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NCCN Guidelines® Insights: Distress Management, Version 1.2026
Fann, Jesse R., Vanderlan, Jessica, Brewer, Benjamin W. , Corbett, Cheyenne , Keller, Jennifer A. , Lahijani, Sheila , Niazi, Shehzad K. , Riba, Michelle B., Braun, IIana, Breitbart, William S., Channa, Yamna, Farabelli, Jill P., Fleishman, Stewart B., Garcia, Sofia F. , Greenberg, Donna B., Handzo, George , Horyna, Amy, Hutchinson, Sean Z., Johns, Shelley A. , Cava, Shannon La, Martin, Sara , Mukherjee, Debraj, Pailler, Megan E. , Parnes, Francine, Rocha-Cadman, Xiomara, Scher, Eli D. , Schuster, Jessica, Thompson, Lora M.A., Usher, A., Valentine, Alan , Darlow, Susan, Mukherjee, Debraj , Mukherjee, Debraj , Garcia, Sofia F , Fann, Jesse R. , Andersen, Barbara L. , Atreya, Chloe Evelyn , Breitbart, William S., Greenberg, Donna, Huang, Chao‐Hui , Leeper, Heather , Rao, Vinay P. , Rocha‐Cadman, Xiomara , Thompson, Lora M.A., Montgomery, Sarah E.

Journal of the National Comprehensive Cancer Network | April 9, 2026 | Volume: 24 | Issue: 4 | Pages: No page available

10.6004/jnccn.2026.0018 | PMID 41956112 Get It

These NCCN Guidelines for Distress Management discuss the identification and treatment of psychosocial problems in patients with cancer. They are intended to assist oncology teams to identify patients who require referral to psychosocial resources and to give oncology teams guidance on interventions for patients with significant distress. These guidelines also provide guidance for social workers, certified chaplains, and mental health professionals by describing treatments and interventions for various psychosocial problems as they relate to patients with cancer. These NCCN Guidelines Insights summarize the panel’s most recent recommendations regarding standards of care for distress management in patients with cancer and implementation of these standards, including application of evidence-based care delivery models, such as the collaborative care model.
Extent and Progression of Cardiac Damage in Patients With Primary Mitral Regurgitation Undergoing Surgical Repair
Myagmardorj, Rinchyenkhand , Fortuni, Federico , Mantegazza, Valentina , Wijngaarden, A.K.S. van, Wu, Hoi Wai , Palmen, Meindert , Pepi, Mauro, Fusini, Laura , Muratori, Manuela , Essayagh, Benjamin , Tribouilloy, Christophe​, Tourneau, Thierry Le, Bohbot, Y, Michelena, Hector I, Bax, Jeroen J, Marsan, Nina Ajmone, Fortuni, Federico , Wijngaarden, Aniek L. van , van Wijngaarden, Aniek , Pepi, Mauro , Tribouilloy, Christophe , Le Tourneau, Thierry , Bohbot, Yohann , Michelena, Hector I , Enriquez-Sarano, Maurice , Bax, Jeroen J , Marsan, Nina Ajmone , Essayagh, Benjamin , Tribouilloy, Christophe , Tourneau, Thierry Le , Bohbot, Yohann , Michelena, Héctor I. , Enriquez‐Sarano, Maurice , Bax, Jeroen J. , Marsan, Nina Ajmone

European Journal of Cardio-Thoracic Surgery | April 9, 2026 | Volume: 68 | Issue: 5 | Pages: No page available

10.1093/ejcts/ezag149 | PMID 41967857 Get It

Abstract Objectives The progression of extra-mitral valve (MV) cardiac damage in patients with primary mitral regurgitation (MR) following surgical repair has not been described. We aimed to investigate the evolution of extra-MV cardiac damage after MV repair and to assess its prognostic significance. Methods Patients with severe primary MR undergoing surgical repair at 5 referral centres were included when echocardiographic follow-up assessment was available. Based on echocardiographic parameters at baseline and at a median follow-up of 7 (interquartile range [IQR] 4-11) months after MV repair, patients were hierarchically classified as follows: stage 0: no cardiac damage; stage 1: left ventricular dilatation and/or dysfunction; stage 2: left atrial dilatation and/or atrial fibrillation; stage 3: pulmonary hypertension and/or significant tricuspid regurgitation. The primary outcome was all-cause mortality. Results A total of 764 patients (mean age 62 ± 13 years, 70% men) were included. Compared to baseline, 43% improved at least 1 stage, 49% remained unchanged, and 8% worsened at least 1 stage during follow-up after MV repair. At a median follow-up of 91 months after MV repair, 94 patients (12%) died. By multivariate Cox regression analysis, after adjusting for potential confounders, extra-MV cardiac damage staging at follow-up (HR per-1-stage-increase = 1.571; P = .009) and cardiac damage evolution (improved group, HR = 0.467; P = .034; worsened group, HR = 2.481, P = .037) were independently associated with all-cause mortality and had incremental prognostic value over preprocedural assessment. Conclusions Extra-MV cardiac damage improves significantly after MV repair, and its evolution is independently associated with all-cause mortality, suggesting the importance of comparative echocardiographic assessment following MV repair to improve risk stratification.
Primary Care Clinicians’ Attitudes on Digital Care Collaborative Management for Substance Use Disorders
Lai, Benjamin , Bormann, N. L., Arndt, Stephan, Smith, Jamie, Stoppel, Cynthia , Tuen, Kelsey, Cox, Danielle, Breitinger, Scott , Williams, Mark, Paul, Margaret, Lai, Benjamin , Bormann, Nicholas L. , Arndt, Stephan , Paul, Margaret M. , Oesterle, Tyler

INQUIRY: The Journal of Health Care Organization, Provision, and Financing | April 9, 2026 | Volume: 63 | Issue: No issue available | Pages: No page available

10.1177/00469580261440482 | PMID 41954165 Get It

Substance use disorders (SUD) remain a significant source of morbidity and mortality in the United States, and access to treatment continues to be inadequate. Primary Care Clinicians (PCCs) are well-positioned to provide long-term SUD care for patients. However, multiple provider-level barriers exist. Collaborative Care Management (CoCM) has proven successful in supporting PCCs in treating psychiatric conditions, such as depression. Our group proposes an addiction-focused modified CoCM that leverages telemedicine and an electronic platform (Senyo) into primary care. This study assesses PCCs’ attitudes toward this proposed model and their likelihood (with support) of prescribing medications for alcohol and opioid use disorder. To achieve this, an anonymized and confidential electronic survey was deployed to all 489 of our institutions’ PCCs. Eighty-five completed the survey (17.4% response); the majority (94%) agreed that digital CoCM for SUD will be helpful for their practice, and 85% expressed agreement that such a model will increase their confidence and likelihood to prescribe anti-craving medications. Additionally, we found that PCCs’ comfort level in addressing SUD with patients is not associated with years in practice, clinician type (attending physicians, resident/fellow physicians, nurse practitioner or physician assistant), or their perception of currently available SUD treatment resources. Future work to evaluate practice changes, including rates of anti-craving medication prescribing and SUD-treatment outcomes after implementation of our digital CoCM will prove useful in determining the effectiveness of this model.
Development and cross-site validation of machine-learning models for diagnosis and prognosis of stable angina with and without obstructive coronary artery disease: a study protocol
Deng, Jiawen, Patel, Shubh , Fung, Marinda, Heybati, Kiyan , Layard, Briana, Wang, Bo, Rubin, B., Hibbert, Benjamin, Anderson, Todd, Deng, Jiawen , Patel, Shubh K , Subasri, Vallijah , Deng, J , Simard, Trevor , Anderson, Todd J.

BMJ Open | April 8, 2026 | Volume: 16 | Issue: 4 | Pages: e108799

10.1136/bmjopen-2025-108799 | PMID 41951258 Get It

Introduction Angina with no obstructive coronary artery disease (ANOCA) affects millions and is frequently under-recognised because diagnostic pathways and risk tools predominantly target obstructive coronary artery disease (CAD). This protocol describes shared methods for two machine-learning (ML) studies: (1) differentiating ANOCA from stable angina with obstructive CAD and (2) predicting long-term mortality among patients with ANOCA and obstructive CAD. Methods and analysis We will develop and cross-site validate ML classification models using a multicentre retrospective cohort drawn from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease registry and institutional datasets from the University of Ottawa Heart Institute and the University Health Network. Eligible participants are adults (≥18 years) undergoing initial cardiac catheterisation for chest pain/anginal equivalents since 1995, excluding prior revascularisation, major structural heart disease and predefined non-anginal indications. Outcomes are (1) ANOCA (0% to <50% stenosis) versus obstructive CAD (≥50% stenosis) and (2) 1, 3 and 5-year mortality, modelled separately for ANOCA and obstructive CAD. Model development will use nested cross-validation with stratified k-fold inner-loop tuning and leave-one-site-out cross-validation for repeated external validation. Candidate predictors will be harmonised across sites, filtered for missingness and refined using expert/directed acyclic graph-guided selection plus Boruta and Least Absolute Shrinkage and Selection Operator. Preprocessing includes appropriate encoding, missing-data imputation (multivariate imputation by chained equations) and feature scaling. Algorithms will include elastic-net logistic regression, random forest, LightGBM and multilayer perceptron models; hyperparameters will be optimised via Bayesian optimisation. Performance and threshold tuning will be reported. Explainability and subgroup fairness will be assessed using SHapley Additive exPlanations. Final models will be deployed as a web-based clinical risk calculator. Ethics and dissemination Ethics approval has been obtained from the University of Calgary and the University Health Network (#24-5916). Analyses will use deidentified data in secure environments; only aggregate results will be reported. Findings will be disseminated via peer-reviewed publications, conferences and a web-based calculator.
Multi-Contrast MRI Inputs Enable Self-Consistent Tissue Segmentation & Robust Perivascular Space Identification
Gunter, Jeffrey L. , Preboske, Gregory M., Persons, Benjamin D., Przybelski, Scott A. , Petersen, Ronald, Jack, Clifford R, Gunter, Jeffrey L , Persons, Benjamin, Schwarz, Christopher G. , Low, Audrey , Vemuri, Prashanthi , Jack, Clifford R.

No container title available | April 7, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.64898/2026.04.03.716409 | PMID 41993560 Get It

Abstract Different MRI image contrasts are designed to highlight various tissue properties and combining them allows extension of probabilistic segmentation beyond the commonly used “gray-white-CSF” models. This work describes a fully automated method that combines T1-weighted, T2-FLAIR, and conventional T2-weighted images to provide internal consistency across prediction of tissue segmentations including segmentation of superficial and deep gray matter, white matter hyperintensities, and MR-visible perivascular spaces. Results from 773 imaging datasets from 403 participants in the Mayo Clinic Study of Aging and Mayo Clinic Alzheimer’s Disease Research Center (ADRC) are presented.
Comparison of neuropsychological side effects between contemporary radiofrequency ablative neurosurgery for psychiatric disorders and conventional neurosurgical procedures: systematic review and meta-analysis
Vilela-Filho, Osvaldo , Bannach, Matheus A., Lino-Filho, Adriano M. , Nuttin, Bart , Hariz, Marwan , Schulder, Michael , Greenberg, Benjamin David, Cosgrove, Rees, Oliveira-Souza, Ricardo de, Horn, Andreas, Sheth, Sameer A, Kubu, Cynthia S. , Salem, Sherif, Zaccariotti, Alice Jardim, Tavares, Naraiana O, Damasceno, Benito Pereira, Lozano, Andres M, Visser-Vandewalle, Veerle, Kühn, JP, Slavin, K. V., Lopes, A. Dwight, Vattimo, Edoardo FQ, Coyne, Terry, Akram, Harith, Toda, Hiroki , Halpern, Casey H. , Coenen, Volker A., Gorgulho, Alessandra, Andrade, Pablo, Wu, Hemmings , Sun, Bomin, Belmonte-De-Abreu, Paulo, Cosyns, Paul, McLaughlin, Nicole , Giordano, Prof. J., Berk, Michael, Chabardes, Stephan, Abbadi, Najia E, Salles, Antonio Afonso Ferreira De, Enslin, Nico, Sousa, Marcelo Basso de, Oliveira, José Oswaldo, Labruna, Rodrigo, Reis, Antonio Marcos dos , Jiménez-Ponce, Fiacro , Ferragut, Maria Alice, Régis, Jean, Lipsman, Nir , Rezai, Ali R. , Schuurman, Rick, Martínez-Álvarez, Roberto, Broggi, Giovanni, Huys, Daniel, Bervoets, Chris , Oliveira, P. A., Ragazzo, Paulo C., Lazaro-Munoz, Gabriel, Polosan, Mircea , Naesström, Matilda, Ribeiro, Telma MC, Lee, Kendall H, Hodaie, Mojgan , Sitnikov, Andrey, Yilmaz, Atilla, Almahariq, F., Rios, Adriana L Lopez, Gonçalves-Ferreira, António, Lozano, Andrés M. , Huys, Daniel , Enslin, Nico , Nuttin, Bart , Hariz, Marwan , Sheth, Sameer A , Damasceno, Benito Pereira , Kuhn, Jens , Slavin, Konstantin V. , Doshi, Paresh , Toda, Hiroki , Andrade, Pablo , Zrinzo, Ludvic , Chabardes, Stephan , Chang, Jin Woo , Polosan, Mircea , Hodaie, Mojgan , Almahariq, Fadi , Nico Enslin, Johannes M , Hamani, Clement , Greenberg, Benjamin D. , Oliveira‐Souza, Ricardo de , Sheth, Sameer A. , Zaccariotti, Alice Jardim , Tavares, Naraiana de Oliveira , Mayberg, Helen S. , Visser-Vandewalle, Veerle E. R. M. , Falkai, Peter , Lopes, Antonio C, Vattimo, Edoardo Filippo de Queiroz , Akram, Harith , Blomstedt, Patric C. , Quevedo, João , Belmonte-de-Abreu, Paulo Silva , Alkhani, Ahmed M. , Berk, Michael , Yatham, Lakshmi N. , Abbadi, Najia El , Salles, Antonio A. F. De, Chang, Jin Woo , Régis, Jean , Torres, Cristina V. , Taira, Takaomi , Barcia, Juan Antonio , Schuurman, Rick , Dougherty, Darin Dean , Giacobbe, Peter , Lázaro‐Muñoz, Gabriel , Naesström, Matilda , Johansson, Viktoria , Schlaepfer, Thomas Eduard , Neimat, Joseph S. , Sitnikov, A., Yilmaz, Atilla, Almahariq, Fadi, Ríos, Adriana Lucia López , Gonçalves-Ferreira, António JC.

Journal of Neurology, Neurosurgery & Psychiatry | April 7, 2026 | Volume: 97 | Issue: 6 | Pages: 532-541

10.1136/jnnp-2025-337800 | PMID 41946555 Get It

Background Psychiatric disorders are increasingly contributing to global disability. Despite advances in conservative management, the prevalence of treatment-resistant cases remains high. Meanwhile, neurosurgery for psychiatric disorders (NPD) remains underused, largely due to strict regulations and historical concerns, particularly those related to neuropsychological side effects (NPSE). Objective To address this issue, we conducted a systematic review with meta-analysis to compare NPSE associated with radiofrequency ablative NPD to those observed in neuro-oncological, neurovascular and epilepsy surgeries. Methods PubMed, Embase and LILACS databases were searched in April 2024 for articles published in English/Spanish from 1990 to 2022, following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Results A total of 48 articles with 2678 participants were included. The frequency of transient and permanent NPSE in the NPD group ranged from 0.94% to 11.50% and 0.94% to 2.03%, respectively, comparable to the other surgical groups (epilepsy: 0.31–11.70%; vascular: 0.52–22.90%; oncology: 0.94–17.60% for transient NPSE; epilepsy: 0.31–12%; vascular: 0.40–1.96% and oncology: 0.84–1.48% for permanent NPSE). Regarding permanent NPSE, arguably the most critical consideration, the NPD group showed better outcomes in memory, language and social cognition than the epilepsy group, but worse outcomes in executive and perceptual-motor functions. Compared with the vascular group, the NPD group had better executive function but worse complex attention. Finally, the NPD group had fewer permanent deficits than the oncology group in executive function, complex attention and perceptual-motor domains, although language performance was lower. Conclusions Contemporary NPD apparently carries a similar risk of NPSE as other conventional neurosurgical procedures, challenging misconceptions and this unjustified barrier to its broader use.
Retreatment with First-Generation Selective RET Inhibitors in RET -Rearranged NSCLC Pretreated with Selpercatinib or Pralsetinib: Results from the RET-MAP Registry
Marinello, A., Rotow, Julia K., Lomibao, Meghanne , Miliziano, Daniela , Leporati, Rita , Feng, Jamie , Metro, Giulio , Brandão, Mariana , Gorría, Teresa , Nassar, Amin H. , Fila, Matteo, Fallet, V., Ricciuti, Biagio, Taylor, Skyler, Remon, Jordi, Planchard, David, Florez, Narjust, Besse, Benjamin, Drilon, Alexander D., Aldea, Mihaela, Nassar, Amin H. , Rotow, Julia , Metro, Giulio , Marinello, Arianna , Marinello, Arianna , Rotow, Julia K. , Citarella, Fabrizio , Fila, Matteo , Fallet, Vincent , Ricciuti, Biagio , Taylor, Skyler , Remon, Jordi , Planchard, David , Duma, Narjust , Besse, Benjamin , Drilon, Alexander , Aldea, Mihaela , Feng, Jamie , Citarella, Fabrizio , Ricciuti, Biagio , Planchard, David , Florez, Narjust , Besse, Benjamin , Aldea, Mihaela

Clinical Cancer Research | April 7, 2026 | Volume: 32 | Issue: 13 | Pages: 2637-2643

10.1158/1078-0432.ccr-25-4814 | PMID 41945500 Get It

Abstract Purpose: In RET-rearranged non–small cell lung cancer (NSCLC), treatment options after first-generation selective RET inhibitors (SRI) are limited, and the value of SRI retreatment remains unclear. This study evaluates outcomes of SRI retreatment. Experimental Design: This multicenter retrospective study included patients with advanced RET-rearranged NSCLC who received ≥2 SRI-based therapy lines. Of 411 SRI-treated patients, 41 (10%) underwent SRI retreatment. Outcomes included objective response rate (ORR), progression-free survival (PFS), 6-month PFS, time to treatment failure, adverse events (AE). Results: Among 41 patients, 14 (34%) discontinued the initial SRI because of toxicity and 27 (66%) because of progression. After discontinuation for toxicity, all switched to an alternate SRI, achieving an ORR of 67%, median PFS of 9.9 months, and 6-month PFS of 80.3%. AEs reoccurred in nine patients (64%), with grade ≥3 AEs in 3 (21%) who switched at full dose. Among patients who discontinued because of progression, SRI monotherapy (n = 13) achieved an ORR of 23%, median PFS of 7 months, and 6-month PFS of 61.5%. Benefit was observed in patients with brain-only or oligoprogressive disease or dose reduction on first SRI. Combination therapy (n = 14; targeted agents, n = 11; chemotherapy, n = 3) achieved an ORR of 39%, median PFS of 4 months, and 6-month PFS of 27.3%. Conclusions: Same-class SRI switch after toxicity is feasible and clinically active but warrants cautious, dose-adjusted switching to mitigate toxicities. The efficacy of SRI rechallenge after progression seems limited overall. However, selected patients, such as those with brain-only or oligoprogressive disease, may derive benefit.
Risk Factors for Postoperative Cerebrospinal Fluid Leak Following Endoscopic Transsphenoidal Surgery for Craniopharyngioma: A Multicenter Cohort Study with a Contemporary Surgeon Practice Survey
Celda, María Peris, Karsy, Michael, Evans, James J, Kim, Albert H, Kim, W, Bergsneider, Marvin , Pacione, Donato , Gardner, Paul A. , Mukherjee, Raj, Liu, Connor J. , Cheok, Stephanie , Zwagerman, Nathan T. , Christenson, Charles, Blackburn, Spiros, Kshettry, Varun R, Wu, Kyle C, Prevedello, Daniel, Barkhoudarian, Garni, Fernandez-Miranda, Juan C., Zada, Gabriel, Benjamin, Carolina , Catalino, Michael Paul, Mamelak, Adam N, Furlan, André Beer, Zenonos, Georgios, Mendoza, Michelle Magana, Little, Andrew S, Gompel, Jamie J., Karsy, Michael , Palit, Sandhya R. , Shinya, Yuki , Karsy, Michael , Evans, James J., Chicoine, Michael , Kim, Albert H , Patel, Bhuvic , Kim, Won Bae , Gardner, Paul, Mukherjee, Debraj , Liu, C P, Blackburn, Spiros , Kshettry, Varun R. , Rennert, Robert C , Couldwell, William T. , Morshed, Ramin A. , Barkhoudarian, Garni , Fernandez‐Miranda, Juan C. , Zada, Gabriel , BENJAMIN, CAROLINA, Mamelak, Adam N. , Zenonos, Georgios A. , Little, Andrew S. , Gompel, Jamie J. Van

No container title available | April 7, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.21203/rs.3.rs-9285619/v1 | PMID 41994110 Get It

Abstract Purpose: This multicenter, multi-surgeon retrospective study aimed to identify risk factors for postoperative cerebrospinal fluid (CSF) leak following endonasal resection of craniopharyngioma, while evaluating the "perception gap" through a surgeon survey. Methods: A retrospective review was conducted on 416 patients who underwent endoscopic transsphenoidal surgery (ETS) for craniopharyngioma from 20 institutions. Factors were compared between patients with and without postoperative CSF leak, and between Early (2007-2015) and Late (2016-2025) Epochs. Complementing the clinical data, a survey of 19 neurosurgeons captured expert perspectives on risk stratification and management strategies. Results: Overall postoperative CSF leak rate was 13.5% (56/416 patients). Univariate analysis identified predominantly cystic tumors (34% vs. 21%, p = 0.034)and intraoperative lumbar drain (LD) use ( p < 0.028) as associated with postoperative CSF leak. BMI ( p = 0.587), prior surgery ( p = 0.576), and tumor size ( p = 0.363) were not significant. In the multivariable analysis, LD use was associated with a higher postoperative CSF leak rate (OR 1.91, 95% CI 1.06–3.46; p = 0.030). Between Epochs, nasoseptal flap (NSF) utilization increased from 70.7% to 87.6% ( p <0.001). NSF was protective (OR 0.28, 95% CI 0.07–0.92; p = 0.037) in the Early Epoch; no factors were significant in the Late Epoch. The surgeons’ survey identified prior surgery and intraoperative high flow leaks as primary risks; however, their LD protocols diverged from clinical data. Conclusion: Despite increased use of NSF, CSF leak persists. The study highlights a significant divergence between expert perception and clinical data regarding lumbar drains.
Predicted versus observed outcomes in the ALT-FLOW early feasibility study
Fioretti, Francesco , Gray, William A, Hibbert, B, Lindenfeld, JoAnn, Tedford, Ryan J, Zahr, Firas, Butler, Javed , Butler, Javed , Gray, William A. , Hibbert, Benjamin , Lindenfeld, JoAnn , Tedford, Ryan J. , Zahr, Firas

ESC Heart Failure | April 3, 2026 | Volume: 13 | Issue: 3 | Pages: No page available

10.1093/eschf/xvag101 | PMID 42257333 Get It

Abstract Background and Aims Whether hemodynamic and symptomatic benefits of the APTURE left atrial-to-coronary sinus shunt translate into clinical outcome benefit in heart failure with left ventricular ejection fraction &gt;40% remains unknown. Methods In this post hoc analysis of ALT-FLOW EFS patients undergoing APTURE implantation, Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score-predicted 1-year all-cause mortality was compared with observed mortality by Kaplan-Meier analysis of adjudicated events. Heart failure hospitalization (HFH) rates were compared for the 12 months before vs after implantation. Additional analyses included stratification by baseline sodium-glucose cotransporter 2 inhibitor (SGLT2i) use and N-terminal pro-B-type natriuretic peptide (NT-proBNP), recurrent HFH cumulative hazard estimation (Nelson-Aalen), and H2FPEF score calculation. Results Among 95 patients (mean age 70.9 ± 8.5 years; 50% women; 93% New York Heart Association Class III; 85.9% with H2FPEF score &gt;3), MAGGIC-predicted 1-year mortality was 13.0%. Observed 1-year survival was significantly higher than predicted (94.7% vs 87.0%; P=0.04), consistent across SGLT2i subgroups (log-rank P=0.59). The proportion of patients with HFH declined from 37.9% pre implantation to 9.6% post implantation (P&lt;0.0001), with event rates falling from 0.61 to 0.21 per patient-year (P&lt;0.001) and a 1-year cumulative hazard of recurrent HFH of 0.19 (95% confidence interval, 0.12-0.31). HFHs were evenly distributed across NT-proBNP strata. Conclusions In ALT-FLOW EFS, observed 1-year mortality was lower than MAGGIC-predicted mortality, and post implantation HFH rates were lower than pre implantation rates. These hypothesis-generating findings will require confirmation in the randomized, sham-controlled ALT-FLOW II trial.
Abstract 4661: Expression of the ferroptosis suppressor FSP1 but not GPX4 shows significant adverse prognostic effect in diffuse large B-cell lymphoma with wild-type TP53
Lyu, Beibei, Xu-Monette, Zijun Yidan, Zhao, Xiaoxian X., Chen, Ming, Visco, Carlo, Dybkaer, Karen, Wang, Chang , Au, Qingyan , Nunns, Harry , Pan, Zenggang, Montes-Moreno, Santiago, Bernal-Mizrachi, Leon, Zu, Youli , Zhang, Shanxiang , Chen, Weina , Li, Yong, Zu, Youli , Xu‐Monette, Zijun Y. , Hsi, Eric D. , Visco, Carlo , Tzankov, Alexandar , Dybkær, Karen , Wang, Mu‐En , Pan, Zenggang , Parsons, Benjamin M. , Montes‐Moreno, Santiago , Zhan, Fenghuang , Møller, Michael , Bernal‐Mizrachi, Leon , Bhagat, Govind , Young, Ken H.

Cancer Research | April 3, 2026 | Volume: 86 | Issue: 7_Supplement | Pages: 4661-4661

10.1158/1538-7445.am2026-4661 Get It

Abstract Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most common type of malignant lymphoma. Previous studies have shown that DLBCL cells are susceptible to GPX4 (Glutathione peroxidase 4)-regulated ferroptosis, an iron-dependent type of programmed cell death characterized by increased reactive oxygen species and excessive lipid peroxidation. In addition to GPX4, FSP1 (Ferroptosis suppressor protein 1, previously known as AIFM2) is a glutathione-independent repressor of ferroptosis that has shown prognostic significance in solid tumors. In this study, we aimed to reveal the significance of GPX4 and FSP1 in DLBCL. Patients and Methods: We performed immunohistochemistry (IHC) for GPX4 and FSP1 in a large cohorts of patients with de novo DLBCL, and evaluated their cytoplasmic and nuclear expression. Prognostic analysis was performed for FSP1 and GPX4 expression in patients treated with rituximab (R)-CHOP or CHOP chemotherapy, respective of TP53 mutation status, as p53 regulates ferroptosis and TP53 mutation is associated with poorer prognosis in DLBCL. Results: FSP1 expression with a ≥10% cutoff was positive in 42.3% of DLBCL cases. Patients with TP53 mutations had a non-significant trend of higher mean FSP1 expression than those with wild-type (Wt) TP53 (P=0.11). Prognostic analysis revealed that cytoplasmic FSP1+ expression was associated with significantly poorer overall survival and progression-free survival in Wt-TP53 DLBCLs treated with R-CHOP (P=0.016 and P=0.003, respectively), and only showed non-significant unfavorable trends in TP53 mutated DLBCLs and patients treated with CHOP. In contrast, GPX4 expression did not show a significant unfavorable prognostic effect in DLBCL, and in fact, was associated with a non-significant trend of better survival. Previously we have quantified immune cell abundance and PD-1/PD-L1 expression in the tumor microenvironment of the study cohort using multiplex fluorescent IHC. Correlative analysis found that FSP1+ patients had significantly higher mean and median abundance of CD68+ cells (both M1 and M2 macrophages) and CD11c+ cells than FSP1- patients. Further analysis in Wt-TP53 and mutated TP53 subcohorts found that only in the TP53 mutated DLBCL subcohort, FSP1 expression was associated with significantly higher mean and median CD163-CD68+ (M1) and overall CD68+ macrophages, whereas in the Wt-TP53 DLBCL subcohort, FSP1 expression was associated with significantly higher median (but not mean) CD163+CD68+ (M2) macrophages and CD11c+ cells. Summary: Cytoplasmic FSP1 expression but not GPX4 had significantly adverse prognostic effect in patients with Wt-TP53 DLBCL treated with standard immunochemotherapy. Our results also suggest that in addition to ferroptosis regulation, macrophage abundance was relevant for the prognostic effects of FSP1 expression. Citation Format: Beibei Lyu, Zijun Xu-Monette, Xiaoxian X. Zhao, Eric D. Hsi, Ming Chen, Carlo Visco, Alexandar Tzankov, Karen Dybkaer, Mu-En Wang, Chang Wang, Qingyan Au, Harry Nunns, Zenggang Pan, Benjamin Parsons, Santiago Montes-Moreno, Fenghuang Zhan, Michael B. Møller, Leon Bernal-Mizrachi, Youli Zu, Shanxiang Zhang, Weina Chen, Govind Bhagat, Yong Li, KEN H. YOUNG. Expression of the ferroptosis suppressor FSP1 but not GPX4 shows significant adverse prognostic effect in diffuse large B-cell lymphoma with wild-type TP53 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4661.