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6593 citation(s) found for "Ha, Richard".

Identifying consensus and areas for future research in chondrosarcoma
Kurisunkal, Vineet , Botello, Eduardo , Boyle, Richard A. , Ebeid, Walid , Houdek, Matthew T. , Puri, Ajay , Brennan, Bernadette , Laitinen, Minna , Jutte, Paul C. , Lazarides, Alexander L. , Verspoor, F.G.M. , Visgauss, Julia D. , Jeys, Lee M , Morris, Guy V , Kurisunkal, Vineet , Botello, Eduardo , Ebeid, Walid , Houdek, Matthew T , Puri, Ajay , Ruggieri, Pietro , Brennan, Bernadette , Laitinen, Minna K , Couch, Cory , Rose, Peter, Sullivan, Mikaela, Tibbo, Meagan, Jutte, Paul , Visgauss, Julia D , Jeys, Lee , Ruggieri, Pietro

The Bone & Joint Journal | February 1, 2025 | Volume: 107-B | Issue: 2 | Pages: 246-252

10.1302/0301-620x.107b2.bjj-2024-0643.r1 | PMID 39889743 Get It

AimsThe Birmingham Orthopaedic Oncology Meeting (BOOM), held in January 2024, convened 309 delegates from 53 countries to discuss and refine 21 consensus statements on the optimal management of chondrosarcoma.MethodsWith representation from Europe (43%; n = 133), North America (17%; n = 53), South America (16%; n = 49), Asia (13%; n = 40), Australasia (5%; n = 16), the Middle East (4%; n = 12), and Africa (2%; n = 6), the combined experience of treating bone sarcomas among attendees totalled approximately 30,000 cases annually, equivalent to 66 years of experience in the UK alone. The meeting’s process began with the formation of a local organizing committee, regional leads, and a scientific committee comprising representatives from 150 specialist units across 47 countries. Supported by major orthopaedic oncology organizations, the meeting used a modified Delphi process to develop consensus statements through online questionnaires, thematic groupings, narrative reviews, and anonymous pre-meeting polling.ResultsStrong (> 80%) consensus was achieved on 19 out of 21 statements, reflecting agreement among delegates. Key areas of consensus included the role of radiology in diagnosis and surveillance, the management of locally recurrent disease, and the treatment of dedifferentiated chondrosarcoma. Notably, there was agreement that routine chemotherapy has no role in chondrosarcoma treatment, and radiological surveillance is safe for intraosseous chondrosarcomas. Despite the overall consensus, areas of controversy remain, particularly regarding the treatment of atypical cartilage tumours and surgical margins. These unresolved issues underscore the need for further research and collaboration within the orthopaedic oncology community.ConclusionBOOM represents the largest global consensus meeting in orthopaedic oncology, providing valuable guidance for clinicians managing chondrosarcoma worldwide. The consensus statements offer a reference for clinical practice, highlight key research priorities, and aim to improve patient outcomes on a global scale.Cite this article: Bone Joint J 2025;107-B(2):246–252.
Rates of Minimally Invasive Surgery After Introduction of Robotic-Assisted Surgery for Common General Surgery Operations
Wall‐Wieler, Elizabeth , Johnson, Shaneeta, Culbertson, Richard, Fong, Zhi Ven , Johnson, Shaneeta M. , Mitzman, Brian

Annals of Surgery Open | January 31, 2025 | Volume: 6 | Issue: 1 | Pages: e546

10.1097/as9.0000000000000546 | PMID 40134491 Get It

Importance: Many patients who would benefit from minimally invasive surgery (MIS) have open surgery; robotic-assisted surgery (RAS) addresses some of the limitations of laparoscopic surgery and could increase rates of MIS across different patient populations. Objective: To determine whether the introduction of RAS increases MIS rates and whether increases are seen across different patient populations undergoing common general surgery procedures. Design: A retrospective cohort study was performed to compare rates of MIS in the year before and after the index date for hospitals that did and did not introduce RAS. Generalized estimating equation regression models were used to compare rates in MIS over time. Setting: PINC AI Healthcare Database, an all-payor discharge database of hospitals in the United States. Participants: Hospitals that performed cholecystectomy, inguinal hernia repair, ventral hernia repair, and colorectal resection from 2016 to 2022. Exposure: RAS hospitals performing at least 1 common general surgery procedure using RAS. Main Outcome and Measure: The primary analysis examined rates of MIS, defined as the rate of common general surgeries that were minimally invasive (laparoscopic or RAS) in a hospital. The secondary analysis examined MIS rates for common general surgeries, across age, sex, race, ethnicity, and payor. Results: Of 408 hospitals included in the study, 153 (38%) introduced RAS for common general surgeries. The relative MIS rate for hospitals that introduced RAS compared with hospitals that did not went from 1.08 (95% confidence interval [CI], 1.02–1.14; P < 0.01) before the index date to 1.15 (95% CI, 1.09–1.22; P < 0.01) after the index date (P interaction < 0.01), indicating a larger increase in MIS rates among hospitals introducing RAS. MIS rates increased significantly more in hospitals that introduced RAS across patient age, sex, ethnicity, race, and payor compared with hospitals that did not introduce RAS. Conclusions and Relevance: Hospitals that introduced RAS for common general surgery procedures were associated with an increase in MIS rates across different patient populations compared with hospitals that did not introduce RAS.
1386: MECHANICAL VENTILATION TRAINING STANDARDIZATION: INTERNATIONAL MODIFIED DELPHI SURVEY
Manjappachar, Nirmala, Kılıçkaya, Oğuz , Wang, Baiyong , Chu, Kim Duc, Gajic, Ognjen, Oeckler, Richard A. , Dong, Yue , Niven, Alexander S. , Lal, Amos

Critical Care Medicine | January 31, 2025 | Volume: 53 | Issue: 1 | Pages: No page available

10.1097/01.ccm.0001104208.99705.59 Get It

982: EXTERNAL VALIDATION OF THE FRASER EQUATION TO ESTIMATE FREE VALPROATE CONCENTRATION IN THE ICU
Brown, Caitlin S. , Liu, JiTong , Riker, Richard R. , Lopez, Natasha , Gagnon, David J. , Webb, Andrew , Rosenthal, Eric S.

Critical Care Medicine | January 31, 2025 | Volume: 53 | Issue: 1 | Pages: No page available

10.1097/01.ccm.0001102592.08813.34 Get It

Characterization of Factors Associated With Death in Deceased Patients With Mitochondrial Disorders
Ivaniuk, Alina , Anselm, Irina , Bowen, Aaron B. , Cohen, Bruce H. , Eminoğlu, Fatma Tuba , Estrella, Jane , Gallagher, Renata C. , Gannon, Jennifer , Gorman, Gráinne S. , Greene, Carol L. , Haas, Richard , Kapoor, Seema , Karaa, Amel , Koenig, Mary Kay , Kornblum, Cornelia , Lichter‐Konecki, Uta , Lopriore, Piervito , McFarland, Robert , Moe, Aye , Ng, Yi Shiau , Saneto, Russell P. , Scaglia, Fernando , Tarnopolsky, Mark A. , Walker, Melissa , Group, as the Hong Kong Mitochondrial Diseases Interest, Fung, Cheuk Wing , Wong, Tsz-sum, Belaramani, Kiran , Chan, Chun-kong , Chan, Wing-ki, Chan, Wai-lun Larry, Cheung, H. M. E., Cheung, Ka-yin, Chang, Richard Shek‐kwan , Cheung, Sing-ngai, Cheung, Tsz-Fung, Cheung, Yuk-fai, Chong, Shuk-ching Josephine, Chow, Chi-kwan Jasmine , Fan, Florence , Fok, Wai-ming Joshua , Fung, Tsui-hang Sharon , Hui, Kwok-fai, Hui, Ting-hin, Ko, Chun Hung, Kwan, Min-chung, Kwok, Anne Mei Kwun , Kwok, Sung-shing Jeffrey, Lai, Moon-sing, Lam, Yau-on, Lam, Ching‐Wan , Lau, Ming-chung, Law, Hiu-Fung, Lee, Wing‐Cheong , Leung, Kin-hang, Leung, Kit-yan, Li, Siu-hung, Ling, Tsz-ki, Liu, Kam Tim , Lui, Colin H. T., Luk, Ching-on, Luk, Ho‐Ming , Ma, Che-Kwan, Ma, Karen , Ma, Kam-hung , Mew, Yuen-ni, Mo, Alex, Hg, Sui-Fun, Poon, Grace Wing-kit , Sheng, Bun , Szeto, Cheuk-ling Charing, Tai, Shuk‐Mui, Tang, Jing-Liang, Tse, Choi-ting Alan , Tsung, Li-yan Lilian, Wong, Ho-ming June, Wong, Wing-yin Winnie, Wong, Kwok-kui, Wong, Suet-na Sheila , Wong, Chun-nei Virginia, Wong, Wai-shan Sammy, Wong, Chi-kin Felix, Wu, Shun-Ping, Wu, Hiu-fung Jerome , Yau, Man-Mut, Yau, Eric Kin Cheong , Yeung, Wai Lan , Yeung, Hon‐Ming Jonas , Yip, Kin-keung Edwin, Young, Pui-hong Terence, Yuan, Gao , Yuen, Yuet‐Ping , Yuen, Chi-lap, Anselm, Irina A , Bowen, Aaron , Ganetzky, Rebecca D , Gannon, Jennifer , Gorman, Grainne S , Greene, Carol , Gropman, Andrea L , Haas, Richard H , Hirano, Michio , Kapoor, Seema , Karaa, Amel , Koenig, Mary Kay , Kornblum, Cornelia , Kose, Engin , Larson, Austin A , Lichter-Konecki, Uta , Lopriore, Piervito , Mancuso, Michelangelo , McFarland, Robert , Moe, Aye Myat , Ng, Yi Shiau , Saneto, Russell P , Scaglia, Fernando , Sue, Carolyn M , Tarnopolsky, Mark , Walker, Melissa A , Parikh, Sumit , Cheuk-Wing, Fung , Wong, Tsz-Sum , Belaramani, Kiran , Chan, Chun-Kong , Chan, Wing-Ki , Chan, Wai-Lun Larry , Cheung, Hon-Wing , Cheung, Ka-Yin , Chang, Shek-Kwan , Cheung, Sing-Ngai , Cheung, Tsz-Fung , Cheung, Yuk-Fai , Chow, Chi-Kwan Jasmine , Chung, Hon-Yin B , Fan, Sin-Ying Florence , Fok, Wai-Ming Joshua , Fung, Tsui-Hang Sharon , Hui, Kwok-Fai , Hui, Ting-Hin , Hui, Joannie , Ko, Chun Hung , Kwan, Min-Chung , Kwok, Mei-Kwan Anne , Kwok, Sung-Shing Jeffrey , Lai, Moon-Sing , Lam, Yau-On , Lam, Ching-Wan , Lau, Ming-Chung , Law, Chun-Yiu Eric , Law, Hiu-Fung , Lee, Wing-Cheong , Leung, Kin-Hang , Leung, Kit-Yan , Li, Siu-Hung , Liu, Kam-Tim Timothy , Lo, Fai-Man , Lui, Colin , Luk, Ho-Ming , Ma, Che-Kwan , Ma, Karen , Ma, Kam-Hung , Mo, Alex , Hg, Sui-Fun , Poon, Wing-Kit Grace , Sheng, Bun , Tse, Choi-Ting Alan , Wong, Ho-Ming June , Wong, Wing-Yin Winnie , Wong, Kwok-Kui , Wong, Suet-Na Sheila , Wong, Chun-Nei Virginia , Wong, Wai-Shan Sammy , Wu, Hiu-Fung Jerome , Yau, Kin-Cheong Eric , Yeung, Wai-Lan , Yeung, Hon-Ming Jonas , Yip, Kin-Keung Edwin , Young, Pui-Hong Terence , Yuan, Gao , Yuen, Yuet-Ping Liz , Ivaniuk, Alina , Cohen, Bruce H , Ganetzky, Rebecca , Larson, Austin , Morava, Éva , Sue, Carolyn M. , Parikh, Sumit , Group, as the Hong Kong Mitochondrial Diseases Interest, Fong, Ka-Wing, Lee, Han‐Chih Hencher , Tang, Jing-Liang, Wu, Hui-Jun

Neurology | January 30, 2025 | Volume: 104 | Issue: 4 | Pages: No page available

10.1212/wnl.0000000000209779 | PMID 39883904 Get It

Comparative efficacy and safety of stent retrievers as a bailout strategy following failed contact aspiration technique in acute stroke thrombectomy
Ezzeldin, Mohamad , Hukamdad, Mishaal , Kasem, Rahim Abo , Ezzeldin, Rime , Maier, Ilko , Rai, Ansaar , Jabbour, Pascal , Kim, Joon‐Tae , Howard, Brian M. , Wolfe, Stacey Q , Starke, Robert M., Psychogios, Marios‐Nikos , Dye, Justin , Alaraj, Ali , Yoshimura, Shinichi, Tanweer, Omar , Navía, Pedro , Polifka, Adam , Siddiqui, Fazeel , Brinjikji, Waleed , Dağlıoğlu, Ergün , Williamson, Richard A., Altschul, David , Ogilvy, Christopher S. , Crosa, Roberto , Gory, Benjamin , Kan, Peter , Casagrande, Walter, Chowdhry, Shakeel , Stiefel, Michael , Chaubal, Varun , Spiotta, Alejandro M , Abo Kasem, Rahim , Rai, Ansaar , Wolfe, Stacey Quintero , Shaban, Amir , Alaraj, Ali , Fiorella, David , Navia, Pedro , Cuellar-Saenz, Hugo H , Fragata, Isabel , Mascitelli, Justin R , Osbun, Joshua W , Mokin, Maxim , Matouk, Charles , Brinjikji, Waleed , Altschul, David J , Ogilvy, Christopher S , Crosa, Roberto , Levitt, Michael R , Grandhi, Ramesh , Paul, Alexandra R , Kan, Peter , Spiotta, Alejandro M , Howard, Brian M , Jabbour, Pascal , Alawieh, Ali , Goyal, Nitin , Fiorella, David , Romano, Daniele G, Cuellar, Hugo , Fragata, Isabel , Moss, Mark, Limaye, Kaustubh , Matouk, Charles , Park, Min S, Williamson, Richard, Levitt, Michael R. , Grandhi, Ramesh

Journal of NeuroInterventional Surgery | January 30, 2025 | Volume: 18 | Issue: 2 | Pages: 390-398

10.1136/jnis-2024-022781 | PMID 39884851 Get It

Background The contact aspiration (CA) technique is often used to perform endovascular thrombectomy (EVT) for acute ischemic stroke (AIS); however, rescue strategies are necessary if CA fails to achieve recanalization. This study investigates the outcomes of incorporating stent retriever (SR) thrombectomy in the rescue strategy following failed CA. Methods EVT patients with failed CA attempts were identified from a large multicenter registry and stratified by rescue technique: CA alone or incorporating SR in the rescue strategy. Outcomes included successful recanalization, 90-day functional outcomes (defined by the modified Rankin Scale (mRS) score), symptomatic intracranial hemorrhage (sICH), and 90-day mortality. Results Among 1885 patients with failed CA attempts, conversion to SR was associated with higher recanalization rates (85.2% vs 80.6%; p=0.03), higher rates of second-pass recanalization (31.2% vs 23.4%; p<0.001), and better 90-day outcomes (mRS 0–2: 35.2% vs 29.9%; p=0.04) when compared with repeated CA attempts. Trevo SRs showed higher odds of successful recanalization (adjusted odds ratio (aOR)=1.9; p=0.02), second-pass recanalization (aOR=1.7; p=0.01), and reduced odds of sICH (aOR=0.3; p=0.02). EmboTrap SRs were associated with higher odds of 90-day mortality (aOR=2.6; p=0.004) and sICH (aOR=2.9; p=0.04) and lower odds of recanalization (aOR=0.5; p=0.03). Conclusions Incorporating SR in the rescue strategy after a failed CA improves recanalization rates and functional outcomes. Trevo SRs demonstrated superior efficacy and safety when incorporated into the rescue strategy.
Infection‐Related Hospitalization and Incident Heart Failure: The Atherosclerosis Risk in Communities Study
Molinsky, Rebecca , Shah, Amil M. , Yuzefpolskaya, M. , Yu, Bing , Misialek, Jeffrey R. , Bohn, Bruno , Vock, David M. , MacLehose, Richard F. , Borlaug, Barry A. , Colombo, P.C. , Ndumele, Chiadi E. , Ishigami, Junichi , Matsushita, Kunihiro , Lutsey, Pamela L. , Demmer, Ryan T. , Neumark‐Sztainer, Dianne , Molinsky, Rebecca L , Shah, Amil , Yuzefpolskaya, Melana , Vock, David , Colombo, Paolo C , Borlaug, Barry A , Lutsey, Pamela L , Neumark-Sztainer, Dianne , Demmer, Ryan T

Journal of the American Heart Association | January 30, 2025 | Volume: 14 | Issue: 3 | Pages: No page available

10.1161/jaha.123.033877 | PMID 39883116 Get It

Background The immune response to infections may become dysregulated and promote myocardial damage contributing to heart failure (HF). We examined the relationship between infection‐related hospitalization (IRH) and HF, HF with preserved ejection fraction, and HF with reduced ejection fraction. Methods and Results We studied 14 468 adults aged 45 to 64 years in the ARIC (Atherosclerosis Risk in Communities) Study who were HF free at visit 1 (1987–1989). IRH was identified using select International Classification of Diseases ( ICD ) codes in hospital discharge records and was treated as a time‐varying exposure. HF incidence was defined as the first occurrence of either a hospitalization that included an ICD, Ninth Revision ( ICD‐9 ) discharge code of 428 (428.0–428.9) among the primary or secondary diagnoses or a death certificate with an ICD‐9 code of 428 or an ICD, Tenth Revision ( ICD‐10 ) code of I50 among any of the listed diagnoses or underlying causes of death. We used multivariable‐adjusted Cox proportional hazards models to assess the association between IRH and incident HF, HF with reduced ejection fraction, and HF with preserved ejection fraction. Median follow‐up time was 27 years, 55% were women, 26% were Black, mean age at baseline was 54±6 years, 46% had an IRH, and 3565 had incident HF. Hazard ratio (HR) for incident HF events among participants who had an IRH compared with those who did not was 2.35 (95% CI, 2.19–2.52). This relationship was consistent across different types of infections. Additionally, IRH was associated with both HF with reduced ejection fraction and HF with preserved ejection fraction: 1.77 (95% CI, 1.35–2.32) and 2.97 (95% CI, 2.36–3.75), respectively. Conclusions IRH was associated with incident HF, HF with reduced ejection fraction, and HF with preserved ejection fraction. IRH might represent a modifiable risk factor for HF pathophysiology.
Abstract WMP18: The Association between Cerebral Microbleed Patterns and Incident Dementia: The ARIC-Neurocognitive Study
Vuong, Richard, Morrill, Valerie, Graff-Radford, Jonathan, Mosley, Thomas, Johansen, Michelle C. , Jack, Clifford, Gottesman, Rebecca F., Jack, Clifford R. , Jack, Clifford R , Johansen, Michelle C , Graff‐Radford, Jonathan , Knopman, David S. , Mosley, Thomas, Walker, Keenan A. , Pike, James Russell , Schneider, Andrea L.C.

Stroke | January 30, 2025 | Volume: 56 | Issue: Suppl_1 | Pages: No page available

10.1161/str.56.suppl_1.wmp18 Get It

Background: Cerebral microbleeds (CMBs) are associated with incident dementia, but the impact of specific CMB patterns is unclear. CMBs in lobar regions suggest cerebral amyloid angiopathy (CAA), which is sometimes accompanied by superficial siderosis (SS), while subcortical CMBs indicate hypertensive origins. This study investigates the association between CMB patterns and dementia risk in the community-based longitudinal Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS). Methods: All ARIC-NCS participants with a 3T research MRI at visit 5 (2011-13; aged 67-90) without intracerebral hemorrhage or dementia were included. CMB and SS presence and location were coded from T2* GRE sequences. Individuals were classified into one of four patterns: no CMBs, only subcortical, mixed (lobar and/or SS + subcortical), and only lobar and/or SS. Incident dementia diagnoses were defined by cognitive testing (in-person and telephone), informant interviews, and hospital discharge codes or death certificates. Cox proportional-hazards models assessed the association between the presence, patterns, and frequency of CMBs (0,1,2,3+), presence of SS, and incident dementia from visit 5 through 2020. Model covariates included demographics, vascular risk factors, and imaging markers of small vessel disease. Results: Among 1609 participants, 364 had CMBs (Table 1). Participants with CMBs tended to be older and female compared to those without CMBs. Compared to individuals with no CMBs, presence of any CMBs was associated with an increased risk of dementia (Table 2). Compared to individuals without CMBs, individuals with only lobar CMBs and/or SS had an increased risk of incident dementia, as did individuals with mixed CMBs, but individuals with subcortical-only did not. Participants with ≥3 CMBs of any variant had an increased risk of incident dementia vs no CMBs. Although SS was infrequent, its presence (vs no SS) was associated with an elevated risk of dementia. Conclusion: CMBs, particularly in a mixed or lobar and/or SS-only pattern, are linked to an increased risk of incident dementia. The number of recurrent CMBs and any SS also showed an increased dementia risk. These data support that dementia risk is high in individuals with a CAA-type CMB pattern, but also emphasize that a mixed pattern, not typical of CAA alone, is associated with a high risk of dementia. Further studies should evaluate mechanisms by which these different patterns contribute to dementia.
Abstract 100: Association of the Mediterranean Diet with White Matter Integrity Among Hispanics/Latinos. Final Results from the Study of Latinos-Investigation of Neurocognitive Aging-MRI (SOL-INCA-MRI) Ancillary Study
Trifan, Gabriela , Moustafa, Bayan , Lipton, Richard, Sotres‐Alvarez, Daniela , Tarraf, Wassim , Stickel, Ariana M. , Talavera, Gregory, Maillard, Pauline , DeCarli, Charles , Maillard, Pauline , Isasi, Carmen R. , Lipton, Richard B. , Cai, Jianwen , Mattei, Josiemer , Daviglus, Martha , Gonzalez, Hector M , Testai, Fernando D.

Stroke | January 30, 2025 | Volume: 56 | Issue: Suppl_1 | Pages: No page available

10.1161/str.56.suppl_1.100 Get It

Background: High adherence to the Mediterranean Diet (MeDi) was associated with better cognitive performance and decreased memory decline among Hispanic or Latino adults. Objective: Investigate if higher adherence to the MeDi improves white matter (WM) integrity among Hispanic/Latino adults and if this effect is mediated by cardiovascular health (CVH). Methods: We included 2,774 participants from the Study of Latinos-Investigation of Neurocognitive Aging-MRI Ancillary Study. Participants completed 24-hour dietary recalls at baseline (2008-2011) which were used to calculate a MeDi score (MeDiS, range 0-9). Brain MRI and diffusion tensor images were collected between 2018 and 2022 on a 3T MRI scanner using a standardized protocol. WM integrity was ascertained using WM hyperintensity (WMH) volume and fractional anisotropy (FA). WMH volumes were residualized for total cranial volume and Ln-transformed prior to analysis. The association of MRI outcomes with MeDiS and its components was investigated using weighted linear regression analysis with complex survey design adjusting for age, sex, sociodemographic characteristics. Cardiovascular health was assessed using the Life’s Simple 7 (LS7, range 0-14) score. The mediating effect of LS7 on the primary outcome was reported as Average Causal Mediation Effects (ACME) and Average Direct Effects (ADE). Statistical significance was set at p<0.05. Results: Mean age (95% CI) at MRI scan was 64.0 (63.4 to 65.2) and 44% were males. Mean MeDiS was 5.01 (4.89 to 5.12) and LS7 was 7.1 (7.0 to 7.3). In our fully adjusted model, increasing MeDi adherence was associated with decreased LnWMH volume (β=-0.07, 95% CI -0.10 to -0.03) and increased FA (β=0.002, 95% CI 0.001 to 0.003). Increasing LS7 scores partially mediated the relationship between MeDiS and WMHs (ACME=-0.01, ADE=-0.08, p<0.05, percent mediation=9%) and between MeDiS and FA (ACME=0.0001, ADE=0.002, p<0.01, percent mediated=8%). Among the different MeDi components, consumption of whole grains and fish above sex-specific energy adjusted energy median intake predicted lower WMH volume and increase FA (p<0.05 for both). Conclusions: Among diverse Hispanic/Latino adults, high MeDi adherence was associated with preserved WM integrity. This association was partially mediated by CVH. This suggests that the beneficial effect of MeDi on brain health is not fully explained by vascular risk factors. A culturally tailored MeDi may preserve brain health among Hispanic/Latino adults.
Interim safety and efficacy data of [ 212 Pb]VMT-α-NET in somatostatin receptor 2 (SSTR2) expressing neuroendocrine tumors (NETs).
Anthony, Lowell , Sólnes, Lilja B. , Mehr, Samuel H., Baratto, Lucia , Hanna, Alaa , Yang, Wenjing M., Wahl, Richard L. , Yang, Wenjing M., O’Keefe, Stephen J. , Hálfdánarson, Þorvarður R.

Journal of Clinical Oncology | January 27, 2025 | Volume: 43 | Issue: 4_suppl | Pages: 668-668

10.1200/jco.2025.43.4_suppl.668 Get It

668 Background: After the approval of 177Lu DOTATATE, a new generation of radiopharmaceutical therapies (RPT) utilizing alpha-emitting radiometals is being developed as front-line therapies for advanced NETs with the hope of higher clinical efficacy. In this Phase I study, [ 212 Pb]VMT-α-NET, a novel targeted alpha radionuclide therapy (TAT) to SSTR2, is being evaluated in SSTR2-expressing NETs tumors in patients with no prior PRRT treatment. Here we present interim safety and the first efficacy results from dose escalation cohorts 1 and 2. Methods: In this first-in-human dose-escalation study, safety, PK, and efficacy of [ 212 Pb]VMT-α-NET were investigated in a population of well-differentiated adult NETs of any grade which progressed after prior standard of care therapy as assessed by RECIST v1.1 (NCT05636618). No patient may have received prior 177 Lu-DOTATATE or PRRT. The dose escalation design includes four cohorts, 3 mCi, 5 mCi, 7.5 mCi and 10 mCi based on a Bayesian modified toxicity probability interval (mTPI-2) design. Subjects in cohorts 1 and 2 underwent dosimetry evaluations using the therapeutic surrogate [ 203 Pb]VMT-a-NET. Therapeutic [ 212 Pb]VMT-a-NET was administered for 4 cycles Q8W in combination with reno-protective amino acids. The DLT assessment period is defined as the first 6 weeks of cycle 1. The primary objectives include the evaluation of safety and tolerability, the PK and RP2D of [ 212 Pb]VMT-a-NET as well as ORR as assessed by RECIST 1.1 criteria. Results: The current data cut occurred on September 19 th , 2024. A total of 9 patients were enrolled (2 in cohort 1 and 7 in cohort 2). Median exposure for cohort 1 was 2.5 mCi (2.5 mCi, 2.5 mCi) and for cohort 2 was 5.1 mCi (4.7 mCi, 5.2 mCi). No DLTs were observed. Two grade 3 AEs occurred in Cohort 2 (diarrhea, syncope). The most frequent related TEAE were alopecia, fatigue, anemia, lymphopenia and nausea (all grade 1 or 2). One subject in Cohort 2 was discontinued due to progressive disease. Landmark PFS at 9 months is 89%. ORR is not yet mature and will be shown at the time of the meeting. Safety Monitoring Committee (SMC) meeting was held on July 17 th , 2024, recommended dose escalation to cohort 3 at 7.5 mCi. No nephrotoxicity was reported in either cohort. Conclusions: [ 212 Pb]VMT-α-NET is safe up to 185 MBq (5 mCi) dose level, and the SMC supported dose escalate to cohort 3 at 277.5 MBq (7.5 mCi) following a mandated FDA review in fall. Cohort 2 remains open for dose level expansion. Early efficacy results demonstrate encouraging progression-free survival. Clinical trial information: NCT05636618 .