1,720,991 research outputs found
Optimization of brain tumors irradiation, determinig the set-up margin in modern irradiation techniques
Uvod: Možgani so kompleksen organ, ki ob pojavu raka, kot ene najtežjih bolezni v današnji dobi, niso ostali ne prizadeti. Glede na to iz kakšnih celic so možganski tumorji sestavljeni, ločimo primarne in sekundarne tumorje. Zelo pomembno vlogo pri zdravljenju le teh ima radioterapija, kjer se za obsevanje uporabljajo megavoltni fotonski žarki energije 6 megavoltov, tridimenzionalne tehnike obsevanja in sistem slikovno vodene radioterapije. Velikost varnostnega roba pri obsevanju možganov znaša do 2 cm. Namen: Preveriti ali obstoječi varnosti rob kliničnega ciljnega volumna in načrtovanega tarčnega volumna ustreza izračunanemu varnostnemu robu za obsevanje možganov ter definirati varnostne robove potrebne za obsevanje posameznih regij možganov. Metode dela: Na Onkološkem inštitutu Ljubljana smo izvedli presečno retrospektivno raziskavo. Izbrali smo si časovno obdobje enega leta in sicer od 1. 9. 2018 do 1. 9. 2019. V elektronskih/fizičnih obsevalnih kartonih bolnikov, smo glede na lokacijo tumorja, pregledali sistematične napake in na podlagi teh, izračunali povprečne sistematične napake in velikosti varnostnih robov glede na možganski reženj ter naredili primerjavo z že obstoječimi varnostnimi robovi. Podatke smo analizirali s programom za statistično obdelavo. Rezultati: Povprečne sistematične napake glede na možganske regije smo izračunali v štirih smereh: lateralni, longitudinalni, vertikalni in v smeri rotacije. Največjo sistematično napako v lateralni smeri smo izračunali v področju cerebelarno, ki je tudi statistično značilna (p < 0,05). V longitudinalni in vertikalni smeri pri nobeni od regij nismo zaznali statistično značilnih razlik. Smo pa statistično značilno razliko zaznali v smeri rotacije in sicer v frontalnem režnju (p=0,037) in legi tumorja cerebelarno (p=0,002). Največjo velikost varnostnega roba smo izračunali za tumorje, ki ležijo cerebelarno (0,80 mm), medtem ko bi tumorjem v področju parietalnega režnja dodali zgolj 0,31 mm velik varnostni rob. Z linearno regresijo smo ugotovili tudi, da na lateralne premike in rotacijo vpliva zgolj lega tumorja cerebelarno (p < 0,05), medtem ko na longitudinalne in vertikalne premike ne vpliva nobeden izmed faktorjev. Razprava in zaključek: Ugotovili smo, da so velikosti povprečnih sistematičnih napak manjše od velikosti 1 mm, kar lahko pripišemo dobri fiksaciji bolnikov s tri točkovno termoplastično masko. Glede na izračun varnostnega roba (klinični ciljni volumen in planirani tarčni volumen), bi tako varnostni rob iz obstoječih 5 mm zmanjšali na 2-3 mm, v kolikor bi v procesu obsevanja sledili protokolu portalnega slikanja.Introduction: The brain is a complex organ that coordinates the activity of all functions, but in the occurrence of cancer, these have not remained intact. Considering what cells brain tumors are made of, we distinguish between primary and secondary brain tumors. An important part of medical treatment is radiation therapy, which uses megavoltage photon beams, three-dimensional radiation techniques, and the image-guided radiation therapy system. The size of the margins used in radiotherapy of the brain is up to 2 cm. Purpose: The purpose of this thesis was to evaluate whether the excising margin of the clinical tumor volume and planning target volume correspond with calculated radiation margin based on systematic errors and to define radiation margins required for irradiation of individual brain lobes. Methods: A retrospective cross-sectional study was performed at the Institute of Oncology Ljubljana. We chose a period of one year, from September 1, 2018 to September 1, 2019. In the patient\u27s electronic/physical irradiation maps, we checked the systematic errors and calculated their average and the size of radiation margins, both divided by brain lobe. We compared them with the existing ones. The data were statistically analyzed using a statistical data processing program. Results: We calculated the average systematic errors in four directions: lateral, longitudinal, vertical and rotation. The largest average systematic error was calculated in the lateral direction in the cerebellar area, and the error was also statistically significant (p < 0.05). In longitudinal and vertical direction, we did not find statistically significant differences between brain lobes. In rotational direction we notice the statistically significant difference in frontal lobe (p=0.037) and cerebellar area (p=0.002). The largest radiation margin was calculated for tumors in the cerebellar area (0.80 mm), while for tumors in the parietal lobe the calculated margin was only 0.31 mm. Using linear regression, we found that for lateral movements and rotation, only the position of the tumor in the cerebellar area was statistically significant (p < 0.05), while longitudinal and vertical movements were not affected by any of the factors. Discussion and conclusion: We found that the magnitude of the average systematic errors is less than 1 mm. The reason may be the fixation of patients with three-point fixation masks. Depending on the calculated irradiation boundary (clinical tumor volume and planned target volume), the boundary can be reduced from the existing size of 5 mm to a size between 2 and 3 mm if the portal imaging protocol is followed during irradiation
Radiosurgery of brain metastases in melanoma
Melanom spada med tumorje, ki najpogosteje dajejo možganske zasevke. Sicer ne v absolutnem številu temveč relativno. Poleg simtomatskega zdravljenja, operacije, obsevanja celih možganov in sistemske terapije je ena od možnosti zdravljenja možganskih zasevkov tudi radiokirurgija. Radiokirurgija ni nova tehnika, jo je pa napredek tehnologije popeljal na nov nivo. Gre pri radiokirurgiji za neinvaziven poseg in so komplikacije zapleti zdravljenja bistvpomembnoeno nižjie kot pri operativnem zdravljenju. Pri zdravljenju z radiokirurgijo je pomembno to, da je zdravljenje zelo lokalno. Zaradi tega lahko bolnike zdravimo z radiokirurgijo tudi večkrat. Vsekakor je radiokirurgija možganskih zasevkov melanoma še en majhen delec v sestavljanki kako kontrolirati bolezen in je prav zaradi tega posvet strokovnjakov več strok pomembnih pri onkološkem zdravljenju na multidisciplinarnem konziliju bistvenega pomena
Immunohistochemical and genetic markers in glioblastoma multiforme
Glioblastom (GBM) je najpogostejši primarni možganski tumor. Njegova incidenca v Sloveniji znaša 2,9 bolnika na 100.000 prebivalcev. Na Onkološkem inštitutu Ljubljana smo v letih od 1997 do 2013 obravnavali 861 bolnikov z GBM, od teh jih je umrlo 730. Kljub slabi prognozi vedno več bolnikov preživi vsaj 2 leti in pol. Zanimalo nas je, v čem se ta skupina bolnikov razlikuje od večine bolnikov z GBM. Bolnike z GBM lahko razdelimo v prognostične skupine glede na klinične parametre, kot so starost, stanje zmogljivosti in obseg operacije glede na to jih lahko razdelimo naprej z rekurzivno particijsko analizo razrede. Naprej jih lahko opredelimo tudi glede na molekularne in genetske označevalce, kot so metilacija promotorja metil-gvanin-metil transferaze (MGMT), glede na nekatere podatke pa tudi mutacija izocitrat dehidrogenaze 1 (IDH1). Cilji naloge so bili opredeliti pojavljanje MGMT, IDH1in LoH1p/19q pri bolnikih z GBM z dolgim preživetjem in pri podobnih bolnikih, ki so imeli običajno preživetje. Hipoteza naše raziskave je bila, da lahko z uporabo imunohistokemičnih in genetskih označevalcev te skupine bolje opredelimo kakor z dosedaj uporabljanimi metodami. Pregledali smo populacijo bolnikov z GBM. Opredelili smo jih glede na klinične napovedne dejavnike, poiskali bolnike, ki so preživeli več kot 2 leti in pol in jim poiskali ustrezno kontrolno skupino. Pri obeh skupinah smo določili status metilacije promotorja MGMT, mutacije IDH1, IDH2, CDKN2A, CDKN2B in preureditev kromosomov 1p in 19q, opredelili smo tudi potrebo bolnikov po kortikosteroidih. Potrdili pomembnost RPA- razredov za preživetje. Opažamo značilno večjo incidenco metilacije promotorja MGMT, mutacije IDH1 R132H in nižjo potrebo po kortikosteroidih pri bolnikih z dolgim preživetjem. V multivariatni analizi sta se kot značilna za preživetje izkazala metilacija promotorja za MGMT, ki je prognostično ugodna in večja potreba po kortikosteroidih 3 mesece po zaključenem lokalnem zdravljenju, ki korelira s slabšim preživetjem. Izsledki raziskave potrjujejo prognostični pomen metilacije promotorja MGMT, še več, breztega praktično ni dolgega preživetja. Glede na to, da status metilacije promotorja MGMT ni stalno stanje, pač pa se lahko spreminja, se poraja vprašanje o dolgotrajni terapiji s kortikosteroidi. Z raziskavo smo potrdili pomen določanja imunohistokemičnih in genetskih označevalcev za napoved prognoze pri bolnikih z GBM. V prihodnje svetujemo rutinsko določanje metilacije promotorja MGMT ter določanje mutacij IDH1 in IDH2 na biopsijskih vzorcih GBM. Pri bolnikih, ki imajo metiliran promotor MGMT, so potrebne nadaljnje raziskave vpliva kortikosteroidov na metilacijski status promotorja MGMT.Glioblastoma (GBM) is the most common primary brain tumour. Incidence of GBM in Slovenia is 2.9 patients per 100.000 inhabitants. Between 1997 and 2013, 861 patients with GBM were treated at the Institute of Oncology Ljubljana. Of those, 730 patients died. Despite generally poor prognosis, an increasing proportion of GBM patients are surviving 2.5 years and beyond. We were interested in differences between LTS and the control group. The GBM patients can be stratified in the prognostic groups according to clinical parameters: age, performance status and the extent of resection and further by using recursive partitioning analysis into distinctive classes. Further they can be distinguished according to molecular and genetic markers such as methyl guanine methyl transferase (MGMT) promoter methylation and according to some data mutations of izocitrate dehidogenase 1 (IDH1). Our research goals were to determine the frequency of MGMT methylation, IDH1 mutations and 1p/19 chromosomal rearrangements in LTS, in comparison with GBM patients with average survival. The hypothesis being that we can better define prognostic groups by using these methods alongside the clinical parameters. Clinical records of patients with GBM were reviewed. The clinical prognostic parameters were reviewed, and patients surviving more than 2.5 years were selected. We also found a matching control group. In both groups we determined MGMT promoter methylation status, IDH1, IDH2, CDKN2A and CDKN2B mutations and 1p and 19q chromosomal rearrangements. We also determined the corticosteroids needs. RPA- classes importance for survival was confirmed. We are observing significantly higher incidence of MGMT promoter methylation, IDH1 R132H mutations and lower corticosteroids needs in long term survivors. In multivariate analysis methylation of MGMT promoter and lower corticosteroid needs 3 month after completion of local treatment were found to be significant. Our data confirms prognostic significance of MGMT promoter methylation even more, without it there is practically no long term survival. Due to a fact, that a MGMT promoter methylation is not a permanent state, but it changes during the course of disease, the long term corticosteroid therapy is questioned. Our research confirms the importance testing for molecular and genetic markers for the assessment of prognosis in GBM. We advocate routine MGMT promoter methylation testing and testing for IDH1 and IDH2 mutation in GBM samples. In patients with methylated MGMT promoter further research of the corticosteroids impact on MGMT promoter methylation status is needed
Stereotactic surgery of malignant melanoma brain metastases
Since 2007, the Oncology Institute of Ljubljana carried out 97 SRS procedures, 9 of which were performed in patients with malignant melanoma brain metastases. Another patient was treated with hyperfractionated stereotactic radiotherapy (hfSRT), as the irradiated area was too large for irradiation with SRS and, based on the radiobiological characteristics of the tumour, we decided for targeted radiation therapy with a higher daily dose (6). Median survival was 30 weeks for all malignant melanoma patients, with the same survival time until local recurrence of the disease. Following SRS, there were less local recurrences among patients compared to progressions or recurrences of the disease outside the central nervous system (CNS). The irradiation dose delivered to patients treated with SRS was 22.5 Gy (20-25) in a single dose. The patient treated with hfSRT received 30 Gy in total, namely 5 doses of 6 Gy. Eight out of nine patients also received WBRT, and one was treated with WBRT after the first surgery for brain metastases and did not receive it after the SRS. The patient treated with hfSRT due to systemic therapy administered after radiation therapy (vemurafenib) did not receive WBRT and experienced disease progression in the CNS outside the irradiated three months later. The response was achieved in all patients (a stable disease in 4 patients, a partial response in 4 patients, a complete response in 1 patient), with patients with a stable disease experiencing disease progression outside the CNS a few weeks after the therapy. A complete response was achieved in one patient, but six months later, he also experienced disease progression in the CNS outside the SRS area
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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