bluuebunny/crossref_metadata_2025 huggingface dataset:
NCMP-22. SECOND MALIGNANCIES FOLLOWING TREATMENT FOR PRIMARY CENTRAL NERVOUS SYSTEM TUMORS IN PEDIATRIC PATIENTS: A SINGLE-INSTITUTIONAL RETROSPECTIVE REVIEW
Authors: Pytel Nicholas , Dedekam Erik , Salamat Shahriar M , Puccetti Diane
Published: December 2020

Second malignant neoplasms following treatment for primary central nervous system (CNS) tumors in children are rare occurrences but may often have dire consequences, particularly, if thought to be induced by prior therapies. The authors retrospectively reviewed pediatric patients with primary CNS malignancies from the University of Wisconsin over the last 25 years (1994 – 2019) with any secondary malignant neoplasm and determined seven patients met criteria. Treatment modalities were reviewed with all patients receiving surgery, chemotherapy, and radiotherapy for treatment of their first malignancy. The second neoplasms found included 4 high-grade gliomas, 1 meningioma, 1 thyroid carcinoma, and 1 myelodysplastic syndrome. The median latency time between diagnoses was 9 years (range 4 -17 years). The outcomes varied according to histopathology of the second neoplasm with the high-grade glioma patients all deceased from progressive disease. The high-grade gliomas were thought to have been induced by prior radiation in most cases. The remaining patients are still alive, at the time of this writing, and in follow up after treatment for their second neoplasm. Thus, long-term follow up is essential for children treated for a primary CNS tumor given the variety of second neoplasms that could arise with differential consequences. In addition to our single institutional outcomes, we will also present an updated review of the literature of pediatric patients with primary CNS tumors and second malignancies.
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

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

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

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

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

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

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, > 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

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>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< 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

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

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

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).
NIMG-02. 18F-FLUCICLOVINE PET/CT TO DISTINGUISH RADIATION NECROSIS FROM TUMOR PROGRESSION IN BRAIN METASTASES TREATED WITH STEREOTACTIC RADIOSURGERY
Authors: Tom Martin , DiFilippo Frank , Jones Stephen , Suh John , Murphy Erin , Yu Jennifer , Mohammadi Alireza , Barnett Gene , Huang Steve , Wu Guiyun , Obuchowski Nancy , Ahluwalia Manmeet , Peereboom David , Stevens Glen , Chao Samuel
Published: December 2020

PURPOSE/OBJECTIVE(S)

To report descriptive updates of an ongoing pilot trial assessing whether 18F-Fluciclovine PET/CT, a widely available amino-acid radiotracer, is useful to distinguish radiation necrosis (RN) from tumor progression (TP) among patients with brain metastases.

MATERIALS/METHODS

The primary objective is to estimate the accuracy of 18F-Fluciclovine PET/CT in distinguishing RN from TP. We included adults with brain metastases who underwent prior stereotactic radiosurgery and presented with a follow-up MRI brain (with DSC-MR perfusion) which was equivocal for RN versus TP. Within 30 days of equivocal MRI, patients underwent 18F-Fluciclovine PET/CT on a Siemens Biograph mCT scanner with a 10 mCi bolus dose immediately prior to PET. PET data were collected in list-mode for 25 mins post-injection and were reconstructed as a static image of data 10-25 mins post-injection, and as a dynamic series of four 5-min frames between 5-25 mins post-injection. Quantitative metrics for each lesion were documented. Lesion to normal brain ratios were calculated. The reference standard was clinical follow-up with MRI brain (with DSC-MR perfusion) every 2-4 months until multidisciplinary consensus (or tissue confirmation) for diagnosis of RN versus TP.

RESULTS

From 7/2019-6/2020, 12 of 16 planned subjects with 17 lesions underwent 18F-Fluciclovine PET/CT. Primary histology was non-small cell lung cancer in 5 patients, breast in 4, melanoma in 2, and endometrial in 1. Among all 17 lesions, ranges of quantitative metrics were: SUVmax, 2.18-12.10; SUVmean, 1.16-7.37; SUVpeak, 1.06-4.45; normal brain SUVmean, 0.19-0.44; SUVmax/normal ratio, 7.50-45.40; SUVmean/normal ratio, 4.20-26.30; and SUVpeak/normal ratio, 3.90-26.40. Follow-up was completed for 5 patients (6 lesions). No adverse events have occurred.

CONCLUSION

In this population, 18F-Fluciclovine produces a wide range of lesion quantitative metric values and uniformly low uptake in normal brain, which may allow accurate discrimination. Ongoing additional accrual and follow up is required.
NIMG-05. ADVANCED IMAGING TO ASSESS LONGITUDINAL VASCULAR CHANGES IN BRAIN METASTASES TREATED WITH CHECKPOINT INHIBITION
Authors: Kim Albert , Cardona Jonathan , Chang Ken , Beers Andrew , Brown James , Emblem Kyrre , Kalpathy-Cramer Jayashree , Lee Eudocia , Lin Nancy , Tolaney Sara , Nayak Lakshmi , Chukwueke Ugonma , Oh Kevin , Shih Helen , White Michael , Lawrence Donald , Moy Beverly , Cohen Justine , Giobbie-Hurder Anita , Cahill Daniel , Sullivan Ryan , Brastianos Priscilla , Gerstner Elizabeth
Published: December 2020

Immune checkpoint inhibitors (ICI) have recently been shown to be effective for brain metastases (BM) in melanoma and lung cancer. However, accurately assessing intracranial response in patients undergoing ICI is a challenge, as current measures cannot reliably distinguish pseudoprogression from true tumor progression. To identify potential biomarkers of response, we analyzed standard post-contrast and dynamic susceptibility contrast MRI to identify characteristic vascular signatures as part of an ongoing Phase 2 study of pembrolizumab for patients with untreated or progressive, previously treated BM from any histology. Tumor volume measurements were calculated by summating all enhancing voxels. A volumetric increase of >40% was categorized as progressive disease (PD), a decrease of >60% as partial response (PR), and stable disease (SD) as between -60% and +40%. 78 patients have been enrolled, of whom 44 have received at least baseline advanced MR imaging. Histologies include 21 with breast cancer, 5 with non-small cell lung cancer, 4 with melanoma, and 13 with other cancers. At baseline, the total number of BM was 1-50+ per patient. Based on summing the entire enhancing intracranial disease burden, best volumetric responses for the 33 evaluable patients include 4 PR, 10 SD, and 19 PD. On preliminary analysis, there was a correlation between increased tumor cerebral blood volume/flow with tumor progression. Correlation of additional vascular physiologic parameters (e.g. vessel caliber, tissue oxygenation) to volumetric response, patient outcome, and standardized response criteria (iRANO) are ongoing. Our data provides potential evidence that effective ICI is associated with a decrease in perfusion. Ongoing analyses to uncover additional vascular changes – specifically longitudinal metrics reflecting vascular structure and function - within BM to ICI are pending. These findings have potential to explore mechanisms of ICI response and resistance, as well as biomarkers of response.
NIMG-07. LONG-TERM FOLLOW-UP OF SCHWANNOMA GROWTH BEHAVIOR IN ADULT NEUROFIBROMATOSIS TYPE 2 AND SCHWANNOMATOSIS PATIENTS USING WHOLE-BODY MRI
Authors: Ly Ina , Thalheimer Raquel , Cai Wenli , Bredella Miriam , Muzikansky Alona , Merker Vanessa , Herr Hamilton , Da Jennifer , Harris Gordon , Plotkin Scott , Jordan Justin
Published: December 2020

BACKGROUND

Neurofibromatosis type 2 (NF2) and schwannomatosis (SWN) are related genetic tumor predisposition syndromes caused by distinct germline pathogenic variants on chromosome 22. Both conditions are characterized by the presence of cranial, peripheral, and/or spinal nerve schwannomas. The long-term growth behavior of schwannomas is unknown but knowledge thereof would help guide patient surveillance and selection for treatment and improvement of clinical trial design. Whole-body MRI (WBMRI) can detect whole-body schwannoma burden in a single image acquisition session.

METHODS

12 NF2 and 10 SWN patients who underwent a WBMRI between 2007-2010 underwent a repeat WBMRI between 2018-2019. Schwannomas were segmented on short tau inversion recovery (STIR) sequences. Tumor volume was calculated using a three-dimensional tumor quantification software (3DQI). Tumor growth and shrinkage were defined as a volume change ≥ 20% over the entire study period.

RESULTS

Median time between scans was 10 years. A total of 103 schwannomas (46 NF2-associated, 57 SWN-associated) were analyzed. In both NF2 and SWN, 50% of tumors grew. Median growth was 88.3% in NF2 and 100.4% in SWN. All growing NF2-associated schwannomas grew in the setting of exposure to systemic therapy whereas only one growing SWN-associated tumor had been treated systemically. Excluding resected tumors, 19.4% of schwannomas shrank. Median shrinkage was 48.5% in NF2 and 37.4% in SWN. All shrinking NF2-associated tumors had been treated with systemic therapy whereas none of the shrinking SWN-associated tumors had been. 19 new tumors (7 NF2-associated, 12 SWN-associated) developed in 8 patients.

CONCLUSIONS

Half of NF2- and SWN-associated schwannomas grow significantly over a decade. In NF2 patients, growth occurs despite systemic treatment whereas, in SWN patients, schwannomas may shrink spontaneously without treatment. These findings may suggest a more aggressive tumor phenotype in NF2. Continued patient enrollment and correlation of MRI findings with functional outcomes and hormone exposure history are ongoing.
NIMG-16. EXPLORATORY EVALUATION OF Q-SPACE TRAJECTORY IMAGING PARAMETERS AS NOVEL IMAGING BIOMARKERS FOR GLIOMAS
Authors: Juvekar Parikshit , Szczepankiewicz Filip , Noh Thomas , Westin Carl-Fredrik , Golby Alexandra
Published: December 2020

Neuroimaging offers a non-invasive means to probe tumor tissue in order to inform decision making at all phases of brain tumor treatment. Diffusion MRI is particularly sensitive to tumor tissue microstructure, with greater heterogeneity being reflected as a larger diffusional kurtosis. Q-Space Trajectory Imaging (QTI) uses tensor-valued diffusion encoding (encoding along multiple directions per shot) to disentangle Isotropic Mean Kurtosis (MKi) from Anisotropic Mean Kurtosis (MKa), which are otherwise conflated in the Total Mean Kurtosis (MKt). To test whether disentangling MKi and MKa facilitates a more specific probe of tumor tissue heterogeneity and malignancy, we investigated if QTI parameters could distinguish low- from high-grade gliomas and enhancing from non-enhancing regions using pre-operative QTI imaging of 13 W.H.O. grade I-II and 18 grade III-IV glioma patients. We also analyzed these features separately for de novo and recurrent tumors. Regions of Interest (ROIs) were drawn on QTI maps, with support from T1 and T2-weighted images, for enhancing region, non-enhancing region, necrotic cavity, cyst, edema and resection cavity. ROC was used to gauge QTI parameter performance in classifying tumor characteristics. MKi was found to be the strongest predictor of tumor grade (AUC = 0.74, p = 0.019). MKi and MKt separated de novo from recurrent tumors (AUC = 0.80 and 0.76, p < 0.05). MKt separated enhancing regions from non-enhancing regions with an AUC of 0.88 in all tumors and 0.97 in de novo tumors. Our preliminary results highlight that tensor-valued diffusion MRI and QTI analysis have the potential to non-invasively characterize tumor grade. Further, MKt accurately differentiated enhancing from non-enhancing tumors and could potentially substitute for gadolinium injection in some situations thereby decreasing risk, time, and cost. Our ongoing studies in larger groups aim to further correlate molecular tumor markers (eg. IDH1 status) with these diffusion parameters.
NIMG-20. MULTI-HABITAT RADIOMICS UNRAVELS DISTINCT PHENOTYPIC SUBTYPES OF GLIOBLASTOMA WITH CLINICAL AND GENOMIC SIGNIFICANCE
Authors: Won Choi Seung , Cho Hwan-ho , Koo Harim , Cho Kyung rae , Nenning Karl-Heinz , Langs Georg , Furtner Julia , Baumann Bernhard , Woehrer Adelheid , Cho Hee Jin , Kong Doo-Sik , Seol Ho Jun , Lee Jung-il , Nam Do-Hyun , Park Hyunjin
Published: December 2020

BACKGROUNDS

We aimed to evaluate the potential of radiomics as an imaging biomarker for GBM patients and explore the molecular rationale behind radiomics by radio-genomics approach.

METHODS

A total of 144 primary GBM patients were included in this study as a training cohort. Using multi-parametric MR images, radiomics features were extracted from multi-habitats of the tumor. We applied Cox-LASSO algorithm to build a survival prediction model and validated this model using an independent validation cohort (56 patients from Vienna). With the selected radiomics features, GBM patients were consensus clustered to reveal inherent phenotypic subtypes. The subtypes were further explored in terms of genomic signatures.

RESULTS

GBM patients were successfully stratified by the radiomics risk score, a weighted sum of radiomics features, corroborating the potential of radiomics as a prognostic biomarker. Using consensus clustering, we identified three distinct subtypes which significantly differed in the prognosis (‘heterogenous enhancing’, ‘rim-enhancing necrotic’, and ‘cystic’ subtype). Multi-variate cox regression analysis confirmed that radiomics subtype as an independent prognostic factor. Transcriptomic traits enriched in individual subtypes were in accordance with imaging phenotypes summarized by radiomics. For example, rim-enhancing necrotic subtype was well described by radiomics profiling (T2 autocorrelation & flat shape) and highlighted by the inflammatory genomic signatures, which well correlated to its phenotypic peculiarity (necrosis).

CONCLUSIONS

The present study confirmed the feasibility of radiomics as an imaging biomarker for GBM patients with comprehensible biologic annotation. Imaging subtypes derived from radiomics successfully recapitulate the genomic underpinnings of GBM tumors and in turn reinforce their potential as a prognostic biomarker.
NIMG-34. QUANTITATIVE MR PARAMETERS FOR THE PREDICTION OF EGFR AMPLIFICATION AND THE TERT PROMOTER MUTATION STATUS OF IDH-WILDTYPE LOWER-GRADE GLIOMAS
Authors: Won Park Yae , Ahn Sung Soo , Kim Eui Hyun , Kang Seok-Gu , Chang Jong Hee , Kim Se Hoon , Lee Seung-Koo
Published: December 2020

OBJECTIVES

To assess the predictive role of quantitative MRI parameters from DTI, dynamic susceptibility contrast (DSC), and dynamic contrast-enhanced (DCE) imaging in determining the epidermal growth factor receptor (EGFR) amplification and telomerase reverse transcriptase promoter (TERTp) mutation status of isocitrate dehydrogenase-wildtype (IDHwt) lower-grade gliomas (LGGs).

METHODS

A total of 49 patients with IDHwt LGGs with either known EGFR amplification (39 EGFR non-amplified, 10 EGFR-amplified) or TERTp mutation (19 TERTp wildtype, 21 TERTp mutant) statuses underwent preoperative MRI. The mean apparent diffusion coefficient (ADC), fractional anisotropy (FA), normalized cerebral blood volume (nCBV), normalized cerebral blood flow (nCBF), volume transfer constant (Ktrans), rate transfer coefficient (Kep), extravascular extracellular volume fraction (Ve), and plasma volume fraction (Vp) values were assessed. Univariate and multivariate logistic regression models were constructed to predict EGFR amplification and TERTp status.

RESULTS

EGFR-amplified tumors showed lower mean ADC values than EGFR non-amplified tumors (p = 0.019). Mean ADC was an independent predictor of EGFR amplification, with an AUC of 0.75. TERTp mutant tumors showed higher mean nCBV (p = 0.020), higher mean nCBF (p = 0.017), and higher mean Vp (p = 0.002) than TERTp wildtype tumors. With multivariate logistic regression, mean Vp was the only independent predictor of TERTp mutation status, with an AUC of 0.85.

CONCLUSION

Lower ADC values may be a useful marker for the prediction of EGFR amplification, whereas higher Vp values may be a useful marker for the prediction of the TERTp mutation status of IDHwt LGGs.
NIMG-49. VALIDATION OF SIMULTANEOUS PH- AND O2-WEIGHTED MOLECULAR MRI USING 18F-FDG PET, IMMUNOHISTOCHEMISTRY, AND BIOENERGETICS
Authors: Hagiwara Akifumi , Yao Jingwen , Raymond Catalina , Morrow Danielle , Mareninov Sergey , Chun Saewon , Nathanson David , Yong William , Czernin Johannes , Divakaruni Ajit , Everson Richard , Patel Kunal , Salamon Noriko , Pope Whitney , Nghiemphu Phioanh , Liau Linda , Cloughesy Timothy , Ellingson Benjamin
Published: December 2020

This study aimed to investigate the potential of a novel MRI metric related to aerobic glycolysis in patients with diffuse gliomas. All subjects (Study I–III; 7, 26, and 11 subjects, respectively) were scanned on 3-T systems and underwent pH-weighted amine chemical exchange saturation transfer spin-and-gradient-echo echoplanar imaging (CEST-SAGE-EPI) or CEST-EPI, and perfusion imaging. Relative oxygen extraction fraction (rOEF) was calculated by dividing hypoxia-sensitive R2’ by normalized relative cerebral blood volume (nrCBV); a novel metric that characterizes glycolytic status (aerobic glycolytic index, AGI) was calculated by dividing amine CEST contrast by rOEF. Patients in Study I were additionally scanned by 18F-fluorodeoxyglucose (FDG)-PET. Stereotactic image-guided biopsies were performed on patients in Study II and III, and samples were analyzed by immunohistochemistry (IHC) and extracellular flux bioenergetic analysis, respectively. Pairwise correlation between MR metrics and standardized uptake value of 18F-FDG, IHC metrics, or indices of cellular metabolism was calculated using Spearman’s correlation analysis. In Study I, AGI showed very strong significant correlation with 18F-FDG uptake in glioma (correlation coefficient ρ = 0.86, P =0.014). In Study II, AGI was significantly correlated with glucose transporter 3 (ρ = 0.71; P = 0.0041) and hexokinase 2 (ρ = 0.73; P = 0.0029) in IDH wild-type glioma, while it was significantly correlated with monocarboxylate transporter 1 (ρ = 0.59; P = 0.0094) in IDH mutant glioma. This result may reflect the different glycolytic statuses of these gliomas; specifically, the rate-limiting steps in glycolysis. In Study III, a strong significant correlation with cellular AGI derived from the bioenergetic analysis was found for AGI derived from MRI (ρ = 0.79, P = .036). In conclusion, AGI derived from MRI was correlated with FDG, IHC measurements, and cellular AGI. Future studies investigating the clinical utility of AGI in prediction and evaluation of treatment effects are warranted.
NIMG-55. A QUANTITATIVE ANALYSIS OF BRAIN VOLUME DYNAMICS IN PCNSL PATIENTS TREATED WITH HIGH-DOSE METHOTREXATE-BASED THERAPY
Authors: Sivakumar Ananyaa , Kamson David , Estephan Fayez , Lambrecht Sebastian , Dzaye Omar , Wagner-Johnston Nina , Swinnen Lode , Gladstone Douglas , Lin Doris , Grossman Stuart , Holdhoff Matthias
Published: December 2020

BACKGROUND

Primary CNS lymphoma (PCNSL) is a rare, infiltrative disease. High-dose methotrexate (HD-MTX) is the backbone of induction regimens for PCNSL. While MTX-associated white matter changes are well-described, treatment-related brain volume loss is much less understood, especially in radiotherapy-naïve cohorts. Here, we aimed to longitudinally quantify the rates of brain volume loss in PCNSL patients treated with HD-MTX.

SUBJECTS/METHODS

We included 12 radiotherapy-naïve patients (age mean±SD 61±15y, range 37-84y, 9F) with histopathologically confirmed PCNSL who received HD-MTX induction (mean±SD 12±4 cycles, range 8-18) +/-rituximab. MRIs were collected from within 1 month of HD-MTX initiation until the end of follow-up (mean±SD: 3.7±2.9y). Longitudinal whole-brain segmentation was performed on FLAIR images using the Sequence Adaptive Multimodal Segmentation tool of FreeSurfer. Brain volumes were normalized to the initial scan, white matter lesion volumes were normalized to cerebral volume (nWML).

RESULTS

The average rate of cerebral volume change was -2.1±1.9%/year. Half of patients showed marked cerebral volume loss in the first year (-5.6±1.4% vs. -2.0±1.4%; n=10; p=0.003) with the most prominent change occurring within 6-months of treatment initiation (-4.2±1.7% vs. -0.5±1.6; n=12; p=0.004). Cerebral volume loss reached a plateau after the 1-year mark in both groups (0.3±0.8%/year vs. 1.4±3.3%/year; n=8; p=0.4). Patients younger than 61 years exhibited markedly higher rates of cerebral volume loss (-6.2±1.1%/year vs. 2.4±1.5%/year p=0.003), which was corroborated by strong inverse correlation between age and cerebral volume loss (Pearson’s r=-0.82, p=0.004). Neither the cerebellar volume, nor the nWML load correlated with age.

CONCLUSION

In the present cohort, brain volume loss was approximately four-fold higher than what is described in the healthy aging. Younger patients treated with HD-MTX exhibited more severe cerebral volume loss, which may be due to higher initial brain volume reserve. Detailed analyses of a larger sample are underway.
NIMG-60. ATYPICAL POSTERIOR REVERSIBLE LEUKOENCEPHALOPATHY SYNDROME MIMICKING TUMOR IN 1ST TRIMESTER PREGNANCY-’DON’T BELIEVE EVERYTHING YOU SEE’
Authors: Vishwanath Humsini , Shivaprasad Akhil , Tremont-Lukats Ivo , Powell Suzanne
Published: December 2020

Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiographic diagnosis characterized by headache, confusion, visual disturbances, seizures and most commonly bilateral vasogenic edema.　PRES　during first trimester gestation is exceptional and in our report mimicking CNS tumor. An　18-year-old　G1P0　Hispanic woman　was admitted with　headache, left-sided　hemiparesis and left-sided visual loss for 4 days. Exam was consistent for drowsiness, dysarthria,　left homonymous hemianopia, left facial droop and left hemiplegia with left hemi-sensory loss. By pelvic ultrasound she had a single 9-week intrauterine pregnancy with no detectable fetal heart tone. MRI brain: large area of increased T2 signal in the right parietal occipital and upper temporal and posterior right frontal lobe white matter with mass effect of 6mm midline shift and no evidence of hemorrhage. There was high suspicion for a glial neoplasm. MRA of head and neck　and EEG　were unremarkable. IR cerebral angiogram had no evidence of vascular abnormalities. Eventual MR spectroscopy, choline/NAA ratio was　(< 2/1), elevated lactate/fat　peak suggestive of inflammatory versus infectious process. She had D&C for missed abortion and pathology was negative for malignancy.　Further brain biopsy on day 5 demonstrated reactive astrogliosis with microglial activation, scattered macrophages with white matter vacuolation. Biopsy specimen was negative for infections. TPO Ab, NMO/AQP4, Ttg IgA and rheumatologic panel were negative. The pathology was most compatible with PRES. Repeat MRI had decreasing mass effect and　increased patchy subcortical restricted diffusion in the right occipital and temporo-parietal lobes. She had inpatient rehabilitation leading to complete recovery.
NIMG-69. PERSONALIZED CONNECTOMIC SIGNATURES: BRIDGING THE GAP BETWEEN NEURO-ONCOLOGY AND CONNECTOMICS
Authors: Osmanlioglu Yusuf , Parker Drew , Brem Steven , Shokoufandeh Ali , Verma Ragini
Published: December 2020

PURPOSE

Connectomics has led to significant neuroscientific findings within the last two decades, eventually making impact in the clinics. Neuro-oncology can benefit immensely from connectomics in evaluating structural connectivity of brains with tumor for pre- and post-treatment planning, as a tumor connectome along with derived network measures will make it possible to determine the cognitive effects of treatment and quantify the effect of surgery on quality of life. However, generating connectomes in the presence of tumor is a challenging task. Specifically, registration of an atlas to the brain, which is essential in parcellating the brain into regions of interest, fails around the tumor due to mass effect and infiltration related distortions which are not present in the atlas that comes from a healthy brain. We aim to tackle this problem by introducing a novel atlas registration method.

METHOD

Although tumor deforms the geometrical shape of its surrounding regions, it does not violate the connectivity of displaced cortical voxels to the rest of the brain. Leveraging this fact, we represent the brain as an annotated graph with nodes representing ROIs encoding geometric features of regions and weighted edges representing the connectivity between regions. In encoding the surroundings of the tumor into the graph, we subsample the region into smaller patches to represent the area with multiple nodes. We then calculate many-to-one graph matching between the graphs of a tumor patient and a healthy control to associate surroundings of tumor with healthy ROIs.

OUTCOME

A tumor connectome showing how the connectivity is morphed around the tumor, which can further be extended to creating connectomes of recurrence. CLINICAL

IMPLICATIONS

Use of connectomes can revolutionize neuro-oncology by helping surgeons in estimating structural, functional, and behavioral outcomes of resection prior to surgery and in predicting recovery after the surgery, potentially suggesting subject specific treatment plans.