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Background: High-grade gliomas are associated with poor prognosis. Tumour heterogeneity and invasiveness create challenges for effective treatment and use of systemically administrated drugs. Furthermore, lack of functional predictive response-assays based on drug efficacy complicates evaluation of early treatment responses., Methods: We used microdialysis to deliver cisplatin into the tumour and to monitor levels of metabolic compounds present in the tumour and non-malignant brain tissue adjacent to tumour, before and during treatment. In parallel, we collected serum samples and used multivariate statistics to analyse the metabolic effects., Results: We found distinct metabolic patterns in the extracellular fluids from tumour compared to non-malignant brain tissue, including high concentrations of a wide range of amino acids, amino acid derivatives and reduced levels of monosaccharides and purine nucleosides. We found that locoregional cisplatin delivery had a strong metabolic effect at the tumour site, resulting in substantial release of glutamic acid, phosphate, and spermidine and a reduction of cysteine levels. In addition, patients with long-time survival displayed different treatment response patterns in both tumour and serum. Longer survival was associated with low tumour levels of lactic acid, glyceric acid, ketoses, creatinine and cysteine. Patients with longer survival displayed lower serum levels of ketohexoses, fatty acid methyl esters, glycerol-3-phosphate and alpha-tocopherol, while elevated phosphate levels were seen in both tumour and serum during treatment., Conclusion: We highlight distinct metabolic patterns associated with high-grade tumour metabolism, and responses to cytotoxic cisplatin treatment.

Haralick texture features are common texture descriptors in image analysis. To compute the Haralick features, the image gray-levels are reduced, a process called quantization. The resulting features depend heavily on the quantization step, so Haralick features are not reproducible unless the same quantization is performed. The aim of this work was to develop Haralick features that are invariant to the number of quantization gray-levels. By redefining the gray-level co-occurrence matrix (GLCM) as a discretized probability density function, it becomes asymptotically invariant to the quantization. The invariant and original features were compared using logistic regression classification to separate two classes based on the texture features. Classifiers trained on the invariant features showed higher accuracies, and had similar performance when training and test images had very different quantizations. In conclusion, using the invariant Haralick features, an image pattern will give the same texture feature values independent of image quantization., Competing Interests: The authors have declared that no competing interests exist.

In recent years, texture analysis of medical images has become increasingly popular in studies investigating diagnosis, classification and treatment response assessment of cancerous disease. Despite numerous applications in oncology and medical imaging in general, there is no consensus regarding texture analysis workflow, or reporting of parameter settings crucial for replication of results. The aim of this study was to assess how sensitive Haralick texture features of apparent diffusion coefficient (ADC) MR images are to changes in five parameters related to image acquisition and pre-processing: noise, resolution, how the ADC map is constructed, the choice of quantization method, and the number of gray levels in the quantized image. We found that noise, resolution, choice of quantization method and the number of gray levels in the quantized images had a significant influence on most texture features, and that the effect size varied between different features. Different methods for constructing the ADC maps did not have an impact on any texture feature. Based on our results, we recommend using images with similar resolutions and noise levels, using one quantization method, and the same number of gray levels in all quantized images, to make meaningful comparisons of texture feature results between different subjects.

Background/aim: Overall survival for glioblastoma patients is short. Standard treatment is surgery followed by radiochemotherapy and adjuvant temozolomide. The aim of this study was to evaluate the outcome for all patients with progressive disease treated with bevacizumab-based treatment combinations in the northern region of Sweden., Patients and Methods: This was a single-center retrospective analysis after bevacizumab-based second-line treatment for malignant glioma. All patients treated with bevacizumab, between 2007 and 2011 in our Center were retrospectively evaluated., Results: Progression-free survival after the start of bevacizumab-based treatment was 20 weeks and overall survival was 31 weeks. Treatment was well tolerated, but 9% of patients (n=6) suffered from serious adverse events. In 68% of patients, a ≥25% decrease in contrast enhancement was seen at best response., Conclusion: Results from this retrospective study are comparable with earlier phase-II studies and motivate randomized trials of bevacizumab-based treatment in the second-line setting., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: To elucidate the impact of different forms of radiation toxicities (esophagitis, radiation pneumonitis, mucositis and hoarseness), on the survival of patients treated with curatively intended radiotherapy for non-small cell lung cancer (NSCLC)., Patients and Methods: Data were individually collected retrospectively for all patients diagnosed with NSCLC subjected to curatively intended radiotherapy (≥50 Gy) in Sweden during the time period 1990 to 2000., Results: Esophagitis was the only radiation-induced toxicity with an impact on survival (hazard ratio=0.83, p=0.016). However, in a multivariate model, with clinical- and treatment-related factors taken into consideration, the impact of esophagitis on survival was no longer statistically significant (hazard ratio=0.88, p=0.17)., Conclusion: The effect on survival seen in univariate analysis may be related to higher radiation dose and to the higher prevalence of chemotherapy in this group. The results do not suggest that the toxicities examined have any detrimental effect on overall survival., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: In this pilot study we evaluated the performance of a substitute CT (s-CT) image derived from MR data of the brain, as a basis for optimization of intensity modulated rotational therapy, final dose calculation and derivation of reference images for patient positioning., Methods: S-CT images were created using a Gaussian mixture regression model on five patients previously treated with radiotherapy. Optimizations were compared using D max, D min, D median and D mean measures for the target volume and relevant risk structures. Final dose calculations were compared using gamma index with 1%/1 mm and 3%/3 mm acceptance criteria. 3D geometric evaluation was conducted using the DICE similarity coefficient for bony structures. 2D geometric comparison of digitally reconstructed radiographs (DRRs) was performed by manual delineation of relevant structures on the s-CT DRR that were transferred to the CT DRR and compared by visual inspection., Results: Differences for the target volumes in optimization comparisons were small in general, e.g. a mean difference in both D min and D max within ±0.3%. For the final dose calculation gamma evaluations, 100% of the voxels passed the 1%/1 mm criterion within the PTV. Within the entire external volume between 99.4% and 100% of the voxels passed the 3%/3 mm criterion. In the 3D geometric comparison, the DICE index varied between approximately 0.8-0.9, depending on the position in the skull. In the 2D DRR comparisons, no appreciable visual differences were found., Conclusions: Even though the present work involves a limited number of patients, the results provide a strong indication that optimization and dose calculation based on s-CT data is accurate regarding both geometry and dosimetry.

Background: The malignant brain tumour glioblastoma is a devastating disease that remains a therapeutic challenge., Materials and Methods: Effects of combinations of the US Food and Drug Administation (FDA) approved proteasome inhibitor bortezomib and the histone deacetylase (HDAC) inhibitors vorinostat, valproic acid and sodium phenylbutyrate were studied on primary glioblastoma stem cell lines and conventional glioblastoma cell lines. Cell survival, proliferation and death were analyzed by fluorometric microculture cytotoxicity assay (FMCA), propidium iodide labeling and flow cytometry, and cell cloning through limiting dilution and live-cell bright-field microscopy., Results: Bortezomib and the HDAC inhibitors showed synergistic cell killing at clinically relevant drug concentrations, while the conventional cell lines cultured in serum-containing medium were relatively resistant to the same treatments., Conclusion: These findings of synergistic glioblastoma stem cell killing by bortezomib and three different FDA-approved HDAC inhibitors confirm and expand previous observations on co-operative effects between these classes of drugs.