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Real-world early quality of life (QOL) changes on IO-based regimens in the prospective observational ODYSSEY metastatic renal cell carcinoma (mRCC) study.
Ged, Yasser , Maughan, Benjamin L., Bhavsar, Nrupen Anjan, Costello, Brian A. , Kilari, Deepak, Gupta, Sorab , Barbosa, Fernando Maciel, Monk, Paul, Vaishampayan, U., Jabusch, Sarah , Ward, Kimberly T., Wu, Yuan, Zhang, T., George, Daniel J., Vaishampayan, Ulka N. , Vaishampayan, Ulka , Harrison, Michael R. , Wulff, Elizabeth, Maughan, Benjamin L. , Bhavsar, Nrupen Anjan , Appleman, Leonard J. , Kilari, Deepak , Bratton, Melyssa R. , Monk, Paul , Rose, Tracy L. , Page, Courtney B , George, Daniel J.

Journal of Clinical Oncology | March 2, 2026 | Volume: 44 | Issue: 7_suppl | Pages: 476-476

10.1200/jco.2026.44.7_suppl.476 Get It

476 Background: Lack of standardized reporting and collection of patient-reported outcomes (PROs) limits cross-trial comparisons of first-line IO-based regimens for mRCC. Prospectively collected real world data may fill this important knowledge gap. Pts with stable/improved QoL at 3 mo versus baseline have longer median OS than pts with worse/unobserved HRQoL versus baseline (Cella, 2024). Methods: ODYSSEY is a multi-site, prospective observational study of 468 US pts with mRCC. Pts must have mRCC (any histology), no prior systemic therapy (ST), and follow up at a PCORnet study site. Exclusion criteria include treatment for cancer except mRCC. Descriptive statistics are used to show PRO score changes from baseline. We evaluate longitudinal change from baseline in PRO scores using least squares mean (LSM). Minimally important differences (MID) are 3 points for FKSI-19 total score, 1 point for the FKSI-Disease Related Symptoms (DRS) subscale and 7 points for FACT-G. Higher score indicates better QOL. The primary objective is to determine patterns of change in QOL and symptom burden of pts with mRCC. Results: As of 10/1/25, 360 pts were managed with ST, including 266 pts on IO-based combinations: 35 cabozantinib + nivolumab (C+N), 49 lenvatinib + pembrolizumab (L+P), 40 axitinib + pembrolizumab (A+P), and 142 ipilimumab + nivolumab (I+N). Overall median follow-up is 12.1 mos (IQR 6, 24). Age, sex and race were similar across regimens. Prior nephrectomy (50%) was lower than in trials. C+N and L+P pts had less clear cell (56 and 65%) versus A+P and I+N pts (94 and 82%). A+P pts had more favorable IMDC risk (19%) and less poor risk (14%). Baseline QOL was variable across regimens, with L+P generally the lowest. Absolute changes in PROs from enrollment to mo 3 (early change) by regimen are shown in the Table. LSM change from baseline in FKSI-19 and FKSI-DRS favored IO-IO versus IO-TKI at 3 mos but not at 6 mos (not shown). Conclusions: While early change in PROs did not meet the MID threshold between the IO-TKI and I+N cohorts, different patterns of early change are apparent among specific IO-TKI regimens. IO-TKI regimens exhibited higher variation in early PRO change vs I+N. As the data matures, we will associate baseline PROs and early PRO changes with early death and other outcomes. Clinical trial information: NCT04919122 . 3 month change. Instrument C+N (N=35) L+P (N=49) A+P (N=40) All IO-TKI(N=124) I+N(N=142) FKSI-19, N (%) 26 (74) 33 (67) 33 (83) 92 (74) 104 (73) Mean (SD) -0.3 (11) 2.8 (13) -3.2 (12) -0.2 (12) 0.7 (10) Median (IQR) 1.4 (-7, 6) 5.0 (-7, 11) -1.0 (-14, 5) 1.4 (-10, 8) -0.3 (-5, 6) FKSI-DRS, N (%) 26 (74) 33 (67) 33 (83) 92 (74) 104 (73) Mean (SD) -0.8 (5) 1.5 (7) -1.8 (6) -0.3 (6) 0.8 (5) Median (IQR) -0.5 (-5, 3) 2.0 (-5, 5) -1.0 (-5, 3) 0.0 (-5, 4) 0.0 (-2, 4) FACT-G, N (%) 27 (77) 32 (65) 29 (73) 88 (71) 102 (72) Mean (SD) 2.1 (14) 5.2 (16) -3.5 (15) 1.4 (15) 0.3 (13) Median (IQR) 4.0 (-4, 10) 1.2 (-6, 13) -6.4 (-11, 4) 1.6 (-8, 10) 1.6 (-7, 8)
Military-Civilian Partnership to Advance Standards of Performance for Simulated Combat Trauma Medical Skills: Validation of Competency Thresholds
Patel, B. M. , Nicholson, Susannah E. , Okerman, Tiffany S., Lopreiato, Joseph , Tisherman, S A, Frisch, Adam, Noël, P., Poropatich, Ronald , Phrampus, Paul E., Andreatta, Pamela , Athale, Janhave, Bacik, Adam , Jonas, Rachelle B., Brand, Shari, Bowyer, Mark, Butterfield, Duke, Callisen, Hannelisa, Connacher, Hugh, Chung, Yvonne, Colquist, Julie, Davisson, Blake, Gerhardus, Christian , Fitzgerald, Lavana, Phrampus, Paul, Hendrix, Cheralyn, Janicki, Adam, Knott, Camilla, Kunze, Katie, Lopreiato, Joseph, Low, Amy, McLeish, William, McQuillan, Karen , Milaski, Jessie, Mushaben, Mallory, Neustein, Benjamin, Nicholson, Susannah , Okerman, Tiffany, Patel, Bhavesh, Peterson, Paul, Proctor, Jasmine, Puche, Adam, Rorabeck, Janice, Sen, Ayan, Seamans, David, Shusko, Alexander, Sisson, Craig, Skolnick, Aaron, Sorto, Sharon, Tetzlaff, Elizabeth, Tillman, George, Tisherman, Sam, Patel, Bhavesh M , Noël, Pierre, Noel, Pierre, Andreatta, Pamela , Callisen, Hannelisa, Colquist, Julie , Knott, Camilla C., McLeish, William, Noel, Pierre, Rorabeck, Janice Annette, Shusko, Alexander , Thurman, Paul , Tisherman, Samuel A., Yu, Soojie

Military Medicine | February 28, 2026 | Volume: 191 | Issue: Supplement_1 | Pages: 435-443

10.1093/milmed/usag118 | PMID 42560252 Get It

Abstract Introduction Combat casualty care requires standardized proficiency criteria to ensure readiness in austere environments, yet gaps persist in defining performance thresholds for critical trauma skills. The Combat Medical Skills Sustainment Consortium (CMSSC), a novel military-civilian collaboration, aimed to validate competency thresholds for 21 Department of Defense-identified trauma skills. Materials and Methods A prospective cohort study (2022-2025) enrolled 1,495 military and civilian personnel across five academic centers, stratified by experience (novice, intermediate, expert). Skills, including cricothyroidotomy, whole blood transfusion, and ultrasound-guided vascular access, were assessed using validated checklists in Role 2-congruent simulations. Statistical analysis compared checklist performance against participant experience with a priori checklist scores estimated at 40% (novices) and 90% (experts). Results Competency thresholds were established, ranging from 77% (mechanical ventilation) to 100% (handoff). Experts achieved 85%-98% proficiency across most skills, with novices at 34%-97%. A ceiling effect was observed for less complex skills consistent with the power law of practice. Conclusion The Combat Medical Skills Sustainment Consortium validated standardized assessment tools, with potential to address readiness gaps through military-civilian synergy. Findings support consortium-guided curriculum development and highlight the need for longitudinal skill decay studies. Impact This study sets a benchmark for trauma care skills assessment, facilitating rapid adoption across military and civilian settings.
Sarcomatoid urothelial carcinoma with constitutive PD-L1 overexpression
Gupta, Sounak, Kosari, Farhad , Thapa, Prabin , Murphy, Stephen J, Johnson, Sarah H. , Dashti, Nooshin K. , Tekin, Burak, Dasari, Surendra, Kipp, Benjamin R. , Sharma, Vidit, Shah, Paras H, Orme, Jacob J. , Frank, Igor, Karnes, R Jeffrey, Boorjian, Stephen A, Vasmatzis, George , Cheville, John C, Zarka, Jabra G, Orme, Jacob J , Murphy, Stephen J. , Greipp, Patricia T. , Tekin, Burak , Zarka, Jabra , Sharma, Vidit , Shah, Paras H., Frank, Igor, Karnes, R. Jeffrey, Boorjian, Stephen A. , Cheville, John C.

Am J Clin Pathol | February 26, 2026 | Volume: 165 | Issue: 4 | Pages: No page available

10.1093/ajcp/aqag023 | PMID 41969028 Get It

Abstract Objectives Sarcomatoid urothelial carcinoma (sUC) is associated with poor clinical outcomes. Herein, we evaluated clinicopathologic features (including PD-L1 expression) for institutional cases. Methods Sixty-five patients with sUC treated by radical cystectomy were matched for age, sex, and pathologic stage to 190 patients with pure urothelial carcinoma (UC). Outcomes were evaluated using the Kaplan-Meier method. Immunohistochemistry (IHC) results for tumor-specific PD-L1 expression in sUC were quantified using H-scores (range, 0-300). Cases with constitutive PD-L1 expression (cPD-L1; H-score ≥240) were evaluated for amplification events using fluorescence in situ hybridization (n = 28), mate-pair sequencing (Mpseq; n = 6), RNA sequencing (n = 5), and targeted next-generation sequencing (n = 8). PD-L1 regulatory pathways were evaluated using gene set enrichment analysis in the Cancer Hallmark dataset. Results Most patients with sUC had advanced disease (≥pT2, 62/65, 95%), without significant differences in overall and cancer-specific survival, when matched to pure UC. Median PD-L1 H-scores using different clones were 100 (SP142), 120 (SP263), and 195 (22C3). cPD-L1 was seen in 43% (28/65) of cases of sUC that were enriched for TP53, TERT, and CDKN2A/B alterations. PD-L1 amplification was identified in 7 (of 28, 25%) of these cases. Bionformatics analysis consistently identified IL6-JAK-STAT3 and interferon α/γ signaling in sUC with cPD-L1 expression. Conclusions Our results suggest that cPD-L1 expression in most sUC occurs secondary to IL6-JAK-STAT3 and interferon α/γ signaling. This provides a biologic rationale for evaluating response to immunotherapy in this patient population.
Trial Design and Objectives for Patients With Prostate Cancer: Recommendations From the Prostate Cancer Working Group 4
Armstrong, Andrew J., Morris, M., Abida, Wassim , Aggarwal, Rahul R., Antonarakis, Emmanuel S., Attard, Gerhardt , Beltran, Himisha, Bryce, Alan H. , Carducci, Michael A. , Cheng, Heather H., Dahut, William L. , Emmett, Louise , Fizazi, Karim, Gafita, Andrei, George, Daniel J., Hermann, Ken, Hofman, Michael S., Hope, MD Thomas A., Hussain, Maha, Kelly, W. Kevin, Kuo, Phillip H. , Liu, Glenn X., Morgans, Alicia K., McKay, Rana R., Nanus, David, Nelson, P., Reichert, Zachery R. , Ryan, Charles J. , Sartor, A. Oliver, Schwartz, Lawrence H., Sharifi, Nima , Stadler, Walter M., Stein, M., Sternberg, Cora N., Szmulewitz, Russell Z., Tagawa, Scott T., Sokolova, Alexandra O., Wyatt, Alex, Yu, Evan Y., Halabi, S., Scher, Howard I., Group, for the PCWG4 Writing, Alumkal, Joshi J. , Aparicio, Ana, Barata, Pedro C., Drake, Charles G., Hamid, Anis , Heath, Elisabeth I. , Nauseef, Jones, Lage, Daniel E. , Mallak, Nadine , Patnaik, Akash, Prepelica, Kristofer, Rowe, Steven P., Slovin, Susan F. , Taplin, Mary‐Ellen , Zorko, Nicholas, Carducci, Michael A. , Halabi, Susan , Cheng, Heather H. , Antonarakis, Emmanuel S. , Morris, Michael J. , Armstrong, Andrew J. , Nauseef, Jones T. , Antonarakis, Emmanuel S. , Zorko, Nicholas A. , Armstrong, Andrew J , Morris, Michael J , Aggarwal, Rahul , Antonarakis, Emmanuel S , Beltran, Himisha , Bryce, Alan H , Cheng, Heather H , Chen, Delphine L , Chi, Kim N , Childs, Daniel S , Dahut, William , Emmett, Louise , Fizazi, Karim , Gafita, Andrei , George, Daniel J , Hermann, Ken , Hofman, Michael S , Hope, Thomas A , Hussain, Maha H A , Kelly, W Kevin , Kessler, Elizabeth , Lang, Joshua M , Liu, Glenn , Marshall, Catherine H , Morgans, Alicia K , McKay, Rana R , Nelson, Peter S , Paller, Channing J , Reichert, Zachery R , Sartor, A Oliver , Schöder, Heiko , Sharifi, Nima , Stadler, Walter M , Stein, Mark , Sternberg, Cora N , Szmulewitz, Russell Z , Tagawa, Scott T , Sokolova, Alexandra O , Wyatt, Alexander , Yamoah, Kosj , Yu, Evan Y , Halabi, Susan , Antonarakis, Emmanuel S , Zorko, Nicholas A , Nauseef, Jones T , N., Kim , Childs, Daniel S. , Fizazi, Karim , Gafita, Andrei , George, Daniel J. , Hofman, Michael S. , Lang, Joshua M. , Liu, Glenn , Marshall, Catherine H. , Morgans, Alicia K. , McKay, Rana R. , Paller, Channing J. , Sartor, Oliver , Schöder, Heiko , Schwartz, Lawrence H., Stadler, Walter M. , Tagawa, Scott T. , Scher, Howard I. , Aparicio, Ana, Barata, Pedro C. , Drake, Charles G. , Graff, Julie Nicole , Patnaik, Akash , Rathkopf, Dana E , Rettig, Matthew B.

Journal of Clinical Oncology | February 26, 2026 | Volume: 44 | Issue: 13 | Pages: 1249-1265

10.1200/jco-25-02834 | PMID 41744290 Get It

PURPOSE The continuous development of new imaging approaches, molecular phenotyping, genetic subtypes, prognosis assessments, and effective therapies across a range of disease states has created a need to redefine terminology and best practices for clinical trial conduct in patients with advanced prostate cancer. Methods We convened an international expert committee of diverse working groups, the Prostate Cancer Working Group 4 (PCWG4), between 2016 and 2025. Our objective was to formulate updated criteria based on emerging evidence and clinical trial data in a biomarker context to provide guidance for clinical trial design, eligibility, and end point assessments for patients with advanced prostate cancer. RESULTS PCWG4 redefines terminology around the disease state and previous therapies in a patient-centric context and terminology focused on androgen pathway modulation. We consider imaging, with a particular focus on positron emission tomography (PET)–defined disease. New recommendations are provided for disease state terminology, defining eligibility criteria, response and delay/prevent end points, intervals for reassessments including imaging, and patient-reported outcome determination. We provide recommendations in a biomarker-based context of use for the intended indication, reflective of patient benefit for specific interventions. We emphasize the need for development of validated PET imaging and molecular and phenotypic criteria as well as trial designs to appropriately risk stratify patients, predict and assess benefit, and measure post-treatment outcomes reliably in a trial framework. CONCLUSION PCWG4 updates recommendations on patient and tumor characterization, therapy development, and imaging criteria and extends guidance into earlier androgen pathway modulator–naïve/sensitive disease states to reflect an evolving, heterogeneous, and diverse patient population to optimize treatment benefits for all patients.
Recommendations for the Deprescribing of Psychotropic Medications
Goldberg, Joseph F. , McIntyre, R. S., Freeman, Marlene P. , Mago, Rajnish, Citrome, Leslie, Rosenblat, Joshua D., Thase, Michael E., Tohen, Mauricio, Vieta, Eduard, Malhi, Gin S, Sajatovic, M., Shelton, Richard C. , Macaluso, Matthew , Berk, Michael, Perlis, Roy H., Ostacher, Michael J., Khan, Arifulla, Sanacora, Gerard , Kane, John M., D, Goodman, Nierenberg, Andrew A., Correll, Christoph U., Kupka, R. W., Kasper, Siegfried, Furukawa, Toshi A., Davis, Lori L., Aaronson, Scott T., Gitlin, Michael , Jha, Manish K., Cohen, Lawrence J. , Papakostas, George I. , Mitchell, Philip B., Gorwood, P., Gupta, Swapnil , Frye, Mark A., Young, A. H., Zohar, Joseph, Steingard, Sandra , Zarate, Carlos A., Clayton, Anita H. , Shelton, Richard C. , Young, Allan H. , Ostacher, Michael J. , Jha, Manish K. , Young, Allan H , Jha, Manish K , Ostacher, Michael J , McIntyre, Roger S. , Swartz, Holly A. , Citrome, Leslie , Rosenblat, Joshua D. , Thase, Michael E. , Tohen, Mauricio , Vieta, Eduard , Malhi, Gin S. , Sajatovic, Martha, Berk, Michael , Perlis, Roy H , Iosifescu, Dan Vlad , Rubio, Jose M , Kane, John M. , Nierenberg, Andrew A. , Correll, Christoph Ulrich , Kupka, Ralph , Kasper, Siegfried , Furukawa, Toshi A , Aaronson, Scott T. , Mitchell, Philip B , Gorwood, Philip , Frye, Mark A. , Zohar, Joseph , Zarate, Carlos A.

JAMA Network Open | February 25, 2026 | Volume: 9 | Issue: 2 | Pages: e260043

10.1001/jamanetworkopen.2026.0043 | PMID 41739481 Get It

Importance There is a need for greater recognition of clinical psychopharmacology endpoints, including instances where specific psychotropic medications may become unnecessary, redundant, contradictory, or otherwise inappropriate and therefore merit deprescribing. Objective To address circumstances warranting psychotropic medication deprescribing. Evidence Review The American Society of Clinical Psychopharmacology convened a panel of 45 international psychopharmacology experts who developed and completed a multiround Delphi survey and conducted a focused literature review between January and May of 2025, in order to identify areas of consensus or disagreement on key aspects of the deprescribing of psychotropic medications. These included collaborative risk-benefit assessments with patients; pharmacokinetic and pharmacodynamic factors; pharmacogenomics; distinguishing redundant or conflictual from complementary mechanisms of action; managing adverse effects; assuring medication adherence; drug tolerance or tachyphylaxis; medication misuse; and the psychological context and ramifications of deprescribing. Findings Consensus was achieved on 44 of 50 final Delphi statements (88%). Panelists unanimously agreed that components of a pharmacotherapy regimen should undergo periodic review to ensure that treatments target relevant symptoms and have favorable risk-benefit ratios. Key points of consensus were that deprescribing: (1) should not occur without first assessing medication adherence; (2) merits consideration if less than partial therapeutic response is apparent, or if treatment goals have been reached and relapse prevention is not a long-term objective; (3) involves psychological ramifications that warrant attention; (4) should be followed by close clinical monitoring; and (5) risk-benefit decisions should ideally involve active patient participation within a shared decision-making model. Conclusions and Relevance Through this Consensus Statement, the Task Force identified circumstances in which the selective elimination of certain psychotropic medications may be clinically indicated. Empirical trials are needed to assess the implementation of deprescribing protocols and gauge their safe, effective, and acceptable outcomes.
Contemporary Perspectives on J‐Wave Syndromes: An Expert Consensus Statement
Nademanee, K., Wilde, Arthur A.M. , Ackerman, Michael J., Behr, Elijah R, Chen, P S, Chung, Fa Po, Coronel, R F M, Haissaguerre, Michel, Jiang, Chenyang, Khongphatthanayothin, Apichai , Makita, N., Morita, Hiroshi, Nakagawa, Hiroshi , Ngarmukos, Tachapong , Nogami, Akihiko, PAPPONE, CARLO, Priori, Silvia G., Rosso, Raphaël , Shimizu, W, Veerakul, Gumpanart, Makita, Naomasa , Behr, Elijah R. , Coronel, Ruben , Nademanee, Koonlawee , Nademanee, Koonlawee , Wilde, Arthur A M , Behr, Elijah Raphael , Chung, Fa Po , Coronel, Ruben , Makita, Naomasa , Morita, Hiroshi , Nakagawa, Hiroshi , Ngarmukos, Tachapong , Nogami, Akihiko , Shimizu, Wataru , Ackerman, Michael J. , Bezzina, Connie R. , Haissaguerre, Michel , Jiang, Chenyang , Juang, Jyh‐Ming Jimmy , Pappone, Carlo , Priori, Silvia G. , Viskin, Sami

Journal of Arrhythmia | February 21, 2026 | Volume: 42 | Issue: 1 | Pages: No page available

10.1002/joa3.70284 | PMID 41738055 Get It

ABSTRACT J‐wave syndromes (JWS)—comprising Brugada syndrome (BrS) and early repolarization syndrome (ERS)—are important causes of malignant ventricular arrhythmias and sudden cardiac death in patients whose hearts appear structurally normal. Since the 2016 consensus, advances in genetics, pathophysiology, and therapy have redefined both understanding and management. BrS, once viewed as a purely electrical disorder, is now recognized along a microstructural–electrical continuum, with sodium‐channel dysfunction and subtle epicardial fibrosis of the right ventricular outflow tract as key contributors. Likewise, ERS—historically considered benign—carries significant risk when inferolateral J‐waves coexist with arrhythmic events. Genetically, SCN5A remains the sole gene with definitive disease association, while polygenic susceptibility materially modulates risk, underscoring complex inheritance. Risk stratification remains challenging: patients with prior cardiac arrest or arrhythmic syncope are highest risk, whereas asymptomatic individuals warrant multiparametric assessment integrating clinical features, ECG markers, electrophysiologic studies, and genetics. For decades, treatment centered on implantable cardioverter‐defibrillators and quinidine, both limited by availability, tolerance, and device complications. More recently, epicardial substrate ablation has emerged as a transformative therapy, with large registries and randomized trials demonstrating durable suppression of ventricular fibrillation and acceptable safety. This APHRS‐organized international consensus updates and extends the 2016 Expert Consensus and the 2022 ESC Guidelines, providing contemporary diagnostic frameworks, pragmatic risk‐stratification tools, and treatment algorithms for BrS and ERS. It emphasizes JWS as a microstructural–electrical disease spectrum and elevates substrate ablation as a major therapeutic advance, while outlining priorities for genetics, risk‐stratification and treatment algorithms.
Abstract PS3-06-29: Retrieval-augmented GPT-4 improves NCCN-concordant breast cancer treatment recommendations
Yost, Connor , Aseem, A., Callas, Bradley, Monick, Sarah, Bonilla, L., Galamaga, Robert , Osborn, S., Kumar, Y., Ertz-Archambault, N., Nguyen, Ryan H.

Clinical Cancer Research | February 20, 2026 | Volume: 32 | Issue: 4_Supplement | Pages: PS3-06-29-PS3-06-29

10.1158/1557-3265.sabcs25-ps3-06-29 Get It

Abstract Guideline-concordant breast cancer treatment selection is increasingly complex due to rapid evolution in biomarker-driven therapies. Large language models (LLMs), such as GPT-4, offer a potential tool to support clinical decision-making. However, hallucinations and deviation from evidence-based guidelines remain significant concerns. This study evaluated whether retrieval-augmented generation (RAG) using National Comprehensive Cancer Network (NCCN) guidelines improves GPT-4 performance in treatment recommendation tasks. We developed a retrieval-augmented GPT-4 agent (RAG-GPT) by indexing 2025 NCCN Breast Cancer Guidelines into a vector database using sentence embeddings. Forty clinical vignettes were created from published case reports to reflect diverse scenarios, including HER2-low, triple-negative, and BRCA-mutated disease across all stages. Two models—a baseline GPT-4 (without augmentation) and the RAG-GPT—were prompted with structured templates requesting treatment plans, rationale, clinical trial options, and citations.Outputs were independently scored by two blinded oncology-trained reviewers using the modified Generative AI Performance Score (mG-PS). The mG-PS scored outputs for 2 categories, guideline concordance (Gold standard = 1.0, Acceptable = 0.5, Non-concordant = 0.0) and hallucination errors (Severe = -1.0, Moderate = -0.5, Mild = -0.25, None = 0.0). Guideline Concordance was deemed based on NCCN guidelines and what an oncologist would due based on using the guidelines for each case. Hallucinations are a term used for falsehoods in Artificial Intelligence, like made-up facts or studies, incorrect information, improper doses, or inappropriate or wrong treatments. To ensure consistency and minimize inter-rater variability, reviewers were provided with comprehensive scoring guidelines and detailed instructions for each evaluation metric. Scores were normalized between -1.0 and 1.0 for improved evaluation of tools. Readability and rationale clarity were rated on a 5-point Likert scale. Inter-rater reliability was assessed using Cohen’s kappa. The RAG-GPT demonstrated a significantly higher mean mG-PS score (0.599 ± 0.102, 95% CI: 0.498-0.702) compared to the baseline GPT-4, which not only scored lower but had a negative mean (-0.21 ± 0.143, 95% CI: -0.353 to -0.067). For the mG-PS Cohen’s Kappa test resulted in a score of .69 with substantial aggreament. An independent sample t-test showed a difference (t(78) = 29.1, p < 0.0001). Severe hallucinations were also absent in RAG-GPT outputs (0/40) but occurred in 8/40 baseline GPT-4 outputs. The evaluation of readability and rationality also showed notable differences, with the augmented LLM scoring significantly higher (M = 4.35, SD = 0.66) compared to the naïve LLM (M = 3.05, SD = 1.06). An independent samples t-test confirmed this difference t(65.3) = 6.58, p < 0.0001, further supporting the benefit of augmented Large Language models. Cohen’s Kappa test resulted in a score of .76 for a substantial agreement for readability and rational clarity scale. Limitations include small sample size; further fine-tuning and larger real-world validation studies remain necessary. Linking GPT-4 to NCCN guidelines via retrieval-augmented generation significantly improves treatment accuracy and reduces hallucination severity in breast cancer care scenarios. While further refinement is needed, the reduced incidence of severe hallucinations, increase in guideline-concordant recommendations, and enhanced readability findings support further development and prospective validation of guideline-anchored LLMs for clinical use. Citation Format: C. Yost, A. Aseem, B. Callas, S. Monick, L. Bonilla, R. Nguyen, R. Galamaga, S. Osborn, Y. Kumar, N. Ertz-Archambault. Retrieval-augmented GPT-4 improves NCCN-concordant breast cancer treatment recommendations [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-06-29.
Abstract PS2-08-14: Chemokine signatures improve PD-L1-based prediction of pembrolizumab response in triple-negative breast cancer
Deshmukh, S. Kumar, Wu, S., Xiu, Joanne , Sledge, G. W., Trapani, D., Leone, J., Chumsri, S., Lustberg, M. B., Hong, C., Yao, S., Ernstoff, M., Paulos, C. M., Lesinski, G. B., Madabhushi, A., Badve, S., Kalinsky, K., Kalinski, P., Gandhi, Shipra , Trapani, Dario , Leone, J. P. , Chumsri, S., Lustberg, Maryam , Hong, Chi‐Chen , Takabe, Kazuaki , Opyrchal, Mateusz , Chalasani, Pavani , Paulos, Chrystal M. , Lesinski, Gregory B , Badve, Sunil , Kalinsky, K. M.

Clinical Cancer Research | February 20, 2026 | Volume: 32 | Issue: 4_Supplement | Pages: PS2-08-14-PS2-08-14

10.1158/1557-3265.sabcs25-ps2-08-14 Get It

Abstract Background: Triple-negative breast cancer (TNBC) is an aggressive yet immunogenic subtype of breast cancer (BC) and the only one with FDA-approved immune checkpoint inhibitor (ICI) - pembrolizumab. Currently, PD-L1 (22C3) is the companion biomarker for predicting pembrolizumab benefit, but its utility is limited by spatial/temporal heterogeneity, assay variability, and modest correlation with treatment response. Chemokines such as CXCL9, CXCL10, and CCL5 recruit CD8+ T cells into the tumor microenvironment and have been associated with improved response to ICI, but their predictive value alongside PD-L1 remains unclear. Here, we examined the relationship between these chemokines, PD-L1, and pembrolizumab efficacy in TNBC. Methods: We analyzed 3662 TNBC tumors profiled by NGS (592, NextSeq; WES/WTS, NovaSeq; Caris Life Sciences). Immune cells were estimated using WTS deconvolution (Quantiseq). PD-L1 positivity was defined as >10% CPS (PharmDx 22C3). CXCL9/CXCL10/CCL5-high (H) and -low (L) TNBC were classified by RNA expression above or below 50th percentile. Real-world median overall survival (mOS) was derived from insurance claims and calculated from start of pembrolizumab to last contact using Kaplan-Meier. Statistical significance was assessed by chi-square and Mann-Whitney U with multiple comparison adjustments (q<0.05). Results: TNBC expressed higher levels of CXCL9, CXCL10, and CCL5 (N = 3662, median TPM: 5.3, 14.8, and 15.1) compared to HER2+ (N = 1344; 4.8, 10.1, 10.6) and HR+HER2- BC (N = 6097; 2.7, 6.6, 9.4), all q<0.05. Moderate correlations were observed between PD-L1 CPS and each chemokine (r = 0.41, p<.01). PD-L1-positive tumors had better mOS (24.3 months (m) vs 18.6 m, HR 0.75, 95% CI 0.6-0.92, p=0.007) compared to PD-L1-negative TNBC post-pembrolizumab. Among PD-L1-negative tumors, those with CXCL9-H had better mOS (26.9 m vs 15.8 m for CXCL9-L, HR 0.61, 95% CI 0.45-0.82, p=0.001) post-pembrolizumab. Among PD-L1-positive tumors, CXCL10-H and CCL5-H was associated with improved mOS (CXCL10-H: 25.7 m vs. 20.7 m for CXC10-L, p = 0.03; CCL5-H: 26.7 vs. 18.5 m for CCL5-L, p = 0.03) post-pembrolizumab. PD-L1 negative CXCL9-H, PD-L1 positive CXCL10-H and PD-L1 positive CCL5-H groups showed higher infiltration of CD8+ T cell, B cells, M1/M2 macrophages, Tregs. They also exhibited higher T cell inflamed score, IFNy score and MAPK activation score vs. CXCL9-L, CXCL10-L and CCL5-L groups (Table). Conclusions: In TNBC, a chemokine signature comprising CXCL9, CXCL10 and CCL5 refines PD-L1 based prediction of pembrolizumab benefit. Specifically, high CXCL10 or CCL5 expression in PD-L1-positive tumors, and high CXCL9 expression in PD-L1-negative tumors, were associated with improved survival post pembrolizumab and immune-rich microenvironment. These findings support the use of chemokine profiling to complement PD-L1 and enhance patient selection for ICI therapy in TNBC. Citation Format: S. Gandhi, S. Deshmukh, S. Wu, J. Xiu, G. Sledge Jr., D. Trapani, J. Leone, S. Chumsri, M. Lustberg, C. Hong, S. Yao, K. Takabe, M. Ernstoff, M. Opyrchal, P. Chalasani, C. Paulos, G. Lesinski, A. Madabhushi, S. Badve, K. Kalinsky, P. Kalinski. Chemokine signatures improve PD-L1-based prediction of pembrolizumab response in triple-negative breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-08-14.
Collaborative large language models (LLMs) are all you need for screening in systematic reviews
Parmar, Mihir, Naqvi, Syed Arsalan Ahmed , Warraich, Kainat , Saeidi, Amir, Rawal, Samarth, Faisal, Kunwer Sufyan , Kazmi, Syeda Zainab , Fatima, Maurish , He, Huan, Safdar, Mohammad, Liu, Wei, Haddad, Tufia C., Wang, Zhen , Murad, Mohammad Hassan, Baral, Chitta, Haddad, Tufia, Riaz, Irbaz Bin , Saeidi, Amir, Haddad, Tufia C.

No container title available | February 18, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.64898/2026.02.07.26345640 | PMID 41757212 Get It

Abstract Background The ability of large language models (LLMs) to work collaboratively and screen studies in a systematic review (SR) is under-explored. Hence, we aimed to evaluate the effectiveness of LLMs in automating the process of screening in systematic reviews. Methods This is an observational study which included labeled data (title and abstracts) for five SRs. Originally, two reviewers screened the citations independently for eligibility. A third reviewer cross-checked each citation for quality assurance. GPT-4, Claude-3-Sonnet, and Gemini-Pro-1.0 were used using zero-shot chain-of-thought prompting. Collaborative approaches included (i): conflict resolution using benefit of the doubt, (ii) majority voting using an independent third LLM and (iii) conflict resolution using an informed third LLM. Performance was assessed using accuracy, precision for exclusion, and recall for inclusion. Work saved over samples (WSS) was computed to estimate the reduction in manual human effort. Results A total of 11300 articles were included in this study. The individual models, GPT-4, Claude-3-Sonnet, and Gemini-Pro-1.0 exhibited a high precision for exclusion, achieving 99.7%, 99.7%, and 99.2% and high recall for inclusion achieving 95.5%, 96.6% and 85.7%, respectively. However, the collaborative approach utilizing the two best-performing models (GPT-4 and Claude-3S) achieved an average precision of 99.9% and a recall of 98.5% (across all collaborative approaches). Furthermore, the proposed collaborative approach resulted in an average WSS of 63.5%, compared to the average WSS of 45.2% for individual models. Conversational LLM interactions showed a consistent pattern of results. Limitations This study was limited due to reliance on proprietary models, and evaluation on oncology datasets. Conclusion Evidence shows that collaborative LLMs enable efficient, high-performing screening in systematic reviews, supporting continuous evidence updates. Primary funding source NIH (U24CA265879-01-1) and Carolyn-Ann-Kennedy-Bacon Fund.
Abstract GS2-05: Primary Results from the HR+/HER2- Cohort of TBCRC-053 (P-RAD): A Randomized Trial of No, Low, or High Dose Preoperative RADiation with Pembrolizumab and Chemotherapy in Node-Positive, HER2-Negative Breast Cancer
Gupta, G., Ho, A. Y., Gharibpoor, Faeze , Abdou, Y., Anampa, J. D., Blitzblau, R. C., Calhoun, B. C., Dent, S. F., Carey, L. A., Bellon, J. R., Warren, L. E., Lu, J., Hieken, T. J., Taghian, A. G., Bardia, A., Traina, T. A., Plitas, George , Gallagher, K., Daugherty, K., Thompson, A. M., Krop, I., Wolff, A., Mittendorf, E. A., Fox, J., Hwang, E., Khan, A. J., Loene, J. P., Mutter, R., Patil, S., Santa-Maria, C., Vincent, B. V., Wright, J. L., Spring, L., Gupta, Gaorav P , Blitzblau, R.C., Calhoun, B.C., Casey, Dana L. , Dent, Susan , Bellon, J.R., Warren, LE, Hieken, Tina J. , Bardia, Aditya , Gallagher, K.K., Thompson, A. M., Krop, Ian E. , Mittendorf, E. A., Garber, Haven R. , Mutter, Robert W. , Santa-Maria, C.A.

Clinical Cancer Research | February 17, 2026 | Volume: 32 | Issue: 4_Supplement | Pages: GS2-05-GS2-05

10.1158/1557-3265.sabcs25-gs2-05 Get It

Abstract Introduction: Hormone receptor positive (HR+), HER2- breast cancer (BC) is the most common subtype of BC. Despite advances in chemotherapy and endocrine therapy optimization, local and systemic recurrences frequently occur, especially for patients with node-positive disease. Recent data suggest a subset of patients with this tumor phenotype may benefit from the addition of anti-Programmed Death-1(aPD1) to neoadjuvant chemotherapy. However, T-cell infiltration (TCI), a biomarker of response to aPD1 and chemotherapy, is typically low in this BC subtype. Preclinical models show that combining preoperative radiation therapy (preop RT) with immune checkpoint inhibitors can enhance TCI and anti-tumor immunity. We conducted the first randomized trial to test whether no-, low- or high-dose RT combined with aPD1 increases TCI and improves responses in non-irradiated, metastatic lymph nodes in HR+/HER2- BC (NCT04443348). Materials & Methods: Eligible patients had ER and/or PR≥10%, HER2 negative invasive BC with clipped and biopsy-proven positive axillary node(s), cT1c-T4c, cN1-3, and at least one of the following criteria: grade 3 or grade 1-2 with cN2-N3, Ki67 >20%, or high genomic assay score. Between 2022-2024, 51 patients from 10 centers were randomized to no (0Gy; control arm), low (9Gy) or high (24Gy) doses of preop RT to the primary tumor with concurrent pembrolizumab followed by a 2-week tumor biopsy. Stratification factors were T1c vs. T2-4 and N1 vs. N2-3. Patients subsequently received pembrolizumab with 12 weeks of paclitaxel, followed by 4 cycles of adriamycin-cyclophosphamide (q2wk or q3wk) with pembrolizumab (200 mg q3 wks or 400 mg q6 wks). Surgery and adjuvant therapy followed standard-of-care. Dual co-primary endpoints were 2wk tumor TCI and nodal pathologic complete response (ypN0) at time of definitive surgery. TCI was assessed by multiplex immunofluorescence (pan-cytokeratin, CD3, CD8), using a rank-based Immunoscore (range 0-1), compared to baseline reference biopsies via two-tailed Mann-Whitney test. ypN0 was evaluated non-comparatively. Secondary endpoints included pCR and Residual Cancer Burden (RCB) 0/1. Results: Among 51 patients enrolled, 49 were evaluable for TCI and 48 for the ypN0 endpoint. Median age was 49.5 years (range 23-78). The cohort had a high-risk clinical profile: 92% had cT2-4, 50% N2-3, and 62% grade 3 tumors. Median ER and PR positivity were 90% (20-100) and 68% (1-98), respectively. Multifocal or multicentric tumors were present in 32%. TCI was assessed at 2 weeks post-treatment. The proportion of tumors with TCI in the upper quartile increased with RT dose escalation: 31% (0Gy), 40% (9Gy), and 53% (24Gy). Median TCI scores at 2 weeks were 0.60 (0Gy), 0.56 (9Gy), and 0.82 (24Gy), compared to a median baseline value of 0.50 from untreated reference samples. A statistically significant increase in TCI was observed only in the 24Gy cohort relative to the untreated group (p=0.027). 70.8% underwent mastectomy, with 39.6% receiving immediate reconstruction. 8% experienced G2/3 wound complications, balanced across arms. Median number of lymph nodes removed was 6.5 (1-42). The overall ypN0 rate was 29%, and 24%(0Gy), 29%(9Gy) and 33%(24Gy) per arm. pCR/RCB 0-1 rates were 18%/27% in the entire cohort and 6%/18%(0Gy), 29%/29%(9Gy), and 19%/33%(24Gy), respectively. Conclusion: The addition of 24Gy preop RT to aPD1 significantly increased tumor TCI in HR+/HER2- early-stage BC. Non-irradiated nodal response rates were promising despite over one-third of the study population with grade 1/2 tumors and high disease burden, laying the foundation for a future randomized trial comparing the efficacy of this novel approach against standard of care for node-positive HR+/HER2- BC. Citation Format: G. Gupta, A. Y. Ho, F. Gharibpoor, Y. Abdou, J. D. Anampa, R. C. Blitzblau, B. C. Calhoun, D. L. Casey, S. F. Dent, L. A. Carey, J. R. Bellon, L. E. Warren, J. Lu, T. J. Hieken, A. G. Taghian, A. Bardia, T. Traina, G. Plitas, K. Gallagher, K. Daugherty, A. Thompson, I. Krop, A. Wolff, E. Mittendorf, J. Fox, H. Garber, E. Hwang, A. J. Khan, J. P. Loene, R. Mutter, S. Patil, C. Santa-Maria, B. V. Vincent, J. L. Wright, L. Spring.Primary Results from the HR+/HER2- Cohort of TBCRC-053 (P-RAD): A Randomized Trial of No, Low, or High Dose Preoperative RADiation with Pembrolizumab and Chemotherapy in Node-Positive, HER2-Negative Breast Cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr GS2-05.