Pediatric Emergency Department Resource Utilization among Children with Primary Care Clinic Contact in the Preceding 2 Days: A Cross-Sectional Study.

OBJECTIVES: To characterize pediatric patient contacts with their primary care clinic in the 2 days preceding a visit to the emergency department (ED) and explore how the type of clinic contact relates to ED resource use. STUDY DESIGN: We conducted a retrospective chart review of 368 pediatric ED visits in the first 7 days of each month, from September 2012 to August 2013. Visits were included if the family contacted their child's general pediatric clinic in the study health system in the 2 days preceding the ED visit. Descriptive statistics were calculated. Primary outcomes were ED resource use (tests, treatments) and disposition (admission or discharge). Outcomes by type of clinic contact were compared with χ2 statistics. RESULTS: Of 1116 records with ED visits in the 12 study weeks extracted from the electronic medical record, 368 ED visits met inclusion criteria. Most ED visits followed a single clinic contact (78.8%). Of the 474 clinic contacts, 149 were in-person visits, 216 phone calls when clinic was open, and 109 phone calls when clinic was closed. ED visits that followed an in-person clinic contact with advice to go to the ED had significantly greater rates of testing and admission than those advised to go to the ED after phone contact and those never advised to go to the ED. CONCLUSIONS: In-person clinic visits with advice to go to the ED were associated with the greatest ED resource use. Limitations include a study of a single health system without a uniform process for triaging patients to the ED across clinics.

Prostate-Specific Membrane Antigen (PSMA) Expression in Tumor-Associated Neovasculature Is an Independent Prognostic Marker in Patients with Ovarian Cancer.

Prostate-specific membrane antigen (PSMA) is present in the tumor-associated neovasculature of many cancer types. Current data in ovarian cancer are limited and controversial; thus, the aim of this study was to investigate PSMA expression in a larger and homogenous patient cohort. This might lead to further studies investigating the use of imaging and therapeutic modalities targeting PSMA. Eighty patients with advanced stage high-grade serous ovarian cancers were included. Using immunohistochemistry, PSMA and CD31, a marker for endothelial cells, were examined in whole tissue sections. Percentage and intensity of PSMA expression were determined in the neovasculature. Expression levels were correlated with clinicopathological parameters and survival. Low (≤10%), medium (20-80%), and high (≥90%) PSMA expression was found in 14, 46, and 20 ovarian cancer samples, respectively. PSMA expression was confined to tumor-associated neovasculature and significantly correlated with progression-free (HR 2.24, 95% CI 1.32-3.82, p = 0.003) and overall survival (HR 2.73, 95% CI 1.41-5.29, p = 0.003) in multivariate models, considering age, FIGO stage, and residual disease. This is the first study showing a clinical relevance for PSMA in patients with ovarian cancer. PSMA was detected in the vast majority of cancer samples and showed an impact on survival.

Corrected Allele Frequency of BRCA1/2 Mutations Is an Independent Prognostic Factor for Treatment Response to PARP-Inhibitors in Ovarian Cancer Patients.

PARP inhibitors (PARPi) have increased treatment options in ovarian cancer, particularly in patients with BRCA1/2 mutations, although there are still marked differences in the duration of patients' response to this targeted therapy. BRCA testing is routinely performed in tumor tissue of ovarian cancer patients. The resulting molecular pathological findings include the genetic nomenclature of the mutation, the frequency of the mutated allele (variant allele frequency, VAF), and the tumor cell content. VAF measures the percentage of mutated alleles from the total alleles in the cells of the examined tissue. The aim of this study was to investigate the significance of VAF on the therapeutic response to PARPis in ovarian cancer patients. Epithelial ovarian cancer patients harboring BRCA1/2 tumor mutations, who underwent germline testing and received PARPi therapy at the Medical University of Vienna (n = 41) were included in the study. Corrected VAF (cVAF) was calculated based on VAF, tumor cell content, and germline mutation. Patients were divided into two groups based on their cVAF. Median PFS under PARPi in patients with low cVAF was 13.0 months (IQR [10.3-not reached]) and was not reached in the high cVAF group. High cVAF was significantly associated with longer PFS in the multivariate analysis (HR = 0.07; 95% CI [0.01-0.63]; p = 0.017). In conclusion, high cVAF was associated with a significantly better response to PARPi in this study population.

Detection of EGFR Activating and Resistance Mutations by Droplet Digital PCR in Sputum of EGFR-Mutated NSCLC Patients.

BACKGROUND: Proof of the T790M resistance mutation is mandatory if patients with EGFR-mutated non-small cell lung cancer (NSCLC) progress under first- or second-generation tyrosine kinase inhibitor therapy. In addition to rebiopsy, analysis of plasma circulating tumor DNA is used to detect T790M resistance mutation. We studied whether sputum is another feasible specimen for detection of EGFR mutations. METHODS: Twenty-eight patients with advanced EGFR-mutated NSCLC were included during stable and/or progressive disease. The initial activating EGFR mutations (exon 19 deletions or L858R mutations) at stable disease and at progressive disease (together with T790M) were assessed in simultaneously collected plasma and sputum samples and detected by droplet digital polymerase chain reaction (ddPCR). RESULTS: Activating EGFR mutations were detected in 47% of the plasma samples and 41% of sputum samples during stable disease, and in 57% of plasma samples and 64% of sputum samples during progressive disease. T790M was detected in 44% of the plasma samples and 66% of the sputum samples at progressive disease. In ddPCR T790M-negative results for both specimens (plasma and sputum), negativity was confirmed by rebiopsy in 5 samples. Concordance rate of plasma and sputum for T790M was 0.86, with a positive percent agreement of 1.0 and a negative percent agreement of 0.80. CONCLUSIONS: We demonstrated that EGFR mutation analysis with ddPCR is feasible in sputum samples. Combination of plasma and sputum analyses for detection of T790M in NSCLC patients with progressive disease increases the diagnostic yield compared with molecular plasma analysis alone.

Prognostic Significance of SLFN11 Methylation in Plasma Cell-Free DNA in Advanced High-Grade Serous Ovarian Cancer.

BACKGROUND: Epigenetic alterations in ctDNA are highly promising as a source of novel potential liquid biopsy biomarkers and comprise a very promising liquid biopsy approach in ovarian cancer, for early diagnosis, prognosis and response to treatment. METHODS: In the present study, we examined the methylation status of six gene promoters (BRCA1, CST6, MGMT, RASSF10, SLFN11 and USP44) in high-grade serous ovarian cancer (HGSOC). We evaluated the prognostic significance of DNA methylation of these six gene promoters in primary tumors (FFPEs) and plasma cfDNA samples from patients with early, advanced and metastatic HGSOC. RESULTS: We report for the first time that the DNA methylation of SLFN11 in plasma cfDNA was significantly correlated with worse PFS (p = 0.045) in advanced stage HGSOC. CONCLUSIONS: Our results strongly indicate that SLFN11 epigenetic inactivation could be a predictor of resistance to platinum drugs in ovarian cancer. Our results should be further validated in studies based on a larger cohort of patients, in order to further explore whether the DNA methylation of SLFN11 promoter could serve as a potential prognostic DNA methylation biomarker and a predictor of resistance to platinum-based chemotherapy in ovarian cancer.

Precision Medicine Tumor Boards: Clinical Applicability of Personalized Treatment Concepts in Ovarian Cancer.

BACKGROUND: Treating cancer according to its molecular alterations (i.e., targeted treatment, TT) is the goal of precision medicine tumor boards (PTBs). Their clinical applicability has been evaluated for ovarian cancer patients in this analysis. METHODS: All consecutive ovarian cancer patients discussed in a PTB at the Medical University of Vienna, Austria, from April 2015 to April 2019 were included (n = 44). RESULTS: In 38/44 (86%) cases, at least one mutation, deletion or amplification was detected. The most frequently altered genes were p53 (64%), PI3K pathway (18%), KRAS (14%), BRCA1 (11%) and BRCA2 (2%). In 31 patients (70%) a TT was recommended. A total of 12/31 patients (39%) received the recommended therapy. Median time from indication for PTB to TT start was 65 days (15-216). Median time to treatment failure was 2.7 months (0.2-13.2). Clinical benefit rate (CBR) was 42%. Reasons for treatment discontinuation were disease progression (42%), poor performance status (PS > 2; 25%), death (17%) or treatment related side effects (8%). In 61% the TT was not administered-mainly due to PS > 2. CONCLUSION: Even though a TT recommendation can be derived frequently, clinical applicability remains limited due to poor patients' general condition after exploitation of standard treatment. However, we observed antitumor activity in a substantial number of heavily pretreated patients.