bluuebunny/crossref_metadata_2025_split huggingface dataset:
NCMP-23. PEMBROLIZUMAB-ASSOCIATED CD8+ VASCULITIC MONONEURITIS MULTIPLEX IN A PATIENT WITH MESOTHELIOMA: FIRST CASE REPORT
Authors: Baldauf Michaela , Monika Kapauer , Markus Jörger , Lukas Flatz , Rodriguez Regulo , Frank Stephan , Felbecker Ansgar , Thomas Hundsberger 
Published: December 2020

Abstract

INTRODUCTION
Immunotherapy, especially with immune checkpoint inhibitors (ICPI), has increasingly become an attractive treatment modality for various types of cancers. However, many patients develop ICPI-associated autoimmune adverse events such as pneumonitis, colitis or rarely neurological syndromes. Large and medium vessel vasculitis haS only occasionally been reported. Here we report the first case of ICPI-associated mononeuritis multiplex in a patient with malignant mesothelioma, caused by a histological proven small vessel vasculitis.

CASE REPORT
A 61-year old female developed subacute progressive painful and asymmetric sensorimotor deficits on distal extremities. Electrophysiologically, signs of a severe axonal neuropathy of both legs and the right arm were found, and swellings of the corresponding nerves were seen upon nerve ultrasound exam. The clinical and electrophysiological findings were reminiscent of mononeuritis multiplex. Laboratory work up including CSF examination was normal. More than two years prior to developing peripheral nerve deficits, the patient had been diagnosed with malignant pleural mesothelioma and treated with the anti-PD1 monoclonal antibody pembrolizumab on progression after chemotherapy. Biopsy of the right sural nerve revealed a small vessel vasculitis with a lymphocyte predominance of CD8+ T cells over CD4+ T as well as B lymphocytes. Despite discontinuation of pembrolizumab and immunosuppressive treatment (high dose methylprednisone, cyclophosphamide) complemented by opioid therapy, painful allodynia persisted.

CONCLUSION
ICPI-associated autoimmune disorders also include small vessel vasculitis with rare phenotypes such as mononeuritis multiplex. Further studies are required to improve our understanding of the link between ICPIs, and the pathogenic process leading to vasculitis, as well as to optimize treatment options for those rare diseases.
NCMP-24. PRE-INFUSION NEUROFILAMENT LIGHT CHAIN (NFL) LEVELS PREDICT THE DEVELOPMENT OF IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME (ICANS)
Authors: Butt Omar , Zhou Alice , Schindler Suzanne , Fagan Anne , Dipersio John , Ghobadi Armin , Ances Beau 
Published: December 2020

Abstract
Neurological side effects after chimeric antigen receptor-modified (CAR) T cell therapy are common and potentially devastating. Termed immune effector cell-associated neurotoxicity syndrome (ICANS), symptoms range from mild encephalopathy to diffuse cerebral edema. No predictive biomarkers exist to identify individuals at risk for developing ICANS. Serum neurofilament light chain (NfL) is a well-established marker of neural injury known to dynamically change in neuro-inflammatory disorders (e.g. multiple sclerosis). We hypothesized individuals undergoing CAR T cell therapy who ultimately developed ICANS would have early and sustained elevations in serum NfL. We performed a retrospective analysis of serum samples from 11 individuals treated with tisagenlecleucel or axicabtagene ciloleucel (mean age 61.3, 18% female, 27% ICANS, all with peak severity score 3). Most individuals had a longitudinal sampling at baseline, pre-infusion, post-transfusion day (PTD) 1, PTD 3, PTD 7, PTD 14, and PTD 30. Serum NfL were assayed using a Simoa HD-1/HD-X kit (QuanterixTM). We found that individuals who developed ICANS had early and sustained elevations in serum NfL levels at baseline (p = 0.0075), pre-infusion (p = 0.0172), and PTD 3 (p = 0.0026) and PTD 30 (p = 0.0066). All group comparisons survived multiple comparison testing using false-discovery rate (FDR). Receiver operating characteristic (ROC) curve classification by logistic regression of serum NfL revealed an area under the curve (AUC) of 1.0 with a cut-off of 44 pg/mL. No correlation was observed between NfL levels and age, sex, or history of central nervous system involvement of the underlying malignancy. In summary, we found serum NfL levels are a robust, early marker for the development of ICANS. Our findings suggest the risk of developing ICANS reflects pre-transfusion host-factors, permitting the screening well in advance of drug administration.
NCOG-08. A COMPARISON OF RESPONSE-ASSESSMENT AND DATA VISUALIZATION METHODS FOR CHARACTERIZATION OF TIME-DEPENDENT OUTCOMES FOLLOWING RADIOSURGERY (SRS) FOR BRAIN METASTASES
Authors: Kashtanova Tatiana , Keller Andrew , Ramakrishna Naren 
Published: December 2020

Abstract

PURPOSE
We compared multiple response assessment and visualization techniques for characterization of post-SRS treatment outcomes in a cohort of breast cancer patients with long median follow-up.

METHODS
A retrospective IRB-approved review was completed of 75 breast cancer patients treated with SRS for 271 brain metastases with median follow up of 40 months. Tumor dimensions, brain failure events, corticosteroid use, and clinical status were analyzed utilizing RANO-BM, bidimensional product (BDP), and bidimensional sum (BDS) techniques. 46/75 patients were eligible for RANO-BM assessment. Response at each post-treatment assessment were scored as PD, SD, PR, or CR, and the concordance between techniques was determined. A scoring system-based outcome metric labelled ‘average state’ was derived to estimate fractional time/response state by each assessment method. Interactive timeline displays of outcome states were generated.

RESULTS
The concordance of patient response states was determined using either RANO-BM, BDP or BDS among the 46 eligible patients. The overall mean and median concordance between techniques were 0.82 and 0.83, (range 0.52 – 1). The average state for the patient population post-treatment was 1.98 by RANO-BM, 2.29 by BDP, and 2.19 by BDS. For patients excluded from RANO-BM secondary to lack of measurable disease, the average state was determined to be 2.44 by BDP and 2.35 by BDS. The average state for HER2+ vs. HER2- patients was 2.21 vs. 1.75 by RANO-BM, 2.58 vs. 2 by BDP, and 2.39 vs. 1.99 by BDS. An interactive timeline view was generated to display outcome states utilizing the 3 response assessment techniques, and the impact of inclusion of non-target lesions and variable response parameters was assessed graphically.

CONCLUSIONS
These results characterize the concordance and the limitations of multiple outcome assessment methodologies in a post-SRS cohort with long median follow-up. The utility of a novel ‘average state’ outcome metric is demonstrated in this cohort.
NCOG-11. POST-RADIOSURGICAL OUTCOMES OF CYSTIC VESTIBULAR SCHWANNOMAS, A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Hamidi Nima , Massaad Elie , Goetz Jacalynn , Mansouri Alireza 
Published: December 2020

Abstract

INTRODUCTION
Vestibular schwannomas (VS) are benign neoplasms that present as cystic or solid variants. Cystic VS are associated with fast and unpredictable growth patterns, and their adherence to nearby structures can lead to poor surgical outcomes. While radiosurgery (RS) has gained popularity for VS, the heterogeneity of literature necessitates a systematic review.

METHODS
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), PubMed, EMBASE, Web of Science, and Cochrane were searched for observational studies reporting cystic and solid VS radiosurgical outcomes. Pooled estimates were calculated using random-effect models with generic inverse variance to compare tumor control rates between cystic and solid VS. Quality assessment was done using the Newcastle Ottawa Criteria (NOS).

RESULTS
The search yielded 2,989 studies from which 680 were selected for full-text screening and 6 were included in this review and meta-analysis. The quality of studies ranged between good (3 studies, NOS 7/9), fair (2 studies, NOS 6/9), and poor (1 study, NOS 4/9). The patient pool included 1,070 solid and 347 cystic VS, all treated by gamma knife RS. No difference in tumor control was observed (RR: 1.02, 95%CI 0.91-1.16, p=0.7). 3 studies reported post-RS complications. Haseguawa reported hydrocephalus in 7 of 74 cystic cases. Ryu reported 1 case of hydrocephalus and 1 case of trigeminal pain in their 14 cystic cases. Shirato reported 5 transient trigeminal Neuralgia, 1 transient vertigo and 1 shunt operation in their 20 cystic cases.

CONCLUSION
Evidence presented in this meta-analysis supports the safety and efficacy of radiosurgery in treating cystic VS.
NCOG-16. THE IMPACT OF THE TIMING OF HEALTH-RELATED QUALITY OF LIFE ASSESSMENTS ON THE ACTUAL RESULTS IN GLIOMA PATIENTS: A RANDOMIZED PROSPECTIVE STUDY
Authors: Peeters Marthe , Zwinkels Hanneke , Koekkoek Johan , Vos Maaike , Dirven Linda , Taphoorn Martin 
Published: December 2020

Abstract

BACKGROUND
The aim of this study was to explore the impact of the timing of health-related quality of life (HRQoL) measurements in clinical care on obtained HRQoL scores in glioma patients, and the association with feelings of anxiety or depression.

METHODS
Patients completed the EORTC Quality of Life Questionnaires (QLQ-C30 and QLQ-BN20), and the Hospital Anxiety and Depression Scale (HADS) at two time points. All patients completed the first measurement on the day of the MRI-scan (t=0), but the second measurement (t= 1) depended on randomization; group 1 (n= 49) completed the questionnaires before and group 2 (n= 51) after the consultation with the physician.

RESULTS
Median HRQoL scale/item scores on t0/t1 and change scores were comparable between the two groups. Between 8-58% of patients changed to a clinically relevant extent (i.e. ≥ 10 points) on the evaluated HRQoL scales/items in about one week time, in both directions, with only 3% of patients remaining stable in all scales. The mean number of the 26 evaluated HRQoL scales/items that changed to a clinically relevant extent per patient was 7 (SD= 4). Patients with stable role functioning had a lower HADS anxiety change score. However, this association was no longer significant in the multivariable regression when corrected for confounding factors. The HADS depression score was not associated with a change in HRQoL.

DISCUSSION
Measuring HRQoL before or after the consultation did not impact HRQoL scores on group level. However, the large majority of patients reported a clinically relevant difference in at least one HRQoL scale/item between the two time points, which was in general not influenced by feelings of anxiety or depression. Nevertheless, these findings highlight the importance of a standardized timing (e.g. at the day of the scan, consultation or first day of treatment) of patient-reported outcome assessments in clinical trials.
NCOG-21. INTERIM RESULTS OF THREE COGNITIVE REHABILITATION STRATEGIES IN PATIENTS WITH LOWER GRADE GLIOMAS
Authors: Taylor Jennie , Weyer-Jamora Christina , Brie Melissa , Bracci Paige , Smith Ellen , Luks Tracy , Braunstein Steve , Villanueva-Meyer Javier , Gehring Karin , Aguilera Adrian , Bush Nancy Ann Oberheim , Clarke Jennifer , Butowski Nicholas , Chang Susan , Hervey-Jumper Shawn 
Published: December 2020

Abstract

BACKGROUND
Patients with lower grade (2 and 3) gliomas (LrGG) are living longer, but often with cognitive impairments from their tumor and treatments. However, cognitive assessments and access to cognitive rehabilitation are not a standard part of care. We present preliminary results of a pilot study investigating feasibility and efficacy of three cognitive rehabilitation strategies for stable LrGG patients – in-person manualized cognitive rehabilitation; iPad based cognitive rehabilitation program of retraining and compensation strategies (ReMind); or daily instructional text messages (Healthy SMS).

METHODS
Eligible patients were adults with clinically and radiologically stable LrGG, &gt; 6 months from last treatment, and ≥1 standard deviation (SD) below normal on ≥ 2 domains of neuropsychological assessments. Patients were first offered in-person cognitive rehabilitation or randomized to ReMind or Healthy SMS if unable to attend in-person. Interventions lasted 3 months. Neuropsychological and HRQOL assessments, using PROMIS NeuroQOL, were conducted at baseline, 3, and 6 months post-intervention. Feasibility was defined as attending ≥80% of in-person sessions; completing ≥80% of ReMind tasks; or not opting out of Healthy SMS texts.

RESULTS
To date 23/60 patients have enrolled: 11 in-person and 12 randomized to ReMind (5) or Healthy SMS (7). Demographic and clinical characteristics were similar between cohorts. Median age at testing was 46 years, with 65% female, and 78% having received prior radiation (median 4.1 years, range 3.2 – 11.5). At baseline, processing speed was the most common domain of impairment with 43% ≥ 1.5 SD below normal and 36% patients reporting subjective cognitive impairment on HROQL assessment. Feasibility was 71% for in-person rehabilitation; 50% for ReMind; and 100% for Health SMS.

CONCLUSION
These preliminary results demonstrate that stable LrGG patients with subjective and objective cognitive impairments can reasonably engage in cognitive rehabilitation interventions. Updated data including post-intervention neuropsychological and HROQL related changes will be presented.
NCOG-29. O6-METHYLGUANINE DNA METHYLTRANSFERASE (MGMT) PROMOTER METHYLATION STATUS AND THE INCIDENCE OF TEMOZOLOMIDE-INDUCED HEMATOLOGIC TOXICITY: AN ASSOCIATION STUDY
Authors: Strohbusch Alyssa , Pound Heather , Regis Patrick , Cavaliere Robert 
Published: December 2020

Abstract

BACKGROUND
Despite the growing body of evidence demonstrating an increased clinical benefit of alkylating agents in glioblastoma patients with O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, little is known regarding the effect of MGMT status on toxicity. The purpose of this investigation is to provide insight into the potential association between MGMT promoter methylation and the development of Grade 3/4 hematologic toxicities in patients receiving temozolomide.

METHODS
A total of 63 patients with documented glioblastoma or anaplastic astrocytoma diagnoses were evaluated retrospectively. A chi-square test of independence was utilized to evaluate the incidence of hematologic toxicities and patient overall survival was determined by univariate analysis estimated through use of Kaplan-Meier curves. Relative frequencies of treatment discontinuation secondary to myelosuppression were also compared.

RESULTS
At the time of study completion, 71.4% of patients with MGMT promoter hypermethylation had survived compared with 50% of patients with hypomethylation (HR 0.86; 95% CI 0.71 to 1.05; P&gt;0.05). The percentage of patients who experienced Grade 3/4 hematologic toxicities during concurrent treatment was 20% and 5.1% within the hypermethylated and hypomethylated groups, respectively, and 26.7% and 17.9% throughout standard therapy. While a statistical difference was not found between the cumulative incidences of Grade 3/4 hematologic toxicity events throughout both phases of treatment, a statistical difference was noted in the incidence of Grade 4 occurrences with ten events occurring in the hypermethylated group and zero in those with hypomethylated promoter regions (P&lt; 0.01). Furthermore, use of temozolomide in hypermethylated patients resulted in fewer completed cycles of standard therapy and higher rates of treatment delays and drug discontinuation.

CONCLUSIONS
This study showed marked differences in the frequency of temozolomide-induced hematologic toxicities and treatment discontinuation based on tumor MGMT promoter methylation status. Further research is warranted in larger patient populations to both validate and determine the clinical significance of these findings.
NCOG-42. INITIAL PRESENTATION AND OUTPATIENT VISIT COMPLIANCE OF INMATES WITH BRAIN TUMORS
Authors: Alnahhas Iyad , Rayi Appaji , Rauf Yasmeen , Ong Shirley , Giglio Pierre , Puduvalli Vinay 
Published: December 2020

Abstract

INTRODUCTION
While advocacy for inmates with cancer has recently gained momentum, little is known about management of brain tumors in inmates. Delays in acknowledging or recognizing nonspecific initial symptoms can lead to delayed diagnosis and treatment. Inmates with cancer are reported to either be ignored or receive substandard care due in part to cost or logistics (American Civil Liberties Union; ASCO Post 2018).

METHODS
In this retrospective study, we identified inmates with gliomas seen in the Ohio State University Neuro-oncology Center between 1/1/2010-4/20/2019.

RESULTS
Twelve patients were identified. Median age at presentation was 39.5 years (range 28-62). Eleven patients were Caucasian and one was African American. Diagnoses included glioblastoma (GBM) (n=6), anaplastic astrocytoma (n=1), anaplastic oligodendroglioma (n=1), low-grade astrocytoma (n=3) and anaplastic pleomorphic xanthroastrocytoma (n=1). Patients were more likely to present early after seizures or focal neurologic deficits (9/12) than after headaches alone. Patients with GBM started RT 12-71 days after surgery (median 34.5). One patient’s post-RT MRI was delayed by a month and another with GBM had treatment held after 4 cycles of adjuvant temozolomide (TMZ) due to “incarceration issues”. For one patient who received adjuvant TMZ, the facility failed to communicate with the primary team throughout treatment. Two patients suffered significant nausea while on chemotherapy due to inability to obtain ondansetron in prison, or due to wrong timing. 7/12 (58%) patients were lost to follow-up for periods of 3-15 months during treatment. Three patients refused adjuvant treatment.

CONCLUSIONS
Although this is a small series, our results highlight the inequities and challenges faced by inmates with gliomas who are more likely to forego treatments or whose incarceration prevents them from keeping appropriate treatment and follow-up schedules. Additional studies are needed to define and address these deficiencies in the care of inmates with brain tumors and other cancers.
NCOG-43. NEUROCOGNITIVE IMPAIRMENT AND FRAILTY IN GERIATRIC PATIENTS WITH HIGH GRADE GLIOMA AND THORACIC MALIGNANCY
Authors: Haggstrom Daniel , Parala-Metz Armida , Induru Raghava , Kneuss Tiffany , Cooper Markecia , Caprio Anthony , Sumrall Ashley 
Published: December 2020

Abstract

BACKGROUND
The median age at diagnosis for high grade glioma is 64 years. With peak incidence 75-84, malignant glial tumors are frequently a disease of the elderly. Common assessment measures fail to accurately gauge geriatric cancer patient fitness. Comprehensive Geriatric Assessment (CGA) is recommended in patients older than 65 to gauge risk of toxicity and tolerance of therapeutic intervention. We reviewed data for older patients with high grade glioma (HGG) and thoracic malignancy (TM) who underwent CGA via Senior Oncology Clinic (SOC) at Levine Cancer Institute.

METHODS
From 2015 to 2019 104 thoracic malignancy patients and 19 high grade glioma patients completed CGA via SOC before treatment or a required change in therapy. Data was incorporated into the LCI Senior Oncology Database by the REDCap secure web application, allowing for both quantitative and qualitative data analysis.

RESULTS
The median age was 77 in the HGG cohort compared to 80 years with TM. The physician rated Karnofsky Performance Status (KPS) for HGG and TM were similar (76% v 79%) as were the percentages of patients that were frail or prefrail (90% v 87%). Montreal Cognitive Assessment scores were lower in HGG (20 v 23). Considerably more HGG had falls in the 6 months before their assessment (58% v 30%) and gait speed was slower (0.76 m/s v 0.85 m/s).

CONCLUSIONS
Older patients with high grade gliomas compared to similar thoracic malignancies had more neurocognitive impairment, falls in the preceding 6 months, and slower gait speed. Physician rated KPS and frailty were similar in both groups. The results illustrate the limitations of physician-rated performance measures and highlight the importance of CGA in older brain tumor patients.
NCOG-46. A PILOT STUDY OF GERMLINE CODING MUTATIONS ASSOCIATED WITH IMPAIRED DEVELOPMENT AND ADAPTIVE BEHAVIOR IN PEDIATRIC MEDULLOBLASTOMA PATIENTS TREATED ON HEAD START 4
Authors: Sells Blake , Bell Erica , Fleming Jessica , McElroy Joseph , Webb Amy , Zhao Yue , Graham Richard , Guo Yingshi , Liu Tom , Timmers Cynthia , Dhall Girish , Sands Stephen , Finlay Jonathan , Chakravarti Arnab 
Published: December 2020

Abstract
Children with brain tumors often carry germline mutations that have long been known to contribute to tumorigenesis and treatment response. However, less is known about how germline mutations may impact developmental and behavioral outcomes for children with tumors of the central nervous system (CNS). As the molecular mechanisms governing cancerous and normal tissue expand, we hypothesize that particular germline variants may impact baseline neurocognitive function and/or treatment-induced toxicities. In this preliminary study, 10 children on the Head Start 4 trial diagnosed with medulloblastoma were assessed for baseline adaptive functioning using the Adaptive Behavior Assessment System Third Edition (ABAS-III) and germline whole-exome sequencing was performed. After filtering for high impact variants, Welch’s T-tests were used to identify mutations associated with lower ABAS-III General Adaptive Composite (GAC) scores, reflecting developmental and adaptive behavior delays compared with peers their age. We found 20 genes with alterations associated with lower scores with P-values less than 0.05, although none met FDR significance cutoffs. Genes found to be significant included LAMC1 (P=0.04) and KRTAP1-1 (P=0.045), which encode members of the laminin and keratin family and are involved in extracellular matrix adhesion. Mutations in PITX1, a known suppressor of RAS, were also associated with lower ABAS-III GAC scores (P=0.007). We suspect that follow-up studies with more patients will reveal alterations in cell-to-cell communication and signal transduction pathways, as these are common molecular perturbations in tumors that would likely impact regular CNS function. Future research with larger cohorts is essential to validate these findings and to improve our understanding of the functional impact of germline variants on both tumor and regular tissue biology, allowing for a more comprehensive view of the spectrum of neurodevelopmental impairment and novel strategies to circumvent these impairments. Funding: Thrasher Research Fund (JF, AC). R01CA108633, RC2CA148190, U10CA180850(NCI), and OSUCCC (AC).