The relative biological effectiveness for carbon and oxygen ion beams using the raster-scanning technique in hepatocellular carcinoma cell lines.

BACKGROUND: Aim of this study was to evaluate the relative biological effectiveness (RBE) of carbon (12C) and oxygen ion (16O)-irradiation applied in the raster-scanning technique at the Heidelberg Ion beam Therapy center (HIT) based on clonogenic survival in hepatocellular carcinoma cell lines compared to photon irradiation. METHODS: Four human HCC lines Hep3B, PLC, HepG2 and HUH7 were irradiated with photons, 12C and 16O using a customized experimental setting at HIT for in-vitro trials. Cells were irradiated with increasing physical photon single doses of 0, 2, 4 and 6 Gy and heavy ion-single doses of 0, 0.125, 0.5, 1, 2, 3 Gy (12C and 16O). SOBP-penetration depth and extension was 35 mm +/-4 mm and 36 mm +/-5 mm for carbon ions and oxygen ions respectively. Mean energy level and mean linear energy transfer (LET) were 130 MeV/u and 112 keV/um for 12C, and 154 MeV/u and 146 keV/um for 16O. Clonogenic survival was computated and relative biological effectiveness (RBE) values were defined. RESULTS: For all cell lines and both particle modalities α- and β-values were determined. As expected, α-values were significantly higher for 12C and 16O than for photons, reflecting a steeper decline of the initial slope of the survival curves for high-LET beams. RBE-values were in the range of 2.1-3.3 and 1.9-3.1 for 12C and 16O, respectively. CONCLUSION: Both irradiation with 12C and 16O using the raster-scanning technique leads to an enhanced RBE in HCC cell lines. No relevant differences between achieved RBE-values for 12C and 16O were found. Results of this work will further influence biological-adapted treatment planning for HCC patients that will undergo particle therapy with 12C or 16O

Brivaracetam in the Treatment of Patients with Epilepsy—First Clinical Experiences

ObjectivesTo assess first clinical experiences with brivaracetam (BRV) in the treatment of epilepsies.MethodsData on patients treated with BRV from February to December 2016 and with at least one clinical follow-up were collected from electronic patient records. Data on safety and efficacy were evaluated retrospectively.ResultsIn total, 93 patients were analyzed; 12 (12.9%) received BRV in monotherapy. The mean duration to follow-up was 4.85 months (MD = 4 months; SD = 3.63). Fifty-seven patients had more than one seizure per month at baseline and had a follow-up of more than 4 weeks; the rate of ≥50% responders was 35.1% (n = 20) in this group, of which five (8.8%) patients were newly seizure-free. In 50.5% (47/93), patients were switched from levetiracetam (LEV) to BRV, of which 43 (46.2%) were switched immediately. Adverse events (AE) occurred in 39.8%, with 22.6% experiencing behavioral and 25.8% experiencing non-behavioral AE. LEV-related AE (LEV-AE) were significantly reduced by switching to BRV. The discontinuation of BRV was reported in 26/93 patients (28%); 10 of those were switched back to LEV with an observed reduction of AE in 70%. For clinical reasons, 12 patients received BRV in monotherapy, 75% were seizure–free, and previous LEV-AE improved in 6/9 patients. BRV-related AE occurred in 5/12 cases, and five patients discontinued BRV.ConclusionBRV seems to be a safe, easy, and effective option in the treatment of patients with epilepsy, especially in the treatment of patients who have psychiatric comorbidities and might not be good candidates for LEV treatment. BRV broadens the therapeutic spectrum and facilitates personalized treatment

Limitations of a Short Demographic Questionnaire for Bedside Estimation of Patients’ Global Cognitive Functioning in Epilepsy Patients

ObjectivesThe German socio-demographic estimation scale was developed by Jahn et al. (1) to quickly predict premorbid global cognitive functioning in patients. So far, it has been validated in healthy adults and has shown a good correlation with the full and verbal IQ of the Wechsler Adult Intelligence Scale (WAIS) in this group. However, there are no data regarding its use as a bedside test in epilepsy patients.MethodsForty native German speaking adult patients with refractory epilepsy were included. They completed a neuropsychological assessment, including a nine scale short form of the German version of the WAIS-III and the German socio-demographic estimation scale by Jahn et al. (1) during their presurgical diagnostic stay in our center. We calculated means, correlations, and the rate of concordance (range ±5 and ±7.5 IQ score points) between these two measures for the whole group, and a subsample of 19 patients with a global cognitive functioning level within 1 SD of the mean (IQ score range 85–115) and who had completed their formal education before epilepsy onset.ResultsThe German demographic estimation scale by Jahn et al. (1) showed a significant mean overestimation of the global cognitive functioning level of eight points in the epilepsy patient sample compared with the short form WAIS-III score. The accuracy within a range of ±5 or ±7.5 IQ score points for each patient was similar to that of the healthy controls reported by Jahn et al. (1) in our subsample, but not in our whole sample.ConclusionOur results show that the socio-demographic scale by Jahn et al. (1) is not sufficiently reliable as an estimation tool of global cognitive functioning in epilepsy patients. It can be used to estimate global cognitive functioning in a subset of patients with a normal global cognitive functioning level who have completed their formal education before epilepsy onset, but it does not reliably predict global cognitive functioning in epilepsy patients in general, who often do not fulfill these criteria. It is therefore not a useful tool to be applied in the general neuropsychological presurgical evaluation of epilepsy patients

Fitted survival curves after 12C- (on the left) and 16O-irradiation (on the right) of HepG2, Hep3B, HuH7 and PLC cells lines determined by colony forming assay.

<p>Applied doses were 0, 0.125, 1, 2 and 3 Gy for both radiation modalities. All survival curves showed a dose-dependent decrease of clonogenic cells.</p

Fitted survival curves after photon-irradiation of HepG2, Hep3B, HuH7 and PLC cell lines determined by colony forming assay.

<p>Applied doses were 0, 2, 4, 6 and 8 Gy. All survival curves showed a dose-dependent decrease of clonogenic cells.</p

RBE values determined for 12C- and 16O-irradiation of HepG2, Hep3B, HuH7, and PLC cells.

<p>RBE Relative Biological Effectiveness, ph photons.</p><p>RBE values determined for 12C- and 16O-irradiation of HepG2, Hep3B, HuH7, and PLC cells.</p

data_sheet_1.pdf

Objectives<p>The German socio-demographic estimation scale was developed by Jahn et al. (1) to quickly predict premorbid global cognitive functioning in patients. So far, it has been validated in healthy adults and has shown a good correlation with the full and verbal IQ of the Wechsler Adult Intelligence Scale (WAIS) in this group. However, there are no data regarding its use as a bedside test in epilepsy patients.</p>Methods<p>Forty native German speaking adult patients with refractory epilepsy were included. They completed a neuropsychological assessment, including a nine scale short form of the German version of the WAIS-III and the German socio-demographic estimation scale by Jahn et al. (1) during their presurgical diagnostic stay in our center. We calculated means, correlations, and the rate of concordance (range ±5 and ±7.5 IQ score points) between these two measures for the whole group, and a subsample of 19 patients with a global cognitive functioning level within 1 SD of the mean (IQ score range 85–115) and who had completed their formal education before epilepsy onset.</p>Results<p>The German demographic estimation scale by Jahn et al. (1) showed a significant mean overestimation of the global cognitive functioning level of eight points in the epilepsy patient sample compared with the short form WAIS-III score. The accuracy within a range of ±5 or ±7.5 IQ score points for each patient was similar to that of the healthy controls reported by Jahn et al. (1) in our subsample, but not in our whole sample.</p>Conclusion<p>Our results show that the socio-demographic scale by Jahn et al. (1) is not sufficiently reliable as an estimation tool of global cognitive functioning in epilepsy patients. It can be used to estimate global cognitive functioning in a subset of patients with a normal global cognitive functioning level who have completed their formal education before epilepsy onset, but it does not reliably predict global cognitive functioning in epilepsy patients in general, who often do not fulfill these criteria. It is therefore not a useful tool to be applied in the general neuropsychological presurgical evaluation of epilepsy patients.</p

Fitted survival curves after photon, 12C- and 16O-irradiation of Hep3B, HepG2, HuH7 and PLC cell lines determined by colony forming assay (shown in descending order).

<p>Applied photon doses were 0, 2, 4, 6 and 8 Gy and applied ion doses for 12C and O16 were 0, 0.125, 1, 2 and 3 Gy. Survival curves of HCC cell lines after photon and 12C irradiation are shown on the left side, survival curves after photon and O16 irradiation are shown on the right side.</p