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MO_12_2767 - The Role of High B-Value Diffusion MRI in the Molecular Classification of Lower Grade Gliomas

Monday, October 22
10:45 AM - 12:15 PM
Location: Innovation Hub, Exhibit Hall 3

The Role of High B-Value Diffusion MRI in the Molecular Classification of Lower Grade Gliomas
A. M. Laucis1, M. M. Kim1, T. S. Lawrence1, and Y. Cao1,2; 1Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, 2Departments of Radiology and Biomedical Engineering, University of Michigan, Ann Arbor, MI

Purpose/Objective(s):

Molecular glioma features help describe tumor aggressiveness and predict treatment response. However, the role of advanced imaging in characterizing gliomas remains less well-defined. Hypercellularity volume (HCV) identified by a novel diffusion weighted (DW) MRI technique is prognostic for PFS in glioblastoma (GBM), though its relation with prognostic factors in lower grade gliomas has not been elucidated (Pramanik et al IJROBP 2015). We hypothesized a potential correlation between restricted diffusion and poor prognostic molecular features in patients undergoing radiation (RT) for lower grade gliomas.

Materials/Methods: Patients with available advanced MRIs who were given RT for newly diagnosed, previously untreated grade 2-3 gliomas were identified. Tumor volumes were contoured based on T2/FLAIR sequences and T1-post contrast images (if enhancement was present). The HCV was calculated on b-value=3000s/mm2 DW images with a threshold >mean+2SD of the contralateral normal tissue. The normalized max and mean HCV intensities (Dmax and Dmean) were determined from histogram analysis. The Mann-Whitney Test was used to compare HCV metrics with IDH, 1p19q, and Ki-67 (at a threshold of 10%, the median in this cohort). Analysis of variance (ANOVA) was used to compare p53 mutation presence (negative, weak (≤5%), and positive) as defined by IHC and to compare IDH mutant/1p19q co-deleted (IDHm/codel), IDHm/non-codel, and IDH wild-type (IDHwt) molecular subgroups.

Results: Between Nov 2010 and Aug 2017, 39 patients with median age of 49 years (range 22-77) meeting the above criteria were identified. After excluding patients with missing images (n=4) and small (<10mm3) HCV volumes (n=7), 28 total patients were included in this analysis. There were significant differences in Dmean and Dmax between IDHwt and IDHm patients and within the IDHwt, IDHm/codel and IDHm/non-codel subgroups (p<0.05, Table 1). Higher Dmean and p53 positivity were also significantly correlated on ANOVA (p=0.0063).

Conclusion: Hypercellularity MRI metrics Dmean and Dmax may help provide non-invasive estimates of the underlying biology and serve as a biomarker of molecular subgrouping and IDH mutation status in lower grade gliomas. Further analysis in a larger patient population will permit evaluation of a multi-parametric model to help stratify patients with distinct biology and prognosis.    Table 1: Relationship Between High B-value Diffusion MRI and Glioma Characteristics

 

 

Median Values

P-values

 

n

Dmean

Dmax

HCV volume (cm3)

Dmean

Dmax

HCV volume (cm3)

Histology

 

 

 

 

0.70

0.11

0.73

Oligodendroglioma Astrocytoma

12

16

1.6

1.6

2.3

1.5

2.7

4.2

 

 

 

Ki-67

 

 

 

 

0.67

0.89

0.67

Low High

14

10

1.8

1.6

2.2

1.5

3.0

3.9

 

 

 

p53

 

 

 

 

0.0063

0.13

0.36

Negative Weak Positive

6

5

13

1.5

1.5

2.0

2.0

1.4

2.1

6.9

2.4

3.9

 

 

 

IDH

 

 

 

 

0.0008

0.003

0.33

Wild-type Mutated

15

11

1.5

2.1

1.4

2.4

3.2

3.9

 

 

 

1p19q

 

 

 

 

>0.99

0.45

>0.99

Non-codel Codel

12

4

1.9

1.9

2.2

3.2

3.0

5.3

 

 

 

Molecular Subgroup

 

 

 

 

0.0006

0.0136

0.36

IDHwt IDHm/non-codel IDHm/codel

15

8

2

1.5

2.1

2.4

1.4

2.4

4.1

3.2

3.5

11

 

 

 

 

Author Disclosure: A.M. Laucis: None. M.M. Kim: Research Grant; EpicentRx. T.S. Lawrence: royalties; Lippincott, Williams and Wilkins. Honoraria; Massachusetts General Hospital, Pfizer Oncology Innovation Summit, Sidney Kimmel Foundation for Cancer Research. Consultant; Pfizer Oncology Innovation Summit. Advisory Board; ASTRO Radiation Oncology Institute, Dana Farber Cancer Institute, Massachusetts General Hospital, Sidney Kimmel Compreh Cancer Ctr at Johns Hopkins, Sidney Kimmel Foundation for Cancer Research, St. Jude Children's Research Hospital, University of Wisconsin Comprehensive Cancer Ctr. Travel Expenses; AACR, ASTRO Radiation Oncology Institute, Dana Farber Cancer Institute, Lippincott, Williams and Wilkins, Massachusetts General Hospital, Pfizer Oncology Innovation Summit, RSNA, Sidney Kimmel Compreh Cancer Ctr at Johns Hopkins, Sidney Kimmel Foundation for Cancer Research, St. Jude Children's Research Hospital, University of Wisconsin Comprehensive Cancer Ctr. Patent/License Fees/Copyright; Pi Squared Therapeutics. Editor, Cancer Discovery; AACR. Member, Editorial Advisory Board, Cancer Today; AACR. Senior Editor, Cancer Research; AACR. Member, External Advisory Board for Lung SPORE; Dana Farber Cancer Institute. Co-Editor of Principles and Practices of Oncology; Lippincott, Williams and Wilkins. Member, NCI Board of Scientific Advisors; NCI - BSA. President; ROI. Member, External Advisory Board for the Cancer Ctr; Sidney Kimmel CCC at Johns Hopkins University. Member of the Medical Advisory Board; Sidney Kimmel Foundation for Cancer Research. Vice-Chair, St. Jude Scientific Advisory Board; St. Jude Children's Research Hospital. Member, V Foundation Scientific Advisory Board; V Foundation for Cancer Research. Y. Cao: Research Grant; NIH, Siemens. Honoraria; Siemens.

Anna Laucis, MD, MPhil

Disclosure:
No relationships to disclose.

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