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Clinical Oncology

DECEMBER 30, 2019

[Treatment of cholangiocellular carcinoma]

ANDRÁS Csilla, ÁRKOSY Péter

[Tumors of the biliary tract are a rare entity, at the time of diagnosis most of the patients are in advanced stage and operation can’t be effectuated. After operation the risk of recurrence is high. The standard adjuvant therapy is capecitabin based on the results of BILCAP study. In advanced stage or in the presence of metastates the standard fi rst line treatment is gemcitabine and cisplatin therapy, there are noninferiority results from a Japan study with gemcitabin and S1 combination therapy. There was no evidence of second line treatment possibilities after gemcitabine and cisplatin therapy until 2019, but based on the results of ABC-06 study mFOLFOX could be the choice in the future. In the case of MSI-H/dMMR tumors immuntherapy should be considered. Personalised medicine with matched molecular targeted therapy is a new option. There are 2 new molecular targets, FGFR and IDH, the preliminary result are very promising.]

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

SEPTEMBER 30, 2020

Late simultaneous carcinomatous meningitis, temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting with mono-symptomatic vertigo – a clinico-pathological case reporT

JARABIN András János, KLIVÉNYI Péter, TISZLAVICZ László, MOLNÁR Anna Fiona, GION Katalin, FÖLDESI Imre, KISS Geza Jozsef, ROVÓ László, BELLA Zsolt

Although vertigo is one of the most common complaints, intracranial malignant tumors rarely cause sudden asymmetry between the tone of the vestibular peripheries masquerading as a peripheral-like disorder. Here we report a case of simultaneous temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting as acute unilateral vestibular syndrome, due to the reawakening of a primary gastric signet ring cell carcinoma. Purpose – Our objective was to identify those pathophysiological steps that may explain the complex process of tumor reawakening, dissemination. The possible causes of vestibular asymmetry were also traced. A 56-year-old male patient’s interdisciplinary medical data had been retrospectively analyzed. Original clinical and pathological results have been collected and thoroughly reevaluated, then new histological staining and immunohistochemistry methods have been added to the diagnostic pool. During the autopsy the cerebrum and cerebellum was edematous. The apex of the left petrous bone was infiltrated and destructed by a tumor mass of 2x2 cm in size. Histological reexamination of the original gastric resection specimen slides revealed focal submucosal tumorous infiltration with a vascular invasion. By immunohistochemistry mainly single infiltrating tumor cells were observed with Cytokeratin 7 and Vimentin positivity and partial loss of E-cadherin staining. The subsequent histological examination of necropsy tissue specimens confirmed the disseminated, multi-organ microscopic tumorous invasion. Discussion – It has been recently reported that the expression of Vimentin and the loss of E-cadherin is significantly associated with advanced stage, lymph node metastasis, vascular and neural invasion and undifferentiated type with p<0.05 significance. As our patient was middle aged and had no immune-deficiency, the promoting factor of the reawakening of the primary GC malignant disease after a 9-year-long period of dormancy remained undiscovered. The organ-specific tropism explained by the “seed and soil” theory was unexpected, due to rare occurrence of gastric cancer to metastasize in the meninges given that only a minority of these cells would be capable of crossing the blood brain barrier. Patients with past malignancies and new onset of neurological symptoms should alert the physician to central nervous system involvement, and the appropriate, targeted diagnostic and therapeutic work-up should be established immediately. Targeted staining with specific antibodies is recommended. Recent studies on cell lines indicate that metformin strongly inhibits epithelial-mesenchymal transition of gastric cancer cells. Therefore, further studies need to be performed on cases positive for epithelial-mesenchymal transition.

Clinical Oncology

APRIL 10, 2019

[Current views on the male breast cancer]

BAKI Márta

[Breast cancer in men is a rare disease, and accounts for only 1% of all diagnosed breast cancers. Hungarian incidence by available data much higher. The greatest risk factor of male breast cancer the elevated estrogen concentration in the body. Genetic disorders, as a Klinefelter syndrome and estrogen exposures and other metabolic changes might cause the male breast cancer. Symptom duration is longer than female population and the male breast cancers diagnosed in older ages and advanced stages. Frequency of BRCA2 mutation is probably 10% among male patients. The most common type is invasive ductal carcinoma with estrogen and progesterone receptor positivity. Diagnostic, surgical, radiation procedures and chemotherapy probably same as female breast cancer. The guidelines recommend as in adjuvant and curative setting the tamoxifen and other selective estrogen receptor modulators treatment. By large nation based registry the survival rate is different from male and female breast cancers. New biomarkers, genetic changes are under investigation to understand munch better the male breast cancer.]

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 Neuroscience

NOVEMBER 30, 2019

[Early experience with CyberKnife treatment in case of intra-, suprasellar hypernephroma metastasis]

SIPOS László, BAJCSAY András, KONTRA Gábor, CZIRJÁK Sándor, JÁNVÁRY Levente, FEDORCSÁK Imre, POLGÁR Csaba

[Among tumours found in the suprasellar region metastases are very rare and the most frequent primary tumours are lung and breast cancer. Data of a patient with clear cell renal carcinoma with intra-suprasellar metastasis will be discussed. As in most of the tumours in the sellar region, the first symptom was visual deterioration with visual field defect. A transsphenoidal debulking of the tumour was performed and the residual tumor was treated by CyberKnife hypofractionated stereotactic radiotherapy. Both our patient’s visual acuity and visual field impairment improved after the surgery and CyberKnife treatment. At 6-month after irradiation, MR of the sella showed a complete remission of the tumour. This was the first treatment with CyberKnife in our country in case of a tumour close to the optic chiasm. According to our best knowledge, there are 21 cases in the literature with renal cell carcinoma metastasis in the suprasellar region.]

Lege Artis Medicinae

MAY 20, 2019

[Physical inactivity and activity. Damage and benefit]

KÉKES Ede, APOR Péter

[Authors address the issue of inadequate physical activity worldwide and analyze their relationship with cardiovascular diseases and total mortality. In the inactivity "world map" it can be seen that in economically developed countries it is very common but other ethnic and regional factors also play a role and it is significantly more frequent at women. In our country this phenomenon due to combination of advanced civilization and computerization is also frequent. From 2000 to 2015, the trend of the presence of physical inactivity (FI) in the high income populations is steadily rising. Convincing evidence suggests that FI increases the risk of many common, serious diseases, including ischaemic heart disease, type 2 diabetes, breast cancer and colon carcinoma, and reduces the life expectancy. For these four diaseses, the incidence of FI occurs in about 1/3 of cases and 35% of total mortality. Its health value (PAF) ranges from 10 to 18%. Low (non-regular) exercise increases the risk of hypertension with or without family history. In subjects with moderate and intensive levels of physical activity (FA), there is a significantly lower mortality rate and the rate of occurrence of major cardiovasculars (CV) diseases compared to those with lower grade FA. Behind the positive effect of physical activity there is a multiple and complicated mechanism that manifests itself in the vascular system, in the physiological adaptation of the heart and in other metabolic and cellular effects. ]

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.]

Lege Artis Medicinae

AUGUST 30, 2018

[Vision or reality? Can Hungary become hepatitis C virus free by 2030?]

GERVAIN Judit

[According to the WHO, there are 71 million people worldwide and 3 million people in the EU who are infected with hepatitis C virus. Most of these infections, however, remain undiagnosed and only 6-7% of them received antiviral therapy. In Hun-gary, there are an estimated 50.000 infections, out of these 20.000 are identified, the remaining 30.000 infections are outside the reach of the health care sector. Early diagnosis and therapy are of utmost importance as late diagnosis leads to se-vere liver insufficiency, hepatocellular carcinoma and multiple other extrahepatic organ impacts. In Hungary, second generation direct acting enzyme inhibitor antiviral medications with a recovery rate of almost 100% are available since 2015. Since 2018, all patients are treated with this type of therapy. Nevertheless, there are several remaining professional, organisational and health policy issues to solve. Firstly, Hungary should join the EU’s HCV elimination programme which aims to eradicate hepatitis C virus from Europe by 2030. Secondly, the frequency and efficiency of national screening should be increased. Furthermore, better information of the general population, inclusion of general practitioners and civil organisations, and introduction of the compulsory screening of high risk groups and health care professionals would be necessary. This review summarises the evolution of hepatitis C virus diagnostics and therapy over the past three decades, current best practice and the still outstanding tasks. ]