BACKGROUND: Glioblastoma (GBM) is the most common and aggressive primary brain cancer. The treatment of GBM consists of a combination of surgery and subsequent oncological therapy, i.e., radiotherapy, chemotherapy, or their combination. If postoperative oncological therapy involves irradiation, magnetic resonance imaging (MRI) is used for radiotherapy treatment planning. Unfortunately, in some cases, a very early worsening (progression) or return (recurrence) of the disease is observed several weeks after the surgery and is called rapid early progression (REP). Radiotherapy planning is currently based on MRI for target volumes definitions in many radiotherapy facilities. However, patients with REP may benefit from targeting radiotherapy with other imaging modalities. The purpose of the presented clinical trial is to evaluate the utility of 11C-methionine in optimizing radiotherapy for glioblastoma patients with REP. METHODS: This study is a nonrandomized, open-label, parallel-setting, prospective, monocentric clinical trial. The main aim of this study was to refine the diagnosis in patients with GBM with REP and to optimize subsequent radiotherapy planning. Glioblastoma patients who develop REP within approximately 6 weeks after surgery will undergo 11C-methionine positron emission tomography (PET/CT) examinations. Target volumes for radiotherapy are defined using both standard planning T1-weighted contrast-enhanced MRI and PET/CT. The primary outcome is progression-free survival defined using RANO criteria and compared to a historical cohort with REP treated without PET/CT optimization of radiotherapy. DISCUSSION: PET is one of the most modern methods of molecular imaging. 11C-Methionine is an example of a radiolabelled (carbon 11) amino acid commonly used in the diagnosis of brain tumors and in the evaluation of response to treatment. Optimized radiotherapy may also have the potential to cover those regions with a high risk of subsequent progression, which would not be identified using standard-of-care MRI for radiotherapy planning. This is one of the first study focused on radiotherapy optimization for subgroup of patinets with REP. TRIAL REGISTRATION: NCT05608395, registered on 8.11.2022 in clinicaltrials.gov; EudraCT Number: 2020-000640-64, registered on 26.5.2020 in clinicaltrialsregister.eu. Protocol ID: MOU-2020-01, version 3.2, date 18.09.2020.
- MeSH
- dospělí MeSH
- glioblastom * diagnostické zobrazování terapie diagnóza radioterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- methionin * MeSH
- nádory mozku * diagnostické zobrazování terapie radioterapie diagnóza MeSH
- PET/CT metody MeSH
- plánování radioterapie pomocí počítače metody MeSH
- progrese nemoci * MeSH
- prospektivní studie MeSH
- radiofarmaka terapeutické užití MeSH
- radioizotopy uhlíku MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
AIM: Patients with multiple brain metastases (BM) benefit from hippocampal-avoiding whole brain radiotherapy (HA-WBRT), the challenging and less available form of WBRT. This study explores potential of pre-radiotherapy (pre-RT) hippocampal magnetic resonance spectroscopy (MRS) measuring hippocampal neuronal density as an imaging surrogate and predictive tool for assessing neurocognitive functions (NCF). METHODS: 43 BM patients underwent pre-RT hippocampal MRS. N-acetyl aspartate (NAA) concentration, a marker for neuronal density (weighted by creatine (Cr) and choline (Cho) concentrations), and neurocognitive function (NCF) tests (HVLT and BVMT) performed by certified psychologists were evaluated. Clinical variables and NAA concentrations were correlated with pre-RT NCFs. RESULTS: HVLT and BVMT subtests showed pre-RT deterioration except for BVMT recognition. Significantly better NCFs were observed in women in HVLT subsets. Significantly higher NAA/Cr + Cho was measured in women (median 0.63 vs. 0.55; P=0.048) in the left hippocampus (no difference in the right hippocampus). In men, a positive correlation (0.51, P=0.018) between total brain volume and HVLT-TR, between left hippocampal NAA/Cr + Cho and HVLT-R (0.45, P=0.063), and between right hippocampal NAA/Cr + Cho and BVMT-recognition (0.49, P=0.054) was observed. In women, a borderline significant negative correlation was observed between left hippocampal NAA/Cr + Cho and BVMT-TR (-0.43, P=0.076) and between right NAA/Cr + Cho and HVLT-DR (-0.42, P=0.051). CONCLUSION: Borderline statistically significant correlations were observed with speculative interpretation underlying the challenges of hippocampal MRS as a surrogate for neurocognitive impairment. Further studies need to be done to ascertain the opportunities for imaging predictors of benefit from memory sparing radiotherapy.
- MeSH
- cholin metabolismus MeSH
- dospělí MeSH
- hipokampus * diagnostické zobrazování patologie MeSH
- kognitivní dysfunkce etiologie MeSH
- kraniální ozáření škodlivé účinky MeSH
- kreatin metabolismus MeSH
- kyselina aspartová analogy a deriváty metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční spektroskopie * metody MeSH
- nádory mozku * radioterapie sekundární MeSH
- neuropsychologické testy MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The aim of this retrospective study is to analyze a consecutive cohort of brain metastasis (BM) patients treated off clinical trials through combination of surgery and radiotherapy over the last 15 years in a tertiary neurooncology center. MATERIALS AND METHODS: All BM patients operated between 2007-2019 received adjuvant linac-based radiotherapy categorized to whole brain radiotherapy (WBRT) and tumor bed stereotactic radiotherapy. Survival outcomes and local control was analyzed. RESULTS: In total, 118 patients were enrolled, those with stereotactic radiotherapy (41%) had better baseline characteristics mirrored in longer overall survival (OS) [18 vs. 7.1 months, p < 0.001; hazard ratio (HR) 0.47, p = 0.004] with median follow-up of 58 months. Cumulative incidence for local, distant, and extracranial control was not significantly different between groups, with 12-month cumulative control of 22% vs. 18%, 44% vs. 29%, and 35% vs. 32% for stereotactic and WBRT group, respectively. WBRT was an independent factor for better distal brain control. CONCLUSIONS: Real world data demonstrating significantly better overall survival in patients treated with postoperative targeted radiotherapy compared with postoperative WBRT is presented, with no significant difference in cumulative incidence for local or distant brain control. The majority of patients with targeted radiotherapy had a fractionated dose schedule with outcomes comparable to single-dose radiation trials of postoperative targeted radiotherapy.
- Publikační typ
- časopisecké články MeSH
Východiska: Glioblastom představuje nejčastější a zároveň nejagresivnější primární mozkový nádor dospělých. Radioterapii podstupuje naprostá většina pacientů s tímto onemocněním. Význam správného konturingu (stanovení cílových objemů) v radioterapii glioblastomů v současnosti stále stoupá. Dvěma základními přístupy ke konturování glioblastomů jsou postup "americký" dle Pracovní skupiny pro radioterapii v onkologii (Radiation Therapy Oncology Group – RTOG), tzv. RTOG contouring approach s definicí dvou cílových objemů, a postup "evropský" dle Evropské organizace pro výzkum a léčbu nádorových onemocnění (European Organisation for Research and Treatment of Cancer – EORTC), tzv. EORTC contouring approach s definicí jednoho cílového objemu. Oba přístupy v definování cílových objemů jsou považovány za standardní a v praxi se výběr konkrétního postupu liší i dle zvyklostí daného pracoviště. Významným parametrem hodnocení přístupu ke konturingu je prostorové hodnocení následných recidiv, tzv. patterns of failure (PoF). Cíl: Akademická klinická studie GlioART srovnává RTOG a EORTC přístupy v prospektivním nastavení a se zohledněním všech parametrů nutných pro validní hodnocení následných recidiv – definice recidiv, specifikace MR prokazujícího progresi, specifikace techniky plánované radioterapie, molekulárně biologické charakteristiky glioblastomů, rozsah resekce a lokalizace původního glioblastomu. Cílem tohoto textu je představit zmiňovanou studii GlioART a diskutovat přidružená témata spojená s definováním cílových objemů radioterapie. Závěr: Výsledky akademické studie GlioART mohou definovat doporučení ovlivňující každodenní praxi v radioterapii glioblastomů.
Background: Glioblastoma represents the most common and the most aggressive primary brain tumor in adults. Radiotherapy is indicated in almost all patients suffering with this disease. The importance of valid contouring (target volume definition) in radiotherapy of glioblastomas is currently increasing. The two basic contouring approaches in glioblastoma are the "American" approach of the Radiation Therapy Oncology Group (RTOG contouring approach defining two target volumes) and the "European" approach of the European Organization for Research and Treatment of Cancer (EORTC contouring approach with one target volume). Both mentioned approaches are considered standard of radiotherapy care. In daily radiotherapy practice, a specific contouring procedure is often chosen also according to the convention and tradition of the pertinent workplace. An important parameter in assessing the approach to contouring in radiotherapy is the evaluation of patterns of failure (PoF, spatial evaluation of subsequent relapses). Purpose: The GlioART, academic investigator initiated clinical study, compares the RTOG and EORTC approaches in a prospective setup, taking into account all parameters necessary for valid evaluation of progressions – definition of relapses, MR specification demonstrating progression, planned radiotherapy technique, glioblastoma molecular biological characteristics, resection extent and localization of the original glioblastoma. The aim of this paper is to present the GlioART study and to discuss the associated topics associated with defining the target volumes in radiotherapy.Conclusion: The results of the GlioART trial may define recommendations influencing daily clinical practice in glioblastoma radiotherapy.
BACKGROUND AND AIM: Oncologists play a vital role in the interpretation of radiographic results in glioblastoma patients. Molecular pathology and information on radiation treatment protocols among others are all important for accurate interpretation of radiology images. One important issue that may arise in interpreting such images is the phenomenon of tumor "pseudoprogression"; oncologists need to be able to distinguish this effect from true disease progression.Exact knowledge about the location of high-dose radiotherapy region is needed for valid determination of pseudoprogression according to RANO (Response Assessment in Neuro-Oncology) criteria in neurooncology. The aim of the present study was to evaluate the radiologists' understanding of a radiotherapy high-dose region in routine clinical practice since radiation oncologists do not always report 3-dimensional isodoses when ordering follow up imaging. METHODS: Eight glioblastoma patients who underwent postresection radiotherapy were included in this study. Four radiologists worked with their pre-radiotherapy planning MR, however, they were blinded to RT target volumes which were defined by radiation oncologists according to current guidelines. The aim was to draw target volume for high dose RT fields (that is the region, where they would consider that there may be a pseudoprogression in future MRI scans). Many different indices describing structure differences were analyzed in comparison with original per-protocol RT target volumes. RESULTS: The median volume for RT high dose field was 277 ccm (range 218 to 401 ccm) as defined per protocol by radiation oncologist and 87 ccm (range 32-338) as defined by radiologists (median difference of paired difference 31%, range 15-112%). The Median Dice index of similarity was 0.46 (range 0.14 - 0.78), the median Hausdorff distance 25 mm. CONCLUSION: Continuing effort to improve education on specific procedures in RT and in radiology as well as automatic tools for exporting RT targets is needed in order to increase specificity and sensitivity in response evaluation.
- MeSH
- dávka záření * MeSH
- dospělí MeSH
- glioblastom patofyziologie radioterapie chirurgie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mezisektorová spolupráce MeSH
- nádory mozku radioterapie MeSH
- počítačová simulace normy MeSH
- progrese nemoci MeSH
- radiační onkologie normy MeSH
- radiační onkologové MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The aim of this retrospective study is to assess the incidence, localization, and potential predictors of rapid early progression (REP) prior to initiation of radiotherapy in newly diagnosed glioblastoma patients and to compare survival outcomes in cohorts with or without REP in relation to the treatment. METHODS: We assessed a consecutive cohort of 155 patients with histologically confirmed irradiated glioblastoma from 1/2014 to 12/2017. A total of 90 patients with preoperative, postoperative, and planning MRI were analyzed. RESULTS: Median age 59 years, 59% men, and 39 patients (43%) underwent gross total tumor resection. The Stupp regimen was indicated to 64 patients (71%); 26 patients (29%) underwent radiotherapy alone. REP on planning MRI performed shortly prior to radiotherapy was found in 46 (51%) patients, most often within the surgical cavity wall, and the main predictor for REP was non-radical surgery (p < 0.001). The presence of REP was confirmed as a strong negative prognostic factor; median overall survival (OS) in patients with REP was 10.7 vs. 18.7 months and 2-year survival was 15.6% vs. 37.7% (hazard ratio HR 0.53 for those without REP; p = 0.007). Interestingly, the REP occurrence effect on survival outcome was significantly different in younger patients (≤ 50 years) and older patients (> 50 years) for OS (p = 0.047) and non-significantly for PFS (p = 0.341). In younger patients, REP was a stronger negative prognostic factor, probably due to more aggressive behavior. Patients with REP who were indicated for the Stupp regimen had longer OS compared to radiotherapy alone (median OS 16.0 vs 7.5; HR = 0.5, p = 0.022; 2-year survival 22.3% vs. 5.6%). The interval between surgery and the initiation of radiotherapy were not prognostic in either the entire cohort or in patients with REP. CONCLUSION: Especially in the subgroup of patients without radical resection, one may recommend as early initiation of radiotherapy as possible. The phenomenon of REP should be recognized as an integral part of stratification factors in future prospective clinical trials enrolling patients before initiation of radiotherapy.
- Publikační typ
- časopisecké články MeSH
