Clinical Oncology

[Treatment of hepatocellular carcinoma - today]

VÉGH Éva, DEMETER Gyula, BODOKY György

SEPTEMBER 10, 2014

Clinical Oncology - 2014;1(03)

[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.]

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[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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[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.]

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

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[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.]

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[Data from a clinical study should be always viewed with great care, and is recommended to examine and evaluate the data in-depth. First of all should be determined the evidence level of the trial’s results and what recommendations can be made based on them. The study’s type and the study design, the number of participating patients, statistical power, randomisation, stratifi cation, the balance between study arms, the endpoints and the adequacy of follow-up time should be examined. In addition the importance of the observed statistical signifi cance, the clinical relevance of the data and the real magnitude of the detected differences, and the time-dependent variables are worth to consider because these factors can determine the impact of the given clinical trial on the every-day clinical practice. In the era of the “creative study plans” a critical attitude is necessary to be convinced that the study does not contain any typical bias that could infl uence the real value and actual results of the trial.]

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[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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