Clinical Oncology

[Radiochemotherapy - questions/answers]

PIKÓ Béla, LACZÓ Ibolya

FEBRUARY 10, 2017

Clinical Oncology - 2017;4(01)

[During chemoradiotherapy the two main non-surgical anticancer methods are combined to improve the treatment outcomes. The theoretical possibilities of interactions and the most frequently used drugs will be presented here, emphasizing that although both the radiation therapy and the drugs need to be administered in full dose in practice considering the summarization of side effects we often have to make compromises. The treatments of the most frequent indications (brain, head and neck, oesophagus, lung, stomach, pancreas, rectum, bladder, cervix, soft tissue sarcoma) will be demonstrated. Since there are several drugs and drug combinations that are not included in the Hungarian registered anticancer therapies, for their off-label use the permission of the National Institute of Pharmacy and Nutrition is required. To choose the optimal treatment (during planning the optimal place of chemoradiotherapy, agents and doses) the opinion of a multidisciplinary team is necessary]

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[Treatment of neuroendocrine tumors]

PETRÁNYI Ágota

[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.]

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

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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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[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.]

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Clinical Neuroscience

Long-term follow-up results of concomitant chemoradiotherapy followed by adjuvant temozolomide therapy for glioblastoma multiforme patients. The importance of MRI information in survival: Single-center experience

LUKÁCS Gábor, TÓTH Zoltán, SIPOS Dávid, CSIMA Melinda, HADJIEV Janaki, BAJZIK Gábor, CSELIK Zsolt, SEMJÉN Dávid, REPA Imre, KOVÁCS Árpád

Introduction - Glioblastoma multiforme (GBM) is the most common malignant primary anomaly of central nervous system. The GBM infiltrates the nearly sturctures from the initial tumor and its metastatic attribution is well known. The aim of our single-centered retrospective study was to introduce the importance of postoperative medical imaging confirmation of total tumor resection for patient with GBM combined concomitant and adjuvant chemoradiotherapy on a 10 year long patient follow up. Methods - From January 2006 to April 2015 we registered 59 patients with newly diagnosed GBM at the University of Kaposvár Health Center Institute of Diagnostic Imaging and Radiation Oncology. The histological diagnosis was confirmed by a proficient neuropathologist (World Health Organisation WHO; grade IV astrocytoma). According to histological status if the ECOG performance status of patients allowed it the mutidisciplinary oncoteam recommended adjuvant chemoradiotherapy all features strictly by Stupp protocol. (60 Gy dose on the gross tumor volume and 2-3 cm margin for the clinical target volume with parallel 75 mg/m2 TMZ. Four weeks after monotherapial phase patients had to recieve 6 cycles of TMZ first cycle with 150 mg/m2 up to 200 mg/m2). The irradiation was carried out by a conformal three dimensional planning system. Results - 59 patients with the median age of 63 (range 17-84) year. Our sample counted 34 male patients and 25 woman patients. 14 patients underwent gross total tumor resection while, 39 patients underwent partial resection and the rest from our sample 6 patients passed through biopsy. Statistical analysis showed a lengthier survival among males than females, with a median survival of 13 months for males and females, the OS of 26.209 for males, meanwhile 15.625 for females. However, the difference is not considerable (log-rank p=0.203). Our study found that the estimated survival of patients at least 50 years old is significantly shorter at a median survival of 12 months (log rank p=0.027) than that of patients below 50 years of age at a median survival of 23 months. The longest estimated median survival was calculated with patients of ECOG '0' condition (16 months). However, no significant difference was found in the estimated survival of patients of different ECOG conditions (log-rank p=0.146). Based on the extent of surgery, complete resection resulted in the longest average survival of 36.4 months, followed by 21.5 months among patients with biopsy, and 15.8 months among patients with partial resection. Different surgical procedures, however, did not result in significant differences in survival (log-rank p=0.059). The overal survival of patients who had complete resection confirmed by MRI compared with the overal survival of patients with residual tumor confirmed by MRI as well we can estimate that there is significant difference between these two groups (p=0,004). Conclusion - Despite complex and intense treatment, recurrence is inevitable and causes relatively rapid death. In our analysis complete resection, as defined from the neurosurgeon’s report and postoperative MRI, resulted in an independently significant improvement in OS. Our results are the evidences that the treatment of patients with glioblastoma multiforme in Hungary is at least on the same level as any other developed European countries.

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[Is there a role of triple combination in the therapy of hypertension? - Antihypertensive efficiency of perindopril-amlodipine-indapamide]

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[Blood pressure reduction to target level decreases cardiovascular morbidity and mortality. However, in the vast majority of cases, this can be achieved only with a (multiple) combination regimen. The primary objective of the PAINT (Perindopril- Amlodipine plus Indapamide Combination for Controlled Hypertension Non-intervention Trial) study was to evaluate the efficacy of combination therapy with perindopril, amlodipine, and indapamide in patients who had not reached target blood pressure with their pre-existing therapy. Secondary objectives included the monitoring of metabolic parameters and the number of antihypertensive tablets taken by the subjects. In this subgroup-analysis we involved 126 patients (74 females and 52 males, mean age 59.8±12.5 years) who had a valid 24-hour ambulatory blood pressure monitoring both at baseline and at the end of the 4-months follow-up. At the beginning of the study none of the subjects reached blood pressure target despite taking on average 2.4±1.4 antihypertensive drugs. During the study, the subjects received the combination of amlodipine, perindopril, and indapamide instead of their pre-existing antihypertensive regimen. 24-hour mean systolic blood pressure decreased from 139.2±13.4 mmHg to 126.5±12.9 mmHg (p<0.01), as well as mean diastolic blood pressure from 77.3±11.3 mmHg to 71.1±8.7 mmHg (p<0.01). Heart rate remained unchanged. Blood pressure reduction was statistically significant both during the day and the night. We found significant blood pressure reduction in all hours (10.1-15.4/5.1-7.8 mmHg; p<0.001). Hyperbaric impact decreased from 366.9±251.1 mmHg × hour to 166.2±185.4 mmHg × hour (p<0.01) for systolic blood pressure, and from 112±130.6 mmHg × hour to 41.6±65.6 mmHg × hour (p<0.01) for diastolic blood pressure. We also could observe favourable changes in metabolic parameters, not only in lipids, but also in blood sugar level. The mean number of tablets taken by the subjects increased from 2.4 to 2.9, but this led to a significantly improved control of blood pressure. Triple combinations of state-of-the-art antihypertensive agents - such as of perindopril, amlodipine and indapamide - ensure effective blood pressure control in sufficiently compliant patients.]

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[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.]

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[The hepatocellular carcinoma (HCC) is one of the main causes of cancer-related death globally, and at the same time, it is the main event leading to death in cirrhotic patients. In the etiology of HCC, the non-alcoholic liver disease may be an important cause besides the viral cirrhosis. The HCC’s staging systems (Child-Pugh scores, Cancer of the Liver Italian Programme/CLIP, Barcelona Clinic Liver Cancer/ BCLC) play an important role in predicting the prognosis and determining the appropriate therapy. In Europe, the treatment strategy is based on the BCLC staging system. Screening of cirrhotic patient is also important because curative therapy is available only for the early-stage HCC. Several therapeutic options exist in the intermediate stage disease; among them the radiofrequency ablation (RFA), the transarterial chemoembolization (TACE) and the percutan ethanol injection (PEI) are most important. For the advanced disease, the only approved systemic therapy is sorafenib, which has been well-tolerated and yielded a substantially relative improvement in overall survival. For patient in end-stage disease with impaired liver function or a poor performance status, only supportive care is recommended.]

LAM Extra for General Practicioners

[Advantages of fixed Combinations in the treatment of Hypertensive patients ]

FARSANG Csaba

[In 60-70% of patients with hypertension, a significant decrease in blood pressure can only be achieved by a combination of antihypertensive drugs. International as well as national guidelines emphasise the numerous advantages and the importance of combination treatment. Fixed combinations are particularly advantageous, as their use improves patients’ compliance. This paper summarises the available information on the possible combinations of the nine major antihypertensive drug groups distributed in Hungary, and for details the results published on the recently approved and introduced fixed combination of telmisartan and amlodipine.]