To analyse whether ADC values have a correlation with survival or EGFR amplification status in glioblastoma
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1 To analyse whether ADC values have a correlation with survival or EGFR amplification status in glioblastoma R. Zalazar, M. Páramo, M. Hernández, P. Domínguez, J.Etxano, P.García Barquín, H.Quiceno Arias, E. Guillen; M. García de Eulate; Clínica Universidad de Navarra, Pamplona/ES
2 Introduction Glioblastoma is the most common and most aggressive primary brain tumor in adults. Poor prognosis (median survival 15 months). Variable patient survival.
3 Introduction BIOMARKERS IMAGING Perfusion-MRI (rcbv) Diffusion-MRI (ADC) MOLECULAR - MGMT - EGFR - PTEN Epidermal growth factor receptor (EGFR): Is commonly overexpressed in adults with high-grade gliomas
4 Introduction BIOMARKERS IMAGING Perfusion-MRI (rcbv) Diffusion-MRI (ADC) MOLECULAR - MGMT - EGFR - PTEN DWI (ADC): Has an inverse relationship with the tumor cellulary and glioma grade, for that reason it has been proposed as a predictor of prognosis.
5 Objective 1 2 To analyse if:. Values of apparent diffusion coefficient (ADC) correlate with survival.. Values of ADC can predict the amplification status of EGFR.
6 Material and Methods Retrospective Study Oct Feb 2012 Newly diagnosis of GBM without previous treatment Inclusion Criteria At least 12 months follow-up or until their death MRI preoperative EGFR Amplification 78 patients 49 patients were included 29 were excluded
7 MRI examination 4º SWI 1º DWI b1000 2º ADC 3º T1 + G
8 MRI examination 4º SWI 1º DWI b1000 2º 3º ADC T1 + G
9 MRI examination 4º SWI 1º DWI b1000 2º ADC 3º T1 + G
10 MRI examination 4º SWI 1º DWI b1000 2º ADC 3º T1 + G
11 MRI examination ROI 1 DWI b1000 ADC T1 + G
12 MRI examination ROI 2 T2 FLAIR ADC T1 + G
13 Material and Methods ADC index: ADC min SC / ADC mean NCWM
14 Material and Methods Clinical Molecular Surgical Imaging Age Sex Karnofsky Performan ce Score EGFR status Presurgical volume Postsurgical volume ADCmin SC ADCindex: Statistical analyses (SPSS 20.0). T-wilcoxon. ROC curves. Kaplan-Meier method. Cox regression model
15 Material and Methods 1º Group n = 49 2º Group n = 19 3º Group n = 30
16 Material and Methods 1º Group n = 49 Independent of EGFR status ADCindex <0,7 (n=15) ADCindex >0,7 (n=34) 2º Group n = 19 3º Group n = 30
17 Material and Methods 1º Group n = 49 Independent of EGFR status ADCindex <0,7 (n=15) ADCindex >0,7 (n=34) 2º Group n = 19 EGFR amplification ADCindex <0,7 (n=5) ADCindex >0,7(n=14) 3º Group n = 30
18 Material and Methods 1º Group n = 49 Independent of EGFR status ADCindex <0,7 (n=15) ADCindex >0,7 (n=34) 2º Group n = 19 EGFR amplification ADCindex <0,7 (n=5) ADCindex >0,7(n=14) 3º Group n = 30 EGFR non amplification ADCindex <0,7 (n=10) ADCindex >0,7(n=20)
19 Results PATIENT CHARACTERISTICS Age (years) Median (range) 60 (28-78) Sex Men 24 Women 25 KPS Median (range) 75 (40-100) Survival (months) Median (range) PFS 7,4 ( ) TUMOR CHARACTERISTICS EGFR amplification n (%) Yes 19/49 (38,8%) No 30/49 (61,2%) Tumoral Volumen (cm 3 ) Mean ( SD) Presurgical 42,1 ( 26.9) Postsurgical 0,65 ( 2,20) OS 18,7 (4,4-42,6)
20 Results PATIENT CHARACTERISTICS Age (years) Median (range) 60 (28-78) Sex Men 24 Women 25 KPS Median (range) 75 (40-100) Survival (months) Median (range) PFS 7,4 ( ) TUMOR CHARACTERISTICS EGFR amplification n (%) NON AMPLIFICATION 61% No 30/49 (61,2%) Tumoral Volumen (cm 3 ) Mean ( SD) Presurgical 42,1 ( 26.9) Postsurgical 0,65 ( 2,20) OS 18,7 (4,4-42,6)
21 Results PATIENT CHARACTERISTICS Age (years) Median (range) 60 (28-78) Sex Men 24 Women 25 KPS Median (range) 75 (40-100) Survival (months) Median (range) PFS 7,4 ( ) TUMOR CHARACTERISTICS EGFR amplification n (%) Yes 19/49 (38,8%) No 30/49 (61,2%) Tumoral Volumen (cm 3 ) Mean ( SD) Presurgical 42,1 ( 26.9) POST-SURGICAL 0,65 ( 2,20) Postsurgical 0,65 ( 2,20) OS 18,7 (4,4-42,6)
22 Results p=ns AUC: 0,55 non amplification EGFR status amplification
23 Results Univariate analysis PFS OS HR (95% CI) p value HR (95% CI) p value Age 1,01 (0,98-1,04) 0,34 1,04 (1,0-1,08) 0.01 Sex 0,71 (0,36-1,3) NS 1,29 (0,6-2,52) NS KPS 0.98 ( ) NS 0,97 (0,95-1,00) 0.89 EGFR amplif. status 0,59 (0,30-0,38) NS 0,95 (0,48-1,87) NS Presurgical Volumen 0,99 (0,98-1,0) NS 1,00 (0,99-1,01) NS Postsurgical Volumen 0,97 (0,83-1,14) NS 0,96 (0,81-1,15) NS ADCmin Solid Component 0,51 (0,03-6,91) NS 0,01 (0,001-0,3) <0,006 ADCindex 0,75 (0,24-2,31) NS 0,09 (0,01-0,72) <0,02
24 Results Univariate analysis PFS OS Age Sex KPS EGFR amplif. status Presurgical Volumen Postsurgical Volumen ADCmin Solid Component ADCindex HR (95% CI) p value HR (95% CI) p value EGFR amplification status p=ns p=ns
25 Results Univariate analysis PFS OS HR (95% CI) p value HR (95% CI) p value Age 1,01 (0,98-1,04) 0,34 1,04 (1,0-1,08) 0,01 Sex 0,71 (0,36-1,3) NS 1,29 (0,6-2,52) NS KPS 0.98 ( ) NS 0,97 (0,95-1,00) 0.89 EGFR amplif. status 0,59 (0,30-0,38) NS 0,95 (0,48-1,87) NS Presurgical Volumen 0,99 (0,98-1,0) NS 1,00 (0,99-1,01) NS Postsurgical Volumen 0,97 (0,83-1,14) NS 0,96 (0,81-1,15) NS ADCmin Solid Component 0,51 (0,03-6,91) NS 0,01 (0,001-0,3) <0,006 ADCindex 0,75 (0,24-2,31) NS 0,09 (0,01-0,72) <0,02
26 Results Univariate analysis PFS OS HR (95% CI) p value HR (95% CI) p value Age AGE Sex p=0,01 KPS EGFR amplif. status Presurgical Volumen Postsurgical Volumen ADCmin SC ADCmin Solid Component ADCindex ADCindex os HR:0,09 <0,006 <0,02
27 Results Univariate analysis PFS OS HR (95% CI) p value HR (95% CI) p value Age AGE Sex p=0,01 KPS EGFR amplif. status Presurgical Volumen Postsurgical Volumen ADCmin SC ADCmin Solid Component ADCindex ADCindex os HR:0,09 <0,006 <0,02 HR:0,09 Tumors with higher values of ADC had longer SURVIVAL
28 Results Multivariate analysis PFS OS HR (95% CI) p value HR (95% CI) p value Age 3,2 (1,6-6,7) 0,001 1,06 (1,02-1,11) 0,001 ADCmin Solid Component 0,40 (0,02-7,7) 0,54 0,006 (0,00-0,18) 0,003 * Adjusted for, age, sex, EGFR, presurgical and postsurgical volumen.
29 Results Multivariate analysis PFS OS HR (95% CI) p value HR (95% CI) p value Age 3,2 (1,6-6,7) 0,001 1,06 (1,02-1,11) 0,001 ADCmin Solid Component 0,40 (0,02-7,7) 0,54 0,006 (0,00-0,18) 0,003 * Adjusted for, age, sex, EGFR, presurgical and postsurgical volumen.
30 Results Multivariate analysis PFS OS HR (95% CI) p value HR (95% CI) p value Age 3,2 (1,6-6,7) 0,001 1,06 (1,02-1,11) 0,001 ADCmin Solid Component 0,40 (0,02-7,7) 0,54 0,006 (0,00-0,18) 0,003 * Adjusted for, age, sex, EGFR, presurgical and postsurgical volumen.
31 1º Group n = 49 Independent of EGFR status ADCindex <0,7 ADCindex >0,7 Results
32 CUMULATIVE SURVIVAL NIVERSITAS STVDIORV Independent of the EGFR status Results p=0,079 ADCindex Independent of the EGFR status ADCindex >0,7 Progression Free Survival ADCindex <0,7
33 CUMULATIVE SURVIVAL NIVERSITAS STVDIORV Independent of the EGFR status Results p<0,001 ADCindex Independent of the EGFR status ADCindex >0,7 Overall Survival ADCindex <0,7
34 2º Group n = 25 Results EGFR amplification ADCindex <0,7 (n=5) ADCindex >0,7(n=20)
35 CUMULATIVE SURVIVAL NIVERSITAS STVDIORV EGFR amplification Results p=0,35 EGFR amplification ADCindex<0,7 ADCindex>0,7 ADCindex >0,7 ADCindex <0,7
36 CUMULATIVE SURVIVAL NIVERSITAS STVDIORV EGFR amplification Results p=0,02 EGFR amplification ADCindex<0,7 ADCindex>0,7 ADCindex >0,7 ADCindex <0,7
37 3º Group n = 30 Results EGFR non amplification ADCindex <0,7 (n=10) ADCindex >0,7(n=20)
38 CUMULATIVE SURVIVAL NIVERSITAS STVDIORV EGFR non amplification Results p=0,02 EGFR non amplification ADCindex<0,7 ADCindex>0,7 ADCindex >0,7 Progression Free Survival ADCindex <0,7
39 CUMULATIVE SURVIVAL NIVERSITAS STVDIORV EGFR non amplification Results p<0,001 EGFR non amplification ADCindex<0,7 ADCindex>0,7 ADCindex >0,7 Overall Survival ADCindex <0,7
40 Limitations Retrospective nature of the study. Small number of patients. In our study, we did not determine the influence of other molecular markers such as MGMT, that could modify the survival of our patients.
41 Conclusions 1 ADC-index value and ADCmin value could be strong predictors of survival in patients with GBM, independently of the EGFR status.
42 Conclusions 1 ADC-index value and ADCmin value could be strong predictors of survival in patients with GBM, independently of the EGFR status. 2 There were no significant differences in the value of ADCindex in the patients with EGFR amplification and EGFR non amplification status.
43 Conclusions Our findings suggest that ADC values are not useful to predict the EGFR amplification status.. But it is strong independent predictor of OS
44
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