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Clinical Oncology

APRIL 30, 2020

[Hormone replacement therapy in cancer survivors – Review of the literature]

DELI Tamás, OROSZ Mónika, JAKAB Attila

[Rapid advance in oncology leads to increasing survival of oncologic patients. More and more of them live long enough to reach either the natural age of menopause or, as a side effect of their oncotherapy, experience the cessation of gonadal function, leading to premature ovarian insuffi ciency, with disturbing vasomotor symtoms and long-term negative cardiovascular and skeletal effects. Thus, an ever increasing number of cancer survivors search endocrinologic help in the form of hormone replacement therapy (HRT). The misinterpretation of the WHI (Women’s Health Initiative) Study has lead to an irrational fear of female hormone replacement, both by the general population and medical professionals. It has seemed the logical and safe conclusion to many physicians to avoid HRT, supposing that this attitude defi nitely causes no harm, whereas the decision of prescribing estrogen alone or with progestins might bear oncologic and thromboembolic risks and may even lead to litigation in case of a potentially related complication. However, it was known even before the WHI results that premature menopause and hypogonadism decreases the life expectancy of women by years through its skeletal and cardiovascular effects, and this negative effect correlates with the length of the hypoestrogenaemic period. Yet, the oncologic risk of HRT is extremely diffi cult to assess. In this work we review the latest evidence from in vitro experiments to clinical studies. We group tumours regarding the oncologic risk of properly chosen female hormone replacement therapy in cancer survivors as follows: ’HRT is advanageous’ (e.g. endometrial cancer type I, cervical adenocarcinoma, haematologic malignancies, local cutaneous malignant melanoma, colorectal cancer, hepatocellular cancer); ’HRT is neutral’ (e.g. BRCA 1/2 mutation carriers without cancer, endometrial cancer type II, uterinal carcinosarcoma and adenosarcoma, certain types of ovarian cancer, cervical, vaginal and vulvar squamous cell carcinoma, prolactinoma, kidney cancer, pancreatic cancer, thyroid cancer); ’HRT is relatively contraindicated’ for various reasons (e.g. leiomyosarcoma, certain types of ovarian tumours, brain tumours, advanced metastatic malignant melanoma, lung cancer, gastric cancer, bladder cancer); ’HRT is diasadvantageous and thus contraindicated’ (e.g. breast cancer, endometrial stroma sarcoma, meningioma, glioma, hormone receptor positive gastric and bladder cancer).]

Clinical Oncology

AUGUST 30, 2019


KIS Erika Gabriella

[Tumors with standard electrochemotherapy (ECT) has raised over the past decade from skin cancers to locally advanced or metastatic tumors. The procedure became a reliable alternative of other local tumor ablation methods, because of its patient tolerability, effi cacy across histotypes, and repeatability. ECT is based on the physical phenomenon of reversible electroporation; short electric pulses are applied to tumor nodules to achieve transient cell membrane permeabilization to otherwire poorly permeant chemotherapy drugs, which consequently increases cytotoxicity. At present recognized indications include superfi cial metastases of malignant melanoma, breast cancer, head and neck skin tumors, Kaposi sarcoma, primary and recurrent nonmelanoma skin cancers, and in well-selected patients mucosal oropharyngeal cancers. Emerging applications include skin metastases from visceral or hematological malignancies, vulvar cancer, certain benign skin lesions, and the combination of ECT with systemic immunotherapy. Thanks to the technical developments, the new ECT indications are deep-seated tumors, including bone metastases, liver malignancies, pancreatic and prostate cancers with the use of long needle variable geometry electrodes. Herein we review the present status of ECT from the basic principles to emerging applications, and report the effi cacy of standard ECT across histotypes.]

Clinical Oncology

SEPTEMBER 10, 2017

[Targeted therapy in melanoma]

EMRI Gabriella

[The incidence of melanoma is increasing, and although most of the melanomas are diagnosed at low tumour thickness, the number of metastatic cases is also increasing. In systemic treatment of metastatic and/or unresectable melanoma, targeted molecular inhibitor or immunotherapy can be used as fi rst-line option depending on molecular pathological report. Targeted treatment results in rapid decrease of tumour burden in high percentage of cases; however, the loss of effect is also frequent due to acquired drug resistance. Further improvement on prognosis of metastatic disease is expected from proper sequencing and/or combination of targeted and immunotherapy.]

Clinical Oncology

FEBRUARY 10, 2017

[Cell cycle as therapeutic target – CDK4/6 inhibition]


[One of the most important decision of a cell: to live or die. If survival is the choice, there are three options: proliferate, to stay in sleeping state for a while, or differentiate in order to perform its specifi c function. These decisions are under a very strict molecular regulation infl uenced by internal and external factors. Tumor cells more and more disregard the regulations, and move into independency for a continuous proliferation, which has a very similar program in normal and tumor cells. The main route towards mitosis is the cell cycle, under the supervision of positive and negative regulators, forming checkpoints, telling to the cell - under the infl uence of mitogenic signals - to go or to stop. The most critical checkpoint is at the border of G1 and S phases where the main players are cyclinD, CDK4/6 and RB1. It turned out that the best targets to inhibit cell proliferation are the CDKs, but this approach, when used unselected targets, was unsuccessful due to the toxicity. To improve the clinical results, the selection of CDK4/6 as a therapeutic target seems to fulfi l most of the hopes. Today three drugs are the most promising: palbociclib (with an acceptance by FDA and EMA to treat breast cancer patients), abemaciclib and ribociclib (underclinical trials). Now, most of the data concern breast cancer, especially the combinations of CDK4/6 inhibitors and endocrine therapy, but many other malignancies are studied (e.g. liposarcoma, mantel cell lymphoma, melanoma, renal cancer, lung cancer, pancreatic cancer, ovarian cancer, teratomas etc.). The key points are the side-effects, the most frequently observed is neutropenia, but so far it is managed without serious toxicity.]

Journal of Nursing Theory and Practice

APRIL 30, 2016

[Risk factors for naevus pigmentosus]


[Naevi are the most frequent disorders of the skin, which usually do not cause a problem. It can occur though, that some of them develop into a malign tumour, called melanoma malignum. This process, called malignisation, has perceivable introductory symptoms; and if they are detected in time and the affected birthmark is removed expertly, it can save the patient’s life. The article describes these symptoms and provides guidelines to the removal of birthmarks.]

Clinical Oncology

FEBRUARY 10, 2015

[Treatments of brain tumors in adults – an up-date]

BAGÓ Attila György

[The prognosis of brain metastases is very poor. Surgery and radiotherapy provides the fi rst line treatment, while systemic therapy has limited value. Nevertheless, our knowledge is increasing: normal cells contribute signifi cantly to the homing and growth of tumor cells; the molecular profi le of the primary tumor and its metastases could be different, which infl uences the therapeutic strategies; the type of blood supply can change during the tumor growth. It would be very important to optimize the cooperation of the different therapeutic modalities, and to fi nd markers which could predict the risk of metastatization.]

Clinical Oncology

SEPTEMBER 10, 2014

[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.]

Lege Artis Medicinae

MARCH 20, 2015

[The role of hypoxia in tissue regeneration and in development of amplified aggressive fenotypes in malignant cancer]


[Several diseases are accompanied by hypoxic stress; elimination of it is an important physiological process. Our body provides a protective function which delays damage and destruction by hypoxia. In case of necrosis, it provides the mop up of the damaged area. This security system starts the regeneration in cells of the hypoxic zone which surrounds the necrotic area, resulting in the survival of the cells in hypoxic environment and ensuring the handling of the necrosis. The key molecules of the system are the hypoxia-induced factor molecules. The review discusses the physiological role of tissue hypoxia and normoxia and its effects on tissue regeneration. The physiological system triggered by the hypoxia-induced factor plays an important role in embryonic development, in wound healing and in numerous diseases (eg. myocardial infarction, stroke, vaculities, etc). Unfortunately, this system also plays a key role in several malignant tumors by rising the development of cells with increased aggressive fenotypes as well. The physiological process of regeneration starts in the hypoxic tumor cells aided by the hypoxia-induced factor system. The process results in neovascularization, and in the case of tissue damage, in the mop up of the necrotic tissue and in the restoration of tissue oxygenisation. However, after the formation of the new vascular network, tumor cells accustomed to hypoxia will not die but keep their original uncontrolled proliferation and anaerobic nature. Moreover the malignant nature of the cells will be increased by the genetic changes generated by the system of hypoxia- induced factors. The role of the hypoxia-induced factor system in tumor progression is discussed by the example of one of the most malignant tumors, malignant melanoma.]