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.

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.

Use of the Metal Deletion Technique for Radiotherapy Planning in Patients with Cardiac Implantable Devices.

BACKGROUND: The number of cancer patients with cardiac implantable electronic devices receiving radiotherapy is increasing. Irradiation of such patients can cause malfunctions in pacemakers and implantable cardioverter-defibrillators. In this respect, it is necessary to make a proper irradiation plan for such cancer patients to minimize the dose received by both cardiac devices and pacing leads. However, planning computed tomography (CT) scans have metal artifacts that degrade the image quality and make it difficult to create a qualitative radiation plan. In fact, there is a problem of correct contouring not only of critical organs and planning target volume, but also of cardiac devices and pacing leads during the planning of CT scan operations. PATIENTS AND METHODS: To analyze this issue, we tested the Metal Deletion Technique (MDT) on nine cancer patients with different tumor localizations near cardiac implantable electronic devices and device types who were treated at the Masaryk Memorial Cancer Institute. We conducted a radiotherapy planning in Eclipse Treatment Planning System, version 11.0 (Varian, Palo Alto, Canada) (employing three-dimensional conformal radiation therapy, intensity-modulated radiation therapy, volumetric-modulated arc therapy and stereotactic body radiation therapy irradiation techniques). We analyzed the influence of MDT on plan parameters and compared CT scans without and with application of the MDT method. RESULTS: The results confirm the need to use the MDT method for reduction the likelihood of malfunctions in devices. The greatest error in determining the dose received by implantable devices and pacing leads is more than 3% of the total dose. It can significantly change the patients treatment plan. CONCLUSION: The data obtained in this experiment are crucial for physicists when selecting radiation techniques and suitable methods for planning the irradiation of patients with implantable electronic devices. Key words radiation therapy - cardiac devices - Metal Deletion Technique - artifacts - quality improvement.

[MicroRNAs in Prediction of Response to Radiotherapy in Head and Neck Cancer Patients - Pilot Study]. / MikroRNA v predikci odpovedi na radioterapii u pacientu s nádory hlavy a krku - pilotní studie.

BACKGROUND: Radiotherapy plays a key role in the treatment of squamous cell head and neck cancers (HNSCC). The effectivity of radiation therapy is often limited by radioresistance of these tumours. microRNAs (miRNAs) are endogenous, evolutionary conserved, small non-coding RNAs involved in regulation of cellular processes associated with radioresistance. The objective of this study was to identify miRNA profile enabling to predict the radiation treatment outcomes in HNSCC patients. MATERIAL AND METHODS: The retrospective study included HNSCC patients who underwent a definitive radiotherapy. Patients were divided into two groups according to loco-regional control (LRC) as follows - short LRC (n = 22; median 5.1 months (min. 1.3, max, 18.6)) vs. long LRC (n = 21; 60.4 (min. 46.8, max. 98.8)) group. Global miRNA expression profiles were obtained by use of Affymetrix microarray technology (GeneChip miRNA 4.0 Array). RESULTS: We identified 24 miRNAs to be significantly associated with LRC (p < 0.05), all of these miRNAs were upregulated in patients with short LRC. Out of these miRNAs, 12 miRNAs with p < 0.025 and 4 miRNAs with p < 0.01 have been identified. CONCLUSION: miRNAs seems to be promising as potential biomarkers predicting radiotherapy treatment outcomes in patients with HNSCC.Key words: microRNAs - radiotherapy - head and neck cancer 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. Supported by Ministry of Health of the Czech Republic, grant No. 15-31627A. All rights reserved.Submitted: 19. 3. 2018Accepted: 20. 3. 2018.

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.

[The Role of Palliative Radiotherapy in Bleeding from Locally Advanced Gastrointestinal Tumors]. / Role paliativní radioterapie pri krvácení lokálne pokrocilých nádoru gastrointestinálního traktu.

BACKGROUND: Patients with locally advanced gastrointestinal tumors present with typical symptoms including pain, obstructive problems with passage disorders and bleeding. The last of them negatively affects their quality of life and is potentially lethal. Palliative radiotherapy is used in hemostatic indication to control bleeding from locally advanced or recurrent inoperable gastrointestinal tumors for many years. PURPOSE: This review summarizes information and available literature about mechanisms, efficiency and toxicity of palliative radiotherapy used in hemostatic indication, separately for each part of the digestive system. Although most of the published studies are retrospective, all of them show fast, effective and technically safe control of bleeding with minimal risk of toxicity and show an improvement of quality of life. Hypofractionated radiotherapy, with a smaller number of high doses, seems to be the appropriate palliative fractionation schedule. The higher daily dose is associated with faster initiation of hemostatic effect, while few radiotherapy treatment sessions are comfortable for patients; both of them meet the basic principles of state-of-the-art palliative care. In addition to external beam radiotherapy, high dose rate brachytherapy represents another possibility in this indication, especially for locally advanced inoperable anal and rectal cancer. Brachytherapy is simple, practical and most importantly a one-time procedure with high local effect without significant toxicity. CONCLUSION: Radiotherapy is an important treatment possibility for palliative care of bleeding from locally advanced inoperable gastrointestinal cancers. Future prospective studies employing modern radiotherapeutic techniques and procedures are needed to provide consistent and clear evidence in order to weigh risks against benefits of palliative hemostatic radiotherapy in current daily clinical practice.Key words: locally advanced gastrointestinal tumors - bleeding - palliative radiotherapy The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 8. 5. 2017Accepted: 23. 7. 2017.

[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.

[Kombinovaná lécba mekkotkánového sarkomu v oblasti pánve]. / Kombinovaná lécba mekkotkánového sarkomu v oblasti pánve.

Soft tissue sarcomas (STS) constitute a heterogeneous group of rare malignant tumors of mesenchymal cell origin and they may develop in any part of the body. They can form enormous masses in certain localizations. A case report of a young woman with locally advanced liposarcoma in the pelvic cavity is presented. This example emphasizes the significance of early diagnosis, as only radical surgery can be potentially curative in sarcoma therapy.Key words: advanced pelvic sarcoma multimodal treatment multidisciplinary.

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.

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.

Significance of using DICOM communication standard in quality assurance in radiation oncology - an institutional experience.

PURPOSE: The purpose of this article was to highlight the importance of data management systems in radiotherapy. METHODS: We performed a database search to review the errors or potential errors in radiotherapy planning and delivery which could be prevented in case of using the DICOM communication system. RESULTS: We registered the following rates of errors: 1) Errors caused by manual rewriting of treatment plan 30%; 2) Errors caused by wrong assignment of the verification system 15%; 3) Errors during the manual rewriting of treatment data to the verification system 15%; 4) Patient identification 5%; 5) Field verification 15% 6) Wedge orientation 10%. CONCLUSION: DICOM communication system may significantly improve the quality assurance in radiotherapy.

[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.

Stereotactic body radiation therapy for colorectal cancer liver metastases; early results.

BACKGROUND: Stereotactic body radiation therapy (SBRT) is well feasible and effective method for treatment of colorectal cancer liver metastases. MATERIALS AND METHODS: From September 2009 to December 2011, 11 patients with 15 inoperable liver metastases of colorectal cancer were treated by SBRT using Varian Clinac iX linear accelerator. We treated 6 men and 5 women of age from 51 to 81 years (median 68). SBRT doses ranged from 40 to 56 Gy (median 54 Gy) and were administered in 3 to 8 fractions. RESULTS: Local control rates at 2, 4, 6, 9 and 12 months after completion of SBRT were 100%, 91%, 91%, 67% and 50%, respectively. Disease progression-free survival rates at 2, 4, 6, 9 and 12 months were 82%, 82%, 64%, 50% and 50%, respectively. Median follow-up was 15 months. No severe side effects were attributed to the therapy. CONCLUSION: Our study assessed the feasibility of SBRT in selected group of patients with 1 to 3 colorectal cancer liver metastases with no other treatment option. We achieved excellent local control and very moderate acute and late side effects. Distant metastases were the most common recurrence form after SBRT. SBRT demonstrated excellent local control and resulted in occasional long-term survivors without any serious side effects of 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.

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.

[Neoadjuvant chemoradiotherapy of rectal carcinoma with bevacizumab]. / Predoperacní chemoradioterapie v kombinaci s bevacizumabem u karcinomu konecníku.

Concomitant chemoradiotherapy and radical surgery are standard methods of treatment in patients with locally advanced rectal carcinoma. Neoadjuvant chemoradiotherapy with 5-fluorouracil or capecitabine is considered to be an optimal treatment approach. Clinical studies attempt to facilitate treatment response to neoadjuvant chemoradiotherapy by adding targeted biological therapy. Anti-angiogenic effect of bevacizumab may potentiate radiosenzitivity. We present an overview of standard methods of treatment of rectal carcinoma and a summary of published results of neoadjuvant chemoradiotherapy with bevacizumab in the treatment of rectal carcinoma. At present, this combination is not considered to be a standard procedure of neoadjuvant treatment in the Czech Republic. However, based on the results of forthcoming clinical studies, wider use of this concomitant chemobioradiotherapy in clinical practice can be expected, especially in the treatment of locally advanced stages of rectal carcinoma.