Contrast-enhanced T1-weighted subtraction maps for response assessment in recurrent glioblastoma treated with bevacizumab.

2055 Background: Antiangiogenic therapy in glioblastoma (GBM) results in decreased enhancement on post-contrast T1w images, which complicates standard response assessment and is likely the reason no studies have found predictive value in enhancing tumor size or change in size. The current study examined whether contrast-enhanced T1-weighted subtraction maps (CE-ΔT1w) calculated from subtracting pre-contrast (T1) from post-contrast T1w images (T1+C) can improve quantification and predict response in GBM patients treated with bevacizumab. Methods: Recurrent GBM patients (n=160) from the BRAIN trial (AVF3708g), a multicenter Phase II trial evaluating bevacvizumab, were used in the current study. CE-ΔT1w maps were calculated 2 weeks before and 6 weeks after the first dose of bevacizumab by: 1) performing registration between T1 and T1+C images, 2) image intensity normalization of T1 and T1+C images, and 3) subtraction of T1 from T1+C images. The volume of tumor regions with positive contrast enhancement after subtraction was retained for analysis. Results: CE-ΔT1w maps greatly improved detectability of subtly enhancing lesions, particularly post-treatment. Results for PFS and OS are summarized in the table below. In all scenarios, CE-ΔT1w maps outperformed conventional tumor segmentation. Results show that size and change in size are both predictive of PFS and OS. Conclusions: CE-ΔT1w maps improve visualization and quantification of contrast enhancing tumor regions in recurrent GBM, allowing for more accurate response assessment. [Table: see text]

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Effect of antiangiogenic therapy on tumor-associated macrophages in recurrent glioblastoma.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.2010 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 2010-2010 ◽

Cited By ~ 1

Author(s):

Christine Lu-Emerson ◽

Matija Snuderl ◽

Christian Davidson ◽

Nathaniel D. Kirkpatrick ◽

Yuhui Huang ◽

...

Keyword(s):

Flow Cytometry ◽

Massachusetts General Hospital ◽

Antiangiogenic Therapy ◽

Clinical Information ◽

Recurrent Glioblastoma ◽

Tumor Associated Macrophages ◽

Angiogenic Therapy ◽

History Of ◽

Autopsy Specimens ◽

Recurrent Gbm

2010 Background: Antiangiogenic therapy is associated with increased radiographic responses in glioblastoma (GBM), but tumors invariably recur. Tumor associated macrophages (TAMs) have been proposed as a mechanism of resistance to anti-angiogenic therapy in preclinical models. To examine the role of TAMs in recurrent GBM, we analyzed autopsy specimens from patients with or without history of antiangiogenic therapy. Methods: We compared autopsy brain specimens from 17 recurrent GBM patients who received anti-angiogenic treatment and chemoradiation (AAT+) to 7 patients who received chemotherapy and/or radiotherapy without anti-angiogenic therapy, or no treatment (AAT-). TAMs were morphologically and phenotypically identified with flow cytometry and immunohistochemistry (IHC) with CD68, CD11b, CD14, and CD163 markers. All specimens were obtained from the Department of Pathology at Massachusetts General Hospital and clinical information gained through review of the patients’ records. Results: Using flow cytometry, we observed an increase in CD11b+CD14+ cells in the AAT+ patients compared to AAT- patients. Using IHC analysis, we observed a significant increase in CD68+ macrophages in the tumor bulk (p<0.01) and infiltrative areas (p<0.05) in AAT+ versus AAT- patients. We also observed a significant increase in CD11b+ myeloid cells in the tumor bulk (p<0.01) and a significant increase in CD163+ cells in the infiltrative areas (p<0.05) in the AAT+ group. Finally, we noted a trend toward an increase in CD163+ cells in the tumor bulk (p=0.087) in the AAT+ versus the AAT- patients. Conclusions: Patients with recurrent GBM after antiangiogenic therapy showed a significant increase in CD68+ TAMs and in CD11b+ cells in the tumor bulk. Additionally, antiangiogenic treatment induced an increase in CD68+ and CD163+ TAMs in the infiltrative region. These data indicate that TAMs may participate in escape from antiangiogenic therapy and may represent a future therapeutic target in recurrent GBM.

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Radiographic evaluation of recurrent glioblastoma multiforme (GBM) in patients treated with bevacizumab and irinotecan

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.12512 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 12512-12512

Author(s):

J. Andre ◽

K. Spearman ◽

S. Lu ◽

S. Hwang ◽

L. Dorsett ◽

...

Keyword(s):

Spin Echo ◽

Brain Mri ◽

Recurrent Glioblastoma ◽

Post Treatment ◽

Radiographic Evaluation ◽

Recurrent Glioblastoma Multiforme ◽

Post Contrast ◽

Chemotherapeutic Regimen ◽

Mri Scans ◽

Recurrent Gbm

12512 Background: Recurrent GBM carries a poor prognosis after first-line therapies have been exhausted, even in the setting of gross total resection. Bevacizumab and Irinotecan have shown promising results in patients with recurrent GBM (Stark-Vance, et al. Neuro- Oncol, 2005). We sought to retrospectively document the short-term effects of this chemotherapeutic regimen on recurrent GBM, as evidenced by comparative MRI brain scans obtained prior to, and one-month following initiation of treatment. Methods: We collected brain MRI data from August 2005 to December 2006, in which post-contrast spin-echo T1-weighted images demonstrated measurable enhancement and/or GBM tumor mass. Having failed temozolomide and radiation therapy, 14 consecutive patients’ MRI scans were available for review at this institution by a neuro-radiologist, in which both pre- and post-treatment hard and/or soft copy MR images were available for direct measurement. Each was treated with Bevacizumab 5 mg/kg IV and Irinotecan 125 mg/m2 IV infusion every 2 weeks until disease progression, or development of unacceptable toxicity. We measured pre- and post-treatment recurrent GBM bulk tumor in anteroposterior, transverse, and cranio-caudad dimensions, and calculated volumetric data, assuming an ellipsoid tumor configuration. Results: Pre-treatment MRI scans were performed 2 weeks prior to initiation of therapy (Mean: 13 days; Median: 10 days). Post-treatment scans were performed at approximately one month following initial treatment (Mean: 30 days; Median: 28 days). All patients witnessed significant decrease in tumor bulk volume ranging from 15.3 to 89.8%, having received an average of two cycles of chemotherapy. We observed a mean decrease in tumor volume of 46.6% (SD = 22.6%; SEM = 6.0%; 95% CI = 33.6 - 60.0 % decrease). Conclusions: We report 46.6% mean reduction in recurrent GBM tumor bulk at an average of 1-month post-treatment in patients treated with an average of two cycles of Bevacizumab and Irinotecan therapy. These promising initial results necessitate further long-term prospective evaluation of this chemotherapy. No significant financial relationships to disclose.

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Efficacy finding cohort of a cancer peptide vaccine, TAS0313, in treating recurrent glioblastoma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.2038 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 2038-2038

Author(s):

Yoshiki Arakawa ◽

Yoshiko Okita ◽

Yoshitaka Narita

Keyword(s):

Cytotoxic T Lymphocyte ◽

Karnofsky Performance Status ◽

Performance Status ◽

Methylation Status ◽

Peptide Vaccine ◽

Progression Free Survival ◽

Response Assessment ◽

Primary Objective ◽

Recurrent Glioblastoma ◽

Recurrent Gbm

2038 Background: TAS0313 is a cancer vaccine cocktail comprising three long peptides with a total of 12 cytotoxic T lymphocyte (CTL) epitope peptides. These peptides were derived from eight cancer-associated antigens (EGFR, KUA, LCK, MRP3, PTHRP, SART2, SART3, and WHSC2) that are overexpressed in various cancer types including glioblastoma (GBM). We performed a single-arm, multicenter efficacy confirmatory cohort study as part of the TAS0313 Phase I/II study in patients with recurrent GBM. Methods: The enrolled patients with histologically or cytologically confirmed grade IV GBM (including gliosarcoma, giant cell glioblastoma, and epithelioid glioblastoma) had at least one of the following HLA types: HLA-A*02:01, -A*02:06, -A*02:07, -A*11:01, -A*24:02, -A*31:01, or -A*33:03. Eligible patients were those who received standard radiotherapy and temozolomide, had a confirmed first or second recurrence, or progression with measurable disease outcomes with good performance status (Karnofsky Performance Status score > 70). TAS0313 (27mg) was subcutaneously administered on days 1, 8, and 15 of cycles 1 and 2 and day 1 of cycle 3 or later in 21-day cycles until disease progression or unacceptable toxicity occurred. Tumor response was evaluated using The Response Assessment in Neuro-Oncology criteria. The antigen-specific CTL and immunoglobulin G (IgG) were analyzed by ELISPOT assay and Luminex assay, respectively, before and after treatment. The primary objective was to evaluate the efficacy of TAS0313. Secondary and exploratory methods were used to evaluate the safety and immune response of TAS0313. Results: As of 10th September 2020, 10 patients have been treated with TAS0313 (eight with GBM and two with gliosarcoma). The median age of participants was 56.5 [range, 33–69 years], and methylation status of the MGMT promoter was methylated in four patients, unmethylated in four, and unknown in two. The best overall response was partial response 1/10 (10.0%) and stable disease 4/10 (40.0%). One case showed 69.1% tumor shrinkage. The treatment of two patients was ongoing for over 7 months. The 6-month progression-free survival (PFS) rate was 25.0%, and the median PFS was 2.3 months. The most common adverse drug reactions (ADRs) were grade 1–2 injection site reactions and pyrexia. There were no grade 4 or 5 ADRs. In some patients, TAS0313 treatment was confirmed to increase CTL and IgG levels compared with pre-treatment samples. Conclusions: TAS0313 showed promising efficacy with expected immune responses and favorable safety and tolerability in patients with recurrent GBM. Further investigation of TAS0313 is warranted to validate our findings. Clinical trial information: JapicCTI-183824.

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Value of [18F]-FDG positron emission tomography in patients with recurrent glioblastoma receiving bevacizumab

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa050 ◽

2020 ◽

Vol 2 (1) ◽

Cited By ~ 1

Author(s):

Maya S Graham ◽

Simone Krebs ◽

Tejus Bale ◽

Kwaku Domfe ◽

Stephanie M Lobaugh ◽

...

Keyword(s):

Positron Emission Tomography ◽

Fdg Pet ◽

Antiangiogenic Therapy ◽

Multivariable Analysis ◽

Standardized Uptake Value ◽

Recurrent Glioblastoma ◽

Emission Tomography ◽

Fdg Uptake ◽

Positron Emission ◽

Recurrent Gbm

Abstract Background Treatment of recurrent glioblastoma (GBM) with bevacizumab can induce MRI changes that confound the determination of progression. We sought to determine the value of [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) in GBM patients receiving bevacizumab at the time of suspected progression and, thereby, its utility as a potential prognostic adjunct in progressive disease. Methods This retrospective study included patients who underwent brain FDG PET within 4 weeks of receiving bevacizumab for recurrent GBM with suspected progression. Volumes-of-interest were placed over the reference lesion with measurement of maximum standardized uptake value (SUVmax), peak standardized uptake value (SUVpeak), metabolic tumor volume, total lesion glycolysis (TLG), and tumor-to-normal contralateral white matter ratios (TNR-WM). Tumors were additionally categorized as non-avid or avid based on qualitative FDG uptake. Associations between baseline variables and overall survival (OS) were examined using univariable and multivariable Cox proportional hazards regression, with P < .05 considered significant. Results Thirty-one patients were analyzed. Qualitative FDG uptake was significantly associated with OS (P = .03), with a median OS of 9.0 months in non-avid patients versus 4.5 months in avid patients. SUVmax, SUVpeak, TNR-WM, and TLG were significantly associated with OS (P < .001, TLG: P = .009). FDG avidity and SUVmax remained significantly associated with OS (P = .046 and .048, respectively) in the multivariable analysis including age, KPS, and MGMT status. Dichotomizing patients using an SUVmax cutoff of 15.3 was associated with OS (adjusted P = .048). Conclusion FDG PET is a promising imaging tool to further stratify prognosis in recurrent GBM patients on antiangiogenic therapy.

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Differentiation of Recurrent Glioblastoma Multiforme from Radiation Necrosis after External Beam Radiation Therapy with Dynamic Susceptibility-weighted Contrast-enhanced Perfusion MR Imaging

Yearbook of Neurology and Neurosurgery ◽

10.1016/s0513-5117(10)79224-3 ◽

2010 ◽

Vol 2010 ◽

pp. 159-160

Author(s):

A.M. McKinney

Keyword(s):

Radiation Necrosis ◽

External Beam Radiation Therapy ◽

Recurrent Glioblastoma ◽

External Beam Radiation ◽

Dynamic Susceptibility ◽

Recurrent Glioblastoma Multiforme ◽

Beam Radiation ◽

Contrast Enhanced ◽

Perfusion Mr ◽

Perfusion Mr Imaging

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Multi-factorial considerations for intra-thoracic lymph node evaluations of healthy cats on computed tomographic images

BMC Veterinary Research ◽

10.1186/s12917-021-02771-7 ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Ninlawan Thammasiri ◽

Chutimon Thanaboonnipat ◽

Nan Choisunirachon ◽

Damri Darawiroj

Keyword(s):

Lymph Node ◽

Lymph Nodes ◽

Ct Images ◽

Slice Thickness ◽

Maximum Width ◽

Post Contrast ◽

Computed Tomographic ◽

Contrast Enhanced Ct ◽

Contrast Enhanced ◽

Enhanced Ct

Abstract Background It is difficult to examine mild to moderate feline intra-thoracic lymphadenopathy via and thoracic radiography. Despite previous information from computed tomographic (CT) images of intra-thoracic lymph nodes, some factors from animals and CT setting were less elucidated. Therefore, this study aimed to investigate the effect of internal factors from animals and external factors from the CT procedure on the feasibility to detect the intra-thoracic lymph nodes. Twenty-four, client-owned, clinically healthy cats were categorized into three groups according to age. They underwent pre- and post-contrast enhanced CT for whole thorax followed by inter-group evaluation and comparison of sternal, cranial mediastinal, and tracheobronchial lymph nodes. Results Post contrast-enhanced CT appearances revealed that intra-thoracic lymph nodes of kittens were invisible, whereas the sternal, cranial mediastinal, and tracheobronchial nodes of cats aged over 7 months old were detected (6/24, 9/24 and 7/24, respectively). Maximum width of these lymph nodes were 3.93 ± 0.74 mm, 4.02 ± 0.65 mm, and 3.51 ± 0.62 mm, respectively. By age, lymph node sizes of these cats were not significantly different. Transverse lymph node width of males was larger than that of females (P = 0.0425). Besides, the detection score of lymph nodes was affected by slice thickness (P < 0.01) and lymph node width (P = 0.0049). Furthermore, an irregular, soft tissue structure, possibly the thymus, was detected in all juvenile cats and three mature cats. Conclusions Despite additional information on intra-thoracic lymph nodes in CT images, which can be used to investigate lymphatic-related abnormalities, age, sex, and slice thickness of CT images must be also considered.

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Machine-Learning-Based Radiomics MRI Model for Survival Prediction of Recurrent Glioblastomas Treated with Bevacizumab

Diagnostics ◽

10.3390/diagnostics11071263 ◽

2021 ◽

Vol 11 (7) ◽

pp. 1263

Author(s):

Samy Ammari ◽

Raoul Sallé de Chou ◽

Tarek Assi ◽

Mehdi Touat ◽

Emilie Chouzenoux ◽

...

Keyword(s):

Machine Learning ◽

Therapeutic Option ◽

Binary Classification ◽

Progression Free Survival ◽

Recurrent Glioblastoma ◽

Machine Learning Algorithms ◽

Survival Prediction ◽

Classification Models ◽

Angiogenic Therapy ◽

Recurrent Gbm

Anti-angiogenic therapy with bevacizumab is a widely used therapeutic option for recurrent glioblastoma (GBM). Nevertheless, the therapeutic response remains highly heterogeneous among GBM patients with discordant outcomes. Recent data have shown that radiomics, an advanced recent imaging analysis method, can help to predict both prognosis and therapy in a multitude of solid tumours. The objective of this study was to identify novel biomarkers, extracted from MRI and clinical data, which could predict overall survival (OS) and progression-free survival (PFS) in GBM patients treated with bevacizumab using machine-learning algorithms. In a cohort of 194 recurrent GBM patients (age range 18–80), radiomics data from pre-treatment T2 FLAIR and gadolinium-injected MRI images along with clinical features were analysed. Binary classification models for OS at 9, 12, and 15 months were evaluated. Our classification models successfully stratified the OS. The AUCs were equal to 0.78, 0.85, and 0.76 on the test sets (0.79, 0.82, and 0.87 on the training sets) for the 9-, 12-, and 15-month endpoints, respectively. Regressions yielded a C-index of 0.64 (0.74) for OS and 0.57 (0.69) for PFS. These results suggest that radiomics could assist in the elaboration of a predictive model for treatment selection in recurrent GBM patients.

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SURG-13. LASER INTERSTITIAL THERMAL THERAPY FOR RECURRENT GLIOBLASTOMA: A REVIEW OF SURVIVAL OUTCOMES COMPARED TO A MATCHED SURGICAL COHORT

Neuro-Oncology ◽

10.1093/neuonc/noaa215.860 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii206-ii206

Author(s):

Hassan Fadel ◽

Sameah Haider ◽

Jacob Pawloski ◽

Hesham Zakaria ◽

Farhan Chaudhry ◽

...

Keyword(s):

Surgical Resection ◽

Subgroup Analysis ◽

Tumor Volume ◽

Progression Free Survival ◽

Recurrent Glioblastoma ◽

Thermal Therapy ◽

Survival Outcomes ◽

Repeat Surgery ◽

Laser Interstitial Thermal Therapy ◽

Recurrent Gbm

Abstract INTRODUCTION Glioblastoma (GBM) is uniformly associated with a poor prognosis and inevitable recurrence. Management of recurrent GBM remains unclear, with repeat surgery often employed with varying degrees of success. We evaluated the efficacy of Laser Interstitial Thermal Therapy (LITT) for recurrent GBM when compared to a carefully matched cohort of patients treated with repeat surgical resection. METHODS A retrospective single-institution database was used to identify patients who underwent LITT or surgical resection of recurrent GBM between 2014-2019. LITT patients were matched with surgical resection patients according to baseline demographics, comorbidities, tumor location, and eloquence. Subgroup analysis matching similar patients for tumor volume was also completed. Overall survival (OS) and progression-free survival (PFS) were the primary endpoints. RESULTS A LITT cohort of 20 patients was matched to 50 similar patients who underwent repeat surgical resection. Baseline characteristics were similar between both cohorts apart from tumor volume, which was larger in the surgical cohort (17.5 cc vs. 4.7 cc, p< 0.01). On long-term follow-up, there was no difference in OS (HR, 0.72; 95%CI, 0.36-1.45) or PFS (HR, 0.67; 95%CI, 0.29-1.53) between the LITT and surgical cohorts when controlling for tumor volume. Subgroup analysis of 23 LITT patients matched according to tumor volume with 23 surgical patients with similar clinical characteristics also found no difference in OS (HR, 0.66; 95%CI, 0.33-1.30) or PFS (HR, 0.58; 95%CI, 0.90-1.05) between the cohorts. LITT patients had shorter length of stays (1 vs. 4 days, p< 0.001) and a higher rate of home discharge (84% vs. 67%, p=0.172) compared to the surgical cohort. CONCLUSION After matching for demographic, clinical, and tumor characteristics, there was no difference in outcomes between patients undergoing LITT compared to surgical resection for recurrent GBM. LITT patients had similar survival outcomes yet shorter hospital stays and more favorable dispositions, potentially mitigating post-treatment complications.

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BIMG-04. MAPPING HETEROGENEITY OF HIGH-GRADE GLIOMA METABOLISM USING HIGH RESOLUTION 7T MRSI

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab024.003 ◽

2021 ◽

Vol 3 (Supplement_1) ◽

pp. i1-i1

Author(s):

Gilbert Hangel ◽

Cornelius Cadrien ◽

Philipp Lazen ◽

Sukrit Sharma ◽

Julia Furtner ◽

...

Keyword(s):

High Resolution ◽

Imaging Techniques ◽

Basis Set ◽

Metabolic Imaging ◽

Tumor Segmentation ◽

Low Grade ◽

High Grade ◽

Isotropic Resolution ◽

Contrast Enhanced ◽

Definition Of

Abstract OBJECTIVES Neurosurgical resection in gliomas depends on the precise preoperative definition of the tumor and its margins to realize a safe maximum resection that translates into a better patient outcome. New metabolic imaging techniques could improve this delineation as well as designate targets for biopsies. We validated the performance of our fast high-resolution whole-brain 3D-magnetic resonance spectroscopic imaging (MRSI) method at 7T in high-grade gliomas (HGGs) as first step to this regard. METHODS We measured 23 patients with HGGs at 7T with MRSI covering the whole cerebrum with 3.4mm isotropic resolution in 15 min. Quantification used a basis-set of 17 neurochemical components. They were evaluated for their reliability/quality and compared to neuroradiologically segmented tumor regions-of-interest (necrosis, contrast-enhanced, non-contrast-enhanced+edema, peritumoral) and histopathology (e.g., grade, IDH-status). RESULTS We found 18/23 measurements to be usable and ten neurochemicals quantified with acceptable quality. The most common denominators were increases of glutamine, glycine, and total choline as well as decreases of N-acetyl-aspartate and total creatine over most tumor regions. Other metabolites like taurine and serine showed mixed behavior. We further found that heterogeneity in the metabolic images often continued into the peritumoral region. While 2-hydroxy-glutarate could not be satisfyingly quantified, we found a tendency for a decrease of glutamate in IDH1-mutant HGGs. DISCUSSION Our findings corresponded well to clinical tumor segmentation but were more heterogeneous and often extended into the peritumoral region. Our results corresponded to previous knowledge, but with previously not feasible resolution. Apart from glycine/glutamine and their role in glioma progression, more research on the connection of glutamate and others to specific mutations is necessary. The addition of low-grade gliomas and statistical ROI analysis in a larger cohort will be the next important steps to define the benefits of our 7T MRSI approach for the definition of spatial metabolic tumor profiles.

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