Adjuvant accelerated partial-breast irradiation of early-stage breast cancer using stereotactic approach - methodology, technical challenges and early results of prospective randomized trial.

BACKGROUND: The adjuvant radiotherapy (RT) of the early-stage breast cancer patients as local treatment aims to eliminate potential microscopic residual disease in the surgery bed or satellites in its neighborhood. Based on published studies, accelerated partial breast irradiation (APBI) is recommended for strictly selected patients. The aim of this single-institution prospective randomized study was to compare the targeted APBI delivered by stereotactic approach with the currently more commonly used accelerated whole breast irradiation with the boost to the tumor bed in terms of feasibility, safety, tolerance, and cosmetic effects. MATERIALS AND METHODS: Early-stage breast cancer patients after partial mastectomy were screened for eligibility. The inclusion criteria were age > 50 years, non-lobular carcinoma histology, size 2cm, negative margins 2mm, L0, ER-positive, BRCA negative. Enrolled patients were equally randomized into two arms according to radiotherapeutic regiment - external APBI (5× 6 Gy) and accelerated whole breast irradiation with the boost (15× 2,67 Gy + 5× 2 Gy). These preliminary results of the ongoing study evaluated the first 57 from 84 planned patients. RESULTS: The median age was 65 years. The tumors were of grade 1 in 60 % of patients, the median size of 9mm and 70 % were classified as invasive ductal carcinoma. Statistical significant differences between the groups in baseline characteristics were not observed. A total of 29 patients was enrolled in the APBI group by the end of 2020. All enrolled patients were evaluated one month after RT. A total of 40 (70,2 %) a 33 (58 %) had examinations 3 and 6 months after RT, respectively. Toxicity evaluation showed statistically significantly fewer acute adverse events in the APBI group in terms of skin erythema, desquamation, skin tenderness, dryness, edema, pigmentation, breast pain and fatigue. Late toxicity evaluated in 3 and 6 months after RT was significantly higher in the control group. The cosmetic effect (independently evaluated by a physician, nurse and patient) was more favorable to the APBI group. CONCLUSION: The technique using the principles of targeted radiotherapy turned out to be a less toxic and easier feasible approach for adjuvant radiation of early-stage breast cancer patients. Consequently, the presented study increases the level of evidence for RT-indicated patients to the establishment of external APBI into daily clinical practice.

FDG-PET/ CT for initial staging and response assessment in Castleman disease - retrospective single-center study of 29 cases.

BACKGROUND: Castleman disease (CD) is a rare lymphoproliferative disorder including unicentric and multicentric forms which can further be divided into four histopathologic variants (hyaline vascular, plasma cell, mixed, and plasmablastic). Multicentric CD typically behaves as an aggressive, relapsing entity with generalized lymphadenopathy and systemic symptoms. PET/CT following 18F-fluorodeoxyglucose administration (FDG-PET/CT) represents an imaging modality commonly used in malignant lymphomas for staging purposes and response assessment. However, literature data on its role in CD have been limited. PATIENTS AND METHODS: Twenty-nine patients, 18 men and 11 women, dia-gnosed in 1998-2016 were enrolled in our retrospective study. All patients underwent FDG-PET/CT during initial staging and/or as part of response assessment. We measured the maximum diameter of a lesion and established an index value corresponding to the ratio of the maximum standardized uptake value for the observed lesion and for the liver. The information about imaging examinations, patients, and disease extensions was put in a registry and statistically analyzed. RESULTS: Unicentric and multicentric CD was dia-gnosed in 17 and 12 patients, respectively. Median age at the dia-gnosis was comparable between the two groups (51 and 58 years, respectively; P = 0.352). The majority of patients with multicentric CD (83%) were men. In women, the unicentric form prevailed (82 vs. 18%) while the difference between the two forms was of borderline significance in men (44 vs. 56%; P = 0.064). Most of the patients (88%) with unicentric CD had the hyaline vascular pathology type. On the contrary, the plasma cell type was predominant in multicentric CD (42%). The most commonly included anatomic sites included the retroperitoneum (52%) and the thorax (43%). Inguinal node involvement developed only in patients with multicentric CD. In repeatedly examined patients, FDG-PET/CT demonstrated a progressively decreasing size and metabolic activity of a selected lymph node. CONCLUSION: FDG-PET/CT represents a suitable modality for initial staging and response monitoring of CD, especially in patients with a multicentric form.

Different chromosome damage in lymphocytes of newly diagnosed gastrointestinal and breast cancer patients.

Structural chromosome aberrations are a predictive biomarker of cancer risk. Conventional chromosome analysis widely used for these purposes detects unstable chromosome aberrations that are eliminated during cell division. Stable aberrations that may persist in the body and tend to accumulate during a lifetime can be detected by fluorescence in situ hybridization (FISH). The aim of the study was to investigate the level of chromosome damage in newly diagnosed cancer patients and control subjects by FISH. Both groups of untreated cancer patients had increased frequency of aberrant cells. However, chromosome damage affected different cytogenetic endpoints. Stable translocations and cells with complex rearrangements were elevated in breast cancer patients whereas unstable chromosome aberrations (dicentric chromosomes and acentric fragments) were elevated in gastrointestinal cancer patients. These associations observed in nonsmokers were typically not pronounced in smokers (with the exception of dicentric chromosomes in gastrointestinal patients). Exposure to tobacco smoke increased aberrations in healthy controls but not in the cancer patients. Our study suggests an association between cancer and stable chromosomal rearrangements in breast cancer patients. Unstable aberrations elevated in gastrointestinal cancer patients may be at least partly ascribed to the exposure to diagnostic X-rays.

Effect of Tumor Size and p16 Status on Treatment Outcomes - Achievement of Complete Remission in Prospectively Followed Patients with Oropharyngeal Tumors.

BACKGROUND: Oropharyngeal squamous cell tumors associated with human papillomavirus infection (p16 positive tumors) have better prognosis than p16 negative tumors regardless of the more advanced stage of the disease. Tumor volume (GTVt+n) is generally an important factor affecting treatment results of ionizing radiation. The aim of this prospective non-randomized study is to evaluate the effect of tumor volume on the (chemo)radiation treatment results in a group of patients with p16 negative and p16 positive oropharyngeal tumors. PATIENTS AND METHODS: Patients with confirmed squamous cell tumor of the oropharynx of stages III and IV, according to the 7th version of the TNM (tumor-nodes-metastases) classification, were eligible for this study. The main exclusion criteria were palliative treatment, neoadjuvant chemotherapy or planned concomitant therapy with cetuximab. Patients were treated according to standardized protocols with curative intent. Primary tumor volume (GTVt) and involved nodes volume (GTVn) were obtained from radiotherapy planning system for further statistical analysis. The differences in tumor volumes between the groups according to p16 expression were assessed with subsequent testing of probability to achieve complete remission (CR) of the disease in both groups. RESULTS: In total, 49 patients - 84% men, median age 60.5 years, 25 (51%) patients p16 positive, 40 (82%) underwent concomitant chemoradiotherapy. Median of GTVt in the whole patients group is 40.2 ccm, GTVn 11.78 ccm and median volume of the whole tumor burden (GTVt+n) 70.21 ccm (range 11.05-249). Median of GTVn was greater in the p16 positive cohort (p = 0.041). In the entire group, the median time to reach CR was 91 days (95% CI 86-107 days) from the end of radiotherapy. In the group of p16 negative patients, 14 achieved CR (61%) out of 23 patients, in p16 positive group 20 (80%) out of 25 patients (p = 0.111). P16 negative patients had a longer time to CR (p = 0.196, HR 1.58, 95% CI 0.79-3.18). None of the independently assessed volumetric parameters of the tumor (GTVt, GTVn, GTVt+n) affected CR in the p16 positive patients group, while there was a significant impact of the whole tumor burden (GTVt+n) in the p16 negative cohort (median 58.1 ccm in CR patients vs. 101.9 ccm, p = 0.018). CONCLUSION: We have showed less GTVt+n dependence to achieve CR in p16 positive tumors in comparison with p16 negative tumors. Thus, p16 positive oropharyngeal squamous cell cancers should not be withdrawn from the curative treatment intent based on the greater GTVt+n. Key words oropharyngeal neoplasms - p16 status - treatment outcome - tumor burden - complete remission This work was supported by grant of the Ministry of Health of the Czech Republic AZV 15-31627A and by grant of the Ministry of Health of the Czech Republic - Conceptual development of a research organization (MMCI 00209805). 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: 2. 11. 2018 Accepted: 11. 11. 2018.

Ablative dose stereotactic body radiation therapy for oligometastatic disease: a prospective single institution study.

Localized, metastasis-directed stereotactic body radiation therapy (SBRT) of oligometastatic disease (OD) is currently rapidly evolving standard of care in many institutions. Further reports of outcomes are required to strengthen the level of evidence in the absence of comparative trials evaluating different practical procedures. The aim of this prospective single institutional study is to analyse, in unselected cohort of patients from real-world clinical practice, the long-term survival, tumor control outcomes and safety of SBRT in OD (radical ablative radiotherapy with biological equivalent dose BED10>100 Gy). In addition to standard toxicity and survival parameters, we report unique outcomes as FFWD - Freedom from widespread dissemination, FFNT - Freedom from the need of subsequent treatment and functional survival with Karnofsky performance status higher than 70%. A total of 110 patients were prospectively evaluated, 60% and 40% were treated for lung and liver oligometastatic disease, respectively. No grade 3 or 4 acute toxicities (CTCAE) were reported. With median follow up of 22.2 months and 2-year overall survival of 88.3%, four patients (6.1%) experienced local progression in the lung SBRT cohort. In the liver SBRT cohort, median follow up was 33 months, 2-year overall survival was 68.5% and 11 patients (25%) experienced local and 36 (81.8%) distal progression. Higher BED10 of 150-170 Gy compared to 100-150 Gy was an independent positive prognostic factor for local progression-free survival for all patients with hazard ratio 0.25. This confirms SBRT ablative radiobiology effects to be independent of OD primary histology and location. The best outcomes in terms of FFNT were observed in the multivariable analysis of patients with 1-2 lung OD compared to both the liver OD cohort and patients with more than 2 lung metastases. Better FFNT in the liver SBRT cohort was observed in patients with 1-2 liver metastases and in patients whose liver OD was irradiated by higher BED10. In conclusion, SBRT is a suitable option for patients who are not surgical candidates; with approximately 30% of patients not requiring subsequent treatment 2 years after SBRT. We believe that this treatment represents a safe and effective option for oligometastatic involvement in patients with various primary tumors.

[Biomonitoring of Work with Genotoxic Substances and Factors in a Cancer Treatment Facility]. / Biomonitoring práce s genotoxickými látkami a faktory v onkologickém zdravotnickém zarízení.

BACKGROUND: A long-term occupational exposure of healthcare staff to cytostatics and ionizing radiation is associated with a possible manifestation of their genotoxic, carcinogenic and teratogenic effects. MATERIAL AND METHODS: A total number of 101 employees working with cytostatics or ionizing radiation were examined (some of them repeatedly) in a cancer treatment facility. The control group consisted of 119 persons excluded from the risk exposure. Fluorescence in situ hybridization with three pairs of whole-chromosomal probes and a pancrossomeric probe was used and the translocation frequency was determined. RESULTS: The total number of chromosomal rearrangements of healthcare professionals and control group correlates with age. Taking into account the age dependence, an increased level of chromosomal reconstruction was found in the case of 11 individuals, 10 of which were female, working on the positions of pharmacist, general nurse, physician. A total of 9 of those case involved the work with cytostatics. Five of these cases were re-examined two years later and the observed levels dropped to the control level. CONCLUSION: The results of biomonitoring should be evaluated on a group basis and individually, taking into account the personal history and possible non-professional effects on individuals - in particular those related to specific environmental measurement results.Key words: preventive medicine - occupational exposure - cytostatic agents - chromosome aberrations - in situ hybridization - fluorescence The authors declare they have no potential conflicts of interest concern ing drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. This work was supported by project of Ministry of Health Czech Republic. reg. No. 15-33968A.Submitted: 12. 4. 2018Accepted: 16. 4. 2018.

[Magnetic resonance imaging in preoperative diagnosis of invasive lobular carcinomas of the breast - analysis of 230 cases]. / Magnetická rezonance v predoperacní diagnostice invazivních lobulárních karcinomu prsu - analýza 230 prípadu.

INTRODUCTION: In breast cancer patients, magnetic resonance imaging (MRI) is a supportive method characterized by high sensitivity. Its indications in the preoperative assessment are not clearly defined. More likely to benefit from preoperative MRI are younger women, women with a dense breast on mammography and patients with invasive lobular carcinoma (ILC). The aim of this study was to assess utilization of MRI and resulting benefits in preoperative tumour staging of ILC in patients treated in our institution. METHODS: A retrospective evaluation of medical records of all patients with bioptically proven and primarily surgically treated ILC through the years 20142016. RESULTS: Overall, 230 patients were evaluated, among them 131 (57.0%) underwent MRI. These patients were significantly younger than patients without MRI. The results of MRI were as follows: in 28.2% a small unicentric lesion, in 41.2% large infiltration or multifocality, and in 30.5% suspicion of multicentricity. The proportion of conservative surgeries and re-resections did not differ between the patients with and without MRI. The subgroup of patients with a small unicentric lesion on MRI showed a higher proportion of conservative surgeries and fewer re-resections compared to the other subgroups. In 41 women (31.3%) the MRI finding resulted in further assessments; in 29 (22.1%) an additional biopsy was done, with a malignant result in the ipsilateral breast in 8 cases and in the contralateral breast in 3 cases. The MRI finding had a substantial impact on surgery in 35 patients (26.7%) of whom it was evaluated as clinically beneficial in 23 (65.7%) cases. CONCLUSION: At our institution, more than a half of patients with ILC undergo MRI preoperatively. The finding has an impact on the scope of the surgery in approximately one fourth of the cases, being clinically beneficial in most of them. However, a high frequency of additional imaging assessments and biopsies should be taken into account. Due to the low specificity of MRI, every suspicious lesion has to be bioptically verified to avoid inappropriate surgery and patient harm.Key words: breast cancer - invasive lobular carcinoma - magnetic resonance imaging - occult lesion - biopsy.

[Lactate Dehydrogenase - Old Tumour Marker in the Light of Current Knowledge and Preanalytic Conditions]. / Laktátdehydrogenáza - starý nádorový marker ve svetle soucasných poznatku a v preanalytických souvislostech.

With the development and subsequent clinical applications of anticancer immuno-and angiomodulatory therapies and expanded knowledge on significance of tumor microenvironment for disease prognosis and treatment outcome, a classical blood analyte, lactate dehydrogenase (LDH), gains in importance as a tumor marker reflecting to some extent immunosupressive and angiogenic tumour milieu. Physical extravascular hemolysis due to complicated or inaccurate blood sampling interferes strongly with quantification of LDH in serum/plasma samples. Upon correlating circulating hemoglobin level with LDH catalytic activities in 99,937 plasma samples we quantified hemolysis interference with LDH plasma levels. An increment of LDH (µkat/l) caused by hemolysis is equal to 0.002 times circulating hemoglobin level (mg/l). Thus, hemolysis interference can be mathematically subtracted from measured LDH using a formula: [LDH (measured) (µkat/l) - 0.002 × circulating hemoglobin (mg/l) ]. In other words, each increment of hemolysis equal to 100mg/l of circulating hemoglobin will result to LDH increase equal to 0.2 µkat/l. As one of the emerging predictors of treatment outcome, a cancer prognostic biomarker and dynamic tumor marker, serum/plasma LDH concentration needs to be interpreted with respect to reported hemolysis level. Also, for these purposes, quantitative determination of serum/plasma levels of free circulating hemoglobin has to be routinely performed.Key words: lactate dehydrogenase - hemolysis - preanalytical error This work was supported by MEYS via NPS I for RECAMO2020 (LO1413). 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: 13. 3. 2017Accepted: 26. 3. 2017.

[Reverse strategy for synchronous colorectal liver metastases Therapeutic protocol completion, 3-year survival and progression pattern in 32 patients]. / Reverzný prístup k synchrónnym pecenovým metastázam kolorektálneho karcinómuAbsolvovanie liecebného protokolu, strednodobé (trojrocné) prezívanie a vzorec progresie ochorenia u 32 pacientov.

INTRODUCTION: Reverse, liver-first strategy is an alternative for patients with complicated liver metastases where disease progression would prove inoperable, or for patients with locally advanced pelvic disease where postoperative complications after primary tumour resection may lead to delayed treatment of metastatic disease. METHODS: Retrospective unicenter analysis of 32 patients approached liver-first approach between 2011 and 2015. During this period reverse strategy was considered a preferred approach for all initially or potentially resectable synchronous colorectal liver metastases based on multidisciplinary team consensus. RESULTS: 26 patients (81.3%) completed their surgical plan (hepatectomy and primary tumour resection) but only 16 (50%) completed their oncosurgical plan (hepatectomy, primary tumour resection and full dose and length of perioperative or adjuvant systemic (bio)chemotherapy). Median overall survival was 50.5 months with the survival rate of 83.7% at 3 years. 20 patients (62.5%) progressed during the follow-up with median time to progression of 21.6 months. The liver was the most common site of recurrent disease followed by the lungs (65% and 20% of all recurrences, respectively). CONCLUSION: While reverse strategy may allow complete tumour removal in the majority of patients, only half of them complete their oncosurgical plan even with the liver-first approach. The most problematic aspect of the liver-first strategy is the timing and length of perioperative (bio)chemotherapy. When deciding on preoperative chemotherapy in up-front resectable lesions one should take into account the risk of disease progression while on chemotherapy as well as the risks of complete radiologic response. KEY WORDS: colorectal carcinoma reverse strategy liver-first approach liver metastases.

[Immunological Aspects in Oncology--Circulating γδ T Cells]. / Imunologické aspekty v onkologii--cirkulující γδ T lymfocyty.

γδ T cells present a minor population of the T cell family which basically differs in construction of their T cell receptor (TCR). Thanks to the features of γδ TCR, these cells can acquire unique effector functions and play a specific role (not only) in antitumor immune response. In this article, we describe the basic characteristics of this cell population and their connection to cancer. In the experimental part we performed exploratory analysis of circulating γδ T cells in reference population and comparison with melanoma and breast carcinoma patients. The median percentage of γδ T cells from all lymphocytes was 2.9% (interquartile range-IQR 1.7-4%). The median absolute numbers of γδ cells per liter of blood was 5.05×10(7) (IQR 2.9-7.84×10(7)). The median percentage of γδ cells between all CD3 T cells was 3.9% (IQR 2.3-5.6%). No correlation between γδ T cells levels and gender or age was observed in reference population. Detailed immunophenotyping was also conducted describing representation of memory subsets (using CD45RO and CD27 markers) and presence of surface markers HLADr, CD69, CD25, CD28, CCR7, CTLA 4, ICOS, PD 1L and PD 1 between γδ T cells of the controls and breast carcinoma patients. From this analysis, it is evident that γδ T cells do not represent a uniform population but they differ in surface markers as well as in their effector functions.

[Breast cancer patient satisfaction with immediate two-stage implant-based breast reconstruction]. / Spokojenost onkologických pacientek s okamzitou dvoudobou aloplastickou rekonstrukcí prsu.

BACKGROUND: For most breast cancer patients in the Czech Republic, breast reconstruction is available only in a delayed manner. In the Masaryk Memorial Cancer Institute (MMCI), suitable candidates are offered immediate breast reconstruction using tissue expander with later exchange to a permanent silicone implant. The aim of this study was to assess patient satisfaction with this type of reconstruction. PATIENTS AND METHODS: Sixty-two women who had undergone surgery at the MMCI from 2007 through 2013 were sent a simple questionnaire developed by our working team. Fifty-seven patients completed the questionnaire. The data were evaluated by description methods and statistical tests. RESULTS: Patient response was 92%. The absolute majority of patients (56/57) would opt for this method again. The vast majority of patients (48/57) are generally satisfied with their reconstruction. Most women (8/14) younger than 50 years after the unilateral surgery would prefer synchronous contralateral prophylactic mastectomy and bilateral reconstruction if they could choose again. After bilateral surgery, reconstructed breasts are more often regarded as a part of the patients body. Dressed women rate their look substantially better than when they are undressed. As for self-esteem, these women are feeling excellent or good. Their psychosocial well-being in common situations is predominantly excellent. Their sexual well-being is significantly worse, and almost half of these women indicate occasional pain in their reconstructed breasts. The patients emphasize the need for appropriate information before the surgery. CONCLUSION: Immediate two-stage implant-based breast reconstruction is a suitable option for some breast cancer patients. With regard to the less natural cosmetic result and feeling of the implant-reconstructed breast, appropriate selection of women for this type of surgery is necessary and potential candidates must be thoroughly informed in the preoperative setting.

[Colon cancer - evaluation of complications and risks of planned resections]. / Karcinom tlustého streva - zhodnocení komplikací a rizik plánovaných resekcních výkonu

INTRODUCTION: Resection procedures for colorectal cancer are burdened with a relatively high number of complications. The aim of this study is to define risk factors associated with the development of postoperative complications based on retrospective data analysis. MATERIAL AND METHODS: From January 1 st 2007 to December 31st 2012, 1093 patients underwent surgery for colorectal cancer. Retrospectively, we selected a group of 406 patients who underwent planned, elective colon resection for colon cancer. Open surgery was performed in 158 patients (38.9%), laparoscopic resection in 248 patients (61.1%). Based on initial staging of the disease, there were 85 patients (20.9%) in stage I, 137 patients (33.8%) in stage II, 110 patients (27.1%) in stage III and 74 patients (18.2%) in stage IV. Postoperative complications were evaluated according to Clavien - Dindo classification. RESULTS: Grade I complications were observed in 34 patients (8.4%), grade II in 25 patients (6.2%), grade III in 43 patients (10.6%), grade IV in 7 patients (1.7%) and grade V in 8 patients (2.0%). The highest incidence of complications was observed in left colon resection procedures (41.1%), open resections (39.8%), procedures lasting longer than 301 minutes (50%), patients older than 81 years (41.6%) and in procedures performed by the youngest, less experienced surgeon (40.6%). CONCLUSION: Our results confirmed that the type and approach of surgical procedure, patients age and surgeons experience are risk factors associated with a higher incidence of postoperative complications. High-risk surgical patients should be operated on by experienced surgeon who regularly performs a high number of resection procedures.

[Epidemiological and clinico-pathological characteristics of patients with renal carcinoma: a single institution analysis of 544 cases]. / Epidemiologická a klinicko-patologická charakteristika pacientu s renálním karcinomem: analýza 544 prípadu z jednoho centra.

BACKGROUND: The incidence of renal cell carcinoma in the Czech Republic is one of the highest in the world. Curative treatment is still possible only surgically, while in the palliative treatment, partial success was reached using targeted therapies. While prognostic factors and models are commonly used in clinical practice, unfortunately, predictive biomarkers have not been found. The aim of our study was to verify the validity of selected prognostic factors on a consecutive patient cohort from the Czech population. PATIENTS AND METHODS: The patient cohort consisted of 544 patients with RCC diagnosed and/or treated at our institute from 2003 to 2010. Individual clinical and histological prognostic factors and Heng prognostic model were validated. RESULTS: Median time of follow-up for our cohort was 42 months (range 0.3-326 months), median age at diagnosis was 62 years, and almost 64% of patients were men. Distribution of clinical stages was as follows: 46.5% of I, II. 10.7%, III. 13.1%, IV. 20%. 26.4% of patients in stage I-III relapsed. We diagnosed mainly clear cell (84.6%) and papillary carcinoma (9.2%). Initially, 95.8% of patients underwent surgical treatment, systemic adjuvant and palliative treatment was applied in 3.7 and 37.7% of patients, respectively. Palliative targeted therapy was received by a total of 163 patients (30%). In first-line targeted therapy, the following median TTP was reached (in months): 10.8 for sunitinib, 6.3 for sorafenib and 5.2 months for immunotherapy. The most significant prognostic factors (p < 0.00001) were: stage of disease (HR = 9.61), size of the primary tumor (HR = 5.83), lymph nodes (HR = 8.26), presence of sarcomatoid tumor sections in the tumor (HR = 7.29), and tumor grade (HR = 4.0). Besides these, we also confirmed the prognostic importance of presence of eosinophilic granulations in the tumor (HR = 1.91, p = 0.02). When applying the Heng prognostic model, we achieved similar results for patients treated with targeted therapies. CONCLUSION: The obtained epidemiological and clinico-pathological data are consistent with previously published data. These prognostic factors can be used for a differentiated approach to patients with RCC, both for establishing follow-up plan for patients after surgery as well as indication for targeted therapies.

[The number of removed axillary sentinel lymph nodes and its impact on the diagnostic accuracy of sentinel lymph node biopsy in breast cancer]. / Pocet odebíraných axilárních sentinelových uzlin a jeho vliv na diagnostickou presnost sentinelové biopsie u karcinomu prsu.

INTRODUCTION: The number of lymph nodes removed during the sentinel lymph node biopsy in patients with breast cancer usually ranges from 1 to 3. In some cases, multiple nodes are identified and removed, which could be associated with increased risk of postoperative morbidity. The objective of the study was to assess the number of sentinel lymph nodes removed in patients treated in our hospital, to analyze factors that may influence the amount of the removed nodes, and to find if there is an upper threshold number of lymph nodes that should be removed without sacrificing the diagnostic accuracy of the sentinel lymph node biopsy. MATERIAL AND METHODS: Clinical data of four hundred and forty (440) breast cancer patients who underwent sentinel lymph node biopsy in Masaryk Memorial Cancer Institute during the year 2011 were retrospectively collected and analyzed. RESULTS: The number of sentinel lymph nodes ranged from 0 to 9 (average 1.7, median 1). The number of sentinel lymph nodes was significantly influenced by the age of the patient, the operating surgeon and the laterality of the surgery. In 275 cases the sentinel lymph nodes were negative, in the other cases macrometastases (n = 101), micrometastases (n = 46) or isolated tumor cells (n = 17) were found. In all the cases, but one, the staging of the axilla was determined by the status of the first three sentinel lymph nodes removed. Only in one case the first detected macrometastasis was present in the fifth node. CONCLUSION: In the vast majority of cases, the first three sentinel lymph nodes are sufficient to accurately assess the axillary status. However, with respect to the described case of first detected metastasis in the fifth node, to the present literary data and to the variability of clinical situations, we generally recommend to remove all lymph nodes meeting the criteria of the surgical definition of sentinel lymph node.

[Analysis of prognostic factors in osteosarcoma adult patients, a single institution experience]. / Prognostické faktory konvencního osteosarkomu dospelých pacientu

BACKGROUND: The objective of this report was to estimate long-term outcome and prognostic factors in adult patients with high-grade osteosarcoma. The intended therapeutic strategy included preoperative and/or postoperative chemotherapy as well as surgery of all operable lesions. PATIENTS AND METHODS: We reviewed the clinical data of 36 newly diagnosed adult patients (aged 19-82, average 37.5, median 28.5 years) with high-grade osteosarcoma of the trunk or limbs evaluated by a multidisciplinary team and treated between 1999 and 2010 in Brno. Forty-five percent of patients were over thirty, more than 36% over forty. Thirty-one percent of patients had metastasis at the time of diagnosis. Demographic parameters, tumor-related and treatment-related variables included possible prognostic factors and their impact on response, overall survival (OS) and event-free survival (EFS) were analyzed. RESULTS: All the patients were followed up after treatment. Seventy-three percent of patients were poor responders to chemotherapy. Sixteen patients are alive, and twenty patients died. The survival time ranged from 2 to 177 months (average 45 months, median survival 23 months). The 5-year OS of all patients was 52.4%. OS of patients without metastasis was 68.12%, while 2-year OS with metastasis was 26% only. 5-year EFS was 38.7%. Univariate analysis revealed that the prognosis of adult osteosarcoma patients was significantly related to distant metastasis (p = 0.006), surgical stage (p = 0.00582), serum alkaline phosphatase (ALP) level (p = 0.00841) and serum lactatdehydrogenase (LD) level (p = 0.047). The other analyzed prognostic factors including age had no statistically significant influence on outcome of osteosarcoma in adult patients. CONCLUSION: The prognosis of osteosarcoma in adult patients was significantly correlated to surgical stage, distant metastasis, serum ALP and LD.

[Triple-negative breast cancer: analysis of patients diagnosed and/or treated at the Masaryk Memorial Cancer Institute between 2004 and 2009]. / Triple-negativní karcinom prsu: analýza souboru pacientek diagnostikovaných a/nebo lécených v Masarykove onkologickém ústavu v letech 2004 az 2009.

BACKGROUND: Triple-negative breast cancer (TNBC) represents a heterogeneous group of breast cancers that do not express ER-α, PgR and Her-2 receptors. Generally, these tumors are aggressive and more common in younger women, in which an association of TNBC with mutations in the BRCA1 gene was documented. The aim of our study was to create a representative group of patients with TNBC, which could be analyzed and the data gathered to build basic epidemiological, molecular and clinical characteristics of Czech patients with TNBC. PATIENTS AND METHODS: We performed basic clinical-pathologic correlations in a group of 335 patients diagnosed and/or treated for TNBC at the Masaryk Memorial Cancer Institute between 2004 and 2009. We also performed immunohistochemical examination of expression of cytokeratin 5/6, cytokeratin 14 and EGFR to identify the basal-like subset of TNBC. RESULTS: The median age of patients with TNBC was 56 years, range 25-88 years. A total of 9.25% of TNBC cases were diagnosed in patients under the age of 34, and another 15.22% of cases were in the age group of 35 to 44 years. 'Basal-like' carcinomas accounted for 75% of TNBC. We confirmed the aggressive nature of this disease: in the follow-up period we observed a relapse in 25% of patients: 55% of deaths due to disease progression occured within 2 years after diagnosis of the disease. Treatment strategies include chemotherapy, in most cases (88.4%). Chemotherapy was mostly based on regimens with anthracyclines or in combination with taxanes. The most important negative prognostic factors in relation to OS (disease specific OS) were: higher clinical stage (p < 0.0001), pN - positive status (p < 0.0001), high proliferative activity (as measured by Ki-67, cut-off 50%, HR = 0.4740, p = 0.0411) and positive expression of CK5/6 (HR = 0.4274, p = 0.0338). In relation to DFS, the negative prognostic significance was found for these factors: higher clinical stage (p < 0.0001), pN positive status (p < 0.0001), high proliferative activity (Ki-67, cut-off 50%, HR = 0.04993, p = 0.0240). DFS was longer in patients with a higher number of applied cycles of anthracycline-based chemotherapy (> 4 cycles, HR = 1.7273, p = 0.0467). CONCLUSION: TNBC is an aggressive form of breast cancer, which may occur in patients of all ages, but more frequently in younger patients. Only early detection of disease and intensive treatment gives a high chance of cure. Unfortunately, no reliable predictive factors have been identified so far. Better therapeutic results can be expected from targeted therapy.

[Therapeutic results of the treatment brain tumors using radiosurgery and stereotactic radiotherapy]. / Výsledky lécby mozkových tumoru stereotaktickou radioterapií a radiochirurgií

BACKGROUND: We reviewed the results of treatment of patients treated with stereotactic radiation methods in our department. MATERIAL AND METHODS: Patients with primary brain tumor or brain metastases underwent CT and MR examination. Then they were treated on X knife in the Clinic of Radiation Oncology in Masaryk Memorial Cancer Institute Brno. RESULTS: A total of 101 patients with primary brain tumors underwent stereotactic treatment. These were mainly meningeomas, high-grade gliomas and low-grade gliomas. In 37% of cases patients underwent reiradiation. Stereotactic radiosurgery was applied with a median dose of 18 Gy. Hypofrakcionated stereotactic radiotherapy was applied at a doses of mostly 5 × 5 Gy. Total toxicity of treatment was low: 8% acute G1, late toxicity in 1% of cases. In the whole group achieved partial remission 10 patients (9,9%). One patient had complete remission (0,99%). It was a diagnosis of pituitary adenoma. In 69 patients stable disease was observed (68,3%) and 12 patients had progression (11,88%). Median follow up the entire group was 22,4 months. A statistically significant difference in survival was found in the comparison of different diagnosis, patients who received prior radiotherapy and patients without previous irradiation. Another significant difference in survival was observed compared to patients treated with stereotactic treatment or stereotactic radiosurgery and the size of the tumor volume larger / smaller 10 cm3. In the group with brain metastases there were 56 patients. In 10% of cases preceded radiotherapy neurosurgical performance. Twenty four patients underwent cranial irradiation entire dose of 30 Gy. Median stereotactic radiosurgery dose was 20 Gy, the application of stereotactic treatment were mostly of 5 × 5 Gy. G1 acute toxicity occurred in 2 patients (3.8%), grade G2 in one patient (1.9%). Late toxicity was observed in 2 patients (one G1 and one G3). Complete remission was achieved in 4 patients (7.1%), partial remission in 27 patients (48.2%), stable disease in 9 (16.1%) and progression was observed in 5 patients (8.9%). Median follow-up the entire group was 13.3 months. There was no statistically significant difference in survival with respect to gender, age, KI, irradiation of the whole brain or type of treatment used. Patients who have undergone neurosurgery prior to irradiation had no difference in survival compared to patients without surgery, but the time to progression was significantly longer (p = 0.016). CONCLUSION: Stereotactic radiation methods are part of modern radiotherapy. Their indication is necessary to consider with regard to the benefit of the patient. Quality equipment radiotherapy department and trained personnel are the condition for their correct using.