Differential effect of vascularity between long- and short-term survivors with IDH1/2 wild-type glioblastoma

[EN] Introduction: IDH1/2 wt glioblastoma (GB) represents the most lethal tumour of the central nervous system. Tumour vascularity is associated with overall survival (OS), and the clinical relevance of vascular markers, such as rCBV, has already been validated. Nevertheless, molecular and clinical factors may have different influences on the beneficial effect of a favourable vascular signature. Purpose: To evaluate the association between the rCBV and OS of IDH1/2 wt GB patients for long-term survivors (LTSs) and short-term survivors (STSs). Given that initial high rCBV may affect the patient's OS in follow-up stages, we will assess whether a moderate vascularity is beneficial for OS in both groups of patients. Materials and methods: Ninety-nine IDH1/2 wt GB patients were divided into LTSs (OS >= 400 days) and STSs (OS < 400 days). Mann-Whitney and Fisher, uni- and multiparametric Cox, Aalen's additive regression and Kaplan-Meier tests were carried out. Tumour vascularity was represented by the mean rCBV of the high angiogenic tumour (HAT) habitat computed through the haemodynamic tissue signature methodology (available on the ONCOhabitats platform). Results: For LTSs, we found a significant association between a moderate value of rCBV(mean) and higher OS (uni- and multiparametric Cox and Aalen's regression) (p = 0.0140, HR = 1.19; p = 0.0085, HR = 1.22) and significant stratification capability (p = 0.0343). For the STS group, no association between rCBV(mean) and survival was observed. Moreover, no significant differences (p > 0.05) in gender, age, resection status, chemoradiation, or MGMT methylation were observed between LTSs and STSs. Conclusion: We have found different prognostic and stratification effects of the vascular marker for the LTS and STS groups. We propose the use of rCBV(mean) at HAT as a vascular marker clinically relevant for LTSs with IDH1/2 wt GB and maybe as a potential target for randomized clinical trials focused on this group of patients.DPI2016-80054-R (Programa Estatal de Promocion del Talento y su Empleabilidad en I +D+i).; European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 844646; H2020-SC1-BHC-2018-2020 (No. 825750); MTS4up project (National Plan for Scientific and Technical Research and Innovation 2013-2016, No. DPI2016-80054-R); European Union's Horizon 2020 research and innovation programme under Marie Sklodowska-Curie, Grant/Award Number: 844646; Research Council of Norway, Grant/Award Number: 261984; South-Eastern Norway Regional Health Authority, Grant/Award Number: 2017073; European Research Council (ERC) under the European Union's Horizon 2020, Grant/Award Number: 758657Álvarez-Torres, MDM.; Fuster García, E.; Reynes, G.; Juan-Albarracín, J.; Chelebian-Kocharyan, EA.; Oleaga, L.; Pineda, J.... (2021). Differential effect of vascularity between long- and short-term survivors with IDH1/2 wild-type glioblastoma. NMR in Biomedicine. 34(4):1-11. https://doi.org/10.1002/nbm.446211134

MGMT methylation may benefit overall survival in patients with moderately vascularized glioblastomas

[EN] Objectives To assess the combined role of tumor vascularity, estimated from perfusion MRI, andMGMTmethylation status on overall survival (OS) in patients with glioblastoma. Methods A multicentric international dataset including 96 patients from NCT03439332 clinical study were used to study the prognostic relationships betweenMGMTand perfusion markers. Relative cerebral blood volume (rCBV) in the most vascularized tumor regions was automatically obtained from preoperative MRIs using ONCOhabitats online analysis service. Cox survival regression models and stratification strategies were conducted to define a subpopulation that is particularly favored byMGMTmethylation in terms of OS. Results rCBV distributions did not differ significantly (p > 0.05) in the methylated and the non-methylated subpopulations. In patients with moderately vascularized tumors (rCBV 10.73), however, there was no significant effect ofMGMTmethylation (HR = 1.72,p = 0.10, AUC = 0.56). Conclusions Our results indicate the existence of complementary prognostic information provided byMGMTmethylation and rCBV. Perfusion markers could identify a subpopulation of patients who will benefit the most fromMGMTmethylation. Not considering this information may lead to bias in the interpretation of clinical studies.Open Access funding provided by University of Oslo (incl Oslo University Hospital). This study has received funding from MTS4up project (National Plan for Scientific and Technical Research and Innovation 2013-2016, No. DPI2016-80054-R) (JMGG); H2020-SC12016-CNECT Project (No. 727560) (JMGG), H2020-SC1-BHC-20182020 (No. 825750) (JMGG), the European Research Council (ERC) under the European Union's Horizon 2020 (Grant Agreement No. 758657), the South-Eastern Norway Regional Health Authority Grants 2017073 and 2013069, the Research Council of Norway Grants 261984 (KEE). M.A.T was supported by Programa Estatal de Promocion del Talento y su Empleabilidad en I+D+i (DPI2016-80054-R). E.F.G was supported by the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement (No. 844646).Fuster García, E.; Lorente Estellés, D.; Álvarez-Torres, MDM.; Juan-Albarracín, J.; Chelebian-Kocharyan, EA.; Rovira, A.; Auger Acosta, C.... (2021). MGMT methylation may benefit overall survival in patients with moderately vascularized glioblastomas. European Radiology. 31(3):1738-1747. https://doi.org/10.1007/s00330-020-07297-41738174731

Robust association between vascular habitats and patient prognosis in glioblastoma: an international retrospective multicenter study

This is the peer reviewed version of the following article: del Mar Álvarez-Torres, M., Juan-Albarracín, J., Fuster-Garcia, E., Bellvís-Bataller, F., Lorente, D., Reynés, G., Font de Mora, J., Aparici-Robles, F., Botella, C., Muñoz-Langa, J., Faubel, R., Asensio-Cuesta, S., García-Ferrando, G.A., Chelebian, E., Auger, C., Pineda, J., Rovira, A., Oleaga, L., Mollà-Olmos, E., Revert, A.J., Tshibanda, L., Crisi, G., Emblem, K.E., Martin, D., Due-Tønnessen, P., Meling, T.R., Filice, S., Sáez, C. and García-Gómez, J.M. (2020), Robust association between vascular habitats and patient prognosis in glioblastoma: An international multicenter study. J Magn Reson Imaging, 51: 1478-1486, which has been published in final form at https://doi.org/10.1002/jmri.26958. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.[EN] Background Glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by a heterogeneous and abnormal vascularity. Subtypes of vascular habitats within the tumor and edema can be distinguished: high angiogenic tumor (HAT), low angiogenic tumor (LAT), infiltrated peripheral edema (IPE), and vasogenic peripheral edema (VPE). Purpose To validate the association between hemodynamic markers from vascular habitats and overall survival (OS) in glioblastoma patients, considering the intercenter variability of acquisition protocols. Study Type Multicenter retrospective study. Population In all, 184 glioblastoma patients from seven European centers participating in the NCT03439332 clinical study. Field Strength/Sequence 1.5T (for 54 patients) or 3.0T (for 130 patients). Pregadolinium and postgadolinium-based contrast agent-enhanced T-1-weighted MRI, T-2- and FLAIR T-2-weighted, and dynamic susceptibility contrast (DSC) T-2* perfusion. Assessment We analyzed preoperative MRIs to establish the association between the maximum relative cerebral blood volume (rCBV(max)) at each habitat with OS. Moreover, the stratification capabilities of the markers to divide patients into "vascular" groups were tested. The variability in the markers between individual centers was also assessed. Statistical Tests Uniparametric Cox regression; Kaplan-Meier test; Mann-Whitney test. Results The rCBV(max) derived from the HAT, LAT, and IPE habitats were significantly associated with patient OS (P < 0.05; hazard ratio [HR]: 1.05, 1.11, 1.28, respectively). Moreover, these markers can stratify patients into "moderate-" and "high-vascular" groups (P < 0.05). The Mann-Whitney test did not find significant differences among most of the centers in markers (HAT: P = 0.02-0.685; LAT: P = 0.010-0.769; IPE: P = 0.093-0.939; VPE: P = 0.016-1.000). Data Conclusion The rCBV(max) calculated in HAT, LAT, and IPE habitats have been validated as clinically relevant prognostic biomarkers for glioblastoma patients in the pretreatment stage. This study demonstrates the robustness of the hemodynamic tissue signature (HTS) habitats to assess the GBM vascular heterogeneity and their association with patient prognosis independently of intercenter variability. Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019.This work was partially supported by: MTS4up project (National Plan for Scientific and Technical Research and Innovation 2013-2016, No. DPI2016-80054-R) (to J.M.G.G.); H2020-SC1-2016-CNECT Project (No. 727560) (to J.M.G.G.) and H2020-SC1-BHC-2018-2020 (No. 825750) (to J.M.G.G.); M.A.T was supported by DPI2016-80054-R (Programa Estatal de Promocion del Talento y su Empleabilidad en I + D + i). The data acquisition and curation of the Oslo University Hospital was supported by: the European Research Council (ERC) under the European Union's Horizon 2020 (Grant Agreement No. 758657), the South-Eastern Norway Regional Health Authority Grants 2017073 and 2013069, and the Research Council of Norway Grants 261984 (to K.E.E.). We gratefully acknowledge the support of NVIDIA Corporation with the donation of the Titan V GPU used for this research. E.F.G. was supported by the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No. 844646. Figure 1 was designed by the Science Artist Elena Poritskaya.Álvarez-Torres, MDM.; Juan-Albarracín, J.; Fuster García, E.; Bellvís-Bataller, F.; Lorente, D.; Reynés, G.; Font De Mora, J.... (2020). Robust association between vascular habitats and patient prognosis in glioblastoma: an international retrospective multicenter study. Journal of Magnetic Resonance Imaging. 51(5):1478-1486. https://doi.org/10.1002/jmri.2695814781486515Louis, D. N., Perry, A., Reifenberger, G., von Deimling, A., Figarella-Branger, D., Cavenee, W. K., … Ellison, D. W. (2016). The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathologica, 131(6), 803-820. doi:10.1007/s00401-016-1545-1Gately, L., McLachlan, S., Dowling, A., & Philip, J. (2017). 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2-Hydroxyglutarate Detection by Short Echo Time Magnetic Resonance Spectroscopy in Routine Imaging Study of Brain Glioma at 3.0 T

The objective of this study was to assess the effective performance of short echo time magnetic resonance spectroscopy (short TE MRS) for 2HG detection as biomarker of isocitrate dehydrogenase (IDH) status in all grade glioma (GL)

Intensity-modulated radiation therapy and volumetric modulated arc therapy versus conventional conformal techniques at high energy: Dose assessment and impact on second primary cancer in the out-of-field region

The aim of this work was to estimate peripheral neutron and photon doses associated with the conventional 3D conformal radiotherapy techniques in comparison to modern ones such as Intensity modulated radiation therapy and volumetric modulated arc therapy. Assessment in terms of second cancer incidence ought to peripheral doses was also considered. For that, a dosimetric methodology proposed by the authors has been applied beyond the region where there is no CT information and, thus, treatment planning systems do not calculate and where, nonetheless, about one third of second primary cancers occurs

Quality assurance multicenter comparison of different MR scanners for quantitative diffusion-weighted imaging

To propose a magnetic resonance imaging (MRI) quality assurance procedure that can be used for multicenter comparison of different MR scanners for quantitative diffusion-weighted imaging (DWI)