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SRS304 - Beyond the incision: minimally invasive left pancreatectomy offers early gains without oncological compromise—a population-based analysis
Malik, Abdullah , Chang, Yu-Hui, Tingle, Samuel, White, Steven, Qadan, Motaz, Pandanaboyana, Sanjay, Chang, Yu-Hui, Qadan, Motaz , Fong, Zhi Ven

British Journal of Surgery | March 27, 2026 | Volume: 113 | Issue: Supplement_2 | Pages: No page available

10.1093/bjs/znag018.276 Get It

Abstract Background Minimally invasive left-sided pancreatectomy (MIS-LP) is increasingly adopted for pancreatic neuroendocrine tumours (PNETs), yet its oncological safety compared with open surgery (O-LP) remains debated. Robust population-level evidence is required to guide practice. Methods Patients ≥65 years with grade 1–2 PNETs undergoing left pancreatectomy were identified from the SEER-Medicare database (2010–2019). Overall and cancer-specific survival outcomes were analysed using multilevel Cox regression after propensity-score matching (PSM). Landmark analysis from 6 months excluded early postoperative deaths. Results 772 patients were included: 257 (33%) MIS-LP and 515 (67%) O-LP. Median age was 71 years; 87% had grade 1 and 13% grade 2 tumours. Before matching, MIS-LP patients had lower comorbidity (median Charlson Index 2 versus 3, P = 0.011) and fewer with metastatic disease (2.0% versus 5.7%, P = 0.019). After PSM (MIS-LP n = 248; O-LP n = 441), 5-year overall survival was higher with MIS-LP (88.1% versus 84.5%, P = 0.03), while 5-year cancer-specific survival was similar (95.2% versus 93.5%, P = 0.11). O-LP was associated with increased risk of death (HR 1.75, 95% c.i. 1.05–2.91, P = 0.030), though not cancer-specific death (HR 1.97, 95% c.i. 0.86–4.54, P = 0.110). Notably, all 90-day mortalities (n = 15, 1.9%) occurred in the O-LP group. In landmark analysis beyond 6 months, surgical approach was no longer predictive of OS or CSS. Conclusions MIS-LP confers an early survival advantage, driven by reduced perioperative mortality, without compromising long-term oncological outcomes. As the largest population-based analysis in this setting, these findings support MIS-LP as the standard surgical approach for older patients with low- to intermediate-grade PNETs.
Contemporary Adjuvant Chemotherapy for Intraductal Papillary Mucinous Neoplasms
Haugk, Beate , White, Steven, Marchegiani, Giovanni, Holmberg, Marcus, Zerbi, Alessandro, Lu, Zipeng , Inoue, Y., Choi, Munseok , Kang, Chang Moo, Visser, B., Corpelijn, Lieke, Andersson, Bodil, Bereza-Carlson, Paulina, Björnsson, Bergthor, Wennerblom, Johanna, Goh, Brian K. P., Hartman, V., Ahmad, Syed, Patel, Sameer, Berrevoet, Frederik, Mortensen, Kim Erlend, Roberts, K., Lynch, Calum, Gupta, Amit, Kleeff, Joerg, Addeo, Pietro, Friess, Helmut, Koea, Jonathan, Gomez, Dhanny , Gordon-Weeks, Alex, Doria, Cataldo, Tzimas, Georgios, Franklin, O., Månsson, C., Cabús, Santiago Sánchez, Bhogal, Ricky H. , Pathak, Samir, Honselmann, Kim Christin, Balakrishnan, Anita, Mann, Kulbir , Gill, Anthony J., Mittal, A, Samra, Jas, Athwal, Tejinderjit, Loveday, Benjamin, Bhardwaj, Neil, Menon, Krishna, Thapa, Prabin, Matsumoto, Ippei, Jamieson, Nigel, Rebours, Vinciane, Descourvières, Clémence, Davidson, BR, Soreide, Kjetil, Pandanaboyana, Sanjay, Collaborative, Adeno-IPMN2, Kumar, Ajit, González, Carol Natalia Clavijo, Lam, Shi, L’Official-German, Ivan, Bergner, Tina, Rosso, Edoardo , Giulianotti, Pier Cristoforo , Morreau, Mathew , Dili, Alexandra, Sotiropoulou, Maria , Kuzman, Matta , Büyükkasap, Ahmet Çağrı, Uludağ, Gökhan, McGuigan, Mari-Claire , Chouari, Tarak , Dogul, Ahmet, Doğu, Doğukan , Rebelo, Artur, Holewik, Franziska Bernadette, Plesa-Furda, Roxana, Revoredo, Fernando, Galanis, Ilias , Maharjan, Dhiresh, Ghorbani, Poya , Lind, Max, Ami, Katsuya , Vijayashanker, Aarathi , Alsaoudi, Tareq , Lundgren, Linda , Ellisa, Katrina, Hong, Paul , Gupta, Archit, MartinXu, Congde, Konstantoudakis, Georgios, Christophides, Thalis, Spurring, Eleanor Margaret, Iwao, Yasuhito, Pirklc, Martin, Vaitha, Ruhi , Tiwari, Navneet, Sheel, Andrea, Kotecha, Krishna , Stavrou, Gregor A., Patel, Rikhilroy, Misca, Mihaela , Hammond, John, Roalso, Marcus Thomas Thor, Soomro, Faiza H, Halimi, Asif , Kendall, Timothy, Patel, Visad, Stankic, Dunja, Dries, Pieter , Hein, Charlotte, Betram, Julia, Jacob, Rosetta, Wilson, Gregory, Redas, Souheil, Poškus, Augustas, Mosert, Paula Lucia, Šilinskaitė, Ugnė , Hirose, Yuki, Liu, Xue, Standaert, Lars, Kay, Tegan J, Nishida, Kenji, Peddakota, Vivek , Gupta, Amit , Kang, Chang Moo , Ven Fong, Zhi, Kang, Chang Moo , Lucocq, James E. , Marchegiani, Giovanni , Zerbi, Alessandro , Pagnanelli, Michele , Visser, B. , Andersson, Bodil , Bereza‐Carlson, Paulina , Björnsson, Bergþór , Wennerblom, Johanna Hansson , Labori, Knut Jørgen , Goh, Brian K P , Hartman, Vera , Berrevoet, Frederik Christiaan , Ausania, Fabio , Bertrand, Claude , Kleeff, Joerg, Addeo, Pietro , Bellotti, Ruben , Fong, Zhi Ven , Friess, Helmut , Koea, Jonathan , Gordon-Weeks, Alex Nicolas , Doria, Cataldo , Franklin, Oskar , Pathak, Samir , Honselmann, Kim C. , Balakrishnan, Anita , Harrison, Ewen M. , Gill, A J, Mittal, Anubhav, Samra, Jas , Athwal, Tejinderjit , Loveday, Benjamin P. T. , Teh, Catherine , Bhardwaj, Neil , Menon, Krishna, Matsumoto, Ippei , Jamieson, Nigel , Rebours, Vinciane , Søreide, Kjetil , Martlı, Hüseyin Fahri , Roeyen, Geert , Antonakis, Pantelis T. , Bramis, Konstantinos , Hall, Lewis A , Valle, Valentina , Connor, Saxon J. , Kapiris, Stylianos A. , Kerem, Mustafa , Rebelo, Artur , Plesa-Furda, R., Filho, Omero Pereira da Costa , Galanis, Ilias, Konstantoudakis, Georgios, Christophides, Thalis, McGuinness, Matthew James , Yaqub, Sheraz , Pellegrini, Riccardo , Perri, Giampaolo , Sheel, Andrea , Sheen, Amy , Evans, Daisy, Ghamarnejad, Omid , Karavias, Dimitrios D. , Roalsø, Marcus T. T. , Stankic, Dunja , Grubor, Nikica , Gulla, Aistė , Furukawa, Takaaki , Hirose, Yuki , Yin, Lingdi

JAMA Network Open | March 27, 2026 | Volume: 9 | Issue: 3 | Pages: e263688

10.1001/jamanetworkopen.2026.3688 | PMID 41893840 Get It

Importance Adjuvant chemotherapy regimens may be administered after pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMNs), although the evidence supporting their use is limited. Objective To evaluate the survival benefit associated with contemporary adjuvant chemotherapy regimens after resection in A-IPMNs between 2017 and 2023. Design, Setting, and Participants This retrospective cohort study was an international, multicenter study with 69 participating centers across Europe, North America, South America, and the Asia-Pacific region. Patients undergoing resection for A-IPMNs were included. Data were analyzed from May to August 2025. Intervention Contemporary adjuvant chemotherapy regimens, such as gemcitabine-capecitabine (GemCap); 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX), modified FOLFIRINOX (mFOLFIRINOX), and S-1. Main Outcome and Measure Overall survival (months). Results Among 1321 patients (median [IQR] age 70 [63 to 76] years; 713 males [54.0%] and 608 females [46.0%]), 781 patients (59.1%) received adjuvant chemotherapy, while in 181 patients (13.7%) it was omitted due to poor patient fitness. Of patients who received adjuvant chemotherapy, 568 patients (72.6%) received contemporary regimens, including GemCap (232 patients [29.7%]), FOLFIRINOX (176 patients [22.5%]), mFOLFIRINOX (71 patients [9.1%]), and S-1 (70 patients [9.0%]). The median (IQR) follow-up for the cohort was 64.2 (40.4 to 85.0) months, and the median overall survival was 73.8 months (95% CI, 66.4 to 81.9 months). After 90-day landmark analysis and exclusion of patients ineligible for chemotherapy, adjuvant chemotherapy vs no adjuvant chemotherapy (propensity score–matched populations, 243:243 patients) was not associated with improved overall survival (median, 82.3 months; 95% CI, 78.2 months to not applicable [NA] vs not reached; 95% CI, 75.3 months to NA; P = .58). Contemporary regimens vs no adjuvant chemotherapy (propensity score–matched populations, 309:309 patients) was not associated with longer survival, and a mean survival benefit greater than 4.2 months over 5 years was excluded (difference in restricted mean survival, 1.26 months; 95%, −1.72 to 4.24 months). Treatment outcomes did not vary by chemotherapy regimen or disease characteristic (eg, N stage or carbohydrate antigen 19-9 level). Conclusions and Relevance In this study, contemporary adjuvant chemotherapy was not associated with improved overall survival in A-IPMNs, and a randomized clinical trial is indicated.
PCO26-270: Transcriptomic Profiling Reveals Inflammatory and Epithelial-Mesenchymal Transition Pathway Activation in Endoxifen-Resistant Estrogen Receptor–Positive Breast Cancer
Remmel, H. Lawrence , Hawse, John R., Veviorsky, Alexander P., Zhavoronkov, Alex, Quay, S. C., Hammer, Sandra S. , Shneyderman, Anastasia , Veviorskiy, Alexander , Zhavoronkov, Alex , Quay, Steven C.

Journal of the National Comprehensive Cancer Network | March 27, 2026 | Volume: 24 | Issue: 3.5 | Pages: No page available

10.6004/jnccn.2025.7152 | PMID 42055424 Get It

HSR26-206: The Future of Oncology Research: Replacing Case Report Forms With mCODE-Aligned Electronic Health Record Data for Clinical Trial Data Curation (Alliance)
Tevaarwerk, A. J., Campbell, Nancy, Emamekhoo, Hamid, Chow, Selina , Elrahi, Cassandra , Commers, Winnie, Birgin, Alisha, Galanis, E., Piantadosi, Steven , Tevaarwerk, Amye J., Emamekhoo, Hamid

Journal of the National Comprehensive Cancer Network | March 27, 2026 | Volume: 24 | Issue: 3.5 | Pages: No page available

10.6004/jnccn.2025.7420 | PMID 42055437 Get It

Establishment of a canine urothelial carcinoma‐derived organoid biobank: A platform for comparative and translational research
Zdyrski, Christopher , Pawlak, Aleksandra , Nicholson, Hannah, Corbett, Megan P. , Catucci, M., Cheville, John, Cho, H, Melvin, Bryan J. , Peng, Jiayi, Saba, Corey , Hamsher, Hayden, Friedenberg, Steven G. , Mochel, Jonathan P. , Nicholson, Hannah F , Woodward, Andrew P , Douglass, Eugene , Mochel, Jonathan P , Allenspach, Karin , Zdyrski, Christopher , Pawlak, Aleksandra , Cheville, John C.

Clinical and Translational Medicine | March 27, 2026 | Volume: 16 | Issue: 4 | Pages: No page available

10.1002/ctm2.70645 | PMID 41889014 Get It

Empowering Neurosurgical Leadership: Training the Next Generation of Neurosurgical Leaders
Razak, Shahaan S. , Veeravagu, Anand , Stiehl, Emily, Sharan, Ashwini , Levy, Elad, Khalessi, A, Kalkanis, Steven N. , Asmussen, Brian, Langer, David, Chambless, Lola B. , Hilgart, Michele, Ratliff, John K. , Scarrow, Alan M., Scarrow, Alan, Ratliff, John , Stiehl, Emily , Khalessi, Alexander A., Langer, David J., Haydu, Lauren E. , Air, Ellen L. , Nahed, Brian V.

Neurosurgery | March 26, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.1227/neu.0000000000003996 | PMID 41885450 Get It

BACKGROUND AND OBJECTIVES: The Congress of Neurological Surgeons (CNS) Leadership Institute developed the first structured leadership program designed specifically for neurosurgeons. Led by the experts in neurosurgery, health care administration, and business, the program provides formal leadership training and mentorship aimed at advancing neurosurgeons' professional development at local, regional, national, and international levels. METHODS: The CNS Leadership Institute offers 2 curricula tailored for junior and senior faculty. Training begins with assigned readings, webinars, and online lectures that establish essential leadership principles. Core learning occurs during 2 in-person courses featuring interactive lectures, feedback sessions, and a longitudinal leadership project guided by national mentors. Program outcomes were assessed through a 40-question survey of alumni evaluating training effectiveness, skill application, and career advancement. RESULTS: Since 2016, 195 neurosurgeons have completed the CNS Leadership Institute. Among the 77 survey respondents, 70.1% reported significant professional advancement (new leadership role or job transition), and 64.8% directly attributed their advancement in skills and insights acquired through the program. Overall program effectiveness was rated 4.4 of 5, and the mean likelihood-to-recommend was 8.95 (95% CI: 8.70-9.20), yielding a Net Promoter Score of +63 (95% CI: +49 to +77). Alumni have assumed prominent roles including 16 Residency Program Directors, 3 Department Chairs, 1 Vice Dean, 4 Service Line Leaders, 13 CNS Executive Committee members, and over 100 committee or editorial board appointments critical to the specialty. CONCLUSION: The CNS Leadership Institute equips neurosurgeons with structured leadership training, mentorship, and practical tools to enhance their effectiveness as leaders. Survey results confirm that the program has a measurable impact on participants' career trajectories and professional growth. This initiative provides a reproducible model for cultivating the next generation of neurosurgical leaders and advancing the specialty's capacity for strategic, transformational leadership.
Association of GLP-1 receptor agonists versus bariatric surgery with outcomes in obese patients with hypertrophic cardiomyopathy: a multicenter propensity-matched analysis
Mahmoud, Ahmed K, Awad, Kamal, Sheashaa, Hesham, Kandil, Omneya , Farina, Juan M, Ibrahim, Ramzi, Abdelnabi, Mahmoud, Allam, Mohamed , Mital, Rohit , Shipman, Justin , Lester, Steven J, Ommen, Steve R, Geske, Jeffrey B, Patten, Richard D. , Ayoub, Chadi, Arsanjani, Reza, Mahmoud, Ahmed , Mahmoud, Ahmed K , Awad, Kamal , Alsidawi, Said , Ayoub, Chadi , Allam, Mohamed N , Awad, Kamal , Farina, Juan M. , Ibrahim, Ramzi , Abdelnabi, Mahmoud , Alsidawi, Said , Lester, Steven J., Ommen, Steve R. , Geske, Jeffrey B. , Arsanjani, Reza

European Heart Journal - Quality of Care and Clinical Outcomes | March 26, 2026 | Volume: 12 | Issue: 5 | Pages: 731-739

10.1093/ehjqcco/qcag051 | PMID 41910632 Get It

Abstract Aims Obesity is linked with worse outcomes in hypertrophic cardiomyopathy (HCM). While both bariatric surgery (BS) and GLP-1 receptor agonists (GLP-1RA) promote weight loss and may improve cardiometabolic risk, their comparative outcomes in HCM remain unclear. Methods and results Adults with HCM and body mass index (BMI) ≥ 30 kg/m were divided into two cohorts: (i) GLP-1 RA users who never had BS, and (ii) BS patients who never received GLP-1 RA. Propensity score matching (1:1) was performed to balance demographics, comorbidities, and medications. Outcomes over 24 months include all-cause mortality, acute heart failure (HF) hospitalization, arrhythmias, change in BMI, and cardiovascular symptoms. Hazard ratios with 95% confidence intervals were estimated using Cox models. Of 5002 patients, 955 were included in each matched cohort after matching (mean age 54 ± 13 years, 70% female, BMI 40.0 kg/m). GLP-1 RA was associated with a significantly lower observed rate of all-cause mortality compared with BS (2.0% vs. 4.4%; HR 0.46; 95% CI 0.27–0.80; P = 0.004) and HF hospitalization (8.7% vs. 14.0%; HR 0.60; 95% CI 0.46–0.79; P < 0.001). Similarly, GLP-1 RA use was associated with a lower incidence of composite cardiovascular outcomes (10.7% vs. 17.2%; HR 0.60; 95% CI 0.47–0.77; P < 0.001). Rates of arrhythmia and cardiovascular symptoms were comparable between the two groups. BMI reduction was greater after bariatric surgery (−4.0 vs. −2.6 kg/m; P < 0.001). Conclusion In obese patients with HCM, GLP-1 RA therapy was associated with lower all-cause mortality and fewer HF events compared with BS. Future studies are warranted to confirm our findings.
Analytical Performance Evaluation of the Cardiac Troponin T High Sensitivity Gen 6 Assay
Knoll, Marko, Daniels, Lori B. , Mueller, Christian, Mills, Nicholas L, Giannitsis, Evangelos, Rösser, Alisa F A, Kurtoic, Dunja, Wahl, Annika , BODY, R. A. F., Christenson, R H, Cobbaert, Christa, deFilippi, Christopher R, Inoue, Kenji, Jaffe, A. S., McCarthy, C. F., McCord, James, Neumann, Johannes T, Omland, Torbjørn, Papendick, Cynthia , Sandoval, Yader, Than, Martin P, Twerenbold, Raphael, Peacock, W Frank, Meex, Steven J. R., Giannitsis, Evangelos , Body, Richard , Neumann, Franz–Josef , Müller, Christian , Mills, Nicholas L. , Mueller, Christian , Mills, Nicholas L , Giannitsis, Evangelos , Body, Rick , Eggers, Kai M. , Jaffe, Allan S. , Neumann, Johannes T , Sandoval, Yader , Tan, Jack Wei Chieh , Than, Martin , Twerenbold, Raphael , Daniels, Lori B , Cobbaert, Christa M. , deFilippi, Christopher R. , McCarthy, Cian P, McCord, James , Omland, Torbjørn , Sandoval, Yader , Tan, Jack Wei Chieh , Than, Martin , Twerenbold, Raphael , Meex, Steven J.R.

The Journal of Applied Laboratory Medicine | March 26, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.1093/jalm/jfag031 | PMID 41885135 Get It

Abstract Background High-sensitivity cardiac troponin (hs-cTn) assays are recommended for the diagnosis of acute myocardial infarction. Here, we characterize the analytical performance of a next-generation hs-cTn assay, Elecsys® Troponin T hs Gen 6 (Roche Diagnostics International). Methods Surplus lithium-heparin plasma or serum samples from patients or healthy volunteers were run on Cobas® e 801, e 402, and Pro analyzers. Limits of blank (LoB), limits of detection (LoD), and limits of quantitation (LoQ) were determined according to CLSI EP17-A2, with target values of 1.0 and 1.5 ng/L for LoB/LoD and 3.0 ng/L (10% CV) and 1.5 ng/L (20% CV) for LoQ, respectively. Precision was measured, per CLSI EP17-A2, using 3 QC samples (approximately 4, 30, and 220 ng/L), 12 native samples, and 3 reagent lots. Linearity, per CLSI EP06-Ed2, was determined by diluting samples with cardiac troponin T (cTnT) concentration above the measuring range with a low/blank sample. Interference (per Glick) with endogenous and assay components at 5 cTnT concentrations was assessed. Results Measured values for LoB, LoD, and LoQ at 10% and 20% CV were 0.1 to 0.7 ng/L, 0.3 to 1.4 ng/L, 1.0 to 2.9 ng/L, and 0.4 to 1.2 ng/L, respectively. Repeatability CVs were 1.0 to 5.8% for mean cTnT concentrations of 2.6 to 9230 ng/L in lithium-heparin plasma. High precision was shown across lots, and linearity was observed across the measuring range (1.5 to 9500 ng/L, all Pearson's r = 1.00). No interferences were observed, specified up to ≤1000 mg/dL hemoglobin, ≤50 mg/dL [≤855 µmol/L] icterus/bilirubin, and ≤1200 ng/mL biotin. Conclusions The analytical performance characterization of the assay demonstrated high sensitivity, high precision at the low end and across the measuring range, and resistance to interference.
Evolution and Transformation of Hypertrophic Cardiomyopathy From a High Risk to a Treatable Low Mortality Disease With Contemporary Clinical Research Strategies
Maron, Barry J. , Ommen, Steven R., Ra, Nishimura, McKenna, William J. , Rakowski, H., Olivotto, I, Braunwald, Eugene, Maron, Martin S., Nishimura, Rick A. , McKenna, William J. , Olivotto, Iacopo , Ommen, Steve R , Nishimura, Rick A , Rakowski, Harry , Sherrid, Mark , Olivotto, Iacopo , Maron, Martin S , Maron, Barry J. , Ommen, Steve R. , Sherrid, Mark V. , Braunwald, Eugene , Maron, Martin S.

Journal of the American Heart Association | March 25, 2026 | Volume: 15 | Issue: 12 | Pages: No page available

10.1161/jaha.125.047462 | PMID 41878858 Get It

Once considered rare and essentially untreatable with a grim prognosis and reduced life expectancy, hypertrophic cardiomyopathy (HCM) has evolved substantially over 6 decades. Ultimately, HCM has become a contemporary global disease with pharmacologic and interventional options offering effective personalized treatment for all adverse disease pathways. Striking reduction in HCM‐related mortality to ≤0.5%/year in optimally treated cohorts is now comparable to that expected in the US general population, lower than most other disease risks to living, and 10‐fold less than the earliest estimates. The few deaths directly related to HCM are now largely attributable to advanced (end‐stage) heart failure in patients with nonobstructive HCM. Determinants of this transformation to a lower risk disease are evident in hallmark clinical inflection points and breakthroughs, including dedicated HCM programs assembling large clinical databases in which focused (and unfunded) physician‐investigators have derived data directly from patients in clinical practice. Evidence‐based observational studies report emergence of contemporary treatment strategies enhancing survival: implantable defibrillators prevent arrhythmic sudden death globally with 95% sensitive patient selection using an American Heart Association/American College Cardiology risk stratification algorithm; low‐risk, high‐benefit surgical myectomy reverses outflow obstruction and heart failure in >90% with a long‐term survival benefit; and aggressive anticoagulation has reduced embolic strokes. Recent novel pharmacologic alternatives (cardiac myosin inhibitors) are proving effective in relieving obstruction/symptom burden and changing disease management. These principles and time‐tested patient‐centered research strategies uniquely tailored to the heterogeneous HCM clinical spectrum are pivotal in providing practice insights, offering a vulnerable population more optimistic prognosis including opportunity to achieve normal longevity not available to prior generations of patients.
Expanding the molecular grading criteria in IDH-mutant astrocytoma
Virata, Michael , Samanamud, Jorge , Slocum, Connie, Kandoi, Shrishtee , Nguyen, Phuong , Savani, Milan R. , Shi, Diana D, Sharma, Sachein , Hiya, Satomi , Maldonado-Díaz, Carolina , Clare, Kevin, Vij, Meenakshi, Mir, Ema, Nishikawa, Y , Umphlett, Melissa , Yong, Raymund L. , Bederson, Joshua B. , Silva-Hurtado, Thenzing J. , Brem, Steven, Hambardzumyan, Dolores, Snuderl, Matija, Viapiano, Mariano S. , McBrayer, Samuel K. , Hatanpaa, Kimmo J. , Tsankova, Nadejda M. , Richardson, Timothy E. , Virata, Michael Christian , Samanamud, Jorge , Nguyen, Phuong , Yokoda, Raquel T , Vij, Meenakshi , Mir, Ema , Yong, Raymund L , Silva-Hurtado, Thenzing J , Brem, Steven , Hambardzumyan, Dolores , Snuderl, Matija , Viapiano, Mariano S , Abdullah, Kalil G , McBrayer, Samuel K , Tsankova, Nadejda M , Richardson, Timothy E , Shi, Diana D. , Yokoda, Raquel T. , Snuderl, Matija , Walker, Jamie M.

Neuro-Oncology | March 24, 2026 | Volume: 28 | Issue: 8 | Pages: 1921-1932

10.1093/neuonc/noag069 | PMID 41903203 Get It

Abstract Background IDH-mutant astrocytomas are classified as WHO grade 4 in the presence of conventional high-grade histologic features and/or homozygous CDKN2A/B deletion in the 5th edition of the WHO Classification of Central Nervous System Tumour guidelines. However, work over the past decade has indicated a number of other molecular alterations that warrant consideration as potential prognostic markers. Methods We used univariate Kaplan-Meier and multivariate Cox proportional hazards regression analysis to evaluate the prognostic effects of homozygous CDKN2A/B deletion, CDK4 amplification, CCND2 amplification, PDGFRA amplification/mutation, PIK3R1 mutation, PIK3CA mutation, MYCN amplification, EGFR amplification/mutation, TERT promoter mutation, and grade 4 histologic features in two independent cohorts of WHO grade 2-4 IDH-mutant astrocytoma (n = 840 and n = 367). Results The presence of CDK4 amplification, CCND2 amplification, PDGFRA alteration, PIK3R1 mutation, MYCN amplification, and EGFR alteration were each associated with reduced overall survival compared to WHO grade 2/3 astrocytomas without these molecular features. 17.7% (148/837) of otherwise grade 2/3 astrocytomas had one or more of these molecular criteria, with resulting intermediate clinical outcome in terms of overall survival (median survival of 67.3-82.0 months) compared to grade 2/3 astrocytomas without these molecular features (median survival of 135.0-140.7 months) and grade 4 astrocytomas (median survival of 35.3-45.0 months). Conclusions The presence of CDK4, CCND2, PDGFRA, PIK3R1, MYCN, and EGFR alterations result in an intermediate patient survival in IDH-mutant astrocytoma. Adding these molecular alterations should be considered in future diagnostic classification systems to improve stratification of high-risk patients.