scholarly journals MR Spectroscopic Imaging Predicts Early Response to Anti-Angiogenic Therapy in Recurrent Glioblastoma

2021 ◽  
Author(s):  
Pratik Talati ◽  
Mohamed El-Abtah ◽  
Daniel Kim ◽  
Jorg Dietrich ◽  
Melanie Fu ◽  
...  
Keyword(s):  
Patient Outcomes ◽  
Early Response ◽  
Recurrent Glioblastoma ◽  
Time Points ◽  
Angiogenic Therapy ◽  
Longitudinal Mri ◽  
Early Failures ◽  
Assess Treatment Response ◽  
Insight Into ◽  
Mr Spectroscopic Imaging

Abstract Background Determining failure to anti-angiogenic therapy in recurrent GBM (rGBM) remains a challenge. The purpose of the study was to assess treatment response to bevacizumab-based therapy in patients with rGBM using MR spectroscopy (MRS). Methods We performed longitudinal MRI/MRS in 33 patients with rGBM to investigate whether changes in N-acetylaspartate (NAA)/Choline (Cho) and Lactate (Lac)/NAA from baseline to subsequent time points after treatment can predict early failures to bevacizumab-based therapies. Results After stratifying based on 9 month survival, longer-term survivors had increased NAA/Cho and decreased Lac/NAA levels compared to shorter-term survivors. ROC analyses for intratumoral NAA/Cho correlated with survival at 1 day, 2 weeks, 8 weeks, and 16 weeks. Intratumoral Lac/NAA ROC analyses were predictive of survival at all time points tested. At the 8 week time point, 88% of patients with decreased NAA/Cho did not survive 9 months; furthermore, 90% of individuals with an increased Lac/NAA from baseline did not survive at 9 months. No other metabolic ratios tested significantly predicted survival. Conclusions Changes in metabolic levels of tumoral NAA/Cho and Lac/NAA can serve as early biomarkers for predicting treatment failure to anti-angiogenic therapy as soon as 1 day after bevacizumab-based therapy. The addition of MRS to conventional MR methods can provide better insight into how anti-angiogenic therapy affects tumor microenvironment and predict patient outcomes.

TAMI-29. MR SPECTROSCOPY MEASURES OF LAC/NAA AND NAA/CHO DIFFERENTIATE SURVIVORSHIP IN PATIENTS WITH RECURRENT GLIOBLASTOMA TREATED WITH ANTI-ANGIOGENIC THERAPY

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi204-vi204
Author(s):  
Pratik Talati ◽  
Mohamed El-Abtah ◽  
Daniel Kim ◽  
Jorg Dietrich ◽  
Melanie Fu ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Mr Spectroscopy ◽  
Recurrent Glioblastoma ◽  
Spectroscopy Data ◽  
Time Points ◽  
Angiogenic Therapy ◽  
Early Biomarkers ◽  
Conventional Mri

Abstract Patients with recurrent glioblastoma (rGBM) are often started on anti-angiogenic therapy such as bevacizumab. However, determining treatment failure using conventional MRI methods remains challenging. We prospectively collected longitudinal MR spectroscopy data in 33 patients with rGBM and quantified various metabolites including N-acetylaspartate (NAA), Choline (Cho), and Lactate (Lac). After stratifying patients by 9 month survival, we found that longer-term survivors had decreased Lac/NAA and increased NAA/Cho compared to shorter-term survivors. ROC analyses illustrated that intratumoral changes in NAA/Cho were predictive of survival at 1 day (AUC 0.92), 2 weeks (AUC 0.75), 8 weeks (AUC 0.71) and 16 weeks (AUC 0.85) but not 4 weeks (AUC 0.60). Intratumoral changes in Lac/NAA were predictive of survival at all time points tested (AUCs > 0.76 for all time points). At 8 weeks, 90% of patients with increased Lac/NAA from baseline and 88% of patients with decreased NAA/Cho did not survive 9 months. Changes in NAA/Cho and Lac/NAA may serve as early biomarkers of anti-angiogenic treatment failure.

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.

Developing Adaptive Change Capabilities Through Client-Centred Therapy

2012 ◽  
Vol 29 (4) ◽  
pp. 258-271 ◽  
Author(s):  
Terry Bowles
Keyword(s):  
Gender Differences ◽  
Therapeutic Alliance ◽  
Adaptive Change ◽  
The State ◽  
Residual Effects ◽  
Clinical Group ◽  
Therapeutic Experience ◽  
Time Points ◽  
Insight Into

Clients undergo change as a function of engaging in a therapeutic experience. To date, little research into the residual effects of therapy have been completed using client-centred therapy. Some therapies provide didactic experiences to gain and practise skills and understandings so they can be recalled after the conclusion of therapy. Other therapies preclude such interventions and instead emphasise the insights of the client and the transformative therapeutic alliance to facilitate change. This research is an investigation of the possibility that client-centred therapy provides clients with experiences to allow insight into, and understanding of processes to optimally facilitate change through therapy. The aims of the research were to establish: whether factors known to enhance change in therapy increased for clients from the beginning to the end of therapy; whether the clinical group (n = 28; intervention) scores differed from a nonclinical group at both time points (n = 22; control); and establish whether gender differences were present. Analyses showed that nonclinical respondents’ scores at Times 1 and 2 were consistently higher on all factors compared with clinical respondents. The findings indicated that scores did not vary significantly between Time 1 and 2 for either the clinical or the nonclinical groups of respondents. The state/trait-like characteristics of the factors are discussed in reference to their application in therapeutic and applied settings.

scholarly journals Multi-species transcriptome meta-analysis of the response to retinoic acid in vertebrates and comparative analysis of the effects of retinol and retinoic acid on gene expression in LMH cells

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Clemens Falker-Gieske ◽  
Andrea Mott ◽  
Sören Franzenburg ◽  
Jens Tetens
Keyword(s):  
Gene Expression ◽  
Retinoic Acid ◽  
Cellular Response ◽  
Homo Sapiens ◽  
Meta Analysis ◽  
Early Response ◽  
Rna Seq ◽  
Transcriptomic Response ◽  
Time Points ◽  
Lmh Cells

Abstract Background Retinol (RO) and its active metabolite retinoic acid (RA) are major regulators of gene expression in vertebrates and influence various processes like organ development, cell differentiation, and immune response. To characterize a general transcriptomic response to RA-exposure in vertebrates, independent of species- and tissue-specific effects, four publicly available RNA-Seq datasets from Homo sapiens, Mus musculus, and Xenopus laevis were analyzed. To increase species and cell-type diversity we generated RNA-seq data with chicken hepatocellular carcinoma (LMH) cells. Additionally, we compared the response of LMH cells to RA and RO at different time points. Results By conducting a transcriptome meta-analysis, we identified three retinoic acid response core clusters (RARCCs) consisting of 27 interacting proteins, seven of which have not been associated with retinoids yet. Comparison of the transcriptional response of LMH cells to RO and RA exposure at different time points led to the identification of non-coding RNAs (ncRNAs) that are only differentially expressed (DE) during the early response. Conclusions We propose that these RARCCs stand on top of a common regulatory RA hierarchy among vertebrates. Based on the protein sets included in these clusters we were able to identify an RA-response cluster, a control center type cluster, and a cluster that directs cell proliferation. Concerning the comparison of the cellular response to RA and RO we conclude that ncRNAs play an underestimated role in retinoid-mediated gene regulation.

scholarly journals New Insight into the Prevalence and Risk Factors for Three Distinct Hoof Conformation Traits in UK Commercial Sheep Flocks

2021 ◽  
Vol 8 (9) ◽  
pp. 176
Author(s):  
Caroline M. Best ◽  
Janet Roden ◽  
Kate Phillips ◽  
Alison Z. Pyatt ◽  
Malgorzata C. Behnke
Keyword(s):  
Risk Factors ◽  
Global Health ◽  
Prospective Studies ◽  
Exploratory Study ◽  
Predisposing Factors ◽  
Farm Level ◽  
Time Points ◽  
First Time ◽  
Insight Into

Lameness in sheep continues to be a global health, welfare and economic concern. Damaged, misshapen or overgrown feet have the potential to cause lameness either directly, or indirectly. There is a lack of understanding of the predisposing factors for different hoof conformation traits in sheep. Our exploratory study aimed to investigate the prevalence of, and risk factors for, three distinct hoof conformation traits relating to the sole and heel, hoof wall, and hoof wall overgrowth. Feet of 400 ewes from four UK commercial sheep farms were inspected at four time points across 12 months. For each conformation trait, a four-point ordinal system was used to score each individual claw, and foot-level scores were calculated. We present 92.4% of foot-level observations to be affected by ≥1 conformation traits. Whilst hoof conformation traits were correlated to some degree, a unique set of sheep-, foot- and farm-level factors were associated with each distinct conformation trait. We provide, for the first time, key insight into the multifaceted and multifactorial aetiology of hoof conformation in sheep, building upon previous landmark studies. Our results inform hypotheses for future prospective studies investigating the risk factors for adverse hoof conformation in sheep.

scholarly journals Preliminary results using PET/MR in glioblastoma patients treated with regorafenib: an 18F-FET and DWI-ADC comparison

2021 ◽  
Author(s):  
Alessandro Spimpolo ◽  
Giuseppe Lombardi ◽  
Sara Berti ◽  
Cristina Campi ◽  
Maria Giulia Anglani ◽  
...  
Keyword(s):  
Early Response ◽  
Recurrent Glioblastoma ◽  
Response To Treatment ◽  
Fet Pet ◽  
Additional Information ◽  
Rano Criteria ◽  
Percentage Difference ◽  
Before And After ◽  
The Difference ◽  
Cancer Network

Abstract Introduction: The use of regorafenib in recurrent glioblastoma patients has been recently approved by the Italian Medicines Agency (AIFA) and added to the National Comprehensive Cancer Network (NCCN) 2020 guidelines as a preferred regimen. Given its complex effects at the molecular level, the most appropriate imaging tools to assess early response to treatment is still a matter of debate. DWI and 18F–FET PET are promising methodologies providing additional information to the currently used RANO criteria. The aim of this study was to evaluate the variations in DWI/ADC- and 18F-FET PET-derived parameters in patients who underwent PET/MR at both baseline and soon after starting regorafenib. Method: We retrospectively selected 16 consecutive GBM patients who underwent 18F–FET PET/MR before and after two cycles of regorafenib. Patients were sorted into stable (SD) or progressive disease (PD) categories in accordance with RANO criteria. We were also able to analyze 4 SD patients who underwent a third PET/MR after another 4 cycles of regorafenib. 18F–FET uptake greater than 1.6 times the mean background activity was used to define an area to be superimposed on an ADC map at baseline and soon after treatment. A number of metrics were then derived and compared. Result: The average increases in FET and ADC pathological volumes were higher in PD than in SD patients, although in neither case did the difference reach significance. However, when the percentage difference in FET volumes was plotted against the corresponding percentage difference in ADC, a correlation was observed (R = 0.54). Patients with a twofold increase in FET after regorafenib showed a significantly higher increase in ADC pathological volume than the remaining subjects (p = 0.0023). Conclusion: In recurrent glioblastoma patients treated with regorafenib, 18F-FET and ADC metrics, being obtained from completely different measures, could serve as semi-quantitative independent biomarkers of response to treatment. These promising parameters should be tested in a larger cohort of glioblastoma patients treated with regorafenib.

Abstract 18021: Functional Substrates as the Strongest Predictor of Outcomes in Patients Presenting for Ventricular Arrhythmia Ablation

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Justin Hayase ◽  
Yonatan Faiwiszewski ◽  
Stephen Vampola ◽  
Aron Bender ◽  
Gordon Ho ◽  
...  
Keyword(s):  
Ventricular Arrhythmia ◽  
Patient Outcomes ◽  
Roc Analysis ◽  
Youden Index ◽  
History Of ◽  
Forward Stepwise ◽  
Left And Right ◽  
Insight Into ◽  
Procedural Outcome

Introduction: Recent work has shown that rotor characteristics can distinguish sustained versus non-sustained ventricular fibrillation (VF). However, the significance of functional VF substrates on patient outcomes is not studied. Methods: In 26 consecutive patients presenting for ventricular arrhythmia ablation procedures, 64-electrode basket catheters were inserted into both the left and right ventricles and VF was induced and defibrillated at 11±3 seconds. Computational phase analysis was performed and each VF cycle was characterized as rotor, focal, or disorganized activation. Follow-up data were analyzed for arrhythmia recurrence and compared to rotor stability. Forward stepwise regression analysis incorporating age, history of CHF, history of a-fib, history of prior MI, number of VTs induced, and presence of post-procedure inducible VT was performed to determine the strongest predictor of procedural outcome. Results: Of 26 patients, 19 had sustained VF, and 16 underwent attempted ablation (7 VT, 9 PVC). Optimization of the Youden index for the ROC analysis regarding rotor stability and procedural outcome demonstrated that maximum rotor stability of > 14.5 rotations (corresponding to total rotor prevalence of 71%) provided optimal sensitivity of 85% and specificity of 87% for arrhythmia recurrence. Among these, greater rotor stability was significantly associated with ventricular arrhythmia recurrence (86% versus 11%, p = 0.01) (Table 1), and was the strongest predictor of outcomes. Recurrence was independent of presenting arrhythmia. Conclusions: Functional VF/VT metrics were the strongest predictor of ventricular arrhythmia outcomes compared to traditional predictors in this series of patients. This suggests that functional substrate characteristics may provide added insight into recurrence mechanisms. Whether they may identify a target for future interventions requires further study.

Unexpected serious aplastic anemia from PD-1 inhibitors: beyond what we know

2019 ◽  
Vol 105 (6) ◽  
pp. NP48-NP51 ◽  
Author(s):  
Marco Filetti ◽  
Raffaele Giusti ◽  
Arianna Di Napoli ◽  
Daniela Iacono ◽  
Paolo Marchetti
Keyword(s):  
Aplastic Anemia ◽  
Patient Outcomes ◽  
Case Reports ◽  
Stage Iv ◽  
Standard Of Care ◽  
Real World Data ◽  
Case Presentation ◽  
Lung Cancers ◽  
Insight Into ◽  
Made In

Introduction: The recent introduction of checkpoint inhibitor–based immunotherapy has revolutionized the treatment of advanced lung cancers, becoming standard of care in both first- and second-line treatment. New types of toxicity are emerging with the increasingly widespread use of these inhibitors. Case presentation: We describe a case of aplastic anemia in a patient with stage IV non-small cell lung cancer after a single administration of nivolumab. Conclusions: Several similar case reports reported in literature show an increasing rate of toxicities from immunotherapy in this setting. These real-world data provide an insight into patient outcomes and treatment decisions being made in clinical practice.

scholarly journals P60 Efficacy of switching to infliximab biosimilar (Remsima®) in paediatric inflammatory bowel disease (PIBD): a 2-Year retrospective evaluation

2020 ◽  
Vol 105 (9) ◽  
pp. e37.2-e38
Author(s):  
Fatima Yaqub ◽  
Joanne Crook ◽  
John Fell
Keyword(s):  
Inflammatory Bowel Disease ◽  
Treatment Failure ◽  
Disease Activity ◽  
Patient Outcomes ◽  
Bowel Disease ◽  
Adverse Reactions ◽  
Double Blind ◽  
Time Points ◽  
Parallel Group ◽  
Inflammatory Bowel

AimTo evaluate patient outcomes 2 years post switching Infliximab therapy from Infliximab originator molecule Remicade® to biosimilar Remsima®.MethodsPatients with PIBD who experienced induction with Remicade® therapy, were <18 years old at last follow-up and were receiving active treatment with Remsima® 2 years post switching were selected to be included for evaluation. Outcome measures included monitoring disease activity and treatment failure at baseline (before switching) and at selected time points up to 2 years post-switch. Disease activity was assessed looking at a range of parameters: disease activity scores; trough infliximab levels; haematological markers (HGB, platelets, WBC); LFTs (bilirubin, ALT, ALP); inflammatory markers (ESR, CRP) and faecal calprotectin levels. Patients who failed therapy were assessed for adverse reactions and infliximab antibody formation. Data was analysed with the Cochran Q test, repeated measures ANOVA test and Friedman test; with post-hoc Bonferroni and Wilcoxon Signed-Ranks tests if appropriate.ResultsData was available for 18 patients after exclusion criteria were applied. There was a significant increase in trough infliximab levels by the end of the period from an average of 5 ug/L to 12 ug/L at 2 years. The average dose/kg increased over 2 years by 1.5 mg/kg. Disease activity markers showed no changes between time points except a decrease in ALP levels from baseline to 1 year, but values remained within normal ranges. Four patients were discontinued from Remsima® due to side effects or loss of efficacy. The average time to treatment failure on Remsima® was 38 months (~19/20 doses). Three out of four patients developed infliximab antibodies, 2 of these patients went on to suffer adverse reactions; 1 exhibited joint pain which settled weeks after each infusion and the other developed an immediate infusion reaction in the form of a rash with urticaria on the 3rd infusion of Remsima®.ConclusionInfliximab biosimilars, such as Remsima®, were approved for use in PIBD by the EMA after studies in adult populations with rheumatic diseases.1 2 Induction studies have shown efficacy in PIBD but data on switching is limited and short-term.3 4 Our data shows no significant differences in clinical patient outcomes over a 2-year period in a cohort switched from Remicade® to Remsima®. In fact, a significant increase in trough infliximab levels in patients remaining on Remsima® suggests efficacy in producing therapeutic levels in PIBD patients. Increased levels may be explained by dose intensification used by the PIBD multi-disciplinary team (MDT), reflecting careful dose optimisation strategies used at this trust throughout the time period. Patients losing response were not unexpected and are likely not due to the biosimilar switch but rather due to the length of time the patients were on treatment. The small sample size and retrospective nature of this study mean larger cohort studies are required over prolonged time periods to confirm these findings. PIBD MDTs should continue to monitor patients for adverse reactions, particularly in those who develop infliximab antibodies.ReferencesPark W, Hrycaj P, Jeka S, et al. A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study. Ann Rheum Dis 2013;72:1605–1612.Yoo DH, Hrycaj P, Miranda P, et al. Extended report: a randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when co-administered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study. Ann Rheum Dis 2013;72:1613.Sieczkowska J, Jarzębicka D, Banaszkiewicz A, et al. Switching Between Infliximab Originator and Biosimilar in Paediatric Patients with Inflammatory Bowel Disease. Preliminary Observations. J Crohn’s Colitis 2016;10:127–132.Sieczkowska J, Jarzębicka D, Meglicka M, et al. Experience with biosimilar infliximab (CT-P13) in paediatric patients with inflammatory bowel diseases. Therap Adv Gastroenterol 2016;9:729–735.

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