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.

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 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.

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