Hemispheric infiltrative grade II gliomas in adults: association of residual tumour volume and extent of tumour resection with malignant transformation.

OBJECTIVES: Evaluation of the impact of surgical treatment on malignant transformation (MT) of adult supratentorial infiltrative grade II gliomas (G2G) in a series of chemotherapy and radiotherapy-naïve patients. BACKGROUND: Despite G2G are slow-growing tumours, they typically undergo MT with a subsequent fatal disease course. An extensive resection alone likely changes their biological behaviour and defers MT; however, this impact is not unequivocally confirmed. METHODS: Thirty-eight chemotherapy and radiotherapy-naïve adult patients operated from 2005 till 2014 for a G2G were investigated. Based on postoperative magnetic resonance imaging (MRI) and/or positron emission tomography follow-up (FU) scans, the patients were classified as "transformers" (15 patients in whom MT occurred during the FU-period) and "non-transformers" (23 patients). RESULTS: The follow-up period of "non-transformers" was longer (p <0.0001). After adjustment for known risk factors - age, male sex, astrocytoma histology, preoperative tumour volume, preoperative contrast enhancement and positive isocitrate dehydrogenase 1 gene mutation status - a larger log postoperative tumour volume (p=0.031) and a smaller extent of resection (p=0.0086) were associated with a shorter MT-free survival. CONCLUSION: In our series, less extensive resections were associated with a shorter time to MT. Our data support an adoption of techniques enabling extensive G2G resections, such as intraoperative imaging and awake resections, into everyday routine (Tab. 1, Fig. 2, Ref. 40).

Personalities and their contribution to the development of radiation oncology.

Radiotherapy is an integral part of multidisciplinary clinical oncology as one of the basic treatment modalities. Historical evolution of radiation oncology from X-ray discovery, through the discovery of radioactivity by Maria Curie-Sklodowska and her husband Pierre Curie and other worldwide scientists do not appear without the overview of eminent personalities of Czech and Slovak radiotherapy, who have deserved to develop this medical field from its beginnings to the present time.

Magnetic resonance spectroscopy - its added value in brain glioma multiparametric assessment.

OBJECTIVE: In this study, we analysed the results of magnetic resonance spectroscopy (MRS) in the patients with gliomas, including the error rate, MRS parameters variability, correlations with gene mutations and overall usefulness for clinical practice. MATERIAL AND METHODS: Eighty patients with glial tumours were examined by multiparametric MRI completed with single voxel MRS, as one group, then as two separate groups according to progression of the disease after the initial surgery. The error rate between the groups, MRS parameters variability, hazard ratios and correlations between metabolites, genetic markers and tumour grade were all analysed. RESULTS: Variability in Cho/Cr(h) was significantly higher in the group with a disease progression (p = 0.044). In the patients with a stable disease, strong significant negative correlations between Cho/Cr and Cho/NAA with p53 mutation (-0.945 and -0.812 respectively, p < 0.05) and between Cho/Cr and IDH1, 2 mutation (-0.796, p < 0.05) were found. In the patients with tumour progression, a significant positive correlation of NAA/Cr with 1p19q codeletion (0.486, p < 0.05) and of Cho/Cr and Cho/NAA values with p53 mutation (0.477 and 0.416, p < 0.05) were identified. Tumour grade positively correlated with Cho/Cr values (0.304, p = 0.02) in the whole patient group. CONCLUSION: MRS brings an added value to multiparametric MRI evaluation of brain tumours in the patient follow-up after an initial surgery, especially in ambiguous findings (Tab. 5, Fig. 2, Ref. 29).

[Stereotactic Rediosurgery for Uveal Melanoma; Postradiation Complications]. / Stereotaktická rádiochirurgia (LINAC) uveálnych melanómov; postradiacné komplikácie.

OBJECTIVE: The authors evaluate a group of patients with malignant uveal melanoma treated with stereotactic radiosurgery in the year. 2009-2011 on a linear accelerator LINAC. MATERIAL AND METHODS: In 2009-2011 were followed 40 patients with malignant melanoma of the uvea in stage T2 and T3 treated with stereotactic radiosurgery (LINAC), the therapeutic dose of 35,0 Gy TD, TD max 42,0 Gy. We evaluated the influence of factors (age, exposure risk structures, time) to intraocular pressure (IOP) and temporal changes in intraocular pressure after surgery between the control group and the group of patients who underwent enucleation. The normality of data distribution was tested Shapiro-Wilk W test and graphically. The relations between the parameters were tested using simple and multiple linear regression (correlation coefficient r, the significance level p). RESULTS: The mean age of the group of 40 patients with malignant melanoma of the uvea treated by one day session stereotactic radiosurgery on a linear accelerator in the year. 2009-2011 was 55.13±11.11 years. Average maximum radiation dose to sensitive structures has been the target of 12,0 Gy to the optic nerve and the ciliary 10,0 Gy. The analysis in our group confirmed that the prevalence of the tumor independent of sex, increasing with age, with most patients are diagnosed between 60 and 70 years of age. Analysis of the difference in intraocular pressure (IOP) before surgery showed no significant difference between the group of men and women (p=0.54). Using simple linear regression, we confirmed assumptions, related to IOP before stereotactic radiosurgery with age (r=-0.09, p=0.65). Multiple linear regression, we evaluated the relationship between predictors (dose at-risk structures--lens and optic nerve) and the change in IOP from the value before stereotactic radiosurgery at each time interval. Relations between predictors (Dose aperture--L, the dose of the optic nerve--O) and IOP of the file being described partial correlation coefficients after 2 weeks. For the relationship is significant correlation between the dose and the IOP in the lens at the time of 1 year, 1.5 years, and 2 years after the stereotactic radiosurgery. CONCLUSION: A single stereotactic radiosurgery on a linear accelerator LINAC is possible at a dose of 35,0 to 38,0 Gy in intraocular melanomas in stage T1 to T3. According to our results, this is a highly effective method of treatment of uveal melanomas elevation to 6 mm and a capacity of up to 0,4 cm3. Secondary glaucoma is one of the most serious causes of enucleation after one day session stereotactic radiosurgery at linear accelerator (LINAC) for uveal melanoma. The percentage of enucleation in our investigated group (17.5%) for secondary glaucoma is about the same as in other studies.

Pineal germ cell tumors: review.

BACKGROUND: Primary intracranial germ cell tumors represent a rare category of neoplasms, which occur in children and young adults. The WHO classification divides intracranial tumors into germinomas and non-germinomas. The most frequent locality of these tumors is pineal and suprasellar region. Clinical signs and symptoms depend on the localization of the tumour - they most commonly include signs of increased intracranial pressure, Parinauds syndrome, bitemporal hemianopsy and signs of endocrine deficiency. Gadolinium enhanced MRI scan of the brain is the imagining examination of choice in the diagnostic strategy of intracranial germ cell tumors. However, the imagining studies do not provide sufficient information about histological type; therefore, biopsy is necessary. The exception represents cases with characteristically increased levels of tumor markers (AFP and ß-HCG) measured in the serum and cere-brospinal fluid. CASE: A pineal germ cell tumor was observed in a 26-year-old male with presentation of an eye-sight disorder with focusing difficulty and photophobia, accompanied by intensive fatigue and sleepiness, nausea with occasional vomiting, intermittent headaches and Parinauds syndrome. MRI examination of the brain showed tumor expansion in the pineal region and in the right part of the mesencephalon. Radical extirpation of the tumor in the pineal region was performed. The follow-up MRI scan of the brain revealed relapse of the disease. The patient underwent craniospinal radiation therapy with subsequent postoperative chemotherapy (regimen cisplatin and etoposide), three cycles in total. Currently, the patient is 30 months after finishing of oncological treatment in clinical remission of the disease. CONCLUSION: The treatment and prognosis of this neoplasm differ between particular categories. Germinomas have better survival rates than non-germinomas. A 5-year survival rate of germinoma patients after application of radiotherapy alone was > 90% of cases. The addition of chemotherapy lead to a decrease of the dose and minimalization of the irradiated area, with achievement of fewer side effects without a decrease of the curability. Non-germinomas are less radiosensitive than germinomas, but after the application of the adjuvant chemotherapy, survival benefit was achieved. However, the optimal management of these tumors remains controversial.

[Choroidal melanoma stage T1 - comparison of the planning protocol for stereotactic radiosurgery and proton beam irradiation]. / Choroidálny melanóm v stádiu T1 - porovnanie plánu oziarenia pri stereotaktickej rádiochirurgii a pri protónovej terapii.

OBJECTIVE: Comparison of two methods of irradiation of patients with malignant choroidal melanoma - stereotactic radiosurgery and proton beam irradiation. External (non-contact) applied irradiation is used as a source of accelerated protons, respectively helium ions. This method allows applications of ionizing irradiation also despite the low radiosensitivity of cells of malignant melanoma of the uvea (MMU). External source of ionizing radiation is modulated current energy electrons, protons or neutrons, accelerated in linear accelerators. From the external medium voltages resources (4-16 MeV) are irradiated tissues with target dose of 5.0-24.0 Gy. Volume protons permeate straight the structures of the eye to a certain distance. The use of proton radiation density of ionized protons increases in the vicinity of the impact due to energy losses for electrons interacting with the environment. At the end of the track there is a huge increase in the ionization dose ("Bragg spike"). Therefore, the structures surrounding the eye at the point of entry and little affected and increasing the dose at the end of the proton beam is ideal for the desired therapeutic effect. Fractionated application is also possible. CASE REPORT: In December 2011 we performed stereotactic radiosurgery to treat female patient (born 1939) with malignant melanoma of the choroid stage T1 N0 M0. Plan has been drawn up for stereotactic irradiation - model for linear accelerator Clinac, Corvus planning system ver. 6.2, verification and OmniPro IMRT planning system Liebinger ver. 4.3. Patient characteristics were compared with the virtual plan for proton radiation therapy, and we used the scheme in Physical parameters FIAN-technical center in the Russian Federation. We compared both planning protocols and assess in particular the extent of radiation surrounding non-tumor tissue. RESULTS: When comparing the two planning schemes irradiation levels of surrounding tissues and risk structures (lens, optic nerve, chiasm) in both methods were corresponding to the required standard. CONCLUSION: Treatment of uveal melanoma through proton beam irradiation in Slovakia is not available yet, although it has several advantages, such as fractionation and the possibility of achieving a higher dose of irradiation to deposit (more than 50.0 Gy). The fundamental difference between the two methods for an eye is particularly the possibility of proton beam irradiation exposure of tumor of iris and ciliary body, which can not be solved through stereotactic radiosurgery. The dose to the tumor during irradiation can be optimized. The model device allowed us to make OPTMI - Therapy (Proton Treatment with Optimized Modulated Intensity).

[Uterine Sarcomas - a review]. / Sarkómy maternice - prehlad.

Uterine sarcomas are a heterogeneous group, which constitutes about 8% of malignant uterine tumors. This heterogeneousness and rare occurrence were the main cause of non-uniform therapeutical management. In previously published papers, there were mainly retrospective assessments of the experience of individual centres. The basis of relevant conclusions of the studies, beside their prospectiveness, is the use of unified classification criteria. Currently, a completely new classification of uterine sarcomas is being used, which consists of leiomyosarcoma, endometrial stromal sarcomas and adenosarcomas. For classification of carcinosarcomas, there are valid new criteria of endometrial cancer classification. The basic therapeutic approach of leiomyosarcoma and endometrial stromal sarcomas is a surgical intervention. The gold standard is hysterectomy and salpingooophorectomy. Justifiability of lymphadenectomy is being discussed. For carcinosarcomas, the same recommendations as for the surgical treatment of prognostically unfavourable endometrial carcinoma are valid - hysterectomy, salpingooophorectomy, pelvic and paraaortal lymph node dissection and omentectomy. It is necessary to implement the new classification into clinical practice, to publish and evaluate existing papers, which take into account their basic thesis. Only then it will be possible to create unified therapies. They should be aimed to improve patients survival.

Preoperative radiotherapy of locally advanced rectal cancer: clinical outcome of short-course and long-course treatment with or without concomitant chemotherapy.

BACKGROUND: Preoperative radiotherapy is considered to be standard treatment for locally advanced rectal cancer. The timing and dosage of radiotherapy with or without preoperative chemotherapy remain controversial issues. The objective of this study was to evaluate relevant clinical outcomes of two preoperative radiotherapy regimens - the short-course and -long-course radiotherapy with or without chemotherapy for patients with locally advanced rectal cancer. PATIENTS AND METHODS: 151 patients with stage II-III rectal cancer (103 males and 48 females) treated with preoperative radiotherapy between 01/1999 and 01/2008 were involved in this study. Analysed patterns included sphincter preservation, tumor down-staging, pathological complete remission, frequency of local recurrence, acute and late toxicity, peri-operative complications, overall survival and disease-free survival. RESULTS: Tumor downstaging has been achieved by long-course radiotherapy alone (46%) or in combination with chemotherapy (5-FU or capecitabine, 61%). Pathological complete remission has also been achieved only in the group with long-course radiotherapy (13%). Long-course radiotherapy combined with chemotherapy significantly decreased post treatment local recurrence rates (5% versus 15% in the group after long-course radiotherapy alone, p = 0.0132). Statistically significant difference was confirmed in overall survival of patients treated with long-course radiotherapy combined with chemotherapy vs long-course radiotherapy alone (p = 0.015). Significant difference between the rate of perioperative complications, of acute and late toxicity, 3 and 5 years disease-free survival of treated patients after short-course radiotherapy and long-course radiotherapy was not confirmed. CONCLUSION: Our findings provide convincing evidence that in comparison to preoperative short-course radiotherapy, the preoperative long-course radiotherapy in combination with chemotherapy is the most effective treatment modality for patients with operable locally advanced rectal cancer in terms downstaging and pathologic complete response. Increase in overall survival time as well as lower local recurrence rate makes this modality superior to other preoperative radiotherapy alternatives.

Malignant hemophtalmus as a first sign of orbital rhabdomyosarcoma in adult.

We report on a rare case of an adult patient with rhabdomyosarcoma treated at the Dpt Ophthalmology, Comenius University, Medical School in Bratislava as a single case since 1968 (Fig. 2, Ref. 5). Full Text in free PDF www.bmj.sk.

No differences in outcome between radical surgical treatment (enucleation) and stereotactic radiosurgery in patients with posterior uveal melanoma.

To report the treatment outcome and possible survival difference between radical surgical treatment (enucleation) or stereotactic radiosurgery (SRS). LINAC stereotactic radiosurgery is an alternative treatment for posterior uveal melanoma used in Slovakia since 1999. The study analyzed patients treated for posterior uveal melanoma in the period 2001-2008. The aim of the study was to compare the relapse-free survival in the cohort of patients primarily treated with surgery (enucleation) or SRS. A total number of 84 patients were included, treatment was determined on a case-by-case basis. We reviewed the records of patients with ciliary body or choroidal melanoma treated by enucleation - 44 patients (52%) and SRS - 40 patients (48%). The therapeutic attitude was established on the basis of ophthalmoscopy, ultrasound (A, B mode), other ophthalmological findings, visual acuity, and general status of each patient. Volume of the tumor was calculated using the formula: "pi/6 x length x width x height" for each patient. All of the patients before decision to "conservative" attitude therapy underwent MRI examination. The therapeutic dose in SRS patients group was 35.0-38.0 Gy. The data were analyzed using Kaplan - Meier survival method for the differences in survival rates between the treatment groups, and afterwards by Cox s proportional hazard method with predictors involved. Among the baseline covariates evaluated, only age affected the prognosis for survival to a statistically important, however not significant degree. The risk of death among patients treated with enucleation relative to those treated with stereotaxy after adjustment for baseline characteristics of patients, age, and tumor volumes was not significant [1.82] (95% CI, 0.46 to 7.30; P = 0.396). The overall five-year survival rate for patients with posterior uveal melanoma was 72%. Treatment by either primary enucleation or SRS according to our results does not appear to influence the development of metastases in patients with uveal melanoma; the survival prognosis is essentially determined by the stage and character of the tumor. No survival difference attributable to stereotactic irradiation of uveal melanoma has been demonstrated in this retrospective study. A small difference is possible, but a clinically meaningful difference in mortality rates, whether from all causes or from metastatic melanoma, is unlikely. Treatment by either radical surgical attitude (enucleation) or "conservative" LINAC- SRS does not appear to influence the survival rate in patients with uveal melanoma.

MR imaging of late radiation therapy- and chemotherapy-induced injury: a pictorial essay.

Radiation to the brain and adjuvant chemotherapy may produce late delayed changes from several months to years after treatment of intracranial malignancies with a reported prevalence of 5-24%. The pattern of treatment-related injury may vary from diffuse periventricular white matter lesions to focal or multifocal lesions. Differentiation of treatment-related injury from tumor progression/recurrence may be difficult with conventional MR imaging (MRI). With both disease processes, the characteristic but nonspecific imaging features are vasogenic edema, contrast enhancement, and mass effect. This pictorial essay presents MRI spectra of late therapy-induced injuries in the brain with a particular emphasis on radiation necrosis, the most common and severe form. Novel MRI techniques, such as diffusion-weighted imaging (DWI), proton MR spectroscopy (MRS), and perfusion MRI, improve the possibilities of better characterization of treatment-related changes. Advanced MRI techniques allow for the assessment of metabolism and physiology and may increase specificity for therapy-induced changes.

Post-therapeutical changes in the brain: novel trends in imaging and their infuence on external beam radiotherapy.

UNLABELLED: Presented is the analysis of patients who underwent external beam radiotherapy (EBRT) to the brain in the period from 2003 to 2006 at the department of Radiation Oncology of the St. Elisabeth Cancer Institute.

The aim of our analysis was to identify risk factors of late delayed therapy induced injuries (LDTI) in the brain. The patients were regularly examined with magnetic resonance (MRI), including conventional and advanced techniques: perfusion imaging (pMRI), diffusion weighted imaging (DWI), MRI spectroscopy (MRS). The results from MRI were correlated with 18fluoro-deoxyglucose positron emission tomography (18FDG/PET) scans, as none of the listed method is sufficiently sensitive and specific by itself. Also clinical data records and treatment plans of these patients were analyzed.

In our cohort we found 6 patients with abnormal post-therapeutical changes, 4 of them with MR and 18FDG/PET scans characteristics for LDTI - radiation necrosis. In one patient biopsy was performed and radiation necrosis (RN) was confirmed.

Radiation-induced meningioma with a long latency period: a case report.

Multiple meningiomas were diagnosed in a 43-year-old man previously treated with high-dose craniospinal radiotherapy at the age of 7 years for medulloblastoma. We suggest that surveillance MRI after high-dose craniospinal radiotherapy should be extended to several (3-5) decades.

Radiation-induced meningiomas.

High dose radiation-induced meningiomas are a rare, severe and late complication of craniospinal radiotherapy for brain tumors. Radiation-induced meningiomas are, according to the literature, several times more frequent than radiogenic gliomas and sarcomas. It is suggested that every new case of radiogenic meningioma has to be reported to elucidate this particular pathologic entity with its many grey areas. In addition to high dose radiation-induced meningiomas, intracranial meningiomas were observed in patients who underwent low-dose radiation for tinea capitis in childhood, applied en mass to immigrants coming to Israel from the North Africa and the Middle East during the 1950. Authors summarize the data on radiogenic meningiomas from the literature and, as the previous radiotherapy may confer a low, but life-long risk for meningioma occurrence, they suggest that surveillance MRI after high dose cerebrospinal radiotherapy should be extended to several (3-5) decades after radiotherapy.

Long-term (15 years) results of extended field radiotherapy in Hodgkin's disease.

From 1975 to 1990, 214 patients with the pathological Stage IA, IB, IIA, IIB and IIIA of Hodgkin's disease were treated by supradiaphragmatic and/or infradiaphragmatic mantle technique. Complete remission was achieved in 70 patients (8%) by means of radiotherapy only. Partial remission was achieved in 9 patients (2%). The survival at 10 years was 86% and 15 years it was 66%. The most frequent late complications were hypothyreosis, Lhermitte's syndrome and radiation pneumonitis.

Radiation-induced apoptosis and cell cycle alterations in human carcinoma cell lines with different radiosensitivities.

Radiosensitivity of examined human neoplastic cell lines was assessed with the aid of MTT assay. Differences between radiosensitive and radioresistant human neoplastic cell lines were as follow: a) radiation-induced apoptosis detected by flow cytometry was apparent in the most radiosensitive (i.e. CH-1 ovarian carcinoma cell line), but not in the radioresistant (i.e. SKOV-3 ovarian carcinoma) cell lines, b) radiation-induced G2/M arrest appeared early after irradiation (6 hours) in both the radioresistant SKOV-3 cells and in the radiosensitive CH-1 human ovarian carcinoma cell line, but a different pattern was observed 24 hours after irradiation with 2 Gy dose with G2/M arrest only in radiosensitive cell line. The radiosensitivity and resistance to radiation-induced apoptosis in the radioresistant human breast carcinoma MDA-MB-231 cell line were similar to those observed in SKOV-3 cells. These data suggest that radiation-induced apoptosis and cell cycle alterations can predict radiosensitivity at least in some examined human malignant cells in vitro.

Radiation-induced DNA damage and repair evaluated with 'comet assay' in human ovarian carcinoma cell lines with different radiosensitivities.

Radiation-induced DNA damage and kinetics of DNA repair was evaluated in three human ovarian carcinoma cell lines (i.e. CH-1, A-2780 and SKOV-3) with different sensitivities to ionizing radiation and radiation-induced apoptosis with the aid of single cell gel electrophoresis (SCGE, the comet assay). A good correlation was found between the initial level of DNA breaks and radiation induced apoptosis in CH-1 and SKOV-3 cell lines. While the radiation-sensitive CH-1 cell line manifested the highest level of initial DNA breakage and a significant delay in DNA break rejoining, the inverse correlation was found in the radiation-resistant cell line SKOV-3. Intermediate initial level of breaks was induced in the A-2780 cell line characterized by the intermediate sensitivity to X-ray radiation in comparison to CH-1 and SKOV-3 cells, however, the kinetics of DNA repair was comparable with radiation-resistant cell line SKOV-3. Our data suggest that the comet assay could be a promising tool for prediction of intrinsic cell radiosensitivity. This method might be considered as a supplementary technique to the more reliable but time consuming clonogenic assay.

Resistance of human multidrug-resistant neoplastic cell lines to paclitaxel-induced-radiosensitization is reduced by the non-immunosuppressive cyclosporine analog SDZ PSC 833.

The non-immunosuppressive cyclosporine analog SDZ PSC 833 abolished the resistance of human multidrug resistant (MDR-1, P-gp) human promyelocyte leukemia HL-60/VCR cells in vitro to paclitaxel-induced cell cycle- and viability alterations, as well as resistance to paclitaxel-induced radiosensitization. Furthermore, SDZ PSC 833 abolished also the resistance of human multidrug-resistant ovarian A2780/ADR cells to paclitaxel-induced cell cycle alterations and reduced its resistance to paclitaxel-induced radiosensitization. In these multidrug-resistant ovarian carcinoma cells the supra-additive interaction between paclitaxel and SDZ PSC 833 pre-exposure and subsequent irradiation appeared at slightly higher paclitaxel concentrations (40-100 nM) compared to those required for a similar interaction in the parental drug sensitive A2780 cells (40-80 nM paclitaxel).

Taxol-enhanced cytotoxic effect of radiation in human promyelocytic leukemia cells: relative resistance of multidrug-resistant HL-60 cells in vitro.

Cytotoxic effects of sequential taxol (paclitaxel) and X-irradiation on drug-sensitive human cultured promyelocytic leukemia (HL-60) cell line and its multidrug-resistant sublines were examined using photometric MTT test and flow cytometry. Paclitaxel (at concentrations 1-10 nmol) stimulated the cytotoxic effect of irradiation in HL-60 and to a lesser extent also in HL-60/ADR, but not in HL-60/VCR cells. The stimulation of radiation-induced cytotoxic effect by paclitaxel correlated with its potential to induce cell cycle and viability alterations identified with flow cytometric analysis (i.e. increased propidium iodide staining, increased side scatter, decreased forward angle scatter, accumulation of necrotic cell detritus, apoptotic pre-G0 cells and cells in the G2/M phase of the cell cycle).