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Apparent Diffusion Coefficient in recurrent Glioblastoma treated with Bevacizumab Oscar S. Chirife , Teresa Pujol, Joan Berenguer, Javier Moreno, Izaskun Valduvieco, Eugenia Verger, Laura Oleaga.

Apparent Diffusion Coefficient in recurrent Glioblastoma treated with Bevacizumab Oscar S. Chirife, Teresa Pujol, Joan Berenguer, Javier Moreno, Izaskun

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Page 1: Apparent Diffusion Coefficient in recurrent Glioblastoma treated with Bevacizumab Oscar S. Chirife, Teresa Pujol, Joan Berenguer, Javier Moreno, Izaskun

Apparent Diffusion Coefficient in recurrent Glioblastoma treated with Bevacizumab

Oscar S. Chirife , Teresa Pujol, Joan Berenguer, Javier Moreno, Izaskun Valduvieco, Eugenia Verger, Laura

Oleaga.

Page 2: Apparent Diffusion Coefficient in recurrent Glioblastoma treated with Bevacizumab Oscar S. Chirife, Teresa Pujol, Joan Berenguer, Javier Moreno, Izaskun

BACKGROUND

• Glioblastomas (GB) are the most aggressive and lethal primary brain tumors.

• Treatment with bevacizumab (BV) for recurrent GB in patients treated with standard radiotherapy (RT) and temozolamide (TMZ) has demonstrated in different studies a significant overall survival.

• The Apparent Diffusion Coefficient (ADC) as a imaging biomarker has been correlated with prognosis in newly diagnosed gliomas.

Page 3: Apparent Diffusion Coefficient in recurrent Glioblastoma treated with Bevacizumab Oscar S. Chirife, Teresa Pujol, Joan Berenguer, Javier Moreno, Izaskun

•To evaluate ADC values in patients with recurrent GB treated with BV.

•To correlate ADC with clinical and radiological response, progression-free (PFS) and overall survival (OS).

PURPOSE

Page 4: Apparent Diffusion Coefficient in recurrent Glioblastoma treated with Bevacizumab Oscar S. Chirife, Teresa Pujol, Joan Berenguer, Javier Moreno, Izaskun

MATERIAL AND METHODS

PATIENTS•Ten consecutive adult patients with proven recurrent or progressive GB after RT/ TMZ therapy determined by the RANO criteria and treated with BV, were enrolled.

•Clinical status was assessed using the Karnofsky Performance Scale (KPS).

Page 5: Apparent Diffusion Coefficient in recurrent Glioblastoma treated with Bevacizumab Oscar S. Chirife, Teresa Pujol, Joan Berenguer, Javier Moreno, Izaskun

IMAGING PROTOCOL

Sagittal 3D T1W

Diffusion Tensor imaging (30 directions)

Axial T1W SE

Axial FLAIR

SWI 

Sagittal 3D T2W TSE

First-pass echo-planar dynamic susceptibility-weighted contrast-enhanced (DSC)

Sagittal 3D T1-weighted +Gad

Axial T1W SE post Gad

Page 6: Apparent Diffusion Coefficient in recurrent Glioblastoma treated with Bevacizumab Oscar S. Chirife, Teresa Pujol, Joan Berenguer, Javier Moreno, Izaskun

MR ASSESSMENT

• Both pre and first post BV MR were analyzed.

• The evaluation was performed by two experienced neuroradiologists active members of the multidisciplinary brain tumor board (LO y TP).

Page 7: Apparent Diffusion Coefficient in recurrent Glioblastoma treated with Bevacizumab Oscar S. Chirife, Teresa Pujol, Joan Berenguer, Javier Moreno, Izaskun
Page 8: Apparent Diffusion Coefficient in recurrent Glioblastoma treated with Bevacizumab Oscar S. Chirife, Teresa Pujol, Joan Berenguer, Javier Moreno, Izaskun

STATISTICAL ANALYSIS

• The correlation of the ADC value with the response to BV was evaluated using the Fisher’s exact test

• PFS and OS were correlated with the ADC values using Kaplan-Meier and log-rank test

• Statistical analyses were performed using the statistical package SPSS 17

Page 9: Apparent Diffusion Coefficient in recurrent Glioblastoma treated with Bevacizumab Oscar S. Chirife, Teresa Pujol, Joan Berenguer, Javier Moreno, Izaskun

RESULTS

Mean (range)

Age 59 (40-74)

KPS 80 (50-100)

FPS (months) 6 (1-11)

OS (months) 8 (1-13)

mADC CONTRAST ENHANCEMENT PRE BV

1297 (1025-1483)

lowADC CONTRAST ENHANCEMENT PRE BV

828 (568-1050)

mADC FLAIR ABNORMALITY PRE BV

1387 (1068-1631)

Page 10: Apparent Diffusion Coefficient in recurrent Glioblastoma treated with Bevacizumab Oscar S. Chirife, Teresa Pujol, Joan Berenguer, Javier Moreno, Izaskun
Page 11: Apparent Diffusion Coefficient in recurrent Glioblastoma treated with Bevacizumab Oscar S. Chirife, Teresa Pujol, Joan Berenguer, Javier Moreno, Izaskun
Page 12: Apparent Diffusion Coefficient in recurrent Glioblastoma treated with Bevacizumab Oscar S. Chirife, Teresa Pujol, Joan Berenguer, Javier Moreno, Izaskun

ADC VALUES AND PROGRESSION

Page 13: Apparent Diffusion Coefficient in recurrent Glioblastoma treated with Bevacizumab Oscar S. Chirife, Teresa Pujol, Joan Berenguer, Javier Moreno, Izaskun
Page 14: Apparent Diffusion Coefficient in recurrent Glioblastoma treated with Bevacizumab Oscar S. Chirife, Teresa Pujol, Joan Berenguer, Javier Moreno, Izaskun

CONCLUSIONS

Patients with high ADC values (mADC>1300 10-6mm2/s and lowADC>800 10-6mm2/s) in the pretreatment study show a higher OS, and can be useful to predict survival in patients with recurrent GB treated with bevacizumab.

This is a preliminary study (working progress) and more patients should be included to confirm results.

Page 15: Apparent Diffusion Coefficient in recurrent Glioblastoma treated with Bevacizumab Oscar S. Chirife, Teresa Pujol, Joan Berenguer, Javier Moreno, Izaskun

REFERENCES• Murakami R, Sugahara T, Nakamura H et al (2007) Malignant supratentorial astrocytoma treated with postoperative

radiation therapy: prognostic value of pretreatment quantitative diffusion weighted MR imaging. Radiology 243:493–499

• Stupp R, Mason WP, van den Bent MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996

• Norden AD, Drappatz J, Wen PY (2009) Antiangiogenic therapies for high-grade glioma. Nat Rev Neurol 5:610–620

• Macdonald DR, Cascino TL, Schold SC Jr et al (1990) Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8:1277–1280

• Nagane M, Kobayashi K, Tanaka et al (2013) Predictive significance of mean apparent diffusion coefficient value for responsiveness of temozolomide-refractory malignant glioma to bevacizumab: preliminary report. Int J Clin Oncol. DOI 10.1007/s10147-013-0517-x

• Pope WB, Lai A, Mehta R et al (2011) Apparent diffusion coefficient histogram analysis stratifies progression-free survival in newly diagnosed bevacizumab-treated glioblastoma. AJNR Am J Neuroradiol 32:882–889

• Pope WB, Kim HJ, Huo J et al (2009) Recurrent glioblastoma multiforme: ADC histogram analysis predicts response to bevacizumab treatment. Radiology 252:182–189-

• Grupo Neurooncología de la Sociedad Española de Nauroradiología (2011). Criterios de respuesta de los tumores cerebrales. Disponible en: http://www.senr.org/pdf/section_4/Criterios_respuesta_Neuroon2011.pdf