Stereotactic body radiation therapy in the treatment of early-stage non-small cell lung cancer.

BACKGROUND: Stereotactic body radiation therapy (SBRT) is now a standard treatment option for patients with early-stage non-small cell lung cancer (ES-NSCLC) who are unfit for surgery or refuse to undergo an operation. SBRT is a method of external beam radiotherapy that accurately delivers a high dose of irradiation in one or few treatment fractions. Intensive regimens of biologically effective dose ≥ 100 Gy are associated with good local control and overall survival, higher than in conventionally fractionated radiotherapy. There are still controversial areas in the SBRT indication where data are limited - indications for elderly and comorbid patients, indications for treatment without histological verification, treatment of central/ultracentral lesions, indications for tumors larger than 5 cm, indications for operable patients. The optimal follow-up practice of these patients also remains unclear, including the frequency of imaging, the use of PET-CT, and requirements for biopsy. CT changes after SBRT differ from those following conventional radiotherapy and it is difficult to distinguish them from tumor recurrence. Due to the high local control achieved with lung SBRT, data on the treatment of local failure are insufficient. PURPOSE: The aim of the publication is to demonstrate the current information and the importance of SBRT for patients with ES-NSCLC.

Extra-mandibular Osteoradionecrosis after the Treatment of Head and Neck Cancer.

AIMS: Osteoradionecrosis (ORN) is a serious toxicity of head and neck radiotherapy. It predominantly affects the mandible. Extra-mandibular ORN is rare. The aim of this study was to report the incidence and outcomes of extra-mandibular ORNs from a large institutional database. MATERIALS AND METHODS: In total, 2303 head and neck cancer patients were treated with radical or adjuvant radiotherapy. Of these, extra-mandibular ORN developed in 13 patients (0.5%). RESULTS: Maxillary ORNs (n = 8) were a consequence of the treatment of various primaries (oropharynx = 3, sinonasal = 2, maxilla = 2, parotid = 1). The median interval from the end of radiotherapy to the development of ORN was 7.5 months (range 3-42 months). The median radiotherapy dose in the centre of the ORN was 48.5 Gy (range 22-66.5 Gy). Four patients (50%) healed in 7, 14, 20 and 41 months. All temporal bone ORNs (n = 5) developed after treatment to the parotid gland (of a total of 115 patients who received radiotherapy for parotid gland malignancy). The median interval from the end of radiotherapy to the development of ORN was 41 months (range 20-68 months). The median total dose in the centre of the ORN was 63.5 Gy (range 60.2-65.3 Gy). ORN healed in only one patient after 32 months of treatment with repeated debridement and topical betamethasone cream. CONCLUSION: Extra-mandibular ORN is a rare late toxicity and this current study provides useful information on its incidence and outcome. The risk of temporal bone ORN should be considered in the treatment of parotid malignancies and patients should be counselled. More research is required to determine the optimal management of extra-mandibular ORN, particularly on the role of the PENTOCLO regimen.

The influence of excessive stress on medical students in the Czech Republic - national sample.

PURPOSE: The Czech Republic has been dealing with a long-term shortage of doctors, which, according to demographic forecasts, will continue to worsen due to the retirement of stronger generations of doctors in contrast to the gradual aging of the population, which will require more health care over time. The country´s political set is trying to respond to this shortage and demographic forecasts by gradually increasing financial funding of medical faculties with the aim of increasing the number of graduates of the program in the field of general medicine. METHODS: Anonymous questionnaire survey was conducted among students and graduates of general medicine at all eight Czech medical faculties. A total of 3183 respondents participated in the survey. There were 2843 medical students, which represents approximately 28% of all medical students in the Czech Republic. The distribution of respondents within the study years was approximately even and approximately corresponded to the real distribution of students between individual faculties in country, which makes survey a national sample. The statistical processing was performed in the statistical software R. Apart from the basic comparison using percentage relative frequencies and Pearson´s chi-squared test, in this study we used Odds ratios (OR) with CI 0,95 from logistic regression model for a better interpretation of some outputs. RESULTS: The results show that the vast majority of Czech medical students experience excessive stress during their studies, which increases the risk of students´ somatic problems (OR = 4.89, CI 0.95 = (4.11;5.83), p < 0.001)., targeted alcohol use (OR = 2.29, CI 0.95 = (1.73;3.04), p < 0,001) and the use of anxiolytic or antidepressant medication to reduce it (OR = 2.99, CI 0.95 = (2.24;4.01), p < 0.001). Students experiencing higher levels of excessive stress are more likely to leave their studies based on their own decision (4.20 (CI 0.95 (3.39;5.19), p < 0.001) and not to enter clinical practice after graduation (OR = 2.62, CI 0.95 = (2.06;3.33), p < 0.001). CONCLUSIONS: The survey shows the need for an open discussion at the highest level about the possibilities of reasonable reduction of unnecessary stress during medical studies. Medical students in the Czech Republic are exposed to excessive stress with all the consequences described above. All that remains is to state the existence of unnecessary components of stress, which represent an opportunity to reduce it, thereby achieving better conditions for studying, improvement in the staff situation in the Czech healthcare system and a reduction in inefficiently spent financial resources for the education of young doctors. TRIAL REGISTRATION: No registration.

Prognostic and predictive factors of brain meningiomas.

BACKGROUND: Common primary brain tumors are meningiomas with year incidence 3-8 cases per 100 000 people. Even though we mainly speak about benign disease, with its character and localization, it worsens the life quality to its bearer. The main therapeutic methods are neurosurgery extirpation and stereotactic radiosurgery. Despite reaching very good therapeutic results with both methods, some of the patients suffer with recurrence of the disease requiring other interventions with the risk of creating or worsening a neurological deficit. Small meningiomas without growing tendency and with the absence of symptomatology are observed. On the other hand, we cannot be satisfied with long-term results of the therapy of meningiomas with more aggressive bio-logical behavior. A higher grade is a known risk of meningioma recurrence; however, it is often difficult to identify subgroups that show advantage of a combination of neurosurgery and radiosurgery, respectfully at which it is appropriate to look for ways to treatment escalation, and that is with the risk of side effects. The analysis of hormonal, cytogenetics and epigenetics tumor equipment seems to be the most promising for the development of personalized treatment. PURPOSE: The aim of this work is to sum up the facts about epidemiology, treatment algorithms and the prognosis of brain meningiomas and to suggest perspective prognostic and predictive factors for maximally individualized therapy.

Oncology wounds - recommendations for care based on multidisciplinary cooperation.

BACKGROUND: Oncology wounds and wounds of other etiology are rare but serious complications, which significantly impair patients quality of life. Preventive and curative interventions and education of healthcare personnel and patients reduce the risk of either their occurrence or their impact and consequences. A working group of authors from professional groups (the Supportive Care Group of the Czech Society for Oncology, the Czech Society for Wound Healing, the Society for Radiation Oncology, Biology and Physics, and the Czech Nurses Association) prepared recommendations for care. A comprehensive approach to the treatment of oncological wounds, including symptomatic treatment of associated healing complications, prevention, early detection, interdisciplinary cooperation and education are essential to deal with wounds related to chemotherapy administration, radiotherapy and oncological treatment in general. The proper choice of local care products and the eventuality of active oncological treatment are important elements of care in ulcerating tumors. PURPOSE: A basic summary of recommended interventions to prevent and treat oncology wounds in daily practice, defined based on expert societies guidelines, trials and literature data, proven practice and on the consensus opinions of the authors group members. The recommended procedures contribute to the reduction of the development, severity and consequences of oncological wounds and wounds of other etiology in oncological  patients.

Recommendation for preventive and therapeutic skin care of patients undergoing radiotherapy.

BACKGROUND: Radiation dermatitis is a very common reaction to radiotherapy, affecting approx. 95% of patients with varying intensity. It is crucial to minimize its side effects. The working group that prepared this document includes physicians, nurses, representatives of the Society for Radiation Oncology, Biology and Physics of the Czech Medical Association of J. E. Purkyně, the Supportive Treatment and Care Section of the Czech Society for Oncology of the Czech Medical Association of J. E. Purkyně, the Czech Wound Management Association, the Oncological Section of Czech Association of Nurses, and dermatologists. The document has been approved by the committees of these associations. PURPOSE: Recommendation for preventive and therapeutic skin care of patients undergoing radiotherapy in the Czech Republic.

Oral cavity complications in oncological and hemato-oncological patients.

BACKGROUND: Oral cavity injuries are very significant complications in the treatment of oncological and hemato-oncological patients. Preventive and curative interventions and patient education reduce the risk of complications and their consequences. A working group of authors from professional groups prepared recommendations for care. PURPOSE: A basic summary of recommended interventions to prevent and treat oral cavity injuries in daily practice, defined on the basis of expert societies guidelines, trials, literature data and proven practice and on the consensus opinions of the authors group members. RESULTS: Preventive measures and patient education are essential in the approach to dealing with oral injuries in chemotherapy, radiotherapy, risky targeted treatment and osteonecrosis of the jaw. Local care products are an important element of care, in case of infections, their antimicrobial action is essential, in case of graft-versus-host disease or in connection with targeted oncological therapy, corticoids are used. CONCLUSION: The recommended procedures contribute to the reduction of the development, severity and consequences of oral complications in oncological and hemato-oncological patients.

Comparison of surgical intervention to Cyberknife® radiotherapy in the treatment of liver malignancies.

INTRODUCTION: Surgical resection is the method of choice in treating liver malignancies. In patients who are not suitable for radical surgical treatment, the radiotherapeutic system Cyberknife® is a viable treatment option. The aim of this study is to compare short- and long-term results of both treatment methods. METHODS: A retrospective analysis of prospectively collected data was performed, focused on patients undergoing treatment of liver malignancies either by surgical resection or by the Cyberknife® system from 2013 to 2016. Only patients treated using a single treatment method were included in the study. RESULTS: A total of 260 patients were analysed; 142 were treated by performing surgical resection and the remaining 118 using Cyberknife® radiotherapy. Median survival was 30.65 months for the surgical resection and 22.93 for the Cyberknife® therapy; median overall survival was 27.63 months. Three-year cumulative survival was 47.4% for the resection and 19.9% for radiotherapy. Kaplan-Meier analysis did not demonstrate a statistically significant difference in disease-specific survival between both groups (p=0.082, CI 95%). Results limited only to colorectal liver metastases showed a statistically significant difference in disease-specific survival (p=0.031, CI 95%). CONCLUSIONS: Results of this study show statistically indifferent overall disease-specific survival of both groups. However, the significant difference in 3-year survival still indicates a predominant position of surgery in the diagnostic and therapeutic management of patients with liver malignancies. Nevertheless, Cyberknife® radiotherapy may actually represent a viable treatment alternative, particularly in patients unable to undergo surgical resection, although a longer follow-up period is necessary to obtain more robust results.

[Intensity Modulated Hyperfractionated Accelerated Radiotherapy to Treat Advanced Head and Neck Cancer - Predictive Factors of Overall Survival]. / Hyperfrakcionovaná akcelerovaná radioterapie s modulovanou intenzitou u pokrocilých nádoru hlavy a krku - prediktivní faktory celkového prezití.

AIM: The aim of this study was to evaluate overall survival (OS) and prognostic factors in patients ineligible for chemotherapy who were treated with a hyperfractionated accelerated schedule with simultaneous integrated boost. MATERIAL AND METHODS: From May, 2008, to April, 2013, 122 patients with locally advanced nonmetastatic squamous laryngeal (14%), hypopharyngeal (30%), oropharyngeal (30%), and oral cavity (27%) cancer were treated at our institution. The median age, Karnofsky Performance Status (KPS), and gross tumor volume (GTV) of the patients were 63 years (range, 46-87 years), 80% (range, 50-100%), and 46 ml (range, 5-250 ml), resp. The median total dose of radiotherapy was 72.6 Gy (range, 62-77 Gy) at 1.4-1.5 Gy per fraction, and 55 Gy at 1.1 Gy per fraction was delivered for GTV (primary and lymphadenopathy) with a margin of 0.7 cm and regional lymphatic areas with a margin of 0.3 cm. The dose was delivered 2× a day, with a 6-8 hour interval between doses, via a 6 MeV linear accelerator. OS was estimated using the Kaplan-Meier method, and predictors of OS were analyzed using Cox proportional hazards regression. RESULTS: The median duration of the radiotherapy series was 37 days (range, 32-45 days). The incidence of grade 3 acute toxicity was 62% for mucosa (oral cavity and/or pharynx) and 0% for skin. Confluent mucositis cleared in all cases within 21 days. No grade 4 or 5 toxicities were recorded. PEG was introduced before treatment in 55 patients (45%). The 1-and 2-year OS was 65% and 32%, resp. KPS less than 80% (RR 2.4, 95% CI 1.3-4.2; p = 0.004), cancers other than oropharyngeal or laryngeal cancer (RR 2.0, 95% CI 1.1-3.5; p = 0.016), and capacity of high GTV (RR 1.006, 95% CI 1.001-1.011; p = 0.017) were found to be negative prognostic factors for OS. CONCLUSION: More than 30% of patients with poor prognosis survived for longer than 2 years. KPS before treatment was the strongest prognostic factor for better OS.Key words: head and neck cancer - radiotherapy dose fractionation - survival analysis - acceleration - hyperfractionation This work was supported by RVO-FNOs/2016 (HPV status as predictive and prognostic factor for primary and secondary 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.Submitted: 9. 3. 2017Accepted: 19. 4. 2017.

[Stereotactic Body Radiotherapy of Prostate Cancer - Effectiveness and Toxicity]. / Stereotaktická radioterapie karcinomu prostaty - efektivita a toxicita.

BACKGROUND: Prostate cancer is the most prevalent cancer in males and its incidence is steadily increasing. Most cases of prostate cancer are diagnosed during the early asymptomatic period, in which case the prognosis is very good. Therapies differ widely in their efficacies and toxicities, and this is an important consideration when it comes to deciding which treatment is optimal for a particular patient. One treatment method for early stage prostate cancer is stereotactic body radiotherapy (SBRT). We present the first results obtained using this modality at our institution. PATIENTS AND METHODS: A total of 261 patients with low or intermediate risk prostate cancer were treated with SBRT between August 2010 and July 2012. Patients received a total dose of 36.25 Gy in five fractions of 7.25 Gy every other day. The toxicity of the treatment was evaluated according to RTOG criteria. For assessment of quality of life, patients filled out a modified EPIC questionnaire (Expanded Prostate Composite index). RESULTS: Overall survival (OS) in this study was 93.1%. Biochemical relapse free survival (bRFS) was 97.7%. As expected, OS and bRFS were worse in the group of patients with an intermediate risk of recurrence. Acute and chronic urinary and gastrointestinal RTOG toxicity was very low. Quality of life after treatment, as determined using the EPIC questionnaire, was slightly reduced immediately after treatment but returned to baseline or even improved during long term follow-up. CONCLUSION: SBRT is an effective therapeutic modality for early prostate cancer and has acceptable rates of acute and low late toxicity.Key words: prostate cancer - stereotactic body radiotherapy - quality of life 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: 5. 1. 2017Accepted: 1. 2. 2017.

Treatment of high risk prostate cancer with combined radiotherapy and hormonal treatment- results and identification of factors influencing outcome.

PURPOSE: The aim of this work was to prospectively analyze the outcome of combined hormonal treatment and radical radiotherapy in high risk non metastatic prostate cancer patients (T1=4, N0-1, M0). METHODS: Between April 2003 and December 2007 196 patients with high risk prostate cancer were treated with curative intent. The treatment consisted of 2-month neoadjuvant hormonal treatment (LHRH analog), radical radiotherapy (68-78 Gy, conformal technique) and an optional 2-year adjuvant hormonal treatment. RESULTS: The median follow up time was 59 months. Fiveyear overall survival was 86% and 5-year biochemical disease free survival (DFS) 70%. Factors found to be statistically significant relative to outcomes were Gleason score (p=0.017), initial PSA value (p=0.039) and adjuvant hormonal treatment (p=0.035). There was no significant association between radiotherapy dose or volume and biochemical DFS (bDFS). Late genitourinary and gastrointestinal toxicity was acceptable. CONCLUSION: Treatment combining hormonal therapy and radical radiotherapy can be recommended for this subgroup of prostate cancer patients. Adjuvant hormonal treatment should also be used.

[HARDROCK project: parametric data collection and analysis of patients with head and neck cancer in the comprehensive cancer centre of Ostrava - role of fractionation and target volume definition in radiotherapy]. / Projekt HARDROCK: parametrický sber a analýza dat pacientu s nádory hlavy a krku na Klinice onkologické FN Ostrava - duraz na význam frakcionace a definice cílového objemu v radioterapii.

BACKGROUND: The HARDROCK project has been designed as a retrospective data collection study in a locally run database system, which fulfils the requirements on the basic version of electronic medical records of cancer patients. The diagnostic category of head and neck tumors has been selected on purpose, as it presents a major problem in the Comprehensive Cancer Centre of Ostrava, and it is relevant given the high incidence and mortality in the Moravian-Silesian Region. The target parameters of the assessment include short-term as well as long-term treatment results in patients with head and neck tumors, evaluated with standard indicators of treatment response and survival. A special emphasis is put on major treatment modalities, i.e. surgery and radiation therapy, and on related complications. PATIENTS AND METHODS: In this article, we present a sample of collected data. The data from patients has been separated into two groups based on the time of their acquisition: data from patients treated in 2004-2005 versus patients treated in 2006-2010. This division was given by the change of treatment protocols in 2006 introducing accelerated radiotherapy with concomitant boost and expanded lymph node irradiation field compared to normofractionation and hyperfractionation regimes used before 2006. RESULTS: Introduction of new irradiation techniques did not increase the rate of acute toxicity but slightly increased late toxicity. Further, we found a decrease of number of relapse and improved overall survival in patients with stage IV disease treated in 2006-2010. CONCLUSION: The project results will contribute methodically to the exact evaluation of diagnostics and treatment of patients with head and neck cancer and will help to optimize their medical care.

Hyperfractionated accelerated radiotherapy with concomitant integrated boost of 70-75 Gy in 5 weeks for advanced head and neck cancer. A phase I dose escalation study.

BACKGROUND AND PURPOSE: The present study was performed to evaluate the feasibility of a new, 5-week regimen of 70-75 Gy hyperfractionated accelerated radiotherapy with concomitant integrated boost (HARTCIB) for locally advanced, inoperable head and neck cancer. METHODS AND MATERIALS: A total of 39 patients with very advanced, stage IV nonmetastatic head and neck squamous cell carcinoma (median gross tumor volume 72 ml) were included in this phase I dose escalation study. A total of 50 fractions intensity-modulated radiotherapy (IMRT) were administered twice daily over 5 weeks. Prescribed total dose/dose per fraction for planning target volume (PTV(tumor)) were 70 Gy in 1.4 Gy fractions, 72.5 Gy in 1.45 Gy fractions, and 75 Gy in 1.5 Gy fractions for 10, 13, and 16 patients, respectively. Uninvolved lymphatic nodes (PTV(uninvolved)) were irradiated with 55 Gy in 1.1 Gy fractions using the concomitant integrated boost. RESULTS: Acute toxicity was evaluated according to the RTOG/EORTC scale; the incidence of grade 3 mucositis was 51% in the oral cavity/pharynx and 0% in skin and the recovery time was ≤ 9 weeks for all patients. Late toxicity was evaluated in patients in complete remission according to the RTOG/EORTC scale. No grade 3/4 late toxicity was observed. The 1-year locoregional progression-free survival was 50% and overall survival was 55%. CONCLUSION: HARTCIB (75 Gy in 5 weeks) is feasible for patients deemed unsuitable for chemoradiation. Acute toxicity was lower than predicted from radiobiological models; duration of dysphagia and confluent mucositis were particularly short. Better conformity of radiotherapy allows the use of more intensive altered fractionation schedules compared with older studies. These results suggest that further dose escalation might be possible when highly conformal techniques (e.g., stereotactic radiotherapy) are used.

Optimisation of an extraction procedure and chemical characterisation of Croatian propolis tinctures.

Three spectrophotometric methods for the quantitative determination of different flavonoid groups and total phenolics in Croatian propolis samples were optimised and validated. The assay based on the formation of aluminium chloride complex (with galangin as a standard) was applied to the quantification of flavones and flavonols, while the 2,4-dinitrophenylhydrazine method (with pinocembrine as a reference) was used for the quantification of flavanones. Total phenolic content was measured by the Folin-Ciocalteau method using reference solution of caffeic acid:galangin:pinocembrine (1:1:1). Through analytical validation, the most suitable extraction conditions (with respect to time, temperature and concentration of extraction solvent) were determined, and final conditions for the extraction were established (80% ethanol, 1 h at the room temperature). The appropriate ratio between the mass of raw propolis and the extraction solvent volume was also established. By the application of the optimised method of extraction, 10 propolis tinctures were prepared and subjected to the analysis of general pharmacopoeial parameters, which are fundamental for the creation of quality specification (relative density, dry residue of extract, content of ethanol, methanol and 2-propanol). Additionally, the content of waxes as the main inactive constituents was determined in order to observe the level of their migration from crude propolis to the prepared tinctures.