[Prognostic importance of albumin in oncology]. / Az albumin prognosztikai jelentosége az onkológiában.

Diminished serum albumin level can be observed in inflammatory processes. Serum albumin level also reduces - irrespective of the presence of malnutrition - in locally advanced or metastatic malignancies. Low serum albumin level may have an influence also on the results of anticancer therapy (e.g., drug pharmacokinetics, adverse drug reactions). Extensive data of the literature and empirical experience prove the better prognosis of patients involved in nutritional therapy. Based on the most relevent data of the literature, the authors summarize the studies which have revealed the close correlation between the baseline serum albumin level and the prognosis of malignant diseases. Orv Hetil. 2018; 159(3): 96-106.

[Effectivity of bevacizumab rechallenge treatment in liver metastasis of colon cancer]. / Bevacizumab rechallenge kezelés hatékonysága vastagbéldaganat májáttétje esetén.

Since the therapeutic options for colon cancer are limited, the reinduction of treatments (rechallenge) is part of the therapeutic strategy. Our case is an example for that. A 65-year-old female patient was operated on stenotizing sigmoid cancer. Resectio was performed. Surgically incurable multiple hepatic metastases were proven. The histology revealed adenocarcinoma (grade II, pT3pN1cM1). In the first line, 13 cycles of bevacizumab (BEV) + FOLFOX followed by 2 cycles of BEV + capecitabine and 11 cycles of BEV + 5FU/LV were administered. In the second line, 28 cycles of cetuximab (CET) + FOLFIRI were given. In the third line, due to liver limited disease and based on the preference of the patient, two cycles of transarterial chemoembolisation (doxorubicin + lipiodol) were administered. In the fourth line, four cycles of trifluridine/tipiracil were given. In the fifth line, 13 cycles of BEV + FOLFIRI were given, as a rechallenge, which improved the overall survival by 6,5 months. Orv Hetil. 2018; 159(31): 1284-1290.

[Prognostic importance of plasma C-reactive protein (CRP) in oncology]. / A C-reaktív protein (CRP) plazmaszintjének prognosztikai jelentosége az onkológiában.

Chronic inflammation has a key role in the pathogenesis of malignancy. C-reactive protein (CRP) is produced due to the induction of inflammatory cytokines primarily in hepatocytes. In case of malignant diseases CRP might be elevated without any other condition of inflammation. Thus in the literature the authors searched for correlation between CRP levels and the course of malignant diseases. Normal CRP level measured at baseline correlates with longer overall survival in early staged malignancies. Lower CRP level at baseline predicts better prognosis in locally advanced or metastatic stages. Based on the available data, baseline CRP might be a prognostic factor in oncological diseases. Further prospective studies are warranted in various locally advanced and metastatic malignancies to clarify a possible prognostic and predictive role of CRP. Orv. Hetil., 2017, 158(7), 243-256.

[Prognostic importance of lactate dehydrogenase (LDH) in oncology]. / A laktátdehidrogenáz (LDH) prognosztikai jelentosége az onkológiában.

Glycolysis is increased in most of the malignant cells, providing the largest proportion of energy needed for cell proliferation. Lactate dehydrogenase (LDH) catalyses the reversible process of pyruvate to lactate in anaerobic condition. LDHA isoenzyme expressed mainly by malignant cells, significantly increases lactate formation. Lactate induces the proliferation of oxygenated malignant cells, angiogenesis, and inhibits the innate and adaptive immune responses. Baseline serum LDH elevation correlates with shorter survival. The authors review the relevant studies exploring the correlation between LDH elevation and the prognosis of malignant diseases. Orv Hetil. 2017; 158(50): 1977-1988.

[Approaching new pharmacotherapy options in pain treatment]. / A gyógyszeres fájdalomcsillapítás közelgõ új lehetõségei.

The evolution of medicine is noticeable in most therapeutic areas, the worse the current therapeutic result, the more quick the improvement. This is especially true in such areas that require substantial social resources, namely oncology, diabetology and CNS diseases. Pain is not a disease, it is a symptom. Pain is one of the most important components of human suffering thus it deserves special attention. In recent years new formulations of old medicines were introduced rather than new medicines. Maybe ziconitide is the last pain killer with new mechanism of action which was approved by FDA in 2004. However, the new information and techniques are also appearing in the field of analgesia. Nowadays one can talk about genetic/epigenetic targets, RNA therapies, voltage-gated calcium channels, new pain receptors (TRPV1, TRPV4, NMDA, Nav receptors) regarding pain treatment, indicating that the practice of the pharmacotherapy of pain will change fundamentally in the immediate future. This paper is intended to give a short summary of these new options.

[Prognostic importance of cross-linked fibrin degradation products (D-dimer) in oncology]. / A keresztkötött fibrindegradációs termékek (D-dimer) prognosztikai jelentõsége az onkológiában.

Cross-linked fibrin degradation products (D-dimer) are formed in two ways: on the one hand through coagulation cascade and on the other hand through fibrinolytic cascade. In the former case, plasmin cleaves the soluble cross-linked fibrin, and in the latter it cleaves the non-soluble cross-linked fibrin. In patients with malignant diseases, several factors influence the clinical evaluation of the result of D-dimer assay. First, D-dimer level can be elevated in cancer patients without thrombosis, which can be explained by procoagulant factors produced by malignant cells. Second, none of the algorithms used for diagnosing venous thromboembolism have been validated on patients with malignant diseases. Furthermore, the negative predictive value of D-dimer on thrombosis or thromboembolism is lower in cancer patients comparing to those who are not suffering from malignant disease. In patients with malignant disease, where venous thrombosis has not been proven, higher D-dimer level correlates with shorter survival. Based on the available data of the literature, the authors summarize some important studies which revealed the relationship between baseline D-dimer level and prognosis in cancer patients.

[Oncologic aspects of Clostridium difficile]. / A Clostridium difficile onkológiai vonatkozásai.

Clostridium difficile infection is one of the most frequent among cancer patients. Its diagnosis is complicated by the fact that the symptoms of the infection and the side effects of the anticancer treatments could be similar. Chemotherapy itself might facilitate Clostridium difficile infection. Several risk factors are known but Clostridium difficile infection can develop in the absence of these. Neutreopenia is a risk factor for fatal Clostridium difficile infection and also the side effect of chemotherapy. Therefore, if symptoms of the potential infection develop (eg. diarrhoea more than three times a day, fever above 38.5 °C, colitis, rapid increase of serum creatinin) Clostridium difficile infection should be excluded. If the infection is confirmed it should be managed in the most efficient way. Orv. Hetil., 2016, 157(28), 1110-1116.

[Ramucirumab - a new anticancer agent]. / Ramucirumab ­ egy új gyógyszer az onkológiában.

Ramucirumab is a humanized monoclonal antibody against vascular endothelial growth factor receptor-2, which inhibits the binding of vascular endothelial growth factor-A, -C and -D ligands. Furthermore it blocks the ligand stimulated activation of p44/p42 mitogen activated protein kinases, thus neutralizing the ligand induced proliferation and migration of human endothelial cells. Based on the results of the REGARD (Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma) and the RAINBOW (Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma) studies ramucirumab was approved for 2nd line treatment as monotherapy and in combination with paclitaxel for patients with local relapse and unresectable or metastatic gastric cancer (including gastro-esophegal junction adenocarcinoma). Based on the results, in advanced solid malignancies, ramucirumab may prolong progression free survival and overall survival, although it may increase the risk of all adverse events (fatigue, neutropenia, haemorrhage, nausea, stomatitis). The authors review the clinical studies of ramucirumab. Orv. Hetil., 2016, 157(40), 1587-1594.

[Close follow-up of oncologic patients with imaging - advantage or disadvantage?] / Onkológiai betegek szoros képalkotó követése - elony vagy hátrány?

The International Commission on Radiological Protection estimates, that 100 mSv exposure of radiation increases cancer risk by 0.5%. The central hypothesis of the Linear No Threshold model is that low dose ionizing radiation can induce carcinogenesis through the so called "one hit action", that is one or more deoxyribonucleic acid strands can be broken by the hit of only one electron particule. Regardless of the radiation dose, radiation exposure increases cancer risk. In the United States of America, one-third of computed tomographic scans are carried with no clear clinical indication, i.e. non radiating imaging can be applied with equal sensitivity and specificity. Furthermore, computed tomographic scans are repeated unnecessarily. Although technical improvements have reduced the concern of the potential danger of radiation exposure, the cumulative aspects and cancer risk should always be considered. Cancer risk, accompanied by ionizing radiation, should be minimized during the follow up of oncologic patients. It is mandatory, that all diagnostic tools which are not using ionizing radiation should be made widely accessable (eg. whole body diffusion weighted magnetic resonance imaging, positron emission tomography/magnetic resonance imaging). Orv. Hetil., 2016, 157(39), 1538-1545.

[Synovial sarcoma. Case report]. / Sarcoma synoviale.

In 2013 there were 94,770 new cancer patients reported in Hungary. Synovial sarcoma accounts for 0.05-0.1% of all cancers and, therefore its incidence is predicted to be 47-94 patients/year in Hungary. The authors report the history of a 18-year-old man who was operated on a right upper abdominal wall tumor with R1 resection. During the next 5 months the tumor grew up to 8 cm in largest diameter. Histology revealed monophasic synovial sarcoma. Immunohistochemistry showed bcl2, focal CD99 and high molecular weight cytokeratin positivity, while smooth muscle actin, S100 and CD34 immunostainings were negative. Becose of this reoperation was not possible, curative six cycles of doxorubicine and ifosfamide with granulocyte colony stimulating factor support and 60 Gy radiotherapy was given to the tumor bed. After these treatments computed tomography scan was negative and the patient attended regular imaging every 3 months. At the age of 20 years the patient developed two neoplastic lesions in the surgical scar measuring 10 mm and 45 × 10 mm in size. R0 resection, partial rib resection and abdominal wall reconstruction were performed. Histology confirmed residual monophasic synovial sarcoma. Radiotherapy was not given because of a risk of intestinal wall perforation. Staging positron emission tomography-computed tomography proved to be negative. At the age of 22 years magnetic resonance imaging scans indicated no tumor recurrence, but after one month a rapidly growing tumorous lesion was found on ultrasound in the surgical scar measuring 20 × 20 × 12 mm in size. Cytology confirmed local recurrence and fluorescence in situ hibridization indicated t(x;18). R0 exstirpation and partial mesh resection were performed and histology showed the same monophasic synovial sarcoma. Because of the presence of vascular invasion and a close resection margin (1 mm) the patient underwent 3 cycles of adjuvant chemotherapy (doxorubicine and ifosfamide) with granulocyte colony stimulating factor support and 3 cycles of ifosfamide. After 2 years follow up at the age of 24 years, imaging studies did not reveal any local or distant recurrence.

[Chemotherapeutic treatment of metastatic ovarian cancer for 8 years. Case report]. / Metasztatikus ovariumcarcinoma kemoterápiás kezelése nyolc éven át.

The authors present the history of a 48-year-old woman, who developed pleural effusion, abdominal pain and ascites due to an advanced ovarian cancer. She underwent hysterectomy and bilateral adnexectomy in 2006, and histology revealed FIGO IIIB papillary adenocarcinoma. After surgery the patient recieved the standard, 6 cycle taxol-carboplatin therapy. Taxol-carboplatin therapy was reinitiated because of retroperitoneal lymph node metastases in 2008, but soon the therapy had to be changed because of progression. Thereafter the patient recieved 6 different types of chemo- and biological therapy including the off-label FOLFOX-4 treatment at seventh line. Significant regression in response to FOLFOX-4 therapy was confirmed with a progression free survival of about 9 months. The general condition of the patient was satisfying during the whole chemotherapy, and the side effects were tolerable. The overall survival was 98 months. This case history is a good example for the success of individualized, long term chemotherapy even if ovarian tumor diagnosed at advanced stage as it happened in this case. Orv. Hetil., 2016, 157(44), 1769-1773.

[Therapeutic options for synovial sarcoma]. / A sarcoma synoviale kezelési lehetoségei.

Synovial sarcomas account for approximately 5 to 10% of soft tissue sarcomas and 0.05 to 0.1% of all malignant neoplasms. They predominantly affect the extremities but can occur in any part of the body. More than 50% of the patients are expected to develop metastatic disease within 3-5 years. In some patients disease recurrence may develop after 20 years. The 5-year overall survival rate is 10% for patients with metastatic disease and 76% for patients with localized one. Age, tumour size, histological subtype, and adjuvant radiotherapy influence prognosis. The role of adjuvant chemotherapy has not been proven yet. There are several ongoing clinical trials to determine the efficacy of active agents used for therapy of locally advanced, relapsed/refractory or metastatic disease. Better understanding of the biological behaviour of synovial sarcomas would provide the future way for the targeted therapy in combination with conventional treatments.

[Oncology-related issues of angiotensin-receptor blockers]. / Az angiotenzinreceptor-gátlók onkológiai vonatkozásai.

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.

[Individualized therapy of synchronous ovarian and colon cancers with lymph]. / Személyre szabott kezelés szinkrón, nyirokcsomó-pozitív petefészek- és vastagbéldaganatban.

A 71-year-old female patient underwent urgent laparotomy due to severe right lower quadrant abdominal pain and fever. Macroscopically duplex coecal and transverse colon cancer as well as a sigmoid or left ovarian cancer were suspected. Pathological findings revealed synchronous left ovarian and transverse colonic neoplasms. Both primaries metastatized to their regional lymph nodes. Furthermore, the ovarian cancer infiltrating the sigmoid colon gave distant metastasis in the coecum, too. Ovarian cancer histology showed papillary adenocarcinoma, and transverse colon cancer was a tubular adenocarcinoma. The affected lymph nodes were clearly distinguished by immunohistochemistry staining: ovarian metastases were CK7 positive, and colonic metastases were CK20 and CEA positive. The patient was treated with combinated chemotherapy: FOLFOX-4 two weekly and paclitaxel monotherapy every other week. The patient tolerated this combined treatment well. The authors conclude that multiple synchronous neoplasms can be treated with individualized chemotherapeutic protocol with good efficacy and few adverse reactions.

Association between pathological characteristics and recurrence score by OncotypeDX in resected T1-3 and N0-1 breast cancer: a real-life experience of a North Hungarian regional center.

Introduction: The 21-gene analysis (OncotypeDX) is validated test for pT1-3, pN0-1 with hormone receptor (HR) positive and normal expression of human epidermal growth factor receptor-2 (HER2) breast cancer (BC) to determine the aggressiveness of the disease based on the calculation of Recurrence Score (RS). Methods: In this retrospective study the authors correlated pathological characteristics and Recurrence Score (RS) by traditional statistical methods and Observed Oriented Modeling (OOM) in a realistic cohort of BC patients. Results: OncotypeDX tests were performed in 94 tumour specimens of 90 BC patients. >83% of node-negative (pN0) and >72% of node-positive (pN1) cases could avoid chemotherapy. For pN0 cases, non-parametric correlation and tests demonstrated significant association in eight types of characteristics [progesterone receptor (PR) expression, Ki-67 value, Ki-67 group, PR group, grade, estrogen receptor (ER) expression, Nottingham Prognostic Index (NPI) and Clinical Risk]. For pN1 cases, parametric correlation and tests showed significant association in six characteristic types (number of positive nodes, ER and PR expression, PR group, Ki-67 group and NPI). Based on OOM for pN0 cases, significant associations were established in three characteristics (Ki-67 group, grade and NPI group). For pN1 cases OOM found significant associations in seven characteristics (PR group, PNI, LVI, Ki-67 group, grade, NPI group and number of positive nodes). Conclusion: First in oncology, OOM was applied, which found some other significant characteristics associated with RS than traditional statistical methods. There were few patients, where no clinical associations were found between characteristics and RS contrary to statistically significant differences. Therefore, the results of these statistical analyses can be neither applied for individual cases nor able to provide the bases for screening patients, i.e., whether they need for OncotypeDX testing or not. OncotypeDX still provides a personalised approach in BC.

The Role of Cell-Free DNA in Cancer Treatment Decision Making.

The aim of this review is to evaluate the present status of the use of cell-free DNA and its fraction of circulating tumor DNA (ctDNA) because this year July 2022, an ESMO guideline was published regarding the application of ctDNA in patient care. This review is for clinical oncologists to explain the concept, the terms used, the pros and cons of ctDNA; thus, the technical aspects of the different platforms are not reviewed in detail, but we try to help in navigating the current knowledge in liquid biopsy. Since the validated and adequately sensitive ctDNA assays have utility in identifying actionable mutations to direct targeted therapy, ctDNA may be used for this soon in routine clinical practice and in other different areas as well. The cfDNA fragments can be obtained by liquid biopsy and can be used for diagnosis, prognosis, and selecting among treatment options in cancer patients. A great proportion of cfDNA comes from normal cells of the body or from food uptake. Only a small part (<1%) of it is related to tumors, originating from primary tumors, metastatic sites, or circulating tumor cells (CTCs). Soon the data obtained from ctDNA may routinely be used for finding minimal residual disease, detecting relapse, and determining the sites of metastases. It might also be used for deciding appropriate therapy, and/or emerging resistance to the therapy and the data analysis of ctDNA may be combined with imaging or other markers. However, to achieve this goal, further clinical validations are inevitable. As a result, clinicians should be aware of the limitations of the assays. Of course, several open questions are still under research and because of it cfDNA and ctDNA testing are not part of routine care yet.

Corrigendum: Overall Survival Prediction of Advanced Cancer Patients by Selection of the Most Significant Baseline Serum Biomarker Combination.

[This corrects the article DOI: 10.3389/pore.2022.1610004.].

Overall Survival Prediction of Advanced Cancer Patients by Selection of the Most Significant Baseline Serum Biomarker Combination.

Introduction: Consistent association between elevated baseline serum values and C-reactive protein (CRP), cross-linked fibrin degradation products (D-dimer), lactate dehydrogenase (LDH), decreased baseline serum albumin, absolute lymphocyte count to absolute monocyte count ratio (LMR), elevated absolute neutrophil count to absolute lymphocyte count ratio (NLR), elevated platelet count to absolute lymphocyte count ratio (PLR), and between some combinations of these biomarkers and the short overall survival of patients with malignant diseases has already been reported. These biomarkers are independent prognostic factors for cancer. Here, the most significant biomarker combination of these values was searched and studied in real-life advanced cancer patients of a single center. Methods: The authors retrospectively analyzed the association of the aforementioned biomarkers and their combination and OS of 75 consecutive cancer patients with locally advanced, recurrent, or metastatic diseases. Validated cut-off determination was used. Results: CRP, albumin, and PLR showed marked association with OS. Cut-off values for significant shorter OS were 30.65 mg/L (p < 0.001), 44.35 g/L (p < 0.001), and 168.20 (p < 0.001), respectively. Based on assessed biomarker cut-offs, four patient groups were created to determine whether biomarker values were out of range (ORV) compared to cut-off: 1) No ORV biomarkers (n = 24; OS = 26.07 months); 2) one ORV biomarker (n = 21; OS = 13.50 months); 3) two ORV biomarkers (n = 20; OS = 7.97 months), and 4) three ORV biomarkers (n = 10; OS = 3.91 months). Significant differences in OS were detected between the groups: For 1. vs. 2. hazard ratio (HR) = 3.0 (95% CI: 1.5-6.2), p = 0.003; for 1. vs. 3. HR = 4.1 (95% CI: 2.0-8.3), p < 0.001; and for 1. vs. 4. HR = 10.2 (95% CI: 4.2-24.6), p < 0.001. Conclusion: Based on our analysis, we can confirm that the complex monitoring of CRP, albumin, and PLR would provide a good estimation of OS. Large scale prospective studies are warranted to explore this and other useful combinations of prognostic biomarkers and their relationship to the well-established prognostic systems in real-life.

[Investigation of fatty acid profile for diagnostic purposes in mouse melanoma]. / A szérum zsírsavprofil diagnosztikus jelentõségének vizsgálata kísérletes modellben.

The aim of this study was to investigate whether fatty acid profile is a suitable marker for diagnostic purposes in mouse melanoma. Twelve C57Bl/6 male mice were implanted with B16 mouse melanoma cells (106 cells/animal) orthotopically (subcutaneously). After the implantation 4-4 animals were bled by cardiac puncture following narcosis, at days 7, 14, and 21. In order to investigate fatty acid profiles a method based on extraction and HPLC-MS was developed. Signal intensities of 14 fatty acids were determined by mass spectrometry in tumor-free animals as well as tumor bearing animals at the three time points. Mathematical analysis showed non-significant profile changes when control (tumor-free) animals were compared to tumor-implanted ones as well as during tumor progression on week 1, 2 and 3. In case of three fatty acids (myristic acid, palmitoleic acid and eicosadienoic acid) a trend was observed during tumor progression but its statistical significance cannot be evaluated without further investigations. The fatty acid profile cannot be used for early diagnoses in mouse melanoma.

Avemar (wheat germ extract) in cancer prevention and treatment.

Many healthy foods are derived from wheat germ. The molecular composition of these products, however, greatly differs as shown by normal-phase HPLC-mass spectrometry analysis; thus, experimental data obtained by one of them is not necessarily true for the other. Avemar is a nontoxic wheat germ extract registered as a special nutriment for cancer patients in Hungary. It shows potent anticancer activity on cell lines by deeply interfering with glucose metabolism and affecting expressions of several kinases. In in vivo experimental models, Avemar is also effective by enhancing the activity of the immune system such as stimulating NK cell activity (by reducing MHC I molecule expression), enhancing TNF secretion of the macrophages, increasing ICAM 1 molecule expression on the vascular endothelial cells. All of these lead to apoptosis of tumor cells. The wide range of biological activity of Avemar probably cannot be explained by only one active ingredient. Since there are numerous experimental data and the clinical benefit repeatedly confirmed Avemar can be one of the most potent and best researched food supplements available for cancer patients.