Academic Study XR-TEMinDREC - Combination of the Concomitant Neoadjuvant Chemoradiotherapy Followed by Local Excision Using Rectoscope and Accelerated Dispensarisation and Further Treatment of the Patients with Slightly Advanced Stages of Distant Localized Rectal Adenocarcinoma in MOÚ.

BACKGROUND: Miniinvasive approaches are a long-term trend in surgery. Maximum possible quality of life after treatment of rectal cancer is a long-term goal. Adequate radicality of surgery is a long-term necessity. It is sometimes very difficult to fulfill all the above-mentioned requirements in low-level rectal cancer. By applying a multidisciplinary approach in the treatment of mildly advanced stages of low-seated malignant rectal tumor, a treatment procedure resulting in continence preserving can be offered to a selected group of patients meeting the strict indication criteria. We document our results with respect to a small number of patients in several interesting case reports. CASES: We are following up one patient after ideal treatment course achieving downstaging after neoadjuvant treatment, with uncomplicated operation and after operation period and with a long-term complete remission. One patient achieved dehiscence of the rectum suture. After secondary healing we observed a long-term remission. In one patient a rectovaginal fits developed outside the operation site. We were forced to abdominoperineal amputation. The pathological investigation of the specimen proved radically of the local excision and lack of lymphangioinvasion; nevertheless, a positive perirectal lymph node was found. The last case report shows the limits of imaging dia-gnostics. The liver lesions described as benign were in fact liver metastases of the early rectal cancer. CONCLUSION: According to the worldwide data available, the combination of neoadjuvant chemoradiotherapy and local excision by means of an operative rectoscope is a safe alternative to a resection surgery with total mesorectal excision in T2N0 rectal cancer. However, there is a need of other studies with more patients included, optimally randomized and prospective ones, which will support these claims. Supported by MH CR - DRO (MOÚ, 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.

Stereotactic Body Radiotherapy - Current Indications.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is used to treat localized tumor lesions and consists of applying high doses of radiation to a small number of fractions using specially equipped linear accelerators, modern immobilization devices, and imaging methods, which are considered special, advanced techniques in modern day radiotherapy. SBRT is a very well tolerated, non-invasive, short-term treatment that does not require hospitalization or any complicated preparation. Compared to standard radiotherapy techniques, SBRT allows, due to its precision, significantly higher doses to be applied to the target with less damage to surrounding healthy tissues. If dose constraints are not exceeded, the risk of damage to tissues and organs around the irradiated volume is reduced to minimum. The principle of SBRT is the application of ablative doses of radiation that cause necrosis of the irradiated tissue. PURPOSE: The aim of this review is to provide a basic overview of SBRT indications, radiation doses used, and potential side effects. It is not intended to be a detailed description of treatment itself (such as discussion of patient fixation systems, management of respiratory movements, or image guided strategies of treatment). This review also discusses rarer indications for SBRT, such as pancreatic carcinoma or hepatocellular carcinoma. CONCLUSION: Advances in image navigation, radiation planning, and dose application have enabled successful introduction of SBRT as a treatment regimen for many primary tumors and oligometastatic disease. If surgery is not possible or the patient refuses surgery, it is always reasonable to consider SBRT. SBRT has curative potential for the treatment of primary lung or prostate tumors. High-dose irradiation of oligometastases of various primary tumors can lead to long-term survival without disease symptoms, delay administration of toxic systemic therapies, and improve the quality of life of oncological patients. Key words radiotherapy - stereotactic body radiotherapy - review - ablative radiotherapy - lung cancer - prostate cancer - oligometastatic disease This work was supported in part by the Ministry of Health, Czech Republic - Conceptual Development of Research Organization (MMCI 00209805). The results of this research have been acquired within CEITEC 2020 (LQ1601) project with the financial contribution made by the Minis-try of Education, Youths and Sports of the Czech Republic within special support paid from the National Programme for Sustainability II funds. 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: 30. 10. 2018 Accepted: 4. 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.

[Controversy in the Postoperative Treatment of Low-grade Gliomas]. / Kontroverze v pooperacní lécbe low-grade gliomu.

BACKGROUND: The optimal treatment for low-grade gliomas remains controversial. Neurosurgery, radiotherapy, and chemotherapy are the main treatment options. Despite advances in oncology, there are still a lot of uncertainties, and the optimal sequences, combinations, and timings of these procedures have not yet been optimized. It is still unclear whether temozolomide can replace effective, but toxic PCV chemotherapy (procarbazine, lomustine, vincristine) and whether temozolomide can be used upfront alone instead of radiotherapy alone. Mature results from phase III trials (CODEL, EORTC 22033-26033) will provide answers to these questions. Correlative analyses of survival data and molecular marker findings (1p/19q codeletion, IDH1/2 mutation, and MGMT promoter methylation status) are essential. Due to slow progressive nature of the disease, all clinical trials with low-grade gliomas are complicated by the need for long-term follow-up to obtain valid mature data, which makes any new treatment procedures or developments in basic research developed during the course of closed clinical trials difficult to apply in daily clinical practice. An example is the recently published RTOG 9802 study evaluating the role of adjuvant PCV in combination with radiotherapy for the treatment of high-risk low-grade glioma patients where the recruitment of patients was initiated almost two decades ago. Health-related quality of life after treatment of patients with expected long-term survival is also very important and its maintenance is currently the focus of considerable interest. AIM: The main objective of the present review is to summarize the results of key clinical trials and highlight controversial issues that could have an impact on future daily practice. Another aim is to discuss these issues in the light of newly established molecular markers from the new 2016 WHO Classification of Tumors of the Central Nervous System.Key words: glioma - astrocytoma - radiotherapy - temozolomide - PCV - cognition This work was supported by MH CZ - RVO (MMCI, 00209805) and by project of the Ministry of Education, Youths and Sports of the Czech Republic CEITEC 2020 (LQ1601). 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: 21. 2. 2017Accepted: 20. 3. 2017.

[The Role of Chemotherapy in the Treatment of Low-grade Gliomas]. / Postavení chemoterapie v pooperacní lécbe low-grade gliomu.

BACKGROUND: The standard postsurgical options for low-grade gliomas include watchful waiting or radiotherapy depending on the risk factors for recurrence. The use of chemotherapy for the treatment of this disease is generally controversial, although the recently published results of the first of two large randomized phase III clinical trials (RTOG 9802 a EORTC 22033-26033), focusing on the evaluation of chemotherapy for the upfront treatment of newly diagnosed low-grade gliomas, are reassuring in this respect. The long-term results of a RTOG 9802 comparing radiotherapy alone with radiotherapy and six cycles of adjuvant PCV chemotherapy (procarbazine, lomustine, vincristine) in patients with high-risk low-grade gliomas will probably have an impact on daily clinical practice. The increase in median overall survival from 7.8 years to 13.3 years, mainly for patients with oligodendrogliomas, is unprecedented, but the toxicity of PCV is too high and molecular marker analysis remains inadequate. It is still unclear whether less toxic temozolomide can replace PCV and whether temozolomide can be used upfront alone instead of with radiotherapy. This question is addressed by the ongoing EORTC 22033-26033 study. The preliminary results show no significant difference in progression-free survival between patients receiving radiotherapy and those receiving temozolomide alone. Treatment with temozolomide was not associated with an improvement in cognitive function compared with treatment with radiotherapy. Despite limited follow-up, the study clearly confirmed the importance of molecular characterization of low-grade gliomas, as currently defined in the new 2016 WHO Classification of Tumors of the Central Nervous System. AIM: The aim of the review is to summarize available information from listed key clinical trials of chemotherapy for low-grade gliomas and draw attention to unresolved issues concerning the use of chemotherapy for the treatment of this disease.Key words: glioma - astrocytoma - chemotherapy - PCV - temozolomide - RTOG 9802 This work was supported by MH CZ - RVO (MMCI, 00209805) and by project of the Ministry of Education, Youths and Sports of the Czech Republic CEITEC 2020 (LQ1601). 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: 21. 2. 2017Accepted: 20. 3. 2017.

Patterns of failure after brain metastases radiotherapy: reflections on the importance for treatment and clinical trials reporting.

In many ongoing clinical trials, new strategies for radiotherapy of brain metastases are currently being investigated. A post surgical focal cavity stereotactic radiosurgery and the developing role of a hippocampal-sparing whole brain radiotherapy are of the highest importance. The evaluation of spatial patterns of metastases failure after radiotherapy is a powerful tool for assessing the potential benefit of new different radiotherapy approaches, which enables to identify possible directions leading to better radiotherapy techniques and to modify general management for newly diagnosed brain metastases. The purpose of this article is to present a mix between trial data and philosophical point of view for discussion about the importance of systematic evaluation of spatial patterns of failure in all ongoing trials investigating new approaches in local brain metastases treatment.

Utilization of Prognostic Indexes for Patients with Brain Metastases in Daily Radiotherapy Routine -  is the Complexity and Intricacy Still an Issue?

BACKGROUND: Many prognostic indexes are available for patients with brain metastases in order to estimate remaining lifetime before selection of appropriate treatment including palliative radiotherapy. Their routine utilization is often deprecated for their complexity. We developed a practical tool based on widely available spreadsheet editors for facilitation of daily clinical use of selected indexes (RPA, GPA and WBRT 30) and evaluated its usage for retrospective single institutional survival analysis of patients irradiated for brain metastases. PATIENTS AND METHODS: Spreadsheet platform was prepared and adjusted for automatic calculation of selected prognostic indexes after input of the relevant parameters. The consecutive series of newly diagnosed patients referred during 2011 to the palliative brain radiotherapy were analyzed, and real calculated survival parameters of individual subgroups of RPA, GPA and WBRT 30 were compared with estimated ones. Correlation of radiotherapy technique and estimated survival at the time of treatment indication was evaluated. RESULTS: Total of 121 patients (61% with multiple metastases) were irradiated with the majority undergoing whole brain radiotherapy. Median overall survival from the time of radiotherapy indication was 3.13 months. Non balanced distribution into individual scoring systems subgroups was observed with 8 (7%), 89 (73%) and 24 (20%) patients assigned to RPA 1, 2 and 3 subgroup, 3 (3%), 9 (7%), 57 (47%) and 52 (43%) patients assigned to GPA 3.5- 4, GPA 3.0, GPA 1.5- 2.5 and GPA 0- 1.0 subgroup and 10 (8%), 88 (73%) and 23 (19%) patients assigned to WBRT 30 subgroup D, B and A. Entire differences in overall survival between subgroups are significant among all three scoring systems. CONCLUSION: Routine calculation of available prognostic indexes is useful in decision making regarding the best radiotherapy of brain metastases, and their calculation is greatly facilitated by properly prepared widely available spreadsheet tools.

Volumetric modulated arc therapy for hippocampal-sparing radiotherapy in transformed low-grade glioma: A treatment planning case report.

Timing of radiotherapy for low-grade gliomas is still controversial due to concerns of possible adverse late effects. Prevention of possible late cognitive sequelae by hippocampal avoidance has shown promise in phase II trials. A patient with progressive low-grade glioma with gradual dedifferentiation into anaplastic astrocytoma is presented along with description of radiotherapy planning process attempting to spare the hippocampus. To our knowledge, this is the first described case using volumetric modulated arc technique to spare hippocampus during transformed low-grade glioma radiotherapy. Using modern intensity-modulated radiotherapy systems it is possible to selectively spare hippocampus together with other standard organs at risk. For selected patients, an attempt to spare hippocampus can be considered as long as other dose characteristics are not significantly compromised compared to standard treatment plan created without any effort to avoid hippocampus.

Toxicity and survival outcomes of adjuvant chemoradiation for gastric and gastroesophageal junction cancer patients treated in period 2006-2009: an institutional experience.

Surgical resection is the mainstay of gastric or gastroesophageal junction cancer treatment and has curative potential for patients with early-stage disease. In order to improve the poor survival rates, there are two complementary treatment strategies used at most - perioperative chemotherapy based on UK Magic trial or adjuvant chemoradiation based on INT-0116 trial. Daily treatment decision making should be led also by institutional experiences with toxicity evaluation. We evaluated survival and toxicity outcomes of 47 consecutive patients who underwent adjuvant chemoradiation in our institution in the years 2006-2009. 45Gy in 5 weeks with concurrent two cycles of FUFA Mayo regimen chemotherapy were administrated as part of combined treatment. The acute toxicity was relatively mild (CTCAE scale): grade 2 nausea in 26%, vomiting in 13%, and diarrhoea grade 1 in 15% and general abdominal discomfort in 57% of patients. Grade 3 haematological and infectious complications in 6% and 2% respectively. Late adverse events were as follows: grade 1 esophageal toxicity in 17%, signs of mild chronic esophageal ulceration and esophageal stenosis in 9% of patients (50% of them had tracheoesophageal fistula). The Kaplan- Meier estimate of the median overall survival was 30.5 months with median 25.7 months disease free survival. The overall survival was statistically significantly affected by the amount of removed positive lymph nodes. For the proper evaluation of radiotherapy role in multimodal treatment approach, results of other clinical trials investigating role of concurrent radiotherapy in administration of perioperative chemotherapy will be necessary. Meanwhile, two equally approaches are possible, all having their pros and cons. Institutional toxicity evaluation is recommended in order to provide the best care possible.

Toxicity and survival outcomes of adjuvant chemoradiation for gastric and gastroesophageal junction cancer patients treated in period 2006-2009: an institutional experience.

Surgical resection is the mainstay of gastric or gastroesophageal junction cancer treatment and has curative potential for patients with early-stage disease. In order to improve the poor survival rates, there are two complementary treatment strategies used at most - perioperative chemotherapy based on UK Magic trial or adjuvant chemoradiation based on INT-0116 trial. Daily treatment decision making should be led also by institutional experiences with toxicity evaluation. We evaluated survival and toxicity outcomes of 47 consecutive patients who underwent adjuvant chemoradiation in our institution in the years 2006-2009. 45Gy in 5 weeks with concurrent two cycles of FUFA Mayo regimen chemotherapy were administrated as part of combined treatment. The acute toxicity was relatively mild (CTCAE scale): grade 2 nausea in 26%, vomiting in 13%, and diarrhoea grade 1 in 15% and general abdominal discomfort in 57% of patients. Grade 3 haematological and infectious complications in 6% and 2% respectively. Late adverse events were as follows: grade 1 esophageal toxicity in 17%, signs of mild chronic esophageal ulceration and esophageal stenosis in 9% of patients (50% of them had tracheoesophageal fistula). The Kaplan- Meier estimate of the median overall survival was 30.5 months with median 25.7 months disease free survival. The overall survival was statistically significantly affected by the amount of removed positive lymph nodes. For the proper evaluation of radiotherapy role in multimodal treatment approach, results of other clinical trials investigating role of concurrent radiotherapy in administration of perioperative chemotherapy will be necessary. Meanwhile, two equally approaches are possible, all having their pros and cons. Institutional toxicity evaluation is recommended in order to provide the best care possible. Keywords: adjuvant chemoradiation, gastric cancer, early toxicity, late toxicity, survival outcomes.

[Cost analysis of radiotherapy provided in inpatient setting -  testing potential predictors for a new prospective payment system]. / Analýza nákladu na radioterapii v luzkové péci - hledání vhodných prediktoru pro potreby nového prospektivního úhradového modelu.

BACKGROUND: As a part of the development of a new prospective payment model for radiotherapy we analyzed data on costs of care provided by three comprehensive cancer centers in the Czech Republic. Our aim was to find a combination of variables (predictors) which could be used to sort hospitalization cases into groups according to their costs, with each group having the same reimbursement rate. We tested four variables as possible predictors -  number of fractions, stage of disease, radiotherapy technique and diagnostic group. METHODS: We analyzed 7,440 hospitalization cases treated in three comprehensive cancer centers from 2007 to 2011. We acquired data from the I COP database developed by Institute of Biostatistics and Analyses of Masaryk University in cooperation with oncology centers that contains records from the National Oncological Registry along with data supplied by healthcare providers to insurance companies for the purpose of retrospective reimbursement. RESULTS: When comparing the four variables mentioned above we found that number of fractions and radiotherapy technique were much stronger predictors than the other two variables. Stage of disease did not prove to be a relevant indicator of cost distinction. There were significant differences in costs among diagnostic groups but these were mostly driven by the technique of radiotherapy and the number of fractions. Within the diagnostic groups, the distribution of costs was too heterogeneous for the purpose of the new payment model. CONCLUSION: The combination of number of fractions and radiotherapy technique appears to be the most appropriate cost predictors to be involved in the prospective payment model proposal. Further analysis is planned to test the predictive value of intention of radiotherapy in order to determine differences in costs between palliative and curative treatment.

[Results of curative chemoradiotherapy in patients with carcinomas of the anus]. / Výsledky kurativní chemoradioterapie u pacientu s karcinomy anu.

BACKGROUND: Anal carcinoma is a rare cancer. Surgical treatment is applied for small superficial tumors of the anal margin, the more advanced disease is treated with concomitant chemoradiotherapy. The aim of our study was to evaluate treatment outcomes in patients treated at the Masaryk Memorial Cancer Institute in 2006- 2010. PATIENTS AND METHODS: We reviewed the clinical data of 29 newly diagnosed adult patients (aged 40- 84, average 60.7, median 60.6 years) treated between 2006- 2010. Demographic parameters, tumorrelated variables, toxicity of treatment, overall survival were analyzed. RESULTS: Acute dermal toxicity G4 was observed in two patients, G3 in nine patients. Acute intestinal toxicity G4 was not observed in any patient, G3 in four patients. Acute urologic toxicity G3- 4 was not observed in any patient. Acute hematologic toxicity was observed: leukopenia G3/ G4 in 7/ 1 patients, neutropenia G3/ 4 in 9/ 4 patients, anemia G3/ 4 in no patient and thrombocytopenia G3/ 4 in 10/ 0 patients. Severe acute toxicity G3- 4 was observed more frequently in patients treated with concurrent chemoradiotherapy. Chronic dermal toxicity G2 was observed in two patients, G1 in four patients, chronic intestinal toxicity G1 was observed in four patients. One patient had urethral stenosis and three patients had stenosis of anus without invasive solutions. One patient had osteoradionecrosis of the left pubic bone. The 5 years overall survival of all patients was 76%. We failed to demonstrate improved survival due to the small and heterogeneous file in the group of patients in clinical stage I and II compared with patients with clinical stage III disease, or better survival in the group of patients who received concomitant chemoradiotherapy compared with patients treated only with radiotherapy. CONCLUSION: Conservative treatment of locally advanced anal cancer is relatively well tolerated and safe treatment. Efficiency is comparable to surgical therapy, is also advantageous in terms of quality of life of patients due to the sphincter preservation.

[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.

Does the structure of the water-oxidizing photosystem II-manganese complex at room temperature differ from its low-temperature structure? A comparative X-ray absorption study.

Detailed information on room-temperature structure and oxidation state of the Photosystem II (PS II) manganese complex is needed to put mechanistic considerations on solid grounds. Because previously this information had not been available, the tetranuclear manganese complex was investigated by X-ray absorption spectroscopy (XAS) on PS II membrane particles at 290 K. Due to methodical progress (collection of XAS spectra within 10 s or less), significant X-ray radiation damage can be avoided; room-temperature XAS investigations on the PS II in its native membrane environment become feasible. Thus, the ambiguity with respect to the mechanistic relevance of low-temperature XAS results is avoidable. At 290 K as well as at 18 K, the manganese complex in its dark-stable state (S(1)-state) seemingly is a Mn(III)(2)Mn(IV)(2) complex comprising two di-mu(2)-oxo bridged binuclear manganese units characterized by the same Mn-Mn distance of 2.71-2.72 A at both temperatures. Most likely, manganese oxidation states and the protonation state of the bridging oxides are fully temperature independent. Remarkably, at room-temperature manganese-ligand distances of 3.10 and 3.65 A are clearly discernible in the EXAFS spectra. The type of bridging assumed to result in Mn-Mn or Mn-Ca distances around 3.1 A is, possibly, temperature-dependent as suggested by distance lengthening upon cooling by 0.13 A. However, mechanistic proposals on photosynthetic water oxidation, which involve the dimer-of-dimers model [Yachandra, V. K., et al. (1993) Science 260, 675-679] are not invalidated by the presented results.

Chlorophyll fluorescence transients of Photosystem II membrane particles as a tool for studying photosynthetic oxygen evolution.

The rise of the chlorophyll fluorescence yield of Photosystem II (PS II) membranes as induced by high-intensity actinic light comprises only two distinct phases: (1) the initial O-J increase and (2) the subsequent J-P increase. Partial inhibition of the PS II donor side by heating or washing procedures which remove peripheral PS II proteins or cofactors of the oxygen-evolving complex results in decrease of magnitude and rate of the J-P phase. The rate constant of the J-P increase is directly proportional to the steady-state rate of oxygen evolution; complete suppression of the J-P phase corresponds to full inhibition. A characteristic dip after J-level is observed only in Tris-washed or severely heated PS II membranes; manganese release correlates with appearance of the dip after J-level as verified by EPR spectroscopy. Presence of stabilizing cosolutes (glycine betaine, sucrose) or addition of donor-side cofactors (bicarbonate, chloride, calcium) to PS II membranes before heating (47 degrees C, 5 min) diminishes J-P phase suppression and prevents dip appearance, whereas the addition after heating is without effect. In conclusion, analysis of chlorophyll fluorescence transients of PS II membranes is a potentially useful tool for investigations on photosynthetic oxygen evolution. A decreased rate of the J-P phase can be employed as a convenient indicator for partial inhibition of oxygen-evolution activity; the appearance of a dip after J-level is suggestive of manganese release.

Mathematical simulation of chlorophyll a fluorescence rise measured with 3-(3',4'-dichlorophenyl)-1,1-dimethylurea-treated barley leaves at room and high temperatures.

Chlorophyll a fluorescence induction (FI) measured by Plant Efficiency Analyser fluorometer at room temperature shows a typical O-J-I-P pattern which is at high temperature changed to an O-K-P pattern with a new step K. It has been suggested that the appearance of the K step reflects inhibition of an oxygen evolving complex (OEC). When FI is measured at room temperature with the photosystem II (PSII) herbicide 3-(3',4'-dichlorophenyl)-1,1-dimethylurea (DCMU), which blocks electron transport from Q(A) to Q(B) (the first and the second quinone electron acceptors in PSII, respectively), the time course of the FI shows a sigmoidal increase to the maximal fluorescence which is reached at a little longer time than that of the J step. Similarly, the FI measured at high temperature with DCMU reaches the maximal value of fluorescence at the time which is a little longer than that of the K step. On the other hand, the reversible radical pair model (RRP) describes energy utilization and electron transport up to Q(A). In this work we present the first, to our knowledge, RRP model extended by a description of the function of the donor side of PSII. Assuming the inhibition of the OEC or its full function, the extended RRP model successfully simulates the fluorescence rise measured with DCMU at high and room temperatures, respectively. The roles of the initial state of the OEC and the values of the rate constants in the extended RRP on the simulations of the fluorescence rise at room and high temperatures are also discussed.

Enhanced metallosorption of Escherichia coli cells due to surface display of beta- and alpha-domains of mammalian metallothionein as a fusion to LamB protein.

The lamB gene was inserted at with DNA fragments encoding N-terminal beta- and C-terminal alpha-domains of human metallothionein 1A (HMT1A). The hybrid LamB proteins were expressed as full-length products. Virtually whole pool of hybrid LamB proteins was found localized in the outer membrane of E. coli to and cells expressing LamB variants retained sensitivity to lambda phage, indicating their correct folding. Expression of hybrid LamB proteins increased natural ability of E. coli accumulate bivalent heavy metals ions with the highest efficiency observed for cadmium. The order of amount of cadmium accumulated is alpha-domain of HMT1A > HMT1A >> beta-domain of HMT1A. This correlates with affinity for cadmium and stability of metallothionein and its individual domains. This confirms suitability of LamB vehicle for surface display of various bioactive molecules and suggests possibility of engineering of cell surface for bioremediation of heavy metals.

Low and high temperature dependence of minimum F0 and maximum FM chlorophyll fluorescence in vivo

The aim of this paper is to give a global insight into the behaviour of F0 and FM in a wide temperature range from -100 degreesC to 75 degreesC. We show that the F0 increases upon linear freezing, similarly to the widely published increase of the F0 upon linear heating. In contrast to this the FM decreases upon linear heating in the whole temperature range from -100 degreesC to 75 degreesC. A comparison of low and high temperature induced increase of the F0 is presented. Copyright 1998 Elsevier Science B.V.