Advanced ADC Histogram, Perfusion, and Permeability Metrics Show an Association with Survival and Pseudoprogression in Newly Diagnosed Diffuse Intrinsic Pontine Glioma: A Report from the Pediatric Brain Tumor Consortium

Abstract

BACKGROUND AND PURPOSE: Diffuse intrinsic pontine glioma is a lethal childhood brain cancer with dismal prognosis and MR imaging is the primary methodology used for diagnosis and monitoring. Our aim was to determine whether advanced diffusion, perfusion, and permeability MR imaging metrics predict survival and pseudoprogression in children with newly diagnosed diffuse intrinsic pontine glioma. MATERIALS AND METHODS: A clinical trial using the poly (adenosine diphosphate ribose) polymerase (PARP) inhibitor veliparib concurrently with radiation therapy, followed by maintenance therapy with veliparib + temozolomide, in children with diffuse intrinsic pontine glioma was conducted by the Pediatric Brain Tumor Consortium. Standard MR imaging, DWI, dynamic contrast-enhanced perfusion, and DSC perfusion were performed at baseline and approximately every 2 months throughout treatment. ADC histogram metrics of T2-weighted FLAIR and enhancing tumor volume, dynamic contrast-enhanced permeability metrics for enhancing tumors, and tumor relative CBV from DSC perfusion MR imaging were calculated. Baseline values, post-radiation therapy changes, and longitudinal trends for all metrics were evaluated for associations with survival and pseudoprogression. RESULTS: Fifty children were evaluable for survival analyses. Higher baseline relative CBV was associated with shorter progression-free survival (P ¼ .02, Q ¼ 0.089) and overall survival (P ¼ .006, Q ¼ 0.055). Associations of higher baseline mean transfer constant from the blood plasma into the extravascular extracellular space with shorter progression-free survival (P ¼ .03, Q ¼ 0.105) and overall survival (P ¼ .03, Q ¼ 0.102) trended toward significance. An increase in relative CBV with time was associated with shorter progression-free survival (P , .001, Q , 0.001) and overall survival (P ¼ .004, Q ¼ 0.043). Associations of longitudinal mean extravascular extracellular volume fraction with progression-free survival (P ¼ .03, Q ¼ 0.104) and overall survival (P ¼ .03, Q ¼ 0.105) and maximum transfer constant from the blood plasma into the extravascular extracellular space with progression-free survival (P ¼ .03, Q ¼ 0.102) trended toward significance. Greater increases with time were associated with worse outcomes. True radiologic progression showed greater post-radiation therapy decreases in mode_ADC_FLAIR compared with pseudoprogression (means, À268.15 versus À26.11, P ¼ .01.) CONCLUSIONS: ADC histogram, perfusion, and permeability MR imaging metrics in diffuse intrinsic pontine glioma are useful in predicting survival and pseudoprogression. ABBREVIATIONS: DCE ¼ dynamic contrast-enhanced; DIPG ¼ diffuse intrinsic pontine glioma; K ep ¼ rate constant from extravascular extracellular space back into blood plasma; K trans ¼ transfer constant from blood plasma into extravascular extracellular space; OS ¼ overall survival; PBTC ¼ Pediatric Brain Tumor Consortium; PFS ¼ progression-free survival; rCBV ¼ relative CBV; RT ¼ radiation therapy; TMZ ¼ temozolomide; v e ¼ extravascular ext...

Correlation of multimodal 18F-DOPA PET and conventional MRI with treatment response and survival in children with diffuse intrinsic pontine gliomas

“…In the current study we evaluated only static 18 F-DOPA PET parameters; as highlighted in a recent research on adult gliomas 40 , dynamic 18 F-DOPA PET analysis in pediatric gliomas might provide additional information in future investigations. Furthermore, in this study we did not compare 18 F-DOPA PET with advanced MR imaging modalities; as highlighted in a recent study which demonstrated a significant association of different advanced MR imaging metrics with survival 41 , prospective clinical trials should be performed in order to evaluate the synergic role of these techniques. We recognize that in the current study we did not evaluate the prognostic role of T/N, even though we used this parameter to stratify tumor uptake patterns and to delineate tumor volume.…”

Hemodynamic Imaging in Cerebral Diffuse Glioma—Part B: Molecular Correlates, Treatment Effect Monitoring, Prognosis, and Future Directions

“…As a result, they are correlated with a worse prognosis while response to chemoradiotherapy has been associated with a decrease in tumor perfusion and BBB permeability. Increased DSC-CBV was found to be predictive of decreased progression free survival [ 20 , 116 , 117 , 118 , 119 , 125 , 126 , 127 ] and decreased OS [ 20 , 71 , 117 , 119 , 122 , 123 , 124 , 125 , 128 , 129 , 130 , 130 , 131 , 132 , 133 , 134 ] in diffuse cerebral gliomas. These parameters can be also used to follow-up on lower grade glioma lesions and to monitor treatment effects [ 122 , 135 , 136 ].…”

“…DSC-CBF has also shown a trend of significance for predicting time to recurrence but has been less commonly investigated. With respect of the DCE studies, increased Ktrans was shown to be associated with decreased PFS [ 140 , 141 , 142 , 143 ] and OS [ 125 , 143 , 144 , 145 , 146 ] in several studies. Of specific interest, the baseline elevated Ktrans in non-enhancing T2 lesions has been independently associated with negative PFS [ 141 ].…”

ADC Histogram Analysis of Pediatric Low-Grade Glioma Treated with Selumetinib: A Report from the Pediatric Brain Tumor Consortium

“…ADC histograms derived from the ADC of all voxels in a tumor volume are particularly well-suited to characterize the diffusion properties of the entire tumor volume in brain tumors and have been used to differentiate pediatric brain tumors by histologic type 29 and tumor grade. 30 ADC histogram parameters have also been associated with molecular subtype 31 and response to therapy 12,32 in diffuse intrinsic pontine gliomas in children. Herein, we report the use of ADC histogram metrics to identify prognosis and response criteria in refractory, recurrent, or progressive pLGGs treated with selumetinib.…”