Advanced imaging to assess longitudinal vascular changes in brain metastases treated with checkpoint inhibition.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3059-3059
Author(s):  
Albert Eusik Kim ◽  
Ken Chang ◽  
Kyrre E. Emblem ◽  
Jayashree Kalpathy-Cramer ◽  
Eudocia Quant Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Checkpoint Inhibitors ◽  
Mean Transit Time ◽  
Tumor Oxygenation ◽  
Dynamic Susceptibility ◽  
Vascular Changes ◽  
Post Contrast ◽  
Dsc Mri ◽  
Vascular Physiology

3059 Background: Immune checkpoint inhibitors (ICI) have recently been shown to be effective for brain metastases (BM) in melanoma and lung cancer. Several studies demonstrate that 20-50% of BM patients respond to ICI. The reasons behind this wide variability in treatment response is not clear. Therefore, using physiologic imaging, we seek to identify the longitudinal biological changes exerted on BM as a result of ICI administration. Methods: Given the importance of aberrant tumor vasculature in cancer proliferation, we have focused on assessing changes in vascular physiology. We analyzed standard post-contrast and dynamic susceptibility contrast (DSC) MRI to identify characteristic vascular signatures as part of an ongoing Phase 2 study of pembrolizumab for patients with untreated or progressive, previously treated BM from any histology. Tumor volume measurements were calculated by summating all enhancing voxels. As per modified RECIST and RANO criteria for immunotherapy, volumetric increase of > 40% was defined as progressive disease (PD), a decrease of > 60% as partial response (PR), and stable disease (SD) as between -60% and +40%. Results: 35 patients, out of the total cohort of 60, have undergone DSC-MRI analysis. Histologies include 15 with breast cancer, 6 with non-small cell lung cancer, 4 with melanoma, and 10 with other cancers. At baseline, the total number of BM was 1-50+ per patient. Based on summing the entire enhancing intracranial disease burden, best volumetric responses for the 35 evaluable patients include 4 PR, 12 SD, and 19 PD. Thus far, we found that ICI-resistant BM had a 50% increase in cerebral blood flow (CBF), 105% increase in cerebral blood volume (CBV), a 15% increase in mean transit time (MTT), and an 80% increase in vessel caliber at 6 weeks post-treatment. On the other hand, ICI-responsive BM had no change in CBF, a 33% increase in CBV, a 10% decrease in MTT, and no change in vessel caliber. Ongoing analysis to uncover additional vascular changes (e.g. tumor oxygenation, vessel size index) within BM to ICI are pending. Conclusions: Our data provides evidence that effective ICI for BM is associated with unique intra-tumoral vascular physiology. With final analysis, we will uncover other facets of vascular physiology that correlate with ICI response, and may reveal mechanisms of response/resistance within tumors to ICI.

scholarly journals NIMG-05. ADVANCED IMAGING TO ASSESS LONGITUDINAL VASCULAR CHANGES IN BRAIN METASTASES TREATED WITH CHECKPOINT INHIBITION

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii147-ii147
Author(s):  
Albert Kim ◽  
Jonathan Cardona ◽  
Ken Chang ◽  
Andrew Beers ◽  
James Brown ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Tumor Progression ◽  
Cerebral Blood Volume ◽  
Checkpoint Inhibitors ◽  
Dynamic Susceptibility ◽  
Vascular Changes ◽  
Dynamic Susceptibility Contrast ◽  
Post Contrast ◽  
Volume Measurements

Abstract Immune checkpoint inhibitors (ICI) have recently been shown to be effective for brain metastases (BM) in melanoma and lung cancer. However, accurately assessing intracranial response in patients undergoing ICI is a challenge, as current measures cannot reliably distinguish pseudoprogression from true tumor progression. To identify potential biomarkers of response, we analyzed standard post-contrast and dynamic susceptibility contrast MRI to identify characteristic vascular signatures as part of an ongoing Phase 2 study of pembrolizumab for patients with untreated or progressive, previously treated BM from any histology. Tumor volume measurements were calculated by summating all enhancing voxels. A volumetric increase of >40% was categorized as progressive disease (PD), a decrease of >60% as partial response (PR), and stable disease (SD) as between -60% and +40%. 78 patients have been enrolled, of whom 44 have received at least baseline advanced MR imaging. Histologies include 21 with breast cancer, 5 with non-small cell lung cancer, 4 with melanoma, and 13 with other cancers. At baseline, the total number of BM was 1-50+ per patient. Based on summing the entire enhancing intracranial disease burden, best volumetric responses for the 33 evaluable patients include 4 PR, 10 SD, and 19 PD. On preliminary analysis, there was a correlation between increased tumor cerebral blood volume/flow with tumor progression. Correlation of additional vascular physiologic parameters (e.g. vessel caliber, tissue oxygenation) to volumetric response, patient outcome, and standardized response criteria (iRANO) are ongoing. Our data provides potential evidence that effective ICI is associated with a decrease in perfusion. Ongoing analyses to uncover additional vascular changes – specifically longitudinal metrics reflecting vascular structure and function - within BM to ICI are pending. These findings have potential to explore mechanisms of ICI response and resistance, as well as biomarkers of response.

Advanced imaging to assess longitudinal vascular changes in brain metastases treated with immune checkpoint inhibition.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2529-2529
Author(s):  
Albert Eusik Kim ◽  
Ken Chang ◽  
Andrew Beers ◽  
Kyrre E. Emblem ◽  
Jayashree Kalpathy-Cramer ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Tumor Progression ◽  
Immune Checkpoint ◽  
Cerebral Blood Volume ◽  
Checkpoint Inhibitors ◽  
Dynamic Susceptibility ◽  
Vascular Changes ◽  
Dynamic Susceptibility Contrast ◽  
Volume Measurements

2529 Background: Immune checkpoint inhibitors (ICI) have recently been shown to be effective for brain metastases (BM) for melanoma and lung cancer. This breakthrough has prompted interest in evaluating ICI in BM of other histologies. However, accurately assessing intracranial response in patients undergoing ICI is a challenge, as current measures cannot distinguish pseudoprogression from true tumor progression. To shed light on potential biomarkers of response, we prospectively use perfusion MRI to identify characteristic vascular signatures in a BM-specific trial of ICI. Methods: As part of an ongoing phase II study of pembrolizumab for patients with untreated or progressive, previously treated BM from any histology, patients underwent advanced MRI that includes tumor volume measurements and perfusion imaging with dynamic susceptibility contrast MRI. To calculate volumetric radiographic response, all enhancing voxels were summated. A volumetric increase of >40% was categorized as progressive disease (PD), a decrease of >60% as partial response (PR), and stable disease (SD) as between -60% and +40%. Results: 53 patients have been enrolled, of whom 44 have received at least baseline advanced MR imaging. Histologies include 21 with breast cancer, 5 with non-small cell lung cancer, 4 with melanoma, and 13 with other cancers. At baseline, the total number of BM was 1-50+ per patient. Based on summing the entire enhancing intracranial disease burden, best volumetric responses for the 33 evaluable patients include 4 PR, 10 SD, and 19 PD. On preliminary analysis, there was a correlation between increased tumor cerebral blood volume/flow with tumor progression. Correlation of additional vascular physiologic parameters (e.g. vessel caliber, tissue oxygenation) and volumetric response to patient outcome and standardized response criteria (iRANO) are ongoing. Conclusions: Pembrolizumab likely has anti-tumor efficacy in BM. Our data provides potential evidence that effective ICI is associated with a decrease in perfusion. Ongoing analyses to uncover additional vascular changes – specifically longitudinal metrics reflecting vascular structure and function - within BM to ICI are pending. These findings have potential to illustrate mechanisms of efficacy for ICI and biomarkers of response in this patient population.

scholarly journals Intra-tumoural perfusion habitats showed prognostic value in glioblastoma patients

2019 ◽  
Vol 21 (Supplement_4) ◽  
pp. iv3-iv3
Author(s):  
Chao Li ◽  
Chang Sun ◽  
Shuo Wang ◽  
Stephen Price
Keyword(s):  
Cerebral Blood Volume ◽  
Cox Regression ◽  
Mean Transit Time ◽  
Tumour Microenvironment ◽  
Dynamic Susceptibility ◽  
Dynamic Susceptibility Contrast ◽  
Post Contrast ◽  
Dsc Mri ◽  
Contrast Enhanced ◽  
Susceptibility Contrast

Abstract The perfusion within glioblastoma is associated with tumour microenvironment and may create invasive tumor habitats that could potentially be revealed by perfusion imaging. The purpose of this study is to characterize the peritumoural habitats of glioblastoma for treatment target. Dynamic susceptibility contrast-enhancement (DSC) MRI was acquired pre-operatively on 115 newly-diagnosed glioblastoma patients. All images were co-registered to post-contrast T1-weighted images. The relative cerebral blood volume (rCBV), mean transit time (MTT) and relative cerebral blood flow (rCBF) maps were generated from the DSC images. The contrast-enhanced and peritumoural tumor regions were semi-automatically segmented from the post-contrast T1-weighted and FLAIR images. To delineate the habitats of different perfusion levels, a two clusters mixture model with Gaussian distribution was fitted to the rCBV, rCBF, and MTT within both contrast-enhanced and peritumoural regions. Perfusion parameters of the identified habitats were compared, and the prognostic values of habitats were investigated using survival analysis. The results showed that although non-enhanced, the peritumoral high perfusion (PHP) habitat demonstrated similar perfusion level with the contrast high perfusion (CHP) habitat, with similar rCBV (PHP: 1.13 ± 0.18, 95% CI [1.10, 1.15]; CHP: 1.21 ± 0.25, 95% CI [1.16, 1.21]) and rCBF (PHP: 1.08 ± 0.23, 95% CI [1.05, 1.08]; CHP: 1.08 ± 0.19, 95% CI [1.05, 1.08]). Multivariate Cox regression showed that the volumes of both habitats were associated with worse patient overall survival (PHP: P = 0.032; HR= 7.09; CHP: P = 0.008; HR= 12.01). Our results suggest that the intra-tumoural perfusion habitats may potentially offer treatment targets.

scholarly journals Association of Brain Metastases With Immune Checkpoint Inhibitors Efficacy in Advanced Lung Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Yanning Wang ◽  
Qianning Zhang ◽  
Chuansheng Chen ◽  
Yuxuan Hu ◽  
Liyun Miao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Overall Survival ◽  
Brain Metastases ◽  
Cancer Patients ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Advanced Lung Cancer ◽  
Lung Cancer Patients ◽  
Hazard Ratios

BackgroundIn pivotal immunotherapy trials, the efficacy of immune checkpoint inhibitors as treatments for lung cancer patients with brain metastases remains controversial. The aim of this study was to assess the relative efficacy of immunotherapy versus standard systemic therapy in advanced lung cancer patients with and without brain metastases.MethodsSystematic searches of PubMed, Embase, Cochrane database, and conference proceedings up to Aug 6, 2020 without year and language restrictions. The main outcomes were the overall survival in patients with and without brain metastases measured by hazard ratios, and the difference in efficacy between patients with and without brain metastases was measured by ratio of hazard ratios.ResultsNine eligible randomized controlled trials involving 6241 patients (682 [11%] with brain metastases and 5559 [89%] without brain metastases) were included in the analysis. A survival benefit of immunotherapy was observed for both patients with brain metastases (HR, 0.75; 95%CI, 0.53-0.97; P = .026) and patients without brain metastases (HR, 0.75; 95%CI, 0.67-0.83; P <.001). However, patients without brain metastases benefit more from immunotherapy than patients with brain metastases (HR, 1.37; 95%CI, 1.15-1.63; P = .001). Additionally, subgroup analyses indicated that tumor type affect the efficacy of immunotherapy in patients with brain metastases (HR, 1.04 vs 1.54; interaction, P = .041).ConclusionsImmunotherapy can significantly improve overall survival for advanced lung cancer patients with asymptomatic brain metastases, especially in patients with non-small-cell lung cancer, but the magnitude of benefit is brain metastases dependent.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020206597.

scholarly journals CMET-18. IMPACT OF KRAS MUTATION STATUS ON THE EFFICACY OF IMMUNOTHERAPY IN LUNG CANCER BRAIN METASTASES

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi55-vi55
Author(s):  
Adam Lauko ◽  
Assad Ali ◽  
Soumya Sagar ◽  
Addison Barnett ◽  
Hong Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Checkpoint Inhibitors ◽  
Care Center ◽  
Tertiary Care ◽  
Wild Type ◽  
Chi Square ◽  
Kras Mutations ◽  
Mutational Status

Abstract BACKGROUND Immunotherapy is increasingly used in patients with non-small cell lung cancer brain metastases (NSCLCBM). KRAS mutations are associated with worse prognosis and there is no FDA approved targeted therapy. KRAS mutations are associated with increased expression of PD-L1. We evaluated the outcomes of NSCLCBM with KRAS mutations treated with immune checkpoint inhibitors (ICI). METHODS We reviewed 800 patients with NSCLCBM treated at our tertiary care center. 226 had known KRAS mutational status, 121 of which received immunotherapy. Overall survival (OS) was calculated from either the start of immunotherapy (when both groups received immunotherapy) or from the date of diagnosis of brain metastasis. Kaplan-Meier method and Cox Proportional hazard model were utilized to determine differences in OS and the Chi-square test was utilized to determine differences in PD-L1 expression. RESULTS In 109 patients where both KRAS and PD-L1 status were known, KRAS mutations had greater PD-L1 expression (80.1% vs 61.9% positive, p=0.04). There was no difference in OS between KRAS mutant vs KRAS wild-type patients treated with immunotherapy. Median survival from the start of immunotherapy was 15.6 vs 15.5 months respectively (p=0.7), after adjusting for age, KPS, lesion number and extra-cranial metastasis (HR = .91, p=.7). Patients with KRAS mutations treated with immunotherapy versus those who received chemotherapy had a 1-year OS from the diagnosis of brain metastasis of 60.9% vs 38.7% respectively (trending towards significance, p=0.05). KRAS wild-type patients treated with immunotherapy versus those who did not receive immunotherapy had a 1-year OS from the diagnosis of brain metastasis of 61.9% vs 62.5% (p=0.85), respectively. DISCUSSION KRAS mutations are associated with increased PD-L1 expression. Use of immunotherapy negates the poor outcomes seen traditionally in patients with NSCLCBM and KRAS mutations and it improves survival compared to use of chemotherapy. Our experience supports the use of immunotherapy in these patients.

Human leukocyte antigen expression in paired primary lung lesions and brain metastases in non-small cell lung cancer.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 43-43
Author(s):  
Jarrett Failing ◽  
Marie-Christine Aubry ◽  
Aaron Scott Mansfield
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Human Leukocyte ◽  
Small Cell ◽  
Small Cell Lung ◽  
Primary Tumors ◽  
Primary Nsclc

43 Background: Human leukocyte antigens (HLA) are crucial for cytotoxic T cell responses to cancer. Loss of HLA expression is a mechanism of tumor immune escape and may contribute to resistance to immunotherapy. In patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors we have observed discordant responses between brain metastases and extracranial disease and reported on differential PD-L1 expression and clonal T cell infiltration between paired primary lung lesions and brain metastases. In this project we sought to evaluate whether HLA expression was retained in metastatic NSCLC. Methods: Adult patients with paired primary NSCLC and brain metastases were identified from our institution’s tissue registry. HLA-A cell membrane expression on tumor cells was determined by immunohistochemistry with an anti-HLA-A antibody. Tumors with greater than 10% HLA expression were considered positive. Agreement statistics (κ) and Fisher’s exact test were used for analysis. Results: 51 patients with paired primary NSCLC and brain lesions were identified. The median HLA expression was 20% in the primary tumors (IQR 0-65%) and 10% in the brain metastases (IQR 5-40%). 27 primary tumors and 24 brain metastases were positive for HLA expression. There was disagreement in HLA positivity between paired lesions in 11 patients (22%, 95% CI 12-35%)(κ = 0.57, 95% CI 0.35-0.79)(p = 0.0001). There was no significant difference in the time between the primary tumor and brain metastasis resections in patients with HLA expression disagreement compared to those with HLA expression agreement. None of the patients received immune checkpoint inhibitors for treatment of these lesions. Conclusions: We found significant differences in HLA-A expression on tumor cells in nearly one quarter of paired primary lung cancers and brain metastases. Differences in HLA expression may help explain the discrepancies in response to immune checkpoint inhibitors at different sites of disease and warrants further study.

scholarly journals Reliable Estimation of Capillary Transit Time Distributions Using DSC-MRI

2014 ◽  
Vol 34 (9) ◽  
pp. 1511-1521 ◽  
Author(s):  
Kim Mouridsen ◽  
Mikkel Bo Hansen ◽  
Leif Østergaard ◽  
Sune Nørhøj Jespersen
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Transit Time ◽  
Neuronal Response ◽  
Mean Transit Time ◽  
Oxygen Extraction Fraction ◽  
Dynamic Susceptibility ◽  
Arterial Blood ◽  
Dsc Mri ◽  
Wide Range

The regional availability of oxygen in brain tissue is traditionally inferred from the magnitude of cerebral blood flow ( CBF) and the concentration of oxygen in arterial blood. Measurements of CBF are therefore widely used in the localization of neuronal response to stimulation and in the evaluation of patients suspected of acute ischemic stroke or flow-limiting carotid stenosis. It was recently demonstrated that capillary transit time heterogeneity ( CTH) limits maximum oxygen extraction fraction ( OEFmax) that can be achieved for a given CBF. Here we present a statistical approach for determining CTH, mean transit time ( MTT), and CBF using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI). Using numerical simulations, we demonstrate that CTH, MTT, and OEFmax can be estimated with low bias and variance across a wide range of microvascular flow patterns, even at modest signal-to-noise ratios. Mean transit time estimated by singular value decomposition (SVD) deconvolution, however, is confounded by CTH. The proposed technique readily identifies malperfused tissue in acute stroke patients and appears to highlight information not detected by the standard SVD technique. We speculate that this technique permits the non-invasive detection of tissue with impaired oxygen delivery in neurologic disorders such as acute ischemic stroke and Alzheimer's disease during routine diagnostic imaging.

Differentiation between Supratentorial Single Brain Metastases and High Grade Astrocytic Tumors: An Evaluation of Different DSC MRI Measurements

2009 ◽  
Vol 22 (4) ◽  
pp. 369-377 ◽  
Author(s):  
H. Zhang ◽  
L.A. Rödiger ◽  
G. Zhang ◽  
M. Oudkerk
Keyword(s):  
Brain Metastases ◽  
Cerebral Blood Volume ◽  
Mean Transit Time ◽  
Correct Diagnosis ◽  
Threshold Value ◽  
High Grade ◽  
Diagnostic Efficiency ◽  
Astrocytic Tumors ◽  
Dsc Mri ◽  
Mri Measurements

This study evaluated the role of different perfusion MRI measurements in the pre-operative differentiation between single brain metastases and high grade astrocytic tumors. 24 high-grade astrocytic tumors and 29 single metastases were studied. A gradient echo-planar sequence was used for DSC MRI. Relative cerebral blood volume, cerebral blood flow and mean transit time in both tumor parenchyma (T rCBV, T rCBF and T rMTT) and peritumoral edema (P rCBV, P rCBF and P rMTT) were measured. Mann-Whitney tests were used to assess differences between single brain metastases and high grade astrocytic tumors. Receiver operating characteristic analyses were performed to determine optimum thresholds for tumor differentiation. Sensitivity, specificity and accuracy for identifying brain metastases were calculated. Mean T rCBV, T rCBF, P rCBV and P CBF of brain metastases (2.75±1.72, 2.51±2.09, 1.05±0.53, 0.87±0.40) differed statistically (P <0.05) from those of high grade astrocytic tumors (6.00±2.17, 5.68±2.35, 1.77±1.19 and 1.58±0.99). No statistical difference was found between mean rMTTs of these two entities (P >0.05). Based on the area under the ROC curves (AUC), the efficiency of T rCBV and T rCBF for correct diagnosis of brain metastases is almost identical (AUC: 0.899, 0.890 respectively) and superior to other measurements. A threshold value of 3.50 for T rCBF provided the same specificity (86.7) as that of T rCBV but higher sensitivity (86.2) and accuracy (86.3). Different perfusion measurements can be used to differentiate single metastases from high-grade astrocytic tumors. T rCBF showed the highest diagnostic efficiency among these measurements.

scholarly journals Multi-Parametric and Multi-Regional Histogram Analysis of MRI: Revealing Imaging Phenotypes of Glioblastoma Correlated with Patient Survival

2017 ◽  
Author(s):  
Chao Li ◽  
Shuo Wang ◽  
Angela Serra ◽  
Turid Torheim ◽  
Jiun-Lin Yan ◽  
...  
Keyword(s):  
Cerebral Blood Volume ◽  
Cox Regression ◽  
Diffusion Tensor ◽  
Mean Transit Time ◽  
Biological Data ◽  
Histogram Analysis ◽  
Dynamic Susceptibility ◽  
Post Contrast ◽  
Cox Regression Analysis ◽  
Dismal Prognosis

AbstractIntroductionGlioblastoma is characterized by its remarkable heterogeneity and dismal prognosis. Histogram analysis of quantitative magnetic resonance imaging (MRI) is an important in vivo method to study intratumoral heterogeneity. With large amounts of histogram features generated, integrating these modalities effectively for clinical decision remains a challenge.MethodsA total of 80 patients with supratentorial primary glioblastoma were recruited. All patients received surgery and standard regimen of temozolomide chemoradiotherapy. Diagnosis was confirmed by pathology. Anatomical T2-weighted, T1-weighted post-contrast and FLAIR images, as well as dynamic susceptibility contrast (DSC), diffusion tensor imaging (DTI) and chemical shift imaging were acquired preoperatively using a 3T MRI scanner. DTI-p, DTI-q, relative cerebral blood volume (rCBV), mean transit time (MTT) and relative cerebral blood flow (rCBF) maps were generated. Contrast-enhancing (CE) and non-enhancing (NE) regions of interest were manually delineated. Voxel intensity histograms were constructed from the CE and NE regions independently. Patient clustering was performed by the Multi-View Biological Data Analysis (MVDA) approach. Kaplan-Meier and Cox proportional hazards regression analyses were performed to evaluate the relevance of the patient clustering to survival. The histogram features selected from MVDA approach were evaluated using receiver operator characteristics (ROC) curve analysis. The metabolic signatures of the patient clusters were analyzed by multivoxel MR spectroscopy (MRS).ResultsThe MVDA approach yielded two final patient clusters, consisting of 53 and 27 patients respectively. The two patient subgroups showed significance for overall survival (p = 0.007, HR = 0.32) and progression-free survival (p < 0.001, HR = 0.33) in multivariate Cox regression analysis. Among the features selected by MVDA, higher mean value of DTI-q in the non-enhancing region contributed to a worse OS (HR = 1.40, p = 0.020) and worse PFS (HR = 1.36, p = 0.031). Multivoxel MRS showed N-acetylaspartate/creatine (NAA/Cr) ratio between the two clusters, both in the CE region (p < 0.001) and NE region (p = 0.013). Glutamate/Cr (Glu/Cr) ratio and glutamate + glutamine/Cr (Glx/Cr) of the cluster 1 was significantly lower than cluster 2 (p = 0.037, and 0.027 respectively) In the NE region.DiscussionThis study demonstrated that integrating multi-parametric and multi-regional MRI histogram features may help to stratify patients. The histogram features selected from the proposed approach may be used as potential imaging markers in personalized treatment strategy and response determination.

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