Effects of combined spinal–epidural analgesia on first stage of labor: a cohort study

Background: Neuraxial anesthesia is considered as the gold standard in the control labor of pain. Its variants are epidural analgesia and combined spinal–epidural analgesia. Few studies, as yet, have investigated the duration of labor as a primary outcome. Some authors have suggested that combined spinal–epidural analgesia may reduce labor duration but at the moment the benefit of shortening labor is uncertain. The main aim of this study was to compare combined spinal–epidural with epidural analgesia in terms of their effect on duration of stage I labor, maternal, and neonatal outcomes. Methods: A prospective cohort study was conducted. Parturients who requested analgesia at cervical dilatation <6 cm were included. Analgesia was either epidural with low concentration levobupivacaine or combined spinal epidural with subarachnoid sufentanil. The primary outcome was the length of stage I labor. Onset and quality of analgesia, mode of delivery, effects on uterine activity and use of oxytocin, fetal heart rate abnormalities and uterine hyperkinesia, maternal, and neonatal complications were also considered. Results: We enrolled 400 patients: 176 in the combined spinal–epidural group and 224 in the epidural group. Patients in the two treatment groups were similar with regard to demographic characteristics, parity, and incidence of obstetric comorbidities, labor induction, oxytocin infusion, Bishop score, and Visual Analogue Score (VAS) at analgesia request. Duration of stage I labor did not differ, at 195 (120–300) minutes for both the groups (p =.7). Combined spinal–epidural was associated with less reduction in uterine contractility after initial administration: 15.34 versus 39.73%, (p <.001) and with delayed need for oxytocin, at dilations of 7 ± 2.5 cm versus 6. ± 2.7, (p =.002). Onset of analgesia was quicker for combined spinal–epidural analgesia: 31 versus 20%, with VAS <4 after 5 minutes, (p <.001); and lower VAS scores after initial analgesia administration. No differences were found in the other outcomes. Conclusions: Combined spinal–epidural with subarachnoid sufentanil may not reduce the duration of stage I labor, but in our study it appeared to affect uterine contractility less. It also had a more rapid onset and was more effective, without any concomitant increase in maternal or neonatal complications

Immune biomarkers predictive for disease-free survival with adjuvant sunitinib in high-risk locoregional renal cell carcinoma: from randomized phase III S-TRAC study

Purpose: Adjuvant sunitinib therapy compared with placebo prolonged disease-free survival (DFS) in patients with locoregional high-risk renal cell carcinoma in the S-TRAC trial (ClinicalTrials.gov number, NCT00375674). A prospectively-designed exploratory analysis of tissue biomarkers was conducted to identify predictors of treatment benefit. Experimental Design: Tissue blocks were used for immunohistochemistry (IHC) staining of PD-L1, CD4, CD8, and CD68. DFS was compared between < versus ≥ median IHC parameter using the Kaplan–Meier method. For biomarkers with predictive potential, Receiver Operating Characteristics curves were generated. Results: Baseline characteristics were similar in patients with (n=191) and without (n=419) IHC analysis. Among patients with IHC, longer DFS was observed in patients with tumor CD8+ T-cell density ≥ versus < median (median [95% CI], not reached [6.83–not reached] vs. 3.47 years [1.73–not reached]; hazard ratio 0.40 [95% CI, 0.20–0.81]; P=0.009) treated with sunitinib (n=101), but not with placebo (n=90). The sensitivity and specificity for CD8+ T-cell density in predicting DFS were 0.604 and 0.658, respectively. Shorter DFS was observed in placebo-treated patients with PD-L1+ versus PD-L1– tumors (hazard ratio 1.75; P=0.103). Among all patients with PD-L1+ tumors, DFS was numerically longer with sunitinib versus placebo (hazard ratio 0.58; P=0.175). Conclusions: Greater CD8+ T-cell density in tumor tissue was associated with longer DFS with sunitinib but not placebo, suggesting predictive treatment effect utility. Further independent cohort validation studies are warranted. The prognostic value of PD-L1 expression in primary tumors from patients with high-risk non-metastatic renal cell carcinoma should also be further explored

Adjuvant Sunitinib in High-Risk Renal-Cell Carcinoma after Nephrectomy

BACKGROUND Sunitinib, a vascular endothelial growth factor pathway inhibitor, is an effective treatment for metastatic renal-cell carcinoma. We sought to determine the efficacy and safety of sunitinib in patients with locoregional renal-cell carcinoma at high risk for tumor recurrence after nephrectomy. METHODS In this randomized, double-blind, phase 3 trial, we assigned 615 patients with locoregional, high-risk clear-cell renal-cell carcinoma to receive either sunitinib (50 mg per day) or placebo on a 4-weeks-on, 2-weeks-off schedule for 1 year or until disease recurrence, unacceptable toxicity, or consent withdrawal. The primary end point was disease-free survival, according to blinded independent central review. Secondary end points included investigator-assessed disease-free survival, overall survival, and safety. RESULTS The median duration of disease-free survival was 6.8 years (95% confidence interval [CI], 5.8 to not reached) in the sunitinib group and 5.6 years (95% CI, 3.8 to 6.6) in the placebo group (hazard ratio, 0.76; 95% CI, 0.59 to 0.98; P=0.03). Overall survival data were not mature at the time of data cutoff. Dose reductions because of adverse events were more frequent in the sunitinib group than in the placebo group (34.3% vs. 2%), as were dose interruptions (46.4% vs. 13.2%) and discontinuations (28.1% vs. 5.6%). Grade 3 or 4 adverse events were more frequent in the sunitinib group (48.4% for grade 3 events and 12.1% for grade 4 events) than in the placebo group (15.8% and 3.6%, respectively). There was a similar incidence of serious adverse events in the two groups (21.9% for sunitinib vs. 17.1% for placebo); no deaths were attributed to toxic effects. CONCLUSIONS Among patients with locoregional clear-cell renal-cell carcinoma at high risk for tumor recurrence after nephrectomy, the median duration of disease-free survival was significantly longer in the sunitinib group than in the placebo group, at a cost of a higher rate of toxic events. (Funded by Pfizer; S-TRAC ClinicalTrials.gov number, NCT00375674.)</p