A comparison of the diagnostic utility of the sFlt-1/PlGF ratio versus PlGF alone for the detection of preeclampsia/HELLP syndrome.

OBJECTIVE: The Elecsys(®) immunoassay sFlt-1/PlGF ratio and the Triage(®) PlGF assay were compared (in a prospective, multicenter, case-control study) for diagnosis of preeclampsia/hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. METHODS: Women in European perinatal care centers with singleton pregnancies were enrolled: 178 cases had confirmed preeclampsia and 391 controls had normal outcome. Patients in the preeclampsia/HELLP syndrome group were matched pairwise by gestational week to healthy controls (1:2). Maternal blood samples were analyzed using (a) fully automated Elecsys PlGF and Elecsys sFlt-1 immunoassays with two cutoffs (early-onset [<34 weeks] ≤33, ≥85; late-onset [≥34 weeks] ≤33, ≥110), and (b) Triage PlGF immunoassay (single cutoff). Diagnostic performance and utility were assessed. RESULTS: Respectively, 83 and 95 women had early-onset or late-onset preeclampsia/HELLP syndrome. The overall diagnostic performance of the Elecsys immunoassay sFlt-1/PlGF ratio (area under the curve [AUC] 0.941) was higher than for Triage PlGF (AUC 0.917). The Elecsys immunoassay sFlt-1/PlGF ratio sensitivity and specificity was: 94.0% (95% confidence interval [CI] 86.5-98.0) and 99.4% (95% CI: 96.8-99.9) for early-onset preeclampsia; and 89.5% (95% CI: 81.5-94.8) and 95.4% (95% CI: 91.7-97.8) for late-onset preeclampsia. The Triage assay sensitivity and specificity was: 96.4% (95% CI: 89.8-99.3) and 88.5% (95% CI: 82.8-92.8) (early-onset); and 90.5% (95% CI: 83-96) and 64.5% (95% CI: 57.8-70.9) (late onset). CONCLUSIONS: The fully automated Elecsys immunoassay sFlt-1/PlGF ratio provides improved diagnostic utility over the Triage PlGF assay with improved specificity for the clinical management of pregnant women with suspected preeclampsia/HELLP syndrome.

Maternal serum sFlt-1/PlGF ratio in twin pregnancies with and without pre-eclampsia in comparison with singleton pregnancies.

OBJECTIVE: In singleton pregnancies, soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF) and the sFlt-1/PlGF ratio have shown utility as a diagnostic test for pre-eclampsia (PE). The objective of this study was to characterize the maternal serum levels of sFlt-1, PlGF and sFlt-1/PlGF ratio in normal and pre-eclamptic twin pregnancies. METHODS: In a European multicenter case-control study, 49 women with a twin pregnancy were enrolled, including 31 uneventful and 18 pre-eclamptic pregnancies. sFlt-1 and PlGF were measured and receiver-operating characteristics (ROC) analysis was performed. The median sFlt-1 and PlGF serum concentrations and sFlt-1/PlGF ratio were compared with those of a singleton cohort, matched for gestational age, with PE (n = 54) and with an uncomplicated pregnancy outcome (n = 238). RESULTS: In twin pregnancies with PE, sFlt-1 levels and the sFlt-1/PlGF ratio were increased and PlGF levels were decreased as compared with those of twin gestations with an uneventful pregnancy outcome (20 011.50 ± 2330.35 pg/mL vs 4503.00 ± 2012.05 pg/mL (P ≤ 0.001), 164.22 ± 31.35 vs 13.29 ± 319.64 (P ≤ 0.001), and 138.80 ± 20.04 pg/mL vs 403.00 ± 193.10 pg/mL (P ≤ 0.001), respectively). The sFlt-1/PlGF ratio did not differ between twin pregnancies with PE and singleton pregnancies with PE. In twin pregnancies with an uneventful outcome, sFlt-1 levels and sFlt-1/PlGF ratio were increased, but no differences in PlGF concentration were found when compared with that of singleton controls. ROC analysis determined 53 as an optimal cut-off of the sFlt-1/PlGF ratio for diagnosing PE in twin gestations, yielding a sensitivity of 94.4% and a specificity of 74.2%. The cut-off values established for singleton pregnancies, of 33 and 85, led to sensitivities of 100% and 83.3%, and specificities of 67.7% and 80.6%, when used to detect PE in twin pregnancies. CONCLUSIONS: Significant differences in the serum marker levels in singleton vs twin pregnancies were detected. Reference ranges of sFlt-1, PlGF and their ratio in singleton pregnancies are therefore not transferable to twin pregnancies.

Fractionated external beam radiotherapy of skull base metastases with cranial nerve involvement.

BACKGROUND AND PURPOSE: Skull base metastases frequently appear in a late stage of various tumor entities and cause pain and neurological disorders which strongly impair patient quality of life. This study retrospectively analyzed fractionated external beam radiotherapy (EBRT) as a palliative treatment approach with special respect to neurological outcome, feasibility and acute toxicity. PATIENTS AND METHODS: A total of 30 patients with skull base metastases and cranial nerve disorders underwent EBRT with a mean total dose of 31.6 Gy. Neurological status was assessed before radiotherapy, during radiotherapy and 2 weeks afterwards categorizing orbital, parasellar, middle fossa, jugular foramen and occipital condyle involvement and associated clinical syndromes. Neurological outcome was scored as persistence of symptoms, partial response, good response and complete remission. Treatment-related toxicity and overall survival were assessed. RESULTS: Before EBRT 37 skull base involvement syndromes were determined with 4 patients showing more than 1 syndrome. Of the patients 81.1 % responded to radiotherapy with 10.8 % in complete remission, 48.6 % with good response and 21.6 % with partial response. Grade 1 toxicity of the skin occurred in two patients and grade 1 hematological toxicity in 1 patient under concurrent chemoradiotherapy. Median overall survival was 3.9 months with a median follow-up of 45 months. CONCLUSION: The use of EBRT for skull base metastases with symptomatic involvement of cranial nerves is marked by good therapeutic success in terms of neurological outcome, high feasibility and low toxicity rates. These findings underline EBRT as the standard therapeutic approach in the palliative setting.