The findings suggest that the administration of 5-ALA or the combined effect of 5-ALA, anaesthesia and tumour resection can cause a mild and reversible elevation in liver enzymes. It therefore appears safe to change the regime of monitoring. Routine blood samples are thus abolished, though caution remains necessary in patients with known liver impairment.

BACKGROUND Glioblastoma (GBM) is an aggressive and malignant primary brain tumor with limited treatment options and a dismal prognosis. Immunotherapy is advancing in other types of cancer but has not yet proven effective in glioblastoma. Prognostic and predictive biomarkers and new treatment targets are urgently needed. MATERIAL AND METHODS 158 patients with glioma WHO grade II-IV were included in the study. Plasma was analyzed for interleukin (IL)-6, YKL-40 (Gene: CHI3L1) and 91 other immune-related protein biomarkers by ELISA or/and Olink technology. CHI3L1 rs4950928 genotyping was analyzed on DNA extracted from whole-blood. RESULTS Fourteen of 92 immune-related biomarkers in plasma detected with the Olink immuno-oncology array were related with tumor grade or/and type (p< 0.05) (corrected for age), whereas plasma IL-6 and YKL-40 did not change with tumor grade. In univariate analysis of plasma from 94 patients with newly diagnosed GBM higher baseline IL-6 was associated with short OS (HR=1.19 (per 2-fold change in IL-6), p=0.04), YKL-40 showed a similar trend (HR=1.20 (per 2-fold change in YKL-40), p=0.056) and high/low baseline levels of additional 15 immune-related biomarkers (e.g. CD244, Granzyme B, ICOS ligand, IL-8 and Pleiotrophin) were associated with short OS (p< 0.05). Genetic variation in YKL-40 was associated with plasma YKL-40 levels (+/+ vs. -/+ vs. -/-, p=0.0004) but not with OS in patients with GBM (HR= 0.78 (+/+ vs. -/+), p=0.32). CONCLUSION High levels of several immune-related biomarkers in plasma including IL-6, IL-8, CD244, Granzyme B, ICOS ligand, and Pleiotrophin from patients with glioblastoma were related or inversely related to OS.

Glioblastoma multiforme (GBM) is an aggressive brain tumor with a poor prognosis. Standard of care at diagnosis is surgical resection, followed by radiation and temozolomide. Receiving this therapy, the median survival is 14.6 months [1]. We have no standard treatment for relapse and known options have limited effect. There is an urgent need for novel treatment interventions to improve clinical outcomes and quality of life. Recently, improved overall survival has been achieved with immune therapeutics in melanoma and renal cell carcinoma. Accordingly, it has been posited that immunotherapy may offer promise in other difficult cancers such as GBM [2]. We present our translational study; a phase II open label, two-armed translational study of Nivolumab and Bevacizumab for recurrent GBM, who have failed Stupp’s regime [1]. Patients are included in two arms depending on possibly salvage neurosurgical resection. Both arms receive Nivolumab and Bevacizumab administrated every second weekend, but the surgical arm also receive Nivolumab 7 days prior surgery. We expect 40 patients; 20 in each arm. Enrollment period is expected to 20 months, started October 2018. Our primary objective is to make preliminary assessment of immune related biomarkers, including PD-L1; therefore, we perform full genome sequencing on tumor biopsies from the surgical arm and on blood samples from both arms. We evaluate changes in the transcriptomic landscape caused by the check-point inhibition and relation to response as compared with baseline sequencing data, as well as the impact of tumor mutation burden and neoepitope load. We investigate the tumor microenvironment by harvesting tumor infiltrating lymphocytes and study the composition by flow-cytometry. The patients are evaluated by blood samples, FET-PET as wells as clinical examinations to evaluate PFS and OS. Overall the study will provide us with a unique possibility to investigate and thereof predict which patients will profit from the treatment.