Clinical Oncology

[Pharmacological treatment of metastatic melanoma]

OLÁH Judit, GYULAI Rolland

SEPTEMBER 10, 2014

Clinical Oncology - 2014;1(03)

[Malignant melanoma belongs to the group of relatively easily manageable tumors; if detected and removed early, it rarely metastasizes. Although the visible nature of the primary tumor provides opportunity for early diagnosis, there is a signifi cant portion of patients who receive proper management only with substantial delay. The fact that there are annually 300-400 patients with metastatic disease in Hungary, can be mostly attributed to public unawareness about melanoma, and consequent delay in seeking medical treatment. Metastatic melanoma remains - even today - an incurable disease. Molecular genetic research, however, resulted in revolutionary changes in melanoma management. Today, apart from the classic pathological prognostic factors, information regarding specifi c molecular modifi cations (such as in the expression of the BRAF, NRAS, c-KIT genes and proteins) are inevitable for the setting up of a personalized oncological treatment plan. By targeting members of the MAPK signal transmission pathway (using BRAF- and MEK-inhibitors), signifi cant improvement could be achieved in metastatic melanoma. Similarly, new drugs targeting specifi c immune checkpoint regulators (such as CTLA-4 and PD-1/PD-1L) provide previously unprecedented survival benefi t for melanoma patients. In this review the most recent developments in the fi eld of melanoma management are summarized.]

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Clinical Oncology

[Treatment of hepatocellular carcinoma - today]

VÉGH Éva, DEMETER Gyula, BODOKY György

[The hepatocellular carcinoma (HCC) is one of the main causes of cancer-related death globally, and at the same time, it is the main event leading to death in cirrhotic patients. In the etiology of HCC, the non-alcoholic liver disease may be an important cause besides the viral cirrhosis. The HCC’s staging systems (Child-Pugh scores, Cancer of the Liver Italian Programme/CLIP, Barcelona Clinic Liver Cancer/ BCLC) play an important role in predicting the prognosis and determining the appropriate therapy. In Europe, the treatment strategy is based on the BCLC staging system. Screening of cirrhotic patient is also important because curative therapy is available only for the early-stage HCC. Several therapeutic options exist in the intermediate stage disease; among them the radiofrequency ablation (RFA), the transarterial chemoembolization (TACE) and the percutan ethanol injection (PEI) are most important. For the advanced disease, the only approved systemic therapy is sorafenib, which has been well-tolerated and yielded a substantially relative improvement in overall survival. For patient in end-stage disease with impaired liver function or a poor performance status, only supportive care is recommended.]

Clinical Oncology

[Pregnancy and cancer]

NAGY Zsuzsanna, SZILLER István, VALTINYI Dorottya, HORVÁTH Orsolya

[The joint appearance of pregnancy and cancer is rare. It is highly recommended that the tumorous pregnant should be managed by a multidisciplinary team. The early diagnosis is very important, but it is not easy, because the symptoms of pregnancy and cancer are rather similar. Imaging diagnosis has to avoid ionizing radiation (e.g. PET/CT). The same is true for chemotherapy in the fi rst trimester, due to the increased risk of developmental abnormalities. Consequently, radiation therapy is not allowded throughout the pregnancy, and the chemotherapy in the fi rst trimester is a strong indication for the interruption of pregnancy. Surgery, with good practice, usually can be performed without complications. Chemotherapy, given in the second and third trimester generally follows the standard protocols with a low frequency of developmental errors. Early delivery should not be encouraged, except the delay has a hazardous effect on the mother and/or on the child. The pregnant should be informed about all steps to be an active part of the fi nal decision.]

Clinical Oncology

[European examination for clinical oncologists]

HERRMANN Richard

[One of the major tasks of the European Examination Board is to harmonize the knowledge and practice of clinical oncologists throughout the world. The examination consits 100 questions and the positive result is aknowledged by a diploma. More and more countries replace the national exam by ESMO-exam. It is still a challenge how to evaluate the activity of clinical oncologists who are specialized in different area of oncology. The ESMO-exam is available mainly at the ESMO congresses.]

Clinical Oncology

[Targeted therapy: based upon the primary tumor or on its metastases?]

TÍMÁR József

[Most of the primary tumors at various stages are resected or destroied by radiotherapy. Meanwhile, contemporary target therapies are administered in advanced stages, but the required molecular pathologic analysis is performed on the primary tumor supposing stable genetic profi ls durings at different stages of cancer progression. Advanced molecular technologies provided high resolution images on the clonal heterogeneity of the primary tumors and its role in cancer progression. Data indicate that in early and locoregional stages/recurrences the chance for genetic discordance is low while, in late visceral metastases this risk is increasingly higher. The clinical relevance of the genetically discordant metastatic tumors is proven by several retrospective studies. This is the basis of the recommendations that in case of progressing cancer molecular pathologic tests must be performed on metastatic tumors, especially when the primary tumor is resected. On the other hand, it is an unresolved issue what to do in case of discordance between the primary and the metastasis.]

Clinical Oncology

[New aspects in cancer pain relief]

RUZSA Ágnes, HORVÁTH Zsolt

[Authors investigate the new advances in cancer pain relief among the long survival cancer patient, 25-30% of whom suffering from pain. The new molecular targets provide new druggable pain relief options. The changed strategy of pain-killing therapy enhance s the possibility for the long survival cancer patients to decrease problems of the side effects of opiod therapy. The lower doses of opioids in invasive theraputical techniques help patients to live in higher quality of life without the uncomfortable side effects of the drugs.]

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[Cancer-treatment induced peripheral neuropathy]

DEMETER Gyula

[Peripheral neuropathy is caused by structural or functional damage of nervous system. The pathophysiology is not well known. Its clinical features are established but there is a need to standardize CIPN assessment, also considering that health care providers and patients frequently have a different perception of CIPN severity. Neurotoxicity caused by traditional chemotherapy is widely recognized in patients with cancer. The adverse effects of newer therapeutics, such as targeting and immunotherapeutic agents, need more information for the proper management. This review addresses the main neurotoxicities of cancer treatments with a focus on the newer therapeutics. Recognition of these patterns of toxicity is important because drug discontinuation or dose adjustment might prevent further neurological injury. Treatment is symptomatic. For prevention or treatment there is need for further basic research outcomes.]

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[Combination of radiotherapy and immunotherapy]

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[Increasing experimental and clinical evidences demonstrated the synergic effect between the rapidly implemented immunotherapy and advanced forms of focal radiotherapy, not only on the elimination of the irradiated lesion, but also on the enhancement the immune-mediated systemic anti-tumoral activity. It is essential for gaining the most benefi t from the combination of the two modalities to select the appropriate patients, to defi ne the irradiation parameters, such as radiation quality (ie. particle) dosage, (total dose, fraction number) size of the target volume, the use of other supportive and anti-tumor drugs. In this review, we provide an update for the daily oncological practice on the data accumulated up to now on the molecular basis and patomechanism of enhancing radio-immune effect and clinical results, and highlight the most important parameters, which may increase the abscopal effect of ionizing radiation, thereby increasing the effectiveness of immunotherapy. However, development of clinical guidelines for benefi cial integration of immunotherapy and radiotherapy could be expected after evaluation the result of currently ongoing numerous (> 100) clinical trials. If the preclinical results will be confi rmed clinically, it could lead to paradigm shift in the use of ionizing radiation.]

Clinical Oncology

[Immuno(onco)therapy – road to the future]

DANK Magdolna, SZENTMÁRTONI Gyöngyvér, OROSZ Zsuzsanna, TÓTH Andrea, TŐKÉS Tímea

[Our immune system fi ghts effectively against infections, but the same activity exists against invading cancer cells, as well. However, malignant tumors are able to escape from these mechanisms; therefore tumor cells become unrecognizable for the immune system. Immuno-oncology is a novel and innovative discipline, focusing on a long-term purpose: to enhance the immune-response against malignancies. The main goal is to stimulate the immune system to properly recognize and destroy malignant tumor cells. This approach is comprehensive, includes the initiation of antitumor immune-response and enhancing its controlling mechanisms, moreover, provides active, anti-tumor effector cells. Recent results of anticancer research highlighted a new era of oncology, which is based on targeted, personalized medicine over cytotoxic therapies, and mainly focusing on the rapidly evolving discipline of immuno-oncology.]

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[Tumor vaccination]

LACZÓ Ibolya, PIKÓ Béla

[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.]

Lege Artis Medicinae

[Intravenous immunoglobulin immunotherapy in immune mediated habitual abortions]

FÜLÖP Vilmos, PETRÁNYI Győző

[INTRODUCTION - Based upon international and domestic research data authors summerize the humoral and cellular im­munregulatory disorders which can be found in the background of “immune me­diated abortions” (IMA). PATIENTS AND METHODS - Within the frame of a home research program a special examination protocol was elaborated in order to sepatare alloimmune habitual abortions from autoimmune and non immune backgrounds. After all other causes were excluded erythrocyte antibody inhibition assay (EAI) was used for measuring the serum level of FcgRII receptor blocking IgG antibody, because its lack an important diagnostic parameter. Among the cell mediated immunofuntional tests the mixed lymphocyte culture reaction (MLC) was the most useful. During the roughly last 16 years 67 out of 76 selected alloimmun IMA patients were administered Intratect IVIG treatment without any particular selection among them. IVIG treatment was first applied on the completed 5-6th week of pregnancy and doses of 0,3-0,4g/kg bodyweight per oc­casion were given 3 times with 3-week intervals. RESULTS - Altogether a significant rise in the serum level of blocking antibodies was shown after each IVIG treatment although a slight decrease was seen after every given dose. Of the 67 IMA patients 54 carried infants to term during the study period. In 4 cases of abortion no cause was identified with post hoc diagnosis. Thus the success rate of this type of IVIG therapy was 93.1% (58/54). Conclusion - In approprietly selected alloimmun IMA cases the IVIG generated immunoregulatory and antiimflammatory pathways may contribute to its net positive reproductive effect.]