IntroductionGlioblastoma multiforme (GBM) represents the most malignant primary brain tumor characterized by pathological vascularization. Mutations in isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) were observed in GBM. We aimed to assess the intra-tumor hypoxia, angiogenesis and microvessel formation in GBM and to find their associations with IDH1 mutation status and patients prognosis.Methods52 patients with a diagnosis of GBM were included into the study. IDH1 R132H mutation was assessed by RT-PCR from FFPE tumor samples obtained during surgery. The expression of markers of hypoxia (HIF2α), angiogenesis (VEGF), tumor microvascularity (CD31, CD34, vWF, CD105), and proliferation (Ki-67) were assessed immunohistochemically (IHC). IDH1 mutation and IHC markers were correlated with the patient survival.Results20 from 52 GBM tumor samples comprised IDH1 R132H mutation (38.5%). The majority of mutated tumors were classified as secondary glioblastomas (89.9%). Patients with IDH1 mutated tumors experienced better progression-free survival (P = 0.037) as well as overall survival (P = 0.035) compared with wild type tumors. The significantly lower expression of VEGF was observed in GBM with IDH1 mutation than in wild type tumors (P = 0.01). No such association was found for microvascular markers. The increased expression of newly-formed microvessels (ratio CD105/CD31) in tumor samples was associated with worse patient’s progression-free survival (P = 0.026).SummaryNo increase in HIF/VEGF-mediated angiogenesis was observed in IDH1-mutated GBM compared with IDH1 wild type tumors. The histological assessment of the portion of newly-formed microvessels in tumor tissue can be used for the prediction of GBM patient’s prognosis.

Objective To examine whether the levels of procalcitonin (PCT), a new marker of infection and/or inflammation, differ between peritoneal dialysis (PD) patients and healthy volunteers, and whether PCT is detectable in uninfected drained dialysate. Design Observational cross-sectional study. Setting PD unit, department of medicine, in a university hospital. Patients A total of 28 PD patients, free of systemic infection, and 28 age- and sex-matched healthy volunteers. Methods PCT was determined by immunoluminometry; detection range 0.01 – 500 ng/mL, reference range <0.5 ng/mL. Results Plasma levels of PCT were significantly higher (Wilcoxon's paired test, p < 0.001) in PD patients (median 0.33 ng/mL) compared with healthy volunteers (0.18 ng/mL). Spearman's test demonstrated a significant positive correlation between PCT and serum C-reactive protein (CRP) ( r = 0.59, p < 0.01); correlations between PCT and transferrin, total weekly creatinine clearance (ClCr), and the renal components of ClCr and Kt/V urea were negative. PCT levels in dialysate (PCTd) were 0.07 ng/mL and correlated positively with plasma PCT, serum CRP, and dialysate fibrinogen levels. The dialysate-to-plasma ratio (D/P) of PCT was 0.2. Neither PCTd nor D/P PCT correlated with D/P creatinine at 4-hours of dwell. Conclusion Compared with healthy volunteers, PD patients without overt signs of infection showed increased plasma PCT levels. Given the study design, it is impossible to determine to what extent the increase in plasma PCT is due to reduced elimination and to what extent it reflects the microinflammation of uremia. Based on the D/P PCT gradient, we assume that PCT transport is more likely to occur from the systemic circulation to the peritoneal cavity than vice versa.

Background: The aim was to construct a risk score model to predict IGBC, developed through statistical modelling, based on our groups previous findings. Methods: Data from cholecystectomies registered in the Nationwide Swedish Register for Gallstone Surgery were analysed. The derivation cohort underwent surgery 2007-2014 and the validation cohort 2015-2016. From the multivariable logistic regression in the derivation cohort, an additive risk model, based on the odds ratio, was constructed and validated. The scoring model's ability to predict IGBC was estimated by AUROC and Hosmer-Lemeshow (HL) test. Results: The derivation cohort consisted of in total 36,355 patients, including 215 with IGBC, who underwent cholecystectomy. Age (41 years 0 points, 42-66 years 10p, 67 years 50p), female gender (3.5p), previous cholecystitis (1.5p) and the combination jaundice without acute cholecystitis (2.5) and acute cholecystitis without jaundice (1.5p) were significantly associated with IGBC. The accuracy of the model was assessed both on the derivation cohort, and in the validation set of 9,948 patients, including 42 with IGBC. The AUROC scores for predicting IGBC were 0.80 (CI:0.77-0.83) in the derivation cohort and 0.78 (CI:0.72-0.84) in the validation cohort, with a good calibration (HL test, p=0.19). Conclusion: We present the first risk score model to predict IGBC. The model is based on five easily registered clinically relevant variables. This validated model may help to optimize treatment strategies in high risk patients.

10605 Background: Optimal chemotherapy (CT) for advanced breast cancer treatment should be effective, well tolerated and convenient. Although the optimum CT is not defined, oral chemotherapy is an attractive option for many patients. Methods: We report a phase II multicentric study, first and second line metastatic breast cancer (MBC) treatment, at least one measurable lesion, prospectively collected data between 2003 and 2005. Treatment schedule: vinorelbine 60 mg/m2 p.o. day 1 and 8, capecitabine 1000 mg/m2 twice daily, day 1–14 q 21 days. Patients: 84 patients with MBC have been registered. Mean age 58.1 years, ranges (39.7 years–71.9 years). All patients had received prior adjuvant anthracycline based chemotherapy (CT). No adjuvant or palliative CT within the last 12 months, no concomitant hormonal treatment. Results: The median number of oral chemotherapy cycles vinorelbine plus capecitabine was 6 cycles (ranges 1 cycle - 19 cycles), total number of cycles was 550. In 84 evaluable pts the objective tumor response was achieved in 46 pts 55%, (ORR = CR + PR), complete response CR was achieved in 11 (13%) pts, partial response in 35 pts (42%), stable disease in 26 pts (31%). Median follow up was 9.7 months. In the intent-to-treat analysis, median time to progression was 6.7 months, median survival not reached, 58 pts (69%) are still alive. Reported NCI grade 3 - 4 toxicities: neutropenia in 4 pts (5%), febrile neutropenia in 4 pts (5%), vomiting in 6 pts (7%) Conclusion: Oral vinorelbine-capecitabine combination shows very promising activity and low toxicity in the MBC treatment. No significant financial relationships to disclose.

The fusion genes containing neuregulin‐1 (NRG1) are newly described potentially actionable oncogenic drivers. Initial clinical trials have shown a positive response to targeted treatment in some cases of NRG1 rearranged lung adenocarcinoma, cholangiocarcinoma, and pancreatic carcinoma. The cost‐effective large scale identification of NRG1 rearranged tumors is an open question. We have tested a data‐drilling approach by performing a retrospective assessment of a de‐identified molecular profiling database of 3263 tumors submitted for fusion testing. Gene fusion detection was performed by RNA‐based targeted next‐generation sequencing using the Archer Fusion Plex kits for Illumina (ArcherDX Inc., Boulder, CO). Novel fusion transcripts were confirmed by a custom‐designed RT‐PCR. Also, the aberrant expression of CK20 was studied immunohistochemically. The frequency of NRG1 rearranged tumors was 0.2% (7/3263). The most common histologic type was lung adenocarcinoma (n = 5). Also, renal carcinoma (n = 1) and prostatic adenocarcinoma (n = 1) were found. Identified fusion partners were of a wide range (CD74, SDC4, TNC, VAMP2, UNC5D), with CD74, SDC4 being found twice. The UNC5D is a novel fusion partner identified in prostate adenocarcinoma. There was no co‐occurrence with the other tested fusions nor KRAS, BRAF, and the other gene mutations specified in the applied gene panels. Immunohistochemically, the focal expression of CK20 was present in 2 lung adenocarcinomas. We believe it should be considered as an incidental finding. In conclusion, the overall frequency of tumors with NRG1 fusion was 0.2%. All tumors were carcinomas. We confirm (invasive mucinous) lung adenocarcinoma as being the most frequent tumor presenting NRG1 fusion. Herein novel putative pathogenic gene fusion UNC5D‐NRG1 is described. The potential role of immunohistochemistry in tumor identification should be further addressed.