NGS for (Hemato-) Oncology in Belgium: Evaluation of Laboratory Performance and Feasibility of a National External Quality Assessment Program

Next-generation sequencing (NGS) is being integrated into routine clinical practice in the field of (hemato-) oncology to search for variants with diagnostic, prognostic, or therapeutic value at potentially low allelic frequencies. The complex sequencing workflows used require careful validation and continuous quality control. Participation in external quality assessments (EQA) helps laboratories evaluate their performance and guarantee the validity of tests results with the ultimate goal of ensuring high-quality patient care. Here, we describe three benchmarking trials performed during the period 2017–2018 aiming firstly at establishing the state-of-the-art and secondly setting up a NGS-specific EQA program at the national level in the field of clinical (hemato-) oncology in Belgium. DNA samples derived from cell line mixes and artificially mutated cell lines, designed to carry variants of clinical relevance occurring in solid tumors, hematological malignancies, and BRCA1/BRCA2 genes, were sent to Belgian human genetics, anatomic pathology, and clinical biology laboratories, to be processed following routine practices, together with surveys covering technical aspects of the NGS workflows. Despite the wide variety of platforms and workflows currently applied in routine clinical practice, performance was satisfactory, since participating laboratories identified the targeted variants with success rates ranging between 93.06% and 97.63% depending on the benchmark, and few false negative or repeatability issues were identified. However, variant reporting and interpretation varied, underlining the need for further standardization. Our approach showcases the feasibility of developing and implementing EQA for routine clinical practice in the field of (hemato-) oncology, while highlighting the challenges faced.

External Evaluation of the Quality of the Seven Biochemical Parameters in Antananarivo in 2020

The aim of the present study is to assess the performance of the biochemistry laboratory of Joseph Ravoahangy Andrianavalona by the dosage of the most prescribed 7 biochemical parameters. It is a retrospective evaluative study of the performance of the biochemistry laboratory of Joseph Ravoahangy Andrianavalona University Hospital Center on a period of 6 months from January 2020 to June 2020 involving 12 samples of External Evaluation of the Quality provided by the Quality Insurance Association of the clinical Biology Laboratories in France. Uremia, Serum creatinine, blood glucose, natremia, kaliemia, chlorure and were dosed on the 12 samples which carried out 84 dosages. During a period of 6 months the accuracy was 97.61%. The precision had been 100% if the Variation Coefficient Ratio (VCR) was below 1.50. This participation in the External Evaluation of the Quality program can then improve the quality of the laboratory. It is a step towards the accreditation process.

Identification of serum cytokine clusters associated with outcomes in ovarian clear cell carcinoma

Serum cytokine and chemokine networks may reflect the complex systemic immunological interactions in cancer patients. Studying groups of cytokines and their networks may help to understand their clinical biology. A total of 178 cases of ovarian cancer were analyzed in this study, including 73 high-grade serous (HGSC), 66 clear cell (CCC) and 39 endometrioid carcinomas. Suspension cytokine arrays were performed with the patients’ sera taken before the primary surgery. Associations between each cytokine and clinicopathological factors were analyzed in all patients using multivariate linear regression models, and cluster analyses were performed for each histotype. In the multivariate analyses, twelve of 27 cytokines were correlated with histotypes. Cluster analyses in each histotype revealed 2 cytokine signatures S1 and S2 in HGSC, and similarly C1 and C2 in CCC. Twenty-two of 27 cytokines were commonly clustered in HGSC and CCC. Signature S1 and C1 included IL-2,6,8,15, chemokines and angiogenic factors, whereas signature S2 and C2 included IL-4,5,9,10,13, TNF-α and G-CSF. Four subgroups based on a high or low level for each signature were identified, and this cluster-based classification demonstrated significantly different progression-free and overall survivals for CCC patients (P = 0.00097 and P = 0.017).

FIP VIRTUAL 2020 Pharmaceutical Practice: Clinical Biology, Military & Emergency Pharmacy

Accepted abstracts under the theme: CLINICAL BIOLOGY, MILITARY & EMERGENCY PHARMACY (n=12)

External quality assessment for molecular diagnostic laboratories in Belgium: Can we improve it?

External quality assessment (EQA) is an essential part of performance monitoring for molecular laboratories. At the moment, a national law regulates participation in EQA schemes for clinical biology and pathology in Belgium. This study aimed (1) to get insights on how laboratories organize their EQA participation, (2) to poll satisfaction with the current situation (selection of EQA programs in advance by a governmental body), (3) to provide guidance for choosing the most relevant EQA provider and (4) to propose a new model for national performance monitoring. A survey was sent to Belgian laboratories performing molecular tests in the field of microbiology, hematology and pathology with (1) general questions on how they select an EQA provider and (2) their satisfaction of each provider. In total, 25 molecular laboratories [microbiology (N = 13), hematology (N = 8) and pathology (N = 4)] from 14 different hospitals completed the survey regarding their EQA organization. All three laboratory groups indicated to prefer EQA schemes using real patient materials as well as those with varying targets and concentrations. For molecular microbiology and hematology, schemes with a syndromic approach are sought. Since annual participation in EQA becomes burdensome in most laboratories, this paper also offers a risk-based strategy for determining the participation frequency. Based on the needs of Belgian laboratories, three proposals were made: (1) for the proper selection of an EQA scheme, (2) for determining the minimal participation frequency and (3) for the national organization of EQA schemes.

Parasitology, Poverty and Prevention: is there any relationship between the three P? Is it possible to eradicate Parasitic diseases without eliminating Poverty?

ContextTalking about Poverty is not obvious without examples, I would like to understand the link between Parasitology, Poverty and Prevention (the three P). I explain the three P by saying that there is four level of knowledge in Parasitology and the fourth level is the integration with other disciplines including virology with preventive measures, nutrition aspects with denutrition leading by some parasites as Ascaris, economy involving patient’s income and Poverty. As a reminder, the first level in Parasitology is the knowledge of the parasitic cycle with an emphasis on the mode of contamination, the second level is that of the implementation of technical or diagnostic means to identify the parasite in the laboratory or the bench and the third level is that of treating infected cases diagnosed in the laboratory.ObjectiveThe objective of this work is to contribute to reach the first sustainable development goal i.e. no Poverty. Specifically, this manuscript aimed to evaluate poverty with the protective measures against the harmful effects of mosquitoes that contribute to the quality of care given to patients of the University Hospital of Kinshasa (UHK).FindingsResidual mosquito capture, carried out in 31 randomly selected rooms per block and per level in hospital departments, presented the number of 1,144 female mosquitoes (845 Culex, 207 Anopheles and 62 Aedes). Overall considered, the Mean Mosquito Density (MMD) was 36.2 / mosquito per room (6.9 Anopheles / room, 29.1 Culex / room and 2.1 Aedes / room with an extreme between 0 and 144 mosquitoes / room. The lowest MMD (6.2 mosquitoes / room) was observed in Block II (clinical biology and microbiology laboratories, delivery and private hospitalization rooms) compared to other hospital blocks that had the highest MMD and statistically identical (ranging between 29.2 and 45.5 mosquitoes / room).Our observations give a good idea of Poverty inside this hospital and where to concentrate in the prevention of malaria transmission within the hospital. Regardless of the block considered, it was the ground floor with an MMD of 52.8 mosquitoes / room which were the most dangerous places compared with the first and second floors with MMD respectively 17.6 and 25.6 mosquitoes / room.ConclusionIn conclusion, the insufficiency of the UHK anti-mosquito measures was obvious. These should be applied without delay to prevent the risk of infection transmission by mosquitoes, even within the hospital, of hepatitis B virus and strains of Plasmodium falciparum, sometimes highly virulent, which may be concentrated there.LimitsWe were on the right track and this study needs more research because of its limitations: we investigate and did not find if any of the mosquitoes collected were infected; we did not investigate if the hospital had any patients with a mosquito transmitted disease in the rooms where the mosquitoes were collected.RecommendationThe recommendation is if it is not possible to eradicate parasitic diseases as malaria without eliminating poverty, then we need to eliminate them both.

Lobular Breast Cancer

Invasive lobular carcinoma (ILC) is the second most common type of breast cancer, with a unique pathogenesis and distinct clinical biology. These cancers display a characteristic loss of E-cadherin, and the vast majority are estrogen receptor positive (ER+), with a low-to-intermediate grade. These features generally portend a favorable prognosis, but there is a propensity for late recurrences and metastasis to atypical locations. These infiltrative tumors can be more clinically challenging than the more common ductal cancers. Their insidious nature can make them more difficult to diagnose, and they may show a differing response to standard therapies, keeping with the predominantly ER+ phenotype. Although ILC patients comprise a small minority in large breast cancer trials, most fundamentals of locoregional and systemic therapy presently remain shared between all cancer types. Recognizing the nuances of treating ILC remains important, and the recent discovery of novel mutations that are more frequently expressed in ILC holds promise for further investigations into lobular-specific targeted therapies. This review 3 figures, 8 tables and 50 references Key words: aromatase inhibitors, breast cancer, breast conservation, chemotherapy, E-cadherin, invasive lobular carcinoma, mastectomy, The Cancer Genome Analysis