scholarly journals A Comparison of Single- and Multiparametric MRI Models for Differentiation of Recurrent Glioblastoma from Treatment-Related Change

Diagnostics ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 2281
Author(s):  
Felix Eisenhut ◽  
Tobias Engelhorn ◽  
Soheil Arinrad ◽  
Sebastian Brandner ◽  
Roland Coras ◽  
...  
Keyword(s):  
Cerebral Blood Volume ◽  
Multiparametric Mri ◽  
Recurrent Glioblastoma ◽  
Multiple Logistic Regression ◽  
Clinical Routine ◽  
Patient Cohort ◽  
Significant Difference ◽  
Apparent Diffusion ◽  
Using Data ◽  
Recurrent Gbm

To evaluate single- and multiparametric MRI models to differentiate recurrent glioblastoma (GBM) and treatment-related changes (TRC) in clinical routine imaging. Selective and unselective apparent diffusion coefficient (ADC) and minimum, mean, and maximum cerebral blood volume (CBV) measurements in the lesion were performed. Minimum, mean, and maximum ratiosCBV (CBVlesion to CBVhealthy white matter) were computed. All data were tested for lesion discrimination. A multiparametric model was compiled via multiple logistic regression using data demonstrating significant difference between GBM and TRC and tested for its diagnostic strength in an independent patient cohort. A total of 34 patients (17 patients with recurrent GBM and 17 patients with TRC) were included. ADC measurements showed no significant difference between both entities. All CBV and ratiosCBV measurements were significantly higher in patients with recurrent GBM than TRC. A minimum CBV of 8.5, mean CBV of 116.5, maximum CBV of 327 and ratioCBV minimum of 0.17, ratioCBV mean of 2.26 and ratioCBV maximum of 3.82 were computed as optimal cut-off values. By integrating these parameters in a multiparametric model and testing it in an independent patient cohort, 9 of 10 patients, i.e., 90%, were classified correctly. The multiparametric model further improves radiological discrimination of GBM from TRC in comparison to single-parameter approaches and enables reliable identification of recurrent tumors.

scholarly journals CTNI-14. A 3-ARM, PHASE IIA TRIAL OF SAFETY & EFFICACY OF OLINVACIMAB, A MONOCLONAL ANTIBODY TO VEGFR2 IN PATIENTS WITH RECURRENT GLIOBLASTOMA MULTIFORME WITH IMAGING AND PK/PD ASSESSMENTS: FINAL REPORT

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii44-ii45
Author(s):  
Lawrence Cher ◽  
Anna Nowak ◽  
George Iatropoulos ◽  
Samantha Bowyer ◽  
Hui Gan ◽  
...  
Keyword(s):  
Recurrent Glioblastoma ◽  
Final Report ◽  
Recurrent Glioblastoma Multiforme ◽  
Open Label ◽  
Impaired Wound Healing ◽  
Significant Difference ◽  
Angiogenic Effect ◽  
Vegf Pathway ◽  
Recurrent Gbm

Abstract The VEGF pathway remains an important target in GBM given its vascularity and autocrine VEGF signalling. Olinvacimab (TTAC-0001) is a fully humanised VEGFR2 Mab that binds and inhibits the receptor. This report assesses the safety, dosing schedules and efficacy of Olinvacimab in recurrent GBM. We conducted a two-site, 3 arm, open-label study of Olinvacimab in recurrent GBM. Eligible patients were ≥18 years with RANO-measurable lesion, KPS ≥ 80, and had completed chemoradiotherapy without prior bevacizumab therapy. We assessed three arms, 8 mg/kg and 12mg/kg weekly for 3 of every 4 weeks, and 12 mg/kg weekly. Three patients were treated in arms 1 and 2 and 6 in arm 3. Safety assessments were performed prior to dose escalation. The main toxicity was development of grade 1 (67%) and 2 (8%%) cutaneous haemangiomas. Common toxicities seen with other VEGF directed therapies, including hypertension, impaired wound healing, and proteinuria were not seen in this cohort. Efficacy was assessed by MRI using RANO criteria. 6 month PFS was 17%, with disease control in 25%, with steroid dose reduction. The longest response was 15 months. On DCE MRI, there was no significant difference in perfusion parameters between baseline and 1st follow-up MRI comparing those with SD and PD. However, 6 of 12 patients showed decreased Ktrans > 20 % of baseline, consistent with an anti-angiogenic effect of Olinvacimab. Pharmacokinetics showed a decreased clearance rate and increased half-life of Olinvacimab compared to the prior Phase I study. Pharmacodynamic studies showed significantly higher levels of angiogenic markers, particularly VEGF-A in those treated at 12mg/kg vs arm 1. VEGF-A, C and D levels were elevated in patients with SD compared to those with PD. Conclusion: Olinvacimab was well tolerated with a different toxicity profile to other VEGFR directed therapies. There were promising responses in 25% of patients.

scholarly journals Multiparametric MRI assessment of response to convection-enhanced intratumoral delivery of MDNA55, an interleukin-4 receptor targeted immunotherapy, for recurrent glioblastoma

2021 ◽  
Vol 12 ◽  
pp. 337
Author(s):  
Suyash Mohan ◽  
Sumei Wang ◽  
Sanjeev Chawla ◽  
Kalil Abdullah ◽  
Arati Desai ◽  
...  
Keyword(s):  
Cerebral Blood Volume ◽  
Therapeutic Potential ◽  
Mean Diffusivity ◽  
Recurrent Glioblastoma ◽  
Perfusion Mri ◽  
Interleukin 4 ◽  
Convection Enhanced Delivery ◽  
Dismal Prognosis ◽  
Interleukin 4 Receptor ◽  
Recurrent Gbm

Background: Glioblastoma (GBM) is the most common malignant brain tumor and carries a dismal prognosis. Attempts to develop biologically targeted therapies are challenging as the blood–brain barrier can limit drugs from reaching their target when administered through conventional (intravenous or oral) routes. Furthermore, systemic toxicity of drugs often limits their therapeutic potential. To circumvent these problems, convection-enhanced delivery (CED) provides direct, targeted, intralesional therapy with a secondary objective to alter the tumor microenvironment from an immunologically “cold” (nonresponsive) to an “inflamed” (immunoresponsive) tumor. Case Description: We report a patient with right occipital recurrent GBM harboring poor prognostic genotypes who was treated with MRI-guided CED of a fusion protein MDNA55 (a targeted toxin directed toward the interleukin-4 receptor). The patient underwent serial anatomical, diffusion, and perfusion MRI scans before initiation of targeted therapy and at 1, 3-month posttherapy. Increased mean diffusivity along with decreased fractional anisotropy and maximum relative cerebral blood volume was noted at follow-up periods relative to baseline. Conclusion: Our findings suggest that diffusion and perfusion MRI techniques may be useful in evaluating early response to CED of MDNA55 in recurrent GBM patients.

scholarly journals Assessment of tumor hypoxia and perfusion in recurrent glioblastoma following bevacizumab failure using MRI and 18F-FMISO PET

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shiliang Huang ◽  
Joel E. Michalek ◽  
David A. Reardon ◽  
Patrick Y. Wen ◽  
John R. Floyd ◽  
...  
Keyword(s):  
Cerebral Blood Volume ◽  
Tumor Hypoxia ◽  
Volume Ratio ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Free Survival ◽  
Mri Features ◽  
Treatment Considerations ◽  
Hypoxic Volume ◽  
Recurrent Gbm

AbstractTumoral hypoxia correlates with worse outcomes in glioblastoma (GBM). While bevacizumab is routinely used to treat recurrent GBM, it may exacerbate hypoxia. Evofosfamide is a hypoxia-targeting prodrug being tested for recurrent GBM. To characterize resistance to bevacizumab and identify those with recurrent GBM who may benefit from evofosfamide, we ascertained MRI features and hypoxia in patients with GBM progression receiving both agents. Thirty-three patients with recurrent GBM refractory to bevacizumab were enrolled. Patients underwent MR and 18F-FMISO PET imaging at baseline and 28 days. Tumor volumes were determined, MRI and 18F-FMISO PET-derived parameters calculated, and Spearman correlations between parameters assessed. Progression-free survival decreased significantly with hypoxic volume [hazard ratio (HR) = 1.67, 95% confidence interval (CI) 1.14 to 2.46, P = 0.009] and increased significantly with time to the maximum value of the residue (Tmax) (HR = 0.54, 95% CI 0.34 to 0.88, P = 0.01). Overall survival decreased significantly with hypoxic volume (HR = 1.71, 95% CI 1.12 to 12.61, p = 0.01), standardized relative cerebral blood volume (srCBV) (HR = 1.61, 95% CI 1.09 to 2.38, p = 0.02), and increased significantly with Tmax (HR = 0.31, 95% CI 0.15 to 0.62, p < 0.001). Decreases in hypoxic volume correlated with longer overall and progression-free survival, and increases correlated with shorter overall and progression-free survival. Hypoxic volume and volume ratio were positively correlated (rs = 0.77, P < 0.0001), as were hypoxia volume and T1 enhancing tumor volume (rs = 0.75, P < 0.0001). Hypoxia is a key biomarker in patients with bevacizumab-refractory GBM. Hypoxia and srCBV were inversely correlated with patient outcomes. These radiographic features may be useful in evaluating treatment and guiding treatment considerations.

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

Diagnostics ◽  
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.

scholarly journals Quantitative 3-tesla multiparametric MRI in differentiation between renal cell carcinoma subtypes

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Ali Elsorougy ◽  
Hashim Farg ◽  
Dalia Bayoumi ◽  
Mohamed Abou El-Ghar ◽  
Magda Shady
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Multiparametric Mri ◽  
Histopathological Analysis ◽  
Adc Value ◽  
Intensity Index ◽  
Apparent Diffusion ◽  
The Mean

Abstract Background MRI provides several distinct quantitative parameters that may better differentiate renal cell carcinoma (RCC) subtypes. The purpose of the study is to evaluate the diagnostic accuracy of apparent diffusion coefficient (ADC), chemical shift signal intensity index (SII), and contrast enhancement in differentiation between different subtypes of renal cell carcinoma. Results There were 63 RCC as regard surgical histopathological analysis: 43 clear cell (ccRCC), 12 papillary (pRCC), and 8 chromophobe (cbRCC). The mean ADC ratio for ccRCC (0.75 ± 0.13) was significantly higher than that of pRCC (0.46 ± 0.12, P < 0.001) and cbRCC (0.41 ± 0.15, P < 0.001). The mean ADC value for ccRCC (1.56 ± 0.27 × 10−3 mm2/s) was significantly higher than that of pRCC (0.96 ± 0.25 × 10−3 mm2/s, P < 0.001) and cbRCC (0.89 ± 0.29 × 10−3 mm2/s, P < 0.001). The mean SII of pRCC (1.49 ± 0.04) was significantly higher than that of ccRCC (0.93 ± 0.01, P < 0.001) and cbRCC (1.01 ± 0.16, P < 0.001). The ccRCC absolute corticomedullary enhancement (196.7 ± 81.6) was significantly greater than that of cbRCC (177.8 ± 77.7, P < 0.001) and pRCC (164.3 ± 84.6, P < 0.001). Conclusion Our study demonstrated that multiparametric MRI is able to afford some quantitative features such as ADC ratio, SII, and absolute corticomedullary enhancement which can be used to accurately distinguish different subtypes of renal cell carcinoma.

Efficiency of diffusion-weighted MRI for differentiating radiologically similar simple and type I hydatid cysts of the liver

2021 ◽  
pp. 028418512098813
Author(s):  
Ilyas Dundar ◽  
Mesut Ozgokce ◽  
Fatma Durmaz ◽  
Sercan Ozkacmaz ◽  
Saim Turkoglu ◽  
...  
Keyword(s):  
Treatment Options ◽  
Type I ◽  
Hydatid Cysts ◽  
Liver Cysts ◽  
Diffusion Weighted ◽  
Significant Difference ◽  
Mean Diameter ◽  
Apparent Diffusion ◽  
Adc Values ◽  
Hepatic Lesions

Background Determining the nature of purely cystic hepatic lesions is essential because different kinds have different follow-ups, treatment options, and complications. Purpose To explore the potential of apparent diffusion coefficient (ADC) values of diffusion-weighted imaging (DWI) for the differentiation of type I hydatid cysts (HC) and simple liver cysts (SLC), which have similar radiological appearances. Material and Methods This single-center prospective study was conducted during 2016–2019. Round, homogenous, anechoic liver cysts >1 cm were classified according to at least two years of imaging follow-up, radiological features, serology, as well as puncture aspiration injection reaspiration procedure and pathology results. ADC values of 95 cysts (50 type I HCs and 45 SLCs) were calculated on DWI. The differences in ADC values were analyzed by independent t-test. Results Of 51 patients, 28 were female, 23 were male (mean age 32.07 ± 22.95 years; age range 5–82 years). Mean diameter of 45 SLCs was 2.59 ± 1.23 cm (range 1.2–7.6 cm) and ADCmean value was 3.03 ± 0.47 (range 2.64–5.85) while mean diameter of 50 type I HCs was 7.49 ± 2.95 cm (range 2.8–14 cm) and ADCmean value was 2.99 ± 0.29 (range 2.36–3.83). There was no statistically significant difference in ADC values between type I HCs and SLCs Conclusion Some studies report that ADC values of type I HCs are statistically significantly lower than those of SLCs. Others suggest no significant difference. In our study with a higher number of cases, using ADC parameters similar to those in previous studies, we did not find any statistically significant difference.

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

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&lt; 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&lt; 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.

scholarly journals The Effect of Alcohol on Telomere Length: A Systematic Review of Epidemiological Evidence and a Pilot Study during Pregnancy

2021 ◽  
Vol 18 (9) ◽  
pp. 5038
Author(s):  
Andrea Maugeri ◽  
Martina Barchitta ◽  
Roberta Magnano San Lio ◽  
Maria Clara La Rosa ◽  
Claudia La Mastra ◽  
...  
Keyword(s):  
Systematic Review ◽  
Pilot Study ◽  
Alcohol Consumption ◽  
Telomere Length ◽  
Molecular Mechanisms ◽  
Epidemiological Studies ◽  
Potential Association ◽  
Significant Difference ◽  
Periconceptional Period ◽  
Using Data

Several studies—albeit with still inconclusive and limited findings—began to focus on the effect of drinking alcohol on telomere length (TL). Here, we present results from a systematic review of these epidemiological studies to investigate the potential association between alcohol consumption, alcohol-related disorders, and TL. The analysis of fourteen studies—selected from PubMed, Medline, and Web of Science databases—showed that people with alcohol-related disorders exhibited shorter TL, but also that alcohol consumption per se did not appear to affect TL in the absence of alcohol abuse or dependence. Our work also revealed a lack of studies in the periconceptional period, raising the need for evaluating this potential relationship during pregnancy. To fill this gap, we conducted a pilot study using data and samples form the Mamma & Bambino cohort. We compared five non-smoking but drinking women with ten non-smoking and non-drinking women, matched for maternal age, gestational age at recruitment, pregestational body mass index, and fetal sex. Interestingly, we detected a significant difference when analyzing relative TL of leukocyte DNA of cord blood samples from newborns. In particular, newborns from drinking women exhibited shorter relative TL than those born from non-drinking women (p = 0.024). Although these findings appeared promising, further research should be encouraged to test any dose–response relationship, to adjust for the effect of other exposures, and to understand the molecular mechanisms involved.

scholarly journals Lockdown, slow down: impact of the COVID-19 pandemic on physical activity—an observational study

Open Heart ◽  
2021 ◽  
Vol 8 (1) ◽  
pp. e001600
Author(s):  
Joanne Kathryn Taylor ◽  
Haarith Ndiaye ◽  
Matthew Daniels ◽  
Fozia Ahmed
Keyword(s):  
Physical Activity ◽  
New York ◽  
Heart Association ◽  
Evaluation Study ◽  
Activity Data ◽  
Cardiac Devices ◽  
Significant Difference ◽  
New York Heart Association ◽  
Using Data ◽  
The Uk

AimsIn response to the COVID-19 pandemic, the UK was placed under strict lockdown measures on 23 March 2020. The aim of this study was to quantify the effects on physical activity (PA) levels using data from the prospective Triage-HF Plus Evaluation study.MethodsThis study represents a cohort of adult patients with implanted cardiac devices capable of measuring activity by embedded accelerometery via a remote monitoring platform. Activity data were available for the 4 weeks pre-implementation and post implementation of ‘stay at home’ lockdown measures in the form of ‘minutes active per day’ (min/day).ResultsData were analysed for 311 patients (77.2% men, mean age 68.8, frailty 55.9%. 92.2% established heart failure (HF) diagnosis, of these 51.2% New York Heart Association II), with comorbidities representative of a real-world cohort.Post-lockdown, a significant reduction in median PA equating to 20.8 active min/day was seen. The reduction was uniform with a slightly more pronounced drop in PA for women, but no statistically significant difference with respect to age, body mass index, frailty or device type. Activity dropped in the immediate 2-week period post-lockdown, but steadily returned thereafter. Median activity week 4 weeks post-lockdown remained significantly lower than 4 weeks pre-lockdown (p≤0.001).ConclusionsIn a population of predominantly HF patients with cardiac devices, activity reduced by approximately 20 min active per day in the immediate aftermath of strict COVID-19 lockdown measures.Trial registration numberNCT04177199.

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