bluuebunny/crossref_metadata_2025 huggingface dataset:
NIMG-46. MULTI-PARAMETRIC MRI RADIOMIC ANALYSIS USING DEEP LEARNING PREDICTS PERITUMORAL GLIOBLASTOMA INFILTRATION AND SUBSEQUENT RECURRENCE
Authors: Kwak Sunwoo , Akbari Hamed , Garcia Jose , Mohan Suyash , Davatzikos Christos
Published: November 2023

PURPOSE

Glioblastoma (GBM) is the most aggressive and infiltrative brain tumor with a very poor prognosis which hasn’t significantly improved in over 20 years. The almost 100% recurrence rate is due to cancer infiltration beyond the tumor margins currently being targeted by standard of care. Prior studies used traditional supervised machine learning have shown great promise in predicting tumor infiltration beyond these margins. We hypothesize that deep learning methods can further improve such predictive maps and guide intensive, yet targeted and personalized therapies.

METHODS

MRIs from a cohort of 109 de novo GBM patients were collected from Hospital of the University of Pennsylvania. All the patients incorporated in this study had pre-operative multi-parametric MRI scans including T1, T1Gd, T2, T2-FLAIR, ADC, and underwent surgical resection followed by standard chemoradiation therapy and had pathologically confirmed recurrence. A novel, automated deep learning method, informed by results of prior studies using support vector machines, was constructed to train a patch-based ensemble CNN to identify regions of peri-tumoral cancer infiltration. Leave-one-out was used to evaluate the predictive value of this method, against pathology-proven subsequent recurrence.

RESULTS

Probability maps, representing the likelihood of tumor infiltration and eventual recurrence, were binarized using threshold of 50% cutoff, compared with actual recurrence on post-recurrence MRI scans. The average cross-validated accuracy was 92%, specificity was 93%, patient-based sensitivity was 78%, and odds-ratio among all patients was 12.95 (Estimated “hot spots” were 12.95 times more likely to present recurrence in the future).

CONCLUSIONS

This study demonstrates that Multi-parametric MRI pattern analysis using CNN based network can successfully predict tumor infiltration in peritumoral region for Glioblastoma patients. These suggest that new intensive, yet precisely targeted treatments can be developed, guided by AI-driven predictive maps of infiltration.
NIMG-50. TOTAL TUMOR CELLULARITY AND CELLULAR GROWTH RATES ESTIMATED USING A RADIO-PATHOMIC AI MODEL PREDICTS PROGNOSIS AND RESPONSE TO CYTOTOXIC THERAPY IN RECURRENT GBM
Authors: Oshima Sonoko , Yao Jingwen , Bobholz Samuel , Nagaraj Raksha , Raymond Catalina , Teraishi Ashley , Guenther Anna-Marie , Kim Asher , Sanvito Francesco , Cho Nicholas , Eldred Blaine , Connelly Jennifer , Pope Whitney , Nghiemphu Phioanh , Lai Albert , Salamon Noriko , Cloughesy Timothy , LaViolette Peter , Ellingson Benjamin
Published: November 2023

PURPOSE

A radio-pathomic machine learning model trained with postmortem tissue samples has recently been developed to estimate tumor cellularity from standard anatomic MR images (Bobholz SA et al. AJNR 2022). The aim of this study was to use this externally developed, machine learning-based model to assess the impact of tumor cellularity and changes in cellularity on survival in recurrent glioblastoma (rGBM) treated with standard cytotoxic therapies.

METHODS

We retrospectively evaluated 22 cases of rGBM treated with chemotherapy. Radio-pathomic maps of predicted tumor cellularity were generated using the radio-pathomic model using pre- and post-contrast T1-weighted MR images, T2-weighted FLAIR images and apparent diffusion coefficient calculated from diffusion-weighted imaging. Total cellularity was estimated by integrating the cellularity measures within a contrast-enhancing tumor volume of interest. Cellularity growth rates (CGRs) were computed using three pre-treatment scans and available post-treatment scans. Tumor cellularity and CGRs were assessed in terms of their impact on overall survival (OS) using log-rank analysis.

RESULTS

Patients with baseline tumor cellularity < 8.89x108 cells and those with pre-treatment CGR < 7.55x106 cells/day showed significantly longer OS than those with higher cellularity or CGRs (P = 0.001 and 0.008, respectively). Patients with cellularity < 8.90x108 cells at the 1st follow-up (one month after treatment), those with cellularity at 2nd follow-up < 8.89x108 cells (two months after treatment), post-treatment CGR < 1.51x107 cells/day, and change in CGR after treatment < +5.91x106 cells/day showed significantly longer OS than those with higher values (P = 0.03, < 0.001, < 0.001, = 0.02, respectively).

CONCLUSION

These preliminary results suggest the potential value of estimating total cellularity within the enhancing tumor as a biomarker for prognosis prediction and cytotoxic therapy effect evaluation in rGBM. Additional analyses with more cases and treatments are warranted.
NIMG-51. RADIOGRAPHIC IMPROVEMENT IN A PATIENT WITH OLIGODENDROGLIOMA UNDERGOING TREATMENT FOR ACUTE MYELOID LEUKEMIA
Authors: Davila Mauricio Perez , Mendez Lourdes , Baehring Joachim
Published: November 2023

INTRODUCTION: The standard chemotherapy for treating oligodendroglioma consists of a combination of procarbazine, lomustine, and vincristine (PCV). The combination of hypomethylating agents, like azacitidine, and BCL2 inhibitors like venetoclax have not been formally studied in the treatment of glial tumors. The combination of these two drugs is commonly used to treat acute myeloid leukemia, with IDH mutant disease being a particularly sensitive subtype. CASE REPORT: A 48-year-old man was diagnosed with a left frontal, grade II oligodendroglioma following multiple episodes of speech arrest and right-hand numbness. He was subsequently treated with six cycles of PCV with a minor response. After slow progression over eight years, the tumor started displaying contrast enhancement. While planning for radiation therapy, he presented to the Emergency Department with severe fatigue and shortness of breath. Workup led to a diagnosis of pure erythroid leukemia, with molecular and cytogenetic studies suggesting a neoplasm related to prior exposure to cytotoxic chemotherapy. He was treated with three cycles of venetoclax and azacitidine, but unfortunately, the erythroleukemia progressed after a transient response to this treatment. On the other hand, however, a re-staging MRI brain showed a remarkable reduction of his tumor size of approximately 40% per RANO criteria. The patient was off steroids and remained neurologically asymptomatic during this time. Discussion: The use of azacitidine for the treatment of IDH mutant gliomas has been reported in the literature, with mixed results that might suggest at least some benefit in a subtype of patients. Other studies have also suggested that the BCL2 gene is associated with treatment resistance and tumor recurrence in gliomas. Our case presents an interesting observation that combining a hypomethylating agent with a BCL2 inhibitor might convey clinical and radiographic benefits for patients with relapsed IDH mutant gliomas.
NIMG-68. TEMPORAL CHANGES IN TUMOR COMPOSITION DIFFER ACROSS TUMOR GRADE IN GLIOMA
Authors: Duenweg Savannah , Bobholz Samuel , Lowman Allison , Stebbins Margaret , Winiarz Aleksandra , Flatley Michael , Nath Biprojit , Kyereme Fitzgerald , Connelly Jennifer , Coss Dylan , Krucoff Max , Banerjee Anjishnu , LaViolette Peter
Published: November 2023

Gliomas are the most common primary adult brain tumor in the United States and their biological heterogeneity makes it difficult to assess and treat tumor progression over time. This study used conventional MRI tumor segmentations to determine longitudinal growth differences between low grade (≤ G2), G3, and G4 gliomas. A total of 60 patients with at least three scans collected before death were organized into low-grade (n = 9), G3 (n = 13), and G4 (n = 38) gliomas at initial diagnosis. T1, T1C, FLAIR, and T2 images from every timepoint across all patients were used as input for tumor segmentation, using BraTS, to segment contrast enhancement (CE), FLAIR hyperintensity (FH), and the necrotic core (NC). Volumes within each segmentation and the time between each subsequent MRI was calculated, where the first post-surgical MRI was considered time 0. Linear mixed models were fitted for each segmentation volume, where Time, Group (i.e., G2-4) and their interaction (Group*Time) were fixed effects and subject was a random effect. We found that Time and Group*Time interaction were significant predictors of FH growth (p < 0.001 and 0.04, respectively); however, no group-level differences were observed in FH volumes over time. Group was the only significant predictor of CE growth (p = 0.006). Specifically, G4 growth was greater than G2 and had a trending increase than G3 (p = 0.003 and 0.08, respectively). Group, Time, and Group*Time were all significant predictors of NC growth (p = 0.04, 0.001, and 0.01, respectively). G4 NC growth was significantly greater than both G2 and G3 (both p < 0.05). No difference any of these tumor segmentations growth between G2 and G3 was detected. These results further show the heterogeneity in glioma growth over time and the necessity to assess how treatment effects longitudinal tumor composition progression and overall survival.
NCMP-01. TREATMENT STRATEGIES IN PATIENTS WITH RENAL CELL CANCER AND BRAIN METASTASES
Authors: Derks Sophie , van der Meer Edgar , Joosse Arjen , de Jonge Maja , Slagter Cleo , Schouten Joost , Hoop Esther Oomen-de , Smits Marion , van den Bent Martin , Jongen Joost , van der Veldt Astrid
Published: November 2023

BACKGROUND

Brain metastases (BM) significantly impact quality of life and survival in patients with metastatic renal cell cancer (mRCC). Based on the International Metastatic RCC Database Consortium (IMDC) risk classification, treatment strategies for patients with mRCC vary from systemic treatment with vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) and/or immune checkpoint inhibitors (ICIs) to active surveillance (AS). Here, we describe the impact of treatment strategies on survival in patients with RCC and BM.

METHODS

We conducted a single-center, retrospective cohort study at Erasmus MC Cancer Institute (Rotterdam, Netherlands). All consecutive patients with RCC BM between 2011-2022 were included. Primary outcome was the BM-free survival, i.e. the time between diagnosis of extracranial metastases (ECM) and BM. Secondary outcome was overall survival (OS).

RESULTS

46 patients with RCC BM were included: 25 (54.3%) had received prior systemic treatment for ECM, and 21 (45.7%) were treatment naive at diagnosis of BM. IMDC scores (favorable 12% resp. 0%, intermediate 48% resp. 64%, poor 24% resp. 0%, unknown 16% resp. 36%) were not significantly different (p=0.07) between these groups. In 39 (84.8%) of 46 patients, BM were metachronous ( >1 month) after ECM. In these patients (n=39), the median BM-free survival was 22.3 (IQR 5.7-46.7) months and was significantly longer (p=0.02) in previously treated patients (29.0 [IQR 12.6-57.0] months) as compared to treatment naive patients (6.8 [IQR 1.0-7.0] months). However, median OS since ECM diagnosis (39.1 [IQR 16.5-111.5] months) was not significantly different (p=0.62) between previously treated and treatment naive patients.

CONCLUSION

Patients with RCC who received systemic treatment for ECM prior to BM diagnosis, had a longer BM-free survival as compared to patients without previous systemic treatment. These results emphasize the need for careful evaluation of AS in patients with mRCC, even in patients with a favorable prognostic profile.
NCMP-03. SHORT AND LONG TERM EFFICACY OF BEVACIZUMAB THERAPY FOR RADIATION NECROSIS IN BRAIN METASTASES
Authors: Nobel Hila , Ofer Jonathan , Yust-Kayz Schlomit , Borenstein Sara , Sigal Tali , Kaner Andrew , Laviv Yossef , Limon Dror , Gal Omer , Elihaou Ruth , Amiel Alexandra
Published: November 2023

PURPOSE

Brain radionecrosis (RN) is a frequent, and often life devastating complication of stereotactic radiotherapy (SRS) for brain metastases. There is no standard treatment for RN. Bevacizumab is often proposed although data regarding its efficacy is limited. We performed a retrospective study to evaluate the short and long-term efficacy of bevacizumab in RN.

METHODS

We included all the patients who received bevacizumab for RN developed after treatment with SRS for brain metastases. Patients treated in our institution between 31/07/2018 and 31/07/2022 were enrolled into the study. Clinical and radiographic evaluations, immediately, 6, 12 and 24 months after completion of bevacizumab were evaluated. Response was assessed using RANO criteria. Changes in volume lesion were calculated using Brain Lab navigator system.

RESULTS

24 patients were included in the study. Median time from diagnosis of RN to treatment with bevacizumab was 5.1 months. According to RANO criteria first MRI performed after completion of treatment with bevacizumab showed a partial or complete response in 34 % of the patient and a stable disease in 41% of the patient. Volumetric measurements demonstrated significant (above 25%) diminution in the volume of the lesion in 66% of patients. Clinical improvement in neurological symptoms was revealed in 41 % of patients and steroid dosage was reduced in 50% of patients. Among the patients with a stable disease in the first MRI after bevacizumab, 27% demonstrated partial or complete response at the following 6 months MRI. During the entire follow-up period, a regrowth of RN occurred in 45% of patients who demonstrated a partial or complete response in the first MRI after bevacizumab.

CONCLUSION

Bevacizumab is an effective therapy for of RN, with high response rate within the first 6 first months after treatment. However regrowth of radionecrosis is occurs frequently during long term follow-up.
NCMP-11. ASSESSING SURVIVAL OUTCOMES OF PCV-BASED AND TEMOZOLOMIDE-BASED ADJUVANT THERAPY IN OLIGODENDROGLIOMA PATIENTS
Authors: Begley Sabrina , Chen Adrian , Schulder Michael , Goenka Anuj
Published: November 2023

INTRODUCTION

When treating oligodendroglioma, choosing between temozolomide (TMZ) and procarbazine, lomustine, and vincristine (PCV), with concurrent radiotherapy still poses a challenge. Given the commonality of tumor recurrence, optimizing progression-free survival while minimizing adverse effects is crucial to improving quality of life. We compare survival and adverse effects of patients treated for oligodendroglioma with PCV-based vs TMZ-based adjuvant therapy.

METHODS

87 patients treated for oligodendroglioma between 1994-2022 were retrospectively reviewed. Progression-free survival (PFS) and overall survival (OS) from initial resection were compared between PCV-based or TMZ-based treatment groups using Kaplan-Meier and multi-variable Cox survival analysis.

RESULTS

The median age at diagnosis was 41 years and 62% were male. After initial resection, 42.8% received PCV-based treatment and 57.2% received TMZ-based treatment. Treatment groups were balanced in the following variables: age, tumor genetic profiling, extent of resection, and KPS score. However, more patients in the TMZ-based group received concurrent radiation. The entire cohort had a 6.3-year PFS and 21.0-year OS. The median time to recurrence was significantly longer in those treated with PCV (12 years) compared to those treated with TMZ (4.7 years). PFS [HR = 0.46, p = 0.04] and OS [HR = 0.26, p = 0.04] were significantly longer in those receiving PCV-based treatment compared to TMZ-based treatment (Fig. 1). After adjusting for aforementioned variables, Cox regression analysis revealed no difference in OS between PCV- and TMZ-based treatment. The overall adverse effect rate did not significantly differ between PCV-based and TMZ-based treatment (25% vs. 28.1%, p > 0.99).

CONCLUSIONS

PCV treatment confers longer progression-free survival than TMZ treatment for oligodendroglioma patients, noting that most patients in our series received concurrent radiation with TMZ, and those receiving PCV not having received upfront radiation. Pending clinical trial results, our findings suggest PCV-based therapy warrants consideration as the preferred therapeutic option for oligodendroglioma patients.
NCMP-17. IMPROVEMENT IN CRANIAL NEUROPATHIES FOLLOWING STEREOTACTIC RADIOTHERAPY ALONE FOR SKULL BASE MENINGIOMAS
Authors: Hafazalla Karim , Lan Matthews , Piper Keenan , Carey Preston , Khanna Omaditya , Andrews David , Evans James , Judy Kevin , Farrell Christopher
Published: November 2023

Cranial neuropathies are a common presenting symptom in skull base meningiomas. Many of these tumors are not amenable to surgical resection; for these patients, stereotactic radiotherapy (SRT) is a viable option. Our study sought to investigate the efficacy of SRT for improving cranial neuropathies and identify predictors that portend favorable response. A single-institution retrospective analysis was performed for patients with skull base meningiomas causing cranial neuropathies who received SRT as sole treatment from 2001 to 2021. Clinical variables were collected and analyzed for predictors of improvement. Subgroup analysis for each type of cranial neuropathy was also performed. Overall 101 patients were included, of which 51 (50.4%) had an improvement in cranial neuropathy following SRT. There was no difference in gender or age between patients with and without improvement. The most common tumor location was cerebellopontine angle (n=38), followed by cavernous sinus (n=27) and optic canal (n=25). Cranial nerve II was most frequently affected (n=34), followed by VI (n=28) and V (n=27). There was no significant difference in tumor volume, radiation dose, location, or specific cranial nerve affected between patients with and without improvement. Median time to improvement was 8 months (IQR 3-15). In subgroup analysis, patients with optic neuropathy who experienced improvement after SRT were significantly younger (50.7 vs. 60.1 years, p=0.03), while patients with trigeminal neuropathy who experienced improvement were significantly older (69.6 vs. 58.7 years, p=0.03). For patients with extraocular movement neuropathies or vestibulocochlear dysfunction, there were no significant factors associated with improvement. Half of patients with cranial neuropathy from skull base meningiomas experience symptomatic improvement following sole SRT. Age may play a role in predicting improvement, with younger patients more likely to have improved vision and older patients more likely to experience improvement in trigeminal neuropathy.
NCMP-24. RECURRENT BOUTS OF SCURVY DURING GLIOBLASTOMA REMISSION
Authors: Bonm Alipi , Katherine Hicks , Graber Jerome
Published: November 2023

Various nutritional deficiencies are more common in patients with cancer, including thiamine, iron and vitamin B12 deficiences, and can be associated with metabolic stress, treatments given and reduced nutritional intake or absorption. Vitamin C deficiency and scurvy have also been reported as a rare complication in cancer patients, but are not frequently seen in the developed countries. We report a 29 year old woman who underwent partial resection of a bifrontal isocitrate dehydrogenase, methylated glioblastoma followed by radiation and temozolomide four years prior. Her tumor remained stable since that time, but she had ongoing decreased appetite and sensitivity to food smells and tastes, which restricted her diet substantially. She had mild chronic anemia and was underweight, but had remained stable. She presented to us with acutely worsening fatigue, lower limb edema and a new rash that was superficially petechial in appearance. She had gingival hyperplasia and friability, and a jaundiced appearance. No deep venous thrombosis was found and liver tests were normal, giving a picture of scurvy. Her serum vitamin C level was undetectable, B12 was 75, folate 3.4, hemoglobin 6.1, albumin 3.2 and vitamin D 11.5. She was given intravenous and oral ascorbic acid as well as other supplementation and had immediate resolution of limb swelling and greatly improved appetite and energy. One year later, with glioblastoma still stable off treatment, she had recurrent worsening fatigue, appetite and gingivitis, and typical petechia-like rash appeared within minutes of IV placement for MRI contrast in the associated vein. She declined repeat serum testing but symptoms resolved on resuming high dose oral vitamin supplementation. Vitamin C has been studied as a supplement in glioblastomas, but also shown to reduce etoposide toxicity. Vitamin C and other nutritional deficiencies may be more common in brain tumor patients, but under-diagnosed.
NCOG-06. BEVACIZUMAB ALONE VERSUS BEVACIZUMAB PLUS IRINOTECAN IN PATIENTS WITH RECURRENT GLIOBLASTOMA: A NATIONWIDE POPULATION-BASED STUDY
Authors: Lee Yeonhu , Roh Tae Hoon , Kim Se-Hyuk
Published: November 2023

INTRODUCTION

There is no established treatment for recurrent glioblastoma. For the treatment of recurrent glioblastoma, the antiangiogenic antibody, bevacizumab, is used either alone or in combination with Irinotecan. This study aimed to compare the survival of patients receiving bevacizumab monotherapy (BEV) and those receiving bevacizumab plus irinotecan combination therapy (B+I) in recurrent glioblastoma (GBM), using a nationwide population-based dataset.

METHODS

Patients matching the ICD code C71.x were screened from the national database. From January 2008 to November 2021, 846 patients who had undergone surgery or biopsy and received concurrent chemoradiotherapy with Temozolomide were included. Of these, 450 received BEV, while 396 received B+I. The patients' demographic characteristics, inpatient stay duration, prescription frequency, and survival outcomes were compared between the two groups.

RESULTS

The median overall survival from initial surgery was 22.60 months (9% CI: 20.50 – 24.21) and 20.44 months (95% CI: 18.55 – 22.60) in the BEV and B+I groups, respectively (p=0.5079, log rank test). The BEV group was older and had a higher percentage of females compared to the B+I group. Younger age, female gender, and having surgery rather than biopsy were associated with better prognosis.

CONCLUSION

This study found no significant difference in overall survival between bevacizumab alone versus bevacizumab plus irinotecan combination therapy in patients with recurrent GBM. Considering the additional potential toxicity associated with irinotecan, bevacizumab monotherapy may be a suitable treatment option.
NCOG-07. HUB-RELATED GRAPH METRICS AS MARKER FOR COGNITIVE OUTCOMES IN ADULT GLIOMA SURVIVORS AFTER MULTIMODAL THERAPY
Authors: De Roeck Laurien , Blommaert Jeroen , Sunaert Stefan , Dupont Patrick , Clement Paul , De Vleeschouwer Steven , Sleurs Charlotte , Lambrecht Maarten
Published: November 2023

BACKGROUND

Although cognitive impairment is a prevalent long-term side effect in glioma survivors, predictive imaging-based markers remain inconsistent to date. Structural brain network topology could be altered by both the tumor and its’ treatment through reorganization of hubs (i.e. highly interconnected nodes). Here, we explored the role of nodal hub-related graph metrics in cognitive functioning.

METHODS

48 WHO grade 2-3 adult glioma survivors ( > 1y post-therapy) and 42 matched controls, underwent a cognitive assessment. Cognitive scores were transformed into w-scores, corrected for age and education. Weighted nodal graph metrics were calculated based on diffusion weighted imaging. Hubs were calculated based on 4 nodal metrics. Significant differences in nodal graph metrics between patients and controls, and hubs versus non-hubs were tested in a repeated measures ANOVA, using Bonferroni correction for multiple testing. Significant group differences in nodal graph metrics were correlated to cognitive scores per domain.

RESULTS

In controls, 12/78 nodes were defined as hubs. In survivors, the left superior-parietal region and left putamen had a significantly lower likelihood of being a hub (p< .001). These areas showed assortativity to be positively correlated with attention, language and executive function (r(90) > .51,p< .001) and characteristic path length to be negatively correlated with all cognitive domains (r(90) > .51, p< .001). Nodal metrics of clustering coefficient, characteristic path length, local efficiency and assortativity were significantly different between groups in both hub and non-hub regions (p< .001). Except for betweenness centrality, all nodal metrics strongly correlated with cognitive outcomes, occurring more often in hubs (33-50%) than intermediate hubs (10-33%) or non-hubs (4-12%).

CONCLUSION

Reorganization of hubs is frequently observed in this cohort of glioma survivors. Hub connectivity seems to be important in cognitive functioning, more than for non-hub regions. Therefore, structural nodal hub-related graph metrics might be important in predicting cognitive outcomes.
NCOG-20. WEARABLE DEVICE DATA QUANTIFY DISEASE PROGRESSION IN HIGH GRADE GLIOMA AND MAY PROVIDE NOVEL OUTCOME MEASURES
Authors: Dadhania Seema , Williams Matthew
Published: November 2023

BACKGROUND

Functional status is a prognostic measure of survival in high grade glioma (HGG). Real-time monitoring between clinical encounters can extend the reach of care and provide actionable insights to drive more personalized and proactive care. We present data from the completed BrainWear Study, a highly novel study evaluating if data captured via a wrist-worn wearable device in patients with HGG can be used to explain, influence and/or predict cancer-related outcomes. Materials and

METHODS

All participants agreed to wear a wrist-worn Axivity AX3 triaxial accelerometer changed at 14-day intervals. Raw accelerometer data was processed using the UKBiobank Accelerometer analysis package v6.2.3 for Python and inclusion of high-quality wear time selected as ≥72 hours of data over 7-days. We analysed variation in activity by patient demographics and MRI result utilising the Response Assessment in Neuro-Oncology (RANO) criteria. Patient reported outcomes (PROs) were completed at planned study timepoints. Wilcoxin-signed rank test was used to compare participant activity at timepoints of stable or progressive disease (PD). Mixed-effects models were used to evaluate changes in activity.

RESULTS

12512 days of accelerometer data were recorded from 56 patients (36 male; 20 female) with a median age of 60 years. 80% of the data were characterised as high-quality. Mean acceleration(mg) and time spent walking daily(h/day) correlated positively with the global health QOL and physical functioning scores and inversely with the fatigue score from PROs. In the 6-weeks surrounding an MRI scan, patients with PD walked on average 1856 steps less per day than those with stable disease, and spent 22 minutes less walking (p=0.0403). Several wearable data daily physical activity measures demonstrated statistically significant change at the time of PD.

CONCLUSION

Remote monitoring data can complement snapshots of health gathered during clinical visits. Collection of digital data hold promise for novel HGG trial outcome measure development.
NCOG-23. ASSESSMENT OF NON-MEASURABLE DISEASE IN HIGH-GRADE GLIOMA: RANO-BASED 2D VS. 3D VOLUMETRICS
Authors: Farhat Maguy , Chen Melissa , Gule Maria , Talpur Wasif , Langshaw Holly , White Victoria , Chung Caroline
Published: November 2023

Non-measurable disease (NMD) in High grade glioma (HGG), defined as "longest perpendicular dimension of less than 10 mm”, is a limitation of RANO criteria that limits trial enrollment and biases trial populations to exclude patients with smaller tumors that eventually become measurable. Volumetric (3D) measurements may improve sensitivity and precision for measuring HGG of all sizes, however there is limited data comparing volumetric to 2D RANO measurements. AIMS: To investigate the correlation between RANO-based bidimensional 2D and 3D volumetric measurements in the postoperative setting of patients with HGG, including patients with NMD. METHODS: Contrast-enhanced (CE) postoperative and radiotherapy planning MRIs were utilized for 2D RANO measurements by neuroradiologists and volumetric (3D) measurements extracted from segmentations of CE disease. Pearson’s correlation between the 2D and 3D measurements were evaluated at each time point. The percentage of NMD based on RANO criteria and the range of tumor volumes for the NMD cases were reported. RESULTS: For 59 patients, there was lower concordance in the 2D and 3D measures at the postoperative MRI time point (Pearson =0.46) compared to the treatment planning MRI time point (Pearson=0.81). Interestingly, the postoperative time point had a higher percentage of NMD of 38% with the mean tumor volume of 13 cm3 (range: 0-21 cm3) compared to the treatment planning MRI with percentage NMD of 8% and mean tumor volume of 9 cm3 (range: 6-13cm3). CONCLUSION: In this study, higher rate of agreement was observed between RANO-based 2D and 3D volumetric tumor measurements at the time point of MR simulation when there was lower rate of NMD, suggesting NMD may contribute to the discrepancy between 2D and 3D measurements. Volumetric measurement tools may be a superior approach to improve the assessment especially of NMD in the postoperative period, improving trial enrollment for these patients.
NCOG-30. ENVIRONMENTAL ENRICHMENT AND HEALTH OUTCOMES AFTER RADIATION
Authors: Figuracion Karl Cristie , McGranahan Tresa , Lewis Frances , Donald Christine Mac , Hunt David , Rockhill Jason , Halasz Lia , Goldberg Myron , Thompson Hilaire
Published: November 2023

Individuals treated with brain radiation (RT) are at a disproportionately increased risk of accelerated aging and symptom burden. The aim of this abstract is to describe the health outcomes experienced by brain tumor (BT) survivors who received Photon (XRT) and Proton-Beam (PBRT) in relation to levels of environmental enrichment (EE). The study employed a cross-sectional cohort design among persons with glioma (WHO Grade 2 and 3) treated with RT approximately 5 years following diagnosis. EE consists of social network/engagement, physical activity, and employment status/financial stability measured by the Berkman-Syme Social Network Index, International Physical Activity Questionnaire, Vocational Index Scale, and two Socioeconomic Questions, respectively. EE level is classified into low, moderate, or high tertile. Montreal Cognitive Assessment measured cognitive function. Cortical atrophy is measured using temporal brain MRI images from the time of diagnosis, 3 years after, and at the time of enrollment. Images were processed using FreeSurfer. MD Anderson Symptom Inventory – BT module was used to measure functional status. Two-Way ANOVA described the health outcomes among individuals who received XRT and PBRT. Thirty-nine participants, 18 with astrocytoma and 19 with oligodendroglioma, completed the study protocol. Eighteen individuals received XRT (5 were categorized into Low EE, 10 to Moderate EE and 3 had High levels of EE) and 21 received PBRT (8 were categorized into Low EE, 7 had Moderate EE and 6 had High EE). Individuals who received XRT and had High levels of EE had higher scores in MoCA, lower cortical atrophy rate, and lower symptom burden than individuals who had Moderate and Low EE. BT survivors are at an increased risk of accelerated aging and progressive neurological decline. Providing an enriched environment may serve to reduce symptom burden, promote healthy brain aging, and improve cognitive and functional status in BT survivors receiving radiation.
NCOG-39. DOSE-EFFECT RELATIONSHIP OF DEXAMETHASONE ON OUTCOMES OF PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA
Authors: White Jessica , Webb Lauren , Neth Bryan , Sener Ugur , Mustafa Rafid
Published: November 2023

BACKGROUND

Dexamethasone is commonly used for symptomatic management in primary central nervous lymphoma (PCNSL). The optimal dosing scheme for dexamethasone is unknown and practice patterns widely vary among clinicians. In this study, we explored the dose-effect relationship of dexamethasone on PCNSL outcomes to better influence quality care for these patients.

METHODS

We retrospectively identified 24 Mayo Clinic patients (1/1/2018 – 12/31/2022) with pathologically confirmed PCNSL who received dexamethasone. All patients otherwise received standard oncologic care including methotrexate-based systemic chemotherapy and/or radiotherapy. The association between dexamethasone dosing regimens and clinical outcomes (performance status, clinical and radiographic response, survival) in addition to potential adverse effects were evaluated in the acute phase of presentation and at first post-treatment oncology follow up.

RESULTS

Nine patients received less frequent dexamethasone dosing (4 mg twice daily or less), while 15 received more frequent dexamethasone dosing (4 mg four times daily). Fourteen patients received dexamethasone prior to biopsy, 2 of which (1 in each cohort) had a non-diagnostic biopsy and required a second procedure 3 weeks to 3 months later to confirm PCNSL diagnosis. There were no statistically significant differences in time to diagnosis from presentation or clinical and radiographic improvement including Karnofsky Performance Status, reduction in seizures, or survival between the two cohorts. Additionally, there were no differences in the frequency of adverse events (e.g., hyperglycemia, hypertension, infection, psychosis) between the two dosing regimens.

CONCLUSIONS

These results suggest that more frequent dexamethasone dosing is not associated with better clinical outcomes in the symptomatic management of PCNSL. Twice daily or less frequent dosing can be considered without compromising patient outcomes.
EXTH-24. FC-ENHANCED ANTI-CTLA-4 IMMUNE CHECKPOINT BLOCKADE AND ITS COMBINATION WITH ANTI-PD-1 WITH CONCOMITANT DOXORUBICIN AND ULTRASOUND-MEDIATED BBB OPENING: A NOVEL IMMUNOTHERAPY FOR GLIOBLASTOMA
Authors: Kim Kwang-Soo , Habashy Karl , Gould Andrew , Najem Hinda , Zhao Junfei , Amidei Christina , Saganty Ruth , Arrieta Victor , Dmello Crismita , Chen Li , Zhang Daniel , Castro Brandyn , Billingham Leah , Levey Daniel , Morin Benjamin , Muzzio Miguel , Canney Michael , McCortney Katy , Horbinski Craig , Zhang Peng , Miska Jason , Rabadan Raul , Heimberger Amy , Stupp Roger , Chand Dhan , Lee-Chang Catalina , Sonabend Adam
Published: November 2023

Despite the recent success of immune checkpoint blockade in various cancer types, glioblastoma (GBM) remains resistant to immunotherapy due to its immunosuppressive features and the poor penetration of systemic agents across the blood-brain barrier (BBB). Recent clinical trials demonstrated the unprecedented efficacy of Fc enhanced anti-CTLA-4, an anti-CTLA-4 antibody with enhanced affinity to Fcγ receptors (FcE-aCTLA-4), against immunologically inactive (‘cold’) tumors. This agent exhibits a high affinity for FcγRIIIA regardless of its polymorphic variants of FcgRIIIA that are known to influence the binding affinity and efficacy of conventional anti-CTLA-4 antibodies. We observed robust expression of FcγRIIIA in tumor-associated macrophages/myeloid cells (TAM) of human GBM, which was most pronounced in newly diagnosed GBM. FcE-aCTLA-4 demonstrated high-affinity binding to FcγRIV, the mouse ortholog of human FcγRIIIA, which was highly expressed on TAMs in mouse gliomas. We evaluated the efficacy of the murine homologous FcE-aCTLA-4 antibody as monotherapy and in combination with other treatments in several murine glioma models. FcE-aCTLA-4 selectively depleted CTLA-4 expressing intra-tumoral regulatory T cells (Tregs) via antibody-dependent phagocytosis by TAMs while spearing peripheral Tregs and other CD4+ T cell populations. In a cohort of 4 GBM patients, doxorubicin delivered with low-intensity pulsed ultrasound and microbubbles (LIPU/MB), a procedure that temporarily opens the BBB, upregulated FcγRIIIA expression on TAMs. Treatment of immunotherapy-resistant murine gliomas with a combination of FcE-aCTLA-4, anti-PD-1, and doxorubicin with concomitant LIPU/MB resulted in over 90% cure rates, which correlated with increased infiltration of activated CD8+ T cells in the brain, and complete rejection upon subsequent tumor rechallenge. Our findings indicate that FcE-aCTLA-4 exhibits a novel immunomodulatory function in GBM, and its therapeutic potential is significantly improved when combined with anti-PD-1, doxorubicin, and delivered by LIPU/MB. This therapy warrants further evaluation in clinical trials.
EXTH-42. PRECLINICAL INVESTIGATION OF A NOVEL BRAIN PENETRANT MEK INHIBITOR TO TARGET BRAIN METASTASIS
Authors: Yamazawa Erika , Nayyar Naema , Ijad Nazanin , Torrini Consuelo , De Sauvage Magali , Migliarese Christian , Summers Elizabeth , Marion Braxton , Lee Catherine , Suriben Rowena , Perez Michelle , Powell Ben , Miller Nichol , Grandinetti Brooke , Wakimoto Hiroaki , Brastianos Priscilla
Published: November 2023

Melanoma is one of the most common cancers with a high rate of brain metastases, with up to 75% of cases showing brain metastases upon autopsy. BRAF mutations are common in melanoma and found in up to 50-55% of melanoma brain metastases. Despite the clinical success of BRAF/MEK inhibitors for the treatment of advanced melanoma, dabrafenib and vemurafenib have limited intracranial overall response rates of 42-50% and median progression-free survival of 3.6-5.5 months. This limited efficacy is in part attributed to minimal blood-brain barrier penetration of the current available inhibitors. The goal of this study was to characterize a novel MEK inhibitor KIN-7136 as a potential therapeutic agent for brain metastasis driven by aberrant BRAF-MEK signaling, such as BRAF-mutant melanoma, using in vitro assays and an in vivo model of metastasis. KIN-7136 showed improved rodent brain exposure compared to conventional agents; the brain-to-plasma concentration ratio (Kp) of KIN-7136 was >1.0, much higher than comparators binimetinib and mirdametinib. In vitro cell viability assays showed potent cytotoxic effects of KIN-7136, with IC50s ranging from 15.4 to 204.9 nM in models of MAPK dysregulation including A375 (melanoma, BRAFV600E), NCI-H2405 (lung adenocarcinoma, BRAFΔNVTAP), HMVII (melanoma, BRAFG469V), and LN001 (patient derived lung adenocarcinoma, KRASG12V). Western blotting for phospho-ERK confirmed KIN-7136-mediated on-target downstream suppression in the A375 cell line. In vivo, daily oral treatment with KIN-7136 was well tolerated and produced a significant extension of overall survival compared to the vehicle control (p=0.0289, log-rank test) in the A375 intracranial tumor model in athymic mice. These preclinical data confirm activity of KIN-7136 in BRAF-mutant melanoma brain metastases models and support further research to advance its clinical progression.
EXTH-74. TUMOR PHARMACOKINETICS AND PHARMACODYNAMICS IN PATIENT-DERIVED XENOGRAFT MODELS OF GLIOBLASTOMA TREATED WITH THE PRMT5 INHIBITOR SKL27969
Authors: Tien An-Chi , Margaryan Tigran , Molloy Jennifer , McNamara James , Knight William , Hon Raymond , Opachich Zorana , Melendez Ernesto Luna , Elliott Mackenna , White Connor , Sanai Nader , Tovmasyan Artak , Mehta Shwetal
Published: November 2023

Epigenetic regulation plays a key role in the development of several cancers, including glioblastoma (GBM). Protein arginine methyltransferase 5 (PRMT5) has recently emerged as a promising therapeutic target for GBM. PRMT5 is the primary type II methyltransferase that catalyzes symmetric arginine dimethylation in multiple proteins. In this study, we evaluated the pharmacokinetics, pharmacodynamics, and radiation sensitization properties of SKL27969, a highly selective PRMT5 inhibitor, in orthotopic patient-derived xenograft (PDX) models of GBM. Mice with intracranial tumors were randomized to 50 mg/kg (oral) SKL27969 vs. placebo for two cycles either alone or in combination with radiation. SKL27969 levels in plasma and contrast-enhancing tumor tissue were measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). Unbound fractions were determined by equilibrium dialysis. Immunohistochemistry was performed to assess levels of SDMA, phospho-Histone H3, pH2AX, and cleaved caspase 3 (CC3). For survival studies, mice with intracranial tumors were randomized into four cohorts – vehicle, radiotherapy, SKL27969 monotherapy, and SKL27969 plus radiotherapy. The median brain-to-plasma and tumor-to-plasma partition coefficients of unbound SKL27969 were 1.8 and 2.9, respectively – indicating favorable brain and tumor penetration ability of SKL27969. A decrease in SDMA (+) cells (54% vs. 0.1%, p < 0.001) indicated PRMT5 inhibition and was accompanied by an increase in CC3 (+) cells (0.7% vs. 1.2%, p = 0.01). SKL27969 is well tolerated, achieves pharmacologically relevant unbound concentrations in GBM PDX models, and is associated with significant target modulation. Ongoing studies are evaluating in vivo survival benefit from combining PRMT5 inhibition with radiation therapy.
EXTH-76. TRANSLATIONAL BARRIERS IN 5-ALA PHOTODYNAMIC THERAPY FOR GLIOMAS: A SYSTEMATIC REVIEW OF THE IN VIVO LANDSCAPE AND FUTURE DIRECTIONS FOR CLINICAL APPLICABILITY
Authors: Bhanja Debarati , Wilding Hannah , Baroz Angel , Trifoi Mara , Shenoy Ganesh , Slage-Webb Becky , Hayes Daniel , Soudagar Yasaman , Connor James R , Mansouri Alireza
Published: November 2023

INTRODUCTION

Photodynamic therapy (PDT) is an emerging investigational therapeutic for gliomas marked by variable success. Several strategies to increase its efficacy have been attempted, and although promising, challenges that have hindered translational progress persist. The objective of this study was to analyze translational barriers through a systematic review and appraisal of the in vivo literature. Method: PRISMA guidelines were utilized to identify studies that reported translational in vivo data of 5-aminolevulinic acid (5-ALA) PDT in murine glioma models. Databases were searched from inception to 2022, using the terms: “photodynamic therapy” AND (“5-ALA” OR “ALA” OR “PPIX”) AND “in vivo” AND (“glioma” OR “glioblastoma” OR astrocytoma”). Study design parameters were appraised, and mechanistic and translational outcomes across all studies were evaluated and compared. Result: Eight studies (2002-2019) were included. The most common animal model used was immunosuppressed rats orthotopically implanted with glioma cells. Only two studies used syngeneic models. No studies validated findings in external cohorts or patient-derived xenografts. Experimental light power densities ranged widely from 0.5-100mW/ cm2. Only three studies utilized a longitudinal delivery strategy, and all found significantly decreased tumor volume and increased survival compared to high-dose single-session PDT. For mechanistic endpoints, only one study investigated the impact of PDT on the immune response, finding increased TME CD8+ T-cell infiltration in the experimental group. Safety endpoints, including hemorrhage, elevated intracranial pressure (ICP), and off-target cortical damage, were measured in only three studies, in which high power densities were associated with increased hemorrhage and elevated ICP.

CONCLUSION

While in vivo evidence for 5-ALA PDT is compelling, this appraisal uncovers discrepancies in power densities, lack of validation in putative translational models, and limited understanding of PDT impact on the immune response and TME. Future preclinical investigations that address these barriers will offer distinct and necessary steps toward effective clinical translation.
QLTI-10. STANDARD WORK FOR ORAL CHEMOTHERAPY IMPROVES SAFETY WITHOUT INCREASING DELAYS
Authors: Balakrishnan Samantha , Nagpal Seema , Dugala Anisia , Coffey Gwen , Pena Justine
Published: November 2023

Purpose

Oral chemotherapy in the outpatient setting does not have the same level of oversight as chemotherapies delivered in an infusion treatment area. This project aimed to create a standardized process to prescribe outpatient oral chemotherapy to improve patient safety. The primary process-measure was laboratory data review prior to ordering therapy, with primary outcome-measure being number of days between approval to administer therapy and actual administration. A secondary process-measure was documentation quality, and counterbalance-measure was delay in ordering due to lab review.

METHODS

A Failure Mode Effects Analysis was performed. Standard work was developed for each step of prescribing and roles and responsibilities were assigned for each step in the process. A checklist was developed within the medical record to review and document essential steps in the process allowing for greater visibility. Fifty-three patient encounters were reviewed prior to intervention and 39 post-intervention.

RESULTS

FMEA identified 7 high-risk points. For the primary process measure, prior to intervention, 34/53 (64%) encounters had laboratory data review prior to chemotherapy order. After intervention, 38/39 (97%). The change did not delay ordering; we observed a mean 2-day delay between laboratory data review and chemotherapy order (significant difference from zero [p = 0.001]) pre-intervention. After intervention, there was no statistically significant delay (mean -0.74 days, p = 0.376). Documentation improved after intervention; 23/53 (43%) chemotherapy encounters contained complete data pre-intervention, and 36/39 encounters (92%) post-intervention.

CONCLUSIONS

As part of our standardized process, we developed a new chemotherapy checklist and flowsheet in the medical record. While the fraction of patients with zero delay in chemotherapy administration after approval did not change, patient safety improved with more patients having laboratory review prior to chemotherapy order. This review did not increase delays in ordering therapy. Documentation quality also improved. Having a standard process increases patient safety while prescribing outpatient oral chemotherapy.
QOL-01. VARIABILITY IN ANXIETY AND DEPRESSION SYMPTOMS AFTER ELOQUENT GLIOMA RESECTION IS ASSOCIATED WITH CHANGES IN FUNCTIONAL CONNECTOMIC PROPERTIES
Authors: Noll Kyle , Chen Henry , Bradshaw Mariana , Wefel Jeffrey , Sullaway Catherine , Thomas Ashley , Kumar Vinodh , Prabhu Sujit , Liu Ho-Ling
Published: November 2023

Little is known regarding how treatment-related changes in cerebral networks relate to symptoms of anxiety and depression in patients with glioma. Fifteen patients with left perisylvian glioma underwent resting-state fMRI and neuropsychological evaluation before and 1 month after resection. Symptoms of depression and anxiety were characterized with Beck Depression Inventory-II (BDI) and Beck Anxiety Inventory (BAI) Total scores and rates of clinically significant symptom burden. Change scores and reliable change classifications were also examined. Graph theoretical analysis was applied to fMRI connectivity matrices to calculate brain network properties. Comparison of pre- and postoperative measures were performed with Wilcoxon tests. Correlations between changes in anxiety and depression symptom measures and network properties were examined. Pre- and postoperative Total scores did not significantly differ though postoperative symptom burden trended toward reduction [Change: BDI=-1.93(5.73), BAI=-5.80(8.19)] with considerable interindividual variability noted [Change: BDI range=-12 to +6; BAI range=-18 to +6]. Preoperatively, at least mild symptoms were found in 27% of patients on BDI and 60% on BAI. Postoperatively, rates were the same for BDI while BAI was 33%. Using reliable change criteria, improvement was found in 13% of patients on BDI and 33% on BAI without any significant worsening. Significant postoperative connectivity decreases were observed in betweenness centrality [Change = -5.56(12.07), p = .031] and assortativity [Change=-.062(.096), p = .027]. Strong associations were found between pre- to postoperative differences in betweenness centrality and assortativity and changes in BDI [ρ(13)=.58 and .67, p< .02] and BAI Total scores [ρ(13)=.62 and .68, p< .01]. Anxiety and depression symptoms vary considerably postoperatively, though most patients do not show significant worsening. Variability in symptom change appears related to alterations in functional connectomics, with those showing increases in certain connectomic properties exhibiting worse postoperative anxiety and depression symptoms. Surgically-induced connectomic changes may coincide with or potentially contribute to psychological symptom differences in the postoperative setting.