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Clinical Neuroscience

MAY 30, 2019

[The effect of bevacizumab monotherapy on progression free survival in recurrent glioblastoma]

CZIGLÉCZKI Gábor, SINKÓ Dániel, BENKŐ Zsolt, BAGÓ Attila, FEDORCSÁK Imre, SIPOS László

[Introduction, the aim of study - Glioblastoma, WHO grade IV is the most frequent primary malignant brain tumor in adults. There are few articles and result about the efficacy of bevacizumab monotherapy. The aim of our paper is to examine the effect of bevacizumab therapy on progression free and overall survival in an extended database of recurrent glioblastoma patients. Patients and methods - In our retrospective study, patients with recurrent glioblastoma treated with bevacizumab had been collected. All of our patients received first line chemo-irradiation according the Stupp protocol treatment. The histological diagnosis was primary or secondary glioblastoma in every patient. The prognostic features of primary and secondary glioblastomas were statistically analyzed. Results - Eighty-six patients were selected into the retrospective analysis. The histological diagnosis was primary glioblastoma in 65 patients (75.6%) and secondary glioblastoma in 21 patients (24.4%). The mean follow up period was 36.5 months. The mean second progression free survival beside bevacizumab therapy was 6.59 months and the mean overall survival was 24.55 months. In secunder glioblastoma cases, the mean second progression free survival was 6.16 months and the mean overall survival was 91.94 months. Conclusion - The bevacizumab therapy is a safe option in recurrent glioblastoma patients. Bevacizumab therapy has a positive effect both on progression free and overall survival and our results confirm the findings in the literature. There is no statistically significant difference in the second progression free survival between glioblastoma subtypes.]

Clinical Oncology

FEBRUARY 28, 2020

[Neoadjuvant and palliative drug therapy for bladder cancer]

MARÁZ Anikó

[The survival of patients with muscle-invasive localized bladder cancer is more favorable if they receive neoadjuvant or adjuvant cisplatin-based chemotherapy before or after cystectomy. Based on the meta-analyses, in case of neoadjuvant cisplatin-based chemotherapy, the 5-year survival benefi t is 5-16%. The outcome is even more favorable in case of patients who respond well to neoadjuvant chemotherapy (pathological complete remission rate 12–50%). More than 3 months delay of cystectomy does not signifi cantly reduce the survival if chemotherapy is performed before the operation. Results of adjuvant phase III studies and meta-analyses are not so unambiguous as neoadjuvant data, but chemotherapy seems to infl uence favorably PD-L1 expression the survival, especially in case of pT3/4 and/or N+ (and high grade or margin positivity) cases. According to the recent publications, outcome data of patients have been effective in case of progression after platinum therapy, in or after second-line and in fi rst-line therapies for cisplatin ineligible, PD-L1 positive patients, respectively. Survival and tumor response data are very promising; in particular stages, they seem to be more effective than the previously administered chemotherapies. Current and ongoing trials are investigating the combinations of new remedies with other immunotherapeutic agents or chemotherapies as well as trying to identify biomarkers in order to further increase effectiveness.]

Hypertension and nephrology

OCTOBER 20, 2018

[Hungarian Vasculitis Registry – results of the first five years]

HARIS Ágnes, TISLÉR András, ONDRIK Zoltán, FILE Ibolya, MÁTYUS János, ZSARGÓ Eszter, DEÁK György, AMBRUS Csaba

[Launching the Hungarian Vasculitis Registry aimed to collect information about prevalence and outcome of our patients with ANCA-associated vasculitis, and treatment protocols of the disease. The on-line data collection has been developing dynamically since its initiation five years ago, presently 278 patients’ files are available. Patients’ mean age is 58.2±14.5 years, 62% are women; their disease is associated with c-ANCA positivity in 51% and p-ANCA in 49%. At diagnosis GFR was 24.6±21.6 ml/min/1,73 m2, that time 29%, during the total follow up 39% of the registered subjects needed dialysis. Renal replacement therapy could be discontinued in 23% of them. In cases with focal histological changes, also with upper respiratory tract and skin involvement dialysis was significantly less frequently necessary, which underlines the importance of early diagnosis. In induction therapy steroid was administered for 94% of the patients, 85% of them got cyclophosphamide, 59% was treated by plasmapheresis, 11% got rituximab. Maintenance treat ment contained steroid in 80%, per os cyclophosphamide in 23%, parenteral cyclophosphamide in 22%, furthermore 40% of the patients got azathioprin, 8 subjects got mycophenolate and 6 got methotrexate. Median follow up was 30 months (IQR 6-78), during which period 20% of the patients died, 5% got kidney transplantation, and 5% were lost to follow up. Median survival was 14.8 years, five years survival was 85%, and ten years survival was 70%. Long term survival in patients with c-ANCA vasculitis seemed better comparing to p-ANCA vasculitis, but when correcting by age this difference disappeared. Predictors of death were age and dialysis dependent renal failure. Relapses developed in 27% of patients, 28% of them presented in the first year, 21% suffered it after five years of care. Collected data by the Hungarian Vasculitis Registry shows our society’s successful professional activity. Our results are comparable to the published data in the literature, yet there are several areas in our care where further improvements are warranted in order to increase our patient’s survival and quality of life.]

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).]

Hypertension and nephrology

FEBRUARY 24, 2021

[Risk estimates of advanced chronic kidney disease and predicting mortality in dialyzed patients]

KULCSÁR Imre, KULCSÁR Dalma

[In mostly the second part of the last decade lots of epidemiological study have been released about the progression of the chronic kidney disease (CKD) and theirs connection with the risk of death. The fact that lots of nephrologist from all over the world (from Canada to New-Zealand) are pretty much interested in this topic is absolutely proved by national (REIN Study – French Registry) and international (KDIGO Controversies Conference, DOPPS 1-5, or the European AROII Study) researchers with these epidemiological questions in their focus. The risk estimation facts that are able to show the life expectancy of patients with CKD 3-5 (expected time to dialysis or mortality risk before renal replacement therapy – RRT) and the early or hopefully longer survival odds of the dialyzed ones could be very useful not only for the medical stuff but also for the patients. In case of the predialyzed patients the focus has to be on the Bansal score and also on the Kidney Failure Risk Equation (KFRE) scores (with 4 and 8 variable); on the other hand in dialyzed patients the REIN score that prognose a short-term survival and the Cohen model (both are easy calculated with webcalculators) are in the highlight of importance. There is not a big difference (2- 7%) in validated researches between the prognosed and the real survival dates. Despite of this prediction has to always be evaluated individually in favour of the best decision we can make for the patients and in order to choose the right treatment: conservative therapy, dialysis or transplantation.]

Clinical Oncology

DECEMBER 10, 2018

[Advancing therapies in metastatic castration-resistant prostate cancer]

GIULIA Baciarello, MARCO Gicci, KARIM Fizazi

[Introduction: Prostate cancer is the second most common cause of cancer world wide and is the most frequently detected cancer in the European Union in men over 50 years of age. Androgen deprivation therapy remains the corner stone of treatment for recurrent or metastatic disease. Unfortunately, nearly all patients will develop resistance to androgen blockade leading to castration-resistant prostate cancer (CRPC). Over the last 10 years, new treatment shaved ramatically improved overall survival of men with mCRPC. Current therapies are basedon AR-axis inhibitors and taxane-based chemotherapies, aswell as radiopharmaceuticals and Sipuleucel T. Areas covered: The authors provide a review of the current fi eld of systemic therapy in metastatic CRPC. This is followed by an in-depth analysis of recent developments in treatment, and the biological rationale behind these therapies. Expert opinion: Since several trials with docetaxel or novel hormonal agents showed improvement in overall survival in metastatic castration-sensitive prostate cancer, aswell as in non-metastatic castrationresistant patients, it is expected that a growing subgroup of patients will be expose dearlierto chemotherapy and to AR targeted agents. It becomes then fundamental to fi nd novel strategies to over come drug resistance and further improve survival.]

Hypertension and nephrology

MAY 10, 2019

[One-year persistence of fixed-dose combinations of angiotensin-converting enzyme inhibitor and calcium channel blocker in hypertensive patients]

SIMONYI Gábor, FERENCI Tamás, FINTA Ervin, IGAZ Iván, BALOGH Sándor, GASPARICS Roland, MEDVEGY Mihály

[Introduction: The most recent European guidelines for the treatment of hypertension suggest the use of renin-angiotensin-aldosterone system antagonists (RAAS inhibitors) and calcium channel blockers (CCBs) or diuretics fixed-dose combinations (FDCs) as the first therapeutic option. In antihypertensive therapy, the patient’s adherence is one of the most important factors in reducing unwanted cardiovascular events. Aim: Our aim was to assess the one-year persistence of angiotensin-converting enzyme inhibitor (ACEI) and CCB FDCs in hypertensive patients. Method: Authors have analysed the prescription database of the National Health Insurance Fund in Hungary on pharmacy claims between October 1, 2012 and September 30, 2013. Those patients were identified who filled prescriptions for FDCs of ACEI and CCBs prescribed for the first time for hypertensive patients and who had not re ceived similar drugs during the year before. Apparatus of survival analysis was used, where ‘survival’ was the time to abandon the medication. Results: 124,388 patients met the inclusion criteria. One-year persistence rate and hazard ratio (HR) of discontinua tion in patients with ramipril/amlodipine FDC was 54% (HR = 1.00, reference), perindopril/amlodipine 47% (HR = 1.30, p<0.0001), lisinopril/amlodipine 36% (HR = 1.79, p<0.0001), ramipril/felodipine 26% (HR = 2.28, p<0.0001) and trandolapril/verapamil 12% (HR = 4.13, p<0.0001). The average survival time of drug limited to 360 days was 270.2 days for ramipril/amlodipine FDC, 242.7 days for perindopril/amlodipine FDC, 211.2 days for lisinopril/amlodipine FDC, 186.3 days for ramipril/felodipine FDC and 125.7 days for trandolapril/verapamil FDC. Conclusions: The authors demonstrated that the one-year persistence of ACEI/CCB FDCs was significantly different in hypertensive patients. Ramipril/amlodipine FDC was more advantageous for patient adherence.]

Clinical Oncology

APRIL 30, 2020

[Tumor induction by chemotherapy]

[Without chemotherapy, the fi ve-year survival rate of detected cancers would be between 0 and 15%, depending on the tumor, and between 17 and 85% with current therapy. Several warnings call attention to the dangers of chemotherapy-induced side effects, most notably the potential for tumor-inducing ability, which can affect 5-10% of patients who have recovered beyond fi ve years. Some systematically applied drugs used in chemotherapy (alkylating agents, etoposide, arsenic trioxide) are able to cause mutations in healthy cells of the patients, increasing the likelihood that the mutated cells will start a later (secondary) tumor formation. In addition to mutagenic effects, some chemotherapeutic agents exert their effects on normal myeloid and epithelial cells of the body, which, by altering the tissue microenvironment, create the potential for malignant transformation. Tumor-associated macrophages (TAMs), which can alter gene expression patterns by tumor cell secreted factors and promote the survival and invasiveness of tumor cells by pro-carcinogenic signals, are very important in this process. It is of utmost importance that doctors, pharmacists, technicians and nurses working with cancer-causing materials do not come into direct contact with dangerous substances and wear appropriate protective equipment.]

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

DECEMBER 30, 2019

[Targeted and immune therapies for hepatocellular carcinoma: Predictions for 2019 and beyond]

MASATOSHI Kudo

[Systemic therapy for hepatocellular carcinoma (HCC) has markedly advanced since the survival benefi t of a molecular targeted agent, sorafenib, were demonstrated in the SHARP and Asia Pacifi c trials in 2007. Treatment options for patients with advanced HCC increased by sorafenib, and long-term survival for patients with advanced stage HCC has become possible to some extent. However, development of a more potent fi rst-line novel molecular targeted agent replacing sorafenib and a potent second-line agent after disease progression on or intolerant to sorafenib has been warranted because sorafenib lacks tumor shrinking/necrotizing effects and induces relatively severe adverse events such as hand foot skin reaction. Many agents in the 1st line and 2nd line setting were attempted to develop between 2007 and 2016, but all of these clinical trials failed. On the other hand, clinical trials of 4 agents (regorafenib, lenvatinib, cabozantinib, and ramucirumab) succeeded in succession in 2017 and 2018, and their use in clinical practice is possible (regorafenib and lenvatinib) or underway (cabozantinib and ramucirumab). Furthermore, all of 5 clinical trials of combination therapy with transcatheter chemoembolization (TACE) plus a molecular targeted agent failed to date, however, the combination of TACE and sorafenib (TACTICS trials) was reported to be successful and presented at ASCO in 2018. Phase 3 clinical trials of immune checkpoint inhibitors and a combination therapy of immune checkpoint inhibitors and molecular targeted agents are also ongoing, which suggests treatment paradigm of HCC in all stages from early, intermediate and advanced stage, is expected to be changed drastically in the very near future.]