O7.01 * RESPONSE ASSESSMENT IN NEURO-ONCOLOGY (RANO) CRITERIA FOR BRAIN METASTASES

There is a paucity of biomarkers for the prediction of intracranial (IC) outcome in immune checkpoint inhibitor (ICI)-treated non-small cell lung cancer (NSCLC) patients (pts) with brain metastases (BM). We identified 280 NSCLC pts treated with ICIs at Karolinska University Hospital, Sweden, and University Hospital of Heraklion, Greece. The inclusion criteria for response assessment were brain metastases (BM) prior to ICI administration, radiological evaluation with CT or MRI for IC response assessment, PD-1/PD-L1 inhibitors as monotherapy, and no local central nervous system (CNS) treatment modalities for ≥3 months before ICI initiation. In the IC response analysis, 33 pts were included. Non-primary (BM not present at diagnosis) BM, odds ratio (OR): 13.33 (95% CI: 1.424–124.880, p = 0.023); no previous brain radiation therapy (RT), OR: 5.49 (95% CI: 1.210–25.000, p = 0.027); and age ≥70 years, OR: 6.19 (95% CI: 1.27–30.170, p = 0.024) were associated with increased probability of IC disease progression. Two prognostic groups (immunotherapy (I-O) CNS score) were created based on the abovementioned parameters. The I-O CNS poor prognostic group B exhibited a higher probability for IC disease progression, OR: 27.50 (95% CI: 2.88–262.34, p = 0.004). Age, CNS radiotherapy before the start of ICI treatment, and primary brain metastatic disease can potentially affect the IC outcome of NSCLC pts with BM.

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Use of radiomics for the prediction of local control of brain metastases after stereotactic radiosurgery

Neuro-Oncology ◽

10.1093/neuonc/noaa007 ◽

2020 ◽

Vol 22 (6) ◽

pp. 797-805 ◽

Cited By ~ 5

Author(s):

Andrei Mouraviev ◽

Jay Detsky ◽

Arjun Sahgal ◽

Mark Ruschin ◽

Young K Lee ◽

...

Keyword(s):

Brain Metastases ◽

Stereotactic Radiosurgery ◽

Clinical Features ◽

Characteristic Curve ◽

Response Prediction ◽

Response Assessment ◽

Local Failure ◽

Post Contrast ◽

Axial Diameter ◽

Fluid Attenuated Inversion Recovery

Abstract Background Local response prediction for brain metastases (BM) after stereotactic radiosurgery (SRS) is challenging, particularly for smaller BM, as existing criteria are based solely on unidimensional measurements. This investigation sought to determine whether radiomic features provide additional value to routinely available clinical and dosimetric variables to predict local recurrence following SRS. Methods Analyzed were 408 BM in 87 patients treated with SRS. A total of 440 radiomic features were extracted from the tumor core and the peritumoral regions, using the baseline pretreatment volumetric post-contrast T1 (T1c) and volumetric T2 fluid-attenuated inversion recovery (FLAIR) MRI sequences. Local tumor progression was determined based on Response Assessment in Neuro-Oncology‒BM criteria, with a maximum axial diameter growth of >20% on the follow-up T1c indicating local failure. The top radiomic features were determined based on resampled random forest (RF) feature importance. An RF classifier was trained using each set of features and evaluated using the area under the receiver operating characteristic curve (AUC). Results The addition of any one of the top 10 radiomic features to the set of clinical features resulted in a statistically significant (P < 0.001) increase in the AUC. An optimized combination of radiomic and clinical features resulted in a 19% higher resampled AUC (mean = 0.793; 95% CI = 0.792–0.795) than clinical features alone (0.669, 0.668–0.671). Conclusions The increase in AUC of the RF classifier, after incorporating radiomic features, suggests that quantitative characterization of tumor appearance on pretreatment T1c and FLAIR adds value to known clinical and dosimetric variables for predicting local failure.

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OTHR-14. TREATMENT MONITORING OF IMMUNOTHERAPY AND TARGETED THERAPY USING FET PET IN PATIENTS WITH MELANOMA AND LUNG CANCER BRAIN METASTASES: INITIAL EXPERIENCES

Neuro-Oncology Advances ◽

10.1093/noajnl/vdz014.091 ◽

2019 ◽

Vol 1 (Supplement_1) ◽

pp. i21-i21

Author(s):

Norbert Galldiks ◽

Diana Abdulla ◽

Matthias Scheffler ◽

Viola Schweinsberg ◽

Max Schlaak ◽

...

Keyword(s):

Targeted Therapy ◽

Brain Metastases ◽

Treatment Response ◽

Checkpoint Inhibitors ◽

Response Assessment ◽

Treatment Monitoring ◽

Mri Findings ◽

Fet Pet ◽

Additional Information

Abstract BACKGROUND: Due to the lack of specificity of contrast-enhanced (CE) MRI, both the response assessment and differentiation of progression from pseudoprogression (PsP) following immunotherapy using checkpoint inhibitors (ICI) or targeted therapy (TT) may be challenging, especially when ICI or TT is applied in combination with radiotherapy (RT). Here, we evaluated the value of amino acid PET using O-(2-[18F]fluoroethyl)-L-tyrosine (FET) as a problem-solving tool in comparison to CE-MRI in patients with brain metastases (BM) secondary to malignant melanoma (MM) and NSCLC. METHODS: We retrospectively identified 31 patients with 74 BM secondary to MM (n=20 with 42 BM) and NSCLC (n=11 with 32 BM) who underwent 52 FET-PET scans during the course of disease. All patients had RT prior to ICI or TT initiation (61%) or RT concurrent to ICI or TT (39%). In 13 patients, FET-PET was performed for treatment response assessment of ICI or TT using baseline and follow-up scans (median time between scans, 4.2 months). In the remaining 18 patients, FET-PET was used for the differentiation of progression from PsP related to RT plus ICI or TT. In all BM, metabolic activity on FET-PET was evaluated by calculation of tumor/brain ratios. FET-PET imaging findings were compared to CE-MRI and correlated to the clinical follow-up or neuropathological findings after neuroimaging. RESULTS: In 4 of 13 patients (31%), FET-PET provided additional information for treatment response evaluation beyond the information provided by CE-MRI alone. Furthermore, responding patients on FET-PET had a median stable clinical follow-up of 10 months. In 10 of 18 patients (56%) with CE-MRI findings suggesting progression, FET-PET detected PsP. In 9 of these 10 patients, PsP was confirmed by a median stable clinical follow-up of 11 months. CONCLUSIONS: FET-PET may add valuable information for treatment monitoring in individual BM patients undergoing RT in combination with ICI or TT.

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ANG1005 for brain metastases from breast cancer: 18F-FLT-PET and MRI as complementary approaches to response assessment.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.15_suppl.2552 ◽

2015 ◽

Vol 33 (15_suppl) ◽

pp. 2552-2552 ◽

Cited By ~ 2

Author(s):

Susan Elaine Bates ◽

Maria Liza Lindenberg ◽

Christine Bryla ◽

Mauricio Emmanuel Burotto Pichun ◽

Nicholas Patronas ◽

...

Keyword(s):

Breast Cancer ◽

Brain Metastases ◽

Response Assessment ◽

Flt Pet

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Delayed contrast and multiparametric MRI for treatment response assessment in brain metastases following stereotactic radiosurgery

Neuro-Oncology ◽

10.1093/neuonc/noab195.056 ◽

2021 ◽

Vol 23 (Supplement_4) ◽

pp. iv22-iv23

Author(s):

Markand Patel ◽

Dilina Rajapakse ◽

Jian Ping Jen ◽

Sara Meade ◽

Helen Benghiat ◽

...

Keyword(s):

Brain Metastases ◽

Stereotactic Radiosurgery ◽

Treatment Response ◽

Sensitivity And Specificity ◽

Neuroendocrine Tumour ◽

Response Assessment ◽

Multiparametric Mri ◽

Treatment Response Assessment ◽

Measuring Signal

Abstract Aims Following stereotactic radiosurgery (SRS), brain metastases can increase in size in up to a third of cases. Conventional magnetic resonance imaging (MRI) has a limited role to distinguish between tumour recurrence and SRS-induced changes, which can impact patient management. Delayed contrast MRI treatment response assessment maps (TRAM) use the principle of contrast clearance seen in other tumours, where high vascularity shows a rapid rise in contrast as well as rapid clearance, whereas areas of damaged or low vascularity show accumulation of contrast. We aimed to assess the ability of delayed contrast MRI and multiparametric MRI techniques of diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI) and MR spectroscopy (MRS) to distinguish between radiation-related effects and tumour tissue, as these techniques assess tissue physiological and metabolic information. Method A retrospective review was performed on 23 patients who had delayed contrast and multiparametric MRI between October 2018 to April 2020. Studies were restricted to cases with brain metastases enlarging post-SRS with uncertainty at the MDT meeting regarding progression or treatment-related change, impacting the patient’s management. MRI was performed at 3T including DWI, PWI, MRS with short and intermediate echo times, and 3D T1 MPRAGE at 3-5, 20-30 and 70-90 minutes after administration of intravenous contrast. Contrast clearance analysis was performed by selecting an enhancing region of interest (ROI), measuring signal intensities at the three different timepoints and taking apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV) values from the ROI. Choline/Creatine values were calculated from a single-voxel (10 mm isotropic) encompassing the entire contrast-enhancing lesion. Outcome was established from MRI follow-up at 6 months, with a stable or responding lesion considered treatment-related changes and increase considered progression. Results Across 23 patients, 24 metastases were assessed. Two patients were excluded as appropriate follow-up was not available. Sites of primary tumours included breast (n=8), lung (n=6), melanoma (n=4), neuroendocrine tumour from the lung (n=2) and renal cell carcinoma (n=2). Mean age was 56 years and 50% were female. In this cohort, 59% (n=13) were classified as having radiation-related changes on follow-up. Delayed MRI contrast clearance between the 3-5 and 70-90 minute imaging was significantly higher in cases of progression (23.6% vs. 2.5% decrease, p<0.05), as were the rCBV and Cho/Cr ratio (rCBV 3.1 vs. 1.5 and Cho/Cr ratio 2.3 vs. 1.4, p<0.05). Accuracy, sensitivity and specificity of using TRAM alone (contrast clearance decrease of >0%) for progression was 63%/100%/38%, PWI alone (rCBV cut-off 2.0) yielded results of 77%/75%/79% and for both Cho/Cr ratio alone (cut-off 1.8) and combined with TRAM, it was 90%/88%/92%. Neuroradiologist assessment of all techniques was 95%/100%/92%. Conclusion This study shows the effectiveness of delayed contrast and multiparametric MRI for treatment response assessment in patients with brain metastases treated by SRS in clinical practice. Although a delayed contrast MRI study is a very sensitive tool for detecting tumour progression, it lacks specificity. The accuracy of differentiating between tumour and treatment-related effects increases when delayed contrast MRI is used in combination with other advanced techniques such as MRS. By combining all these techniques, neuroradiologists had the highest accuracy, sensitivity and specificity for detecting progression in post-SRS brain metastases.

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

Neuro-Oncology ◽

10.1093/neuonc/noab196.524 ◽

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.

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32. TREATMENT MONITORING OF IMMUNOTHERAPY AND TARGETED THERAPY USING AMINO ACID PET IN PATIENTS WITH BRAIN METASTASES

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa073.020 ◽

2020 ◽

Vol 2 (Supplement_2) ◽

pp. ii5-ii6

Author(s):

Norbert Galldiks ◽

Diana Abdulla ◽

Matthias Scheffler ◽

Fabian Wolpert ◽

Jan-Michael Werner ◽

...

Keyword(s):

Targeted Therapy ◽

Amino Acid ◽

Brain Metastases ◽

Response Assessment ◽

Diagnostic Value ◽

Treatment Monitoring ◽

Fet Pet ◽

Time To Peak ◽

Amino Acid Pet

Abstract PURPOSE Recently, the RANO group has analyzed the additional diagnostic value of amino acid PET in patients with primary and secondary brain tumors and recommended the use of this imaging technique in addition to conventional MRI. Here, we investigated the value of PET using the radiolabled amino acid O-(2-[18F]fluoroethyl)-L-tyrosine (FET) for treatment monitoring of immune checkpoint inhibition (ICI) or targeted therapy (TT) alone or in combination with radiotherapy in patients with brain metastases (BM) since contrast-enhanced MRI often remains inconclusive. METHODS We retrospectively identified 40 patients with 107 BM secondary to melanoma (n=29 with 75 BM) or non-small cell lung cancer (n=11 with 32 BM) treated with ICI or TT who had FET PET (n=60 scans) for treatment monitoring from 2015–2019. The majority of patients (n=37; 92.5%) had radiotherapy during the course of disease. In 27 patients, FET PET was used for the differentiation of treatment-related changes from BM relapse following ICI or TT. In 13 patients, FET PET was performed for response assessment to ICI or TT using baseline and follow-up scans (median time between scans, 4.2 months). In all lesions, static and dynamic FET PET parameters were obtained (i.e., mean tumour-to-brain ratios (TBR), time-to-peak values). Diagnostic accuracies of PET parameters were evaluated by receiver-operating-characteristic analyses using the clinical follow-up or neuropathological findings as reference. RESULTS A TBR threshold of 1.95 differentiated BM relapse from treatment-related changes with an accuracy of 85% (P=0.003). Metabolic Responders to ICI or TT on FET PET had a significantly longer stable follow-up (threshold of TBR reduction relative to baseline, ≥10%; accuracy, 82%; P=0.004). Furthermore, at follow-up, time-to-peak values in metabolic responders increased significantly (P=0.019). CONCLUSIONS FET PET may add valuable information for treatment monitoring in BM patients treated with ICI or TT.

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The predictive capacity of apparent diffusion coefficient (ADC) in response assessment of brain metastases following radiation

Clinical & Experimental Metastasis ◽

10.1007/s10585-016-9778-x ◽

2016 ◽

Vol 33 (3) ◽

pp. 277-284 ◽

Cited By ~ 16

Author(s):

Raphael Jakubovic ◽

Stephanie Zhou ◽

Chris Heyn ◽

Hany Soliman ◽

Liyang Zhang ◽

...

Keyword(s):

Diffusion Coefficient ◽

Brain Metastases ◽

Apparent Diffusion Coefficient ◽

Response Assessment ◽

Predictive Capacity ◽

Apparent Diffusion

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

Journal of Oncology ◽

10.1155/2013/690585 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 33

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.

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Society for Neuro-Oncology 2014 annual meeting updates on central nervous system metastases

Neuro-Oncology Practice ◽

10.1093/nop/npv009 ◽

2015 ◽

Vol 2 (2) ◽

pp. 57-61 ◽

Cited By ~ 1

Author(s):

Rimas V. Lukas ◽

Minesh P. Mehta ◽

Maciej S. Lesniak

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Brain Metastases ◽

Annual Meeting ◽

Tumor Biology ◽

Response Assessment ◽

Clinical Work ◽

Leptomeningeal Carcinomatosis ◽

Cns Metastases ◽

Central Nervous System Metastases

Abstract Introduction The 19th Annual Meeting of the Society for Neuro-Oncology (SNO) took place in November of 2014. The focus of many abstracts, as well as the Education Day, was on recent advances in the study of central nervous system (CNS) metastases. Tumor Biology Key studies evaluating the factors in tumors and their microenvironment associated with the development and growth of brain metastases are reviewed. Prognostication Studies investigating the factors that independently influence survival in participants with brain metastases are presented. Response Assessment The Response Assessment for Neuro-Oncology criteria for brain metastases (RANO-BM) and the Neurological Assessment in Neuro-Oncology (NANO) criteria, which were both presented, are recapped. Radiotherapy Studies are reviewed evaluating factors that influence survival outcomes in participants with brain metastases who were treated with radiotherapy. Studies investigating the potential risk of radiation necrosis with the combination of radiotherapy and immunotherapies are presented. Systemic Therapies Brain metastases-focused subset analyses from the ASCEND-1 trial for ALK-translocated non–small cell lung cancer are presented. Preclinical and clinical work on solid tumor leptomeningeal carcinomatosis is also covered. Sequelae of Central Nervous System Metastases and Their Treatments An overview is provided of treatment- related toxicities as well as important concepts that may influence strategies to protect against these toxicities. Conclusions Key concepts regarding tumor biology, prognostication, response assessment, therapeutic management, and sequelae of treatment for CNS metastases are summarized. Advances in our understanding of the basic and clinical science of CNS metastases have the potential to improve outcomes for patients.

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