NIMG-28. VALIDATION OF MODIFIED RESPONSE ASSESSMENT IN NEURO ONCOLOGY (mRANO) DETERMINED PFS AS A STRONG PREDICTOR OF OVERALL SURVIVAL IN RECURRENT GLIOBLASTOMA TREATED WITH A TARGETED IMMUNOTOXIN

Abstract INTRODUCTION The current study compared the modified response assessment in neuro-oncology (mRANO)(1), iRANO (2), and standard RANO criteria (3) as well as quantified the association between progression-free (PFS) and overall survival (OS) in an immunotherapy trial in recurrent glioblastoma (rGBM). METHODS A total of 47 patients with rGBM were enrolled in a phase II convection-enhanced delivery of an IL4R-targeted immunotoxin (MDNA55-05, NCT02858895). Bidirectional tumor measurements were created by local sites and an independent radiologic faculty (IRF), then standard RANO, iRANO, and mRANO criteria were applied. Differences of PFS and the association between PFS and OS were evaluated. RESULTS 41 of 47 patients were evaluable for response. Both local site and IRF-determined PFS was significantly shorter using standard RANO compared to iRANO (log-rank, P< 0.0001; HR=0.3) and mRANO (P< 0.0001; HR=0.3). No difference in PFS was observed between iRANO and mRANO (Local, P=0.67; IRF, P=0.59). In patients who died and had confirmed progression on standard RANO, no correlation was observed between PFS and OS (Local, P=0.47; IRF, P=0.34). Using the iRANO, a weak association driven by a few outliers was observed between confirmed PFS and OS via local site measurements (P=0.017), but not central IRF measurements (P=0.18). Importantly, 24 of 41 patients (59%) were censored using iRANO and not included because they did not have confirmation of progression 3 months after initial progression. A strong correlation was observed between mRANO PFS and OS for both local (R2=0.66, P< 0.0001) and IRF-determined reads (R2=0.57, P=0.0007). CONCLUSION No correlation between PFS and OS was observed for standard RANO or iRANO, but a strong correlation was identified between both locally-determined and centrally-determined PFS and OS using the mRANO criteria. Also, the iRANO criteria was difficult to implement due to need to confirm progression 3 months after initial progression, censoring more than half the patients.

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Treatment of Recurrent Glioblastoma by Chronic Convection-Enhanced Delivery of Topotecan

10.1101/2021.12.04.21266935 ◽

2021 ◽

Author(s):

Eleonora F. Spinazzi ◽

Michael G. Argenziano ◽

Pavan S. Upadhyayula ◽

Matei A. Banu ◽

Justin A. Neira ◽

...

Keyword(s):

Drug Delivery ◽

Drug Distribution ◽

Response Assessment ◽

Recurrent Glioblastoma ◽

Normal Brain ◽

Convection Enhanced Delivery ◽

Before And After ◽

Treatment Response Assessment ◽

Slow Cycling ◽

Novel Drug

ABSTRACTGlioblastoma, the most common primary brain malignancy, is invariably fatal. Systemic chemotherapy is ineffective mostly because of drug delivery limitations. To overcome this, we devised an internalized pump-catheter system for direct chronic convection-enhanced delivery (CED) into peritumoral brain tissue. Topotecan (TPT) by chronic CED in 5 patients with refractory glioblastoma selectively eliminated tumor cells without toxicity to normal brain. Large, stable drug distribution volumes were non-invasively monitored with MRI of co-infused gadolinium. Analysis of multiple radiographically localized biopsies taken before and after treatment showed a decreased proliferative tumor signature resulting in a shift to a slow-cycling mesenchymal/astrocytic-like population. Tumor microenvironment analysis showed an inflammatory response and preservation of neurons. This novel drug delivery strategy and innovative clinical trial paradigm overcomes current limitations in delivery and treatment response assessment as shown here for glioblastoma and is potentially applicable for other anti-glioma agents as well as other CNS diseases.

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Extent of radiological response does not reflect survival in primary central nervous system lymphoma

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab007 ◽

2021 ◽

Vol 3 (1) ◽

Author(s):

Matthijs van der Meulen ◽

Alida A Postma ◽

Marion Smits ◽

Katerina Bakunina ◽

Monique C Minnema ◽

...

Keyword(s):

Central Nervous System ◽

Overall Survival ◽

Nervous System ◽

Central Nervous System Lymphoma ◽

Response Assessment ◽

Complete Response ◽

Rank Test ◽

Central Response ◽

Radiological Response ◽

Tumor Measurements

Abstract Background In primary central nervous system lymphoma (PCNSL), small enhancing lesions can persist after treatment. It is unknown whether a difference in response category (complete response [CR], complete response unconfirmed [CRu], or partial response [PR]) reflects survival. We aimed to determine the value of a central radiology review on response assessment and whether the extent of response influenced progression-free and/or overall survival. Methods All patients in the HOVON 105/ALLG NHL 24 study with at least a baseline MRI and one MRI made for response evaluation available for central review were included. Tumor measurements were done by 2 independent central reviewers, disagreements were adjudicated by a third reviewer. Crude agreement and interobserver agreement (Cohen's kappa) were calculated. Differences in progression-free and overall survival between different categories of response at the end-of-protocol-treatment were assessed by the log-rank test in a landmark survival-analysis. Results Agreement between the central reviewers was 61.7% and between local and central response assessment was 63.0%. Cohen's kappa's, which corrects for expected agreement, were 0.44 and 0.46 (moderate), respectively. Progression agreement or not was 93.3% (kappa 0.87) between local and central response assessment. There were no significant differences in progression-free and overall survival between patients with CR, CRu, or PR at the end-of-protocol-treatment, according to both local and central response assessment. Conclusions Reliability of response assessment (CR/CRu/PR) is moderate even by central radiology review and these response categories do not reliably predict survival. Therefore, primary outcome in PCNSL studies should be survival rather than CR or CR/CRu-rate.

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PET/MR in recurrent glioblastoma patients treated with regorafenib: [18F]FET and DWI-ADC for response assessment and survival prediction

British Journal of Radiology ◽

10.1259/bjr.20211018 ◽

2021 ◽

Author(s):

Giuseppe Lombardi ◽

Alessandro Spimpolo ◽

Sara Berti ◽

Cristina Campi ◽

Maria Giulia Anglani ◽

...

Keyword(s):

Overall Survival ◽

Response Assessment ◽

Early Response ◽

Recurrent Glioblastoma ◽

Response To Treatment ◽

Rank Test ◽

Survival Prediction ◽

Fet Pet ◽

Rano Criteria ◽

Percentage Difference

Objectives: 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 after starting regorafenib. Methods: We retrospectively reviewed 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 after treatment. Several metrics were then derived and compared. Log-rank test was applied for overall survival analysis. Results: Percentage difference in FET volumes correlates with the corresponding percentage difference in ADC (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). Kaplan-Meier analysis, performed to compare the performance in overall survival prediction, revealed that the percentage variations of FET and ADC derived metrics performed at least as well as RANO criteria (p = 0.02, p = 0.024 and p = 0.04 respectively) and in some cases even better. TBR Max and TBR mean are not able to accurately predict overall survival. Conclusion In recurrent glioblastoma patients treated with regorafenib, [18F]FET and ADC metrics, are able to predict overall survival and being obtained from completely different measures as compared to RANO, could serve as semi-quantitative independent biomarkers of response to treatment. Advances in knowledge Simultaneous evaluation of [18F]FET and ADC metrics using PET/MR allows an early and reliable identification of response to treatment and predict overall survival.

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[177Lu]Lu-DOTA-ZOL bone pain palliation in patients with skeletal metastases from various cancers: efficacy and safety results

EJNMMI Research ◽

10.1186/s13550-020-00709-y ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Madhav Prasad Yadav ◽

Sanjana Ballal ◽

Marian Meckel ◽

Frank Roesch ◽

Chandrasekhar Bal

Keyword(s):

Overall Survival ◽

Pain Assessment ◽

Bone Pain ◽

Performance Status ◽

Response Assessment ◽

Assessment Criteria ◽

Skeletal Metastases ◽

Efficacy And Safety ◽

Pain Palliation ◽

Global Pain

Abstract Background [177Lu]Lu-DOTA-ZOL has shown promising results from the dosimetry and preclinical aspects, but data on its role in the clinical efficacy are limited. The objective of this study is to evaluate the efficacy and safety of [177Lu]Lu-DOTA-ZOL as a bone pain palliation agent in patients experiencing pain due to skeletal metastases from various cancers. Methods In total, 40 patients experiencing bone pain due to skeletal metastases were enrolled in this study. The patients were treated with a mean cumulative dose of 2.1 ± 0.6 GBq (1.3–2.7 GBq) [177Lu]Lu-DOTA-ZOL in a median follow-up duration of 10 months (IQR 8–14 months). The primary outcome endpoint was response assessment according to the visual analogue score (VAS). Secondary endpoints included analgesic score (AS), global pain assessment score, Eastern Cooperative Oncology Group Assessment performance status (ECOG), Karnofsky performance status, overall survival, and safety assessment by the National Cancer Institute’s Common Toxicity Criteria V5.0. Results In total, 40 patients (15 males and 25 females) with a mean age of 46.6 ± 15.08 years (range 24–78 years) were treated with either 1 (N = 15) or 2 (N = 25) cycles of [177Lu]Lu-DOTA-ZOL. According to the VAS response assessment criteria, complete, partial, and minimal responses were observed in 11 (27.5%), 20 (50%), and 5 patients (12.5%), respectively with an overall response rate of 90%. Global pain assessment criteria revealed complete, partial, minimal, and no response in 2 (5%), 25 (62.5%), 9 (22.5%), and 4 (10%) patients, respectively. Twenty-eight patients died and the estimated median overall survival was 13 months (95% CI 10–14 months). A significant improvement was observed in the VAS, AS, and ECOG status when compared to baseline. None of the patients experienced grade III/IV haematological, kidney, or hepatotoxicity due to [177Lu]Lu-DOTA-ZOL therapy. Conclusion [177Lu]Lu-DOTA-ZOL shows promising results and is an effective radiopharmaceutical in the treatment of bone pain due to skeletal metastases from various cancers.

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208 E7777 (denileukin diftitox) enhances anti-tumor activity and significantly extends survival benefit of anti-PD-1 in syngeneic solid tumor models

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0208 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A224-A225

Author(s):

Mary Woodall-Jappe ◽

A Raghav Chari ◽

Anil Namboodiripad ◽

Chandrasekhar Goda

Keyword(s):

Overall Survival ◽

Tumor Growth ◽

Solid Tumor ◽

Therapeutic Benefit ◽

Tumor Models ◽

Treg Depletion ◽

Immune Biomarkers ◽

Group 5 ◽

Tumor Measurements ◽

Anti Tumor Activity

BackgroundRegulatory T cell (Tregs) inhibit activity of anti-tumor T cells, and have been shown to limit checkpoint inhibitor effectiveness. Depletion of Tregs seems desirable during immunotherapy, but chronic Treg depletion with antibody therapies can lead to serious autoimmune adverse events. Compared to antibodies, the fusion protein E7777 (IL-2/diphtheria toxin) has a relatively short half-life in circulation, which allows for transient and selective Treg depletion. The potential therapeutic benefit of combining E7777 with anti-PD-1 was tested in syngeneic solid tumor models.MethodsCT26 colon and H22 liver cancer tumors were implanted subcutaneously in immunocompetent BALB/c mice. E7777 (2.5 mcg/mouse, i.v.) was given on a Q7Dx3 schedule. Anti-murine PD-1 was given (100 mcg/mouse, i.v.) Q4Dx5. Groups of 16 mice received each agent as monotherapy or in combinations. Sequencing of combination administration was also varied: Group 4 started treatment on the same day; Group 5 received E7777 2 days prior to start of anti-PD-1; Group 6 received anti-PD-1 first. Tumor growth was compared across all groups. In survival studies, mice were treated for 3 weeks and observed with twice weekly tumor measurements. In other experiments, tumors, tumor-draining lymph nodes, and spleens were examined by IHC and by flow cytometry of immune cells from dissociated tissues at defined points, for immune biomarkers.ResultsFigure 1 shows additive benefit from the E7777 + anti-PD-1 combinations over either monotherapy. Most importantly, figure 2 and table 1 show significantly enhanced overall survival from a 3 week course of combinations compared to either agent alone (p<0.005) or to vehicle controls (p<0.000001). There was no clear distinction among different sequencing regimens. Benefit correlated with enhanced CD8:Treg ratios in tumors.Abstract 208 Figure 1Tumor growth in s.c. syngeneic solid tumors. N=16/groupAbstract 208 Figure 2Overall survival in s.c. syngeneic models. N=16/groupAbstract 208 Table 1Calculated median survivalConclusionsDepletion of Tregs by E7777 significantly increased anti-tumor activity and durably extended overall survival compared to treatment with anti-PD-1 alone in syngeneic solid tumor models. Clinical studies of a combination of the two agents are planned.Ethics ApprovalAll studies were conducted at Crown Bio, and were approved by the Crown Bio IACUC.

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PATH-13. PLEOMORPHIC XANTHOASTROCYTOMA INTEGRATED GENOMIC CHARACTERIZATION - WHAT HAVE WE LEARNED?

Neuro-Oncology ◽

10.1093/neuonc/noaa222.648 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii426-iii427

Author(s):

Rachael Vaubel ◽

Valentina Zschernack ◽

Alissa Caron ◽

Dragana Milosevic ◽

Robert Jenkins ◽

...

Keyword(s):

Overall Survival ◽

Strong Predictor ◽

Progression Free Survival ◽

Genetic Alterations ◽

Pleomorphic Xanthoastrocytoma ◽

Who Grade ◽

Targeted Next Generation Sequencing ◽

Genomic Characterization ◽

Promoter Mutations ◽

Methylation Profiling

Abstract Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytoma occurring predominantly in children and young adults. It is characterized histologically by large pleomorphic, spindled and lipidized cells with frequent eosinophilic granular bodies and pericellular reticulin deposition. BRAF p.V600E mutation and CKDN2A/B deletion are the most common genetic alterations. We report the integrated genomic characterization of a cohort of 67 patients (37 F, 30 M; median age 20.3 years (interquartile 13.4–32.9) with histologically defined PXA (52, 78%) or anaplastic PXA (A-PXA) (15, 22%), using genome-wide cytogenetic (ThermoFisher Oncoscan, n=67), methylation profiling (Illumina EPIC array, n=43), and targeted next generation sequencing (n=32). BRAF p.V600E mutation (n=51, 76.1%) and CDKN2A/B deletion (n=63; 94%) were the most frequent alterations. Of 16 BRAF p.V600E negative cases, 7 showed an alternative BRAF activating mutation (n=2), NF1 (n=3) mutation or ATG7-RAF1 fusion (n=2). Targeted TERT analysis found promoter mutations in 3 (of 58) cases, but TERT amplification was absent. Supervised and unsupervised methylation profiling against a comprehensive reference cohort demonstrated consensus grouping with the PXA class in 36 of 43 cases; while the minority grouped with a ganglioglioma class (n=3), with reactive brain or had no resolvable subgroup (n=4). Follow-up was available in 61 patients (91.0%) (median 63 months). Overall survival was significantly different between PXA and A-PXA (5-year:80.4% vs. 55.1%; p=0.001), but not progression-free survival (5-year:61.7% vs. 39.8%; p=0.128). Our data confirm the high frequency of MAP-K abnormalities and CDKN2A/B deletion in PXA. WHO grade remains a strong predictor of patient overall survival.

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CTIM-14. RANDOMIZED PHASE II OPEN LABEL STUDY OF NIVOLUMAB PLUS STANDARD DOSE BEVACIZUMAB VS NIVOLUMAB PLUS LOW DOSE BEVACIZUMAB IN RECURRENT GLIOBLASTOMA (RGBM). NIVOLUMAB BENEFITS OLDER POPULATION

Neuro-Oncology ◽

10.1093/neuonc/noab196.206 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi52-vi52

Author(s):

Manmeet Ahluwalia ◽

David Peereboom ◽

Yasmeen Rauf ◽

Patrick Wen ◽

David Reardon

Keyword(s):

Overall Survival ◽

Low Dose ◽

Standard Dose ◽

Performance Status ◽

Methylation Status ◽

Progression Free Survival ◽

Recurrent Glioblastoma ◽

Dose Effect ◽

Open Label ◽

Anti Vegf

Abstract BACKGROUND Approaches using anti-PD1 therapy alone in rGBM is of limited efficacy. VEGF is upregulated proangiogenic growth factor in GBM that contributes to tumor-associated immunosuppression. Preclinical data suggests a potential dose effect of anti-VEGF therapy on immunomodulation. Hence, a combination of anti-PD1 and anti-VEGF may be a promising approach in rGBM. METHODS 90 patients with GBM at first recurrence were randomized (1:1) to nivolumab (240 mg IV Q2 weeks) with bevacizumab at standard (10 mg/kg; Arm A) or at low dose (3 mg/kg; Arm B) IV Q2 weeks. Stratification included extent of resection, age, performance status and MGMT methylation status. Progression-free survival (PFS) and overall survival (OS) were compared between two arms. RESULTS 90 patients (Median age 60.6 years ranged 27.4-86.4, 67.8% male, median KPS 80) were enrolled between May 2018 and Jan 2020. Patients were followed in median 7.7 months (Range 0.7, 28.2). 35 patients were MGMT methylated and 53 patients were MGMT not hypermethylated and 2 were indeterminate. Overall Survival was not significantly different between arm A and arm B (1 year: 41.1 vs 37.7%, p=0.14), while OS was better for arm A in age > 60 (At 1-year: 46.2% vs 23.8%; Median: 10.6 vs 5.9 months; P=0.046). OS was no different in the two arms for age ≤ 60 years (At 1-year: 35.6% vs 56.4; Median 8.0 vs 12.4 months; P=0.90). Most frequent toxicities ( >20%) included fatigue (45.6%), proteinuria (34.4 %), diarrhea (28.9%), hypertension (23.3%) and lipase increase (21.1%). Toxicities in grade 3-4 were hypertension (7.8%), fatigue (5.6) and other non-neurological toxicities including DVT, PE, infection, and abnormal liver function. CONCLUSIONS Overall PFS and OS rates appear similar for nivolumab with either standard or low-dose bevacizumab compared to historical benchmarks of bevacizumab monotherapy. Nivolumab with standard bevacizumab seem to benefit patients older than 60 years old.

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CTIM-28. MDNA55, AN INTERLEUKIN-4 RECEPTOR TARGETED IMMUNOTHERAPY, FOR RECURRENT GBM DELIVERED BY CONVECTION ENHANCED DELIVERY (CED)

Neuro-Oncology ◽

10.1093/neuonc/noab196.220 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi56-vi57

Author(s):

John Sampson ◽

Achal Singh Achrol ◽

Manish K Aghi ◽

Krystof Bankiewiecz ◽

Martin Bexon ◽

...

Keyword(s):

De Novo ◽

Symptom Control ◽

Recurrent Glioblastoma ◽

Interleukin 4 ◽

External Control ◽

High Dose ◽

Open Label ◽

Convection Enhanced Delivery ◽

High Concentrations ◽

Dose Volumes

Abstract BACKGROUND MDNA55 is an IL4R-targeted toxin in development for treatment of recurrent glioblastoma (rGBM). MDNA55 binds to IL4R expressed by tumor cells and non-malignant cells of the tumor microenvironment. METHOD MDNA55-05 was an open-label, single-arm study of MDNA55 delivered by CED as a single treatment in patients with 1st or 2nd recurrence following de novo GBM, IDH wild type status and not indicated for resection at relapse. Dose volumes (up to 60mL) and concentration of MDNA55 (1.5 to 9.0 μg/mL) were studied. RESULTS MDNA55 showed an acceptable safety profile at all doses tested. Median OS (mOS) amongst all subjects was 11.9 months, OS-24 was 20%, and PFS-12 was 27%. Among subjects expressing high levels of IL4R (irrespective of MDNA55 dose) and low levels of IL4R expression administered high dose (≥ 180μg) of MDNA55 (IL4Rhi + IL4Rlo/hd), mOS further improved to 14.0 months with OS-24 of 20%. Unmethylated MGMT promoter status did not affect MDNA55 treatment outcomes. In the IL4Rhi + IL4Rlo/hd population (N=17), mOS was 14.9 months with OS-24 of 22%. Following treatment with high concentrations of MDNA55 (6.0 or 9.0 μg/mL), transient (median of 3 cycles) low dose Avastin (5mg/kg q2w or 7.5mg/kg q3w) was used for symptom control and steroid sparring. Among these subjects, mOS amongst all comers (N=9) and the IL4Rhi + IL4Rlo/hd group (N=8) increased to 21.8 and 18.6 months with OS-24 of 44% and 38%, respectively. CONCLUSIONS MDNA55 shows potential to benefit all rGBM patients treated at high dose irrespective of IL4R expression. In the 1:1 randomized Phase 3 trial, the study will enrol two-thirds of subjects in the SOC arm from a matched external control arm. Unlike conventional RCTs, the hybrid design sets a new precedent for GBM trials, allowing robust OS analysis while significantly reducing the number of subjects randomized to SOC arm.

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NIMG-54. RADIOMIC FEATURES FROM LESION HABITAT PREDICT RESPONSE TO COMBINATION OF NIVOLUMAB AND BEVACIZUMAB IN PATIENTS WITH RECURRENT GLIOBLASTOMA: A FEASIBILITY STUDY

Neuro-Oncology ◽

10.1093/neuonc/noab196.552 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi141-vi141

Author(s):

Ruchika Verma ◽

Yasmeen Rauf ◽

Ipsa Yadav ◽

Volodymyr Statsevych ◽

Jonathan Chen ◽

...

Keyword(s):

Progression Free Survival ◽

Poor Response ◽

Response Assessment ◽

Complete Response ◽

Recurrent Glioblastoma ◽

Proportional Hazard ◽

Free Survival ◽

Cox Proportional Hazard ◽

Expert Radiologist ◽

Mri Scans

Abstract PURPOSE The use of immunotherapy in glioblastoma management is under active investigation. Glioblastomas are “cold” tumors, meaning that they have inactivated or fewer tumor infiltrative lymphocytes in addition to substantial tumor necrosis, attributing to their poor response to immunotherapy. A significant challenge is the apriori identification of Glioblastoma patients who will respond favorably to immunotherapy. In this work, we evaluated the ability of computerized MRI-based quantitative features (radiomics) extracted from the lesion habitat (including enhancing lesion, necrosis, and peritumoral hyperintensities) to predict response and progression-free survival (PFS) in recurrent GBM patients treated with combination of Nivolumab and Bevacizumab. METHODS Immunotherapy response assessment in neuro-oncology (iRANO) criteria along with PFS were used to analyze n=50 patients enrolled in a randomized clinical trial where patients received Nivolumab with either standard or low dose Bevacizumab. These patients were assessed to see if they had complete response, partial response, stable disease (i.e. responders, n=31), or disease progression (i.e. non-responders, n=19). Lesion habitat constituting necrotic core, enhancing tumor, and edema were delineated by expert radiologist on Gd-T1w, T2w and FLAIR MRI scans. COLIAGE radiomic features from each of the delineated regions were selected using minimum redundancy maximum relevance (mRMR) via cross-validation, to segregate non-responder patients from responders. A multivariable cox proportional hazard model was used to predict survival (PFS). RESULTS CoLlAGe correlation, sum average, and sum variance features (capture local heterogeneity) from the lesion habitat, were found to segregate non-responder patients from responders with an accuracy of 86%, followed by 80% using features from peritumoral hyperintensities and 78% from enhancing tumor. In our survival analysis, C-index of 0.688 was obtained using features from the entire lesion habitat, followed by peritumoral hyperintensities (0.675) and enhancing tumor (0.656). CONCLUSION Radiomic features from the lesion habitat may predict response to combination of Nivolumab and Bevacizumab in recurrent Glioblastomas.

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