Objective The presence of T cells within the epithelial component of tumors, as histologic evidence of anti-tumor immunity, has been associated with a survival advantage in multiple studies across diverse patient cohorts. We performed a meta-analysis of studies evaluating the prognostic value of tumor-infiltrating lymphocytes (TIL) on survival among women with ovarian cancer and to investigate factors associated with variations in this effect, including patient characteristics, surgical outcomes, tumor histology, and study protocols. Method Published studies that evaluated the association between TIL and patient survival were identified. Descriptive statistics, outcome data, and study quality were extracted from studies that met inclusion criteria. Hazard ratios and 95% confidence intervals were pooled across studies using the random-effects model. Publication bias was investigated using a funnel plot and heterogeneity was assessed with subgroup analysis and I2 statistics. Results Ten suitable studies comprising 1,815 patients with ovarian cancer were analyzed. Our results demonstrate that a lack of intraepithelial TILs is significantly associated with a worse survival among patients (pooled HR: 2.24, 95% CI; 1.71–2.91). Variations in the prognostic value of TIL status based on debulking status, scoring method, and geographic regions were identified. Conclusions Intraepithelial TILs are a robust predictor of outcome in ovarian cancer and define a specific class of patients, whose distinct tumor biology should be taken into account in devising appropriate therapeutic strategies.

Opt-out defaults, where clinically appropriate, could be a useful approach for increasing the generalizability of low-risk trials testing behavioral interventions in clinical settings.

Purpose Breast cancer metastases differ biologically from primary disease; therefore, metastatic biopsies may assist in treatment decision-making. Commercial genomic testing of both tumor and circulating tumor DNA have become available clinically, but utility of these tests in breast cancer management remains unclear. Methods Patients undergoing a clinically indicated metastatic tumor biopsy were consented to the ongoing METAMORPH registry. Tumor and blood were collected at time of disease progression before subsequent therapy, and patients were followed for response on subsequent treatment. Tumor testing (n=53) and concurrent cell-free DNA (n=32) in a subset of patients was performed using CLIA-approved assays. Results The proportion of patients with a genomic alteration was lower in tumor than in blood (69% vs 91%; p=0.06). After restricting analysis to alterations covered on both platforms, 83% of tumor alterations were detected in blood, while 90% of blood alterations were detected in tumor. Mutational load specific for the panel genes was calculated for both tumor and blood. Time to progression on subsequent treatment was significantly shorter for patients whose tumors had high panel-specific mutational load (HR 0.31, 95%CI 0.12–0.78) or a TP53 mutation (HR=0.35, 95%CI 0.20–0.79), after adjusting for stage at presentation, hormone receptor status, prior treatment type and number of lines of metastatic treatment. Conclusions Treating oncologists must distinguish platform differences from true biological heterogeneity when comparing tumor and cfDNA genomic testing results. Tumor and concurrent cfDNA contribute unique genomic information in metastatic breast cancer patients, providing potentially useful biomarkers for aggressive metastatic disease.

Between March 5 and July 25, 2020, the total number of SARS-CoV-2 confirmed cases in Bosnia and Herzegovina (BH) was 10 090 corresponding to a cumulative incidence rate of 285.7 per 100 000 population. Demographic and clinical information on all the cases along with exposure and contact information was collected using a standardized case report form. In suspected SARS-CoV-2 cases, respiratory specimens were collected and tested by real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) assay. The dynamic of the outbreak was summarized using epidemiological curves, instantaneous reproduction number Rt and interactive choropleth maps for geographical distribution and spread. The rate of hospitalization was 14.0 % (790/5646) in Federation of Bosnia and Herzegovina (FBH) and 6.2 % (267/4299) in Republic of Srpska (RS). The death rate was 2.2% (122/5646) in FBH and 3.6% in the RS (155/4299). After the authorities lifted mandatory quarantine restrictions, the basic reproduction number increased from 1.13 on May, the 20th to 1.72 on May the 31st. The outbreak concerns both entities, Federation of Bosnia and Herzegovina and Republika Srpska, and it is more pronounced in those aged 20-44 years. It is important to develop the communication and emergency plan for the SARS-CoV-2 outbreak in BH, including the mechanisms to allow the ongoing notification and updates at the national level.