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Lege Artis Medicinae

SEPTEMBER 30, 2020

[Analysis of factors influencing the efficacy of Hungarian acute cardiac care]

BECKER Dávid, SKODA Réka, BOKOR Laura, BÁRCZI György, VÁGÓ Hajnalka, MERKELY Béla, GAJDÁCSI József, BELICZA Éva, NEMES Attila, DINYA Elek, TÖRŐCSIK Klára

[Despite the modern invasive acute cardiac care available for all, as opposed to short-term mortality, the long-term mortality of Hungarian myocardial infarction patients exceeds significantly those of European patients getting similar treatment. In order to change this situation, it is necessary to assess and analyse exactly the factors behind. While analysing retrospectively the data of Hungarian acute myocardial infarction patients, we identified the influencing factors of short- and long-term mortality. This study processed data from 2003 to the present days from a number of registries (Heart- and Vascular Center of Semmelweis University VMAJOR I and VMAJOR II registry, Stent for Life I and II Programs of the European Society of Cardiology, National Public Health Service’s registry about Cardiac Care in Central Hungary, Budapest Modell database). According to our detailed examination, the proportion of primary per­cutaneous coronary intervention in ST-segment elevation myocardial infarction is at Western-European level, however the invasive treatment of acute coronary attack patients with Non-ST segment myocardial infarction is below the required. The so-cal­led hesitation span of Hungarian pa­tients with ST-segment myocardial infarc­tion is substantially longer than that of neighbouring countries thus the average cardiovascular risk of relevant Hungarian patients is significantly higher than those of the GRACE Register’s population. Based on our results a complex strategy can be developed which may have impact also on strategic health­care decisions in order to reduce the long-term mortality of patients surviving myocardial infarction.]

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 Oncology

APRIL 30, 2020

[Development and 10-year history of a biosimilar: the example of Binocrit®]

AAPRO Matti, KRENDYUKOV Andriy, HÖBEL Nadja, SEIDL Andreas, GASCÓN Pere

[Patent expirations for several biological products have prompted the development of alternative versions, termed ‘biosimilars’, which have comparable quality, safety and effi cacy to a licensed biological medicine (also referred to as the ‘reference’ medicine). The fi rst biosimilars developed in oncology were the supportive-care agents fi lgrastim and epoetin. Binocrit® (HX575) is a biosimilar version of epoetin alfa, indicated in the oncology setting for the treatment of chemotherapy-induced anemia (CIA). The process for development and approval of Binocrit® as a biosimilar included extensive analytical characterization and comparison with the reference epoetin alfa. This was followed by a clinical development program comprising phase I pharmacokinetic/pharmacodynamic studies to show bioequivalence to the reference medicine and a confi rmatory phase III study to confi rm therapeutic effectiveness in CIA. Since its approval, Binocrit® has been extensively used and studied in real-world clinical practice. The accumulated data confi rm that Binocrit® is an effective and well-tolerated option for the treatment of CIA in patients with cancer.]

Clinical Oncology

APRIL 30, 2020

[Coronavirus pandemic – new challenges in oncotherapy]

MINÁROVITS János

[This review outlines some of the basic observations related to coronaviruses infecting animals and describes – in a nutshell – the characteristics of human coronaviruses causing mild or severe respiratory diseases in infected individuals. A special attention is given to SARS-CoV-2, the causative agent of the current coronavirus disease (Covid-19) pandemic, and to the pathomechanism of severe acute respiratory syndrome (SARS) which is also accompanied with multiorgan failure in a subset of infected patients. Recently discovered unique molecular features of SARS-CoV-2 are described as well. These molecular cues may affect human to human virus transmission whereas they are absent, remarkably, from the other lung-targeting highly pathogenic human coronaviruses (SARS-CoV-1 and MERS-CoV) which did not spread all over the world. The possibilities of active immunization to prevent SARS-CoV-2 infection and the development of selective small molecule inhibitors curbing the replication of the virus are also touched upon. The review closes with a few remarks regarding the Hungarian and international recommendations concerning the treatment of SARSCoV- 2 infected cancer patients.]

Clinical Oncology

APRIL 30, 2020

[Immunotherapy of hepatocellular carcinoma]

DEMETER Gyula

[The systemic treatment of HCC was based exclusively on sorafenib near 10 years. In the past 2-3 years some new molecules demostrated their effectivites in phase III clinical trials. So the immuncheckpoint-inhibitors (ICI) demands their place in systemic treatment of HCC. Nivolumab and pembrolizumab are recommended already in second line in NCCN and ESMO clinical guidelines. Nivolumab demostrated his effectivity against the standard treatment sorafenib in a phase III clinical trial, although the results were not signifi cant. However, the combination treatment of atezolizumab and bevacizumab seems better than sorafenib in a phase III clinical trial, so the combination is recommended already in fi rst line in the NCCN guideline. There are more clinical trials with ICIs in progress as in monotherapy as in combination therapy with other modalities.]

Lege Artis Medicinae

NOVEMBER 30, 2020

[Lung cancer – a review of thirty years. Thoughts about the past struggles, the present results and promises of the future]

OSTOROS Gyula

[In the past thirty years there was a huge development in the complex treatment of lung cancer. This development is due mostly to the last decade. Nihilism of lung cancer treatment is over and it is a reality that even patients in advanced stage turn out curable by appropriate therapy and their condition may be changed for a chronic disease while using anti-tumour therapy. Thirty years ago, the realistic life expectancy of six to eight months in advanced stage mounted nowadays significantly, and may surpass even five years in a number of cases. It required adequate diagnostic background, which provided the biomarker based treatment. In early stage surgical resection has a fundamental role, coupled with modern complex neoadjuvant and adjuvant treatment, while new surgical techniques also contributed to the improvement of therapeutic results. The same is true for radiation therapy. The same complex strategy is prevailing also in pharmaceutical options, which are dominated by modalities of cytotoxic chemotherapies and targeted immunothe­rapies. Multidisciplinary teams play a significant role in strategic decisions of lung cancer treatment. The future ways are indicating repeated innovations of tar­geted therapies and extended indica­tions of immunotherapy in terms of precision medicine. However, we must keep in mind also the primary and secondary prevention with effective smoking cessation programs and low-dose chest CT scree­ning applied as usual soon in the risk groups. ]

Clinical Oncology

FEBRUARY 28, 2020

[The treatment of the locally advanced and the metastatic gastric cancer]

SIPŐCZ István

[Although signifi cant progress has been made in the treatment of stomach cancer recently, survival results are still quite modest. The purpose of this overview is to take a look into the history of the treatment of locally advanced and metastatic stomach cancer and to present the current treatment standards. It focuses on recent changes in perioperative treatment, as well as the changing of treatment of metastatic patients. The use of multiple line of palliative chemotherapy and the place of the available targeted treatments in metastatic tumours will be analysed in detail. The increasing use and the future possibilities of immunocheckpoint inhibitors will also be discussed. Molecular subtypes of gastric cancer are also mentioned as possible indicators of the choice of therapy. Finally, it intends to give therapeutic proposals to make recommendations to treat the disease taking into account the opportunities in Hungary.]

Clinical Oncology

FEBRUARY 28, 2020

[Treatment sequencing in metastatic colorectal cancer]

MODEST D. P., PANT S., SARTORE-BIANCHI A.

[Metastatic colorectal cancer (mCRC) remains incurable in most cases, but survival has improved with advances in cytotoxic chemotherapy and targeted agents. However, the optimal use and sequencing of these agents across multiple lines of treatment is unclear. Here, we review current treatment approaches and optimal treatment sequencing across the fi rst-, second- and third-line settings in mCRC, including biological aspects affecting sequencing and rechallenge. Effective fi rst-line therapy is a key determinant of treatment outcomes and should be selected after considering both clinical factors and biological markers, notably RAS and BRAF. The second-line regimen choice depends on the systemic therapies given in fi rst-line. Anti-angiogenic agents (e.g. bevacizumab, ramucirumab and afl ibercept) are indicated for most patients, whereas epidermal growth factor receptor (EGFR) inhibitors do not improve survival in the second-line setting. Molecular profi ling is important in thirdline treatment, with options in RAS wild-type patients including EGFR inhibitors (cetuximab or panitumumab), regorafenib and trifl uridine/tipiracil. Immunotherapy with pembrolizumab or nivolumab ± ipilimumab may be considered for patients with high microsatellite instability disease. Targeting HER2/neu amplifi cation shows promise for the subset of CRC tumours displaying this abnormality. Sequencing decisions are complicated by the potential for any treatment break or de-escalation to evoke a distinct clinical progression type. Ongoing trials are investigating the optimal sequencing and timing of therapies for mCRC. Molecular profi ling has established new targets, and increasing knowledge of tumour evolution under drug pressure will possibly impact on sequencing.]

Clinical Oncology

FEBRUARY 28, 2020

[Opportunities and challenges in online support of cancer patients]

B. PAPP László

[The online support of oncological care may increase patients’ adherence, and by this it can contribute to the effectiveness of treatment, the improvement of quality of life and physician-patient communication as well as to a higher sense of control over the disease. With the online support of supportive care, patients and their relatives can get information on what they can do in order to improve their conditions, how they can recognize side effects and alarming symptoms of complications, what kind of changes they need to make in their lifestyle and how they can reduce the level of distress. Though the positive outcomes are feasible in many cases, quite considerable number of reports in the fi eld do not meet the requirements of evidence. The online support of oncological care may offer considerable opportunities, however, it may further increase inequality: the more educated and well-off patients with higher level of health awareness may benefi t more, meanwhile for the ones at the bottom of digital divide, the disadvantages may increase. The Hungarian internet coverage and accessibility make the broader online support technologically possible, however, its effectiveness may be hindered by the lack of human skills. Therefore, it is a real challenge to establish such platforms that can be used by the broadest spectrum of society, they are comprehensible for patients and their relatives with lower education, but also satisfying for patients and their relatives with higher level of literacy and expectations.]

Clinical Oncology

FEBRUARY 28, 2020

[Non-surgical treatment of ovarian cancer]

PIKÓ Béla, LACZÓ Ibolya,, MARIK László

[The primary surgery with an optimal cytoreduction is an essential step during the treatment of the epithelial ovarian cancer because it determines the effectiveness of other therapeutic options as well. Immediately after the surgery a cytostatic infusion typically 40-42.5 degrees Celsius is pumped directly to the abdomen. During the systemic therapy the main point is the 6 months progression free survival because beyond this time the disease could be considered as platinum sensitive, inside this time as platinum refracter or resistant disease. The cytostatic treatment improved during the years from the alkylating agents through the platinum derivates to the administration of paclitaxel with several combinations of them and with more and more signifi cant results and less side effects. The most signifi cant targeted agents are the angiogenesis inhibitors (mainly the bevacizumab) and the PARP-inhibitors which prevents DNA repairs. In order to a PARP-inhibitor could be administered a platinum sensitivity is required while BRCA mutation not. Recently there are promising clinical researches with immunotherapy as well. The main benefi t of the hormonal therapy is the tolerability. Besides the signifi cant improvement in the systemic agents the role of radiotherapy is more and more decreasing, however the treatment of the whole peritoneal surface – mainly with the modern radiation techniques – could be an alternative solution for the chemotherapy. The palliative irradiation which relieve the symptoms could extend the drug-free period and the combination of radiation and chemotherapy could provide further possibilities.]