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Lege Artis Medicinae

APRIL 18, 2020

[Digitally-assisted treatment planning in precision oncology]

PETÁK István, VÁLYI-NAGY István

[The progress of molecular information based on personalized precision medicine has reached a new milestone. Actually, about 6 million mutations of 600 genes may be related to the development of cancer, and on average, 3-4 of these “driver” mutations are present in each patient. Due to the progress in molecular diagnostics, we can now routinely identify the molecular profile of tumors in clinical settings. By clinical translation, there are actually available more than 125 targeted pharmaceuticals and hundreds of such therapies are under clinical trial. As a result, we have many first-line and licenced treatment options to be elected by molecular information as the optimal one for every patient. There is an increasing need for complex informatics solutions by medical software. Geneticists, molecular biologists, molecular pathologists, molecular pharmacologists are already using bioinformatics and interpretation software on their daily work. Today, online digital tools of artificial intelligence are also available for physicians for assisted treatment planning. Telemedicine, videoconferencing provide solutions for interdisciplinary virtual molecular tumor boards, which democratizes the access to precision oncology for all doctors and patients. ]

Clinical Oncology

FEBRUARY 28, 2020

[Neoadjuvant and palliative drug therapy for bladder cancer]

MARÁZ Anikó

[The survival of patients with muscle-invasive localized bladder cancer is more favorable if they receive neoadjuvant or adjuvant cisplatin-based chemotherapy before or after cystectomy. Based on the meta-analyses, in case of neoadjuvant cisplatin-based chemotherapy, the 5-year survival benefi t is 5-16%. The outcome is even more favorable in case of patients who respond well to neoadjuvant chemotherapy (pathological complete remission rate 12–50%). More than 3 months delay of cystectomy does not signifi cantly reduce the survival if chemotherapy is performed before the operation. Results of adjuvant phase III studies and meta-analyses are not so unambiguous as neoadjuvant data, but chemotherapy seems to infl uence favorably PD-L1 expression the survival, especially in case of pT3/4 and/or N+ (and high grade or margin positivity) cases. According to the recent publications, outcome data of patients have been effective in case of progression after platinum therapy, in or after second-line and in fi rst-line therapies for cisplatin ineligible, PD-L1 positive patients, respectively. Survival and tumor response data are very promising; in particular stages, they seem to be more effective than the previously administered chemotherapies. Current and ongoing trials are investigating the combinations of new remedies with other immunotherapeutic agents or chemotherapies as well as trying to identify biomarkers in order to further increase effectiveness.]

Clinical Oncology

FEBRUARY 28, 2020

[Role of infl ammation in the carcinogenesis]

KOPPER László, TÍMÁR József

[Chronic infl ammation is an important promoter of the carcinogenesis of several cancer types and also an important contributor to mutagenicity beside the known carcinogens. Beside the continous regeneration of the affected epithelia chronic infl ammation provide a special microenvironment intra and extracellular environment which support malignant transformation and block emerging immune reactions. On the other hand, cancer is generating chronic infl ammation itself independent from its role in the carcinogenic process. It is due to cancer necrosis as well as to the production of infl ammatory cytokines. Cancer-induced infl ammatory reactions block antitumoral immune responses and continous monitoring of this process provide valuable clinical parameter of cancer progression.]

Clinical Oncology

DECEMBER 30, 2019

[Treatment of cholangiocellular carcinoma]

ANDRÁS Csilla, ÁRKOSY Péter

[Tumors of the biliary tract are a rare entity, at the time of diagnosis most of the patients are in advanced stage and operation can’t be effectuated. After operation the risk of recurrence is high. The standard adjuvant therapy is capecitabin based on the results of BILCAP study. In advanced stage or in the presence of metastates the standard fi rst line treatment is gemcitabine and cisplatin therapy, there are noninferiority results from a Japan study with gemcitabin and S1 combination therapy. There was no evidence of second line treatment possibilities after gemcitabine and cisplatin therapy until 2019, but based on the results of ABC-06 study mFOLFOX could be the choice in the future. In the case of MSI-H/dMMR tumors immuntherapy should be considered. Personalised medicine with matched molecular targeted therapy is a new option. There are 2 new molecular targets, FGFR and IDH, the preliminary result are very promising.]

Clinical Oncology

DECEMBER 30, 2019

[Sequential therapy of metastatic renal cell carcinoma]

TORDAY László

[The incidence of renal carcinoma is on the rise in developed countries, with the tumor being among the 10 most common malignancies. However, the survival of patients with irresecable renal carcinoma has improved signifi cantly in recent years, mainly due to signifi cant advances in oncology treatment. The use of agents acting on the VEGF and mTOR signaling pathways is widespread and has become a standard clinical practice in fi rst and later line therapy. Recent clinical trials have provided many new drugs with new targets (cMET and AXL, FGFR, PD-1/PD-L1, CTLA-4) and combinations thereof, and have completely redrawn the treatment landscape of metastatic renal carcinoma and signifi cantly improved clinical results. This report reviews data on targeted drug therapy of renal cell carcinoma and discusses the therapeutic position of various drugs and combinations to our knowledge.]

Clinical Oncology

DECEMBER 30, 2019

[Targeted and immune therapies for hepatocellular carcinoma: Predictions for 2019 and beyond]

MASATOSHI Kudo

[Systemic therapy for hepatocellular carcinoma (HCC) has markedly advanced since the survival benefi t of a molecular targeted agent, sorafenib, were demonstrated in the SHARP and Asia Pacifi c trials in 2007. Treatment options for patients with advanced HCC increased by sorafenib, and long-term survival for patients with advanced stage HCC has become possible to some extent. However, development of a more potent fi rst-line novel molecular targeted agent replacing sorafenib and a potent second-line agent after disease progression on or intolerant to sorafenib has been warranted because sorafenib lacks tumor shrinking/necrotizing effects and induces relatively severe adverse events such as hand foot skin reaction. Many agents in the 1st line and 2nd line setting were attempted to develop between 2007 and 2016, but all of these clinical trials failed. On the other hand, clinical trials of 4 agents (regorafenib, lenvatinib, cabozantinib, and ramucirumab) succeeded in succession in 2017 and 2018, and their use in clinical practice is possible (regorafenib and lenvatinib) or underway (cabozantinib and ramucirumab). Furthermore, all of 5 clinical trials of combination therapy with transcatheter chemoembolization (TACE) plus a molecular targeted agent failed to date, however, the combination of TACE and sorafenib (TACTICS trials) was reported to be successful and presented at ASCO in 2018. Phase 3 clinical trials of immune checkpoint inhibitors and a combination therapy of immune checkpoint inhibitors and molecular targeted agents are also ongoing, which suggests treatment paradigm of HCC in all stages from early, intermediate and advanced stage, is expected to be changed drastically in the very near future.]

Clinical Oncology

DECEMBER 30, 2019

[Prevention and treatment of venous thromboembolism in cancer patients]

[Venous thromboembolism (VTE) is a common and severe complication of cancer. Deep vein thrombosis and pulmonary embolism are the second most common cause of death in cancer patients. Cancer, tumor-related factors as well as patient’s general condition and comorbidities are responsible for the increased risk of VTE. Chemotherapy is one of the most important risk factors for VTE, increasing incidence of VTE by 6.5-fold. In my paper, current guidelines for cancer VTE prevention and treatment are reviewed. Hospitalized patients with active tumor are at higher risk for VTE, and thrombosis prophylaxis is recommended in all cases. Extensive, routine prophylaxis for advanced cancer patients receiving chemotherapy is not recommended, but may be considered in high-risk ambulatory cancer patients (Khorana-score ≥ 3). Risk factors may change during the course of cancer disease, and the score should be continually reviewed and prophylactic treatment changed as necessary. LMWH is the recommended agent for both primary and secondary prophylaxis/treatment. Direct oral anticoagulants (DOACs) are knocking on our door, but results from further clinical trials are pending to determine their exact role.]

Clinical Oncology

DECEMBER 30, 2019

[Chemicals and tumors]

MARCSEK Zoltán

[Tumorigenesis is driven usually by non-lethal genetic alterations such as malfunctioning regulatory systems; mainly by inactivating suppressor genes or activating proto-oncogenes or malfunctioning of apoptatic system or decresed activity of the DNA repair system. Several chemicals induces mutations in the regulatory genes forces the cell for continous divisions increasing the chance of accumulation of further mutations. Chemicals, inducing mutations (mutagens) increase the rate of tumor occurrence, are carcinogens.]

Clinical Oncology

AUGUST 30, 2019

[Role of calcium metabolism in malignant diseases]

MÉSZÁROS Szilvia, TAKÁCS István

[Calcium plays a key role in a wide range of biologic functions. It is involved in skeletal mineralization, muscle functions, nerve transmission, and hormonal secretion and modulate various cellular functions too. Lines of research, on possible association of calcium metabolism regulation with tumorigenesis have been extensively studied in the recent decades. Implying disruptions and/or alterations of known regulatory and molecular pathways can lead to severe, sometimes life-threatening complications. The shift in physiological regulation and pathological factors also affect bone metastases and hypercalcaemia in cancer patients. For this reason, it is important to know about the changes in calcium metabolism and its treatment options in cancerous diseases.]

Clinical Oncology

AUGUST 30, 2019

[Electrochemotherapy]

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.]