Clinical Oncology

[Fusions in solid tumors]

KOPPER László

MAY 10, 2018

Clinical Oncology - 2018;5(02)

[Genetic fusions are the cosequence of genomic rearrangement including chromosomal inversion, interstitial deletion, duplication, amplifi cation, translocation. Fusions can influence tumor development and progression. Fusions fi rst discovered in hematological malignances (e.g. BCR-ABL), butlater more and more were identified dueto the higly sensitive NGS. It has been found that the oncogenic fusions are in minority in a given tumor. Today, some fusions were apprevedas targets (ALK, ROS1, PDGFB) by FDA. Asino ther targeted therapy resistance is in evitable, which is a very important challenge for newly designed drugs.]

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[Fluid in preformed cavity to malignancy]

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[The malignancy associated fl uids like pleural effusion, ascites and pericardiac fl uid are a common problems in patients with cancer. Despite the existence of typical types of cancer for these fl uid accumulations, nearly all types of cancer can cause malignancy associated fl uids. The presentation of these fl uids is generally a sign for disease progression, and forecast a poor prognosis. The prognostic factors include the type of cancer, the response to antitumorous therapy and the general condition of the patient, which include age, ECOG status and so on. In most of the cases, the treatment of these fl uid accumulations is supposed to decrease the symptoms, and guarantee an acceptable quality of life, consequently the treatment has a palliative intent. Indeed, there are some exceptions such as cardiac tamponade. From the large scale of available treatments, we have to choose upon careful risk analysis.]

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[Although cancer immunotherapy was initiated by William Coley more than a century ago, the fi eld of cancer vaccines is in an early stage of development. Only recently, major advances in cellular and molecular immunology have allowed a comprehensive understanding of the interaction between the immune system and the tumor. Data from several preclinical and clinical trials have confi rmed the positive effect of the cancer vaccines which accompanied in several cases by positive clinical outcomes. In our article we try to discuss the new cancer vaccine strategies which are under development or in a clinical phase stage.]

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[Tumor-associated neurological syndromes]

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[Tumor associate neurological symptoms are heterogeneous clinical entities with diverse etiologies, that may infl uence both the central, and peripheral neural system, as a primary or secondary tumor, may due to immune mediated processes. In our review, we summarize the neural syndromes frequently occurring in oncological practice. We focus on the most frequent neuronal tumors, the brain metastases, that are recently affected by the new targeted and immunotherapies showing increasing intracranial activities. We provide details on paraneoplastic neurological syndromes, because, in spite of their relatively rare occurrence, the modern diagnostic protocols may contribute to early diagnosis that are mandatory for detecting the underlying tumor. Finally we describe the neurological side effects of various oncotherapies, such as PD1 inhibitors, that are accompanied by 3% incidence of neurological complications, and chemotherapy related polyneuropathies. We provide support for anticonvulsive drug selection also, based on their drug-interaction profi le.]

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[Immunotherapy of lungcancer – an update]

OSTOROS Gyula

[Ten years ago the median survival of small cell lung cancer (SCLC) and non small cell lung cancer (NSCLC) was less than one year. In the case of SCLC the situation did not change. There are revolutionary new possibilities in the treatment of NSCLC (histology based cytotoxic chemotherapy, molecular targeted therapy etc.). Unfortunately there is no signifi cant development in treatment strategy of SCLC in the last 30 years. Nowadays in NSCLC immune check point inhibitor therapy is a novel treatment method in the clinical praxis as well. The integration of the PD axis and the CTLA4 inhibitors in the complex therapy of the management of NSCLC is a new challenge. The pembrolizumab monotherapy in fi rst line setting is a new standard of care with high PDL1 expression. In second line setting the pembrolizumab, nivolumab and atezolizumab widely used in clinical praxis as well. In locally advanced disease of NSCLC after radiochemotherapy the durvalumab maintenance monotherapy showed a signifi cant progression free survival benefi t, comparing to placebo. We have got new treatment possibilities in the treatment of SCLC as well. The results of clinical trials with antibody conjugate therapy are promising. The nivolumab monotherapy and the combination treatment of nivolumab + ipilimumab gave promising results as well. In the treatment of SCLC and NSCLC there is a need for biomarker selected therapy (tumor mutational burden [TMB], DLL3, cMyc etc.). Based on the new positive results of the clinical trials there is a possibility to transform lung cancer from a subacute disease to a chronic illness.]

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[Hematopoietic stem cell transplantation for solid tumors in adults]

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[Clinical impact of acetylsalicylic acid resistance in patients with cerebrovascular disease]

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[INTRODUCTION - In the past few years, a number of studies have been published about acetylsalicylic acid resistance and its potential clinical consequences. PATIENTS AND METHODS - 281 patients with chronic cerebrovascular disease have been involved in our study. The patients were divided in two groups on the basis of their optical aggregometer results (acetylsalicylic acid responder vs. resistant). We compared the risk profiles, drug therapies, laboratory parameters and clinical outcomes of the two groups. RESULTS - Acetylsalicylic acid resistant patients were more likely to be women [23 (45.1%) vs. 92 (40%) (p<0.05)], to smoke (38% vs. 25%), have hypertension (92 vs. 78%), hypercholesterolaemia (5.69 vs. 4.85 mmol/l), and elevated LDL-levels (3.71 vs. 2.85 mmol/l), triglyceride levels (2.78 vs. 1.97 mmol/l) and hsCRP levels (17.89 vs. 7.09 mmol/l) (p<0.01). The use of statins was more frequent (56% vs. 36%) in the responder group (p<0.01). Platelet aggregation values (triggered by agonists) were significantly correlated with cholesterol, LDL, triglyceride and hsCRP levels (p<0.05). Adverse outcomes were reached in 13 (25.5%) acetylsalicylic acid nonresponders and 32 (13.9%) acetylsalicylic acid responder patients (p<0.01). In a multivariate analysis, however, only smoking (OR: 2.38, CI: 1.77-5.44) and increased LDL (OR: 3.01, CI: 2.34-5.67) and hsCRP levels (OR: 2.44, CI: 1.55-7.02) (p<0.05) were independent risk factors of adverse vascular outcomes. CONCLUSION - On the basis of our results, acetylsalicylic acid resistance was associated with a worse clinical outcome, but it was not an independent risk factor of future ischaemic events. Our results implicate that inappropriate prevention therapy might have a role in this phenomenon.]

Clinical Oncology

[MEK and ERK - against RAS and RAF ]

KOPPER László

[In most cases, the targeted therapy is able to produce clinical response, but after a certain interval it turns to be ineffective due to secondary resistance against the therapy. One of the most demanding challenge in treatment of cancer is to prevent or inhibit such resistance, which could have several forms, e.g. appearance of new driver activating mutations in the treated tumor, clon(s) existed in minority with different mutations (targets) can grow and replace the temporarely sensitive tumor cells (on the basis of tumor heterogeneity); another pathway takes over the role in cancer progression, etc. Such problems are very common in the RAS-RAF-MEK-ERK pathway. These are very important proteins to collect extracellular signals in order to regular different cell functions, especially proliferation. With activating mutations make the RAS-pathway independent from the normal .regulation. To inhibit the consequence of the mutations is largely still an unsolved problem, with few exceptions (e.g. inhibition of BRAF mutations). Theoretically, the inhibition of the next steps of the pathway, MEK and ERK, may stop the pathologically activated signals, partly due to their inhibition, and party to effi ciently decrease the feedback inside the pathway. This review discusses aspects of this possibilities, especially to overcome resistance and prolong the effectiveness of therapy.]

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SÁRÓ Enikő, MISIK Ferenc, BANCZEROWSKI Péter

[Objective - There is no internationally accepted guideline for treatment of spondylolisthesis in the literature, otherwise this degenerative disease has great social and economical impact. There is no hungarian study examining the efficacy of instrumented fusion procedure in surgical treatment of spondylolisthesis. In current study we examined the effectiveness of fusion technique focusing on the impact of quality of life. Methods - Between 1st January, 2011 and 30th June, 2012 we examined a group of patients - who were operated on by instrumented fusion technique because of spondylolisthesis -, in the National Institute of Clinical Neurosciences, using the Oswestry Low Back Disability Questionnaire. All patients were treated after ineffective conservative treatment. The question was wheather how has changed the patients’ quality of life after the operation. Paired-sample t-test was used in this study. Results - Eighty-eight of the 97 examined patients reported different levels of impovement in the postoperative period, two patient’s condition has not changed in spite of the surgery, seven patient’s condition showed progression in average one year after the surgery. The pain improved most significantly (55.5%) (p<0.0001). Using the 16 point borderline according to the Questionnaire (over moderate disability), significant improvement was detected in 50 patients (51.5%). Succesful surgical result - according to the quality of life - was seen in 77.41% of male and in 50.98% of female patients. According to the different age groups, 72.72% of the younger (before retirement), and 53.06% of the retired patients belonged to this group. At least 15 point improvement was detected 35.05% of the patients, the overall improvement was 10.5 point. Discussion - Our results proved effectiveness of instrumented surgical fusion procedure in the treatment of degenerative spondylolisthesis. According to our results the younger male population with significant symptoms is the group, where improvement in quality of life is more pronaunced after the surgical procedure. Conclusion - The instrumented fusion surgical technique provides successful clinical and surgical outcome in patients with degenerative spondylolisthesis. It could improve the quality of life. Althought multicentre follow-up studies are needed to determine the exact indication and optimal therapy.]

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[Examination of the efficacy of clopidogrel-hydrogen-sulphate in patients with cerebrovascular disease]

SZAPÁRY László, FEHÉR Gergely

[INTRODUCTION - On the basis of current guidelines, acetylsalicylic acid plus dipyridamole or clopidogrel monotherapy should be used for the long-term treatment of patients with cerebrovascular disease, whereas acetylsalicylic acid monotherapy is not recommended. The efficiency of recently introduced generic clopidogrels has not been assessed in patients with a history of acute stroke. PATIENTS AND METHODS - 100 patients with a history of acute stroke or transient ischaemic attack were involved in our study. The patients received acetylsalicylic acid monotherapy in the first 48 hours, followed by clopidogrel-hydrogen sulphate (Egitromb®) monotherapy. The efficiency of the therapy was assessed on day 7 and 28 of medical therapy. RESULTS - At the first measurement (day 7) after clopidrogel-hydrogen sulphate treatment, the therapy seemed to be inefficient in 11 patients (11%). A strong, clinically significant correlation was found between blood pressure values, blood glucose and lipid parameters, hsCRP levels and platelet aggregation values. At the second measurement (day 28), an aggressive secondary preventive threapy resulted in the normalisation of the above mentioned parameters, and the efficiency of platelet aggregation inhibtion therapy was also improed, whereas no patients proved to be resistant. No unwanted events or haemorrhagic complications were registered. CONCLUSIONS - On the basis of the result of our study, treatment with clopidogrel- hydrogen sulphate is safe and efficient both clinically and on the basis of optical aggregometry. The significance of an aggressive secondary preventive therapy should be considered as a factor that might influence the efficiency of thrombocyte aggregation inhibitory therapy.]