Bart Roelf Jan van Dijken1, Chao Li2,3, Peter Jan van Laar1, Shuo Wang4,5, Stephen J Price2, and Anouk van der Hoorn1,2
1Radiology, Medical Imaging Center (MIC), University Medical Center Groningen, University of Groningen, Groningen, Netherlands, 2Brain Tumour Imaging Group, Division of Neurosurgery, Department of Clinical Neurosciences, Addenbrooke’s hospital, University of Cambridge, Cambridge, United Kingdom, Cambridge, United Kingdom, 3Department of Neurosurgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, China, Shanghai, China, 4Department of Radiology, University of Cambridge, Cambridge, UK, Cambridge, United Kingdom, 5The Centre for Mathematical Imaging in Healthcare, Department of Pure Mathematics and Mathematical Statistics, University of Cambridge, Cambridge, United Kingdom
Synopsis
The purpose of this study was to investigate the prognostic value of anisotropic diffusion abnormality in 30 treated glioblastoma patients. Diffusion tensor imaging was performed after chemoradiotherapy and volumes of diffusion abnormalities were extracted. Our results showed that a larger volume of high anisotropic abnormality was associated with worsened patient survival. Anisotropic diffusion can therefore potentially be employed as a prognostic imaging marker in longitudinal management of glioblastoma patients.
Introduction
Glioblastomas are highly malignant brain tumors characterized by diffuse infiltration into the peritumoral brain parenchyma. Anatomical imaging features such as contrast enhancement are known to have limitations in identifying tumor infiltration and progression. Moreover, although often being integrated into clinical assessment, the hyperintensity shown on FLAIR is also prone to be non-specific in differentiating tumor infiltration from edema due to white matter changes associated with radiotherapy. Diffusion tensor imaging (DTI) is capable of detecting microstructural changes caused by tumor infiltration and has been reported to be useful in revealing tumor infiltration.1 Previous studies showed that the anisotropic diffusion is associated with higher tumor burden and can be of particular prognostic value.2,3 However, the prognostic value of anisotropic diffusion in post-treatment management of glioblastomas is still unclear. Therefore, the purpose of this study was to investigate whether the post-treatment anisotropic abnormality could indicate treatment failure and tumor recurrence, in a patient cohort undergoing standard treatment.Methods
Patients:
Thirty newly diagnosed glioblastoma patients (median age 56.7 years, range 31 – 68 years, 70% males) undergoing standard treatment were retrospectively recruited. Diagnosis was histopathologically confirmed after maximal safe resection (N=24) or biopsy (N=5). Concomitant chemoradiation therapy (CCRT) followed by 6 cycles of temozolomide chemotherapy according to the Stupp protocol4 was received by all patients. The Response Assessment in Neuro-Oncology (RANO)5 criteria were used to evaluate recurrent disease.
Imaging
All MRI images were acquired on the same 1.5T scanner after completion of CCRT. Sequences included pre- and post-contrast T1 weighted, T2-weighted, FLAIR images, and DTI. All sequences were co-registered to the post-contrast T1 weighted images. The diffusion tensor was deconstructed into isotropic and anisotropic components.6 The peritumoral FLAIR signal outside the contrast enhancement was semi-automatically delineated. Volumes of FLAIR signal, isotropic abnormality and anisotropic abnormality were extracted.
Statistics
Volumes of diffusion abnormalities with survival data using Cox proportional hazards model. Subsequently, a 12-month cut-off was used to categorize tumors into early and late recurrence and differences in volume were compared using independent sample t-tests.
Results
Median volumes of FLAIR, isotropic and anisotropic abnormalities were 18.2 cm3, 17.6 cm3 and 14.0 cm3, respectively. A larger volume of high anisotropic abnormality was negatively associated with progression-free survival (PFS) (hazard ratio 1.013, 95%CI 1.001–1.025, p=0.029) and overall survival (OS) (hazard ratio 1.025, 95%CI 1.012–1.038, p<0.001). Isotropic abnormalities were not associated with survival, while FLAIR volume was only associated with OS (hazard ratio 1.020, 95%CI 1.010–1.032, p<0.001), but not with PFS. Patients with early recurrence (≤12 months) demonstrated a significantly larger volume of high anisotropic abnormalities than patients with later recurrence, 41.4 ±39.4 cm3 vs 12.4 ±10.7 cm3 respectively(p=0.008). Discussion
Our results showed that larger volumes of high anisotropic abnormalities were associated with worsened patient survival in a cohort that has received standard temozolomide chemoradiotherapy. In accordance with previous findings, our results showed that the hyperintensity region on FLAIR images is non-specific for tumor progression.2 The higher anisotropic diffusion, however, may be particularly associated with tumor progression and worse patient survival. High anisotropic abnormalities possibly indicate a sub-region which facilitates tumor infiltration3 along white matter tracts and hence be responsible for tumor recurrence. Conclusion
Our findings suggest that anisotropic diffusion can potentially be employed as an early imaging marker for prognostic stratification in longitudinal management of glioblastoma patients. Acknowledgements
No acknowledgement found.References
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