Response assessment in neuro-oncology (RANO) criteria: application in clinical research and routine practice

Pharmateca ◽  
2021 ◽  
Vol 11_2021 ◽  
pp. 21-33
Author(s):  
E.A. Kobyakova Kobyakova ◽  
D.Yu. Usachev Usachev ◽  
O.V. Absalyamova Absalyamova ◽  
N.G. Kobyakov Kobyakov ◽  
K.S. Lodygina Lodygina ◽  
...  
2014 ◽  
Vol 16 (suppl 2) ◽  
pp. ii15-ii15 ◽  
Author(s):  
P. Y. Wen ◽  
E. Q. Lee ◽  
M. Van Den Bent ◽  
R. Soffieti ◽  
M. Bendszus ◽  
...  

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi133-vi133
Author(s):  
Gilbert Youssef ◽  
Mary Jane Lim-Fat ◽  
Camden Bay ◽  
Omar Arnaout ◽  
Wenya Linda Bi ◽  
...  

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.


2010 ◽  
Vol 21 (2p2) ◽  
pp. e446-e449 ◽  
Author(s):  
Stefano Miceli Sopo ◽  
Roberta Onesimo ◽  
Valentina Giorgio ◽  
Carlo Fundarò

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Paulo Linhares ◽  
Bruno Carvalho ◽  
Rita Figueiredo ◽  
Rui M. Reis ◽  
Rui Vaz

Introduction. The aim of this study was to determine the frequency of pseudoprogression in a cohort of glioblastoma (GBM) patients following radiotherapy/temozolomide (RT/TMZ) by comparing Macdonald criterial to Response Assessment in Neuro-Oncology (RANO) criteria. The impact on prognosis and survival analysis was also studied.Materials and Methods. All patients receiving RT/TMZ for newly diagnosed GBM from January 2005 to December 2009 were retrospectively evaluated, and demographic, clinical, radiographic, treatment, and survival data were reviewed. Updated RANO criteria were used for the evaluation of the pre-RT and post-RT MRI and compared to classic Macdonald criteria. Survival data was evaluated using the Kaplan-Meier and log-rank analysis.Results and Discussion. 70 patients were available for full radiological response assessment. Early progression was confirmed in 42 patients (60%) according to Macdonald criteria and 15 patients (21%) according to RANO criteria. Pseudoprogression was identified in 10 (23.8%) or 2 (13.3%) patients in Macdonald and RANO groups, respectively. Cumulative survival of pseudoprogression group was higher than that of true progression group and not statistically different from the non-progressive disease group.Conclusion. In this cohort, the frequency of pseudoprogression varied between 13% and 24%, being overdiagnosed by older Macdonald criteria, which emphasizes the importance of RANO criteria and new radiological biomarkers for correct response evaluation.


Author(s):  
Kosuke Takigawa ◽  
Nobuhiro Hata ◽  
Yuhei Michiwaki ◽  
Akio Hiwatashi ◽  
Hajime Yonezawa ◽  
...  

Abstract Purpose Although we have shown the clinical benefit of bevacizumab (BEV) in the treatment of unresectable newly diagnosed glioblastomas (nd-GBM), the relationship between early radiographic response and survival outcome remains unclear. We performed a volumetric study of early radiographic responses in nd-GBM treated with BEV. Methods Twenty-two patients with unresectable nd-GBM treated with BEV during concurrent temozolomide radiotherapy were analyzed. An experienced neuroradiologist interpreted early responses on fluid-attenuated inversion recovery (FLAIR) and gadolinium-enhanced T1-weighted images (GdT1WI). Volumetric changes were evaluated using diffusion-weighted imaging (DWI) and GdT1WI according to the Response Assessment in Neuro-Oncology (RANO) criteria. The results were categorized into improved (complete response [CR] or partial response [PR]) or non-improved (stable disease [SD] or progressive disease [PD]) groups; outcomes were compared using Kaplan–Meier analysis. Results The volumetric GdT1WI improvement was a significant predictive factor for overall survival (OS) prolongation (p = 0.0093, median OS: 24.7 vs. 13.6 months); however, FLAIR and DWI images were not predictive. The threshold for the neuroradiologist’s interpretation of improvement in GdT1WI was nearly 20% of volume reduction, which was lesser than 50%, the definition of PR applied in the RANO criteria. However, even less stringent neuroradiologist interpretation could successfully predict OS prolongation (improved vs. non-improved: p = 0.0067, median OS: 17.6 vs. 8.3 months). Significant impact of OS on the early response in volumetric GdT1WI was observed within the cut-off range of 20–50% (20%, p = 0.0315; 30%, p = 0.087; 40%, p = 0.0456). Conclusions Early response during BEV-containing chemoradiation can be a predictive indicator of patient outcome in unresectable nd-GBM.


2021 ◽  
Vol 11 ◽  
Author(s):  
Lei She ◽  
Lin Su ◽  
Liangfang Shen ◽  
Chao Liu

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.


2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi134-vi134
Author(s):  
Jan-Michael Werner ◽  
Elena Bauer ◽  
Philipp Lohmann ◽  
Caroline Tscherpel ◽  
Anna Brunn ◽  
...  

Abstract BACKGROUND The REGOMA phase 2 trial showed an encouraging overall survival benefit of the multikinase inhibitor regorafenib in glioblastoma patients at first progression. We used O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET for the early assessment of response to regorafenib in patients with progressive glioma in an advanced disease stage. METHODS Thirty patients with progressive glioma were treated according to the REGOMA trial and prospectively followed. FET PET and MRI were performed at baseline and after the second cycle of regorafenib. Static PET parameters such as maximum and mean tumor-to-brain ratios (TBRmax, TBRmean) and metabolic tumor volumes (MTV) were calculated. Threshold values of FET PET parameters to predict a response were established by ROC analyses using an overall survival of ≥ 6 months as reference. The predictive value of FET PET parameters and their changes concerning overall survival was subsequently evaluated using the Kaplan-Meier test. MRI changes were evaluated according to the RANO criteria. RESULTS Up to now, 18 of 30 patients (glioblastoma, 83%; age range, 24-71 years) were eligible for data evaluation. The median number of tumor relapses before regorafenib was 2 (range, 1-4). During regorafenib (median cycles, 4; range, 2-9 cycles), CTCAE grade 3 or 4 side effects occurred in 56% and 11%, respectively. The median overall survival was 6 months (range, 3-18 months). After two cycles of regorafenib, a TBRmean reduction of 13% predicted a significantly longer overall survival (12 vs. 6 months; P=0.034). In contrast, MRI changes evaluated according to RANO criteria (i.e., Stable Disease or Partial Response vs. Progressive Disease) were not predictive (11 vs. 8 months; P=0.644). CONCLUSION Data suggest that amino acid PET using the tracer FET may be clinically valuable for identifying responders to regorafenib early after treatment initiation.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1323-1323
Author(s):  
Mohamed Touati ◽  
Jeremy Assenat ◽  
Jacques Monteil ◽  
Philippe De Souza ◽  
Magdalena Munyamahoro ◽  
...  

Abstract Introduction: The lymphomas stages are currently determined by Ann Arbor-Cotswolds classification that have been created during the “Committee On Hodgkin Disease Staging Classification”, in Ann Arbor (Michigan, USA) in 1971, and modified in Cotswolds (England) in 1988. The classification is used in routine hematology, by doctors and Clinical Research Associates (CRA), in order to estimate the lymphomas' spread, stratify patients and select therapies. In spite of its user-friendliness, every clinician knows that certain scenario depends upon operators. Despite lots of progress, there is no computerized tool that could help to establish an easy disease staging. A French hematological network, HEMATOLIM, in association with the University Hospital of Limoges, developed an information technology (IT) tool to calculate lymphoma's Ann Arbor stage thanks to 3D interactive model. The aim of this work is to make available online an easy to use calculator for mapping all the lymphoma localizations on a 3D interactive mannequin and then obtain quickly a standardized Ann Arbor's staging. Methods: That project has been developed by a mechatronic engineer from the “Ecole Nationale Supérieure d'Ingénieur de Limoges, France” since April 2013. This software is a 3D interactive model interfacing with Ann Arbor stage's calculator. We used anatomical 3D library files, which represent human body's tissues and organs. This free sharing and use database has been created by a Japanese team (Database Center for Life Science Research Organization of Information and Systems Faculty of Engineering Bldg.12; The University Of Tokyo; 2-11-16 Yayoi, Bunkyo-ku, Tokyo). That base concerns only males and doesn't include lymphatic system. We modified it and added in this database the simplified lymphatic system and created female body's tissues and organs. An expert radiologist approved the resulted projections. To make easier the selection of pathological areas, different tools were created (sectional view tools, magnifying glass, dissection scissors, list selection modality, display of territory's names…). This tool is PC compatible and uses OpenGL (Open Graphics Library) 3D engine. It should be used with updated Windows software and accepts all OpenGL versions (See figures 1, 2 and 3). With this 1.0 software version, 20 patients with Hodgkin lymphoma (n = 8) and non-Hodgkin lymphomas (n = 12), managed in our institution between May and July 2014, were evaluated. The Ann Arbor stages determined by physicians during multi-disciplinary team sessions (MDT) were compared with the results of software calculated by a junior CRA. Results: The rate of agreement between the two methods is 81%. MDT staging and Ann Arbor calculator results were in disagreement in 1 patient (6%). Finally, 3D dynamics model was unable to determinate stages in 2 patients' files because some parts of body are not yet included in the model. Kappa coefficient was estimated to 0.827 ± 0.163 (CI 95%: 0.508 – 1.000), meaning a very good agreement. Discussion: We have planned a thorough study to confirm these preliminary results with 80 patients for each stage, in total 320 patients, to obtain a sensitivity or specificity of 95% and 5% of precision. This software represents a consistent help for physicians, hematologists or not. Easy to use, intuitive and fast, it could be an Ann Arbor reference calculator. Improvements are planned for better completeness of the affected tissues. This device could help during MDT to have a standardized and rapid staging. Moreover, that software may be used in educational methods for medical students especially with sectional view tools. It should be very useful in clinical research units to assist in collecting lymphomas data. This software can also help to calculates main scores and prognostic indexes (IPI, FLIPI, IPS…). Conclusion: Online and full versions of this 3D lymphoma's stage calculator assistant will be developed by our network to standardize the staging of disease and to optimize treatment decisions. This software developed initially for lymphoma, can be adapted to the TNM classification of cancers. It should be developed with isotopists and radiologists colleagues to create a new tool, in order to deliver the disease stage automatically from CT-scan or PET/CT. Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures No relevant conflicts of interest to declare.


2020 ◽  
Author(s):  
Benjamin M Ellingson ◽  
Matthew S Brown ◽  
Jerrold L Boxerman ◽  
Elizabeth R Gerstner ◽  
Timothy J Kaufmann ◽  
...  

Abstract Determination of therapeutic benefit in intracranial tumors is intimately dependent on serial assessment of radiographic images. The Response Assessment in Neuro-Oncology (RANO) criteria were established in 2010 to provide an updated framework to better characterize tumor response to contemporary treatments. Since this initial update a number of RANO criteria have provided some basic principles for the interpretation of changes on MR images; however, the details of how to operationalize RANO and other criteria for use in clinical trials are ambiguous and not standardized. In this review article designed for the neuro-oncologist or treating clinician, we outline essential steps for performing radiographic assessments by highlighting primary features of the Imaging Charter (referred to as the Charter for the remainder of this article), a document that describes the clinical trial imaging methodology and methods to ensure operationalization of the Charter into the workings of a clinical trial. Lastly, we provide recommendations for specific changes to optimize this methodology for neuro-oncology, including image registration, requirement of growing tumor for eligibility in trials of recurrent tumor, standardized image acquisition guidelines, and hybrid reader paradigms that allow for both unbiased measurements and more comprehensive interpretation.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii137-ii138
Author(s):  
Rusdy Ghazali Malueka ◽  
Henry Sofyan ◽  
Tiara Aninditha ◽  
Rini Andriani

Abstract INTRODUCTION Gliomas are one of the most common central nervous system tumors in adults. The Response Assessment Criteria in Neuro-Oncology (RANO) was developed to standardize the radiographic parameters used to assess therapeutic outcomes in glioma patients. A previous study has shown an association between therapeutic response based on RANO criteria and overall survival in glioma patients. However, the feasibility of applying RANO criteria in settings with limited resources has never been reported. This study aims to assess the feasibility of applying RANO criteria in clinical settings in Indonesia. This study also wants to see the role of the RANO criteria as a prognostic factor for gliomas in Indonesia. METHOD Data of glioma patients were retrospectively collected from Dharmais Cancer Hospital in Jakarta, Indonesia. Dharmais Cancer Hospital is the highest referral hospital for brain tumors in the country. Clinical and demographic data were collected from the medical record. RESULTS From 138 identified glioma patients from 2017 to May 2020, only 34 patients can be assessed using RANO criteria. The majority of the patients do not have post-surgical MRI that can be used as a baseline. Among 34 included patients, 38.2% were categorized as responsive, 23.5% as stable disease and 38.2% were categorized as progressive. Kaplan-Meier analysis showed that the median overall survival in the progressive group is significantly shorter than the median survival of responsive/stable group (21.2 vs. 57.5 months respectively, p=0.001). Multivariate cox regression analysis was performed to see the association of RANO criteria and other confounding variables (sex, age, glioma grade, glioma location, and therapy) with overall survival. The result showed that RANO progression was significantly associated with decreased survival (HR 18.38, p=0.045). CONCLUSION This retrospective analysis demonstrates the feasibility of applying RANO criteria in Indonesia and its association with overall survival.


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