, TBI with loss of consciousness [LOC], TBI without LOC), and sport participation. Multivariable logistic regressions examined the effects of soccer, TBI group, and their interaction on PD diagnosis. Cox proportional hazards examined associations with time to PD diagnosis. Covariates included age, sex, race, education, income, body mass index, heart disease/diabetes, and family PD history. Results Among 1231 participants (mean[SD] age = 66.12[10.60]), 278 played soccer (953 non–contact and collision sport [CCS] athletes). Participants reported no TBI (390[33%]), TBI without LOC (495[43%]), or TBI with LOC (258[23%]). Overall, 768(62%) reported a PD diagnosis (mean[SD] age at diagnosis = 59.02[9.86]). A significant soccer × TBI interaction indicated that soccer players with TBI with LOC had 2.6× higher odds of PD compared to non‐CCS athletes without TBI (OR [95% CI] = 2.600[1.085–6.305], P = 0.033). Former soccer players with TBI with LOC had a 15.6% higher hazard of early PD diagnosis (HR = 1.469, P = 0.027) compared to non‐CCS athletes with no TBI. Conclusion Cumulative head trauma (RHI + TBI) increased PD risk and lowered age at onset. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
SDAMPP report #1: Holistic review for medical physics residency applicant selection
Yu, Amy S. , Besemer, Abby, Buckey, Courtney, Cetnar, Ashley, DeWeese, Lindsay, Gao, Yu, Lindsay, Patricia, Rodrigues, Anna, Schubert, Leah, Wilson, Joshua, Wisnoskie, Sarah, Yu, Amy Shu-Jung , Buckey, C, Cetnar, Ashley J. , DeWeese, Lindsay , Lindsay, Patricia E, Schubert, Leah , Wisnoskie, Sarah, Juang, Titania

Journal of Applied Clinical Medical Physics | June 4, 2026 | Volume: 27 | Issue: 6 | Pages: No page available

10.1002/acm2.70649 | PMID 42240068 Get It

Abstract Clinical medical physics is a profession that intersects with various groups as part of a broader healthcare team, including dosimetrists, radiation therapists, radiologic and MRI technologists, IT specialists, and physicians. Success in this field requires academic and technical excellence as well as comprehensive skills for working effectively within an interdisciplinary healthcare team. When hiring medical physics residents, the selection of well‐rounded and highly qualified candidates can be facilitated through a holistic review process that ensures consideration of traditional metrics such as academic performance while also accounting for the importance of various experiences, personal attributes, and intrinsic motivations that impact clinical performance and patient care. The Association of American Medical Colleges (AAMC) emphasizes an overall consideration of Experiences, Attributes, Competencies, and Metrics (EACM) as important for the search process. As part of the healthcare community, medical physics shares the same commitment to high‐quality patient care. By adopting the AAMC's EACM framework, medical physics residency programs can strengthen the fairness, rigor, and overall effectiveness of their application review processes—ultimately benefiting applicants, the medical physics community, and the patients we serve. This Society of Directors of Academic Medical Physics Programs (SDAMPP) task report aims to provide information and resources for applying holistic review to the applicant selection process for medical physics residency programs. Our objective is to enable program directors to reevaluate their selection methods in the context of institutional and program missions and goals and to improve the quality and specificity of recruitment by integrating holistic review concepts into their residency recruitment processes. This initiative can inspire change in recruitment practices, aid programs in hiring well‐rounded and well‐qualified residents, and support the professional growth of our trainees in healthcare. This report provides an overview of holistic reviews and its core principles. We review the current literature and provide evidence from successful implementations of holistic review in other medical fields to illustrate how it can benefit our field. Furthermore, we outline actionable recommendations to facilitate transitioning to a holistic review framework and address potential barriers with practical solutions. A supplemental workbook is provided to guide residency programs in developing their own holistic application review and interview processes. With this report, we aim to provide practical implementation guidelines that will allow residency program directors to implement a selection methodology that comprehensively assesses the full qualifications of individual candidates and ultimately fosters the development of versatile and competent clinical medical physicists who are best equipped to advance the field, meet patient needs, and improve patient care.
Diagnostic Yield of Cardiac CT to Detect Cardiac Thrombi in Patients With Acute Ischemic Stroke (AIS of HEARTS)
Nio, Shan Sui , Green, Daniel S. , Berry-Noronha, Alexander , Rinkel, Leon A. , Beemsterboer, Chiel F.P. , Hasnain, Md Golam , Planken, R. Nils , Randen, Adriënne van , Al-Hadethi, Sinan , Hilt, Mirre G.M. , Ruhe, Deborah S.A., Boekholdt, S Matthijs, Chew, Beng Lim Alvin , Fridgant, Joshua, Mena-Romo, Luis , Kim, Dong Hyun, Guo, Shuyu, Winders, Joel, Senadeera, Sajith C. , Lim, Anthony , Fink, John, Leung, Melissa , Cordato, Dennis, Spratt, N., Collaborators, on behalf of the AIS of HEARTS, Green, Daniel S , van Randen, Adrienne , Bouma, Berto J , Boekholdt, S Matthijs , Fridgant, Joshua , Mena-Romo, Luis , Alamri, Yassar , Lim, Anthony T , Leung, Melissa , Cordato, Dennis , Parsons, Mark W , Spratt, Neil J , Garcia-Esperon, Carlos , Wu, Teddy Y , Coutinho, Jonathan M , Beemsterboer, Chiel F P , Planken, R Nils , Berry‐Noronha, Alexander , Hasnain, Md Golam , Hilt, Mirre , Ruhe, Deborah, Bouma, Berto J. , Boekholdt, S. Matthijs , Kim, Dong Hyun, Fink, John

Stroke | June 2, 2026 | Volume: 57 | Issue: 8 | Pages: 2408-2416

10.1161/strokeaha.126.055575 | PMID 42227105 Get It

BACKGROUND: Cardiac computed tomography (CT) acquired during the acute stroke imaging protocol is an emerging modality to detect cardiac thrombi. We determined its yield in patients with acute ischemic stroke. METHODS: We performed a 1-stage individual patient data meta-analysis of 4 prospective observational cohorts (AIS of HEARTS [Acute Ischemic Stroke of Heart-Related Embolic Sources Detected on Acute Cardiac CT Scans]), including patients with acute ischemic stroke who underwent ECG-gated or non–ECG-gated cardiac CT between May 2018 and June 2024. We excluded patients with transient ischemic attack or stroke mimics. The primary outcome was the proportion of patients with a thrombus on cardiac CT. Secondary outcomes were additional scan time, radiation dose, comparison with echocardiography, and 90-day outcomes. We performed logistic regression analyses to compare 90-day outcomes between patients with and without thrombus, adjusting for age, sex, history of atrial fibrillation, ischemic heart disease, chronic heart failure, stroke or transient ischemic attack, anticoagulant use, prestroke modified Rankin Scale score, National Institutes of Health Stroke Scale score, large vessel occlusions, and intravenous thrombolysis, as appropriate for each outcome. RESULTS: We included 3919 patients (median age, 74 [interquartile range (IQR), 63–82], 58% male, median National Institutes of Health Stroke Scale score 6 [IQR, 3–12]). Cardiac CT detected a thrombus in 243 (6.2%) patients. Among 1323 patients that underwent both cardiac CT and transthoracic echocardiography, cardiac CT had a higher yield than transthoracic echocardiography (odds ratio, 7.4 [95% CI, 4.0–15.1]; P <0.001). Median additional scan time was 6 minutes (IQR, 5–7) for ECG-gated and 13 seconds (IQR, 12–61) for non–ECG-gated cardiac CT. Median additional radiation dose was 2.9 mSv (IQR, 1.6–4.1). Patients with thrombi had higher 90-day mortality (33% versus 15%, adjusted odds ratio, 1.6 [95% CI, 1.1–2.3]) and worse modified Rankin Scale scores (median modified Rankin Scale score 3 versus 2, adjusted odds ratio, 1.6 [95% CI, 1.2–2.0]), but similar recurrent stroke rates (5% versus 4%, adjusted odds ratio, 1.4 [95% CI, 0.7–2.5]). CONCLUSIONS: Implementing cardiac CT into the acute stroke imaging protocol is feasible, detects thrombi in ≈6% of patients, and has a higher yield than transthoracic echocardiography. Cardiac thrombi were associated with higher mortality, but not higher stroke recurrence. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT07165093.
Variability in Clinical Performance of the FDA-Cleared Lumipulse P-Tau217/β-Amyloid 1-42 Plasma Ratio
Algeciras-Schimnich, Alicia, Reyes, Ramiro Eduardo Rea , Ashrafzadeh-Kian, Susan, Wilson, Rachel, MD, Miller, Johnson, D H, Botha, Hugo, Day, Gregory S., Graff-Radford, Jonathan, Ramanan, Vijay K., Jack, Clifford R., Johnson, Sterling C., Zetterberg, Henrik, Petersen, Ronald C., Bornhorst, Joshua A. , Algeciras‐Schimnich, Alicia , Bornhorst, Joshua , Figdore, Daniel J. , Ashrafzadeh‐Kian, Susan , Burkett, Brian J. , Botha, Hugo , McCarter, Stuart J. , Day, Gregory S. , Graff‐Radford, Jonathan , Ramanan, Vijay K. , Jack, Clifford R. , Johnson, Sterling C. , Zetterberg, Henrik , Petersen, Ronald C.

JAMA Neurology | June 1, 2026 | Volume: 83 | Issue: 8 | Pages: 823

10.1001/jamaneurol.2026.1565 | PMID 42223932 Get It

This cross-sectional study evaluates the performance of the US Food and Drug Administration–cleared phosphorylated tau 217 (p-tau217) to β-amyloid 42 ratio cut points used to detect amyloid pathology associated with Alzheimer disease.
WeCare intervention to improve breast cancer screening and research preparedness in rural and low-socioeconomic women: study protocol for a community-engaged feasibility trial
Min, Hoon‐Ki , Imsande, Kaylynn G, Vitriago, Anni, Seibel, Maria, Rudder, B. de, Watson, Dave , Beenken, Madison, Larson, Stephanie, Flock, Carolyn, Murphy, Crystal, Puljas, Tracy L, Asiedu, Gladys B. , Odedina, Folakemi T, Lynch, Brian , Haddad, Tufia C. , Min, Hoon-Ki Paul , Pritchett, Joshua C. , Rudder, Bongi, Beenken, Madison J, Larson, Stephanie L., Murphy, Crystal M, Patten, Christi A. , Haddad, Tufia C , Tran, Linh Thuy Khanh , Larson, Stephanie L, Flock, Carolyn R.

BMJ Open | June 1, 2026 | Volume: 16 | Issue: 6 | Pages: e113154

10.1136/bmjopen-2025-113154 | PMID 42225362 Get It

Introduction Women residing in rural areas or belonging to lower socioeconomic status (SES) strata experience disproportionately low rates of breast cancer screening, contributing to delayed diagnoses and poorer prognoses. In addition, their participation in clinical trials remains markedly limited, reducing opportunities to access preventive and screening interventions. Promoting research preparedness among women before disease onset may empower them to make informed decisions regarding their health and willingness to participate in clinical research with fewer emotional and logistical barriers. Methods and analysis This project applies a community-based participatory research approach to develop and refine the WeCARE (Women’s Engagement for Cancer Awareness, Resources and Education) intervention for women aged 50–74 years who have either never undergone breast cancer screening or have not received screening in the past 5 years and who reside in rural areas or belong to low SES groups. The intervention consists of two components. Component 1 is a single-day, in-person community forum that includes (a) an educational seminar led by an oncologist to address breast cancer risk and screening guidelines, (b) survivor storytelling to enhance emotional engagement and cultural resonance and (c) facilitated navigation to breast cancer screening and future research participation. Component 2 involves structured post-forum follow-up through multiple touchpoints (phone calls and mailed boosters) to reinforce knowledge, address barriers and support screening completion and research enrolment. Quantitative data (eg, screening completion, satisfaction and follow-up engagement) will be summarised using descriptive statistics to assess feasibility and reach on 50 participants. Qualitative feedback from participants will undergo thematic analysis to identify barriers, facilitators and perceived cultural relevance. Integrated mixed-method interpretation will inform iterative refinement of the WeCARE intervention and guide design of subsequent larger trials. Ethics and dissemination Approved by the Mayo Clinic Institutional Review Board (IRB #25–008934). All participants will provide informed consent. Procedures ensure confidentiality, cultural sensitivity and participant safety. Data will be stored in REDCap and disseminated through publications, conferences, local town halls and community reports.
PubMetric : Empowering Researchers and Improving Systematic Reviews/Meta‐Analyses
Smith, Clay, Rouleau, S, Smith, Joshua, Long, Brit, Rouleau, Samuel G. , Rouleau, Samuel, Long, Brit

Academic Emergency Medicine | May 30, 2026 | Volume: 33 | Issue: 6 | Pages: No page available

10.1111/acem.70326 | PMID 42216680 Get It

MC240701: Decentralized pilot study of triple oral metronomic chemotherapy in recurrent/metastatic oral cavity cancer.
Baral, Binav, Nguyen, Anna C., Meyers, Jordan E., Fazer-Posorske, Casey, Lewis, Akeem Ronell, Zhao, Yujie, Chintakuntlawar, Ashish V., Asiedu, Gladys, Bayne, Harry E. Fuentes, Price, Katharine A. , Fazer-Posorske, Casey , Pritchett, Joshua C. , McGarrah, Patrick W. , Zhao, Yujie, Chintakuntlawar, Ashish V.

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

10.1200/jco.2026.44.16_suppl.tps6126 Get It

TPS6126 Background: Oral cavity cancers (OCC) are a rare subtype of head and neck cancer (HNC) with poor outcomes and limited second-line treatment options in the recurrent or metastatic (R/M) setting. Treatment-related morbidity and repeated local recurrences in OCC result in significant impairment of function and quality of life. Rural OCC patients comprise a sizable portion (50%) of our practice and are usually of lower socioeconomic status with lack of access to specialist care. They also have multiple barriers to treatment access and ancillary services, translating to poorer clinical outcomes. There is a critical need for effective and accessible therapies for R/M OCC in rural patients. Triple oral metronomic chemotherapy (TOMC) with Methotrexate, Erlotinib and Celecoxib (MEC) suppresses angiogenesis and activates antitumor microenvironment in HNC. Studies using TOMC in R/M OCC outside the US show reasonable efficacy (6-month OS 52.9%), better safety and lower cost compared to standard second line options. We hypothesize that a decentralized clinical trial with TOMC in R/M OCC is feasible, safe and effective in addition to being economical and accessible for rural patients. Methods: MC240701 is a single institution, open label, decentralized, single arm pilot study of MEC in patients with R/M OCC. Eligible pts must be ≥18 years old, have pathologically confirmed R/M OCC not amenable to curative-intent therapy, ECOG 0-2 and adequate organ function. At least 1 measurable lesion by RECIST 1.1 OR non-measurable disease (evident mucosal lesions, CNS/bone disease, lesions not meeting RECIST criteria) is permitted. Patients must have received standard first line immunotherapy with or without chemotherapy OR should be unable/unwilling to receive first line treatment. Key exclusion criteria include patients unable to take pills by mouth, serious medical co-morbidity or autoimmune disease, immunocompromised patients and other active malignancy. Primary endpoint is to demonstrate feasibility of decentralized clinical trials, secondary outcomes include overall response rate, progression free and overall survival and toxicity. Additional goals are to evaluate patient impact of decentralized treatment through surveys and interviews After initial screening and evaluation, patients are remotely consented and will receive study drugs by mail. All patients will receive the same treatment of Methotrexate 9mg/m 2 PO weekly, Erlotinib 150 mg PO daily, and Celecoxib 200 mg PO BID, each cycle will be 28 days. Treatment will continue until disease progression or treatment tolerance, study duration is for 2 years. All subsequent clinical and laboratory monitoring and response assessments (every 3 cycles) will be remotely performed or have an option for local testing. Enrollment began July 2025 and 4 out of planned 25 patients have been accrued. FDA IND:174540. Clinical trial information: NCT06997068 .
A phase 2 randomized trial of radium-223 dichloride and cabozantinib in patients (pts) with renal cell carcinoma (RCC) with bone metastases (BM): RADICAL (Alliance A031801).
McKay, Rana R., Atherton, Pamela J. , Ballman, Karla V., Jacene, Heather, Chen, Ronald C., Cole, Suzanne, Baghdadi, Tareq Al, Kwok, Young , Tan, Alan, Berg, S., Beltran, H, Morris, M J, Zhang, Tian, Galsky, Matthew D. , Rosenberg, Jonathan E., George, Daniel J., Choueiri, Toni K., McKay, Rana R. , Ballman, Karla V. , Jacene, Heather A. , Choudhury, Atish D. , Lang, Joshua M. , Cole, Suzanne , Morris, Michael J. , McGregor, Bradley A. , Zhang, T., Rosenberg, Jonathan E , George, Daniel J. , Choueiri, Toni K.

Journal of Clinical Oncology | May 27, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 4500-4500

10.1200/jco.2026.44.16_suppl.4500 Get It

4500 Background: BM occur in ~30% of RCC pts and are associated with poor survival and symptomatic skeletal events (SSEs). Radium-223, an alpha-emitting bone-seeking radioisotope, prolongs survival in advanced prostate cancer. A pilot study of radium-223 with VEGF tyrosine kinase inhibitors (TKI) in RCC with BM showed safety and early efficacy (McKay, CCR, 2018). Cabozantinib is a TKI that showed efficacy in BM. RADICAL (NCT04071223) was designed to investigate cabozantinib ± radium-223 in RCC with BM. Methods: This open label multicenter study enrolled RCC pts with ≥1 symptomatic BM not previously irradiated and Karnofsky performance status ≥60%. Prior therapies were allowed; non-clear cell population was limited to 20%. Randomization was 1:1 to cabozantinib with (Arm A) or without (Arm B) radium-223, stratified by osteoclast-targeted therapy (OTT), prior therapy, baseline opioid use, and IMDC risk. In Arm A, cabozantinib was 40 mg daily cycle 1, 60 mg thereafter if tolerated; radium-223 was 1.49 microcurie/kg IV every 28 days for 6 doses. In Arm B, cabozantinib was 60 mg daily. The primary endpoint was SSE-free survival (SSE-FS). Secondary endpoints were safety, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). The study was designed with 85% power to detect improvement in 6-month SSE-FS from 65% to 78% (one-sided α=0.05), with planned interim futility analysis at 50% of expected events. Results: From 12/2019 to 9/2025, 90 pts were enrolled and evaluable for the interim analysis. Median age was 63 years; 74.4% male, 90.0% White, 83.3% clear cell histology. 11.1% were treatment naïve, 80.0% received OTT, 51.1% had baseline opioid use. IMDC risk was 16.7% favorable, 68.9% intermediate, 14.4% poor. Median cabozantinib dose was 31.4 mg (Arm A) and 40.0 mg (Arm B); median radium-223 cycles was 6. Median follow-up was 13.1 (range 0.1-49.4) months with 50 events, 17 SSEs (Arm A: 10; Arm B: 7) and 33 deaths (Arm A: 13; Arm B: 20). Outcomes are in Table. 71 pts were evaluable for response. ORR was 22.2% (Arm A), 22.9% (Arm B). Any grade treatment-related adverse events were 97.7% (Arm A), 93.2% (Arm B); grade ≥3 were 65.9% (Arm A), 56.8% (Arm B). The trial closed after interim analysis as SSE-FS did not meet the prespecified futility boundary (HR≤1). Conclusions: Radium-223 did not improve the primary endpoint of SSE-FS when added to cabozantinib but a numerical prolongation in OS was observed. Combination treatment was safe. Alternative radiotherapeutics warrant investigation in RCC. Clinical trial information: NCT04071223 . Interim efficacy analysis. Arm Median(95% CI) HR (95% CI) Stratified SSE-FS A 17.9 (15.0-NE) 1.24 (0.62-2.48) B 17.6 (10.9-NE) Unstratified SSE-FS A 17.9 (15.0-NE) 0.90 (0.51-1.59) B 17.6 (10.9-NE) OS A 32.2 (17.9-NE) 0.77 (0.42-1.41) B 21.3 (12.3-NE) Stratified PFS A 11.0 (5.8-17.4) 1.39 (0.72-2.66) B 11.2 (9.0-18.5)