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.

Fecal microbiota transplantation - new possibility to influence the results of therapy of cancer patients.

BACKGROUND: The intestinal microbio-me is essential for the function of the human body, it affects not only metabolism and digestion, but also the immune and neurobehavioral systems. The composition of the human intestinal microbio-me has been of interest to many scientific teams around the world in recent years, aided by the rapid development of molecular genetics methods. Intestinal microbio-me imbalance (so-called dysbio-sis) can help develop several pathological conditions such as autoimmune diseases or can be involved in the process of carcinogenesis. Microbio-me research in oncology has so far focused most on the effect of intestinal microbio-me composition on the effectiveness of checkpoint inhibitors. Differences in the relative proportions of individual bacterial strains and the overall microbio-me diversity in patients treated with checkpoint inhibitors appear to be related to the efficacy of this therapy. Many projects are currently studying the possibility of manipulating the composition of the intestinal microbio-me, especially by means of fecal microbial transplantation (FMT). Two published clinical studies have confirmed that it is possible to overcome resistance to checkpoint inhibitor therapy in malignant melanoma with this method and to re-establish a clinical response after FMT. One of the problems of this effort is the significant diversity in the composition of the microbio-me in different populations. Therefore, knowledge of the microbial composition in a particular population is of key importance. The Department of Oncology of the 1st Faculty of Medicine at Charles University and the General University Hospital in Prague is part of this effort, where a program to investigate intestinal microbio-me composition in patients with non-small cell lung cancer, renal cell carcinoma and malignant melanoma during checkpoint inhibitor therapy has been running for several years. PURPOSE: The aim of the publication is to demonstrate the current information and the importance of fecal transplantation in oncology and also to present our currently ongoing research project.

Quality of life after extended pelvic exenterations.

BACKGROUND: The aim of the study was to compare health-related quality of life (QoL) and oncological outcome between gynaecological cancer patients undergoing pelvic exenteration (PE) and extended pelvic exenteration (EPE). EPEs were defined as extensive procedures including, in addition to standard PE extent, the resection of internal, external, or common iliac vessels; pelvic side-wall muscles; large pelvic nerves (sciatic or femoral); and/or pelvic bones. METHODS: Data from 74 patients who underwent PE (42) or EPE (32) between 2004 and 2019 at a single tertiary gynae-oncology centre in Prague were analysed. QoL assessment was performed using EORTC QLQ-C30, EORTC CX-24, and QOLPEX questionnaires specifically developed for patients after (E)PE. RESULTS: No significant differences in survival were observed between the groups (P > 0.999), with median overall and disease-specific survival in the whole cohort of 45 and 49 months, respectively. Thirty-one survivors participated in the QoL surveys (20 PE, 11 EPE). No significant differences were observed in global health status (P = 0.951) or in any of the functional scales. The groups were not differing in therapy satisfaction (P = 0.502), and both expressed similar, high willingness to undergo treatment again if they were to decide again (P = 0.317). CONCLUSIONS: EPEs had post-treatment QoL and oncological outcome comparable to traditional PE. These procedures offer a potentially curative treatment option for patients with persistent or recurrent pelvic tumour invading into pelvic wall structures without further compromise of patients´ QoL.

[Neoadjuvant Use of Isolated Limb Perfusion in Large Myxoid Liposarcoma of the Thigh: a Case Report]. / Neoadjuvantní uzití izolované perfuze koncetiny u objemného myxoidního liposarkomu stehna: kazuistika.

Large unresectable STS presents a therapeutic challenge. Several options are being explored to avoid amputation without compromising the oncological outcome. Neoadjuvant chemotherapy delivers inconsistent and rather unsatisfactory results, preoperative radiotherapy compromises healing, hence it can impede adjuvant systemic treatment. We present a case report of neoadjuvant use of isolated limb perfusion with TNF-alfa and Alkeran (Melphalan) in a patient with initially unresectable large myxoid liposarcoma of the thigh. We achieved 55% reduction in size of the tumor that allowed for wide resection with a safe margin. Pathology confirmed 99% tumor necrosis. The patient has a full function of his extremity and is disease-free at one year follow-up. ILP should be considered as a treatment option which, in selected cases, can contribute to limb sparing surgery. Key words: sarcoma, soft tissue, regional perfusion, chemotherapy, surgery, orthopedic, limb salvage.

Robotic-assisted surgery for rectal cancer results of a non-randomized study.

INTRODUCTION: The Czech Republic belongs to countries in which colorectal cancer significantly contributes to the overall oncological burden. Radical removal of tumor-affected tissues plays a key role in the multimodal therapy of rectal cancer. In the first decade of the third millennium the mini-invasive approach in rectal cancer surgery gradually expanded to include robotic-assisted surgeries. The aim of this paper is to present the results of a non-randomized study with prospectively collected data from robotically assisted rectal cancer surgeries. METHODS: 204 patients with rectal cancer (.

Novel spectroscopic biomarkers are applicable in non-invasive early detection and staging classification of colorectal cancer.

Colorectal cancer (CRC) remains a significant threat to human health because of the lack of awareness of physical examination or the limitations of an early diagnostic level. Despite the improving standard of modern medicine, mortality from CRC is still remarkably high and the prognosis remains poor in many cases because of disease detection at advanced clinical stages. Raman spectroscopy yields precise information, not only regarding the secondary structure of proteins but also regarding the discrimination between normal and malignant tissues. We investigated whether this method can be used for the diagnosis of CRC including initial stages. To acquire more detailed structural information, we tested a novel diagnostic approach based on a suitable combination of conventional methods of molecular spectroscopy (Raman and Fourier transform infrared) with advanced, highly structure-sensitive chiroptical techniques as electronic circular dichroism (ECD) and Raman optical activity (ROA) to monitor the CRC pathogenesis relating compositional, structural and conformational changes in blood biomolecules, some of which may be caused by pathological processes occurring during cancer growth, also at the beginning of the disease. Sixty-three blood plasma samples were analyzed using the combination of ECD and ROA supplemented by Raman and Fourier transform infrared (FT-IR) spectroscopies. The obtained spectra were evaluated together by linear discriminant analysis. The accuracy of sample discrimination reached 100% and the subsequent leave-one-out cross-validation resulted in 90% sensitivity and 75% specificity. There were also found the differences between the patients according to the clinical stage. The achieved results suggest a panel of promising biomarkers and indicate that chiroptical methods combined with conventional spectroscopies might be a new minimally invasive powerful tool for producing high-quality data, obtaining an accurate diagnosis of colorectal cancer through a peripheral blood sample, which is also able to determine the extent of this pathology. Further work needs to be carried out for these techniques to be implemented in the clinical setting.

PIPAC - overview of the method and first use in the Czech Republic.

PIPAC is a new technique for intra-abdominal administration of aerosol chemotherapy in a gaseous environment (capnoperitoneum). It can be indicated for peritoneal spread of various origins, most commonly ovarian cancer, stomach cancer and colorectal cancer. Due to its mini-invasiveness, the application can be repeated. The article provides a brief overview of current views of PIPAC and describes the first experience with PIPAC in the Czech Republic.

Neoadjuvant Hypertermic Isolated Limb Perfusion in Treatment of Undifferentiated Spindle Cell Sarcoma of Lower Limb with Achieved Complete Pathologic Response.

BACKGROUND: Hyperthermic isolated limb perfusion uses therapeutic effect of hyperthermia in the bounded compartment of the limb together with increased concentration of chemotherapy effect than what would be achieved in systemic application. Gold standard was melphalan (Alkeran) in combination with tasonermin (Beromun, tumor necrosis factor alpha). The efficacy of this combination has been demonstrated in limb soft tissue sarcomas and in patients with limb isolated bulky disease of malignant melanoma. CASE: We describe a case of a 65-year-old female patient with undifferentiated spindle-cell sarcoma treated by a multidisciplinary team at the 2nd Surgical Clinic of Cardiovascular Surgery and Clinic of Oncology General University Hospital in Prague and at the Department of Orthopaedics Na Bulovce Hospital with the aim of preserving the limb despite the advanced disease. The patient underwent hyperthermic isolated limb perfusion with tasonermin and melphalan with partial response on magnetic resonance imaging. Subsequent wide resection was done with complete pathological remission according to histological examination maintaining a fully functional limb. The patient is followed without signs of recurrence. CONCLUSION: Hyperthermic isolated limb perfusion with tasonermin and melphalan is an important part of a multimodal approach in the treatment of extremity sarcomas with a high percentage of responses that increase the percentage of limbs retaining resections. Multidisciplinary team should consider this option in patients with localized limb sarcomas and should be performed in specialized centers with experience in this procedure. This work was supported by project Progres Q28-LF1. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Assessment of anastomosis perfusion by fluorescent angiography in robotic low rectal resection: the results of a non-randomized study.

INTRODUCTION: Colorectal cancer is a major contributor to the overall cancer burden in the Czech population. Anastomotic healing defects are a feared complication which may have a fatal impact on the patient. Fundamental conditions for proper anastomotic healing include sufficient blood supply. Fluorescent angiography using indocyanine green in the spectrum of near-infrared light facilitates the monitoring of tissue perfusion during a surgery. The aim of this article is to present the results of a non-randomized study in which we assessed prospectively obtained data from a perioperative assessment of anastomosis perfusion by fluorescent angiography using indocyanine green during robotic resection of the rectum with a malignant tumor. METHOD: Thirty patients with rectal cancer who underwent a robotic resection with primary anastomosis were consecutively included in the study between 1 April 2017 and 21 June 2018. The study included patients due to undergo a minimally invasive procedure with guaranteed health insurance coverage. During the operation, we monitored and assessed the quality of perfusion of the resection line of the sigmoid colon and subsequent anastomosis by means of fluorescent angiography using indocyanine green in the spectrum of near-infrared light. The data were obtained prospectively and subsequently analyzed. RESULTS: Between 1 April 2017 and 21 June 2018, we consecutively included 30 rectal cancer patients in the project: 16 men and 14 women. Monitoring of perfusion of the resection line and anastomosis was successful in all cases and perfusion quality was satisfactory across the sample. Perfusion insufficiency requiring a change in the resection line level or anastomosis adjustments was not detected with any patient. In two cases (12.5 %) of TME, we gave up the planned protective ileostomy owing to good perfusion of the anastomosis. One patient (3.3%) suffered from defective anastomotic healing without clinical symptoms (type A). We found no technical complications related to fluorescent angiography or undesirable effects due to the application of indocyanine green. CONCLUSION: Fluorescent angiography using indocyanine green in the spectrum of near-infrared light is a fast and safe option to monitor the level of blood supply to an anastomosis during surgery, which is a fundamental condition for proper healing. Even though we did not record insufficient perfusion in our sample and hence we did not need to change the resection line level or adjust the anastomosis, we may state that fluorescent angiography performed by an experienced colorectal surgeon may potentially reduce the frequency of complications linked to defective anastomotic healing.

[The Inclusion of a Gemcitabine + Nab-paclitaxel Regimen as a 2nd Line Treatment for Advanced Pancreatic Cancer - First Experience]. / Zarazení rezimu gemcitabin + nab-paklitaxel do 2. linie lécby pokrocilého karcinomu slinivky brisní - první zkusenosti.

INTRODUCTION: Pancreatic cancer is the fourth leading cause of cancer-related death worldwide. The outcomes at all stages of the disease are the worst among patients with solid tumors. PATIENTS AND METHODS: Analyses were conducted on 19 patients treated with gamcitabine + nab-paclitaxel for locally advanced or metastatic pancreatic cancer as a second line treatment between October, 2014, and December, 2016, at Department of Oncology of First Faculty of Medicine and General University Hospital in Prague. Patients were treated with gemcitabine (1,000 mg/sqm) + nab-paclitaxel (125 mg/sqm) at days 1, 8 and 15 of each 28-day cycle. Antitumor efficacy (disease control rate (DCR), time to progression (TTP), and overall survival (OS)) and adverse events were monitored. RESULTS: Disease control according to RECIST criteria was achieved in nine cases (56.3%, two partial regressions were observed). The median TTP was 5.5 months and median OS was 10.1 months. CONCLUSION: In patients with advanced or metastatic pancreatic cancer with good performance statuses (0-1) gemcitabine + nab-paclitaxel as a second line treatment led to a prolongation in time to progression and higher overall survival with good quality of life.Key words: pancreatic cancer - gemcitabine - nab-paclitaxel - efficiency - toxicity This project was supported by grant PROGRES-Q-25/LF1, The League Against Cancer a AZV CR 15-28188A. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 11. 7. 2017Accepted: 20. 9. 2017.

[Isolated Perfusion of the Upper Extremity with TNF-α - Double Venous Cannulation]. / Izolovaná perfuze horní koncetiny s TNF-α - dvojitá kanylace zilního systému.

BACKGROUND: The authors present a technical variation of the standard cannulation for cardiopulmonary bypass perfusion during hyperthermic isolated limb perfusion (ILP) procedures in selected patients with unresectable soft tissue sarcoma or malignant melanoma. PATIENTS: Of 55 ILP procedures performed at our institution since the procedure was established in 2009, nine were performed at the upper extremity. Standard single venous cannulation was used in five cases, and extended, double venous cannulation in the last four. The standard technique for brachial vein cannulation in a small compartment of the upper extremity entails a problematic and longer perfusion of the upper extremity. This is due to the lower flow rate in the venous system and relatively large surface area with respect to weight. We present a simple technique based on a "Y" cannulation of the venous system via the deep brachial vein and superficial venous system via the basilic vein, delivering a 20% increase in flow rate in the extracorporeal circulation. Faster heating of the upper extremity and a stable thermal environment throughout upper-extremity ILP are essential for successful treatment. CONCLUSION: Extended technique of venous cannulation for extracorporeal circulation setting, due to their advantages, became standard in the upper limb ILP procedure at our institution.Key words: isolated limb perfusion - malignant melanoma - soft tissue sarcoma - upper limb - extracorporeal circulation The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 8. 1. 2017Accepted: 15. 1. 2017.

Mutation analysis of the PALB2 gene in unselected pancreatic cancer patients in the Czech Republic.

Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis among common solid cancer diagnoses. It has been shown that up to 10% of PDAC cases have a familial component. Characterization of PDAC-susceptibility genes could reveal high-risk individuals and patients that may benefit from tailored therapy. Hereditary mutations in PALB2 (Partner and Localizer of BRCA2) gene has been shown to predispose, namely to PDAC and breast cancers; however, frequencies of mutations vary among distinct geographical populations. Using the combination of sequencing, high-resolution melting and multiplex ligation-dependent probe amplification analyses, we screened the entire PALB2 gene in 152 unselected Czech PDAC patients. Truncating mutations were identified in three (2.0%) patients. Genotyping of found PALB2 variants in 1226 control samples revealed one carrier of PALB2 truncating variant (0.08%; P = 0.005). The mean age at PDAC diagnosis was significantly lower among PALB2 mutation carriers (51 years) than in non-carriers (63 years; P = 0.016). Only one patient carrying germline PALB2 mutation had a positive family breast cancer history. Our results indicate that hereditary PALB2 mutation represents clinically considerable genetic factor increasing PDAC susceptibility in our population and that analysis of PALB2 should be considered not only in PDAC patients with familial history of breast or pancreatic cancers but also in younger PDAC patients without family cancer history.

Hereditary truncating mutations of DNA repair and other genes in BRCA1/BRCA2/PALB2-negatively tested breast cancer patients.

Hereditary breast cancer comprises a minor but clinically meaningful breast cancer (BC) subgroup. Mutations in the major BC-susceptibility genes are important prognostic and predictive markers; however, their carriers represent only 25% of high-risk BC patients. To further characterize variants influencing BC risk, we performed SOLiD sequencing of 581 genes in 325 BC patients (negatively tested in previous BRCA1/BRCA2/PALB2 analyses). In 105 (32%) patients, we identified and confirmed 127 truncating variants (89 unique; nonsense, frameshift indels, and splice site), 19 patients harbored more than one truncation. Forty-six (36 unique) truncating variants in 25 DNA repair genes were found in 41 (12%) patients, including 16 variants in the Fanconi anemia (FA) genes. The most frequent variant in FA genes was c.1096_1099dupATTA in FANCL that also show a borderline association with increased BC risk in subsequent analysis of enlarged groups of BC patients and controls. Another 81 (53 unique) truncating variants were identified in 48 non-DNA repair genes in 74 patients (23%) including 16 patients carrying variants in genes coding proteins of estrogen metabolism/signaling. Our results highlight the importance of mutations in the FA genes' family, and indicate that estrogen metabolism genes may reveal a novel candidate genetic component for BC susceptibility.

[PALB2 as Another Candidate Gene for Genetic Testing in Patients with Hereditary Breast Cancer in Czech Republic]. / PALB2 jako dalsí kandidátní gen pro genetické testování u pa-cientu s hereditárním karcinomem prsu v Ceské republice.

BACKGROUND: The PALB2 (FANCN) gene was identified as a component of endogenous BRCA2 complex that encodes a DNA repair protein participating along with BRCA1 and BRCA 2 proteins in DNA double-strand break repair. Hereditary PALB2 mutations are associated with an increased risk of breast and pancreatic cancers in heterozygotes. Breast cancer risk for PALB2 mutation carriers has recently been estimated at 33-58% depending on family history of breast cancer; pancreatic cancer risk in carriers of PALB2 mutations has not been precisely quantified, yet. MATERIALS AND RESULTS: Results of a study identifying PALB2 mutations in high-risk, BRCA1/2-negative, breast and/or ovarian cancer patients in the Czech Republic indicate that the frequency of hereditary PALB2 mutations in our population is quite high. Interestingly, almost 20% of all recognized mutations comprised large genomic rearrangements. The highest proportion of PALB2 mutations (comparable with the number of mutations reported for BRCA2) was found in a subgroup of hereditary breast cancer patients (5.5%). Frequency of mutations in an independent group of Czech unselected pancreatic cancer patients was approximately 1.3%. CONCLUSION: Considering the frequency of pathogenic, hereditary PALB2 mutations in our population, their phenotypic similarity to BRCA2, and expected risk of breast cancer associated with PALB2 mutations, its screen-ing (including large genomic rearrangements) should be encouraged in patients from hereditary breast cancer families. The follow-up of pathogenic PALB2 mutation carriers should be similar to that in BRCA2 mutation carriers, enabling early diagnosis, prevention, and possible targeted therapy. Preventive surgical interventions for the carriers could be considered in case of strong family cancer history and evident segregation of a pathogenic mutation with a tumor phenotype. Additional analysis of various cancer patient populations and further meta-analyses will be necessary for accurate assessment of PALB2 gene penetrance and its significance for the risk of pancreatic and other cancers.

[Immunoscore and Its Predictive Value for Colorectal Cancer]. / Immunoscore a jeho prediktivní hodnota u kolorektálního karcinomu.

Recent studies suggest that immune  classification (immune-score) in cancer patients has a prognostic value in some cases that seems to be superior to the AJCC/ UICC TNM  classification. The clinical outcome can vary significantly among patients with a particular diagnosis within the same TNM stage. Immunoscore methodology quantifies and detects different types of immune cells in tumor tissue, and also determines the density of their infiltration and localization at the tumor site. Currently within an international collaboration of 23 centers in 17 countries (including our department), immunoscore is being evaluated in more than 7,000 colorectal cancer patients in terms of the tumor microenvironment, focusing on the presence of immune cells both in the tumor tissue and the tumor invasive margin. Immunoscore results are assessed in correlation with: 1. patients response to the treatment, 2. rate of progression, disease prognosis and other immune parameters. It appears that the TNM classification and tumor invasiveness is statistically dependent on the immune response of the patient (there is an inverse correlation between the density of the infiltration of CD8⁺, CD3⁺ lymphocytes and the tumor stage). High densities of T-lymphocytes (CD8⁺, CD3⁺) both in the core and the invasive margin of the primary tumor are associated with longer term asymptomatic survival, overall survival, lower risk of relapse and reduced likelihood of metastases. The project of the international collaboration aims to introduce immunoscore in routine diagnostics.

Trefoil factor family (TFF) proteins as potential serum biomarkers in patients with metastatic colorectal cancer.

Trefoil factor family (TFF) is composed of three secretory proteins (TFF1, TFF2 and TFF3) that play an important role in mucosal protection of gastrointestinal tract. Their overexpression in colorectal tumors seems to be associated with more aggressive disease. We collected serum samples from 79 healthy controls and 97 patients with metastatic colorectal cancer at the time of diagnosis or at progression. Serum levels of TTF1-3, CEA and CA19-9 were measured by ELISA. Serum TFF1 and TFF3 levels were significantly higher in patients with colorectal cancer compared to healthy controls (p < 0.0001). Moreover, serum levels of TFF3 correlated with extent of liver involvement in patient without pulmonary metastases and patients with higher TFF3 levels had significantly worse outcome (p < 0.0001). Compared to CEA and CA19-9, TFF3 had higher sensitivity and the same specificity. Our results indicate that TFF3 is an effective biomarker in patients with metastatic colorectal cancer with higher sensitivity than CEA a CA19-9. TFF3 levels strongly correlate with extension of liver disease and seem to have prognostic value.

Cellular and humoral immunodeficiency in breast cancer patients resistant to hormone therapy.

In view of the fact that insufficiency in immune response often correlates with poor prognosis, research in recent years has focused on the task of describing the precise status and function of the immune system and its possible effect on cancer patients. Although more than two thirds of treated patients respond to endocrine therapy, most patients with metastatic breast cancer develop a resistance to it. Estrogen modulates angiogenesis, partially through its effects on vascular endothelial growth factor (VEGF). It also appears that transforming growth factor-beta (TGF beta) could be another factor contributing to this resistance. TGF beta is a highly immunosuppressive factor that inhibits natural and specific immunity against tumors and stimulates the production of VEGF. The purpose of the study was to monitor immune responses in patients with hormone receptor-positive breast cancer who were resistant to hormone therapy. The examination of cellular components (CD4, CD8, HLA-DR, NK cells) and humoral immunity (IgG, IgG subclasses, IgA, IgM,). TGF beta and VEGF production were monitored with special attention, along with an analysis of the changes that occurred during the hormonal treatment. 68 patients included in the research project were implemented with routine cancer treatment with endocrine therapy. Basic parameters (the histological type and grade, the degree of expression of estrogen receptors (ER) and progesterone receptors (PR), human epidermal growth factor receptor 2 (HER2), and the proliferative marker) were established. Patients were evaluated by a cancer clinical immunologist to exclude immune disorders, allergic or autoimmune origin. TGF beta and VEGF were measured by ELISA and antitumor cellular immunity (CD4, CD8) was measured by flow cytometry. Patients who failed in the first line of hormone therapy treatment were considered as resistant to hormone therapy.Depression in cellular immunity was found especially in patients with resistance to endocrine therapy. In addition, immunoglobulin plasma levels were decreased (mainly IgG4 subtype). Most patients showed clinical symptoms of immunodeficiency (frequent infections of respiratory or urinary tract, herpetic infections). Significant increases in TGF beta and VEGF plasma were also detected.The correlation of these factors with resistance to hormonal therapy and the state of anticancer immunity could be helpful in the task of predicting resistance to hormonal therapy and could contribute to the selection of targeted immune therapy in cancer patients in the future.

[Trabectedin registry]. / Lékový registr--trabectedin.

BACKGROUNDS: The Yondelis (trabectedin) project was initiated in January 2011 with the aim to obtain basic epidemiological information on patients with soft tissue sarcomas, standard treatment procedures, and results of trabectedin therapy in routine clinical practice. Expert patronage is provided by the Czech Society for Oncology, CzMA JEP. The project covers a representative sample of Comprehensive Cancer Care centres established to provide systematic treatment to patients with soft tissue sarcoma. PATIENTS AND METHODS: 45 patients diagnosed with soft tissue sarcoma were retrospectively included in the database. Median age at the initiation of trabectedin therapy was 51 years (23-72 years). Leiomyosarcoma was the most frequent tumour (35.6%), synovial sarcoma occurred in 13.3% of patients; liposarcoma, peripheral nerve sheath tumours and unspecified sarcomas contributed 6.7% each. 62.2% of sarcomas were larger than 5 cm. Trabectedin was administered in a dose of 1.5 mg/m2 once in 3 weeks. 40% of patients received trabectedin as the 2nd line treatment, 35.6% as the 3rd line, and 34.4% as the 4th line. RESULTS: Median number of administered cycles was 4 (1-10 cycles). Neutropenia (28.9% of patients) and elevated liver enzymes (26.7% of patients) were the most frequent adverse affects. 73.8% of patients terminated the therapy due to disease progression. Treatment response was recorded in 6.6% of patients (complete and partial remission), stable disease in 26.7%, and progression in 53.3%. Median overall survival (95% CI) was 11.7 months (9.6; 13.8), median progression-free survival (95% CI) was 3 months (2.4; 3.6). CONCLUSION: Expert cancer societies have recently recommended trabectedin as the 2nd line palliative treatment for soft tissue sarcomas with documented effectiveness, particularly in liposarcomas and leiomyosarcomas, and good safety profile.