Angiotensinogen and HLA class II predict bevacizumab response in recurrent glioblastoma patients

Background Bevacizumab combination therapy is among the most frequently used treatments in recurrent glioblastoma and patients who achieve response to bevacizumab have improved survival as well as quality of life. Accordingly, the aim of this study was to identify predictive biomarkers for bevacizumab response in recurrent glioblastoma patients. Methods The study included a total of 82 recurrent glioblastoma patients treated with bevacizumab combination therapy whom were both response and biomarker evaluable. Gene expression of tumor tissue was analyzed by using a customized NanoString platform covering 800 genes. Candidate gene predictors associated with response were analyzed by multivariate logistic and Cox regression analysis. Results Two genes were independently associated with response: Low expression of angiotensinogen (2‐fold decrease in AGT; OR = 2.44; 95% CI: 1.45–4.17; P = 0.0009) and high expression of a HLA class II gene (2‐fold increase in HLA‐DQA1; OR = 1.22; 95% CI: 1.01–1.47; P = 0.04). These two genes were included in a model that is able predict response to bevacizumab combination therapy in clinical practice. When stratified for a validated prognostic index, the predictive model for response was significantly associated with improved overall survival. Conclusion Two genes (low angiotensinogen and high HLA‐class II expression) were predictive for bevacizumab response and were included in a predictive model for response. This model can be used in clinical practice to identify patients who will benefit from bevacizumab combination therapy

Incidence of and survival from oligodendroglioma in Denmark, 1943–2002

We established the nationwide, population-based incidence of oligodendroglioma in Denmark during 59 years of monitoring and compared the overall survival of patients with oligodendroglial tumors during the periods 1943–1977 and 1978–2002. On the basis of reports in the Danish Cancer Registry, 1,304 cases of oligodendroglioma were included in the study. We calculated sex- and age-specific incidence rates in 5-year age intervals and for 5-year calendar periods. Overall survival was estimated by the Kaplan-Meier method. In the period 1943–2002, the incidence rate of oligodendroglioma was less than 1 case per 100,000 person-years, but varied somewhat when viewed across isolated periods. Comparison of the incidence rate before and after the introduction of CT scanning did not reveal a significant difference in the incidence rate. The median survival increased from 1.4 years (95% confidence interval [CI], 1.0–1.6) to 3.4 years (95% CI, 2.6–4.2) during the period of study. The overall incidence of oligodendroglioma showed a relatively stable pattern over nearly 60 years of monitoring. Overall survival improved significantly during the study period, which could partly be due to improved diagnostic methods and treatment options

Prevalence, birth incidence, and penetrance of von Hippel-Lindau disease (vHL) in Denmark

Von Hippel–Lindau disease (vHL) is a rare hereditary tumour predisposition with multiorgan involvement that is not always easily recognized. The disease is reported to be almost fully penetrant at age 60 years. Previous estimates of vHL prevalence and incidence are all regional and vary widely. Most are >20 years old and prone to selection bias because of inclusion of only clinically affected vHL patients who were diagnosed before genetic testing was available. In an unselected cohort of all known Danish carriers of a disease-causing VHL variant, we assessed vHL penetrance on a national basis. We further used national health registers to identify individuals who fulfilled the clinical diagnostic vHL criteria based on their registered diagnostic codes, but had not been diagnosed with vHL. We also assessed the medical histories of first-degree relatives to identify familial cases. This study gives the first national estimates of vHL prevalence (1 in 46 900 individuals) and birth incidence (1 in 27 300 live births). vHL has been underdiagnosed in Denmark, and as many as 25% of the overall vHL cohort (diagnosed+undiagnosed patients) have a missed diagnosis in spite of fulfilling the international diagnostic criteria. We found an overall penetrance of 87% at age 60 years. When considering only vHL patients who have not attended surveillance, 20% will still be asymptomatic at age 60 years. This should be considered in the context of genetic counselling, especially when assessing the risk of vHL in asymptomatic adult first-degree relatives who are often not genetically tested

Brain perfusion CT compared with ¹⁵O-H₂O PET in patients with primary brain tumours

PURPOSE: Perfusion CT (PCT) measurements of regional cerebral blood flow (rCBF) have been proposed as a fast and easy method for identifying angiogenically active tumours. In this study, quantitative PCT rCBF measurements in patients with brain tumours were compared to the gold standard PET rCBF with (15)O-labelled water ((15)O-H(2)O). METHODS: On the same day within a few hours, rCBF was measured in ten adult patients with treatment-naïve primary brain tumours, twice using (15)O-H(2)O PET and once with PCT performed over the central part of the tumour. Matching rCBF values in tumour and contralateral healthy regions of interest were compared. RESULTS: PCT overestimated intratumoural blood flow in all patients with volume-weighted mean rCBF values of 28.2 ± 18.8 ml min(−1) 100 ml(−1) for PET and 78.9 ± 41.8 ml min(−1) 100 ml(−1) for PCT. There was a significant method by tumour grade interaction with a significant tumour grade rCBF difference for PCT of 32.9 ± 15.8 ml min(−1) 100 ml(−1) for low-grade (WHO I + II) and 81.5 ± 15.4 ml min(−1) 100 ml(−1) for high-grade (WHO III + IV) tumours, but not for PET. The rCBF PCT and PET correlation was only significant within tumours in two patients. CONCLUSION: Although intratumoural blood flow measured by PCT may add valuable information on tumour grade, the method cannot substitute quantitative measurements of blood flow by PET and (15)O-H(2)O PET in brain tumours