Elies Fuster-Garcia1, David Lorente Estellés2, María Del Mar Álvarez-Torres3, Javier Juan-Albarracín3, Eduard Chelebian3, Alex Rovira4, Cristina Auger Acosta4, Jose Pineda5, Laura Oleaga5, Enrique Mollá-Olmos6, Silvano Filice7, Paulina Due-Tønnessen8, Torstein R Meling9,10, Kyrre E Emblem11, Juan M García-Gómez3. 1. Department of Diagnostic Physics, Oslo University Hospital, Sognsvannsveien 20, 0372, Oslo, Norway. elies.fuster@gliohab.eu. 2. Medical Oncology Service, Hospital Provinicial de Castellón, Castellón de La Plana, Castellón, Spain. 3. Instituto Universitario de Tecnologías de la Información y Comunicaciones, Universitat Politècnica de València, València, Spain. 4. Section of Neuroradiology, Hospital Universitari Vall d'Hebron, Barcelona, Spain. 5. Hospital Clínic, Barcelona, Spain. 6. Hospital Universitario de La Ribera, València, Spain. 7. Department of Medical Physics, University Hospital of Parma, Parma, Italy. 8. Department of Radiology, Oslo University Hospital, Oslo, Norway. 9. Department of Neurosurgery, Oslo University Hospital, Oslo, Norway. 10. Department of Neurosurgery, Geneva University Hospitals, Geneva, Switzerland. 11. Department of Diagnostic Physics, Oslo University Hospital, Sognsvannsveien 20, 0372, Oslo, Norway.
Abstract
OBJECTIVES: To assess the combined role of tumor vascularity, estimated from perfusion MRI, and MGMT methylation 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 between MGMT and 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 by MGMT methylation 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), MGMT methylation was a positive predictive factor for OS (HR = 2.73, p = 0.003, AUC = 0.70). In patients with highly vascularized tumors (rCBV > 10.73), however, there was no significant effect of MGMT methylation (HR = 1.72, p = 0.10, AUC = 0.56). CONCLUSIONS: Our results indicate the existence of complementary prognostic information provided by MGMT methylation and rCBV. Perfusion markers could identify a subpopulation of patients who will benefit the most from MGMT methylation. Not considering this information may lead to bias in the interpretation of clinical studies. KEY POINTS: • MRI perfusion provides complementary prognostic information to MGMT methylation. • MGMT methylation improves prognosis in glioblastoma patients with moderate vascular profile. • Failure to consider these relations may lead to bias in the interpretation of clinical studies.
OBJECTIVES: To assess the combined role of tumor vascularity, estimated from perfusion MRI, and MGMT methylation 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 between MGMT and 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 by MGMT methylation 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), MGMT methylation was a positive predictive factor for OS (HR = 2.73, p = 0.003, AUC = 0.70). In patients with highly vascularized tumors (rCBV > 10.73), however, there was no significant effect of MGMT methylation (HR = 1.72, p = 0.10, AUC = 0.56). CONCLUSIONS: Our results indicate the existence of complementary prognostic information provided by MGMT methylation and rCBV. Perfusion markers could identify a subpopulation of patients who will benefit the most from MGMT methylation. Not considering this information may lead to bias in the interpretation of clinical studies. KEY POINTS: • MRI perfusion provides complementary prognostic information to MGMT methylation. • MGMT methylation improves prognosis in glioblastoma patients with moderate vascular profile. • Failure to consider these relations may lead to bias in the interpretation of clinical studies.
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