Search results

Clinical Oncology

APRIL 10, 2019

[Metals and cancer]

VETLÉNYI Enikő, RÁCZ Gergely

[We often tend to forget about our environment when looking for the origin of a disease. Inhaled air, drinking water and food, substances in contact with the skin all have an effect on the human body. Metals are indispensable parts of our everyday lives, their mining, processing and use cause a continuous exposure to them. Metal exert their effects on the body in various ways. Many of them are essential for maintaining homeostasis, but excessive or harmful metal intake can lead to health damage, including tumour formation through multiple attack points. Metals substitute each other during different transport processes and in the structure of proteins, they cause oxidative stress and bind to DNA, thereby damaging it. Applying them appropriately, the proapoptotic effect of the metal compounds is brought to the fore, thus becoming a therapeutic tool for tumours. Nowadays, platinum(II) compounds are widely used as chemotherapeutic agents and there are many ongoing studies to fi nd metal compounds with an ideal therapeutic and side-effect profi le. The aims of this article were to draw the attention to the dangers of metals in relation to cancer and to highlight their diverse application possibilities in current and future cancer therapy and diagnostics.]

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.]

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

[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.]

Clinical Oncology

DECEMBER 30, 2019

[Sequential therapy of metastatic renal cell carcinoma]

TORDAY László

[The incidence of renal carcinoma is on the rise in developed countries, with the tumor being among the 10 most common malignancies. However, the survival of patients with irresecable renal carcinoma has improved signifi cantly in recent years, mainly due to signifi cant advances in oncology treatment. The use of agents acting on the VEGF and mTOR signaling pathways is widespread and has become a standard clinical practice in fi rst and later line therapy. Recent clinical trials have provided many new drugs with new targets (cMET and AXL, FGFR, PD-1/PD-L1, CTLA-4) and combinations thereof, and have completely redrawn the treatment landscape of metastatic renal carcinoma and signifi cantly improved clinical results. This report reviews data on targeted drug therapy of renal cell carcinoma and discusses the therapeutic position of various drugs and combinations to our knowledge.]

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.]

Clinical Neuroscience

NOVEMBER 30, 2020

Risk factors related to intracranial infections after transsphenoidal pituitary adenomectomy under endoscope

YIFAN Xu, YUXIN He, WU Xu, TIANYU Lu, WEIBANG Liang, WEI Jin

Background – Up to now, the risk factors related to intracranial infections after transsphenoidal pituitary adenomectomy remain controversial. Purpose – To analyze the risk factors related to intracranial infections after transsphenoidal pituitary adenomectomy under an endoscope, and to provide evidence for preventing and controlling the occurrence and development of infections. A total of 370 patients receiving endoscopic transsphenoidal pituitary adenomectomy in our hospital from January 2014 to October 2017 were selected. The risk factors related to postoperative intracranial infections were analyzed. The hospitalization lengths and expenditures of patients with and without intracranial infections were compared. Of the 370 patients, 18 underwent postoperative intracranial infections, with the infection rate of 4.86%. Intraoperative blood loss >120 mL, cerebrospinal leakage, diabetes, preoperative use of hormones, macroadenoma as well as surgical time >4 h all significantly increased the infection rate (P<0.05). Preoperative use of antibacterial agents prevented intracranial infection. Compared with patients without intracranial infections, the infected ones had significantly prolonged hospitalization length and increased expenditure (P<0.05). Discussion – It is of great clinical significance to analyze the risk factors related to intracranial infection after endoscopic transsphenoidal pituitary adenomectomy, aiming to prevent and to control the onset and progression of infection. Intracranial infections after endoscopic transsphenoidal pituitary adenomectomy were affected by many risk factors, also influencing the prognosis of patients and the economic burden.

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.]

Lege Artis Medicinae

SEPTEMBER 30, 2020

[Frequency and risk factors of “de novo” tumors after kidney transplantation ]

BORDA Bernadett, HÓDI Zoltán, SZEDERKÉNYI Edit, OTTLAKÁN Aurél, SEREGÉLY Edit, LÁZÁR György, KERESZTES Csilla, VIRÁG Katalin

[After kidney transplantation, the administration of immunosuppressive therapy not only renders the patient susceptible to infections, but it may also damage the function of tumor cell recognition and elimination. Our study was performed at the Department of Surgery, University of Szeged. After establishing the inclusion criteria, 570 patients were involved in the study. We examined the age, sex, immunosuppressive therapy of the patients, and searched for the rela­tionship between the different immunosuppressive agents and the type of the tumor. In 81 cases, de novo cancer was diagnosed. Among patients treated with cyclosporin and tacrolimus there was no significant difference in the mean age (p = 0.734) and body mass index (p = 0.543). There was no significant difference in graft function between the two groups of patients (Tac vs Cyc; 44 vs 20). Related to the time passed since the trans­plantation to diagnosing the tumors the earliest were prostate and cervix cancers however without significant difference. Skin cancers are the most frequent followed by post-transplant lym­pho­prolife­ra­tive diseases. The increasing risk of developing tumors is mainly due to immunosuppressive therapy. ]