Association of triple positivity with prognostic parameters and overall survival in a population-based study of 6,122 HER2-positive breast cancer patients: analysis of real-world clinical practice based on a research database.

Triple-positive breast cancer (TPBC), i.e. HER2-positive (HER2+) and hormone receptors-positive breast cancer, is a specific subgroup of breast cancers. TPBC biology is characterized by strong mutual interactions between signaling pathways stimulated by estrogens and HER2 amplification. The present study aims to carry out a population-based analysis of treatment outcomes in a cohort of hormone receptor (HR) positive and negative breast cancer patients who were treated with anti-HER2 therapy in the Czech Republic. The BREAST research database was used as the data source for this retrospective analysis. The database covers approximately 95% of breast cancer patients treated with targeted therapies in the Czech Republic. The analysis included 6,122 HER2-positive patients. The patients were divided into two groups, based on estrogen receptor (ER) or progesterone receptor (PR) positivity: hormone receptor negative (HR-) patients had both ER- and PR-negative tumors (n=2,518), unlike positive (HR+) patients (n=3,604). HR+ patients were more often diagnosed premenopausal at the time of diagnosis, presented more often at stage I or II and their tumors were less commonly poorly differentiated. The overall survival (OS) was significantly higher in subgroups of HR+ patients according to treatment setting. When evaluated by stages, significantly higher OS was observed in HR+ patients diagnosed at stages II, III, and IV and regardless of tumor grade.

Biomarker analysis beyond angiogenesis: RAS/RAF mutation status, tumour sidedness, and second-line ramucirumab efficacy in patients with metastatic colorectal carcinoma from RAISE-a global phase III study.

Background: : Second-line treatment with ramucirumab+FOLFIRI improved overall survival (OS) versus placebo+FOLFIRI for patients with metastatic colorectal carcinoma (CRC) [hazard ratio (HR)=0.84, 95% CI 0.73-0.98, P = 0.022]. Post hoc analyses of RAISE patient data examined the association of RAS/RAF mutation status and the anatomical location of the primary CRC tumour (left versus right) with efficacy parameters. Patients and methods: Patient tumour tissue was classified as BRAF mutant, KRAS/NRAS (RAS) mutant, or RAS/BRAF wild-type. Left-CRC was defined as the splenic flexure, descending and sigmoid colon, and rectum; right-CRC included transverse, ascending colon, and cecum. Results: RAS/RAF mutation status was available for 85% of patients (912/1072) and primary tumour location was known for 94.4% of patients (1012/1072). A favourable and comparable ramucirumab treatment effect was observed for patients with RAS mutations (OS HR = 0.86, 95% CI 0.71-1.04) and patients with RAS/BRAF wild-type tumours (OS HR = 0.86, 95% CI 0.64-1.14). Among the 41 patients with BRAF-mutated tumours, the ramucirumab benefit was more notable (OS HR = 0.54, 95% CI 0.25-1.13), although, as with the other genetic sub-group analyses, differences were not statistically significant. Progression-free survival (PFS) data followed the same trend. Treatment-by-mutation status interaction tests (OS P = 0.523, PFS P = 0.655) indicated that the ramucirumab benefit was not statistically different among the mutation sub-groups, although the small sample size of the BRAF group limited the analysis. Addition of ramucirumab to FOLFIRI improved left-CRC median OS by 2.5 month over placebo (HR = 0.81, 95% CI 0.68-0.97); median OS for ramucirumab-treated patients with right-CRC was 1.1 month over placebo (HR = 0.97, 95% CI 0.75-1.26). The treatment-by-sub-group interaction was not statistically significant for tumour sidedness (P = 0.276). Conclusions: In the RAISE study, the addition of ramucirumab to FOLFIRI improved patient outcomes, regardless of RAS/RAF mutation status, and tumour sidedness. Ramucirumab treatment provided a numerically substantial benefit in BRAF-mutated tumours, although the P-values were not statistically significant. ClinicalTrials.gov number: NCT01183780.

Analysis of angiogenesis biomarkers for ramucirumab efficacy in patients with metastatic colorectal cancer from RAISE, a global, randomized, double-blind, phase III study.

Background: The phase III RAISE trial (NCT01183780) demonstrated that the vascular endothelial growth factor (VEGF) receptor (VEGFR)-2 binding monoclonal antibody ramucirumab plus 5-fluororuracil, leucovorin, and irinotecan (FOLFIRI) significantly improved overall survival (OS) and progression-free survival (PFS) compared with placebo + FOLFIRI as second-line metastatic colorectal cancer (mCRC) treatment. To identify patients who benefit the most from VEGFR-2 blockade, the RAISE trial design included a prospective and comprehensive biomarker program that assessed the association of biomarkers with ramucirumab efficacy outcomes. Patients and methods: Plasma and tumor tissue collection was mandatory. Overall, 1072 patients were randomized 1 : 1 to the addition of ramucirumab or placebo to FOLFIRI chemotherapy. Patients were then randomized 1 : 2, for the biomarker program, to marker exploratory (ME) and marker confirmatory (MC) groups. Analyses were carried out using exploratory assays to assess the correlations of baseline marker levels [VEGF-C, VEGF-D, sVEGFR-1, sVEGFR-2, sVEGFR-3 (plasma), and VEGFR-2 (tumor tissue)] with clinical outcomes. Cox regression analyses were carried out for each candidate biomarker with stratification factor adjustment. Results: Biomarker results were available from >80% (n = 894) of patients. Analysis of the ME subset determined a VEGF-D level of 115 pg/ml was appropriate for high/low subgroup analyses. Evaluation of the combined ME + MC populations found that the median OS in the ramucirumab + FOLFIRI arm compared with placebo + FOLFIRI showed an improvement of 2.4 months in the high VEGF-D subgroup [13.9 months (95% CI 12.5-15.6) versus 11.5 months (95% CI 10.1-12.4), respectively], and a decrease of 0.5 month in the low VEGF-D subgroup [12.6 months (95% CI 10.7-14.0) versus 13.1 months (95% CI 11.8-17.0), respectively]. PFS results were consistent with OS. No trends were evident with the other antiangiogenic candidate biomarkers. Conclusions: The RAISE biomarker program identified VEGF-D as a potential predictive biomarker for ramucirumab efficacy in second-line mCRC. Development of an assay appropriate for testing in clinical practice is currently ongoing. Clinical trials registration: NCT01183780.

[Evaluation of Anti-cancer Therapies with Reimbursement Limited to Comprehensive Cancer Centres Using the European Society for Medical Oncology Magnitude of Clinical Benefit Scale]. / Hodnocení klinického benefitu protinádorových léku limitovaných na komplexní onkologická centra podle metodiky ESMO-MCBS.

BACKGROUND: The costs of oncology treatments are increasing, due to the rising prevalence of malignant diseases and the introduction of expensive novel anti-cancer agents. The new European Society for Clinical Oncology (ESMO) has recently developed a new parametric system to evaluate the clinical benefit of drugs. The Magnitude of Clinical Benefit Scale (ESMO-MCBS) compares the contribution of a novel drug based on overall and progression-free survival and quality of life with those of current treatment options. MATERIAL AND METHODS: An expert group of the Czech Oncological Society conducted an assessment based on published data and an ESMO-MCBS methodology for antineoplastic agents used for the treatment of solid tumors with limited reimbursement to Comprehensive Cancer Centers. We evaluated drugs categorized as "S" that were eligible for public health insurance as of January 1, 2017. RESULTS AND CONCLUSION: The ESMO-MCBS score is a promising new parameter for the evaluation of new anticancer drugs. The ESMO-MCBS method for assessing the clinical benefit of drugs is simple, robust, and reproducible. The advantage of the assessment is that it is not based on a single index but rather combines several dimensions of drug performance. This parameter will be gradually added to Czech cancer guidelines. Scores obtained in the majority of cases correspond to the observed benefit of a drug in routine clinical practice.Key words: tumors - farmacotherapy - assesment study as a subject - survival - protocols of anti-cancer therapy 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: 3. 5. 2017Accepted: 20. 6. 2017.

Subgroup analysis in RAISE: a randomized, double-blind phase III study of irinotecan, folinic acid, and 5-fluorouracil (FOLFIRI) plus ramucirumab or placebo in patients with metastatic colorectal carcinoma progression.

BACKGROUND: The RAISE phase III clinical trial demonstrated that ramucirumab + FOLFIRI improved overall survival (OS) [hazard ratio (HR) = 0.844, P = 0.0219] and progression-free survival (PFS) (HR = 0.793, P < 0.0005) compared with placebo + FOLFIRI for second-line metastatic colorectal carcinoma (mCRC) patients previously treated with first-line bevacizumab, oxaliplatin, and a fluoropyrimidine. Since some patient or disease characteristics could be associated with differential efficacy or safety, prespecified subgroup analyses were undertaken. This report focuses on three of the most relevant ones: KRAS status (wild-type versus mutant), age (<65 versus ≥65 years), and time to progression (TTP) on first-line therapy (<6 versus ≥6 months). PATIENTS AND METHODS: OS and PFS were evaluated by the Kaplan-Meier analysis, with HR determined by the Cox proportional hazards model. Treatment-by-subgroup interaction was tested to determine whether treatment effect was consistent between subgroup pairs. RESULTS: Patients with both wild-type and mutant KRAS benefited from ramucirumab + FOLFIRI treatment over placebo + FOLFIRI (interaction P = 0.526); although numerically, wild-type KRAS patients benefited more (wild-type KRAS: median OS = 14.4 versus 11.9 months, HR = 0.82, P = 0.049; mutant KRAS: median OS = 12.7 versus 11.3 months, HR = 0.89, P = 0.263). Patients with both longer and shorter first-line TTP benefited from ramucirumab (interaction P = 0.9434), although TTP <6 months was associated with poorer OS (TTP ≥6 months: median OS = 14.3 versus 12.5 months, HR = 0.86, P = 0.061; TTP <6 months: median OS = 10.4 versus 8.0 months, HR = 0.86, P = 0.276). The subgroups of patients ≥65 versus <65 years also derived a similar ramucirumab survival benefit (interaction P = 0.9521) (≥65 years: median OS = 13.8 versus 11.7 months, HR = 0.85, P = 0.156; <65 years: median OS = 13.1 versus 11.9 months, HR = 0.86, P = 0.098). The safety profile of ramucirumab + FOLFIRI was similar across subgroups. CONCLUSIONS: These analyses revealed similar efficacy and safety among patient subgroups with differing KRAS mutation status, longer or shorter first-line TTP, and age. Ramucirumab is a beneficial addition to second-line FOLFIRI treatment for a wide range of patients with mCRC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01183780.

Prognostic factors in renal cell carcinoma patients treated with sorafenib: results from the Czech registry.

The aim of this study was to describe the characteristics and outcomes of a large cohort of patients treated with sorafenib in clinical practice and to identify predictive factors associated with prognosis. Patient data were obtained from the national Czech registry (RenIS). Data of virtually all Czech patients receiving targeted therapies are entered into this non-interventional post-registration database. Demographics and clinical data, as well as all treatment sequences and clinical outcomes, are reported in this registry. A total of 836 patients treated with sorafenib before March 2013 were included in the analysis. Median age was 63 years and 70% were men. Most patients had received prior treatment with cytokines, sunitinib or both. Sorafenib was the first-line treatment in 15% of patients. Median overall survival and progression-free survival were 21.7 months and 7.5 months, respectively. Median overall survival and progression-free survival was 26.3 and 8.3 months, respectively, in patients receiving sorafenib as first-line therapy. Cox proportional models identified several parameters associated with poor outcome including time ≤1 year from diagnosis to first-line systemic treatment, performance status ≥2, low hemoglobin, and LDH >1.5 times the upper limit of normal. Our data demonstrate that the outcomes of real-life patients are comparable to those enrolled in clinical trials. Prognostic factors identified in the present study were consistent with previously reported models.

Influence of neoadjuvant treatment of rectal carcinoma on operability and incidence of distant metastases.

In the Czech Republic, rectal carcinoma does not only represent a medical problem, but also a socio-economic one. At our department, we treated totally 266 patients with rectal carcinoma in the years 1998 through 2006. Among our patients, neoadjuvant treatment led to a reduction in size of the tumour in 37.6 %, in 50.8 % the size did not change. In T3 tumours, the reduction in size was observed in 36.7 % of the patients and did not change in 56 %; in T4 tumours, the reduction in size was observed in 60% of the patients. In 88 % of the patients who underwent the operation, no residual tumour was found, in 9 % of patients, a residual tumour was detected. In 19 % of the patients, a local recurrence of the tumour was detected. A statistically significant relationship was proved between the appearance of the metastatic disease and the presence of angioinvasion and the size of the primary tumour according to the Duke's classification (Tab. 1, Fig. 4, Ref. 20).

Cationic liposomal paclitaxel plus gemcitabine or gemcitabine alone in patients with advanced pancreatic cancer: a randomized controlled phase II trial.

BACKGROUND: Paclitaxel embedded in cationic liposomes (EndoTAG™-1; ET) is an innovative agent targeting tumor endothelial cells. This randomized controlled phase II trial evaluated the safety and efficacy of ET in combination with gemcitabine (GEM) in advanced pancreatic cancer (PDAC). PATIENTS AND METHODS: Chemotherapy-naive patients with locally advanced or metastatic disease were randomly assigned to receive weekly GEM 1000 mg/m(2) or GEM plus twice-weekly ET 11, 22 or 44 mg/m(2) for 7 weeks. After a safety run-in of 100 patients, a second cohort continued treatment. End points included overall survival (OS), progression-free survival (PFS), tumor response and safety. RESULTS: Two hundred and twelve patients were randomly allocated to the study and 200 were treated (80% metastatic, 20% locally advanced). Adverse events were manageable and reversible. Transient thrombocytopenia and infusion reactions with chills and pyrexia mostly grade 1 or 2 occurred in the ET groups. Disease control rate after the first treatment cycle was 43% with GEM and 60%, 65% and 52% in the GEM + ET cohorts. Median PFS reached 2.7 compared with 4.1, 4.6 and 4.4 months, respectively. Median OS was 6.8 compared with 8.1, 8.7 and 9.3 months, respectively. CONCLUSIONS: Treatment of advanced PDAC with GEM + ET was generally well tolerated. GEM + ET showed beneficial survival and efficacy. A randomized phase III trial should confirm this positive trend.

[IKARUS Project--incidence of bone events in breast cancer: retrospective analysis of patients in oncological centres in the Czech Republic and Slovakia]. / Projekt IKARUS--zjistení incidence kostních príhod u karcinomu prsu: retrospektivní analýza nemocných dispenzarizovaných v onkologických centrech Ceské a Slovenské republiky.

BACKGROUND: Bone incidents today represent, in terms of frequency and the overall effect on the quality of life of patients with breast cancer, a serious health problem. In a number of clinical studies bisphosphonates have been shown to have a positive impact on reducing the risk of bone events and therefore to be effective in the prevention of bone events. The primary objective of this project was to identify the incidence of bone events in patients with metastatic breast cancer treated in the Czech and Slovak Republics. SUBJECTS: Retrospective, multi-centre, non-interventional, epidemiological and explorative studies to identify the incidence of bone events in the defined group of patients and a description of the practice of prevention and treatment of skeletal events in the years 2000-2005. Enrolled were patients with advanced metastatic breast cancer diagnosed in 2000. METHODS AND RESULTS: Analysis of overall survival and survival to disease progression, analysis of patterns of treatment of bone events and the practice of the use of bisphosphonates in the prevention of bone events in metastatic skeleton affection in the normal conditions of clinical practice, analysis of patient compliance in the treatment with bisphosphonates, analysis of the time interval between the occurrence of bone metastases and the occurrence of bone events and, last but not least, survival analysis of patients in relation to bone events. CONCLUSION: This work has shown that the practice of treatment with bisphosphonates since 2000 and assessed the survival of patients with metastatic breast cancer.

[Incidence and prognostic significance of mesorectal extranodal tumor deposits in patients with rectal carcinoma following neoadjuvant therapy]. / Výskyt a prognostický význam extranodálních nádorových depozit v mezorektu u pacientus karcinomem rekta po neoadjuvantní terapii.

BACKGROUND: Extranodal mesorectal deposits (ENDs) occur frequently in advanced rectal tumors. It is supposed they are related to a higher incidence of local recurrence and a poor prognosis. AIM: To discover both occurrence and impact of ENDs in patients with advanced rectal cancer after neoadjuvant therapy and surgery. PATIENTS, METHOD: 325 patients meeting following criteria were enrolled: rectal adenocarcinoma, neoadjuvant therapy, anterior or AP rectal resection, complete check up information. Both fresh and archive specimens were examined using standard histopathologic methods. RESULTS: ENDs were discovered in 45 from 325 cases. The occurrence of ENDs was significantly higher in increasing stage of tumor (p < 0.001) and in increasing tumor grade (p < 0.001). Positive correlation between number of involved lymph nodes and occurrence of ENDs (p = 0.005) was proved. The 5-year survival rates were border significantly decreased in patients with ENDs (p = 0.052). CONCLUSION: ENDs are the form of metastatic spreading of primary rectal cancer and have negative prognostic impact in 5 year survival and increase local recurrence of cancer.

Clinical, pathological and molecular characteristics of newly diagnosed breast cancers.

Selection of breast carcinoma therapy is based on standard prognostic markers, such as tumor size, infiltration of regional lymph nodes, tumor grade, and expression of hormonal receptors. Insufficient treatment results stimulate a search for new markers which may lead to a more precise characterization of these tumors and to a more effective treatment. In our study we determined essential clinical and histopathological characteristics of non-metastasizing breast cancer - primary tumor size, involvement of the regional lymph nodes, expression of hormonal receptors and a status of ERBB-2 protein (HER-2), DNA ploidy, and their possible inter-correlation. In this study 77 patients were analyzed. The mean age was 59.3 years. Tumor stage T1 was found in 53%, T2 in 39%, T3 in 5% of patients. 57% of patients did not show any metastases in the axillary lymph nodes. A higher tumor grade 3 was seen mainly in larger tumors, in 62% of T2 and 66% of T3 tumors; 77% of carcinomas expressed hormonal receptors. HER-2 expression was shown in 21 T1 tumors, 13 T2 tumors, and 1 T3 tumor. 47 tumors were diploid. 13 T1 tumors, 14 T2 tumors, and 2 T3 tumors were aneuploid. Any significant correlation among staging T, N and ERBB-2 expression, hormonal receptors expression, tumor grade and DNA ploidy was found.

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%).

[Peripheral primitive neuroectodermal tumor -- PNET]. / Periferní primitivní neuroektodermový tumor -- PNET.

The authors describe three cases of peripheral primitive neuroectodermal tumor. The tumor was found in soft tissues of the crus, shoulder girdle and perineum, and was also located paravertebrally and epidurally at the level of L1-L2 vertebrae. Radiological findings were not specific for this disease. The results of imaging methods (sonography, CT, MRI, DSA) were important for the assessment of tumor size, its boundary and invasion of the surrounding tissues, and for the evaluation of tumor response to therapy and detection of recurrent disease. The PNET diagnosis was based on immunohistochemical, biochemical and cytogenetic examinations. One patient died 5 months after the first clinical signs were manifested; the two patients surviving for 2 and 1 3/4 years after first sign manifestation, respectively, remained in the care of cancer specialists. Key words: skeletal Ewing's sarcoma, extra-skeletal Ewing's sarcoma, Ewing's sarcoma family of tumors, peripheral primitive neuroectodermal tumor.

Implantation of central venous ports with catheter insertion via the right internal jugular vein in oncology patients: single center experience.

AIM OF WORK: Evaluation of suitability and safety of venous port implantation with catheter insertion via the right internal jugular vein in oncology patients. PATIENTS AND METHODS: One hundred one totally implantable venous ports were placed in 100 patients with malignancies from January 1, 2003 until March 31, 2005. Catheter of venous port was preferably inserted via the right internal jugular vein. We recorded a number of successful implantations using this venous approach and the rate of complications during the procedure and follow-up. MAIN RESULTS: Ninety-seven catheters (96%) of totally implantable venous ports were inserted via the right internal jugular vein in 96 patients, and only in four cases were we not able to access this vein. We had no complications related to catheter insertion via the right internal jugular vein. Follow-up was made in all 96 patients with a total access days of 41 in 151 days (mean: 407 days). Premature catheter removal was required in six (6.2%, 0.144 per 1,000 access days) due to complications: three catheter dislocations/malfunctions (3.1%, 0.072 per 1,000 access days), one port-related sepsis, one pocket port infection, and one decubitus over port (1%, 0.024 per 1,000 access days). Six venous ports were removed after completion of the treatment at the patient's request. CONCLUSION: The placement of totally implantable venous ports with catheter insertion via the right internal jugular vein has a high success rate without any early complications. Follow-up also demonstrates a low incidence of late complications requiring port removal.

[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.

[Enzyme therapy in the treatment of lymphedema in the arm after breast carcinoma surgery]. / Enzymoterapie v lécbe lymfedému paze po operaci pro karcinom prsu.

The authors evaluate the contribution of proteolytic enzymes used in the treatment of the lymphatic oedema of the arm after mastectomy and radiotherapy for breast cancer. Proteolytic enzymes were successfully administered in monotherapy of lymphatic oedema as well as supportive therapy in other therapeutically ways.

[Primitive neuroectodermal tumors of the minor pelvis in women--case report]. / Primitivní neuroektodermový nádor malé pánve u zeny--kazuistika.

A primitive neuroectodermal tumour (PNET) of the minor pelvis is a rare malignant small-cell tumour developing from the neural groove. It metastatizes into the lungs, bones, liver and brain. Treatment involves radical surgical extirpation followed by chemotherapy and actinotherapy. The author presents the case-history of PNET of the pelvis minor in a 33-year-old woman.