BACKGROUND AND OBJECTIVES:Time to endovascular thrombectomy (EVT) is a critical determinant of outcomes for large vessel occlusion (LVO) strokes presenting within 6 hours of onset. Its impact in the extended (6-24-hour) window remains uncertain. We aimed to evaluate the association between treatment times and outcomes in this window. METHODS:Individual patient-level data from 6 randomized trials enrolling patients in the extended window were pooled. The primary outcome was degree of disability at 90 days (modified Rankin Scale [mRS] 0-6). Secondary outcomes included functional independence (mRS 0-2), mortality, and symptomatic intracranial hemorrhage. RESULTS:Among 505 participants (median age 70 years; baseline NIH Stroke Scale 16; 51.3% female; advanced imaging selection 86.5%), 266 (52.7%) received EVT and 239 (47.3%) medical therapy alone. In EVT-treated patients, longer onset-to-randomization times were not associated with differences in disability (adjusted odds ratio [aOR] per 60 minutes 1.02; 95% CI 0.96-1.08; p = 0.53) or functional independence (aOR 1.06; 95% CI 0.95-1.17; p = 0.28). Conversely, control patients exhibited worse outcomes with increasing onset-to-randomization times (aOR for disability 0.93; 95% CI 0.87-1.00; p = 0.041; functional independence 0.84; 95% CI 0.73-0.97; p = 0.019), resulting in greater treatment benefit at later times (p-interaction = 0.033 and 0.003, respectively). No association was observed between onset-to-puncture or onset-to-reperfusion and outcomes in EVT patients. However, longer randomization-to-reperfusion times correlated with worse disability (aOR 0.58; 95% CI 0.37-0.91; p = 0.018) and lower functional independence (aOR 0.51; 95% CI 0.28-0.96; p = 0.038). DISCUSSION:This study demonstrates that the benefit of EVT is consistently preserved across the extended (6-24-hour) time window when patients are selected using advanced imaging criteria. In this highly selected population, enriched with slow progressors, the apparent increase in treatment effect with longer onset-to-presentation times reflects the validity of physiologic selection rather than true time insensitivity. However, this observation should not diminish the critical importance of time: imaging-based selection effectively resets the treatment clock, masking the harmful impact of prehospital delays. Notably, longer in-hospital delays were strongly associated with worse outcomes, reinforcing that "time is brain," even in extended-window cohorts.
Breast-conserving surgery (BCS) followed by adjuvant radiotherapy is the standard of care for early-stage breast cancer. However, reoperations after BCS may compromise aesthetic outcomes, increase surgical complications, and cause psychological distress. This study aimed to determine the reoperation rate after BCS in a multi-institutional cohort from Brazil and to identify predictive factors associated with reoperation. This retrospective multicenter cohort study included female breast cancer patients (AJCC clinical stage 0–III) who underwent BCS followed by adjuvant radiotherapy at six treatment centers in Brazil between January 2016 and December 2022. Logistic regression was used to assess the association between potential risk factors and reoperation. The overall reoperation rate was 5.2
Triple-negative breast cancer (TNBC) accounts for 15-20% of breast cancers and lacks expression of estrogen receptor, progesterone receptor, and HER2, limiting targeted options. Recent neoadjuvant therapy (NAT) advances include immune checkpoint inhibitors (ICIs) and PARP inhibitors, improving pathologic complete response (pCR) and survival but raising concerns about severe toxicity. Despite broader adoption of these regimens, a systematic analysis of Grade ≥3 adverse events (AEs) from contemporary phase III trials is lacking. We conducted a PRISMA-guided systematic review and meta-analysis (PROSPERO: CRD42024562785). MEDLINE, Embase, and Cochrane were searched for phase III randomized trials (Jan 2010-Jun 2025) evaluating NAT in non-metastatic TNBC and reporting Grade ≥3 AEs (CTCAE). One phase II trial (WSG-ADAPT-TN; n=336) with robust comparative design and AE reporting was also included. Pooled prevalence and risk ratios (RR) with 95% CI were calculated using DerSimonian-Laird random-effects models. Subgroup analyses included: Group A (PARP inhibitors), B (immunotherapy), and C (platinum-based regimens). Heterogeneity was assessed via I2. Six trials with 3,316 TNBC patients were included (BrighTNess, IMpassion031, KEYNOTE-522, NeoTRIP, PARTNER, WSG-ADAPT-TN). Neutropenia was the most common Grade ≥3 AE, highest with immunotherapy (33.5%), followed by PARP inhibitors (23.7%) and platinum regimens (16.0%) (Q=71.8, p<0.0001). PARP inhibitors significantly increased neutropenia risk (RR=1.84), while immunotherapy showed no increase (RR=1.00, p=0.94). Grade ≥3 anemia was higher with PARP inhibitors (20.6%) vs. immunotherapy (9.9%), with doubled risk vs. placebo (RR=2.08, p=0.02). Thrombocytopenia was most prevalent with immunotherapy (7.9%), but PARP inhibitors showed the highest risk (RR=3.56, p=0.0001). Febrile neutropenia was more common with ICIs (14.9%) than PARP inhibitors (3.0%). ALT elevation was more frequent in platinum regimens (6.4%), without significant differences across groups. Fatal AEs were <1% in all trials. Modern NAT regimens improve outcomes in TNBC but confer significant Grade ≥3 toxicity. PARP inhibitors pose the highest hematologic risk, while ICIs increase febrile neutropenia. Platinum regimens showed the most favorable toxicity profile. Findings highlight the need for biomarker-driven, individualized treatment and vigilant AE monitoring in early TNBC. M. Antonini, A. Mattar, F. P. Cavalcante, F. P. Zerwes, E. C. Millen, F. P. Brenelli, A. L. Frasson, M. D. Teixeira, M. Madeira, G. Facina, H. L. Couto, G. T. Tosello, R. Arakelian, A. D. Lima, G. N. Garcia, F. Bagnoli, A. G. Amorim, M. F. de Figueiredo, L. R. Soares, R. Freitas Júnior, L. H. Gebrim. Adverse Events in Neoadjuvant Therapy for Triple-Negative Breast Cancer: A Systematic Review and Meta-Analysis of Phase III Trials [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 PS4-07-03.
Neoadjuvant chemotherapy (NAC) has become a cornerstone in breast cancer treatment, especially for locally advanced tumors and aggressive subtypes such as triple-negative and HER2-positive disease. NAC can reduce tumor size, increase breast-conserving surgery (BCS) eligibility, improve cosmetic outcomes, and allow early systemic control. However, concerns persist regarding whether BCS following NAC achieves oncologic outcomes comparable to those of BCS followed by adjuvant chemotherapy (AC). This study aimed to compare long-term survival outcomes in patients undergoing BCS after NAC versus AC in a real-world Brazilian cohort. We conducted a retrospective, multicenter cohort study across six Brazilian institutions (five private, one public). Women aged 18 years or older with clinical stage 0-III breast cancer who underwent BCS (either standard lumpectomy or therapeutic mammoplasty) between 2016 and 2022 were included. Patients were divided into two groups according to whether they received NAC or AC. Data on demographics, tumor characteristics, and treatments were collected from institutional registries. The outcomes assessed were locoregional recurrence-free survival (LRRFS), distant recurrence-free survival (DRFS), breast cancer-specific survival (BCSS), progression-free survival (PFS), and overall survival (OS). Survival outcomes were estimated using Kaplan-Meier methods, and Cox proportional hazards models were used to assess hazard ratios (HRs) and 95% confidence intervals (CIs). This study was approved by the IDOR Ethics Committee (reference 6,907,736). A total of 268 women underwent breast-conserving surgery; 138 (51.5%) received NAC and 130 (48.5%) received AC. The mean age of the cohort was 53.1 years (SD 12.1), with patients in the NAC group being slightly younger (mean 51.1 vs. 55.2 years). Over half of the patients (56.8%) were over 50 years old, and 51.1% identified as white. Invasive ductal carcinoma was the predominant histological type (84.7%), and the majority of patients (73.8%) presented with early-stage disease (≤ stage IIA). Most underwent lumpectomy (72.4%), while 27.6% had therapeutic mammoplasty. In the NAC group, 57.2% had tumors classified as stage >IIB. After a median follow-up of 60 months, no statistically significant differences were observed in survival outcomes between the NAC and AC groups. The hazard ratio for LRRFS was 1.29 (95% CI: 0.28-5.88; p=0.816), for BCSS was 0.52 (95% CI: 0.10-2.61; p=0.473), for DRFS was 1.05 (95% CI: 0.31-3.52; p=0.955), for PFS was 1.19 (95% CI: 0.36-3.96; p=0.869), and for OS was 0.73 (95% CI: 0.18-2.91; p=0.710). In this multicenter Brazilian cohort, breast-conserving surgery following neoadjuvant chemotherapy was associated with survival outcomes comparable to those of surgery followed by adjuvant chemotherapy. These findings support the oncologic safety of BCS after NAC and reinforce its role as a safe and effective option in the individualized surgical management of breast cancer. A. Dominique Nascimento Lima, A. Mattar, F. Pimentel Cavalcante, F. Pereira Zerwes, M. Antonini, M. Leite Kraft, A. Oliveira de Alencar, A. de Queiroz Germano, D. Pitanga Torres, E. Goulart Carneiro, C. Freitas de Lima, R. Zocchio Torresan, F. Palermo Brenelli, M. Lichtenfels, A. Frasson, J. Bines, E. Camargo Millen. Is it safe to offer breast-conserving surgery after neoadjuvant chemotherapy? A Brazilian multicenter cohort study [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 PS2-03-09.
RESUMO Objetivo: Comparar funcionalidade pulmonar e biomarcadores de lesão endotelial entre pacientes em hemodiálise com doença renal em estágio terminal (DRET) e receptores de transplante renal (TR). Métodos: Estudo transversal incluindo 23 pacientes em diálise por ≥24 meses e 23 pacientes transplantados há ≥ 12 meses, com taxa de filtração glomerular ≥ 40 mL/min/1,73 m2, pareados por sexo e idade. A funcionalidade pulmonar foi analisada por meio da pressão inspiratória e expiratória máxima (PIM e PEM), capacidade vital forçada (CVF), volume expiratório forçado no primeiro segundo (VEF1) e índice de Tiffeneau. O dano endotelial foi avaliado utilizando sindecano-1, molécula de adesão intercelular-1 (ICAM-1), molécula de adesão celular vascular (VCAM-1) e angiopoietina-2 (Ang-2). Resultados: Ambos os grupos apresentaram baixo desempenho nos testes de funcionalidade pulmonar. A porcentagem de pacientes que atingiram os valores previstos de PIM, PEM, VEF1 e CVF foi baixa e semelhante entre os grupos (43,5%, 4,3%, 0% e 17,4%, respectivamente). Não houve diferenças nas razões observado/previsto de PEM (66 ± 17%), VEF1 (60 ± 18%) e CVF (76 ± 22%), nem no índice de Tiffeneau (0,8 [IIQ 0,6–0,9]). Os pacientes submetidos a transplante renal apresentaram menor porcentagem de PIM (82 ± 19% vs. 94 ± 12%; p = 0,019). No grupo TR, o dano endotelial apresentou correlação inversa significativa com os parâmetros de funcionalidade pulmonar, e esse grupo apresentou níveis mais baixos de VCAM-1 (1.589 [IIQ 1.009–1.827] vs 2.302 [IIQ 1.642–3.540] ng/mL; p = 0,001), Ang-2 (0,17 [IIQ 0,01–1,14] vs 0,75 [IIQ 0,30–1,29] ng/mL; p = 0,040) e sindecano-1 (47,9 [IIQ 33,1–67,8] vs 195,8 [IIQ 126,9–286,8] ng/mL; p < 0,001). Conclusão: Apesar da melhor função endotelial, o transplante renal não esteve associado a uma funcionalidade pulmonar superior, sugerindo uma fisiopatologia multifatorial para o comprometimento pulmonar.
