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Diffuse large B-cell lymphoma (DLBCL) is a high-grade lymphoproliferative disease of mature B cells, representing the most common lymphoid malignancy of adulthood. There are multiple distinct subgroups of DLBCL in the 2008 WHO classification, organ specific forms, DLBCL associated with immunodeficiency and viral infections and rare CD20 negative and intermediate forms. However, most of the cases are still classified under the DLBCL not otherwise specified (NOS) category. This group of disease shows remarkable heterogeneity with respect to clinical presentation, biology and response to treatment, reflecting several molecular subgroups: the origin of B cells at various developmental stages, the oncogenic pathways that drive tumor development and also epigenetic changes and mutations involving the escape of immune surveillance. Contemporary chemo-immunotherapy does not result in durable remissions in as many as 30% of the cases. To achieve longer survival, the definition of new biomarkers are needed for targeted therapy based on better subgrouping of tumors according to the molecular pathways involved in lymphomagenesis. This paper summarizes the most important features influencing the outcome of this broad disease at the level of morphology, phenotype and genotype and gives a guideline for the routine pathological practice at present for the diagnostics of DLBCL treated by chemo-immunotherapy.

Recently controversial data emerged regarding the cancer inducing activity of angiotensin-receptor blockers. There may be several reasons which may explain the controversial data published in the scientific literature including wrong trial design or misinterpretation of data. Considering the large number of patients receiving treatment for hypertension, it is essential to have a clear view of the cancer-related safety of these drugs. This paper tries to give an overview on this issue based on data available in the literature. According to our present knowledge, angiotensin-receptor blockers exert more likely anticancer activity rather than carcinogenesis inducing effect. In fact, some oncologic trials point to this direction, because angiotensin-receptor blockers are suggested as co-treatment to chemotherapy in cases of pancreatic, oesophageal and gastric cancers.

Prostate cancer is one of the most common cancers in men. In case of metastatic disease, bone manifestation is presented in 85-90% of the patients. The new targeted treatments are the denosumab RANK-ligand monoclonal antibody and Ra-223-chloride radioisotope therapy. This paper summarizes the treatment possibilities of bone metastasis and presents the results of phase III trials of denosumab and Ra-223-chloride. The upcoming change in financial support underlines the actuality of this paper.

Glioblastoma multiforme has one of the worst prognoses of all cancers. A substantial progression in its treatment has been achieved only eight years ago when a new adjuvant radiochemotherapy regimen containing temozolomid has been introduced to the clinical practice. In this paper we evaluate the treatment results in adjuvant radiochemotherapy of glioblastoma carried out by two neurosurgery and oncology centers in Budapest, Hungary and we compared our results to the data of the reference phase III registration trial of the EORTC/NCIC. We analyzed the data of 210 patients treated for glioblastoma between 2005 and 2013. The primary endpoints of our study were overall survival and side effects. We studied and statistically analyzed the influence of multiple factors on survival. We compared our results with the data of the reference study and other results published in the literature. The median follow-up for the surviving patients in our study was 52 months. The median age of our patients was 58 (18-79) years. Seventy-two women and 138 men have been treated. The median overall survival was 17 (3-96) months, the progression-free survival 11 (3-96) months. The radiochemotherapy phase was completed in 95.2% and the monotherapy phase in 68% of all cases.Univariate analysis showed that age, ECOG status and RPA class had significant influence on survival. In multivariate analysis only RPA class remained statistically significant (RR 1.86, 95% CI 1.14-3.05). The proportion of grade III and worse side effects during the chemoradiation phase was 3.8% and in the monotherapy phase 1.9%. These were hematological side effects only. Serious hematological sequelae occurred nearly exclusively in women. Comparing to the reference study the demographic distribution of the patients was similar in our study but among our patients there were less patients with unfavorable prognosis (ECOG 2 or RPA V), and it resulted in a longer median survival than in the original trial (17 vs. 14.6 months). With this analysis of our patients treated according to the Stupp-protocol for glioblastoma multiforme we validated the results of the original EORTC/NCIC study in a Hungarian patient population. Moreover, this comparison proves that the comprehensive Hungarian neuro-oncology service is not at all inferior when compared to any of the developed countries in Europe.

A new trend has been taking place in the daily oncology practice in the past twenty years: we are progressively moving toward individualized and personalized treatments. The treatment of breast cancer is one of the best examples to underline the outstanding effectiveness of the individualized approach. The modern molecular pathology features are capable of predicting the biological behavior of the tumors which gives a new basis for our therapeutic choices, both for neoadjuvant and adjuvant settings, as well as for metastatic disease. In our paper we review the currently used monoclonal antibodies in the treatment of breast cancer and provide an overview of the new research and future directions in this field.

Angiogenesis is essential for tumor growth and metastasis. The main regulators of the process are the signaling cascades of VEGF-, PDGF- and FGF receptors. Inhibition of these pathways holds potential therapeutic benefit not only for cancer patients, but also for the treatment of other diseases. This paper summarizes the experimental and clinical results of studies available so far on the multi-target tyrosine kinase inhibitor nintedanib (BIBF 1120). According to these studies, nintedanib effectively inhibits VEGFR-, PDGFR- and FGFR signalization and thus the proliferation and survival of cell types which highly express these receptors (i.e. endothelial and smooth muscle cells and pericytes). In vitro studies and in vivo xenograft experiments have provided promising results. In the clinical setting, BIBF 1120 seems to be effective and well tolerated in various tumor types, such as lung, prostate, colorectal and hepatocellular carcinoma, as well as in gynecological tumors. The main adverse events are gastrointestinal toxicities and the reversible elevation of liver enzyme levels. Nintedanib might also be combined with paclitaxel, carboplatin, pemetrexed and docetaxel. There are several ongoing clinical trials testing the efficacy of BIBF 1120.

Imiquimod belongs to the family of synthetic small nucleotid-like molecules of imidazoquinolinamines. It is an immune response modifier with potent antiviral and antitumor effects, which are mediated by Toll-like receptors (TLR7 and TLR8). Imiquimod targets predominantly TLR7 expressing plasmacytoid dendritic cells and Langerhans cells, with secondary recruitment and activation of other inflammatory cells. Activation of TLR7 results in the stimulation of the innate and acquired immune responses, in particular cell mediated immune pathways. Topical imiquimod cream 5% (Aldara, MEDA Pharma) has been found to be effective for the treatment of actinic keratoses, superficial basal cell carcinoma and anogenital warts. Topical imiquimod is especially recommended for the treatment of large clinically asymptomatic fields containing tumor cells ("field cancerization"). Treatment with imiquimod applied at home by patient gives excellent cosmetic results. There are some data on its efficacy in nodular basal cell carcinoma and in some other skin cancers. The drug appears to be well tolerated with mild to moderate to local inflammation at the site of application. This paper provides a review about current experience and possible future development of imiquimod.

The unapproved (off-label) therapies represent a special problem in oncology since they are in the borderline of legal regulation and of free medical practice. Although in Hungary the off-label therapies were regarded as clinical trials without permission until the new regulation came into action at the end of October 2008, certain experts were even so arguing for its use because clinical practice changes more rapidly than the prescription label. Moreover, manufacturers are not obliged to submit Supplemental New Drug Application in spite of the fact that enough evidence is generated to do so. The regulation of off-label therapies should meet the conditions of free medical practice, evidence-based medicine, demand of patients for new chances and expectations of regulatory authorities. In this paper, following the criticism of the Hungarian status and the new regulation, as well as the review of international practice, the author outlines the frame of a potential regulation separately indicating the role of practicing physicians and authorities.

Chemotherapy-induced vomiting and nausea is the most common adverse event of anticancer therapy. In different guide-lines (MASCC, NCCN, ESMO and ASCO) antiemetic prophylaxis is directed toward the emetogenic potential of the chemotherapy and the type of vomiting and nausea. Chemotherapeutic agents are classified into four emetic risk groups: high, moderate, low, and minimal. Steroids, dexamethasone, metoclopramide, cannabinoids, benzodiazepines, 5-HT3 receptor antagonists (ondansetron, granisetron, tropisetron) and a new group of antiemetics, the neurokinin1 receptor antagonists are used to prevent anticipatory, acute and delayed vomiting and nausea. This paper examines evidence-based recommendations for optimal use of antiemetics.

The aggressive radiotherapy and chemotherapy used for treatment of oncological patients--through the damage of germ cells--may cause decrease of fertility or complete infertility. There are relatively few effective clinical options for preserving female fertility. The results of clinical experiments connected with ovarian tissue cryopreservation and oocyte freezing are very promising and indicate that we may have tools for female fertility preservation in the future. In this paper, 1) the future role of oocyte cryopreservation in fertility preservation of female oncological patients, and 2) the authors' preliminary results with oocyte cryopreservation are summarized.

The paper reviews current data on the use of imatinib in acute lymphoid leukemia. A brief description of classification of acute lymphoid leukemia and the therapeutic developments of the last 30 years are presented with particular emphasis on the clinical and biological features of Philadelphia positive acute lymphoid leukemia. The main therapeutic principles of acute lymphoid leukemia and the role of minimal residual disease in therapeutic indications are summarized. In Philadelphia positive acute lymphoid leukemia, in addition to chemotherapy and bone marrow transplantation, the tyrosine kinase inhibitor imatinib mesylate has been increasingly administered. The results of major clinical studies are presented along with the author's own clinical experience. Based on the above considerations the current indications of imatinib treatment in Philadelphia positive acute lymphoid leukemia can be summarized as follows: a) during the induction phase along with chemotherapy; b) alternating with cycles of consolidation or maintenance treatment; c) before stem cell transplantation to eradicate minimal residual disease; d) in relapsed or refractory cases; e) after stem cell transplantation for the treatment of minimal residual disease and/or relapse, alone or in combination with donor lymphocyte immunotherapy.

Multiple myeloma is a relatively common hematologic malignancy with no definitive treatment available. Although, therapy may include allogenic bone marrow transplantation, high-dose ablative chemotherapy followed by bone marrow or peripheral stem cell transplantation, melphalan/corticosteroid therapy, alpha-interferon treatment, and combined cytostatic chemotherapy, currently none of these alternatives offers cure for the disease. Thalidomide is an infamous molecule for its teratogenicity, yet it possesses potent immunomodulatory, anti-angiogeneic and, in higher concentrations, direct anti-myeloma-cell properties. At present, the drug is only approved for the treatment of erythema nodosum of leprosy, however, there are several preliminary results that show clinical efficacy in multiple myeloma. This drug has especially potent anti-myeloma effects in combinations with dexamethasone and certain cytostatic chemotherapeutic agents. The effects are evident both in polyresistant, and relapsing myeloma, a form with no accepted effective treatment options. In this paper, the fundamental molecular and cellular effects of thalidomide are summarized then the most important clinical studies with thalidomide are reviewed. It is the authors' hope that thalidomide will soon be a full member of the medical arsenal in the fight against multiple myeloma.

This paper deals with results of the search for anticancer agents achieved at IDR during the period of 1953-1983. This research activity concentrated on the following four topics: 1) biological alkylating agents, 2) nucleoside type antimetabolites, 3) anthracyclin antibiotics and 4) analogs of tamoxifen. Among those the first one was the most successful, resulting in five new cytostatics, which were marketed under the tradename Degranol [1,6-bis-(2-chloroethylamino)-1,6-dideoxy-D-mannitol], Mannogranol [1,6-dibromo-1,6-dideoxy-D-mannitol], Myelobromol [1,6-dibromo-1,6-dideoxy-galactitol], Zytostop [1,2,5,6-tetra-O-methanesulfonyl-D-mannitol] and Lycurim [1,4-bis-(mesyloxiethylamino)-1,4-dideoxy-eryhtritol].

Chromosomal aberrations were studied in peripheral blood lymphocytes from only surgery treated testicular cancer patients and treated with chemo- and/or radiotherapy. A distinct increase in spontaneous aberration frequency over the level of 27 healthy controls in 27 patients treated with surgery alone was found. Our data suggest the existence of a certain degree of chromosome instability, which may be a factor to the development of testicular tumour. The frequency of aberrant cells was much higher in 102 treated patients than in the controls. The decrease in aberrant cells was only time-dependently gradual in VPB and X-ray treated patients, while the second line combined treatment modalities caused the highest frequency of aberrant cells in the first two years after the end of courses. The possible relationship between the persistence of chromosomal aberrations and the development of malignancies are discussed in this paper.

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