Clinical Oncology

[Diffuse large B-cell lymphoma – a road to personal therapy]


FEBRUARY 10, 2017

Clinical Oncology - 2017;4(01)

[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.]



Further articles in this publication

Clinical Oncology

[The role of PET in clinical oncology]


[Positron emission tomography (PET) has earned an important role in clinical imaging, where it is used almost exclusively as hybrid modality such as PET/CT and PET/MR. The driving force behind the development of the method and the increasing clinical penetration of PET in the past two decades was clearly its use in Oncology. The most used tracer in PET is the 18 F-labeled fl uoro-deoxy-glucose (FDG). With the help of this molecule malignant tumors and their metastases, in which anaerobic glycolysis is typically increased, can be identifi ed with high sensitivity in the total body volume. However, FDG is not a tumor specifi c tracer, thus both false positivity and false negativity may occure which reduces the diagnostic accuracy. Indications of FDG PET studies in Oncology continuously evolved, owing to scientifi c publications, large scale national programs and even health-economic considerations. This publication describes the well-established indications of FDG PET/CT(MR) tests in cancer diagnostics and furthermore discusses more recent new PET tracers already being applied as well as those expected to be used in the future.]

Clinical Oncology


A szerkesztők

Clinical Oncology

[Treatment of neuroendocrine tumors]


[Recently, the therapeutic possibilities for the locally invasive or metastatic neuroendocrine tumors developed signifi cantly, although we have no widely accepted predictive or prognostic factors, which could help to design the most effective sequential therapy. To make therapeutic strategy the internationally accepted clinical guidelines should be considered. The therapeutic activity has to be performed in oncological centers with the support of a multidisciplinary team.]

Clinical Oncology

[Gene modifi ed T cell therapy for patients with cancer]


[T cells genetically modifi ed to express chimeric antigen receptors can combine the antigen specifi city of monoclonal antibodies with the cytotoxic function, active biodistribution and long term persistence of T cells. The approach can induce 90% complete remission rate in patients with CD19+ lymphoid leukemias; however, the in patients with solid tumors the antitumor effi cacy of CAR T cells have not reached similar levels yet. The increased levels of interleukin-6 due to T cell activation play key roles in the majority of side effects and using anti-IL-6 monoclonal antibody, tocilizumab can effectively treat these complications. Novel gene modifi cation strategies and improvements in CAR T cell manufacturing, the approach has the potential to fundamentally change the way patients with cancer are treated in the not too distant future.]

Clinical Oncology

[Cancer treatment induced gastrointestinal complications]

AL-FARHAT Yousuf, AUTH Péter

[Systemic therapy (ST) (including chemotherapy, targeted therapy, and immunotherapy) or radiation therapy (RT) can induce gastrointestinal side effects, which frequently affect patient’s quality of life. Sometimes side effects could be dose-limiting, or a reason to stop the treatment. The incidence and severity of gastrointestinal complications in patient’s receiving ST, RT, or chemoradiotherapy are affected by numerous factors, including: therapeutic agents, doses and route of administration, target of the RT (upper, lower abdomen or body) and individual patient variability (age, sex, prior cancer therapy, comorbidities, performance status). Mucositis occurs in approximately 20% to 40% of patients receiving conventional chemotherapy, 80% of patients receiving high-dose chemotherapy, nearly all patients receiving head and neck radiation therapy. mTOR inhibitor-associated stomatitis (mIAS) is the most frequent dose-limiting toxicity (52.5%). More than 90% of patients receiving highly emetogenic chemotherapy will have episodes of vomiting. However, only about 30% of these patients will vomit if they receive prophylactic antiemetic regimens.]

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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.]

Clinical Oncology

[Signaling pathways in cancer stem cells (Notch, Hedgehog, Wnt)]


[OThe key regulators in the embryonic life, and later in the differentiation of tissues and organs are the evolutionary reserved signalling pathways, as Notch, Hedgehog and Wnt. Mutations of these pathways have been identifi ed in many tumor types, increasing the risk to the appearance of cancer stem cells (CSC), with very similar geno- and phenotype as normal stem cells have. Such CSCs with stemness functions can be developed not only from normal stem cells, but also from progenitor and differentiated cells. The main characteristics of CSC are the self maintenance, slow growth rate, very effective DNA-repair system, etc. All of these can contribute to the resistance. Further problems are the low number of CSC in the whole tumor mass, which makes rather diffi cult to achieve the effective drug concentration in CSC. The mentioned ancient pathways interact with many other pathways to form a network, which can infl uence the strategy of therapy. No doubt, that these pathways are promising targets, however, till now the clinical effectiveness is very low due to some reasons mentioned above. Nevertheless, some drugs are already in clinical use, either as monotherapy or part of the combinations. Little is known about the relationship between the pathways and the microenvironment, which has an outstanding role in the cellular activities, sometimes resulting opposite output. It is a great challenge to design effective drugs against CSC, similarly to fi nd reliable predictive biomarkers, which unfortunately still missing, since a reasonable drug-marker interactions would speed up the personalized treatment.]

Clinical Oncology

[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

[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”.]

Lege Artis Medicinae

[New possibilities in the management of hepatocellular carcinoma]

DANK Magdolna

[The prognosis of primary hepatocellular carcinoma (HCC) has been poor until recently. Most patients are diagnosed at an advanced stage, with a poor liver function, thus therapeutic possibilities are limited. In high-risk patients, active surveillance and HCC screening is essential for early diagnosis. Experience with systemic chemotherapy has been disappointing with low response rates and high rates of adverse effects. Recently, novel treatment options have emerged, including the use of specific targeted agents, blockers of signaling pathways involved in hepatocarcinogenesis. Sorafenib, an oral multikinase- inhibitor is the first systemic agent to demonstrate survival benefit in advanced hepatocellular cancer. Several new, promising therapeutic options are being tested in clinical trials. The present review gives an overview of evolving diagnostic and therapeutic strategies.]