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OBJECTIVES: To determine clinical significance of preoperative and pre-chemotherapy CA-125 in high-risk early-stage epithelial ovarian cancer patients. METHODS: All patients with stage IA/IB and grade 3, stage IC, clear cell, or completed resected stage II cancer were enrolled in a phase III trial and treated with chemotherapy. Kaplan-Meier method and Cox proportional hazards model were used for statistical analyses. RESULTS: 427 patients with high-risk early-stage ovarian cancer were enrolled. Of 213 patients with preoperative CA-125 data, 79% had elevated CA-125. Median preoperative CA-125 level was 103 U/mL. Patients with ≤10, 11-15, and > 15 cm tumors had median preoperative CA-125 levels of 62, 131 and 158 U/mL, respectively (p = 0.002). For the 350 patients with data for pre-chemotherapy CA-125 level, 69% had elevated pre-chemotherapy CA-125 above 35 U/mL with median value of 65 U/mL. However, age, race, stage, cell type and grade of disease were not correlated with CA-125 levels before and after surgery. On multivariate analysis, elevated pre-chemotherapy CA-125 independently predicted worse recurrence-free survival (HR = 2.13, 95% CI: 1.23-3.69; p = 0.007) and overall survival (HR = 1.99, 95% CI: 1.10-3.59; p = 0.022) after adjusting for age, stage, cell type and grade of disease. Compared to those with normal CA-125, patients with elevated pre-chemotherapy CA-125 had lower recurrence-free survival (RFS, 87% vs. 75%; p = 0.007) and overall survival (OS, 88% vs. 82%; p = 0.02). However, preoperative CA-125 was not prognostic of RFS (p = 0.699) or OS (p = 0.701). CONCLUSIONS: Preoperative CA-125 was elevated in nearly 80% of high-risk early-stage ovarian cancer patients. Pre-chemotherapy CA-125 was associated with recurrence-free and overall survival; however, preoperative CA-125 was not prognostic.
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Neoplasias Ovarianas , Feminino , Humanos , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/patologia , Análise Multivariada , Estadiamento de Neoplasias , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Prognóstico , Estudos RetrospectivosRESUMO
OBJECTIVE: Investigate racial disparities in outcomes and molecular features in Black and White patients with endometrioid endometrial carcinoma (EEC). METHODS: Black and White patients diagnosed with EEC who underwent hysterectomy ± adjuvant treatment in SEER, National Cancer Database (NCDB), the Genomics Evidence Neoplasia Information Exchange (GENIE) project (v.13.0), and eight NCI-sponsored randomized phase III clinical trials (RCTs) were studied. Hazard ratio (HR) and 95% confidence interval (CI) were estimated for cancer-related death (CRD), non-cancer death (NCD), and all-cause death. RESULTS: Black (n = 4397) vs. White (n = 47,959) patients in SEER had a HR (95% CI) of 2.04 (1.87-2.23) for CRD and 1.22 (1.09-1.36) for NCD. In NCDB, the HR (95% CI) for death in Black (n = 13,468) vs. White (n = 155,706) patients was 1.52 (1.46-1.58) dropping to 1.29 (1.23-1.36) after propensity-score matching for age, comorbidity, income, insurance, grade, stage, LVSI, and treatment. In GENIE, Black (n = 109) vs. White (n = 1780) patients had fewer PTEN, PIK3R1, FBXW7, NF1, mTOR, CCND1, and PI3K-pathway-related gene mutations. In contrast, TP53 and DNA-repair-related gene mutation frequency as well as tumor mutational burden-high status were similar in Black and White patients. In RCTs, Black (n = 187) vs. White (n = 2877) patients were more likely to have advanced or recurrent disease, higher grade, worse performance status and progressive disease. Risk of death in Black vs. White patients in RCTs was 2.19 (1.77-2.71) persisting to 1.32 (1.09-1.61) after matching for grade, stage, and treatment arm while balancing age and performance status. CONCLUSIONS: Differences exist in clinical presentation, outcomes, and molecular features in Black vs. White patients with EEC in real-world registries and RCTs. Targeted-drug development, strategies to modify social determinants, and diverse inclusion in RCTs are approaches to reduce disparities.
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Negro ou Afro-Americano , Carcinoma Endometrioide , Progressão da Doença , Neoplasias do Endométrio , População Branca , Humanos , Feminino , População Branca/estatística & dados numéricos , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/terapia , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/etnologia , Carcinoma Endometrioide/mortalidade , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/terapia , Neoplasias do Endométrio/etnologia , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Pessoa de Meia-Idade , Negro ou Afro-Americano/estatística & dados numéricos , Idoso , Ensaios Clínicos Controlados Aleatórios como Assunto , Estados Unidos/epidemiologia , Programa de SEER , Sistema de Registros , Ensaios Clínicos Fase III como Assunto , AdultoRESUMO
PREMISE: In frequently burned southeastern USA pine-grassland communities, wiregrass (Aristida stricta and A. beyrichiana) are dominant bunchgrasses whose flowers are infected during flowering by a smut fungus (Langdonia walkerae). We hypothesized that because prescribed fire timing affects wiregrass flowering patterns, it could affect smut incidence (occurrence of smut on plants) and severity of infection in inflorescences and spikelets. Because soil order could influence plant susceptibility, we hypothesized that these patterns would differ between soil orders. We hypothesized differences between species as representative of geographic variation in this ecosystem. METHODS: We surveyed the incidence and severity of L. walkerae in wiregrass populations (85 populations at 14 sites) that had been prescription burned at different times during the previous year. We used binomial regressions to test whether incidence and severity differed by burn day, soil order, or species, with site as a random effect. RESULTS: Fires that occurred in the winter were associated with significantly lower incidence than fires later in the year (as the months progressed into summer). Plants growing on Spodosol soils were significantly less likely to be infected than those on other soils. More variation in incidence, however, was explained by site, suggesting that site-specific characteristics were important. Smut severity in inflorescences and spikelets was greater overall in populations of A. stricta than in southern populations (A. beyrichiana). CONCLUSIONS: Our findings indicate that fire timing and soil order affect L. walkerae incidence in wiregrass plants, but neither appears to be associated with greater severity. Patterns of smut infection are related to site history and geographic variation.
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Ecossistema , Incêndios , Incidência , Poaceae , Solo , FungosRESUMO
PURPOSE: The interleukin-6/Janus kinase (JAK)/signal transducers and activators of transcription 3 axis is a reported driver of chemotherapy resistance. We hypothesized that adding the JAK1/2 inhibitor ruxolitinib to standard chemotherapy would be tolerable and improve progression-free survival (PFS) in patients with ovarian cancer in the upfront setting. MATERIALS AND METHODS: Patients with ovarian/fallopian tube/primary peritoneal carcinoma recommended for neoadjuvant chemotherapy were eligible. In phase I, treatment was initiated with dose-dense paclitaxel (P) 70 mg/m2 once daily on days 1, 8, and 15; carboplatin AUC 5 intravenously day 1; and ruxolitinib 15 mg orally (PO) twice a day, every 21 days (dose level 1). Interval debulking surgery (IDS) was required after cycle 3. Patients then received three additional cycles of chemotherapy/ruxolitinib, followed by maintenance ruxolitinib. In the randomized phase II, patients were randomly assigned to paclitaxel/carboplatin with or without ruxolitinib at 15 mg PO twice a day for three cycles, IDS, followed by another three cycles of chemotherapy/ruxolitinib, without further maintenance ruxolitinib. The primary phase II end point was PFS. RESULTS: Seventeen patients were enrolled in phase I. The maximum tolerated dose and recommended phase II dose were established to be dose level 1. One hundred thirty patients were enrolled in phase II with a median follow-up of 24 months. The regimen was well tolerated, with a trend toward higher grade 3 to 4 anemia (64% v 27%), grade 3 to 4 neutropenia (53% v 37%), and thromboembolic events (12.6% v 2.4%) in the experimental arm. In the randomized phase II, the median PFS in the reference arm was 11.6 versus 14.6 in the experimental, hazard ratio (HR) for PFS was 0.702 (log-rank P = .059). The overall survival HR was 0.785 (P = .24). CONCLUSION: Ruxolitinib 15 mg PO twice a day was well tolerated with acceptable toxicity in combination with paclitaxel/carboplatin chemotherapy. The primary end point of prolongation of PFS was achieved in the experimental arm, warranting further investigation.