Discrepant longitudinal volumetric and metabolic evolution of diffuse intrinsic Pontine gliomas during treatment: implications for current response assessment strategies

Löbel, Ulrike; Hwang, Scott N.; Edwards, Aaron; Li, You; Li, Xingfeng; Broniscer, Alberto; Patay, Zoltán

doi:10.1007/s00234-016-1724-8

Cited by 15 publications

(14 citation statements)

References 29 publications

(31 reference statements)

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“…These data suggest that both the −50% and the +25% thresholds have poor correlation with clinical reality and are inadequate for partial response and progressive disease determinations. This finding is in keeping with reports showing that advanced MRI techniques, such as proton magnetic resonance spectroscopy (MRS) show little, if any, improvement in the lesions’ metabolic profile, even during the period of apparent volume reduction of the tumor 17,18 .…”

Section: Discussionsupporting

confidence: 90%

Measurable Supratentorial White Matter Volume Changes in Patients with Diffuse Intrinsic Pontine Glioma Treated with an Anti-Vascular Endothelial Growth Factor Agent, Steroids, and Radiation

Svolos¹,

Reddick²,

Edwards³

et al. 2017

AJNR Am J Neuroradiol

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Background and Purpose Assessing response to treatment in infiltrative brain tumors by using lesion volume-based response criteria is challenging. We hypothesized that, in such tumors, volume measurements alone may not accurately capture changes in actual tumor burden during treatment. We longitudinally evaluated volume changes in both normal-appearing supratentorial white matter and the brainstem lesion in patients treated for diffuse intrinsic pontine glioma to determine to what extent adjuvant systemic therapies may skew the accuracy of tumor response assessments based on volumetric analysis. Materials and Methods The anatomical MRI and diffusion tensor imaging data of 26 patients with diffuse intrinsic pontine glioma were retrospectively analyzed. Treatment included conformal radiation therapy in conjunction with vandetanib and dexamethasone. Volumetric and diffusion data were analyzed over time, and differences between time points were evaluated statistically. Results Normalized brainstem lesion volume decreased during combined treatment (slope = −0.222, P < 0.0001) and increased shortly after completion of radiation therapy (slope = 0.422, P <0.0001). Supratentorial white matter volume steadily and significantly decreased over time (slope = −0.057, P < 0.0001). Conclusion Longitudinal changes in brainstem lesion volume are robust; less pronounced but measurable changes occur in supratentorial white matter. Volume changes in non-irradiated supratentorial white matter during the disease course reflect effects of systemic medication on the water homeostasis of normal parenchyma. Our data suggest that adjuvant non-tumor-targeted therapies may have a more substantial effect on lesion volume changes than previously thought; hence, apparent volume decrease in infiltrative tumors receiving combined therapies may lead to overestimation of actual response and tumor control.

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Section: Discussionsupporting

confidence: 90%

Measurable Supratentorial White Matter Volume Changes in Patients with Diffuse Intrinsic Pontine Glioma Treated with an Anti-Vascular Endothelial Growth Factor Agent, Steroids, and Radiation

Svolos¹,

Reddick²,

Edwards³

et al. 2017

AJNR Am J Neuroradiol

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“…Advanced MR imaging techniques such as DSC and DCE-MR perfusion imaging, [22][23][24] arterial spin-labeling, 8 diffusion imaging including ADC histograms and functional diffusion maps, 6,22,25 MR spectroscopy, 26 and PET 27 have proved increasingly useful in characterizing the heterogeneity in DIPG for predicting survival and may even provide insight into molecular subgroups. 28,29 Our DCE-MR imaging findings show that increased baseline mean K trans was associated with shorter survival, which again suggests that greater perfusion in enhancing tumors indicates a worse prognosis.…”

Section: Discussionmentioning

confidence: 99%

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

Vajapeyam

Brown

Billups³

et al. 2020

AJNR Am J Neuroradiol

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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...

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“…Additionally, volume alone does not necessarily reflect grade and aggressiveness, as has been shown in a study where patients with the largest pre-radiotherapy tumor volumes showed the longest progression-free survival (54). Instinctively, volumetric MRI measurement seems to be inadequate as a response criterion in DIPG since tumor volume measurement might not reflect tumor burden to the patient, while the value of metabolic evaluation by 1 H magnetic resonance spectroscopy remains to be determined (55). The use of targeted molecular imaging methods in DIPG management, however, could play a decisive role in characterizing tumors to personalize treatment strategies.…”

Section: Discussionmentioning

confidence: 99%

Biomarker-Based PET Imaging of Diffuse Intrinsic Pontine Glioma in Mouse Models

et al. 2017

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Diffuse intrinsic pontine glioma (DIPG) is a childhood brainstem tumor with a universally poor prognosis. Here, we characterize on a positron emission tomography (PET) probe for imaging DIPG in vivo. In human histological tissues, the probes target, poly(ADP)ribose polymerase 1 (PARP1), was highly expressed in DIPG compared to normal brain. PET imaging allowed for the sensitive detection of DIPG in a genetically engineered mouse model (GEMM), and probe uptake correlated to histologically determined tumor infiltration. Imaging with the sister fluorescence agent revealed that uptake was confined to proliferating, PARP1 expressing cells. Comparison to other imaging technologies revealed remarkable accuracy of our biomarker approach. We subsequently demonstrated that serial imaging of DIPG in mouse models enables monitoring of tumor growth, as shown in modeling of tumor progression. Overall, this validated method for quantifying DIPG burden would serve useful in monitoring treatment response in early phase clinical trials.

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Discrepant longitudinal volumetric and metabolic evolution of diffuse intrinsic Pontine gliomas during treatment: implications for current response assessment strategies

Cited by 15 publications

References 29 publications

Measurable Supratentorial White Matter Volume Changes in Patients with Diffuse Intrinsic Pontine Glioma Treated with an Anti-Vascular Endothelial Growth Factor Agent, Steroids, and Radiation

Measurable Supratentorial White Matter Volume Changes in Patients with Diffuse Intrinsic Pontine Glioma Treated with an Anti-Vascular Endothelial Growth Factor Agent, Steroids, and Radiation

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

Biomarker-Based PET Imaging of Diffuse Intrinsic Pontine Glioma in Mouse Models

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