Feasibility of implementation of the early tumor shrinkage as a potential predictive marker to daily clinical practice in patients with RAS wild type metastatic colorectal cancer, treated with cetuximab - a non-interventional observational study.

BACKGROUND: With the aim to show the feasibility of early tumor shrinkage (ETS) concept implementation into daily clinical practice in the Czech Republic, a non-interventional, multicentric, single arm, prospective study in real world set-up was performed. MATERIAL AND METHODS: The study objectives were to explore the time interval from the treatment starting date to the date of the first radiographic control (TFRC) and evaluate the proportion of patients who achieved ≥ 20% tumor regression within the first 8 weeks of first-line therapy, in the real-world settings. RESULTS: The medians of TFRC in all individual participating centers were > 12 weeks (range 14.0-36.4 weeks). TFRC ≤ 8 weeks was reported for only 3% of patients in the cohort with first-line therapy, and there were only 3 patients (1%) who achieved tumor regression of ≥ 20% by day 60 (8.6 weeks). CONCLUSION: These findings indicate that the basic time parameter of ETS could not realistically be employed in routine oncology care of patients with metastatic colorectal cancer (mCRC) in the Czech Republic, unless there would be a strict request to perform TRFC by week 8 since the initiation of the therapy. In addition, the frequency of objective tumor response to first-line therapy with cetuximab + chemotherapy was evaluated. Based on the relative regression in the sum of diameters of measurable metastatic lesions, unconfirmed partial responses were achieved in 42.4 % and unconfirmed complete response in 8.6% of patients, altogether corresponding to the overall response rate of 51% with first-line therapy. The frequency of responses was higher among patients with left than right sided primary tumors. It seems that the regimen of cetuximab/FOLFOX might be more active in frontline therapy of right sided RAS wild type mCRC than cetuximab/FOLFIRI.

[Adverse effects of modern treatment of malignant melanoma and their treatment/ management]. / Nezádoucí úcinky novodobé lécby maligního melanomu a jejich lécba/ management.

BACKGROUND: Malignant melanoma belongs to the most deadly human tumours and despite all preventive programs its incidence continues to rise. Until 2011, chemotherapy was the only therapeutic option for inoperable or metastatic disease in the Czech Republic. However, new treatment modalities (e. g. targeted therapy) have been introduced recently. AIM: Since most of the modern drugs are still available only in clinical trials, the aim of this article is to provide a brief and comprehensive review of current treatment options for metastatic disease. The attention is focused on their potential side effects, so that doctors who do not usually deal with these drugs would get acquainted with them. This could contribute to a prompt management of associated symptoms or an early referral of the patient to an appropriate clinical centre without undue delay.

[High-dose interferon alpha in treatment of patients with malignant melanoma, monitoring of predictive and prognostic biomarkers]. / High-dose interferon alfa v lécbe pacientu s maligním melanomem, sledování prediktivních a prognostických biomarkeru.

BACKGROUNDS: The incidence of malignant melanoma is increasing by about 2-5% per year, exceeding an incidence of all other tumors. Adjuvant immunotherapy with high-dose interferon (HDI) as per the ECOG 1684 trial Kirkwood's schema is still recommended as a standard. HDI should be started within 60 days after a surgical procedure. Meaningful adjuvant immunotherapy is based on radical surgical excision, an investigation of the sentinel node and regional lymph node dissection, if indicated. Current research aims to utilize routinely usable biomarkers in order to define patients who would explicitly profit from HDI. DESIGN: The authors present a review of HDI trials, focusing on the management of adverse effects of HDI and on biomarkers. This review also discusses the initial own experiences at the Oncology Centre in Hradec Králové. CONCLUSION: Malignant melanoma is a very immunogenic tumour. Immunotherapy with HDI is considered to be the only therapeutic modality so far that has been proven to prolong relapse-free survival and overall survival (in short-time criterion) in adjuvant setting. However, the results of these trials are inconsistent and particular biomarkers of therapeutic response have not been defined yet.

[Chemotherapy and biological treatment in the complex management of large intestinal and rectal carcinomas. When, why, how?]. / Chemoterapie a biologická lécba v komplexní lécbe karcinomu tlustého streva a konecníku. Kdy, pro, jak?

The colorectal cancer treatment has significantly changed in last few years. Use of new drugs such as oxaliplatin, irinotecan, or capecitabine improved long term survival of patient with this disease. Research of biologic and genetic behavior of CRC has brought new ways in therapy called "biologic therapy". Standard today's treatment consist of three drugs: bevacizumab (antiVEGF antibody), cetuximab and panitumimab (anti EGFR antibodies). Biology therapy should be used simultaneously with chemotherapy only and after genetic examination of the cancer (K ras mutation). For patients with stage III the adjuvant therapy with combination of FOLFOX (oxaliplatin, fluorouracil, and leukovorin) is recommended to reduce the probability of recurrence and improve survival. In stage IIB there is a clear need to determine further risks which classify the high risk patients who should be enrolled in adjuvant chemotherapy. In palliative treatment of colorectal cancer there are several chemotherapy combinations (FUFA, FOLFOX, FOLFIRI, XELOX, XELIRI) used with biologic therapy. International recommendation for the biologic therapy is in the first line treatment bevacizumab and cetuximab or panitumumab in the second line is recommended. The new discoveries in biology of colorectal cancer show the need of tailoring.

[Resection of metastatic nondifferentiated carcinoma of sternum with thoracic wall reconstruction and simultaneous myocardial revascularization for ischemic heart disease--case report]. / Resekce sterna s rekonstrukcí hrudní steny pro metastázu nediferencovaného karcinomu v kombinaci s revaskularizací myokardu pro ischemickou chorobu srdecní--kazuistika.

Authors offer the case report of a patient with metastatic non differentiated carcinoma of sternum simultaneously suffering from ischemic heart disease. The patient underwent actinotherapy & hyperthermia followed by resection of sternum and coronary artery bypass grafting in one session. Chest wall defect was closed by means of latissimus dorsi muscle rotation. Postoperative palliative chemotherapy started 16 weeks postoperatively. Primary tumor was not found, neither preoperatively nor during the 36 months' postoperative remission.

Preoperative radiotherapy for locally advanced rectal cancer and prognostic factors influencing outcome.

The aim of presented study was to evaluate the impact of different factors on survival, local recurrence and development of metastatic disease in patients with rectal cancer treated with preoperative radiotherapy or 5-fluorouracil (5-FU) based concurrent chemoradiation. Retrospective clinical evaluation was performed in 165 patients (33% women and 67% men) with locally advanced rectal adenocarcinoma treated with preoperative radiotherapy or chemoradiotherapy in the period January 1998 - March 2003. Tumor extent was evaluated by CT and/or MRI and/or TRUS examination and tumor biopsy was performed during colonoscopy. The median follow up is 21 month. All patients received preoperative external beam radiation to primary tumor, adjacent lymphnodes and presacral region. Computed tomography localisation of target volume was used for 3D radiotherapy treatment planning. Accelerated short term regimen (25 Gy/5 fraction/1 week) was performed in 14% of patients especially in year 1998-2000 and normofractionated regimen (40-50 Gy/20-25 fractions/4-5 weeks) was performed in 86% of patients. Chemoradiotherapy with 5-FU was carried out in 22% of patients. Radical resection underwent 85% of patients, inoperable tumor persisted in 7% and distant metastases were detected peroperatively in 8%. The 2-year overall survival (OS) was 84% and 5-year OS was 60% following radical resection. The important prognostic factors affecting survival were postradiotherapy determined pathological staging (p=0.005), postradiotherapy tumor grade (p<0.001) and the presence of angioinvasion and/or perineural spread (p=0.023). Prognostic factors for disease-free survival were identical with those for OS. Higher local recurrence rate was associated in preradiotherapy tumor staged T4 (p=0.048) and in presence of angioinvasion and/or perineural spread (0.049). Age, tumor location, histological grade before radiotherapy and tumor downstaging were not statistically significant for survival and/or for local recurrence rate. The best survival rates were obtained in patients with postradiotherapy grade 1 tumors (5-years survival 100%), tumors without angioinvasion and perineural spread (5-years survival 65%) and in patients who obtained complete remission after preoperative radiotherapy (5-years survival 86%).

[Irinotecan in combination with 5-fluorouracil and leucovorin in the treatment of metastatic colorectal cancer]. / Irinotecan v kombinaci s 5- fluorouracilem a leukovorinem v lécbe metastatického kolorektálního karcinomu.

BACKGROUND: Introducing irinotecan and oxaliplatin in to the treatment of advanced colorectal cancer substantially improved the therapeutic results for this malignancy. The first results of clinical trials with these two drugs were published in 2000. METHODS AND RESULTS: Between 1999 to 2004 we treated 51 patients with the combination of irinotecan 180mg/m2 on day 1 and two hour infusion of leucovorin 200mg/m2 and 5-FU push of 400mg/m2 followed by infusion of 5- FU for 22 hours on days 1 and 2 every 2 weeks. Six patients (11.7%) achieved complete response, 11 (21.57%) partial response, stabilisation was observed by 23 patients (45.1%) and 21 patients were progressive (21.5%). The median survival time was 18 months (95% CI, 16.93-19.7), median duration of response was 9 months (Cl 95% 8.25-11.5). CONCLUSIONS: The combination of FOLFIRI is an effective and tolerable treatment of advanced colorectal cancer. However new treatment modalities to improve further the results of the treatment are still warranted.

Vinorelbine, epirubicin, and methotrexate (VEM) as primary treatment in locally advanced breast cancer.

PURPOSE: This phase II trial of VEM (vinorelbine + epirubicine + methotrexate) in the treatment of locally advanced breast cancer was conducted to obtain downstaging to allow surgery and breast conservation. PATIENTS AND METHODS: This multicenter study recruited 58 patients with locally advanced breast cancer (two patients ineligible); 56 were evaluable for response and tolerance. RESULTS: Downstaging was obtained in 77% of the patients with a pathological complete response (pCR) rate of 9%. At 33 months of follow-up, median survival has not been reached. Neutropenia grade 3-4 was reported in 31% of cycles with 3% of cycles with infection grade 3. Alopecia grade 3 was noticed for 71% of patients. CONCLUSION: VEM represents an effective regimen for patients with locally advanced breast cancer, allowing an important pCR. Moreover, this regimen appears to be particularly well tolerated.

Effects of intracerebral administration of IL-1beta on reactive behaviors of astrocytes and macrophages in the injured brain of newborn rats.

Newborn male rats were subjected to a mechanical lesion of the left cerebral hemisphere. Thereafter, a single dose 5 or 500 units (U) of recombinant rat interleukin-1beta (IL-1beta) was injected into the lesion cavity. One or 2 days after the injury, the rats were injected with 3H-thymidine to label dividing cells. Brain sections were subjected to GFAP immunocytochemistry or BSI-B4 lectin histochemistry to visualise astrocytes or macrophages, respectively. Autoradiography was used to detect cells proliferating within the region of injury in the immunocytochemically stained brain sections. The strongest mitogenic effect of IL-1beta on astrocytes (labeling index) was observed on day 1 after injury while a dose-dependent increase in their GFAP-immunoreactivity occurred on day 2. At 500U dose, IL-1beta significantly reduced infiltration of macrophages on posttraumatic days 1 and 2 but did not influence their proliferation. Thus, effects of IL-1beta on the occurrence of macrophages were opposite to those on the GFAP-immunoreactivity of astrocytes and their proliferation. It appears to suggest existence of different mechanisms controlling reactive behaviors of the two cell populations.

[Interleukin-6: friend or enemy? Latest findings on the clinical aspects of IL-6]. / Interleukin-6: Ertünk vagy ellenünk? Ujabb eredmények az IL-6 klinikai vonatkozásairól.

The authors summarize the recent findings obtained in the field of inflammatory cytokines with particular attention on interleukin-6 (IL-6). After a short review of the molecular biology and of the cellular effects of IL-6, the most important clinical relations of IL-6 in hepatic diseases, in non-specific inflammatory bowel diseases (Crohn's disease and ulcerative colitis) and in certain autoimmune diseases are provided. The simultaneous discussion of molecular and clinical data contribute to the understanding of pathomechanisms.

Agreement and disagreement between laboratories in species identification of mycobacteria.

Twenty coded strains of the following species: Mycobacterium avium, M. fortuitum, M. gordonae, M. chelonei, M. intracellulare, M. kansasii, M. nonchromogenicum, M. scrofulaceum, M. terrae, M. triviale and M. xenopi, were subjected to identification in a co-operative study undertaken by seven laboratories of four countries (CSSR, GDR, PRP and USSR). Three of these laboratories recognized 18-19 (90-95%) of the strains, three others 15-17 (75-85%) and one laboratory recognized 8 (40%) strains. In the correctly identified species, agreement between the tests used by all participants was evaluated. The highest rates of agreement in positive or negative results (04-100%) were obtained for nitrate reduction, detection of arylsulphatase, urease and nicotinamidase in M. kansasii, M. avium-intracellulare and M. fortuitum.

A co-operative numerical analysis of Mycobacterium gastri, Mycobacterium kansasii and Mycobacterium marinum.

A co-operative taxonomic study has been performed on slowly growing photochromogenic mycobacteria (Runyon Group I) and closely related organisms. Phenetic data on 54 strains, studied in seven laboratories, were collected and analysed by numerical taxonomic methods. Immunological properties and phage susceptibility patterns were analysed independently to establish correlation with numerical classification. Mycobacterium gastri, M. kansasii and M. marinum appeared as distinct well-defined clusters and the serological and phage data supported the resolution of these three species. A table of definitive properties is presented. Two strains each of M. simiae and M. asiaticum formed a loose cluster which was clearly separated from the previously mentioned three species; the small number of strains examined precluded the establishment of a list of definitive properties of these two species. It is concluded that the Runyon Groups, which provided a practical though arbitrary basis for establishment of a series of co-operative studies, have served their purpose and should now be supplanted by classification and nomenclature based on species.