bluuebunny/crossref_metadata_2025_split huggingface dataset:
NIMG-91. DOTATATE PET/MR-GUIDED POSTOPERATIVE MANAGEMENT IN WHO-2 MENINGIOMA: ACTIVE SURVEILLANCE BASED ON PET/MR EVIDENCE OF GROSS TOTAL RESECTION
Authors: Knisely Jonathan , Chang Se Jung , Kim Sean H , Haghdel Arsalan , Roytman Michelle , Madera Gabriela , Magge Rajiv , Liechty Benjamin , Stieg Philip , Pannullo Susan , Schwartz Theodore , Cisse Babacar , Brandmaier Andrew , Juthani Rupa , Noch Evan , Fine Howard , Pisapia David , Ramakrishna Rohan , Karakatsanis Nicolas , Osborne Joseph , Lin Eaton , Ivanidze Jana 
Published: November 2022

Abstract

BACKGROUND
MRI, the standard of care (SOC) for meningioma radiotherapy planning, lacks sensitivity for postoperative small volume disease and osseous or parenchymal invasion. BN003 (NCT03180268) randomizes patients with WHO-2 meningiomas and MRI-determined GTR to observation or 60 Gy IMRT to the resection bed. More sensitive and specific imaging biomarkers may improve clinical outcomes in meningioma by limiting unnecessary radiation of normal tissues and improving radiation targeting. [68Ga]-DOTATATE is a PET radiotracer targeting somatostatin receptor 2 (SSTR2), a highly sensitive and specific meningioma biomarker. We developed a dedicated DOTATATE brain PET/MRI protocol allowing meningioma differentiation from post-treatment change, using SUV analysis and Patlak modeling. Our prospective observational trial (NCT04081701) has imaged over 90 patients with meningioma. This IRB-approved study evaluated PFS in patients with WHO-2 tumors and postoperative GTR by [68Ga]-DOTATATE PET/MRI who were managed solely with active surveillance. We hypothesized that the PFS of patients with GTR by PET/MRI managed with active surveillance would be higher than for patients with MRI-determined GTR, using NRG-BN003’s observation arm (randomized trial comparing observation to fractionated radiotherapy) as a reference standard.

METHODS
92 patients with SSTR2-positive brain neoplasms were enrolled between 9/2019 and 5/2022 and imaged according to our previously published protocol. 8 patients met inclusion criteria (WHO-2 meningioma & postoperative PET/MR GTR) and were followed with SOC MRI. Kaplan-Meier survival analysis was performed.

RESULTS
5/8 subjects (62.5%) were women; the mean age was 67 years. MRI follow-up data were available for a mean of 19.75 months (range: 7-38 months). One subject (12.5%) progressed at 21 months; the remainder remain progression-free. Kaplan-Meier analysis demonstrated 3-year PFS to be 80%, which is substantially higher than the reported 3-year PFS of 69% in the literature.

CONCLUSIONS
[68Ga]-DOTATATE PET can improve the specificity of imaging-based assessment of the extent of resection of WHO-2 meningiomas.
NIMG-92. DOTATATE PET/MR-GUIDED POSTOPERATIVE RADIOTHERAPY IN SUBTOTALLY RESECTED WHO-2 MENINGIOMA: EVALUATION OF PROGRESSION-FREE SURVIVAL IN A PROSPECTIVE COHORT
Authors: Knisely Jonathan , Chang Se Jung , Kim Sean H , Haghdel Arsalan , Roytman Michelle , Madera Gabriela , Magge Rajiv , Liechty Benjamin , Pisapia David , Noch Evan , Fine Howard , Pannullo Susan , Juthani Rupa , Ramakrishna Rohan , Schwartz Theodore , Stieg Philip , Cisse Babacar , Brandmaier Andrew , Karakatsanis Nicolas , Osborne Joseph , Lin Eaton , Ivanidze Jana 
Published: November 2022

Abstract

BACKGROUND
Current postoperative management recommendations for meningioma lack Level 1 evidence. NRG-0539 (NCT00895622) treated recurrent WHO-1 and newly diagnosed and completely resected (by postoperative MRI) WHO-2 meningiomas with postoperative fractionated radiotherapy to 54 Gy, but 3 year PFS remained below 60%. MRI, the standard of care (SOC) for meningioma radiotherapy planning, lacks sensitivity for postoperative small volume disease and osseous or parenchymal invasion. More sensitive and specific imaging biomarkers are needed to improve RT guidance and thereby clinical outcomes in meningioma. [68Ga]-DOTATATE is a PET radiotracer targeting somatostatin receptor 2 (SSTR2), a highly sensitive and specific meningioma biomarker. We developed a dedicated DOTATATE brain PET/MRI protocol allowing meningioma differentiation from post-treatment change, using SUV analysis and Patlak modeling. Our prospective observational trial (NCT04081701) has imaged over 90 patients with meningioma. This IRB-approved study evaluated PFS in patients with WHO-2 tumors who did not achieve GTR by [68Ga]-DOTATATE PET/MRI, managed with PET/MR guided RT, hypothesizing that the PFS of patients with STR by PET/MRI managed with PET/MR guided RT would be higher than for comparable patients enrolled on NRG 0539.

METHODS
92 patients with SSTR2-positive brain neoplasms were enrolled between 9/2019 and 5/2022 and imaged according to our previously published protocol. 7 patients met inclusion criteria (WHO-2 meningioma; postoperative PET/MR with residual activity) who underwent PET/MR-guided RT, followed with SOC MRI. Kaplan-Meier survival analysis was performed.

RESULTS
5/7 subjects (71%) were women; the mean age was 50.7 years. MRI follow-up data were available for a mean of 18.7 months (range: 16-24 months). All patients remain progression-free at this time; Kaplan-Meier analysis demonstrated 2-year PFS to be 100%, which is substantially higher than reported PFS in this clinical population using standard-of-care MRI-guided RT.

CONCLUSIONS
[68Ga]-DOTATATE PET/MR-guidance can improve PFS following postoperative RT in subtotally resected WHO-2 meningiomas.
NIMG-95. IMAGING CHARACTERISTICS OF POLYMORPHOUS LOW GRADE NEUROEPITHELIAL TUMOR (PLNTY)
Authors: Gordon Camille , Quintana Javier , Gonzalez-Gomez Ignacio 
Published: November 2022

Abstract
Polymorphous low grade neuroepithelial tumor of the young (PLNTY) was first described in 2017 in the pathology literature based on the unique histologic and molecular characteristics. Most of the patients in the original article presented with seizures linked to a temporal lobe lesion. We report a pediatric patient who presented with seizures found to have a lesion which was consistent with PLNTY on biopsy. We will review the radiology and pathology of this case with a quick review of the characteristic findings of PLNTY.
NIMG-106. WHAT’S BEHIND TSPO PET LABELLING: DIGGING FOR THE HISTOLOGICAL, CELLULAR AND MOLECULAR CORRELATES
Authors: Weidner Lorraine , Lorenz Julia , Dekorsy Franziska , Quach Stefanie , Ruf Victoria , Bartos Laura , Hau Peter , Tonn Joerg-Christian , Bartenstein Peter , von Baumgarten Louisa , Brendel Matthias , Albert Nathalie , Riemenschneider Markus 
Published: November 2022

Abstract
TSPO is frequently upregulated in glioblastoma. Despite its use as an imaging biomarker for PET in glioma, the interpretation is challenging due to the heterogeneity of cell populations that could contribute to the TSPO-PET signal. We therefore dissected TSPO labelling in connection with the underlying histopathological and molecular features in biopsy samples from glioma patients. Comparing regions of high and low TSPO-PET signal in 58 patients, we assessed TSPO protein expression and expression of cell differentiation markers by use of immunohistochemistry on consecutive sections and by multiplex stains. Our results suggest that apart from microglia and macrophages the glial tumor cells relevantly contribute to the overall TSPO signal in glioma patients. To identify hallmarks and GO terms associated with TSPO labelling/expression we next performed RNAseq in 33 patients. Using DESeq2 followed by FUMA and Reactome as well as GSEA with normalized counts, we identified three TSPO-dependent functional clusters, i.e. apoptosis/DNA repair, extracellular matrix organization and immune system. On the DNA level, we analyzed the TSPO promoter by direct bisulfite sequencing suggesting that a loss of TSPO methylation may mechanistically contribute to the TSPO overexpression observed in high-grade gliomas. Exceeding our investigations on glioma biopsies we stained tissue microarrays (130 individuals) for TSPO that cover a broader spectrum of both human brain pathologies (13 different entities) and non-neoplastic tissues (14 different brain regions). We here found a high degree of heterogeneity of TSPO expression between entities and regions. Merging this information with TSPO-PETs from respective patients/brain regions allows to generate a map of TSPO expression in healthy and diseased brain for clinical use. Altogether, our approach of integrating histological, molecular and imaging data will provide unique insights into TSPO-PET enrichment patterns which may help to better understand and to comprehensively describe the clinical relevance of this novel imaging biomarker.
NIMG-110. FIRST CLINICAL EXPERIENCE WITH BELZUTIFAN IN VON HIPPEL-LINDAU DISEASE-ASSOCIATED CNS HEMANGIOBLASTOMA
Authors: Dhawan Andrew , Peereboom David , Stevens Glen 
Published: November 2022

Abstract
The authors present two cases of von Hippel-Lindau (VHL) disease-associated hemangioblastomas in the central nervous system (CNS) treated with the newly-approved HIF-2α inhibitor, belzutifan. The first case is that of a 31-year-old female with confirmed pathogenic germline VHL mutation who presented with multiple hemangioblastomas diagnosed at 25 years of age. The patient was first managed surgically with resection of three posterior fossa hemangioblastomas but re-presented five years later with headaches and paresthesias of the fingers. She was found to have interval progression of an intramedullary cervical lesion that was monitored radiographically, as well as a new cerebellar lesion. A cerebellar lesion was resected, but the cervical hemangioblastoma was not. Four months after surgery, the patient was started on belzutifan, which she tolerated without issue, and a brisk reduction in peri-lesional edema was observed in the cervical spine and remaining intracranial foci after 2 months of treatment. The second patient is a 30-year-old male with familial VHL disease, initially diagnosed after the discovery of a retinal hemangioblastoma at age 10. He was found to have multiple cerebellar hemangioblastomas, treated with resection at age 24 and then with stereotactic radiosurgery (SRS) at age 25, complicated by radiation necrosis. Imaging surveillance revealed disease progression at age 29 for which he was started on belzutifan. Follow-up imaging after three one month cycles revealed a reduction in perilesional edema and reduced lesion mass effect. Both patients tolerated belzutifan well, with only anemia and fatigue. We highlight in this report our initial experience and early imaging findings associated with belzutifan used for VHL disease-associated CNS hemangioblastomas.
NCMP-02. RENAL CELL CARCINOMA WITH METASTASIS TO THE CHOROID PLEXUS
Authors: Kim Emily , Nadeem Danial , Nguyen James , Ammar Hussam 
Published: November 2022

Abstract

BACKGROUND
Intraventricular brain tumors make up only 0.9–4.5% of all cases of metastatic brain cancer.1 Involvement of the choroid plexus (CP) is even rarer with only a handful of documented cases. 2,3 Here we describe a case of bilateral multifocal metastasis to the choroid plexus appearing 10 years after nephrectomy in a male with stage IV renal cell carcinoma (RCC). CASE PRESENTATION: Our patient is a 74-year-old male with stage IV RCC diagnosed in 2006 and treated with radical nephrectomy and immunotherapy in 2011. In 2020, he presented to the emergency department with altered mental status. Brain magnetic resonance imaging (MRI) revealed an enhancing hemorrhagic lesion in the trigone of the right lateral ventricle (LV) and nodular thickening in the center of the right LV and trigone of the left LV, suggestive of metastatic disease. In 2021, the patient developed refractory seizures, and serial MRIs showed disease progression. He underwent several craniotomies with pathology confirming metastatic clear cell carcinoma, consistent with a renal primary. In 2022, the patient again presented with altered mental status. MRI revealed new avidly enhancing subcentimeter solid nodules in the CP of both LVs consistent with metastatic disease. Per the wishes of the family, palliative measures were pursued, and the patient was discharged home.

CONCLUSION
RCC can reappear several years after nephrectomy. 4 Metastatic RCC appears to have a unique propensity to spread to the ventricular system and the CP, which indicates late progression of disease. 1,5,6 While surgery may be viable if tumor burden is low, therapeutic options are limited in the advanced disease stages, as in our patient. Palliative care should be offered early to maximize remaining quality of life.
NCMP-09. IMPACT OF TUMOUR CHARACTERISTICS AND CANCER TREATMENT ON CEREBROVASCULAR MORTALITY AFTER GLIOMA DIAGNOSIS: EVIDENCE FROM A POPULATION-BASED CANCER REGISTRY
Authors: Brennan Paul , Jin Kai , Figueroa Jonine , Sudlow Cathie 
Published: November 2022

Abstract

BACKGROUND
Brain tumour patients have the highest stroke mortality rates among cancer types, but the factors associated with fatal stroke remain unknown. We aimed to examine to what extent brain tumour grade, a marker of biological aggressiveness, tumour size and cancer treatment are associated with cerebrovascular mortality among patients with malignant glioma, the most common and aggressive brain tumour.

METHODS
We conducted a retrospective, observational cohort study using the US National Cancer Institute’s state and regional population-based cancer registries (NCI SEER). We identified adult patients with a diagnosis of malignant glioma (2000 to 2018, Nf72,916). The primary outcome of interest was death from cerebrovascular disease. Cox regression modelling estimated the associations with cerebrovascular mortality of tumour grade, tumour size and treatment (surgery, radiotherapy, chemotherapy), calculating hazard ratios (HR) adjusted for these factors as well as for age, sex, race, marital status and calendar year.

RESULTS
Higher grade (Grade IV vs Grade II: HR=2.47, 95% CI=1.69-3.61, p&lt; 0.001) and larger brain tumours (size 3 to &lt; 6 cm: HR=1.40, 95% CI=1.03 -1.89, p&lt; 0.05; size ≥ 6 cm: HR=1.47, 95% CI=1.02-2.13, p&lt; 0.05 compared to size &lt; 3cm) were associated with increased cerebrovascular mortality. Having cancer treatment was associated with decreased risk (surgery: HR= 0.60, p&lt; 0.001; chemotherapy: HR=0.42, p&lt; 0.001; radiation: HR= 0.69, p&lt; 0.05). However, among patents surviving five years or more from their cancer diagnosis radiotherapy was associated with higher risk of cerebrovascular mortality (HR 2.73, 95% CI 1.49-4.99, p&lt; 0.01).

CONCLUSIONS
More aggressive tumour characteristics are associated with increased cerebrovascular mortality, and treatment was associated with lower risk within 5 years of diagnosis. Radiotherapy increased risk of fatal cerebrovascular outcome five-years after cancer diagnosis. Further research is needed to better understand the long-term cardiovascular consequences of radiation therapy, and whether the consequent risk can be mitigated.
NCMP-17. PLASMA EXCHANGE FOR IMMUNE CHECKPOINT INHIBITOR INDUCED ACUTE DEMYELINATING POLYNEUROPATHY REFRACTORY TO IVIG
Authors: Kolli Avinash , Pina Yolanda , Peguero Edwin , Gatewood Tyra , Mokhtari Sepideh , Verma Neha 
Published: November 2022

Abstract
The use of immune checkpoint inhibitors in the treatment of cancer has gained prominence due to their effectiveness. Unfortunately, neurological immune-related adverse events represent a growing problem in neuro-oncology practice. Many of these cases are rare and their diagnoses and management can be challenging. We present a case of a 69-year-old male with urothelial carcinoma status post left nephrectomy who developed bilateral lower extremity weakness that began following his first dose of Atezolizumab. After three doses, his lower extremity weakness worsened to the point where he could not walk. A NCV study was performed and was consistent with acute demyelinating polyneuropathy. A cervical MRI (Magnetic Resonance Imaging) showed an enhancing lesion at C6-C8. He was treated with three days of intravenous methylprednisolone every six hours for three days followed by three days of 0.4gm/kg IVIG. He regained his ability to walk after IVIG treatment. The enhancing lesion noted on MRI remained. Three weeks after the first IVIG treatment, he declined significantly, redeveloping symptoms where he could not ambulate and required assistance to use the toilet. He had no lower extremity reflexes and had loss of proprioception of his hands. He was scheduled for another IVIG infusion at .4gm/kg followed by a dose of IVIG .6gm/kg the next day, and then four more days of IVIG .25gm/kg. His lower extremity weakness and difficulty walking remained so he was arranged for plasmapheresis x five cycles. His weakness improved, reflexes returned, and he no longer had proprioceptive loss of his hands. A cervical MRI obtained one month after plasma exchange showed resolution of the C6-C8 enhancing lesion. He is now ambulating with a cane. This case highlights the effectiveness of plasma exchange in a case that was refractory to IVIG
NCMP-23. A UNIQUE CASE OF CHOREIFORM DYSKINESIAS IN A PATIENT WITH METASTATIC RENAL CELL CARCINOMA
Authors: Jaffer Ali-Musa , Graves Andrew , Verma Neha , Mokhtari Sepideh , Pina Yolanda 
Published: November 2022

Abstract

BACKGROUND
Dyskinesias in cancer patients present a diagnostic challenge to clinicians. Etiologies can include paraneoplastic syndromes, chemotherapy related side effects, or primary movement disorders. This is a unique case of choreoathetotic dyskinesias in a patient with metastatic renal cell carcinoma while undergoing treatment with cabozantinib in combination with either placebo or the investigational drug CB-839 (telanglenastat) while on the clinical trial MCC 19671.

RESULTS
We present a 69 year old gentleman with a history of metastatic renal cell carcinoma who developed choreoathetotic dyskinesias eleven months after enrolling in a phase 2 blind study MCC 19671. His CSF paraneoplastic panel and MRI brain imaging were unremarkable. His symptoms abated with stopping his clinical trial drug, after which he withdrew from the trial and opted to continue cabozantinib alone. Unfortunately he developed worsening dyskinesias a week after restarting cabozantinib which was then stopped permanently. He was treated with prednisone and plasma exchange with improvement in his symptoms. Unfortunately, he passed away due to progression of disease two months later.

CONCLUSIONS
This case highlights the first case of choreiform dyskinesias most likely associated with CB-839/cabozantinib, since the patient’s symptoms significantly improved upon stopping the medications. The patient could also have had a novel paraneoplastic-associated antibody which has not been discovered yet. As the investigation into novel chemotherapeutic agents for malignancies continues, the incidence of drug related dyskinesias will need to be monitored.
NCOG-06. CASE REPORT: EXTENDED REMISSION OF HER2-POSITIVE BREAST CARCINOMA WITH BRAIN METASTASES AND LEPTOMENINGEAL DISEASE FOLLOWING INTRATHECAL AND SYSTEMIC TRASTUZUMAB
Authors: Gregory Timothy , Loghin Monica 
Published: November 2022

Abstract
Leptomeningeal disease (LMD) in breast cancer carries a poor prognosis with median overall survival (OS) of 3-4 months. Recent series have indicated prolongation of OS up to 10-13 months in HER2-positive breast LMD treated with intrathecal (IT) trastuzumab. Here we present an unprecedented long-term survival with clinical, radiographic, and molecular response for more than 10 years on IT trastuzumab. A 52-year-old woman presented in 12/2011 with newly diagnosed LMD with previously treated brain and systemic metastases. Her initial diagnosis of HER2-positive left intraductal carcinoma in 5/2005 was treated with bilateral mastectomy, adjuvant chemotherapy with doxorubicin and cyclophosphamide followed by paclitaxel and trastuzumab, as well as local RT. She was disease free until 10/2009 when she presented with headache due to two brain metastases involving the vermis and right occipital lobe. She underwent resection and SRS, followed by chemotherapy with capecitabine and lapatinib. In 12/2010 she received further RT to the posterior fossa for recurrent disease and later required gamma knife to a left occipital metastasis. In 8/2011 she developed back pain and cauda equina syndrome. MRI spine revealed LMD from T11- L2. CSF studies showed &gt; 500 protein, 17 WBCs and malignant cells consistent with her breast primary. Both cerebellar metastasis and cells in the spinal fluid showed over-expression and amplification of HER2neu. She completed RT to the lower spine, and in 1/2012 began IT trastuzumab with continuation of capecitabine and lapatinib. There was progressive LMD in 2/2012 prompting escalation of IT trastuzumab dosing and addition of IT topotecan with systemic trastuzumab. In 10/2019, CSF showed rare malignant cells and IT topotecan was switched to cytarabine while continuing IT trastuzumab, now with durable remission ever since. The low LMD burden and aggressive therapeutic approach, including IT trastuzumab, combined with radiation and systemic therapy may explain the exceptional survival.
NCOG-39. DISCOVERY OF CLINICAL AND DEMOGRAPHIC DETERMINANTS OF SYMPTOM BURDEN IN PRIMARY BRAIN TUMOR PATIENTS USING NETWORK ANALYSIS AND UNSUPERVISED CLUSTERING
Authors: Bergsneider Brandon , Vera Elizabeth , Gal Ophir , Christ Alexa , King Amanda , Acquaye Alvina , Choi Anna , Leeper Heather , Mendoza Tito , Boris Lisa , Burton Eric , Lollo Nicole , Panzer Marissa , Penas-Prado Marta , Pillai Valentina , Polskin Lily , Wu Jing , Gilbert Mark , Armstrong Terri , Celiku Orieta 
Published: November 2022

Abstract

BACKGROUND
Precision health approaches to managing symptom burden in primary brain tumor (PBT) patients are imperative to improving patient outcomes and quality of life. Network Analysis (NA) identifies complex symptom co-severity patterns across large patient cohorts. Unsupervised clustering unbiasedly stratifies patients into clinically relevant subgroups based on symptom patterns. This is the first study to use NA and unsupervised clustering to explore PBT patients’ clinical and demographic determinants of symptom burden.

METHODS
Symptom severity data reported using the MDASI-BT from a two-institutional cohort of 1,128 PBT patients was analyzed. Gaussian Graphical Model networks were constructed for the entire cohort and for subgroups identified by unsupervised clustering. Network characteristics were analyzed and compared using permutation-based statistical tests.

RESULTS
NA on the entire cohort revealed that the majority of PBT patients experience symptoms on four core dimensions that drive overall symptom burden: cognitive, physical, focal neurologic, and affective. These dimensions substantially overlap with factor groupings defined during initial construct validation of the MDASI-BT. Fatigue/drowsiness scored the highest in all network centrality measures, indicating a pivotal role in the symptom experience. Unsupervised clustering identified four patient subgroups: PC1 (n = 683), PC2 (n = 244), PC3 (n = 92), and PC4 (n = 109). Moderately accurate networks could be constructed for PC1 and PC2, but not for PC3 and PC4 due to their small size. The PC1 network closely resembles the all-patient network, and these patients have the highest interference scores among the subgroups with fatigue/drowsiness as the primary driver. PC2 represents an older subgroup in which cognitive symptoms drive symptom burden.

CONCLUSIONS
This novel study identified clinically relevant subgroups of patients with unique symptom burdens. With further validation, our approach may inform more personalized and effective symptom management by identifying symptoms to prioritize for targeting in individual patients.