Citations

Abstract PURPOSE: CDK4/6 inhibitors (CDK4/6i), used in combination with endocrine therapy (ET), are standard of care for advanced and higher risk early stage hormone receptor-positive (HR+), HER2 negative (HER2-) breast cancer. PALLAS investigated the addition of 2 years (y) of palbociclib to adjuvant ET (ET/P) compared to ET alone in patients (pts) with stage II-III HR+/HER2- breast cancer. We now present overall survival (OS) with 7-y outcomes and impact of post-recurrence therapy. PATIENTS AND METHODS: This global phase III trial randomized pts to ET for at least 5 y with or without 2 y of P. Primary endpoint was iDFS; distant recurrence-free survival (DRFS) and OS were preplanned endpoints. Kaplan Meier estimates and hazard ratios (HR) from Cox and Fine & Gray models were performed. Post-recurrence OS was analyzed as time from first distant recurrence (DR) until death. The post-recurrence OS model adjusted for both clin/path factors (including DR-free y, DR site) and time-dependent post-DR therapy (chemo, CDK4/6i). Results: 5,796 pts enrolled at 406 centers in 21 countries worldwide over 3 y. In the intent-to-treat (ITT) population, with a median follow-up of 82.7 months (mo), 7-y outcomes for iDFS, DRFS and OS are shown in the table. DR occurred in 781 pts (377 ET/P, 404 ET alone) with balanced pt/disease characteristics between arms. ET/P had more visceral (46% vs. 36%) and fewer non-visceral (61% vs. 68%) DR compared to ET alone (p=0.03). Unadjusted post-recurrence OS was significantly worse for ET/P vs. ET (median 22.6 vs. 27.9 mo, HR 1.21 (95% CI 1.01-1.46, p=0.04). However, receipt of any post-recurrence CDK4/6i was significantly higher on ET vs. ET/P arms (41% vs. 66%) and time to post-progression CDK4/6i initiation was significantly shorter for those in the ET vs. ET/P arms (HR 0.50, 95% CI 0.41-0.61, p<0.001) adjusting for region, bone/visceral DR type, DR-free time and age. Conversely, time to post-progression chemotherapy initiation was significantly longer for ET alone vs. ET/P arms (HR 1.31, 95% CI 1.07-1.61, p=0.01). However, after adjustment for clinical factors and post-DR treatment, the OS difference was no longer seen (HR 1.05, 95% CI 0.85-1.28, p=0.65). 3-mo landmark analysis showed similar effect on OS after adjusting for CDK4/6i initiation within 3 mo from DR (unadjusted HR 1.24, p=0.03 vs. adjusted HR 1.15, p=0.22). CONCLUSION: The PALLAS trial revealed significant differences in treatment post-DR that impact OS. Reduced/delayed use of metastatic CDK4/6i after adjuvant P was associated with significantly poorer OS, suggesting that patients who relapse after adjuvant CDK4/6i may still benefit from metastatic CDK4/6i. This has implications for optimal treatment in those who relapse after adjuvant CDK4/6i and warrants further study to determine if this is therapy-specific or an overarching biological effect. SUPPORT: AFT, ABCSG, NRG, PrECOG; Pfizer Citation Format: A. DeMichele, A. Dueck, M. Gnant, D. Hlauschek, M. Martin, A. Wolff, G. Rubovsky, F. Henao, O. Hahn, A. Chan, A. Brusky, P. Morris, H. Burstein, G. Huber, D. Anderson, L. Garcia-Estevez, G. Pfeiler, H. Rugo, N. Zdenkowski, S. Gampenrieder, N. Wolmark, D. Sabanathan, K. Miller, D. Cameron, E. Winer, C. Brunner, E. Gauthier, P. O’Brien, C. Fesl, E. Mayer. Adjuvant Palbociclib for ER+ Breast Cancer in the PALLAS Trial (ABCSG-42/AFT-05/PrE0109/BIG-14-13): Post-Recurrence Treatment and Overall Survival [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 RF7-07.

Abstract Background: The association of TILs with pathologic complete response (pCR) and survival in HER2+ breast cancer is not well established with several prior studies showing inconsistent results. In this secondary analysis of EA1181, we evaluated the association between stromal TILs (sTILs) and pCR rates. Methods: EA1181 (NCT04266249) enrolled patients (pts) with anatomic clinical stage II/III HER2+ breast cancer who preoperatively received 4 cycles of trastuzumab and pertuzumab with 12 weeks of paclitaxel or docetaxel q3w x 4 (THP), followed by surgery. sTILs density was assessed on full-face hematoxylin and eosin (H&E)-stained tumor biopsy sections. sTILs scores were analyzed per protocol as a continuous variable (every 10% increment) and as a categorical variable (<10% vs 10-60% vs >60% as per Denkert et al, 2018), and also with an exploratory 30% cutoff commonly used in TNBC. Cox proportional hazards models were used to examine the association between sTILs and pCR, adjusting for available baseline factors. The associations between sTILs (by category) and clinicopathologic characteristics were examined using Fishers’ exact test. Results: Among 2141 pts with HER2+ BC treated on EA1181, H&E slides were available for 1328 (62%). The study population evaluated for sTILs was comparable to the overall population. pCR rates were 44.5% overall, 64% for HER2+/ER- and 33% for HER2+/ER+ disease. sTILs distribution was: 623 (47%) <10%, 698 (52%) 10-60%, and 7 (0.5%) >60%, which led us to merge the latter two groups (705 [53%] had ≥10% sTILs). In univariable and multivariable analyses, increasing sTILs (as a continuous variable) were associated with increasing pCR rates in both HER2+/ER+ and HER2+/ER- disease (p<0.001; Table). sTILs analyzed as a categorical variable (<10% vs ≥10%) were significantly associated with pCR for all patients (combined) and for those with HER2+/ER+ disease. In exploratory analysis using a cutoff of <30% vs ≥30% sTILs, an association with pCR was also seen in univariable analysis for both HER2+/ER+ disease (p<0.001) and HER2+/ER- disease (p=0.045), though in multivariable analysis with clinical factors, sTILs >30% remained a significant predictor for pCR only in HER2+/ER+ disease. Additional exploratory analysis with other molecular biomarkers, intrinsic subtypes, and immune signatures will be presented. Conclusion: sTILs were associated with pCR after THP, further supporting the important role of immune mechanisms in HER2+ breast cancer, and highlighting a potentially robust predictive tool to assess pathologic response. Baseline sTILs could potentially inform the preoperative design of future trials of therapy optimalization. Association of baseline sTILs with recurrence free survival in EA1181 will be reported in the future. Citation Format: S. S. Badve, F. Zhao, N. Tung, Y. Gokmen-Polar, C. C. O'Sullivan, A. Prat, E. P. Winer, J. L. Wright, A. Recht, A. C. Weiss, J. A. Tjoe, S. M. Feldman, G. B. Rocque, M. Smith, N. Unni, S. Sardesai, S. Tang, S. Modi, W. J. Irvin, P. Villagrassa, C. Battelli, A. K. Krie, N. Bagegni, M. A. George, M. L. Telli, V. F. Borges, N. D’Abreo, P. Shah, K. D. Miller, A. H. Partridge, L. A. Carey, A. M. DeMichele, A. C. Wolff, ECOG-ACRIN.Tumor infiltrating lymphocytes (TILs) and pathologic complete response (pCR) in stage II/III HER2+ breast cancer treated with taxane, trastuzumab, and pertuzumab (THP): secondary results from the ECOG-ACRIN EA1181/CompassHER2 pCR trial [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 GS1-04.

INTRODUCTION: The American College of Gastroenterology assembled a multidisciplinary task force to evaluate the current state and future direction of artificial intelligence (AI) in gastroenterology, hepatology, and endoscopy leading to the development of consensus-based recommendations for responsible AI integration in clinical practice. METHODS: A total of 32 subject-matter experts and 12 industry partners, representing diverse practice settings and expertise, conducted subgroup literature reviews across 5 key areas (endoscopy, practice management clinical applications, training and education, inflammatory bowel disease and liver disease, ethics and equity). Draft statements were developed and rated on a 5-point Likert scale using a modified Delphi process. A consensus was set at ≥70% combined agreement. Nonconsensus items were revised and revoted electronically. RESULTS: A total of 43 statements, 40 (93%) reached consensus in round 1 and the remaining 3 achieved consensus after round 2. Evidence supports computer-aided detection improving adenoma detection rate and miss rate in controlled studies, with mixed real-world impact and insufficient long-term outcomes (e.g., interval colon cancer rate). Recommendations emphasize thorough validation and reduction of bias by heterogeneous Data sets. Outside endoscopy, ambient AI scribes, natural language processing (NLP)-enabled coding, workflow optimization, and previous authorization support show potential. Training recommendations endorse a structured AI curriculum while preserving independent procedural competence to avoid deskilling. In inflammatory bowel disease and hepatology, AI could help improve diagnostic accuracy, help predict risk of disease progression, and help guide therapy. Equity, governance, and reimbursement statements call for chain-of-custody data protections, specialty-society oversight, and payment models that reward quality and cost reduction. DISCUSSION: This consensus outlines how AI can augment rather than replace clinical expertise while promoting safety, transparency, interoperability, and equity. Priorities include pragmatic and prospective trials, multi-institutional data-sharing consortia, bias mitigation, and workforce training to enable trustworthy and clinically impactful AI adoption in gastroenterology, liver, and endoscopy care.

Background: Upfront resectable pancreatic ductal adenocarcinoma (PDAC) is defined by the NCCN as disease with ≤180° portomesenteric vein (PMV) abutment. However, the clinical significance of PMV abutment in this cohort remains unexplored, and we sought to investigate its impact. Methods: This multi-institutional study included patients who underwent pancreatoduodenectomy (PD) for upfront resectable PDAC from 2002 to 2023. Patients with PDAC with ≤180° PMV abutment were compared with those without. Overall survival (OS) was compared and stratified based on whether patients underwent upfront surgery or neoadjuvant therapy (NAT). Results: Among 1,446 patients included, 521 (36.0%) had PMV abutment. Median OS for patients with PMV abutment was 28.8 months compared with 31.2 months for those without ( P =.17). In a stratified analysis of patients who underwent upfront surgery, patients with PMV abutment had worse OS (19.2 vs 27.6 months; P <.05) and lower R0 resection rates (63.1% vs 87.2%; P <.05) compared with those without. However, in patients who underwent NAT, this difference in R0 resection rate was not observed (91.4% vs 94.0%, respectively; P =.27). Furthermore, there was no significant difference in median OS with NAT (42.5 vs 51.6 months, respectively; P =.48). Conclusions: In this largest cohort to date of patients with upfront resectable PDAC, PMV abutment was associated with worse OS compared with no PMV abutment when an upfront resection strategy was used. The use of NAT in patients with PMV abutment mitigated this survival difference with increased R0 resection rates. These findings suggest that patients with upfront resectable PDAC with PMV abutment benefit from a NAT approach for optimal survival outcomes, and that the current criteria guidelines need to be redefined.

Abstract Background In randomized clinical trials (RCTs), anticipating control arm outcomes is important for power calculations and enrollment goals. Unexpected overperformance of the control arm can underpower RCTs. The objective of this study was to estimate the prevalence of control arm overperformance in phase 3 oncology RCTs. Methods The authors conducted a meta‐epidemiological study of two‐arm, superiority‐design, phase 3 oncology RCTs. They reviewed articles/publications and protocols for power calculations, justification, and outcomes. Control arm performance was measured as the ratio of observed control arm outcomes relative to pretrial estimates, and overperformance was defined as a 10% improvement. Results In total, 385 RCTs met inclusion criteria. The primary end point was overall survival (OS) in 134 RCTs (35%). Of 311 RCTs (81%) that provided a pretrial estimate for control arm performance, 138 RCTs (44%) cited a justification for the estimate. Greater than expected control arm performance was associated with lower odds of meeting the primary end point (adjusted odds ratio, 0.989; 95% confidence interval, 0.981–0.998; p = 0.015). Of 244 RCTs that were evaluable for control arm performance, 104 (43%) exhibited overperformance. RCTs that used OS as a primary end point were more likely to exhibit control arm overperformance compared with RCTs that used other primary end points (56% vs. 33%; adjusted odds ratio, 2.43; 95% confidence interval, 1.42–4.15; p = .001). Conclusions Control arm overperformance is common in phase 3 oncology RCTs and is associated with trial outcomes, suggesting an effect on study power. Because overperformance appears to be especially prevalent when OS is the primary end point, the effects of postprogression therapies on OS may be underappreciated. Alternative strategies for designing trials should be considered for reliable estimation of treatment effects.

Abstract Background Quantitative myocardial blood flow (MBF) and myocardial flow reserve (MFR) provide incremental diagnostic and prognostic value in cardiac PET, but their widespread use is limited by the technical demands of dynamic imaging protocols. We evaluated the feasibility of using artificial intelligence (AI) to predict MBF and MFR from static and gated PET images, without the need for dynamic acquisition. Methods A machine learning (XGBoost) model was trained on 82Rb PET multi-center dataset using static perfusion imaging, injected dose, hemodynamic measures, clinical data and CT-derived features (including body composition) from the hybrid CT attenuation scan. Model performance was evaluated externally in an independent cohort. Results In total, 10,566 (derivation-cohort) and 7,842 (external-cohort) patients were included in this multi-center study. On the external-cohort, AI approach achieved an Area under the curve (AUC) of 0.92 (0.92–0.93) for abnormal stress MBF and 0.91 (0.90–0.92) for abnormal MFR; Intra-class correlation (ICC) 0.80 (0.78–0.82) and 0.78 (0.76–0.79), respectively. AI MFR closely mirrored the prognostic performance of measured MFR, showing nearly identical Kaplan–Meier risk stratification (both p<0.0001) and maintaining strong, and independently significant associations with all-cause mortality (HR 3.4 [2.8–4.2] vs. 4.6 [3.6–5.8]; both p<0.001), and demonstrated similar added value to perfusion for mortality prediction. Conclusion AI-predicted virtual stress MBF and MFR assessment using static and gated PET data is feasible and generalizable across cohorts. By removing the dependency on dynamic acquisitions, this approach has the potential to broaden the clinical adoption of flow quantification. STRUCTURED GRAPHICAL ABSTRACT PET: Positron Emission Tomography, CT: Computed Tomography, MFR: Myocardial Flow Reserve Key Question: Can machine learning models trained on dynamic PET datasets accurately predict regional stress myocardial blood flow (MBF) and myocardial flow reserve (MFR) from static image features, physiological parameters, and CT-based anatomical measures? Key Finding: Artificial intelligence can accurately estimate MBF and MFR from non-dynamic PET data, with strong agreement to reference standards. Take-home Message: By eliminating reliance on dynamic PET acquisitions, machine-learning has the potential to broaden clinical adoption of quantitative flow assessment.

Abstract In a real-world analysis of brexucabtagene autoleucel recipients with relapsed/refractory B-cell acute lymphoblastic leukemia (N = 278), lack of response to prior blinatumomab correlates with significantly worse following chimeric antigen receptor T-cell therapy outcomes.

BACKGROUND AND OBJECTIVES: Myelomeningocele is defined by the presence of a fluid-filled sac that contains the neural placode and cerebrospinal fluid (CSF) at the level of the spinal defect. Alternatively, the term myeloschisis is used when the neural placode is not contained within a CSF-filled sac. While both are eligible for prenatal closure, few studies have characterized the impact of the type of lesion on postnatal outcomes. This study compares the outcomes of these 2 types of open spinal dysraphism using data from the Fetal Myelomeningocele Consortium registry sponsored by the North American Fetal Therapy Network. METHODS: The prospective observational Fetal Myelomeningocele Consortium registry was used to extract deidentified data corresponding to patients who underwent fetal closure of myelomeningocele vs myeloschisis. Demographics, operative characteristics, perioperative complications, and postnatal outcomes were collected. RESULTS: A total of 1327 patients were identified, including 991 (74.7%) with myelomeningocele and 336 (25.3%) with myeloschisis. Compared with myelomeningocele, myeloschisis was associated with lower rates of prenatal talipes (11% vs 24%, P < .001) and higher rates of favorable prenatal movement (94% vs 86%, P < .001). Postnatally, myeloschisis conferred higher rates of leg movement (97% vs 90%, P = .002) and an increased likelihood of ambulation in the household (10.4% vs 4.1%, P = .009) and outside (7.2% vs 1.9%, P = .004) at 1 year. However, myeloschisis was also linked to greater use of skin patches during closure (49% vs 27%, P < .001), higher CSF leak rates among those with wound dehiscence (26% vs 8%, P = .014), and more frequent CSF diversion and tethered cord surgeries at follow-up. CONCLUSION: Myeloschisis and myelomeningocele demonstrate distinct clinical profiles. Although patients with myeloschisis may have favorable motor outcomes, they are also characterized by higher rates of CSF leakage, CSF diversion, and tethered cord surgery. These findings highlight the need for lesion-specific prognostication and may inform surgical planning and parental counseling in the context of prenatal spina bifida closure.

This cohort study evaluates the reduction in risk of high-grade serous carcinoma among women undergoing opportunistic bilateral salpingectomy in Canada.

Abstract INTRODUCTION Associations of short‐term use of menopausal hormone therapy (mHT) with Alzheimer's disease (AD) and structural magnetic resonance imaging (MRI) biomarkers were investigated 10 years after an mHT trial. METHODS Recently menopausal women with good cardiovascular health were randomized to oral conjugated equine estrogens (oCEE) or transdermal 17β‐estradiol (tE2) and micronized progesterone, or placebo for 4 years. Amyloid beta (Aβ) on positron emission tomography, hippocampal atrophy, and dorsolateral prefrontal cortex thickness on MRI were assessed 10 years after completion of the mHT trial ( n = 266). RESULTS Aβ and structural MRI biomarkers were not different in the oCEE and tE2 groups compared to placebo. Apolipoprotein E ε4 status did not modify the findings. DISCUSSION There was no evidence of adverse effects or benefits associated with 4 years of use of oral or transdermal mHT on Aβ and structural MRI biomarkers in relatively healthy women, 10 years after mHT. Findings support the long‐term safety of short‐term use of mHT on brain health. CLINICAL TRIALS REGISTRATION NCT00154180 Kronos Early Estrogen Prevention Study (KEEPS) Highlights There were no menopausal hormone therapy–related adverse effects or benefits on amyloid beta and magnetic resonance imaging biomarkers in the long term. Apolipoprotein E ε4 carrier status did not modify these findings. Findings align with neutral cognitive and cerebrovascular outcomes in this cohort.