Personalized Treatment of Glioblastoma: Current State and Future Perspective.

Glioblastoma (GBM) is the most aggressive glial tumor of the central nervous system. Despite intense scientific efforts, patients diagnosed with GBM and treated with the current standard of care have a median survival of only 15 months. Patients are initially treated by a neurosurgeon with the goal of maximal safe resection of the tumor. Obtaining tissue samples during surgery is indispensable for the diagnosis of GBM. Technological improvements, such as navigation systems and intraoperative monitoring, significantly advanced the possibility of safe gross tumor resection. Usually within six weeks after the surgery, concomitant radiotherapy and chemotherapy with temozolomide are initiated. However, current radiotherapy regimens are based on population-level studies and could also be improved. Implementing artificial intelligence in radiotherapy planning might be used to individualize treatment plans. Furthermore, detailed genetic and molecular markers of the tumor could provide patient-tailored immunochemotherapy. In this article, we review current standard of care and possibilities of personalizing these treatments. Additionally, we discuss novel individualized therapeutic options with encouraging results. Due to inherent heterogeneity of GBM, applying patient-tailored treatment could significantly prolong survival of these patients.

Estimated collective effective dose to the population from nuclear medicine diagnostic procedures in Croatia: A comparison of 2010 and 2015.

OBJECTIVE: This study presents national surveys of patient exposure from nuclear medicine (NM) diagnostic procedures in 2010 and 2015 in the Republic of Croatia. METHODS: The survey was performed according to the European Commission Dose DataMed (DDM) project methodology. 28 most frequent NM diagnostic procedures were identified. Data about frequencies of procedures and average administered activities of radioisotopes used in those procedures were collected. Average administered activities were converted to effective doses according to the dose conversion coefficients. Then the collective effective dose to the population and an effective dose per capita were calculated based on the number of the most frequent NM diagnostic procedures and the average effective dose per procedure. RESULTS: In 2010, 41200 NM diagnostic procedures led to 146.7 manSv collective effective dose to the population and in 2015, 42000 NM diagnostic procedures led to 146.8 manSv collective effective dose to the population. The frequencies of NM diagnostic procedures were 9.7 and 9.8 annually per 1000 population with 34.1 µSv and 34.2 µSv effective dose per capita for 2010 and 2015, respectively. The main contributors to the annual collective dose from NM in Croatia are examinations of the bone, heart, thyroid and PET/CT tumour diagnostic. Average administered activities have not changed considerably from 2010 to 2015. Nevertheless, within the frequency of some of the procedures, significant changes were found in five-year period. CONCLUSIONS: Frequencies, average administered activities and collective effective dose to the population from NM diagnostic procedures in Croatia are comparable to the values reported by other European surveys. Changes were found between 2010 and 2015 and we intend to perform this study periodically to identify possible trends, but also to raise awareness about the potential dose optimization.

Implementation of Elastography Score and Strain Ratio in Combination with B-Mode Ultrasound Avoids Unnecessary Biopsies of Breast Lesions.

The aim of this study was to evaluate whether the combination of B-mode ultrasound, elastography score (ES) and strain ratio (SR) improves diagnostic performance with respect to breast lesions. One hundred thirty lesions were prospectively evaluated by B-mode ultrasound and strain elastography, followed by fine-needle aspiration cytology/biopsy in 117 woman who were scheduled for regular breast BUS. The median ES (4.5 vs. 2.9, p < 0.001) and SR (4.9 vs. 2.3, p < 0.001) were significantly higher for malignant than for benign lesions. A sensitivity of 90.5% and specificity of 93.2% for the ES (cutoff point = 3.8) and a sensitivity of 87.5% and specificity of 87.6% for the SR (cutoff point = 3.5) were obtained. Elastography combined with B-mode ultrasound improved the specificity, accuracy and positive predictive value. Receiver operating characteristic curves yielded a higher value for the combined technique for diagnosis of breast lesions. Routine use of such a diagnostic algorithm could reduce the number of unnecessary biopsies.

Brain tissue adaptability to slow-growing tumors: case report of clivus meningioma.

A 46-year-old female patient with a large slow-growing craniocervical junction tumor is presented. Her complaints began 6 months before with sensory and painful sensations, sphincter impairment, and motor events (spastic tetraparesis, more pronounced on the left extremities). Magnetic resonance of the head revealed a rounded tumor of 2.5 cm in diameter, by its characteristics corresponding to meningioma, at the level of C1 vertebra and craniocervical junction, with the base at spinal canal anterior wall, occupying most of the craniocervical junction, compressing spinal cord and medulla oblongata. Intracerebral computed tomography angiography showed spared lumen and a satisfactory image of vertebral arteries bypassing the expansive growth at the occipital foramen, confirming slow tumor growth. Antiedematous therapy led to transient improvement in extremity strength and partial recovery of neurologic deficit, which resolved completely upon neurosurgical operation and rehabilitation. This case report exemplifies brain adaptability to slowly growing expansive neoplasms, based on its volume reduction up to the moment when further adaptation is not possible anymore, i.e. breaking of the mechanism of adaptation. Because of brain adaptability, such slowly growing tumors may stay asymptomatic for a long time. Brain plasticity also includes adaptation and autoregulation of the circulation, thus ensuring stable blood flow.

Computer-aided evaluation of radiologist's reproducibility and subjectivity in mammographic density assessment.

Mammographic density is an independent risk of breast cancer. This study has evaluated the radiologists' reproducibility and subjectivity in breast density estimation and in order to decrease the radiologists' subjective errors the computer software was developed. The very good reproducibility existed in the strong correlation with the first and the second mammogram assessment after three month period for each radiologist (correlation coefficient 0.73-1, p < 0.001). The strong correlation was present in the case of all 5 radiologists when compared among themselves and compared with software aided MDEST-Mammographic Density Estimation (correlation coefficient 0.651-0.777, p < 0.001). Detected differences in glandular tissue percentage determination occurred in the case of two experienced radiologists, out of 5 (one radiologist with more than 5 year experience and one with more than 10 year experience, p < 0.01), but in the case of breast type determination (American College of Radiology-ACR I-IV), the detected difference occurred in one radiologist with the least experience (less than 5 years, p < 0.001). It can be concluded that the estimation of glandular tissue percentage in breast density is rather subjective method, especially if it is expressed with absolute percentage, but the determination of type of breast (ARCI-IV) depends on the radiologist's experience. This study showed that software aided determination of glandular tissue percentage and breast type can be of a great benefit in the case of less experienced radiologists.

Image quality of mammography in Croatian nationwide screening program: comparison between various types of facilities.

PURPOSE: The study was aimed to provide objective evidence about the mammographic image quality in Croatia, to compare it between different types of MG facilities and to identify the most common deficiencies and possible reasons as well as the steps needed to improve image quality. MATERIALS AND METHODS: A total of 420 mammographic examinations collected from 84 mammographic units participating in the Croatian nationwide breast cancer screening program were reviewed in terms of four image quality categories: identification of patient and examination, breast positioning and compression, exposure and contrast, and artifacts. Those were rated using image evaluating system based on American College of Radiology and European Commission proposals. The results were compared among different types of mammographic units, and common image quality deficiencies were identified. RESULTS: Total image quality scores of 12.8, 16.1, 13.0 and 13.7 were found for general hospitals, university hospitals, private clinics and public healthcare centres, respectively. Average score for all mammographic units was 13.5 (out of 25 points). University hospitals were significantly better than all other mammography units in overall image quality, which was mostly contributed by better breast positioning practices. Private clinics showed the worst results in identification, exposure, contrast and artifacts. CONCLUSIONS: Serious deficiencies in identification and breast positioning, which might compromise breast cancer screening outcome, were detected in our material. They occur mainly due to subjective reasons and could be corrected through additional staff training and improvement of working discipline.

Good reasons to implement quality assurance in nationwide breast cancer screening programs in Croatia and Serbia: results from a pilot study.

The purpose of this study is to investigate the need for and the possible achievements of a comprehensive QA programme and to look at effects of simple corrective actions on image quality in Croatia and in Serbia. The paper focuses on activities related to the technical and radiological aspects of QA. The methodology consisted of two phases. The aim of the first phase was the initial assessment of mammography practice in terms of image quality, patient dose and equipment performance in selected number of mammography units in Croatia and Serbia. Subsequently, corrective actions were suggested and implemented. Then the same parameters were re-assessed. Most of the suggested corrective actions were simple, low-cost and possible to implement immediately, as these were related to working habits in mammography units, such as film processing and darkroom conditions. It has been demonstrated how simple quantitative assessment of image quality can be used for optimisation purposes. Analysis of image quality parameters as OD, gradient and contrast demonstrated general similarities between mammography practices in Croatia and Serbia. The applied methodology should be expanded to larger number of hospitals and applied on a regular basis.

"Signet-ring" cell invasive lobular carcinoma of the breast - accidental finding associated with intraductal papilloma: a case report.

BACKGROUND: A 57-year old woman had only unilateral milky dischardge of the right breast. Clinical and mammography findings were normal. CASE PRESENTATION: Cytological diagnosis of intraductal papilloma was established which was galactographically confitmed and patient underwent to surgery. Ductulolobular segmentectomy was made. Histopathologically beside intraductal papilloma numerous single dispread malignant "signet ring" cells in the fibrous retromammilary stroma were found. Imunohistochemically findings were: cytokeratin 8 positive, ER H-score 80, PR H-score 50, HER-2/neu negative. Diagnosis of "signet ring" cell lobular invasive carcinoma was made, followed by mastectomy, axillary limphadectomy and contra lateral breast biopsy. CONCLUSION: Residual tumor were found only in the breast tissue, while axillary lymph nodes and contra lateral breast biopsy were negative. Patient underwent to oncology therapy.

Survey of mammography practice in Croatia: equipment performance, image quality and dose.

A national audit of mammography equipment performance, image quality and dose has been conducted in Croatia. Film-processing parameters, optical density (OD), average glandular dose (AGD) to the standard breast, viewing conditions and image quality were examined using TOR(MAM) test object. Average film gradient ranged from 2.6 to 3.7, with a mean of 3.1. Tube voltage used for imaging of the standard 45 mm polymethylmethacrylate phantom ranged from 24 to 34 kV, and OD ranged from 0.75 to 1.94 with a mean of 1.26. AGD to the standard breast ranged from 0.4 to 2.3 mGy with a mean of 1.1 mGy. Besides clinical conditions, the authors have imaged the standard phantom in the referent conditions with 28 kV and OD as close as possible to 1.5. Then, AGD ranged from 0.5 to 2.6 mGy with a mean of 1.3 mGy. Image viewing conditions were generally unsatisfying with ambient light up to 500 lx and most of the viewing boxes with luminance between 1000 and 2000 cd per m(2). TOR(MAM) scoring of images taken in clinical and referent conditions was done by local radiologists in local image viewing conditions and by the referent radiologist in good image viewing conditions. Importance of OD and image viewing conditions for diagnostic information were analysed. The survey showed that the main problem in Croatia is the lack of written quality assurance/quality control (QA/QC) procedures. Consequently, equipment performance, image quality and dose are unstable and activities to improve image quality or to reduce the dose are not evidence-based. This survey also had an educational purpose, introducing in Croatia the QC based on European Commission Guidelines.

Underestimation of DCIS at MRI-guided vacuum-assisted breast biopsy.

OBJECTIVE: The study objective was to assess the rate of underestimation of ductal carcinoma in situ (DCIS) at MRI-guided 9-gauge vacuum-assisted breast biopsy. MATERIALS AND METHODS: An institutional review board-approved retrospective review was performed of 373 consecutive lesions that had undergone MRI vacuum-assisted breast biopsy. In 34 lesions with subsequent surgery, vacuum-assisted breast biopsy yielded DCIS without frank microinvasion or invasion. DCIS underestimates were lesions for which vacuum-assisted breast biopsy yielded DCIS without frank microinvasion or invasion at biopsy and surgery yielded invasive cancer. Records and pathology findings were reviewed. RESULTS: Among 34 lesions, vacuum-assisted breast biopsy histology was DCIS in 29 and DCIS with possible microinvasion in five. Of 29 lesions yielding DCIS at MRI vacuum-assisted breast biopsy, surgical excision revealed invasive cancer in five (17%; 95% CI, 6-36%). The DCIS underestimation rate was significantly higher in lesions 6 cm or larger versus smaller lesions (60% vs 8%, p = 0.02). MRI lesion type, kinetics, number of specimens, menopausal status, and target sampling versus excision did not significantly affect underestimation. Of five lesions yielding DCIS with possible microinvasion at MRI vacuum-assisted breast biopsy, surgery revealed invasive carcinoma in four (80%; 95% CI, 28-99%). DCIS underestimation was significantly more likely if MRI vacuum-assisted breast biopsy showed possible microinvasion than if it did not (80% vs 17%, p =0.01). CONCLUSION: Underestimation occurred in 17% of lesions yielding DCIS and in 80% of lesions yielding DCIS with possible microinvasion at MRI vacuum-assisted breast biopsy. DCIS underestimation was significantly more likely in lesions measuring 6 cm or larger. No other patient or lesion factors significantly affected DCIS underestimation at MRI vacuum-assisted breast biopsy.

Patients review: drug-induced movement disorders.

Objective of this paper is to review drug-induced movement disorders (D-IMD) treated patients on Department of Neurology in University Hospital Osijek. We reviewed patients treated during 10 years period (from 1992 to 2002). Analysed group consisted of 14 patients. Reasons for hospitalisation were swallowing problems in 6 patients, neuroleptic malignant syndrome (NMS) in 3 patients, stroke in 2 patients, bolus choking in 2 patients, and speech disturbance in 1 patient. Working diagnosis for most of our patients was neurological disease, yet only later D-IMD diagnosis was established excluding primary neurological disease, or as associated disease to basic neurological disorder. Nine patients have diagnosed as Parkinson syndrome, 3 patients as NMS, and 4 as orolingual dyskinesia, either autonomously, or in combination with Parkinson syndrome. D-IMD was most frequently caused by neuroleptics. Thus the small number of patients hospitalised regarding this syndrome on Department of Neurology.