Clinical Oncology

[Treatment of hepatocellular carcinoma - today]


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.]



Further articles in this publication

Clinical Oncology

[Pharmacological treatment of metastatic melanoma]

OLÁH Judit, GYULAI Rolland

[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.]

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]


[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]


[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.]

All articles in the issue

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Clinical Oncology

[Radiological response evaluation of targeted therapy]


[The objective assessment of the changes in the tumor burden along with cancer therapy has essential importance. Recently, the quantitative evaluation of the radiological tumor response was undergone several changes. For conventional chemotherapy of solid tumors the standard procedure has been RECIST since 2000. The targeted therapies trigger other pathophysiological changes in the cells than the cytotoxic agents, accordingly the morphological changes show a new picture. Therefore the targeted therapies require a new evaluation system, that takes into consideration not only the tumor size, but other changes as well, the changes of attenuation that corresponds with the proportion of the viable cells. In case of the targeted therapies in substantial clinical was experienced even without signifi cant morphological changes in the tumour size. As a consequence, the traditional, size-based criteria system can underestimate the effi ciency of the new types of treatments. To eliminate this problem new evaluation systems were created taking the tumortypes and treatment protocolls into consideration. The estimation of the early tumor response to targeted therapy also has high importance. In assessment of the response functional imaging methods are used more frequently. The role of PET has already been defi ned in numerous tumortypes, however the determination of the position of some promising functional examinations still require further studies.]

Clinical Oncology

[Current management of GIST]


[Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. GISTs are generally resistant to chemotherapy and radiotherapy. The understanding of pathology at molecular level promised the development of novel treatment modalities. KIT and PDGFRA gene mutations play an important role in the pathogenesis of GIST. IMutational analysis should be considered as standard practice during the diagnostic work-up, since it has a predictive value for sensitivity to molecular-targeted therapy and also has prognostic value. The aim of this review is to summarize recent knowledge about diagnosis, treatment and follow up of GIST.]

Clinical Oncology

[Signaling pathways in cancer stem cells (Notch, Hedgehog, Wnt)]


[OThe key regulators in the embryonic life, and later in the differentiation of tissues and organs are the evolutionary reserved signalling pathways, as Notch, Hedgehog and Wnt. Mutations of these pathways have been identifi ed in many tumor types, increasing the risk to the appearance of cancer stem cells (CSC), with very similar geno- and phenotype as normal stem cells have. Such CSCs with stemness functions can be developed not only from normal stem cells, but also from progenitor and differentiated cells. The main characteristics of CSC are the self maintenance, slow growth rate, very effective DNA-repair system, etc. All of these can contribute to the resistance. Further problems are the low number of CSC in the whole tumor mass, which makes rather diffi cult to achieve the effective drug concentration in CSC. The mentioned ancient pathways interact with many other pathways to form a network, which can infl uence the strategy of therapy. No doubt, that these pathways are promising targets, however, till now the clinical effectiveness is very low due to some reasons mentioned above. Nevertheless, some drugs are already in clinical use, either as monotherapy or part of the combinations. Little is known about the relationship between the pathways and the microenvironment, which has an outstanding role in the cellular activities, sometimes resulting opposite output. It is a great challenge to design effective drugs against CSC, similarly to fi nd reliable predictive biomarkers, which unfortunately still missing, since a reasonable drug-marker interactions would speed up the personalized treatment.]

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.]

Clinical Oncology

[Tyrosine-kinase inhibitors and bisphosphonates in the treatment of metastases from renal cell carcinoma]

EDUARD Vrdoljak, TOMISLAV Omrčen

[Bone metastases (BMs) are common in patients with renal cell carcinoma (RCC) and approximately in 30% of patients with metastatic RCC (mRCC) will develop. Inhibition of vascular endothelial growth factor (VEGF) has been pursued as a therapeutic target in the treatment of metastatic clear cell RCC (mRCC). Tyrosine kinase inhibitors (TKIs), such as sunitinib, pazopanib, sorafenib, and axitinib, became the therapy of choice for patients with mRCC. Apart from the undisputed effi cacy of TKI in treatment of mRCC, the problem of metastatic bone disease still remains. There is evidence that the presence of BMs in m-RCC patients has a signifi cant and clinically-relevant negative impact on survival and potentially on the outcome of VEGF-targeted therapy. Also, common practice in the treatment of such patients is bonedirected therapy with BPs. Recent evidence shows a potentially synergistic effect on effi cacy but also a potential impact on increased toxicity of combining TKIs and BPs. This review highlights the importance of this subject and aims to facilitate further research and optimize the treatment of this important and common group of RCC patients.]