scholarly journals Early Pseudoprogression following Chemoradiotherapy in Glioblastoma Patients: The Value of RANO Evaluation

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Paulo Linhares ◽  
Bruno Carvalho ◽  
Rita Figueiredo ◽  
Rui M. Reis ◽  
Rui Vaz
Keyword(s):  
Survival Data ◽  
Response Assessment ◽  
Rank Analysis ◽  
Rano Criteria ◽  
Macdonald Criteria ◽  
Kaplan Meier ◽  
Early Progression ◽  
Radiological Response ◽  
The Impact ◽  
True Progression

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.

scholarly journals Pseudoprogression Following Chemoradiotherapy for Glioblastoma Multiforme

2010 ◽  
Vol 37 (1) ◽  
pp. 36-42 ◽  
Author(s):  
Paul Sanghera ◽  
James Perry ◽  
Arjun Sahgal ◽  
Sean Symons ◽  
Richard Aviv ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Median Survival ◽  
Imaging Features ◽  
Rank Analysis ◽  
Kaplan Meier ◽  
Early Progression ◽  
Disease Stabilization ◽  
Radiological Response ◽  
Radiographic Data

Purpose:Pseudoprogression (psPD) is now recognised following radiotherapy with concurrent temozolomide (RT/TMZ) for glioblastoma multiforme (GBM). The aim of this study was to determine the incidence of psPD following RT/TMZ and the effect of psPD on prognosis.Materials/Methods:All patients receiving RT/TMZ for newly diagnosed GBM were identified from a prospective database. Clinical and radiographic data were retrospectively reviewed. Early progression was defined as radiological progression (RECIST criteria) during or within eight weeks of completing RT/TMZ. Pseudoprogression was defined as early progression with subsequent disease stabilization, without salvage therapy, for at least six months from completion of RT/TMZ. The primary outcome was overall survival (Kaplan-Meier) and log rank analysis was used to compare groups.Results:Out of 111 patients analyzed, 104 were evaluable for radiological response. Median age was 58 years and median follow-up 55 weeks. Early progression was confirmed in 26% and within this group 32% had psPD. Median survival for the whole cohort was 56.7 weeks [95% CI (51.0, 71.3)]. Median survival for patients with psPD was significantly higher than for patients with true early progression (124.9 weeks versus 36.0 weeks, p=0.0286).Conclusions:Approximately one third of patients with early progression were found to have psPD which was associated with a favourable prognosis. Maintenance TMZ should not be abandoned on the basis of seemingly discouraging imaging features identified within the first three months after RT/TMZ.

Survival analyses

2021 ◽  
pp. 229-244
Author(s):  
Sarah Cubaynes ◽  
Simon Galas ◽  
Myriam Richaud ◽  
Ana Sanz Aguilar ◽  
Roger Pradel ◽  
...  
Keyword(s):  
Survival Data ◽  
Complex Life Cycle ◽  
Mortality Data ◽  
Human Populations ◽  
Imperfect Detection ◽  
Survival Analyses ◽  
Kaplan Meier ◽  
Animal Populations ◽  
Free Ranging ◽  
The Impact

Survival analyses are a key tool for demographers, ecologists, and evolutionary biologists. This chapter presents the most common methods and illustrates their use for species across the Tree of Life. It discusses the challenges associated with various types of survival data, how to model species with a complex life cycle, and includes the impact of environmental factors and individual heterogeneity. It covers the analysis of ‘known-fate’ data collected in lab conditions, using the Kaplan–Meier estimator and Cox’s proportional hazard regression analysis. Alternatively, survival data collected on free-ranging populations usually involve individuals missing at certain monitoring occasions and unknown time at death. The chapter provides an overview of capture–mark–recapture (CMR) models, from single-state to multi-state and multi-event models, and their use in animal and plant demography to estimate demographic parameters while correcting for imperfect detection of individuals. It discusses various inference frameworks available to implement CMR models using a frequentist or Bayesian approach. Only humans are an exception among free-ranging populations, with the existence of several consequent databases with perfect knowledge of age and cause of death for all individuals. The chapter presents an overview of the most common models used to describe mortality patterns over age and time using human mortality data. Throughout, focus is placed on eight case studies, which involve lab organisms, free-ranging animal populations, plant populations, and human populations. Each example includes data and codes, together with step-by-step guidance to run the survival analysis.

scholarly journals A novel, reproducible, and objective method for volumetric magnetic resonance imaging assessment of enhancing glioblastoma

2014 ◽  
Vol 121 (3) ◽  
pp. 536-542 ◽  
Author(s):  
Charles W. Kanaly ◽  
Ankit I. Mehta ◽  
Dale Ding ◽  
Jenny K. Hoang ◽  
Peter G. Kranz ◽  
...  
Keyword(s):  
Interobserver Variability ◽  
Intraclass Correlation ◽  
Evaluation Criteria ◽  
Correlation Coefficients ◽  
Response Assessment ◽  
Volumetric Method ◽  
Kappa Statistics ◽  
Macdonald Criteria ◽  
Automated Method ◽  
Radiological Response

Object Robust methodology that allows objective, automated, and observer-independent measurements of brain tumor volume, especially after resection, is lacking. Thus, determination of tumor response and progression in neurooncology is unreliable. The objective of this study was to determine if a semi-automated volumetric method for quantifying enhancing tissue would perform with high reproducibility and low interobserver variability. Methods Fifty-seven MR images from 13 patients with glioblastoma were assessed using our method, by 2 neuroradiologists, 1 neurosurgeon, 1 neurosurgical resident, 1 nurse practitioner, and 1 medical student. The 2 neuroradiologists also performed traditional 1-dimensional (1D) and 2-dimensional (2D) measurements. Intraclass correlation coefficients (ICCs) assessed interobserver variability between measurements. Radiological response was determined using Response Evaluation Criteria In Solid Tumors (RECIST) guidelines and Macdonald criteria. Kappa statistics described interobserver variability of volumetric radiological response determinations. Results There was strong agreement for 1D (RECIST) and 2D (Macdonald) measurements between neuroradiologists (ICC = 0.42 and 0.61, respectively), but the agreement using the authors' novel automated approach was significantly stronger (ICC = 0.97). The volumetric method had the strongest agreement with regard to radiological response (κ = 0.96) when compared with 2D (κ = 0.54) or 1D (κ = 0.46) methods. Despite diverse levels of experience of the users of the volumetric method, measurements using the volumetric program remained remarkably consistent in all users (0.94). Conclusions Interobserver variability using this new semi-automated method is less than the variability with traditional methods of tumor measurement. This new method is objective, quick, and highly reproducible among operators with varying levels of expertise. This approach should be further evaluated as a potential standard for response assessment based on contrast enhancement in brain tumors.

P14.86 Predictive value of MGMT promoter (pMGMT) methylation status on pseudoprogression (PsP) and survival analysis in Glioblastoma (GBM) patients: a retrospective single institutional analysis

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii54-ii54
Author(s):  
V Interno’ ◽  
P De Santis ◽  
L Stucci ◽  
C Porta
Keyword(s):  
Survival Analysis ◽  
Brain Mri ◽  
Methylation Status ◽  
Response Assessment ◽  
Potential Effect ◽  
Primary Brain Tumor ◽  
Survival Outcome ◽  
Maximal Extension ◽  
Radiological Response ◽  
True Progression

Abstract BACKGROUND Glioblastoma is the most common and aggressive primary brain tumor. Conventional therapies, such as maximal extension of surgery followed by radiotherapy (RT) and chemotherapy with Temozolomide (TMZ) have not resulted in major improvements in terms of patients’ outcome, overall survival (OS) still remaining poor. In this context, radiological response assessment after radiotherapy remains challenging due to the potential effect of radionecrosis, often mimicking tumor progression. Differentiation between PsP and true progression is required to avoid further unnecessary surgeries, or the premature discontinuation of TMZ. It is known that pMGMT methylated patients respond better to chemotherapy than unmethylated counterpart, so, tumor cells necrosis can be enhanced in this setting. The aim of the study is to observe the correlation between pMGMT methylation status with the incidence of PsP in GBM patients at the first radiological evaluation after RT. MATERIALS AND METHODS Patients with histologically diagnosis of GBM from 2017 to 2021 and availability of pMGMT methylation status were enrolled. PsP was radiologically defined at first brain MRI after RT in case of increasing size of the enhancing component and of peritumoral oedema that remain stable or decrease after antioedema therapy, such as a clinical improvement was observed. RESULTS We analysed 55 GBM patients, 35 (64%) displayed pMGMT methylation whereas 20 (36%) resulted pMGMT unmethylated. PsP was evident in 29 patients (53%), all of them showed methylation of pMGMT. In our analysis, none of pMGMT unmethylated patients experienced PsP. Regarding survival outcome for pMGMT methylated patients, our analysis shows a mPFS of 8.7 (95% CI: 5–10) months versus 9.3 (95%CI: 4.6–12.3) months in methylated and unmethylated respectively (p=0.87). CONCLUSIONS Methylation status of pMGMT showed to be predictor of PsP in GBM patients. If validated, this information could be very useful to guide clinicians in differentiating PsP from true progression. To date, our survival analysis regarding PFS showed no statistical difference among methylated patients with respect to the presence or absence of PsP. Thus, PsP seems not to be a marker of responsiveness to common treatment. Further data are needed to validate our results.

scholarly journals Impact of gender on the survival of patients with glioblastoma

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Minjie Tian ◽  
Wenying Ma ◽  
Yueqiu Chen ◽  
Yue Yu ◽  
Donglin Zhu ◽  
...  
Keyword(s):  
Sex Hormones ◽  
Survival Data ◽  
Cox Regression ◽  
Population Based ◽  
Cancer Specific Survival ◽  
Term Survival ◽  
Kaplan Meier ◽  
Male Patients ◽  
Stratified Analysis ◽  
The Impact

Background: Preclinical models have suggested a role for sex hormones in the development of glioblastoma multiforme (GBM). However, the impact of gender on the survival time of patients with GBM has not been fully understood. The objective of the present study was to clarify the association between gender and survival of patients with GBM by analyzing population-based data. Methods: We searched the Surveillance, Epidemiology, and End-Results database who were diagnosed with GBM between 2000 and 2008 and were treated with surgery. Five-year cancer specific survival data were obtained. Kaplan–Meier methods and multivariable Cox regression models were used to analyze long-term survival outcomes and risk factors. Results: A total of 6586 patients were identified; 61.5% were men and 38.5% were women. The 5-year cancer-specific survival (CSS) rates in the male and female groups were 6.8% and 8.3%, respectively (P=0.002 by univariate and P<0.001 by multivariate analysis). A stratified analysis showed that male patients always had the lowest CSS rate across localized cancer stage and different age subgroups. Conclusions: Gender has prognostic value for determining GBM risk. The role of sex hormones in the development of GBM warrants further investigation.

scholarly journals Volumetric study reveals the relationship between outcome and early radiographic response during bevacizumab-containing chemoradiotherapy for unresectable glioblastoma

2021 ◽  
Author(s):  
Kosuke Takigawa ◽  
Nobuhiro Hata ◽  
Yuhei Michiwaki ◽  
Akio Hiwatashi ◽  
Hajime Yonezawa ◽  
...  
Keyword(s):  
Response Assessment ◽  
Complete Response ◽  
Early Response ◽  
Radiographic Response ◽  
Rano Criteria ◽  
Kaplan Meier ◽  
Fluid Attenuated Inversion Recovery ◽  
Volumetric Study ◽  
Definition Of ◽  
The Relationship

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.

scholarly journals NCOG-40. IMPLEMENTING RANO CRITERIA IN A RESOURCE-LIMITED SETTING AND ITS ASSOCIATION WITH OVERALL SURVIVAL OF GLIOMA PATIENTS: EXPERIENCE FROM A NATIONAL CANCER CENTER IN INDONESIA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii137-ii138
Author(s):  
Rusdy Ghazali Malueka ◽  
Henry Sofyan ◽  
Tiara Aninditha ◽  
Rini Andriani
Keyword(s):  
Overall Survival ◽  
Cox Regression ◽  
Demographic Data ◽  
Response Assessment ◽  
Cancer Center ◽  
Cox Regression Analysis ◽  
Rano Criteria ◽  
Cancer Hospital ◽  
Resource Limited ◽  
Kaplan Meier

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.

PRRT neuroendocrine tumor response assessment using blood transcript analysis: The NETest.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 625-625
Author(s):  
Lisa Bodei ◽  
Mark A. Kidd ◽  
Aviral Singh ◽  
Wouter A van der Zwan ◽  
Stefano Severi ◽  
...  
Keyword(s):  
Surrogate Marker ◽  
Peptide Receptor Radionuclide Therapy ◽  
Response Prediction ◽  
Response Assessment ◽  
Complete Response ◽  
Kaplan Meier ◽  
Monitoring Accuracy ◽  
Radiological Response ◽  
Imaging Response

625 Background: Peptide receptor radionuclide therapy (PRRT) is effective for metastatic/inoperable neuroendocrine tumors (NETs). Imaging response assessment is most effective after treatment completion. Blood biomarkers such as PRRT Predictive Quotient (PPQ) and NETest are effective in real-time. PPQ predicts PRRT efficacy, NETest monitors disease. We prospectively evaluated: 1) NETest as a surrogate biomarker for RECIST; 2) Correlation of NETest levels, PPQ prediction and treatment efficacy. Methods: Three independent 177Lu-PRRT-treated GEP-NET and BPNEN cohorts (Rotterdam, Netherlands: n=41; Bad-Berka, Germany: n=44; Meldola, Italy: n=72). Treatment response: RECIST1.1 [Responder (stable, partial/complete response) vs Non-Responder]. Blood sampling: pre-PRRT, prior to each cycle and 6 months (median) after completion of all cycles. PPQ (positive/negative) and NETest (0-100 score) by PCR. Stable<40; progressive >40). CgA (ELISA) as comparator. Samples deidentified, measurement and analyses blinded. Kaplan-Meier survival and Mann-Whitney analyses. Results: 122 of 157 were evaluable. RECIST stabilization or response in 67%; 33% progressed. NETest significantly ( p<0.0001) decreased in RECIST-“responders” (-47±3%); in “non-responders” it elevated (+79±19%, p<0.0005). NETest monitoring accuracy 98% (119/122). Follow-up levels >40 (progressive) vs stable (<40) significantly correlated with mPFS (not reached vs. 10 months; HR 0.04, 95%CI: 0.02-0.07). PPQ response prediction was accurate in 118 (97%); 99% accurate positive and 93% accurate negative prediction. NETest significantly ( p<0.0001) decreased in PPQ-predicted responders (-46±3%) and remained increased in PPQ-predicted non-responders (+75±19%). Follow-up NETest categories stable vs progressive significantly correlated with PPQ prediction and mPFS (not reached vs. 10 months; HR 0.06, 95%CI: 0.03-0.12). CgA failed to identify response to PRRT ( p=NS). Conclusions: NETest accurately (98%) monitors PRRT response and is an effective surrogate marker for radiological response (image concordance 98%). A NETest decrease identified responders and correlated (>97%) with the pretreatment PPQ response predictor.

scholarly journals Volumetric Study Reveals the Relationship Between Outcome and Early Radiographic Response During Bevacizumab-Containing Chemoradiotherapy for Unresectable Glioblastoma

2021 ◽  
Author(s):  
Kosuke Takigawa ◽  
Nobuhiro Hata ◽  
Yuhei Michiwaki ◽  
Akio Hiwatashi ◽  
Hajime Yonezawa ◽  
...  
Keyword(s):  
Response Assessment ◽  
Complete Response ◽  
Early Response ◽  
Radiographic Response ◽  
Rano Criteria ◽  
Kaplan Meier ◽  
Fluid Attenuated Inversion Recovery ◽  
Volumetric Study ◽  
Definition Of ◽  
The Relationship

Abstract Purpose: Although we have shown the clinical benefit of bevacizumab (BEV) in the treatment of unresectable newly diagnosed glioblastomas (nd-GBMs), the relationship between early radiographic response and survival outcome remains unclear. We performed a volumetric study of the early radiographic responses in nd-GBMs treated with BEV.Methods: Twenty-two patients with unresectable nd-GBM treated with BEV during concurrent temozolomide radiotherapy were analyzed. Early responses in fluid-attenuated inversion-recovery (FLAIR) and gadolinium-enhanced T1-weighted images (GdT1WI) were interpreted by an experienced neuroradiologist. 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-interpretation of improvement in GdT1WI was nearly 20% of volume reduction, which was lesser than 50%, the definition of PR applied in 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 to 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 for patient outcome in unresectable nd-GBMs.

EP.TU.142Impact of PC-CRC on curative intent and survival of patients

2021 ◽  
Vol 108 (Supplement_7) ◽  
Author(s):  
Karim Elsayeh ◽  
Alexander Brown ◽  
Srinivas Chintapatla ◽  
Michael Lim
Keyword(s):  
Median Survival ◽  
Metastatic Disease ◽  
Survival Data ◽  
Delayed Diagnosis ◽  
Rank Test ◽  
P Value ◽  
Curative Intent ◽  
Kaplan Meier ◽  
Diagnosis Of Cancer ◽  
The Impact

Abstract Introduction PC-CRC is an important benchmark of endoscopy performance and results in a delayed diagnosis of cancer for patients. Little is known of the impact of PC-CRC on survival; we chose to study this in a cohort of patient at our institution. Methods A retrospective analysis was performed on all PC-CRC from 2015 to 2020. Electronic endoscopic records and case-note review were performed to identify cases. Suitable patients underwent surgery in the absence of widespread metastatic disease after MDT discussion. Survival data were recorded, Kaplan-Meier curves were constructed; the log rank test was used to compare groups, a p-value of &lt; 0.05 was deemed significant. Results There were 32 (24 male) patients with a PC-CRC out of 1207 patients during this interval. The 5-year PC-CRC rate was 2.6%. Median age was 72 (IQR 63-79) years. 10 patients had metastatic disease, 9 with large volume disease that was not resectable. All 9 were palliated with a median survival of 3 (IQR 2-23) months. Twenty-three had potentially curative disease and all underwent surgery. On follow-up a further seven patients died with recurrent disease at a median of 19 (IQR 13-35) months. Sixteen are alive with a median survival of 38 (IQR 27-52) months. The survival curves for the 3 groups are significantly divergent, p-value &lt;0.001. Conclusion The impact of PC-CRC on individual patients is significant as a quarter die within 3 months of diagnosis. A further quarter die within 24 months despite a potentially curative operation due to metastatic disease.

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