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Blay J.-Y.,University Claude Bernard Lyon 1 | Rutkowski P.,Center of Oncology of Poland
Cancer Treatment Reviews | Year: 2014

Imatinib mesylate, an oral tyrosine kinase inhibitor, is indicated for first-line treatment of patients with unresectable and/or metastatic gastrointestinal stromal tumors (GIST). Imatinib also is approved as adjuvant therapy for patients following resection of primary GIST. Despite the efficacy of imatinib for the treatment of patients with GIST, adherence to treatment can prove difficult.Clinical studies have identified a number of factors that have a significant association with non-adherence to therapy, including age >51. years, female sex, a high number of concomitant medications, and complications with patients' therapy or the disease itself. Moreover, treatment-related adverse events and increased healthcare costs have been shown to have an impact on patients' adherence to therapy. A study of perceptions of adherence to therapy found discrepancies between actual and perceived adherence rates; both patients and physicians overestimate adherence to treatment.Non-adherence to treatment is not exclusive to oncology, and occurs in other disease areas, particularly with chronic conditions. Evidence from other disease areas suggests that routine assessment of adherence and the implementation of adherence programs can lead to improvements in health status and reduced healthcare costs.Improving patient adherence to imatinib treatment for patients with unresectable/metastatic GIST is particularly important, because non-adherence has a significant impact on clinical outcomes and healthcare costs. Therefore, the effective management of treatment-related adverse events along with patient education may be important in keeping patients compliant with continuous therapy. © 2013 Elsevier Ltd.


Lewandowska M.A.,Center of Oncology of Poland | Lewandowska M.A.,Nicolaus Copernicus University
International Journal of Clinical and Experimental Pathology | Year: 2013

Proper gene splicing is highly dependent on the correct recognition of exons. Among the elements allowing this process are the "cis" (conserved sequences) and "trans" (snRNP, splicing factors) elements. Splicing mutations are related with a number of genetic disorders and usually induce exon skipping, form new exon/intron boundaries or activate new cryptic exons as a result of alterations at donor/acceptor sites. They constitute more than 9% of the currently published mutations, but this value is highly underestimated as many of the potential mutations are located in the "cis" elements and should be confirmed experimentally. The most commonly detected splicing mutations are located at donor (5') and acceptor (3') sites. Mutations at the branch point are rare (only over a dozen are known to date), and are mostly searched and detected when no alteration has been detected in the sequenced exons and UTRs. Polypyrimidine tract mutations are equally rare. High throughput technologies, as well as traditional Sanger sequencing, allow detection of many changes in intronic sequences and intron/exon boundaries. However, the assessment whether a mutation affects exon recognition and results in a genetic disorder has to be conducted using molecular biology methods: in vitro transcription of the sequence of interest cloned into a plasmid, with and without alterations, or mutation analysis via a hybrid minigene system. Even though microarrays and new generation sequencing methods pose difficulties in detecting novel branch point mutations, these tools seem appropriate to expand the mutation detection panel especially for diagnostic purposes.


Maciejczyk A.,Center of Oncology of Poland
Advances in Clinical and Experimental Medicine | Year: 2013

For many years, the age of the patient, the condition of axillar lymph nodes, the size of the tumour, histological traits (in particular histological grade of malignancy and invasion of lymphatic vessels), condition of hormonal receptors and HER2 represented principal factors used for the stratification of breast cancer patients for the purposes of evaluating the prognosis and determining the appropriate strategy of treatment. Although the variables are useful for the prognostic evaluation of individual groups of breast cancer patients, their role in determining the individual risk level of the patient and in the selection of supplementary treatment is quite restricted. This article shows the prognostic value of additional parameters, whose expression is associated with chemioresistance (MRP2, BCRP, YB1) or individual assessment of the dynamics of tumor progression (S100P, BUBR1). In addition, it describes the role of an online database of "The Kaplan-Meier plotter" which contains the assessment of the effects of expression of various genes on the clinical outcome of patients with breast cancer. © Copyright by Wrocław Medical University.


Rutkowski T.,Center of Oncology of Poland
Radiation Oncology | Year: 2014

The assumption that the larger tumor contains a higher number of clonogenic cells what may deteriorate prognosis of patients treated with RT has been confirmed in many clinical studies. Significant prognostic influence of tumor volume (TV) on radiotherapy (RT) outcome has been found for tumors of different localizations including patients with head and neck cancer (HNC). Although TV usually is a stronger prognostic factor than T stage, commonly used TNM classification system dose not incorporate TV data. The aim of the paper is to refresh clinical data regarding the role of TV in RT of patients with HNC. At present somehow new meaning of TV could be employed in the aspect of modern RT techniques and combined treatment strategies. For larger TV more aggressive treatment options may be considered. In modern RT techniques escalated dose could be provided highly conformal or RT can be combined with systemic treatment increasing therapeutic ratio. In the study several reports estimating prognostic value of TV for patients with HNC treated with RT has been reviewed.Due to substantially various reported groups of patients as to tumor site, stage of disease or treatment strategies, precise cut-off value could not be establish in general, but the significant association between TV and treatment outcome had been found in almost all studies. There is a strong suggestion that TV should supplement clinical decision in the choice of optimal treatment strategy for patients with HNC. © 2014 Rutkowski; licensee BioMed Central Ltd.


Kepka L.,Center of Oncology of Poland | Socha J.,Center of Oncology of Poland
Radiotherapy and Oncology | Year: 2015

Aim: Current guidelines do not recommend the use of elective nodal irradiation for NSCLC, for several reasons. One of these is that PET-CT provides adequate nodal staging. We compared the published rates of elective nodal failures (ENFs) defined as regional failures that occur without local recurrence irrespectively of distant metastases status in patients who did or did not undergo PET-CT for staging. Methods: Reports of the occurrence of ENFs were considered. Only studies that used involved fields and specified the number of ENFs in patients with and without PET-CT use were included. A chi-squared test was used for the comparison of the risk of ENF in patients staged with and without PET. Results: Forty-eight studies were included; 2158 and 1487 patients with and without PET-CT performed before radiotherapy were identified. The proportion of patients treated with SBRT was higher in the group with PET-CT (71%) than it was in the group without PET-CT (20%; p <.001). There were 136 (6.3%) and 98 (6.6%) ENFs in patients with and without PET-CT, respectively (p =.74). Conclusion: The failure to reduce ENF by PET-CT was demonstrated. These data should be regarded in the context of the adequacy of reporting the rate of ENF and recognized value of PET-CT in NSCLC treatment. © 2015 Elsevier Ireland Ltd. All rights reserved.


A comprehensive review of the histological classification and genetics of serrated colorectal lesions and their relationship with CRC is presented. Sessile serrated lesions might be precursors in approximately one third of CRC cases. The criteria for the diagnosis of HPSP, its incidence, and relationship with CRC are provided and thoroughly discussed. The most recent guidelines for colonoscopy surveillance after screening and polypectomy concerning both serrated lesions and conventional adenomas presented by expert panels are provided. Copyright © 2013 by the American Society for Gastrointestinal Endoscopy.


Niwinska A.,Center of Oncology of Poland | Murawska M.,Erasmus Medical Center
International Journal of Radiation Oncology Biology Physics | Year: 2012

Purpose: The aim of the study was to present a new breast cancer recursive partitioning analysis (RPA) prognostic index for patients with newly diagnosed brain metastases as a guide in clinical decision making. Methods and Materials: A prospectively collected group of 441 consecutive patients with breast cancer and brain metastases treated between the years 2003 and 2009 was assessed. Prognostic factors significant for univariate analysis were included into RPA. Results: Three prognostic classes of a new breast cancer RPA prognostic index were selected. The median survival of patients within prognostic Classes I, II, and III was 29, 9, and 2.4 months, respectively (p < 0.0001). Class I included patients with one or two brain metastases, without extracranial disease or with controlled extracranial disease, and with Karnofsky performance status (KPS) of 100. Class III included patients with multiple brain metastases with KPS of ≤60. Class II included all other cases. Conclusions: The breast cancer RPA prognostic index is an easy and valuable tool for use in clinical practice. It can select patients who require aggressive treatment and those in whom whole-brain radiotherapy or symptomatic therapy is the most reasonable option. An individual approach is required for patients from prognostic Class II. © 2012 Elsevier Inc.


Roszkowski K.,Center of Oncology of Poland
Frontiers in Bioscience - Landmark | Year: 2014

Oxidative stress represents a deregulation of the homeostasis between the reactive oxygen species and the mechanisms of detoxification and repair. By analyzing the level of oxidatively damaged DNA bases and nucleosides in urine we can assess the extent of DNA repair within the whole body. High levels of markers of oxidative DNA damage excreted in the urine indicate elevated levels of oxidative stress, but can also reflect a high level of efficiency of the processes that work to repair this damage (oxidative stress can be high and the repair processes eliminate its effects). In the present review we discuss the role of oxidative stress, oxidative DNA damage repair mechanisms, potential sources of 8-oxoGua and 8-oxodG (basic markers of oxidative stress) content in urine, effect of antioxidant supplementation on the levels of oxidative DNA lesions, potential application of oxidative DNA damage determination in clinical practice.


Rutkowski T.,Center of Oncology of Poland
Strahlentherapie und Onkologie | Year: 2014

Background: The aim of this study was to quantify the impact of initial tumor volume (TV) on radiotherapy (RT) outcome in patients with T2 glottic cancer. Materials and methods: Initial TV was calculated for 115 consecutive patients with T2 glottic cancer who had been treated with definitive RT alone at a single institution. Results: The results showed strong correlations of TV with 3-year local tumor control (LTC) and disease-free survival (DFS). For TV≤0.7 cm3, 3-year LTC was 83%; for TV 0.7-3.6 cm3 this was 70% and for TV 3.6-17 cm3 44%. Analysis of total dose vs. initial TV showed that larger T2 glottic tumors with a TV of around 5 cm 3 (2-2.5 cm in diameter with 1010 cancer cells) need an extra 6.5 Gy to achieve similar 3-year LTC rates as for small tumors with a TV of 0.5 cm;bsupesup& (~1 cm in diameter with 109 cancer cells). Conclusion: Although classification of tumors according to TV cannot replace TNM staging in daily practice, it could represent a valuable numerical supplement for planning the optimal dose fractionation scheme for individual patients. © 2014 The Author(s).


The aim of this work was to create a model of a wide-bore Siemens Somatom Sensation Open CT scanner for use with GMCTdospp, which is an EGSnrc-based software tool dedicated for Monte Carlo calculations of dose in CT examinations.The method was based on matching spectrum and filtration to half value layer and dose profile, and thus was similar to the method of Turner etal. (Med. Phys. 36, pp. 2154-2164). Input data on unfiltered beam spectra were taken from two sources: the TASMIP model and IPEM Report 78. Two sources of HVL data were also used, namely measurements and documentation. Dose profile along the fan-beam was measured with Gafchromic RTQA-1010 (QA+) film. Two-component model of filtration was assumed: bow-tie filter made of aluminum with 0.5mm thickness on central axis, and flat filter made of one of four materials: aluminum, graphite, lead, or titanium.Good agreement between calculations and measurements was obtained for models based on the measured values of HVL. Doses calculated with GMCTdospp differed from the doses measured with pencil ion chamber placed in PMMA phantom by less than 5%, and root mean square difference for four tube potentials and three positions in the phantom did not exceed 2.5%. The differences for models based on HVL values from documentation exceeded 10%. Models based on TASMIP spectra and IPEM78 spectra performed equally well. © 2014 Associazione Italiana di Fisica Medica.

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