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1. Geometrical Measures Obtained from Pretreatment Postcontrast T1 Weighted MRIs Predict Survival Benefits from Bevacizumab in Glioblastoma Patients.

Author

Molina, David, Pérez-Beteta, Julián, Martínez-González, Alicia, Sepúlveda, Juan M., Peralta, Sergi, Gil-Gil, Miguel J., Reynes, Gaspar, Herrero, Ana, De Las Peñas, Ramón, Luque, Raquel, Capellades, Jaume, Balaña, Carmen, and Pérez-García, Víctor M.

Subjects
GLIOBLASTOMA multiforme, GLIOBLASTOMA multiforme treatment, BEVACIZUMAB, NEOVASCULARIZATION, BIOMARKERS, IMAGE quality analysis, DIAGNOSIS
Abstract

Background: Antiangiogenic therapies for glioblastoma (GBM) such as bevacizumab (BVZ), have been unable to extend survival in large patient cohorts. However, a subset of patients having angiogenesis-dependent tumors might benefit from these therapies. Currently, there are no biomarkers allowing to discriminate responders from non-responders before the start of the therapy. Methods: 40 patients from the randomized GENOM009 study complied the inclusion criteria (quality of images, clinical data available). Of those, 23 patients received first line temozolomide (TMZ) for eight weeks and then concomitant radiotherapy and TMZ. 17 patients received BVZ+TMZ for seven weeks and then added radiotherapy to the treatment. Clinical variables were collected, tumors segmented and several geometrical measures computed including: Contrast enhancing (CE), necrotic, and total volumes; equivalent spherical CE width; several geometric measures of the CE ‘rim’ geometry and a set of image texture measures. The significance of the results was studied using Kaplan-Meier and Cox proportional hazards analysis. Correlations were assessed using Spearman correlation coefficients. Results: Kaplan-Meier and Cox proportional hazards analysis showed that total, CE and inner volume (p = 0.019, HR = 4.258) and geometric heterogeneity of the CE areas (p = 0.011, HR = 3.931) were significant parameters identifying response to BVZ. The group of patients with either regular CE areas (small geometric heterogeneity, median difference survival 15.88 months, p = 0.011) or those with small necrotic volume (median survival difference 14.50 months, p = 0.047) benefited substantially from BVZ. Conclusion: Imaging biomarkers related to the irregularity of contrast enhancing areas and the necrotic volume were able to discriminate GBM patients with a substantial survival benefit from BVZ. A prospective study is needed to validate our results. [ABSTRACT FROM AUTHOR]

Published
2016
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2. Geometrical Measures Obtained from Pretreatment Postcontrast T1 Weighted MRIs Predict Survival Benefits from Bevacizumab in Glioblastoma Patients

Author

R. Luque, Víctor M. Pérez-García, Gaspar Reynes, Jaume Capellades, Julián Pérez-Beteta, Miguel Gil-Gil, David Molina, Sergi Peralta, Ana Herrero, Ramon De Las Penas, Juan Manuel Sepúlveda, Alicia Martínez-González, Carmen Balana, [Molina, David] Univ Castilla La Mancha, Inst Matemat Aplicada Ciencia & Ingn, Lab Math Oncol MoLAB, Edificio Politecn,Avda Camilo Jose Cela 3, E-13071 Ciudad Real, Spain, [Perez-Beteta, Julian] Univ Castilla La Mancha, Inst Matemat Aplicada Ciencia & Ingn, Lab Math Oncol MoLAB, Edificio Politecn,Avda Camilo Jose Cela 3, E-13071 Ciudad Real, Spain, [Martinez-Gonzalez, Alicia] Univ Castilla La Mancha, Inst Matemat Aplicada Ciencia & Ingn, Lab Math Oncol MoLAB, Edificio Politecn,Avda Camilo Jose Cela 3, E-13071 Ciudad Real, Spain, [Perez-Garcia, Victor M.] Univ Castilla La Mancha, Inst Matemat Aplicada Ciencia & Ingn, Lab Math Oncol MoLAB, Edificio Politecn,Avda Camilo Jose Cela 3, E-13071 Ciudad Real, Spain, [Sepulveda, Juan M.] Hosp Univ 12 Octubre, Med Oncol Serv, Madrid, Spain, [Peralta, Sergi] Hosp St Joan de Reus, Med Oncol Serv, Reus, Spain, [Gil-Gil, Miguel J.] Inst Catala Oncol IDIBELL, Med Oncol Serv, Barcelona, Spain, [Reynes, Gaspar] Hosp Univ La Fe, Med Oncol Serv, Valencia, Spain, [Herrero, Ana] Hosp Miguel Servet, Med Oncol Serv, Zaragoza, Spain, [De Las Penas, Ramon] Hosp Prov Castellon, Med Oncol Serv, Castellon de La Plana, Spain, [Capellades, Jaume] Hosp Univ Virgen de las Nieves, Med Oncol Serv, Granada, Spain, [Capellades, Jaume] Hosp del Mar, Radiol Serv, Neuroradiol Sect, Barcelona, Spain, [Balana, Carmen] Hosp Badalona Germans Trias & Pujol, IGTP, Inst Catala Oncol, Med Oncol Serv, Badalona, Spain, Ministerio de Economia y Competitividad/FEDER, Spain, Consejeria de Educacion Cultura y Deporte from Junta de Comunidades de Castilla-La Mancha, Spain, James S. Mc. Donnell Foundation 21st Century Science Initiative in Mathematical and Complex Systems Approaches for Brain Cancer, [Molina,D, Pérez-Beteta,J, Martínez-González,A, Pérez-García,VM] Laboratory of Mathematical Oncology (MôLAB), Instituto de Matemática Aplicada a la Ciencia y la Ingeniería, Universidad de Castilla-La Mancha, Ciudad Real, Spain. [Sepúlveda,JM] Medical Oncology Service, Hospital Universitario, 12 de Octubre, Madrid, Spain. [Peralta,S] Medical Oncology Service, Hospital Sant Joan de Reus, Reus, Spain. [Gil-Gil,MJ] Medical Oncology Service, Institut Catalá d’Oncologia IDIBELL, Hospitalet de Llobregat, Barcelona, Spain. [Reynes,G] Medical Oncology Service, Hospital Universitario La Fe, Valencia, Spain. [Herrero,A] Medical Oncology Service, Hospital Miguel Servet, Zaragoza, Spain. [De Las Peñas,R] Medical Oncology Service, Hospital Provincial de Castellón, Castellón, Spain. [Luque,R] Medical Oncology Service, Hospital Universitario Virgen de las Nieves, Granada, Spain. [Capellades,J] Neuroradiology Section. Radiology Service. Hospital del Mar, Barcelona, Spain. [Balaña,C] Medical Oncology Service, Institut Català d’Oncologia, IGTP, Hospital Universitari Germans Trias i Pujol, Badalona, Spain., and This work has been supported by Ministerio de Economía y Competitividad/FEDER, Spain [grant number MTM2015-71200-R], Consejería de Educación Cultura y Deporte from Junta de Comunidades de Castilla-La Mancha, Spain [grant number PEII-2014-031-P] and James S. Mc. Donnell Foundation 21st Century Science Initiative in Mathematical and Complex Systems Approaches for Brain Cancer [Special Initiative Collaborative – Planning Grant 220020420 and Collaborative award 220020450].

Subjects
Male, Cervell Tumors, medicine.medical_treatment, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Globulins::Serum Globulins::Immunoglobulins::Antibodies::Antibodies, Monoclonal::Antibodies, Monoclonal, Humanized::Bevacizumab [Medical Subject Headings], Cancer Treatment, United-states, lcsh:Medicine, Diagnóstico por imagen, Angiogenesis Inhibitors, Kaplan-Meier Estimate, Biochemistry, Diagnostic Radiology, 0302 clinical medicine, Estudios prospectivos, Antineoplastic Combined Chemotherapy Protocols, Medicine and Health Sciences, Image Processing, Computer-Assisted, Blastomas, Inhibidores de la angiogénesis, Prospective Studies, lcsh:Science, Prospective cohort study, Neurological Tumors, Neoadjuvant therapy, Multidisciplinary, medicine.diagnostic_test, Brain Neoplasms, Radiology and Imaging, Middle Aged, Dacarbazina, Prognosis, Magnetic Resonance Imaging, Neoadjuvant Therapy, Tumor Burden, Bevacizumab, Treatment Outcome, Oncology, Neurology, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Growth Substances::Angiogenesis Modulating Agents::Angiogenesis Inhibitors [Medical Subject Headings], Research Design, 030220 oncology & carcinogenesis, Marcadors bioquímics, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging [Medical Subject Headings], Female, Radiology, Research Article, medicine.drug, Tractament adjuvant del càncer, Clinical Oncology, Adult, medicine.medical_specialty, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Imaging Techniques, Chemicals and Drugs::Biological Factors::Biomarkers [Medical Subject Headings], Radiation Therapy, Antineoplastic Agents, Cancer adjuvant treatment, Image Analysis, Research and Analysis Methods, Brain tumors, 03 medical and health sciences, Diagnostic Medicine, Chemicals and Drugs::Biological Factors::Biological Markers [Medical Subject Headings], medicine, Temozolomide, Tumors cerebrals, Humans, Aged, Proportional Hazards Models, Chemicals and Drugs::Organic Chemicals::Triazenes::Dacarbazine [Medical Subject Headings], Radiotherapy, business.industry, Proportional hazards model, lcsh:R, Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Germ Cell and Embryonal::Neuroectodermal Tumors::Neoplasms, Neuroepithelial::Glioma::Astrocytoma::Glioblastoma [Medical Subject Headings], Biology and Life Sciences, Cancers and Neoplasms, Magnetic resonance imaging, Surgery, Radiation therapy, Biomarcadores, Concomitant, Waves, lcsh:Q, Clinical Medicine, business, Glioblastoma, Glioblastoma Multiforme, 030217 neurology & neurosurgery, Biomarkers
Abstract

BACKGROUND: Antiangiogenic therapies for glioblastoma (GBM) such as bevacizumab (BVZ), have been unable to extend survival in large patient cohorts. However, a subset of patients having angiogenesis-dependent tumors might benefit from these therapies. Currently, there are no biomarkers allowing to discriminate responders from non-responders before the start of the therapy. METHODS: 40 patients from the randomized GENOM009 study complied the inclusion criteria (quality of images, clinical data available). Of those, 23 patients received first line temozolomide (TMZ) for eight weeks and then concomitant radiotherapy and TMZ. 17 patients received BVZ+TMZ for seven weeks and then added radiotherapy to the treatment. Clinical variables were collected, tumors segmented and several geometrical measures computed including: Contrast enhancing (CE), necrotic, and total volumes; equivalent spherical CE width; several geometric measures of the CE 'rim' geometry and a set of image texture measures. The significance of the results was studied using Kaplan-Meier and Cox proportional hazards analysis. Correlations were assessed using Spearman correlation coefficients. RESULTS: Kaplan-Meier and Cox proportional hazards analysis showed that total, CE and inner volume (p = 0.019, HR = 4.258) and geometric heterogeneity of the CE areas (p = 0.011, HR = 3.931) were significant parameters identifying response to BVZ. The group of patients with either regular CE areas (small geometric heterogeneity, median difference survival 15.88 months, p = 0.011) or those with small necrotic volume (median survival difference 14.50 months, p = 0.047) benefited substantially from BVZ. CONCLUSION: Imaging biomarkers related to the irregularity of contrast enhancing areas and the necrotic volume were able to discriminate GBM patients with a substantial survival benefit from BVZ. A prospective study is needed to validate our results. This work has been supported by Ministerio de Economía y Competitividad/FEDER, Spain [grant number MTM2015-71200-R], Consejería de Educación Cultura y Deporte from Junta de Comunidades de Castilla-La Mancha, Spain [grant number PEII-2014-031-P] and James S. Mc. Donnell Foundation 21st Century Science Initiative in Mathematical and Complex Systems Approaches for Brain Cancer [Special Initiative Collaborative – Planning Grant 220020420 and Collaborative award 220020450]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Published
2016

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