Clinical Oncology

[Radiological response evaluation of targeted therapy]


MAY 20, 2014

Clinical Oncology - 2014;1(02)

[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.]



Further articles in this publication

Clinical Oncology

[Molecular profi les in therapeutic strategy]

PETÁK István, SCHWAB Richárd

[In 2013, 10 years after the completion of the human genome, the cancer genome project has identifi ed almost all possible cancer genes, which could be responsible for the malignant transformation and progression. These genes are called „driver” genes, and the pathogenic mutations to be „driver” mutations. The census of „driver genes” in 2013 counted 138 genes and 1.5 million mutations. The situation is further complicated by the fact that up to 8 „driver” gene can be activated simultaneously in the same tumor, furthermore, the profi le may change during tumor growth and metastatization. 2013 was a turning point also because several targeted therapies were registered. Currently there are about 30 targeted drugs in clinical use and more than 200 targeted compounds in clinical development. This means that in 3-4 years the number of drugs will at least double. Most of the current patients can only access these compounds in clinical trials. But, patient already benefi t signifi cantly more even from phase I clinical trials, if they are selected based on the molecular profi le of the tumor. Fortunately, the advancements of next generation sequencing technologies provide the opportunity to identify all „driver” genes, - the whole molecular profi le, - in the patient’s tumor for the cost of one month targeted therapy. But the information generated can be only used in clinical practice if the results are processed by „molecular info-bionics”.]

Clinical Oncology

[Management of prostate cancer today]

PETRÁNYI Ágota Eszter, BODROGI István

[Although metastatic prostate cancer remains an incurable disease, the past years witnessed an extraordinary progress in the management of patients with castration resistant prostate cancer (CRPC). Development of novel agents that modulate the androgen receptor pathway, growth factor signaling pathways, immune functions and bone targeting machinery has been the focus of therapeutic strategies because of its signifi cance in the biology of prostate cancer progression. The arrival of several new agents — cabazitaxel, abiraterone acetate, enzalutamide, sipuleucel-T, denosumab and radium-223 — is changing the options and management of patients with metastatic castration resistant prostate cancer (mCRPC). Prostate cancer is a heterogeneous disease, therefore, in treatment must be considered the clinical characteristics of the disease as it manifests in an individual patient. The aim of this review is to summarize the most important new fi ndings for metastatic prostate cancers according to the different molecular pathways and to discuss their potential role on the management of this disease.]

Clinical Oncology

[EGFR family and gynecologic cancers]


[The HER family of receptor tyrosine kinases may potentially play an important role in gynecologic malignancies. Amplifi cation and overexpression of various HER family members including epidermal growth factor receptor (EGFR/HER1) and HER2 have been reported in epithelial ovarian cancer and endometrial carcinoma as well as in cancer of the uterine cervix. High expression of EGFR has been associated with poor prognosis independent from histiotype while HER2 expression may be more histotype dependent. This review summarizes the clinical experience with anti EGFR/HER2 directed monoclonal antibody therapy in the three major gynecologic cancer types to date.]

Clinical Oncology

[Thromboprophylaxis in cancer patients]


[Cancer- and chemotherapy-associated venous thromboembolism (VTE) is a serious complication in patients with malignancies. Most important questions and challenges are summarized in the review and an attempt is made to answer some of them. Epidemiology, causes of thrombophilia and risk factor analysis including thrombogenicity of both tumorous disease and chemotherapy are discussed. The following special risk groups are detailed: (a) postoperative, (b) hospitalized non-surgical patients, (c) ambulatory patients with chemotherapy, (d) tumorous patients without chemotherapy. As conclusion, most important messages of the recent guidelines for preventing and treating cancer-associated thrombosis are discussed.]

Clinical Oncology

[Neoadjuvant therapy in breast cancer – an update]

KAHÁN Zsuzsanna, RUSZ Orsolya, UHERCSÁK Gabriella, NIKOLÉNYI Alíz

[Traditionally, neoadjuvant systemic therapy (NST) serves as treatment of advanced breast cancer to achieve technical operability by resulting in tumor regression. Nowadays, NST is advantageous in all cases if adjuvant systemic therapy is needed, since the in vivo study of its effect provides possibility for the estimation of prognosis, the treatment may be modifi ed according to the therapeutic response, the systemic therapy starts earlier as compared to adjuvant therapy, and fi nally, it may result in the reduction of surgical and radiotherapeutical radicality. The type of NST should be selected on the basis of tumor features refl ecting treatment sensitivity. In case of chemosensitive cancers, chemotherapy is taxane- and anthracycline-based, and the planned dose should be delivered prior to surgery. In HER2-positive cancers, the addition of an anti-HER2 agent doubles the rate of pathological complete regressions. In hormone-sensitive tumors, the standard neoadjuvant endocrine therapy consists of an aromatase inhibitor (postmenopause), or tamoxifen or an aromatase inhibitor combined with an LHRH analog (premenopause) for 4-8 months that is continued following the surgery in the adjuvant setting. For the early evaluation of the effect of NST, serial tumor biopsy or imaging studies (MRI, PET) seem promising. Sentinel lymph node biopsy around the NST should be practiced with prudence; it may warrant the avoidance of axillary blockdissection in some cases. For the design of radiotherapy, the initial stage and the degree of regression are considered.]

All articles in the issue

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[Non-surgical treatment of the biliary tract and gallbladder cancer]

PIKÓ Béla, LACZÓ Ibolya

[Biliary tract cancers are rare, hence only a few high level of evidences related to their treatment are available. The successful treatment and the only chance for long-term survival are based on the radical surgical resection. After the fl uoropyrimidin based protocols chemotherapy regimens prefer gemcitabine combinations (cisplatin, oxaliplatin, capecitabine) or FOLFIRINOX, considering the patient performance status as well. There are no registered targeted therapy in this indication, the most experiences were acquired with erlotinib; nowadays the optimal treatment can be selected by the molecular genetic profi le of the tumour and not by the results of the clinical studies. The radiotherapy and the radiochemotherapy can be administered preoperatively, postoperatively and for palliation as well, in addition to the conventional percutaneous radiotherapy, brachytherapy, intensity-modulated radiotherapy, intraoperative irradiation, radioembolization can also be administered depending on the technical equipments. Besides the photodynamic therapy and several ablation therapies, even interventional radiological procedures can play a signifi cant role.]

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[Precision medicine proposes the personalization of health services in order to make the best individual decisions about the interventions and treatments for the patient. Molecular genetic diagnostic tests help to select the appropriate therapy, so-called targeted therapy. In the case of extensive lung cancer with EGFR mutation, EGFR tyrosine kinase inhibitors are immediately applicable; they are very effective and can reach long-term remission of the disease. However, resistance mutation can develop during the treatment, which causes the progression of the disease; therefore change of therapy is needed. In our case, we show the possibility of targeted treatment beyond the progression, emphasizing the importance of detecting resistance mutation. ]

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[The majority of patients with diffuse large B-cell lymphoma can be cured using the standard rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) based therapy. However, approximately 30-40% of the patients are refractory to the therapy or they relapse. The currently available salvage therapies represent a realistic curative approach only for approximately one quarter of the patients. Therefore, there is unmet clinical need for more effi cient fi rst line and salvage therapies in DLBCL. The rapid advances in the fi eld of molecular genetic techniques lead to a better understanding of the biological heterogeneity as well as the discovery of the key factors involved in the pathogenesis of the disease. Nowadays, the distinction between the cases with germinal center B-cell and activated B-cell origin characterized with different prognosis has therapeutic implications. Presently, the therapy of the so-called double-hit lymphomas also represents an unmet clinical need. The next generation sequencing based studies lead to the discovery of novel molecular targets, including components of different cellular signaling pathways, immune checkpoints and components of the microenvironment. Targeted therapies against many of these molecular targets are being tested in different clinical trials. Due the heterogeneity of the disease, it is of critical importance to identify those patient groups who will benefi t from a particular targeted therapy. Hopefully, this risk-adopted therapeutic approach will become soon available for patients with DLBCL. Currently, the R-CHOP therapy still represents the gold standard in treatment of patients with DLBCL.]

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[Oncological management of gastro-entero-pancreatic neuroendocrine neoplasias]


[Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are unusual and relatively rare neoplasms. They characteristically synthetize, store and secrete a variety of peptides and neuroamines, which can lead to development of disctinct clinical syndromes. Clinical symptoms and presentations vary depending on the location and hormones produced by the tumor. The diagnosis of NETs is established by histological examination and the immunohistochemical detection of general neuroendocrine markers, such as chromogranin A (CgA) and synaptophysin. An update of the WHO classifi cation has resulted in a new classifi cation dividing neuroendocrine neoplasms into neuroendocrine tumors (NETs) including G1 (Ki67 index ≤2%) and G2 (Ki67 index 3-20%) tumors and neuroendocrine carcinomas (NECs) with Ki67 index >20%, G3. The different available therapeutic approaches, including surgery, liver-directed ablative therapies, peptide receptor radionuclide therapy, and systemic hormonal, cytotoxic or targeted therapy, are discussed in this overview.]

Clinical Oncology

[Management of renal cancer]

MARÁZ Anikó, SZŰCS Miklós

[Targeted anti-cancer agents are used as standard therapies in case of advanced or metastatic clear cell renal carcinoma. Neovascularisation plays an important role in the progression of hypervascularized cancers. Vascular endothelial growth factor (VEGF) is the key molecule in this mechanism. Most of the registered agents inhibit the angiogenesis by blocking the VEGF signalling pathway. It can occur if an antibody binds to the VEGF, so the linkage to the receptor is blocked. This happens in case of bevacizumab. Another mechanism is the inhibition of the intracellular compound of VEGF receptor by tyrosine kinase inhibitors (TKI). Sorafenib, sunitinib, pazopanib and axitinib belong to this group. Other well-known mechanism of action is the inhibition of mammalian target of rapamycin (mTOR) receptor, like temsirolimus and everolimus. Based on randomised controlled trials sunitinib, pazopanib or IFNα-bevacizumab combination is recommended fi rst-line according to the international recommendations in case of good and moderate prognosis. For patients with poor prognosis temsirolimus is the standard therapy. In second-line, after ineffective cytokine therapy, sorafenib, pazopanib and axitinib are the supported options. If TKI is ineffective, everolimus or axitinib can be administered. In the latest recommendations sorafenib is another possible option (off label). After two TKIs, only everolimus is registered for third-line therapy. Life expectancy of patients can further be improved as the number of targeted drugs increases, more effective agents appear and as appropriate sequences and their benefi cial effects are recognised.]