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Clinical Oncology

APRIL 10, 2019

[Current views on the male breast cancer]

BAKI Márta

[Breast cancer in men is a rare disease, and accounts for only 1% of all diagnosed breast cancers. Hungarian incidence by available data much higher. The greatest risk factor of male breast cancer the elevated estrogen concentration in the body. Genetic disorders, as a Klinefelter syndrome and estrogen exposures and other metabolic changes might cause the male breast cancer. Symptom duration is longer than female population and the male breast cancers diagnosed in older ages and advanced stages. Frequency of BRCA2 mutation is probably 10% among male patients. The most common type is invasive ductal carcinoma with estrogen and progesterone receptor positivity. Diagnostic, surgical, radiation procedures and chemotherapy probably same as female breast cancer. The guidelines recommend as in adjuvant and curative setting the tamoxifen and other selective estrogen receptor modulators treatment. By large nation based registry the survival rate is different from male and female breast cancers. New biomarkers, genetic changes are under investigation to understand munch better the male breast cancer.]

Clinical Oncology

APRIL 10, 2019

[New perspectives in the treatment of lung cancer]

SZONDY Klára, BOGOS Krisztina

[In recent years, huge research is going on in the fi eld of oncology and as a result, we can see a signifi cantly longer survival in this area of medicine. Lung cancer, which has been taken places in the back for decades, it has not become a curable disease, but begins to belong to the chronic diseases. As a result of brilliant surgical technics and stereotactic radiotherapy, or as a result of changes in drug treatment, 5-year survival is not uncommon in metastatic lung cancer patients, next to relatively long progression free survive. After the third-generation cytotoxic combinations the added growth inhibition (VEGF inhibitor) maintenance therapy or continuous pemetrexed cytotoxic chemotherapy were resulted in high survival benefi ts. The fi rst real breakthrough, long progression-free survival was achieved by targeted treatment, which proved to be effective with known driver mutations. The other great result, especially in squamous cell carcinoma, was the immunotherapy, the inhibition of immune checkpoints, which effi cacy was confi rmed in adenocarcinoma also. Several studies are going on with adjuvant or neoadjuvant immunotherapy, and combined use of immunotherapy (either in combination with radiotherapy or cytotoxic chemotherapy).]

Clinical Oncology

APRIL 10, 2019

[Oncological treatment on certain special cases]

FUTÓ Ildikó, HORVÁTH Dorottya Katalin, LANDHERR László

[Even in the absence of clinically signifi cant co-morbidities, cancer care is a major challenge for both patients and healthcare professionals. Routine anticancer treatment may be complicated by special clinical situations such as pregnancy or organ transplantation. The dosage of certain oncotherapy agents may be further affected by impaired renal and hepatic function or diabetes mellitus. These days, given the improved prognosis of cancerous diseases and increased survival, personalized therapy and prevention of long-term side effects is becoming particularly important, especially in the above-mentioned oncological situations. In this summary, we review the anticancer treatments recommended by ESMO in specifi c clinical situations.]

Clinical Oncology

FEBRUARY 20, 2019

[The role of the microbiome in the etiology and treatment of neoplastic diseases]

SCHWAB Richárd, BACSUR Emese, TORDAI Attila, PETÁK István

[Experimental data on the role of the microbiome in the onset and progression of infl ammatory diseases and cancer have been accumulated for years. An important milestone in this respect was the discovery that APC mutant mice in sterile conditions do not develop colon cancer of the FAP type. The direct role of the Enterobacteriaceae and Fusobacteriaceae bacterial families were also shown in the pathomechanism of the same experimental model. The toxic effect of chemotherapy on the gut fl ora has been well documented, but it may very well be that this putative side effect is part of the effi cacy, primarily in the case of adjuvant chemotherapy. The fi rst reproducible methods of microbiome molecular diagnostics are already available today. In addition to standard large clinical studies, we can increasingly rely on evidence of molecular pathomechanism and „real-world” clinical experience in the clinical interpretation of the microbiome. The overview summarizes the results of the fi eld research and its translation possibilities in terms of routine clinical practice.]

Clinical Oncology

FEBRUARY 20, 2019

[Practical use of meta-analyses in predicting disease risk, outcome, and therapy response in breast cancer]

MENYHÁRT Otília, GYŐRFFY Balázs

[Breast cancer is globally the most frequent malignant disease in women with increasing incidence. Meta-analyses using data from a large set of patients combining genetic and standard clinicopathological features provide valuable models in predicting disease risk, outcome and therapy response. With the advent of molecular technologies, the amount of available data generated for each tumor and each patient is growing exponentially. The increased data availability allows the development of new innovative systems enabling to discover more effective prognostic and predictive biomarkers. The goal of this review is to summarize meta-analyses that utilize data from countless patients to provide breast cancer risk prediction (Gail-model, Claus-model, BRCApro, IBIS, BOADICEA), and prediction of prognosis and expected therapy response (PREDICT, Magee). In the last part of the review we introduce online analytical tools (KMplot, ROCplot) developed to examine, rank and validate new prognostic and predictive biomarker candidates.]

Clinical Oncology

FEBRUARY 20, 2019

[Molecular subtypes and the evolution of treatment decisions in metastatic colorectal cancer]

RODRIGO Dienstmann, RAMON Salazar, JOSEP Tabernero

[Colorectal cancer (CRC) has clinically-relevant molecular heterogeneity at multiple levels: genomics, epigenomics, transcriptomics and microenvironment features. Genomic events acquired during carcinogenesis remain drivers of cancer progression in the metastatic setting. For example, KRAS and NRAS mutations defi ne a population refractory to EGFR monoclonal antibodies, BRAFV600E mutations associate with poor outcome under standard therapies and response to targeted inhibitors in combinations, while HER2 amplifi cations confer unique sensitivity to double HER2 blockade. Multiple rare gene alterations driving resistance to EGFR monoclonal antibodies have been described with signifi cant overlap in primary and acquired mechanisms, in line with a clonal selection process. In this context, sequential analysis of circulating tumor DNA has the potential to guide drug development in a treatment refractory setting. Rare kinase fusion events and complex alterations in genes involved in DNA damage repair have been described, with emerging evidence for targetability. On the other hand, transcriptomic subtypes and pathway activation signatures have also shown prognostic and potential predictive value in metastatic CRC. These markers refl ect stromal and immune microenvironment interactions with cancer cells. For example, the microsatellite instable (MSI) or POLE ultramutant CRC population is particularly sensitive to immune checkpoint inhibitors, while tumors with a mesenchymal phenotype are characterized by activation of immunosuppressive molecules that mandate stratifi ed development of novel immunotherapy combinations. In this manuscript we review the expanding landscape of targetable oncogenic alterations and signatures in metastatic CRC and discuss the clinical implementation of novel molecular diagnostic tests.]

Clinical Oncology

FEBRUARY 20, 2019

[Practical use of meta-analyses in predicting disease risk, outcome, and therapy response in breast cancer]

KAHÁN Zsuzsanna, TARI Gergely, ENYEDI Márton, HARACSKA Lajos

[Germinal BRCA status infl uences patient care both in early and advanced/metastatic breast cancer. Ideally, the patient should make the decision on the type of surgery or the avoidance of radiotherapy being aware of the BRCA status; based on the most recent clinical studies, this knowledge may infl uence the type of chemotherapy in the neoadjuvant, adjuvant, or metastatic setting or may raise the use of emerging targeted therapies. DNA-targeting cytostatic agents, mostly platinum agents and PARP inhibitors that act by inducing synthetic lethality, provide specifi c therapies in BRCA-mutant cases. The optimum place and sequence of these specifi c agents in treatment, however, are not known yet. International guidelines promote BRCA testing for the specifi cation of treatment strategy in all HER2-negative advanced/metastatic breast cancer cases (NCCN) or at least in all cases when, based on certain predictors, the presence of mutations is likely (ESMO). Recently, the methods employed for BRCA testing have improved immensely and are widely available through the services of various providers. For the identifi cation of the mutation, sequencing of the whole genes is needed, which can be achieved faster and more cost-effi ciently using next-generation sequencing (NGS) platforms compared to previous methods. It is the responsibility of the physician to consider the possibility of BRCA mutations and to raise the issue of BRCA testing to the patient if the family history, the age, previous malignant disease(s) of the patient, or the cancer features are suggestive of genetic risk.]

Clinical Oncology

DECEMBER 10, 2018

[Treatment of head and neck cancer]

KATONA Csilla, LANDHERR László

[Head and neck cancers cause worldwide a signifi cant problem in health care systems. Despite great advances in therapeutic modalities its prognosis has not changed in the past few decades. It is mainly caused by classical risk factors, like alcohol consumption and smoking, but in a signifi cant number of oropharyngeal cancers HPV infection plays a major role, which is associated with a new patient group characterized by a much better prognosis and therapeutic response. In the diagnostic phase staging examinations (CT scan, MRI, FDG-PET) are also involved which are necessary to multidisciplinary decision making. It can be largely infl uenced by the patient’s preference. The therapy is based on multimodality approach; surgery, radiotherapy, chemoirradiation, chemotherapy and the combination of these are used in early or locally advanced tumours. Targeted agents like EGFR inhibitors are partly used in the recurrent/metastatic setting or in combination with radiotherapy. Immun checkpoint inhibitors are new therapeutic options for pretreated, recurrent/metastatic patients and their role is under investigation in earlier therapeutic lines. Several clinical trials aim treatment desintensifi cation strategies in HPV positive tumours. Molecular genetic tests try to defi ne subgroups of patients to plan individualized treatment. Regarding the signifi cant functional and aesthetic damage of both disease and treatment, supportive care and rehabilitation are of great importance.]

Clinical Oncology

DECEMBER 10, 2018

[Advancing therapies in metastatic castration-resistant prostate cancer]

GIULIA Baciarello, MARCO Gicci, KARIM Fizazi

[Introduction: Prostate cancer is the second most common cause of cancer world wide and is the most frequently detected cancer in the European Union in men over 50 years of age. Androgen deprivation therapy remains the corner stone of treatment for recurrent or metastatic disease. Unfortunately, nearly all patients will develop resistance to androgen blockade leading to castration-resistant prostate cancer (CRPC). Over the last 10 years, new treatment shaved ramatically improved overall survival of men with mCRPC. Current therapies are basedon AR-axis inhibitors and taxane-based chemotherapies, aswell as radiopharmaceuticals and Sipuleucel T. Areas covered: The authors provide a review of the current fi eld of systemic therapy in metastatic CRPC. This is followed by an in-depth analysis of recent developments in treatment, and the biological rationale behind these therapies. Expert opinion: Since several trials with docetaxel or novel hormonal agents showed improvement in overall survival in metastatic castration-sensitive prostate cancer, aswell as in non-metastatic castrationresistant patients, it is expected that a growing subgroup of patients will be expose dearlierto chemotherapy and to AR targeted agents. It becomes then fundamental to fi nd novel strategies to over come drug resistance and further improve survival.]

Clinical Oncology

DECEMBER 10, 2018

[PI3K–AKT–mTOR pathway as a therapeutic target]

KOPPER László

[The PI3K-AKT-mTOR is one of the most busy signalling pathway, accepting and sending the message to the effector compartment. The pathway is very complex with activators (see the name), and inhibitors, as PTEN. Depending of the cell type this pathway participates in almost all functions of a given cell. The members of the pathway may have genetic failures, as a consequence, the risk for the development of different diseases, including cancer is high. Therefore it is logical to produce drugs to inhibit the dysregulated function. Unfortunately, despite the promising preclinical effectivity, so far only 4 drugs can be used to treat cancer patients. There are some hypothesis for the in effectivity, e.g. no useful marker for patient selection, high toxicity, false drivers for targeting. What is sure, combination therapy is much better than monotherapy]