Demographic and MRI characteristics of patients involved in stage 1, stage 2, and stage 3.

Evaluating the effect on model performance (AUC) when performing ensemble across an increasingly larger number of models. Five independent sets of 5-fold cross-validation were evaluated. One 5-fold cross-validation set denotes performing ensemble across the resulting k = 5 models. Two 5-fold cross-validation sets denote ensemble across 10 models, three sets denote ensemble across 15 models, four sets denote ensemble across 20 models, and five sets denote ensemble across 25 models.

Cartoon comparing AUC and cross entropy loss on five GBM patients and five CNS-DLBCL cases. Grey denotes GBM and black denotes CNS-DLBCL. All models have the same AUC (AUC=100%); however, Model 4 has the smallest cross entropy loss.

Abstract Background: Pembrolizumab has been increasingly used off label for recurrent gliomas, yet biomarkers predicting response are poorly defined. Gliomas exhibit substantial molecular heterogeneity across Glioblastoma, IDH-wildtype (GBM), Astrocytoma, IDH-Mutant (A-IDHm), and Oligodendroglioma, 1p/19q co-deleted (OLIGO), which may influence immunotherapy efficacy. This study aimed to identify molecular predictors of progression-free survival (PFS) in recurrent glioma patients treated with pembrolizumab. Methods: Adults ≥18 years with recurrent glioma receiving ≥2 cycles of pembrolizumab between 2014 - 2024 were retrospectively identified across Mayo Clinic. Next-generation sequencing (NGS) reports were reviewed and archival tumor tissue resected prior to pembrolizumab initiation was analyzed when available. Comprehensive molecular profiling was performed using the Mayo Clinic Solid Tumor Panel which employs the Illumina Tru-Sight Oncology 500 High-Throughput NGS assay. Progression was assessed using RANO 2.0 criteria. Genomic alterations (clinically relevant sequences and/or copy-number variants) were evaluated using the Kaplan-Meier method, with differences in PFS compared using the log-rank test. Results: Thirty-three patients were included [median (range) age: 44.0 (21-76) years; 63.6% male]. The interval between tumor tissue sampling and pembrolizumab initiation was 9.9 (0.9-176.1) months, and median treatment duration was 2.8 (1.4-10.4) months. Median PFS for the overall cohort was 2.4 (0.8-15.2) months, and median overall survival from pembrolizumab initiation was 6.9 (0.9-48.2) months. Patients with OLIGO (n=8) had a longer PFS [4.6 (1.9-15.2) months] than either A-IDHm [n=11; PFS 2.1 (1.1-4.4) months] or GBM [n=14; PFS 2.3 (0.8-9.2) months]. Within OLIGO, CDKN2A/B heterozygous deletion (n=3) predicted a shorter PFS (3.9 vs 10.9 months; p=0.0462), while in A-IDHm, FANC mutation (n=2) was associated with a longer PFS (4.17 vs 1.61 months; p=0.0224). No significant associations with PFS were observed for other altered genes or pathways evaluated, including but not limited to Tumor Mutational Burden, EGFR, RB1, TP53, FUBP1, NF 1 or 2, PTEN, PDGFRA, PIK3CA, PIK3R1, CDK4, KRAS, MLH1, MLH2, MSH6 genomic alterations or CDKN2A/B homozygous deletion (all p>0.05). Conclusions: Pembrolizumab shows limited overall efficacy in recurrent gliomas, however, exploratory analyses identified several subtype-specific genomic alterations that may correlate with PFS. These hypothesis-generating findings highlight the potential influence of underlying tumor biology on immunotherapy response and warrant further validation in larger, prospective cohorts. Citation Format: Shameel Shafqat, Muhammad Asad Maqbool, Hussam Al Kateb, Terry C. Burns, Jian L. Campian, Shannon P. Fortin Ensign, Evanthia Galanis, Julie E. Hammack, Cristaine M. Ida, Mitch L. Klebig, Timothy J. Kaufmann, Autumn C. Moon, Maciej M. Mrugala, Bryan J. Neth, Alyx B. aPorter, Michael W. Ruff, Ugur T. Sener, Wendy J. Sherman, Joon H. Uhm, Rachael A. Vaubel, Sani H. Kizilbash. Molecular correlates of progression-free survival in recurrent gliomas treated with pembrolizumab [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5253.

Model performance on the 256 GBM and 73 CNS-DLBCL independent test cases from stage 3 from the model developed using the ensemble approach (A) overall, (B) stratified by sex, and (C) stratified by age. Results for the model developed using the loss approach (D) overall, (E) stratified by sex, and (F) stratified by age. AUCs (95% CI) are provided.

Violin plots showing the model scores from the 240 retrospective GBM cases in stage 2 from the models developed using the (A) ensemble approach and (B) loss approach.

Background:The current treatment of glioblastoma involves resection followed by radiotherapy (RT) and temozolomide. Rapid early progression (REP) of tumor in the surgery-to-radiotherapy interval (SRI) has been described using categorical or semi-quantitative assessments and is associated with inferior clinical outcomes. This study seeks to establish and validate a quantitative definition for REP and examine how REP could inform future therapy. Methods:Volumes of tumor and resection cavity at 3 time points-preoperative, postoperative and RT-planning (pre-RT)-were contoured among patients who had undergone standard of care. A minimal, but clinically appreciable, threshold for defining REP based on change in tumor volume was established, validated, and subsequently used to assess actionable predictors of REP and its prognostic value. Results:An increase of >2 cc in volume or a new satellite tumor between the post-operative to planning MRI was found to be a sensitive, pragmatic, and statistically significant cutoff for REP (P = .002). Actionable predictors such as SRI of 6 weeks and a > 5 cc residual immediate post-operative tumor volume were found to be statistically significant predictors of REP. REP was also found to be a statistically significant prognostic indicator for overall survival (P = .002) and progression-free survival. Conclusion:These findings support that an increase in tumor volume between post-operative and pre-RT MRI of >2 cc is the ideal working definition of REP in this clinical setting. Furthermore, REP could serve as a prognostic -biomarker to track treatment response. Additionally, 2 actionable predictors of REP, post-op residual tumor volume and SRI, are identified.

Toxicities from CAR-T cell therapy are complex, severe, and often require multidisciplinary management. To standardize care, our institution established a Serious Adverse Event Oversight Committee (SAEOC), comprising specialists from hematology, neurology, nephrology, infectious diseases, intensive care, cardiology, and pharmacy. Once activated, the committee convenes virtually twice daily until SAE resolution or deactivation. We retrospectively examined outcomes in patients with macrophage activation syndrome/ hemophagocytic lymphohistiocytosis (MAS/HLH) treated before and after SAEOC implementation in December 2022. Provider perceptions were evaluated through a survey.The SAEOC was activated for 19 patients, most frequently for MAS-like syndromes (n=7), MAS/HLH (n=4), and high-grade ICANS (n=14). Additional triggers included CD8+ T-cell lymphoproliferative disorder, delayed IEC neurotoxicity and enterocolitis, massive pulmonary embolism, and diffuse alveolar hemorrhage.To assess outcomes, we focused on a more homogeneous subgroup of patients with MAS/HLH, comparing all patients treated prior to SAEOC implementation (n=8; 3 axi-cel, 1 tisa-cel, 1 ide-cel, 1 cilta-cel, 2 investigational CAR-Ts) with those treated after (n=6; 3 axi-cel, 1 brexu-cel, 2 cilta-cel). In the post-SAEOC cohort, 30- and 100-day treatment-related mortality were numerically lower, compared with the pre-SAEOC cohort (Table 1). Although these differences did not reach statistical significance, the findings may suggest a potential benefit of structured multidisciplinary oversight, acknowledging the limitations of small sample size and treatment-era differences.A total of 21 providers completed surveys (Figure 1), with ≥80% reporting perceived improvements in timeliness of interventions, consistency and comprehensiveness of management, interdisciplinary communication, and confidence in SAE management (Figure 2). Respondents valued SAEOC contributions to management of complex cases such as IEC-parkinsonism, MAS/HLH, CNS infection, and multiorgan involvement. SAEOC implementation also contributed to refinement of institutional standard operating practices. Reported challenges included workload and meeting frequency. One respondent provided uniformly negative Likert ratings but described the intervention as highly beneficial in free text; this discordant response was kept but interpreted cautiously. Suggested improvements included streamlining activation, reducing meeting frequency when appropriate, formal recognition of provider effort, and greater incorporation of evidence-based frameworks.The SAEOC represents a model for early multidisciplinary engagement and provides a practical framework for harmonizing CAR-T toxicity management, particularly for complex cases.

Sensitivity and specificity of the loss model applied to the stage 3 cohort. All possible model score thresholds from the loss model are shown. The yellow highlighted row denotes the score threshold required to obtain 90% sensitivity. The orange highlighted row denotes the score threshold required to obtain 90% specificity.

Background Isocitrate dehydrogenase (IDH)-mutant gliomas are infiltrative tumors with limited treatment options at recurrence. Early studies suggest IDH inhibition has therapeutic activity. We evaluated clinical outcomes associated with IDH-1 inhibitor ivosidenib in recurrent IDH-1-mutant gliomas and molecular predictors of response.Methods We retrospectively analyzed adults treated with ivosidenib from January 2021 to August 2025 with predominantly recurrent, pretreated CNS WHO grade 2-4 astrocytoma IDH-mutant or grade 2-3 oligodendroglioma, IDH-mutant and 1p/19q codeleted. Prior anticancer treatments, toxicities, enhancement status at ivosidenib initiation, and genomic alterations were collected. The primary endpoint was progression-free survival (PFS); secondary analyses evaluated associations between PFS, genomic complexity, and CDKN2A/B homozygous deletion.Results Ninety-two adults, median age 43, were included: 61 astrocytomas and 31 oligodendrogliomas, mostly grade 2. Before ivosidenib, 69 had surgery, 64 chemotherapy, and 64 radiation. Median time from diagnosis to ivosidenib was 4.8 years, with median of two prior progressions. Median treatment duration was 5.8 months. Median PFS was 15.2, 4.6, and 2.1 months for astrocytoma grades 2-4, 14.0 and 6.9 months for oligodendroglioma grades 2-3. Increasing genomic complexity was associated with shorter PFS in univariate analysis. Patients without CDKN2A/B homozygous deletion had median PFS of 19.2 months. Two patients with homozygous deletion had median PFS of 0.6 months.Conclusions In this retrospective analysis of predominantly recurrent IDH-1-mutant glioma, ivosidenib was associated with longer PFS in lower-grade, non-enhancing tumors that received little or no prior anticancer treatment and less complex genomic profiles. These findings support a context-dependent benefit of IDH inhibition in recurrent disease. Gliomas with mutations in the gene called isocitrate dehydrogenase (IDH) typically occur in younger adults and can be treated with a combination of surgery, radiation therapy, chemotherapy, and with IDH inhibitors such as vorasidenib or ivosidenib. In this study, we evaluated patients with recurrent IDH-mutant gliomas treated with ivosidenib at our institution. Ninety-two patients with IDH-mutant astrocytomas or oligodendrogliomas were studied. Individuals with lower-grade tumors that had less genetic complexity and fewer prior tumor-directed treatment experienced longer progression-free survival with ivosidenib treatment. Treatment was generally well-tolerated. Ivosidenib can be considered as a treatment option for individuals with recurrent IDH-mutant gliomas.

Cognitive symptoms are among the most frequently reported issues in cancer patients treated with cranial radiation, yet they remain inadequately assessed in clinical practice and are suboptimally treated. Cranial radiation is an integral part of treatment for primary and metastatic brain tumors that contributes to progressive and irreversible cognitive decline with currently limited therapeutic options. Development of effective interventions that can prevent or delay this neurocognitive toxicity requires accurate assessment of symptom burden. However, formal neuropsychological testing is resource intensive and time consuming. Repeated in-person assessments are often not feasible for cancer patients who must travel great distances to specialized cancer centers. The Neuro-Oncology Anywhere (NOA) study is a fully decentralized clinical trial with an overarching goal to evaluate remote cognitive assessments while simultaneously evaluating benefits of health promotion through use of a wearable watch device and metformin in preventing radiation-related cognitive decline. The primary objective of this study is to determine the feasibility of completing serial remote cognitive, activity/sleep, and self-reported assessments among patients who have previously received cranial radiation. Key secondary objectives are to assess satisfaction of patients with remote monitoring, evaluate adherence to study drug, and compare neurocognitive function scores and the impact of receiving metformin and health promotion with a wearable device compared to wearable device alone. Determination of the remote platform’s feasibility among patients with brain tumors will provide a strong scientific foundation for routinely integrating scalable remote cognitive assessment strategies into future clinical trials, enabling accelerated evaluation of potentially effective interventions unconstrained by geographic limitations. Trial registration ID NCT06377696

The MRI model was run on 34 patients with tumefactive demyelination. (A) Distribution of predicted MRI score for the 34 patients. (B) Distribution of predicted MRI score by age at diagnosis. The blue line denotes a loess fit and the grey shaded area denotes the 95% confidence interval. (C) Distribution of predicted MRI score by gender (F=female, M=Male). (D) Distribution of predicted MRI score by MRI manufacturer. (E) Distribution of predicted MRI score by MRI field strength. (F) Distribution of predicted MRI score by T1Gd acquisition type. T2 acquisition type is not shown because 33 of the 34 patients were sequenced using 2D.

Violin plots showing the model scores for the 256 GBM and 73 CNS-DLBCL cases in stage 3, obtained from the models developed using the (A) ensemble approach and (B) loss approach.

Background Isocitrate dehydrogenase-1 (IDH-1) inhibitor ivosidenib and dual-IDH1/2 inhibitor vorasidenib have demonstrated clinical activity in the treatment of IDH-mutant gliomas. We evaluated the efficacy of vorasidenib in patients with prior exposure to ivosidenib.Methods Retrospective review of patients with IDH-mutant glioma treated with vorasidenib who had prior treatment with ivosidenib. Previous treatments, radiographic response, and adverse events were collected and analyzed descriptively.Results Twenty-nine patients (median age 42, 34% female) were evaluated. Tumor types included IDH-mutant astrocytoma (grade 2 n = 9, 31%; grade 3 n = 3, 10%; grade 4 n = 3, 10%) and oligodendroglioma (grade 2 n = 10, 34%; grade 3 n = 4, 14%). Treatments received prior to ivosidenib included surgical resection (n = 23, 79%), radiation (n = 16, 55%), temozolomide (n = 15, 52%), procarbazine, lomustine, vincristine (PCV, n = 2, 7%), bevacizumab (n = 3, 10%), lomustine (n = 2, 7%), and pembrolizumab (n = 1, 3%). Four patients received additional treatment in between ivosidenib and vorasidenib treatment. Ten of 16 (63%) patients who experienced disease progression on ivosidenib achieved stable disease and remain on vorasidenib, while 6 (37%) had continued progression. Eleven patients with stable disease on ivosidenib transitioned to vorasidenib following FDA approval and remained without progression. Two patients who transitioned to vorasidenib due to ivosidenib-related adverse effects (diarrhea and fatigue) experienced symptom resolution and maintained disease stability.Results Twenty-nine patients (median age 42, 34% female) were evaluated. Tumor types included IDH-mutant astrocytoma (grade 2 n = 9, 31%; grade 3 n = 3, 10%; grade 4 n = 3, 10%) and oligodendroglioma (grade 2 n = 10, 34%; grade 3 n = 4, 14%). Treatments received prior to ivosidenib included surgical resection (n = 23, 79%), radiation (n = 16, 55%), temozolomide (n = 15, 52%), procarbazine, lomustine, vincristine (PCV, n = 2, 7%), bevacizumab (n = 3, 10%), lomustine (n = 2, 7%), and pembrolizumab (n = 1, 3%). Four patients received additional treatment in between ivosidenib and vorasidenib treatment. Ten of 16 (63%) patients who experienced disease progression on ivosidenib achieved stable disease and remain on vorasidenib, while 6 (37%) had continued progression. Eleven patients with stable disease on ivosidenib transitioned to vorasidenib following FDA approval and remained without progression. Two patients who transitioned to vorasidenib due to ivosidenib-related adverse effects (diarrhea and fatigue) experienced symptom resolution and maintained disease stability.Conclusions Vorasidenib demonstrated clinical efficacy in patients with IDH-mutant gliomas previously treated with ivosidenib. Notably, stable patients who transitioned maintained disease stability, while some of those with progressive disease achieved stabilization with vorasidenib. These findings support vorasidenib as a viable therapeutic option following ivosidenib exposure. People with isocitrate dehydrogenase (IDH)-mutant gliomas are often diagnosed at a young age and may live with their disease for many years. New targeted treatments called IDH inhibitors have improved care for these patients, but little is known about what happens when one IDH inhibitor is used after another. This study aimed to understand whether a newer IDH inhibitor, vorasidenib, remains effective and safe in patients who were previously treated with an earlier drug, ivosidenib.We reviewed medical records of 29 patients with IDH-mutant glioma who received vorasidenib after prior treatment with ivosidenib. Some patients switched because their tumor was progressing, others because vorasidenib became newly approved, and a few due to side effects from ivosidenib. We examined tumor imaging results, treatment tolerance, and patient outcomes.Many patients whose tumors were stable on ivosidenib remained stable after switching to vorasidenib. Importantly, some patients whose tumors had worsened on ivosidenib experienced disease stabilization with vorasidenib. Vorasidenib was generally well tolerated, and patients who switched due to side effects often had symptom improvement.These findings show that vorasidenib can remain effective after prior IDH inhibitor treatment and support its use as a meaningful next treatment option for patients with IDH-mutant gliomas.

1633 Background: CAR-T cell therapy has transformed outcomes of hematologic malignancies and is poised to expand into solid malignancies. However, broader use of CAR-T remains constrained by the need for timely cytokine release syndrome (CRS) detection. Current episodic monitoring may miss early physiologic changes. Wearable digital health technologies (DHTs), offering continuous monitoring and real-time alerts, could enable earlier CRS detection, further support outpatient delivery, and expand access to CAR-T and potentially other immunotherapies associated with CRS. Methods: This single-center observational study (NCT05018208) enrolled patients receiving FDA-approved CAR-T products in the outpatient setting at Mayo Clinic, Rochester MN. Management of post-CAR-T complications (e.g. CRS) followed the institution’s standard of care. Patients were monitored from day -5 to day +30 post infusion with intermittent remote patient monitoring (SoC) and an arm-worn wearable device for continuous monitoring (DHT). Patients were included in this analysis if DHT data were available for ≥ 5h of data/day or ≥ 2h of data/night on ≥2 days or nights for baseline and ≥1 day or night within 72h prior to CRS, or at least 2h within 4h of CRS onset, or if DHT was available for ≥7 days/nights post infusion with no CRS event. CRS detection time by DHT was defined as the onset of pyrexia or threshold-based deviation from an individual’s baseline pulse distributions. Results: 32 patients were included in this report (median age 64 years, gender 12 F/20 M, diagnoses 18 MM/14 NHL). 25 patients experienced a CRS event, with maximum CRS grades ranging from 1-3 (16 G1, 8 G2, 1 G3). 24/25 patients with CRS required tocilizumab/steroid. Median CRS onset time was 3.4 days (range 0.4-18.4). 12/32 patients had sufficient DHT data (7 CRS, 5 no CRS) for analysis. 5 patients with CRS had a DHT detection time in advance of the SoC by a median of 13h (range 2.8 - 69.2). The DHT prediction of CRS by baseline HR change was earlier than the first episodic fever by a median of 14.5h (range 13-77.5). The remaining 2/7 patients who did not have CRS detected by the DHT had missing DHT data for more than 45h before a treated CRS event. DHT detected CRS in 2/5 patients without CRS according to SoC. One patient had fever caught with intermittent monitoring. The other was treated for neutropenia fever with suspicion of CRS and/or infection. Conclusions: These results offer evidence that continuous DHT can identify CRS events earlier than intermittent monitoring (SoC). Despite limitations related to compliance with wearable device use and data missingness, and variability in clinical management of CRS, we highlight the usability of DHT and its potential for future studies with optimized strategies to address these limitations. Clinical trial information: NCT05018208 .

Description of the three-stage study design.

Background Imaging-based glioma monitoring is confounded by treatment-related changes. D-2-hydroxyglutarate (D-2-HG), produced by the isocitrate dehydrogenase (IDH) mutation, is detectable in cerebrospinal fluid (CSF), which can be sampled from cranial or lumbar compartments. We evaluated CSF D-2-HG as a serially accessible biomarker for IDH-mutant gliomas, including the optimal compartment for longitudinal sampling.Methods Lumbar and cranial CSF samples were collected from patients with IDH-mutant gliomas or IDH-wild-type central nervous system pathologies via surgical field collection, lumbar punctures, and CSF access devices. CSF D-2-HG was quantified via our CLIA-certified gas chromatography mass spectrometry assay.Results D-2-HG was significantly higher in cranial than lumbar CSF from IDH-mutant glioma patients. Consistent with low D-2-HG abundance in lumbar CSF, lumbar samples could not discriminate IDH-mutant gliomas from IDH-wild-type lesions. In contrast, cranial CSF D-2-HG was significantly higher in IDH-mutant gliomas than wild-type lesions, providing an adequate baseline for initial evaluations of monitoring capabilities. Across 75 samples from 7 consecutive patients with grade 4 IDH-mutant astrocytomas, serial cranial CSF D-2-HG decreased with cytoreduction, remained unchanged with stable disease, and increased with disease progression, but not pseudoprogression.Conclusions Serial cranial CSF D-2-HG shows promise as a monitoring biomarker for IDH-mutant gliomas.

Glioblastoma (GBM), isocitrate dehydrogenase wild-type (IDHwt) and central nervous system diffuse large B-cell lymphoma (CNS-DLBCL) are aggressive brain tumors with overlapping MRI features, yet distinct treatment approaches. Noninvasive tools are needed to aid in differential diagnosis. Deep learning on T1 postcontrast and T2-weighted MRI sequences were used to differentiate GBM and CNS-DLBCL. A three-stage temporal study design was utilized. Model development was performed on 146 patients with CNS-DLBCL and 146 age-matched, sex-matched, and MRI year-matched patients with GBM diagnosed at Mayo Clinic between 1998 and 2019. Models were tested on independent temporal test cohorts. Initial testing included 240 independent GBM diagnosed at Mayo Clinic between 1998 and 2019. The prospective test cohort included 37 patients with CNS-DLBCL and 256 patients with GBM diagnosed at Mayo Clinic after January 1, 2020, and 36 patients with CNS-DLBCL diagnosed at an external institution. Of the patients diagnosed at Mayo Clinic, 47% had MRIs generated from non-Mayo institutions. Two different model approaches were compared: (i) ensemble approach using area under the receiver operating characteristic curve (AUC) and cross-validation for model selection and (ii) loss approach minimizing cross-entropy loss and cross-validation to evaluate prediction performance. The AUCs on the prospective test cohort were 0.84 [95% confidence interval (CI), 0.78-0.90] and 0.83 (95% CI, 0.77-0.88) for the ensemble and loss approaches, respectively. Stability of ensemble prediction improved with the increasing number of models. Stratified AUC analysis demonstrated consistent performance across sex and age. We utilized a robust temporal study design and applied 2 different analytic approaches to develop a classification model. The findings confirm the feasibility of using MRI-based deep learning models to differentiate GBM from CNS-DLBCL. SIGNIFICANCE:GBM, IDHwt and CNS-DLBCL are aggressive brain tumors with overlapping MRI features, yet distinct treatment approaches. Noninvasive tools are needed to aid in differential diagnosis. We developed MRI-based deep learning models to differentiate GBM, IDHwt from CNS-DLBCL using a rigorous three-stage temporal design that included prospective validation. The model AUC on a prospective cohort was 0.84.

Glioma diagnosed during pregnancy and pregnancy following glioma treatment present complex management challenges. Safety of glioma treatment during pregnancy is not well established. The ability to counsel patients on timing of conception after treatment remains limited. The aim of this study was to describe our institution’s experience with pregnancy during and/or after treatment for glioma. In this single-institution study, we retrospectively identified patients diagnosed with glioma during or prior to pregnancy and described treatment courses and maternal and neonatal outcomes. Twenty-one female patients were included. Glioma diagnoses included 12 high-grade tumors and 9 low-grade tumors. Cohort A consisted of 8 patients who presented with glioma during pregnancy, of which, 7 underwent glioma treatment during pregnancy. All pregnancies in cohort A were without significant maternal complications and resulted in delivery of a healthy neonate. Cohort B consisted of 13 patients who experienced pregnancy after a prior diagnosis of glioma, totaling 18 pregnancies that resulted in delivery of a neonate. Antepartum course was complicated by seizure in 3/18 pregnancies. Functionally inconsequential anatomic abnormalities in childhood offspring of cohort B occurred in 5/18 pregnancies. Anatomic abnormalities occurred in 4/13 (31

BackgroundPrior investigations of the impact of social determinants of health (SDH) on people with primary central nervous system cancers (PCNSC) have considered limited SDH-factors and pathologies. This study examines how the Social Vulnerability Index (SVI) influences disparities in outcome for people with PCNSC across the United States (US).MethodsThis population-based retrospective cohort study assessed adults with PCNSC between 1975-2017 from the Surveillance-Epidemiology-End Results database, categorized using the Central Brain-Tumor-Registry of the US (CBTRUS) classifications. SDH-vulnerability/SVI scores were assigned to patients' county-of-residence based on 15 SDH-factors of socioeconomic status (SES), proportions using a minority language (ML), household composition (HC), and infrastructure/housing-transportation (HT) characteristics, plus an overall composite of these four themes. Survival and logistic regressions were obtained for survival period and multimodal treatment receipt across all PCNSC-patients based on their SVI-scores/SDH-vulnerability.ResultsAcross 116,373 PCNSC-patients (64,841 [55.7%] male; 92,476 [79.5%] non-Hispanic white race-ethnicity), increasing overall SDH-vulnerability is associated with relative mean survival period decreases between 22.12%-45.81% across 8/8 CBTRUS-classes, with the largest-magnitude effects among HC, HT, and SES-vulnerabilities. There are decreased odds of external beam radiation for 4/8 CBTRUS-classes (lowest-embryonal: OR, 0.87; 95%CI, 0.80-0.96) and surgery for 3/8 CBTRUS classes (lowest-oligodendroglial: OR 0.96; 95%CI 0.95-0.97). The largest-magnitude effects are among those using ML, followed by impact of HC and HT characteristics.ConclusionsSDH-vulnerability associates with worse survival and treatment effects for PCNSC patients. Some specific SDH more strongly influence disparity associations, so resources could be focused more on reducing these disparity drivers.