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Lege Artis Medicinae

APRIL 18, 2020

[Digitally-assisted treatment planning in precision oncology]

PETÁK István, VÁLYI-NAGY István

[The progress of molecular information based on personalized precision medicine has reached a new milestone. Actually, about 6 million mutations of 600 genes may be related to the development of cancer, and on average, 3-4 of these “driver” mutations are present in each patient. Due to the progress in molecular diagnostics, we can now routinely identify the molecular profile of tumors in clinical settings. By clinical translation, there are actually available more than 125 targeted pharmaceuticals and hundreds of such therapies are under clinical trial. As a result, we have many first-line and licenced treatment options to be elected by molecular information as the optimal one for every patient. There is an increasing need for complex informatics solutions by medical software. Geneticists, molecular biologists, molecular pathologists, molecular pharmacologists are already using bioinformatics and interpretation software on their daily work. Today, online digital tools of artificial intelligence are also available for physicians for assisted treatment planning. Telemedicine, videoconferencing provide solutions for interdisciplinary virtual molecular tumor boards, which democratizes the access to precision oncology for all doctors and patients. ]

Clinical Neuroscience

SEPTEMBER 30, 2020

[Prognostic significance of invasion in glioblastoma]

SZIVÓS László, VIRGA József, HORTOBÁGYI Tibor, ZAHUCZKY Gábor, URAY Iván, JENEI Adrienn, BOGNÁR László, ÁRKOSY Péter, KLEKNER Álmos

[Glioblastoma is the most common malignant CNS tumor, its surgical removal is hindered by the tumors invasive nature, while current anti-tumor therapies show limited effectiveness – mean overall survival is 16-24 months. Some patients show minimal response towards standard oncotherapy, however there are no routinely available prognostic and predictive markers in clinical practice to identify the background of mentioned differences in prognosis. This research aims to identify the prognostic significance of invasion-related extracellular (ECM) components. Patient groups with different prognoses were created (OS: group A <16 months, group B > 16 months), and internationally recognized prognostic markers (IDH1 mutation and MGMT promoter hyper-methylation) were tested in the flash-frozen tumor samples. Furthermore, the mRNA levels of 46 invasion-related ECM molecules were measured. Clinical data of the patients who have been operated on at the University of Debrecen Clinical Center Department of Neurosurgery and treated at the Department of Clinical Oncology showed no significant differences except for survival data (OS and PFS), and reoperation rate. All samples were IDH wild type. MGMT promoter hypermethylation rate showed significant differences (28.6% vs 68.8%). The expressional pattern of the invasion-related ECM molecules, i.e. the invasion spectrum also showed major differences, integrin β2, cadherin-12, FLT4/VEGFR-3 and versican molecules having signficantly different mRNA levels. The accuracy of the inivasion spectrum was tested by statistical classifier, 83.3% of the samples was sorted correctly, PPV was 0.93. The difference found in the reoperation rate when comparing different prognostic groups aligns with literature data. MGMG promoter region methylation data in Hungarian samples has not been published yet, and further confirming current knowledge urges the implementation of MGMT promoter analysis in clinical practice. Studying the invasion spectrum provides extra information on tumors, as a prognostic marker it helps recognizing more aggressive tumors, and calls attention to the necessity of using anti-invasive agents in GBM therapies in the future.]

Clinical Neuroscience

MARCH 30, 2016

[Computed tomographic examination of cranial lesions, a paleoradiological approach]

ZÁDORI Péter, BAJZIK Gábor, BÍRÓ Gergely, LELOVICS Zsuzsanna, BALASSA Tímea, BERNERT Zsolt, ÉVINGER Sándor, HAJDU Tamás, MARCSIK Antónia, MOLNÁR Erika, ŐSZ Brigitta, PÁLFI György, WOLFF Katalin, REPA Imre

[Background and purpose - Introducing the multidisciplinary paleoradiology research at the Institute of Diagnostic Imaging and Radiation Oncology of the Kaposvár University, highlighting the cases with potential central nervous system involvement - from the scanning methods to the 3D printing - in order to draw attention to the historical background and clinical aspects of certain pathological conditions. Methods - The authors developed the examination protocols for three different CT scanners. Among the examined archaeological remains cranial lesions were identified in 26 cases, from which 4 cases with potential central nervous system involvement are demonstrated. The scanning parameters and the advantages of secondary image reconstructions (multiplanar reconstruction, maximum intensity projection, three-dimensional volume rendering technique) are presented with the cases. Results - The authors demonstrate a case with destructive skull lesions due to syphilis from the 15th century AD, a condition rarely seen or even unknown nowadays in the modern world. With the CT images of the skull base fracture from the Iron Age, signs of healing could be verified. Using the CT images a non-invasive approach is presented in the case of the craniofacial osteosarcoma in order to visualize the local status and the direct intracranial propagation. Advantages of the 3D VRT reconstructions are shown in the case of unilateral coronal suture synostosis. Conclusion - Paleoradiological CT examinations serve as a non-invasive, non-destructive tool for studying archaeological remains and artifacts. The special applications provided by the imaging modality contribute to the conventional paleopathological investigations. Keywords: paleoradiology, computed tomography, 3D reconstruction, skull lesions, paleopathology]

Clinical Oncology

APRIL 10, 2019

[New perspectives in the treatment of lung cancer]

SZONDY Klára, BOGOS Krisztina

[In recent years, huge research is going on in the fi eld of oncology and as a result, we can see a signifi cantly longer survival in this area of medicine. Lung cancer, which has been taken places in the back for decades, it has not become a curable disease, but begins to belong to the chronic diseases. As a result of brilliant surgical technics and stereotactic radiotherapy, or as a result of changes in drug treatment, 5-year survival is not uncommon in metastatic lung cancer patients, next to relatively long progression free survive. After the third-generation cytotoxic combinations the added growth inhibition (VEGF inhibitor) maintenance therapy or continuous pemetrexed cytotoxic chemotherapy were resulted in high survival benefi ts. The fi rst real breakthrough, long progression-free survival was achieved by targeted treatment, which proved to be effective with known driver mutations. The other great result, especially in squamous cell carcinoma, was the immunotherapy, the inhibition of immune checkpoints, which effi cacy was confi rmed in adenocarcinoma also. Several studies are going on with adjuvant or neoadjuvant immunotherapy, and combined use of immunotherapy (either in combination with radiotherapy or cytotoxic chemotherapy).]

Clinical Oncology

FEBRUARY 20, 2019

[The role of the microbiome in the etiology and treatment of neoplastic diseases]

SCHWAB Richárd, BACSUR Emese, TORDAI Attila, PETÁK István

[Experimental data on the role of the microbiome in the onset and progression of infl ammatory diseases and cancer have been accumulated for years. An important milestone in this respect was the discovery that APC mutant mice in sterile conditions do not develop colon cancer of the FAP type. The direct role of the Enterobacteriaceae and Fusobacteriaceae bacterial families were also shown in the pathomechanism of the same experimental model. The toxic effect of chemotherapy on the gut fl ora has been well documented, but it may very well be that this putative side effect is part of the effi cacy, primarily in the case of adjuvant chemotherapy. The fi rst reproducible methods of microbiome molecular diagnostics are already available today. In addition to standard large clinical studies, we can increasingly rely on evidence of molecular pathomechanism and „real-world” clinical experience in the clinical interpretation of the microbiome. The overview summarizes the results of the fi eld research and its translation possibilities in terms of routine clinical practice.]

Clinical Oncology

FEBRUARY 20, 2019

[Liquid biopsy in clinical oncology – fine-tuning precision medicine]

PRISKIN Katalin, PINTÉR Lajos, JAKSA Gábor, PÓLYA Sára, KAHÁN Zsuzsa, SÜKÖSD Farkas, HARACSKA Lajos

[The classical method of genetically characterising a tumour requires tissue biopsy with which a small sample is removed from the affected organ. This sample represents the tumour in the further analyses. However, the localised nature of sample collection limits representative characterisation. The so-called circulating tumour DNA, isolated from blood plasma after a simple sample collection, potentially enables the oncological analysis of all tumour tissues carrying genetic alterations that can be identifi ed as markers. In order to maximally exploit the potentials of circulating tumour DNA, we must adjust the analytical tools to its specifi c features. The preanalytical handling and storage of the sample signifi cantly infl uences its further usability. In order to be able to detect a potential mutation in a mostly wild-type background, the development of new, specifi c methods is needed, most of which are based on next-generation sequencing techniques. In the past decades, the pronounced decrease in the costs of such techniques led to an accumulation of an immense amount of genetic information on tumorigenesis. Due to the development of sequencing technologies, the turnaround times of tests also decreased enabling their employment in routine care besides research. Starting from our research, this can be realised via three approaches: technological development, the implementation of our already existing diagnostic methods in liquid biopsy, and the construction of well-planned disease-specifi c gene panels. Based on international trends and our experience in serum diagnostics, we are certain that liquid biopsy will become a central pillar of oncological screening and precision oncology in the near future.]

Clinical Oncology

DECEMBER 10, 2018

[The use of NGS in oncology in diagnostic setting]

BECSÁGH Péter

[Today the information could be the basis of further development by collecting, saving, structuring and analyzing them. Inside the living organism and inside viruses the biochemical storage system was evolved. The linear coding inside macromolecular structures could create and store a series of building block combinations along the chain structure. Those chemical structures are the so called information coding macromolecules, for example, the polypeptides and nucleic acids. Analysis of the genetically coded functionalities of tumor cells has a great impact in the oncological setting. The connected functions of inherited or acquired alterations inside the tumor cell clones are the main contributors of tumor evolution and surviving, although provide a way to target possible mechanism and touch points. Today the oncodiagnostic use of next generation sequencing technology focus on tumor evolution and tumor surviving connected gene set analysis. This kind of gene panel analysis connected to NGS technology is enough enforced - enforced enough - to reach the diagnostic level, but one still need to take care about the quality and standardization to meet the IVD conditions.]

Clinical Oncology

DECEMBER 10, 2018

[Medical use of marihuana especially in oncology]

VÉGH Éva

[The medical use of marijuana has gained a considerable attention among wide range of cancer patients lately in Hungary. Consequently, oncologist sare facing questions related to cannabinoids more and more in their clinical practice. This article aims to clarify some basic concepts and to give a brief introduction on the current international and national legislation on their accessibility. Numerous publications have dealt with the application of marijuana in various indications. Among the tumour related indications, the concerned studies mainly refer to chemotherapy induced nausea and vomiting, chronic pain, sleep disorders, anorexia and cachexia. The article also to uches upon on knowledge connected to the causal treatment of malignant tumours, which are currently limited to glioblastoma. Information on the carcinogenic potential of cannabis and information on the popularity and attitudes of American oncologists can be found in this article. This paper gives a literature review in the above mentioned themes.]

Lege Artis Medicinae

NOVEMBER 15, 2019

[Specialists’ opinions about the introduction of colorectal cancer screening ]

MAGDA Lilla, TEREBESSY András

[ INTRODUCTION - The number of new cases of colorectal cancer is over 10 000 and there are around 5000 deaths per year in Hungary. A nationwide colon cancer screening program was launched in 2018. AIMS - Concerning the upcoming national screening, our aim was to explore attitudes, preferences and knowledge of specialists (family medicine, gastroenterology, surgery, oncology, pathology) who will be engaged in screening, diagnosis and treatment of colorectal cancer. METHOD - Before the start of the program we conducted semi-structured interviews with 20 representatives of specialties mentioned above. Interview-questions focused on knowledge (epidemiology, screening methods, program-related), preferences (screening method, protocol) and impact of the program on medical practice. Quan­ti­ta­tive and qualitative methods were used for analysis. RESULTS - Incidence of colon cancer was well known but its mortality in Hungary was underestimated. The public health significance of colorectal cancer scored 7 on a 10-point Likert scale and all participants agreed with introduction of the program. 12 people knew the chosen protocol (two-stage), only a single person mentioned one-stage (colonoscopy), and 7 had no information. 16 people prefer colonoscopy as the best screening method. 11 support two-stage protocol, 5 do not support but accept it, 4 would only accept the one-stage approach. 13 people think their duties will increase considerably. CONCLUSIONS - Our review partners consider colorectal screening in Hungary as an initiative to be supported. They expect increase of workload in their everyday medical practice and assume that the current endoscopic capacity will be overburdened. The majority prefers two-stage protocol because of cost-effectiveness while arguing that the colonoscopy has a bad reputation among the general population, nevertheless they consider colonoscopy as the best method of screening. ]

Lege Artis Medicinae

MAY 20, 2019

[Immuno-oncology therapy in patients with non-small cell lung cancer]

CSÁNKY Eszter

[Despite decades of smoking cessation programs, and lung cancer screening programs, mortality due to bronchial cancer leads the mortality statistics among cancer deaths worldwide. Platinum-based chemotherapy has not fundamentally altered the effectiveness of treating non-small cell lung cancer (NSCLC). One of the newest approaches to the use of immunotherapeutic treatments in recent years is the so-called. use of immune checkpoint blocking agents. PD-1 and PD-L1 blockers of this type have been subjected to a large number of clinical trials in lung cancer and were reported by the tumor III.b / IV. stage. Last year, in 2018, we again came up with a milestone in the treatment of lung cancer immuno-oncology, as compared to the previous stage, III.a / III.b Durvalumab con­solidation therapy for non-small cell lung cancer after inoperative, non-chemo-radiotherapy phase I, is based on the results of the PACIFIC clinical trial. PACIFIC was a triple-phase, randomized, double-blind, placebo-controlled, multicentre study to evaluate the efficacy and safety of durvalumab consolidation therapy, irresistible, III. patients with non-small cell lung carcinoma who have not progressed after platinum-based chemo-radiotherapy. The PD-L1 expression level of the tumor was not an admission criterion. In the study, 713 patients were randomized to durvalumab and placebo for 2:1, progression-free survival (PFS) and over­all survival (OS) as their primary endpoint. Summarizing the results of the study, durvalumab provided significant benefit to patients at both endpoints. PFS and OS values were also significantly longer for durvalumab than placebo, and the safety profile of durvalumab was consistent with previous PD-1, PD-L1 inhibition tests.]