Colorectal cancer is the second most common cancer in Europe. Most antineoplastic regimens in first-line treatment involve 5-fluorouracil or oral prodrug capecitabine, combined with other antineoplastic agents such as oxaliplatin or irinotecan. It is well known that 5-fluorouracil and capecitabine are agents that can be toxic in cases of decreased dihydropyrimidine dehydrogenase activity because this enzyme is the main limiting factor in the metabolism of both agents. In this paper, we describe the case of a patient who developed severe toxicity to 5-fluouracil and who had a mutation in the gene encoding the enzyme dihydropyrimidine dehydrogenase.

The assessed protocol has shown to be a very fast and economical approach to perform genetic analyses in the clinical laboratory for pharmacological purposes.

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Background Therapeutic drug monitoring (TDM) is a valuable tool to optimize anti-TNF biologics in inflammatory bowel disease (IBD). However, for the non-anti-TNF agents (such as Ustekinumab-UST- an anti-IL12/23) TDM value and evidence in real-world IBD patients is scarce although emerging data suggest that higher drug concentration (>4.5 µg/ml) of these biologics agents predicts better clinical outcomes. We evaluated associations between UST levels and clinical outcomes in real-world IBD patients. Methods A cross-sectional study was performed in IBD patients who received maintenance therapy (≥16 weeks) with UST and followed in our IBD unit between June 2020 and May 2021. UST trough concentration was assessed at the time of inclusion and clinical outcome were reviewed by starting UST use (PRE), at the time of blood extraction (inclusion-EXT), and after 6 months of follow-up (POST). Clinical response was determined by Harvey-Bradshaw Index (HBI) (clinical remission; HBI≤4 points or pMayo ≤2 points) and biochemical response by fecal calprotectin (FC) (biochemical response CF>50 % reduction from basal value and biochemical remission CF <150 g/kg). The need for surgery, intensification, or change of treatment at the end of the follow-up was registered. Results A total of 62 patients (53.2% male; mean age 46 (41-50) years; Crohn’s disease n=57/ ulcerative colitis n=3/indeterminate colitis n=2) were included. The time from diagnosis to initiation of UST treatment was 149 (122-176) months. 35.5% of patients received co-treatment with immunosuppressors and 95,6% had received previous biologic agents (15,6% more than 2 previous biologics). The mean time of UST use was 13 (10-16) months. The mean UST level was established at 7.1 µg/ml (SD 4.3) with higher levels in intensified patients (UST every 4 weeks; n=17) at the time of extraction (9.4 µg/ml (4.3) vs. 6.2 µg/ml (4.0); p= 0.03). However, no differences were found in UST levels between patients achieving clinical remission (n=52,83.9%)) compared to non-responders (7.2 µg/ml (4.4) vs. 6.7 µg/ml (4.4), respectively; p=0. 71); nor in those achieving biological remission at 6 months (n= 31, 56.4%)) compared to non-responders ((7.0 µg/ml (4) vs 6.6 µg/ml (4.5), respectively; p= 0.7). Only 2 patients discontinued UST treatment and 7 patients needed to intensify treatment every 4 weeks during follow-up. In logistic regression analysis, the UST level lower than 4.5 µg/ml showed an independent predictive value for the need for UST intensification in the subsequent 6 months (OR 5.7, 95% CI 1.01-32.9). Conclusion UST is an effective drug for achieving clinical and biological remission in patients with IBD. UST level (<4.5 µg/ml ) may guide the need for treatment intensification at 6 months.

Background: The DNA-damage repair (DDR) system is essential for the preservation of genomic stability. Deleterious somatic and germline mutations involved in DDR pathway confer sensitivity to poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitions and implicate prognosis. However, few data explored the spectrum of DDR pathways in Chinese patients with prostate cancer.Methods: A total of 982 patients conducted genetic testing by next-sequencing (NGS) technology were used for screening. A hundred and eighty-seven DDR genes were analyzed. Deleterious mutations were defined as pathogenic or likely pathogenic alterations. Only patients with qualified tissue NGS results performed by 381-and 733 gene panel were included in the following study. Matched blood sample were used for germline detection. Data analyses were conducted by R 3.6.2. abstracts Annals of Oncology Volume 31 -Issue S4 -2020 S533

Background/Aim: L-Asparaginase (L-ASNase) is used as a tumor-inhibitory drug on paediatric acute lymphoblastic leukemia (ALL). ERW-ASNase is commercialised as a lyophilized powder stable only for 8 hours once reconstituted and, consequently, the leftover is usually discarded. The aim of this study will be to analyse the stability of the reconstituted lyophilised ERW-ASNase. Materials and Methods: In the present study, we analysed the enzymatic stability of reconstituted ERW-ASNase after conservation in three different temperature conditions for 2 and 5 days. Results: Our results show that ERW-ASNase is stable at 4˚C,-20˚C and-80˚C for up to 5 days, retaining 95% of the initial enzymatic activity in all three storage temperatures tested. Conclusion: It is feasible to reuse the remaining content of ERW-ASNase vial after reconstitution, which allows the optimization of the content of ERW-ASNase vials use and reduces the cost of this formulation usage, making it more accessible.

D.M.A contributed to data collection, database generation, statistical analysis, writing and editing of the manuscript. F.B.Z assisted with data collection and database generation. F.D.F assisted with data collection from the laboratory and sample analysis. M.J.M.A, L.G.S and V.P.P. contributed to the screening and sample collection from the drug treatment centres. F.G.N collaborated with the analysis of the samples. M.H.G. contributed to the project design, coordination and final review and manuscript approval.

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