e23549 Background: We aimed to determine the impact of early recurrence on the prognosis of patients who have undergone resection of primary retroperitoneal sarcoma (RPS) and to discover which preoperative patient/tumor features predict early recurrence. Methods: Consecutive patients with primary non-metastatic RPS who were managed at two high volume RPS referral centers between 03/2012 and 10/2019 were identified from prospectively maintained institutional databases. The primary study endpoint was Overall Survival (OS), defined as the time from diagnosis to death from any cause, estimated by the KM method. Patients were grouped by Disease-Free Interval following resection (DFI = 0-6, 7-12, 13-18, 19-24, > 24 mos). Univariate and multivariable analyses (UVA, MVA) were performed. The Sarculator risk calculator and the Inflammatory Biomarkers Prognostic Index (IBPI) were assessed as potential predictors of early recurrence, defined as DFI 0-6 mos. Results: 651 patients (median age = 62.7yrs, IQR = 51.9-71.3; F:M = 301:350) met inclusion criteria and form the study cohort. Median follow-up time was 75.9 mos (IQR 58.6-99.5). 566 of the 651 (87%) patients underwent resection of their primary RPS, while 85 (13%) did not, most commonly due to suboptimal PS. Of the 566 patients who underwent resection, 259 (46%) had developed a recurrence by the time of last follow-up, while 307 patients (54%) had not recurred. In the 259 patients whose tumor recurred, 49 (19%) recurred within 6 mos of primary RPS resection, 42 (16%) between 7 and 12 mos, 35 (14%) between 13 and 18 mos, 31 (12%) between 19 and 24 mos, and 102 (39%) after 24 mos. Patients who developed recurrence within 6 mos of resection had similar OS from the time of diagnosis to the 85 patients who did not have a resection (1-year estimates: 77.3% [95% CI: 66.4-90.1] vs 65.7% [56.1-76.8], respectively; 2-year estimates: 51.6% [39.1-68.0] vs 42.7% [33.1-55.1], p = 0.32), while patients who relapsed more than 6 mos after resection had longer OS than either of these groups (p < 0.001). Upon MVA, the HR for death in patients who recurred within 6 mos vs. that of patients who were not resected was 0.96 (95% CI: 0.60-1.53). No standard clinico-pathologic variable available preoperatively could be identified that predicted recurrence within 6 mos of primary resection. Neither composite score (Sarculator, IBPI) was able to reliably predict recurrence within 6 mos. Conclusions: DFI from primary RPS resection to first recurrence was less than 6 mos in ≈20% of patients. DFI directly correlated with OS from time of diagnosis. Patients who recurred within 6 mos of resection had an equivalent OS to patients who didn’t undergo resection, raising the question of whether resection was of any benefit. Current efforts focus on discovery of genomic characteristics that reflect adverse biology/host response and are discoverable preoperatively, in order to improve patient selection for surgery and for neoadjuvant therapy.
5502 Background: Treatment options for advanced endometrial cancer after failure of first-line chemotherapy are limited. In the KEYNOTE-158 study, pembro demonstrated durable antitumor activity (ORR, 48%; median DOR, not reached [NR]; median PFS, 13.1 mo; median OS, NR) and an acceptable safety profile in patients (pts) with previously treated advanced microsatellite instability-high/dMMR endometrial cancer. The immune checkpoints TIGIT and PD-L1 are upregulated in several tumor types, including endometrial cancer, and are heavily coexpressed in dMMR tumors, suggesting that dual TIGIT/PD-(L)1 blockade may be an effective therapeutic approach in advanced dMMR endometrial cancer. We present data from cohort B1 of the open-label phase 2 KEYVIBE-005 study (NCT05007106), which evaluated vibo/pembro (anti-TIGIT/anti–PD-1) in pts with previously treated advanced dMMR endometrial cancer. Methods: Eligible pts were aged ≥18 y with advanced dMMR endometrial cancer with progressive disease after 1 platinum-based chemotherapy regimen (or ≤2 lines if 1 was given in the [neo]adjuvant setting), no prior anti–PD-(L)1 therapy, and an ECOG PS of 0 or 1. Pts received vibo 200 mg coformulated with pembro 200 mg Q3W for ≤35 cycles (2 y). The primary end point was ORR per RECIST v1.1 by investigator assessment. Secondary end points included DOR and PFS per RECIST v1.1 by investigator assessment, OS, and safety. Results: A total of 40 pts were enrolled. Median age was 63 y and 60% of pts had ECOG PS 1; 31 pts had previously received 1 line of therapy in any setting and 9 pts had previously received ≥2 lines of therapy in any setting. The median time from first dose to data cutoff (Oct 24, 2023) was 17.2 mo (range, 7.7-23.4). At data cutoff, 23 pts had discontinued treatment and 17 were ongoing. The ORR was 65% (n = 26; 95% CI, 48-79); 5 pts (13%) had a complete response and 21 (53%) had a partial response. Median DOR was 13.7 mo (95% CI, 12.7-NR), and 75% of responders remained in response for ≥12 mo based on the Kaplan-Meier method for censored data. Median PFS was 15.0 mo (95% CI, 8.1-15.6) and the 12-mo PFS rate was 58%. Median OS was NR (95% CI, 16.1-NR) and the 12-mo OS rate was 82%. Treatment-related adverse events (AEs) occurred in 38 pts (95%). Grade 3 or 4 treatment-related AEs occurred in 14 pts (35%), of which the most common were arthritis (5%) and maculopapular rash (5%). Nine pts (23%) discontinued treatment due to a treatment-related AE. Any-grade immune-mediated AEs or infusion reactions occurred in 21 pts (53%) and grade 3 or 4 events occurred in 7 pts (18%). No deaths due to treatment-related AEs or immune-mediated AEs or infusion reactions occurred. Conclusions: Vibo/pembro demonstrated durable antitumor activity and a manageable safety profile in pts with previously treated advanced dMMR endometrial cancer. Clinical trial information: NCT05007106 .
The tropical forest carbon sink is known to be drought sensitive, but it is unclear which forests are the most vulnerable to extreme events. Forests with hotter and drier baseline conditions may be protected by prior adaptation, or more vulnerable because they operate closer to physiological limits. Here we report that forests in drier South American climates experienced the greatest impacts of the 2015–2016 El Niño, indicating greater vulnerability to extreme temperatures and drought. The long-term, ground-measured tree-by-tree responses of 123 forest plots across tropical South America show that the biomass carbon sink ceased during the event with carbon balance becoming indistinguishable from zero (−0.02 ± 0.37 Mg C ha −1 per year). However, intact tropical South American forests overall were no more sensitive to the extreme 2015–2016 El Niño than to previous less intense events, remaining a key defence against climate change as long as they are protected.
Naturalista es una plataforma para registrar e identificar la biodiversidad utilizando inteligencia artificial y la contribución de una comunidad que incluye expertos en distintas disciplinas del conocimiento y aficionados. En este estudio la aplicación Naturalista se utilizó para monitorear la biodiversidad local no doméstica de febrero a junio de 2021 con el objetivo de reforzar el programa de estudios de la materia Ecología en el Centro de Bachillerato Tecnológico agropecuario #147, en Meoqui, Chihuahua, y crear una cultura ambiental que detenga el actual deterioro ambiental del entorno local. El proceso de intervención consistió en el registro de la flora y fauna casera y local, no doméstica, por parte de los estudiantes, para su posterior identificación por la comunidad de Naturalista, la contestación de cuestionarios al inicio y término del proyecto y una bitácora electrónica, para determinar la percepción de conocimiento de la biodiversidad local y la problemática ambiental local. Además, se utilizó el diario docente para el registro y categorización de la información de la investigación. El método investigación-acción se utilizó para documentar el proyecto. En este proyecto se encontró que monitoreando la biodiversidad en un contexto educativo e investigativo se promueve la inclinación del estudiante por el contacto con la naturaleza, se fomenta la interacción interpersonal y emociones positivas y se permite apreciar la diversa problemática ambiental local, incidiendo en el desconocimiento del entorno local y la ingenuidad sobre la biodiversidad en adolescentes, relacionado a periodos largos frente a pantallas.
