scholarly journals Assessment of Sodium MRI at 7 Tesla as Predictor of Therapy Response and Survival in Glioblastoma Patients

2021 ◽  
Vol 15 ◽  
Author(s):  
Daniel Paech ◽  
Sebastian Regnery ◽  
Tanja Platt ◽  
Nicolas G. R. Behl ◽  
Nina Weckesser ◽  
...  
Keyword(s):  
Therapy Response ◽  
Progression Free Survival ◽  
Initial Response ◽  
Response Prediction ◽  
Response Assessment ◽  
Sodium Concentration ◽  
7 Tesla ◽  
Clinical Parameters ◽  
Clinical Value ◽  
Rano Criteria

The purpose of this work was to prospectively investigate sodium (23Na) MRI at 7 Tesla (T) as predictor of therapy response and survival in patients with glioblastoma (GBM). Thus, 20 GBM patients underwent 23Na MRI at 7T before, immediately after and 6 weeks after chemoradiotherapy (CRT). The median tissue sodium concentration (TSC) inside the whole tumor excluding necrosis was determined. Initial response to CRT was assessed employing the updated response assessment in neuro-oncology working group (RANO) criteria. Clinical parameters, baseline TSC and longitudinal TSC differences were compared between patients with initial progressive disease (PD) and patients with initial stable disease (SD) using Fisher’s exact tests and Mann-Whitney-U-tests. Univariate proportional hazard models for progression free survival (PFS) and overall survival (OS) were calculated using clinical parameters and TSC metrics as predictor variables. The analyses demonstrated that TSC developed heterogeneously over all patients following CRT. None of the TSC metrics differed significantly between cases of initial SD and initial PD. Furthermore, TSC metrics did not yield a significant association with PFS or OS. Conversely, the initial response according to the RANO criteria could significantly predict PFS [univariate HR (95%CI) = 0.02 (0.0001–0.21), p < 0.001] and OS [univariate HR = 0.17 (0.04–0.65), p = 0.005]. In conclusion, TSC showed treatment-related changes in GBM following CRT, but did not significantly correlate with the initial response according to the RANO criteria, PFS or OS. In contrast, the initial response according to the RANO criteria was a significant predictor of PFS and OS. Future investigations need to elucidate the reasons for treatment-related changes in TSC and their clinical value for response prediction in glioblastoma patients receiving CRT.

NIMG-24. RANO CRITERIA DETECTS EARLY PROGRESSION SOONER THAN MODIFIED RANO CRITERIA IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi133-vi133
Author(s):  
Gilbert Youssef ◽  
Mary Jane Lim-Fat ◽  
Camden Bay ◽  
Omar Arnaout ◽  
Wenya Linda Bi ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Final Analysis ◽  
Response Assessment ◽  
Newly Diagnosed ◽  
Imaging Data ◽  
Treatment Change ◽  
Free Survival ◽  
Rano Criteria ◽  
Newly Diagnosed Glioblastoma ◽  
Post Radiation

Abstract BACKGROUND Accurate response criteria are crucial for determining treatment efficacy. The response assessment in neuro-oncology (RANO) criteria was developed to standardize response assessment in neuro-oncology. Modified RANO (m-RANO) criteria were recently proposed to address some limitations of the initial criteria including the use of a post-radiation baseline and an additional scan to confirm progression. We sought to identify differences in the association of progression-free survival (PFS) and overall survival (OS) using RANO and m-RANO criteria. METHODS We conducted a retrospective review of newly diagnosed glioblastoma (GBM) patients treated at Dana-Farber Cancer Institute from January 2013 until December 2019. Patients with available clinical and imaging data obtained before initiation of treatment, after radiation completion and at intervals of 1 to 3 months were included. MRIs were evaluated by two independent readers, and PD dates determined using RANO and m-RANO criteria. RESULTS 552 patients were included. 97.1% of the tumors were IDH wild-type. MGMT promoter was unmethylated in 51.4%, methylated in 35.1% and undetermined in 8.5%. Median OS among patients was 18.1 months. 72 patients (13%) did not have PD at the end of the study. 83 patients had treatment change while being clinically stable and without a confirmation scan and were excluded from the final analysis. PFS was 8.2 months with RANO and 8.4 months with mRANO. Difference in PD dates between RANO and m-RANO was detected in 76 patients (14%), where PFS was 3.5 months with RANO and 5.1 months with m-RANO. These patients had a worse median OS than those with identical RANO and m-RANO PD dates (15.2 vs. 22.4 months, p< 0.0001). CONCLUSION RANO and m-RANO criteria resulted in identical PFS for most patients. 14% of patients had discordant PD dates and a worse prognosis. These patients progressed early, and their PD was identified sooner with RANO criteria.

scholarly journals Retrospective Study of the Safety and Efficacy of Anlotinib Combined With Dose-Dense Temozolomide in Patients With Recurrent Glioblastoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Lei She ◽  
Lin Su ◽  
Liangfang Shen ◽  
Chao Liu
Keyword(s):  
Survival Curve ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Complete Response ◽  
Recurrent Glioblastoma ◽  
First Line ◽  
Rano Criteria ◽  
First Line Therapy ◽  
Line Therapy ◽  
Dose Dense

PurposeThe purpose of this study was to retrospectively analyze the safety and clinical efficacy of anlotinib combined with dose-dense temozolomide (TMZ) as the first-line therapy in the treatment of recurrent glioblastoma (rGBM).Patients and MethodsWe collected the clinical data of 20 patients with rGBM. All patients received anlotinib (12 mg daily, orally for 2 weeks, discontinued for 1 week, repeated every 3 weeks) combined with dose-dense TMZ (100 mg/m2, 7 days on with 7 days off) until the disease progressed (PD) or adverse effects (AEs) above grade 4 appeared. Grade 3 AEs need to be restored to grade 2 before continuing treatment, and the daily dose of anlotinib is reduced to 10 mg. The patients were reexamined by head magnetic resonance imaging (MRI) every 1 to 3 months. The therapeutic effect was evaluated according to Response Assessment in Neuro-Oncology (RANO) criteria. The survival rate was analyzed by Kaplan-Meier survival curve analysis. The baseline of all survival index statistics was the start of anlotinib combined with dose-dense of TMZ. National Cancer Institute-Common Terminology Criteria Adverse Events version 4.0 (NCI-CTCAE 4.0) was used to evaluate AEs.ResultsTwenty cases of rGBM were evaluated according to the RANO criteria after treatment with anlotinib and dose-dense TMZ, including five cases of stable disease (SD), thirteen cases of partial response (PR), one case of complete response (CR), and one case of PD. The median follow-up time was 13.4 (95% CI, 10.5–16.3) months. The 1-year overall survival (OS) rate was 47.7%. The 6-month progression-free survival (PFS) rate was 55%. In the IDH wild type group, the median PFS and median OS were 6.1 and 11.9 months, respectively. We observed that AEs associated with treatment were tolerable. One patient stopped taking the drug because of cerebral infarction. There were no treatment-related deaths.ConclusionAnlotinib combined with dose-dense TMZ for the first-line therapy showed good efficacy in OS, PFS, ORR, and DCR in the treatment of rGBM, and the AEs were tolerant. Randomized controlled clinical trials investigating the treatment of rGBM with anlotinib are necessary.

Quantitative MRD Assessments Predict Progression Free Survival in CLL Patients Treated with Fludarabine and Cyclophosphamide with or without Rituximab – a Prospective Analysis in 471 Patients from the Randomized GCLLSG CLL8 Trial

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 326-326 ◽  
Author(s):  
Sebastian Boettcher ◽  
Kirsten Fischer ◽  
Stephan Stilgenbauer ◽  
Raymonde Busch ◽  
Günter Fingerle-Rowson ◽  
...  
Keyword(s):  
Randomized Clinical Trials ◽  
Cox Regression ◽  
Residual Disease ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Initial Response ◽  
Response Assessment ◽  
Free Survival ◽  
Treatment Regimens ◽  
Clear Cut

Abstract Data from randomized clinical trials investigating the clinical significance of minimal residual disease (MRD) quantification during and immediately after standard therapy in CLL are still lacking. We therefore related 4-color MRD flow results to progression free survival (PFS) and achievement of complete clinical remission (CCR) in patients (pts) from the GCLLSG CLL8 trial who were randomized to receive 6 cycles of fludarabine and cyclophosphamide (FC) or FC plus Rituximab (FCR). MRD was assessed before therapy, after 3 cycles (interim staging, IS), 1 month (mo) after therapy (initial response assessment, IRA) and 2 mos after IRA (final restaging, FR). 1402 samples from 471 patients who had received at least 3 cycles of therapy were included in the analysis (1162 peripheral blood, PB, 240 bone marrow, BM samples). While initial disease levels were identical between the treatment arms, median PB MRD levels were significantly lower within the FCR arm at IS, IRA, and FR (IS 5.8×10−3 vs. 5.8×1−4, IRA 3.6×1−4 vs. 0, FR 4.4×1−4 vs. 0, all p < 0.0001). Likewise, median BM infiltration was higher after FC than after FCR at IRA (1.6×10−3 vs. 2.1×10−4, p = 0.05) and at FR (8.1×10−4 vs. 1.2×10−4, p<0.0001). The proportion of PB samples with MRD below 10−4 was significantly higher in the FCR arm than in the FC arm (33.6% vs. 6.4% at IS, 67.6% vs. 36.6% at IRA, 66.4% vs. 34.2% at FR, all p < 0.0001). BM samples with MRD levels below 10−4 at FR accounted for 47.6% and 27.3% of samples from the FCR and FC arms, respectively (p=0.005). MRD results were classified into 5 cohorts (<10−4, >=10−4 to < 10−3, >= 10−3 to <10−2, >= 10−2 to < 10−1, and >10−1) in order to assess the prognostic significance of MRD for PFS. Significant differences in median PFS were obtained when PB MRD levels at IS were grouped into <10−2 (70.2% of pts, PFS 44 mos), >= 10−2 to < 10−1 (19.7% of pts, PFS 27 mos) and >10−1 (10.1 % of pts, PFS 11 mos). The PFS of all pts who experienced an MRD reduction below 10−2 was similar, regardless of the exact level. Considering PB MRD levels at FR, clear cut differences in median PFS were observed between pts demonstrating levels < 10−4 (49.6 % of pts, PFS not reached), >= 10−4 and < 10−2 (36.8% of pts, 34 mos) and >= 10−2 (13.6% of pts, 15 mos). Further subdivisions within those 3 cohorts resulted in very similar Kaplan-Meier estimates. BM MRD levels at FR were best classified into two groups, comprising pts with MRD levels of at least 10−2 and below 10−2, respectively. Pts from the former group (11.9 % of pts) experienced a median PFS of 15 mos, compared to a median PFS of 43 mos in the latter group (88.1 %). When MRD levels and treatment regimens were analyzed simultaneously for prognostic significance, only MRD levels were identified as prognostic parameter for PFS using Cox regression in this model. This was tested for PB at IS as well as for PB and for BM at FR. Pts who received FCR achieved up to the FR significantly lower MRD levels and were more often MRD negative. However, once low-level MRD was achieved it had the same prognostic significance in both treatment arms. MRD levels at IS were also associated with the achievement of CCR. Thus, only 14.7% of patients with an MRD level of at least 10−2 achieved a CCR after therapy compared to 49.4% of pts with an MRD level below that threshold (p<0.0001). In summary higher MRD levels were generally associated with shorter PFS whereas lower MRD levels predict longer PFS, regardless of sampling time point, sample material and treatment regimen. Identical MRD levels are associated with similar PFS in both treatment arms. We show that the addition of Rituximab to FC leads to lower median MRD levels compared to FC alone, resulting in longer overall PFS in the FCR group.

scholarly journals DIFFERENCES OF TEMOZOLAMIDE RESPONSE IN GLIOBLASTOMA MULTIFORME: REPORT OF TWO CASES

2020 ◽  
Vol 3 (3) ◽  
pp. 118-126
Author(s):  
Djohan Ardiansyah ◽  
Vita Kusuma Rahmawati ◽  
Sri Andreani Utomo
Keyword(s):  
Prognostic Factors ◽  
Glioblastoma Multiforme ◽  
Clinical Manifestations ◽  
Brain Magnetic Resonance Imaging ◽  
Therapy Response ◽  
Response Assessment ◽  
Complete Response ◽  
Adult Brain ◽  
Rano Criteria ◽  
Standard Management

Background: Glioblastoma multiforme (GBM) is about 20% of primary adult brain neoplasms which has poor prognosis; life expectancy is no more than 12 months after the diagnosis. Temozolomide (TMZ) has become GBM standard therapy, combined with the surgery and radio-chemotherapy. Evaluation is important since its relation with the continuity or termination of therapy. Several studies are improving to measure therapy response of GBM. Response Assessment in Neuro-Oncology (RANO) criteria which is published in 2010, became a major criterias to evaluate TMZ response in patients with GBM. This criteria combines clinical manifestation, steroid therapy, and brain magnetic resonance imaging (MRI). Case: We report two GBM cases with standard management. Two women in productive ages and specific clinical manifestations, diagnosed with GBM in left temporal lobes. A 24-year-old woman showed complete response; while a-41-year old one showed progressive response. Discussion: We analyze TMZ response based on RANO criteria. Prognostic factors that differentiate TMZ response in both cases were presence of comorbidity, intratumoral hemorrhage on MRI, and surgery initiation in early diagnosis. Conclusion: Based on RANO criteria and prognostic factors which support TMZ response, the role of adjuvant TMZ become important in standard management of GBM. Keywords: Glioblastoma Multiforme, Response Assessment in Neuro-Oncology, Temozolomide.

scholarly journals Impact of PET/CT for Assessing Response to Immunotherapy—A Clinical Perspective

2020 ◽  
Vol 9 (11) ◽  
pp. 3483
Author(s):  
David Lang ◽  
Gerald Wahl ◽  
Nikolaus Poier ◽  
Sebastian Graf ◽  
David Kiesl ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Therapy Response ◽  
Response Prediction ◽  
Response Assessment ◽  
Ct Imaging ◽  
Positron Emission ◽  
Pet Ct

Cancer immunotherapy using immune-checkpoint inhibitors (ICI) has revolutionized the therapeutic landscape of various malignancies like non-small-cell lung cancer or melanoma. Pre-therapy response prediction and assessment during ICI treatment is challenging due to the lack of reliable biomarkers and the possibility of atypical radiological response patterns. Positron emission tomography/computed tomography (PET/CT) enables the visualization and quantification of metabolic lesion activity additional to conventional CT imaging. Various biomarkers derived from PET/CT have been reported as predictors for response to ICI and may aid to overcome the challenges clinicians currently face in the management of ICI-treated patients. In this narrative review, experts in nuclear medicine, thoracic oncology, dermatooncology, hemato- and internal oncology, urological and head/neck tumors performed literature reviews in their respective field and a joint discussion on the use of PET/CT in the context of ICI treatment. The aims were to give a clinical overview on present standards and evidence, to identify current challenges and fields of research and to enable an outlook to future developments and their possible implications. Multiple promising studies concerning ICI response assessment or prediction using biomarkers derived from PET/CT alone or as composite biomarkers have been identified for various malignancies and disease stages. Of interest, additional major incentives in the field may evolve from novel tracers specifically targeting immune-checkpoint molecules which could allow not only response assessment and prognosis, but also visualization of histological tumor cell properties like programmed death-ligand (PD-L1) expression in vivo. Despite the broad range of existing literature on PET/CT-derived biomarkers in ICI therapy, implications for daily clinical practice remain elusive. High-quality prospective data are urgently warranted to determine whether patients benefit from the application of PET/CT in terms of prognosis. At the moment, the lack of such evidence as well as the absence of standardized imaging methods and biomarkers still precludes PET/CT imaging to be included in the relevant clinical practice guidelines.

scholarly journals NEIM-05. [GA68]DOTATATE PET/MRI-BASED RADIOSURGICAL RESPONSE ASESSMENT IN MENINGIOMA

2021 ◽  
Vol 3 (Supplement_4) ◽  
pp. iv7-iv7
Author(s):  
Jana Ivanidze ◽  
Sean Kim ◽  
Michelle Roytman ◽  
Rohan Ramakrishna ◽  
Susan Pannullo ◽  
...  
Keyword(s):  
Radiation Treatment ◽  
Prospective Trial ◽  
Standardized Uptake Value ◽  
Progression Free Survival ◽  
Response Assessment ◽  
P Value ◽  
Who Grade ◽  
Rano Criteria ◽  
Clinically Significant

Abstract PURPOSE Postoperative PET/MRI with [68Ga]-DOTATATE can differentiate residual meningioma from postsurgical change, aid in target delineation, and portend a more favorable dosimetry with decreased PTV and organ-at-risk dose. Our purpose was to demonstrate utility of DOTATATE PET/MR for radiosurgical treatment (RT) response assessment in meningiomas. METHODS Patients underwent postoperative radiation treatment planning using DOTATATE PET/MRI as part of our IRB-approved prospective trial. Both DOTATATE PET and gadolinium-enhanced T1 weighted MR imaging were incorporated in RT-planning. All patients underwent follow-up DOTATATE PET/MRI at 6-12 months following completion of radiosurgery. Maximum absolute standardized uptake value (SUV) and SUV ratio (SUVR) of lesion/ superior sagittal sinus SUV were obtained. RANO criteria were applied to determine significance of change in size. Statistical analyses were performed using paired t-tests. RESULTS 13 patients (15% WHO-I, 54% WHO-II, 23% WHO-III, 8% WHO grade unknown) were followed postoperatively with pre- and post-RT DOTATATE PET/MRI. 29 meningiomas were treated. 46% (6/13) of subjects received SBRT and 54% (7/13) received SRS. Post-RT DOTATATE PET/MRI demonstrated a 46.4% SUV decrease (p-value = 0.0001) and a 60.8% SUVR decrease (p-value < 0.0001). Of 21 measurable lesions, the size product decreased by 21%; while this decrease was statistically significant (p-value = 0.0008), it was below the 25% decrease defined as clinically significant by RANO guidelines. To date, all patients remain stable radiographically without evidence of recurrence (mean follow-up post RT: 14 months; range: 6-24 months). CONCLUSIONS DOTATATE PET SUV and SUVR demonstrated marked, significant decrease post radiosurgery. Lesion size decrease was statistically significant but not clinically significant by RANO criteria. DOTATATE PET/MR thus represents a promising approach to aid in response assessment for radiosurgically treated meningiomas. Longer-term follow-up is needed to determine the correlation between the degree of post-RT SUV and/or SUVR decrease and progression-free-survival.

scholarly journals Robustness of radiomic features in CT images with different slice thickness, comparing liver tumour and muscle

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lorena Escudero Sanchez ◽  
Leonardo Rundo ◽  
Andrew B. Gill ◽  
Matthew Hoare ◽  
Eva Mendes Serrao ◽  
...  
Keyword(s):  
Large Fraction ◽  
Therapy Response ◽  
Response Assessment ◽  
Ct Images ◽  
Optimal Number ◽  
Image Features ◽  
Liver Tumour ◽  
Slice Thickness ◽  
Invasive Method ◽  
Feature Values

AbstractRadiomic image features are becoming a promising non-invasive method to obtain quantitative measurements for tumour classification and therapy response assessment in oncological research. However, despite its increasingly established application, there is a need for standardisation criteria and further validation of feature robustness with respect to imaging acquisition parameters. In this paper, the robustness of radiomic features extracted from computed tomography (CT) images is evaluated for liver tumour and muscle, comparing the values of the features in images reconstructed with two different slice thicknesses of 2.0 mm and 5.0 mm. Novel approaches are presented to address the intrinsic dependencies of texture radiomic features, choosing the optimal number of grey levels and correcting for the dependency on volume. With the optimal values and corrections, feature values are compared across thicknesses to identify reproducible features. Normalisation using muscle regions is also described as an alternative approach. With either method, a large fraction of features (75–90%) was found to be highly robust (< 25% difference). The analyses were performed on a homogeneous CT dataset of 43 patients with hepatocellular carcinoma, and consistent results were obtained for both tumour and muscle tissue. Finally, recommended guidelines are included for radiomic studies using variable slice thickness.

scholarly journals Vasculogenic mimicry, a negative indicator for progression free survival of lung adenocarcinoma irrespective of first line treatment and epithelial growth factor receptor mutation status

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xuejun He ◽  
Jijun You ◽  
Haibing Ding ◽  
Zhisheng Zhang ◽  
Lin Cui ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Target Therapy ◽  
Vasculogenic Mimicry ◽  
Therapy Response ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
First Line Treatment

Abstract Background Vascular mimicry (VM) was associated with the prognosis of cancers. The aim of the study was to explore the association between VM and anticancer therapy response in patients with lung adenocarcinoma. Methods This was a single-center retrospective study of patients with lung adenocarcinoma between March 1st, 2013, to April 1st, 2019, at the Second People’s Hospital of Taizhou City. All included patients were divided into the VM and no-VM groups according to whether VM was observed or not in the specimen. Vessels with positive PAS and negative CD34 staining were confirmed as VM. The main outcome was progression-free survival (PFS). Results Sixty-six (50.4%) patients were male. Eighty-one patients received chemotherapy as the first-line treatment, and 50 patients received TKIs. Forty-five (34.4%) patients were confirmed with VM. There was no difference regarding the first-line treatment between the VM and no-VM groups (P = 0.285). The 86 patients without VM had a median PFS of 279 (range, 90–1095) days, and 45 patients with VM had a median PFS of 167 (range, 90–369) days (P < 0.001). T stage (hazard ratio (HR) = 1.37, 95% confidence interval (CI): 1.10–1.71), N stage (HR = 1.43, 95%CI: 1.09–1.86), M stage (HR = 2.85, 95%CI: 1.76–4.61), differentiation (HR = 1.85, 95%CI: 1.29–2.65), therapy (HR = 0.32, 95%CI: 0.21–0.49), VM (HR = 2.12, 95%CI: 1.33–3.37), and ECOG (HR = 1.41, 95%CI: 1.09–1.84) were independently associated with PFS. Conclusion The benefits of first-line TKIs for NSCLC with EGFR mutation are possibly better than those of platinum-based regimens in patients without VM, but there is no difference in the benefit of chemotherapy or target therapy for VM-positive NSCLC harboring EGFR mutations.

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