bluuebunny/crossref_metadata_2025 huggingface dataset:
NCMP-08. EFFICACY OF ANTIEPILEPTIC DRUGS IN GLIOMA PATIENTS WITH EPILEPSY: A SYSTEMATIC REVIEW
Authors: de Bruin Marjolein , van der Meer Pim , Dirven Linda , Taphoorn Martin , Koekkoek Johan
Published: December 2020

BACKGROUND

Epilepsy is a common symptom in glioma patients, requiring antiepileptic drug (AED) treatment. However, comprehensive data on the efficacy and tolerability of AED treatment is currently lacking. In this systematic review we specifically assessed the efficacy of AEDs in patients with a grade II-IV glioma.

METHODS

Electronic databases PubMed/MEDLINE, EMBASE, Web of Science, and Cochrane library were searched up to April 2020. Three different outcomes were extracted from all eligible articles: (I) seizure freedom; (II) ≥50% reduction in seizure frequency; and (III) treatment failure. To overcome variation with respect to sample sizes, weighted averages (WA) were calculated for outcomes at 6 and 12 months.

RESULT

A total of 64 studies were included. For monotherapy, the 6-months seizure freedom rate was highest for phenytoin (WA=72%), whereas the 12-months seizure freedom rate was highest for pregabalin (WA=75%). For achieving ≥ 50% seizure reduction, levetiracetam was the most effective AED at 6 and 12 months, with WA of 82 and 97% respectively. Considering the provided polytherapy combinations, levetiracetam combined with phenytoin was most effective followed by levetiracetam with valproic acid. Seizure freedom rates with polytherapy at 6 months and 12 months were highest for combinations with phenytoin and topiramate, respectively. For achieving a ≥ 50% seizure reduction, combinations with perampanel were found to be the most effective at 6 and 12 months.

CONCLUSION

Based on the current literature, phenytoin, levetiracetam and pregabalin are most effective as AED monotherapy in glioma patients with epilepsy. Well-controlled prospective studies are needed to help further guide clinician’s treatment choices.
NCMP-18. NEUROTOXICITY AS A POTENTIAL SURROGATE MARKER FOR THERAPEUTIC RESPONSE WITH COMMERCIAL ANTI-CD19 CAR T-CELL THERAPY
Authors: Yuen Carlen , Riedell Peter , Artz Andrew , Kosuri Satyajit , Kelly Thomas , Wu Shasha , Reder Anthony , Rezania Kourosh , Soliven Betty , Xie Tao , Mastrianni James , Park Deric , Klejch Wesley , Ali Saad , Bishop Michael
Published: December 2020

Neurotoxicity is a common occurrence and a major form of morbidity in adult patients with relapsed or refractory (R/R) diffuse large B cell lymphoma (DLBCL) patients treated with anti-CD19 directed chimeric antigen receptor (CAR) T-cell therapy. Variables related to the incidence and severity of neurotoxicity have been relatively well delineated, but the association between neurotoxicity and the efficacy of CAR T-cell therapy has not been well studied. We performed a retrospective analysis of the outcomes of DLBCL patients who developed neurotoxicity following anti-CD19 CAR T-cell treatment. The analysis included 26 patients with R/R DLBCL who received commercial anti-CD19 CAR T-cell therapy. All patients received a lymphodepleting chemotherapy regimen consisting of fludarabine and cyclophosphamide. Twenty-five patients received axicabtagene ciloleucel, and 1 received tisagenlecleucel. The overall incidence of neurotoxicity was 88%; 31% developed severe neurotoxicity (Grade III-IV by CTCAE). Higher neurotoxicity was associated with better PFS by both CTCAE (CR 2.4 ± 1.1 vs. PD 1.4 ± 1.3, p = 0.051) and CARTOX-10 (CR 3.78 ± 4.6 vs. PD 7.7 ± 3.8, p = 0.044) grading systems. Higher neurotoxicity continued to show a trend at 6, 9, and 12 months by the CTCAE grading system (CR 2.4 ± 1.0 vs. PD 1.7 ± 1.3, p = 0.085), and no patients had disease recurrence after 6 months. In this limited cohort, neurotoxicity severity was paradoxically positively correlated with progression-free survival with commercial CAR T-cell therapy and may therefore indicate an effective therapeutic response.
NCMP-26. RECOGNITION OF PARANEOPLASTIC SYNDROMES TRIGGERED BY TRADITIONAL CYTOTOXIC CANCER TREATMENT, TUMOR RECURRENCE AND DEVELOPMENT OF SECOND CANCER
Authors: Tummala Sudhakar
Published: December 2020

BACKGROUND

Paraneoplastic syndromes traditionally precede tumor diagnosis. With recent greater use of immune checkpoint blockade therapy there is ever-increasing recognition of various immune related adverse effects. This abstract highlights PCA 1 paraneoplastic syndrome triggered by non-immune based chemotherapy, surgery, tumor recurrence and prior to development of second cancer.

METHODS

This is retrospective case review of patients seen at MD Anderson Cancer Center who developed PCA 1 paraneoplastic syndrome.

RESULTS

64 yr old female with ovarian cancer on ERK inhibitor develops lower extremity weakness, ataxia and difficulty ambulation. Serum and CSF showed positive PCA-1 antibody. 59 yr old female with ovarian serous carcinoma develops cerebellar dysfunction after receiving caroboplatin and doxil. Serum and CSF were positive for PCA-1 antibody. 57 yr old female with ovarian carcinoma develops tremors, progressive ataxia after second cycle of carboplatin,taxol and avastin. Serum was positive for PCA-1 antibody. 45 yr old female with ovarian carcinoma completes 6 cycles of taxol and carboplatin. 3 months later develops gait ataxia. CSF was positive for PCA-1 antibody. Workup showed progressive ovarian carcinoma. 59 yr old with invasive ductal breast cancer develops lower extremity weakness and ataxia. Serum and CSF were positive for PCA-1 antibody. Work up revealed ovarian carcinoma. 63 yr old female with newly diagnosed breast cancer undergoes mastectomy. In the immediate postoperative time period develops diplopia, gait ataxia. Serum and CSF were positive for PCA-A antibody. All patients were aggressively treated with steroids. Most received additional therapies including plasma exchange, IVIG, tacrolimus, Rituxan, Cytoxan. All patients remained with permanent cerebellar dysfunction.

CONCLUSIONS

Case series highlights the recognition of paraneoplastic syndrome following traditional cytotoxic chemotherapy. There is need for early recognition of this neurological urgency. Work up includes prompt LP, serum and CSF paraneoplastic antibody panel, and evaluation for primary tumor recurrence or development of second cancer.
NCMP-27. THE USE OF INTRAVENOUS IMMUNOGLOBULIN (IVIG) DURING SEVERE NEUROTOXICITY AMONG THE RECIPIENTS OF CHIMERIC ANTIGEN RECEPTOR T-CELLS (CAR-T) THERAPY
Authors: Mokhtari Sepideh , Asquith Justin , Bachmeier Christina , Faramand Rawan , Kim Youngchul , Peguero Edwin , Sahebjam Solmaz , Jain Michael , Vogelbaum Michael , Davila Marco , Forsyth Peter , Locke Frederick , Aleksandr Lazaryan
Published: December 2020

INTRODUCTION

Severe Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS) occurs in ~ 30% of Diffuse Large B Cell Lymphoma (DLBCL) patients treated with CAR-T cell therapy. The current treatment for severe ICANS is glucocorticoids, and this may be combined with tocilizumab for concurrent cytokine release syndrome. Even with these treatments, neurotoxicity can persist. It is essential, therefore, to find additional treatments to more effectively reverse CAR-T neurotoxicity.

OBJECTIVE

We summarize our institutional experience using IVIG to treat severe or refractory ICANS after glucocorticoids alone.

METHOD

This is a single center retrospective cohort study of neurologic and oncologic outcomes among patients who received axicabtagene ciloleucel (axi-cel) for DLBCL or its variants from May 2015 to February 2019. We identified those patients who developed severe ICANS subsequently treated with glucocorticoids alone (n = 10) or glucocorticoids plus IVIG (n = 9).

RESULTS

The median age of all 19 patients was 63 (range 47-75, and 68% were males). All IVIG recipients received glucocorticoids prior to IVIG administration. There was no significant difference in time to resolution (TTR) of severe ICANS between both groups (median 3 vs. 3 days, Log-rank p = 0.331). However, we found that all IVIG recipients had experienced either escalation of their neurotoxicity grade or persistent severe neurotoxicity after initiation of steroids (p = 0.001). Moreover, IVIG recipients had worse ECOG performance status prior to axi-cel therapy (p = 0.03).

CONCLUSION

Although we found no difference in TTR of severe ICANS with addition of IVIG to glucocorticoids, our analysis suggests that the addition of IVIG blunted the effects of steroid-refractory neurotoxicity. Patients who received IVIG had worsening ICANS despite administration of steroids and therefore might have benefited from the earlier addition of IVIG. Controlled studies may clarify the potential efficacy of IVIG in severe neurotoxicity after CAR-T therapy.
NCMP-28. BEVACIZUMAB ASSOCIATED INTRACEREBRAL HEMORRHAGE IN PATIENTS WITH PRIMARY CNS MALIGNANCY
Authors: Clarke Nathan
Published: December 2020

The risk of intracranial hemorrhage (ICH) associated with the use of bevacizumab (BEV) has been a topic of several reviews in the literature, and is considered to be a potential adverse effect of BEV when used in patients with malignant glioma. We performed a single-center retrospective chart-review identifying glioma patients treated with BEV at our institution. 595 unique patients who received BEV with documented follow up were identified. Of these patients, 23 (3.9%) developed ICH within 12 weeks (five half-lives) of a BEV infusion (median 9 days post infusion, 1-24 days IQR). There was a trend towards statistical significance between dose administered and the incidence of hemorrhage (P=0.06), with all 23 hemorrhages occurring in patients treated with 10 mg/kg (n=21/490) per infusion or 15 mg/kg per infusion (n=2/35) (n=525, 88.2% of cohort). No patient on dosing regimens of 7.5 mg/kg (n=72) or 5 mg/kg per infusion (n=16) (n=88, 14.7% of cohort) developed ICH. Therapeutic anticoagulation and concomitant BEV therapy was observed in 103 (17%) patients with 10 patients (10/93, 9.7%) developing an ICH (n=10), at a rate significantly higher than in patients treated with bevacizumab alone (13/479, 2.6%) (p=0.0025). When hemorrhages occurred (with or without concomitant anticoagulation) they were associated with high morbidity and mortality (ECOG 3.54 versus 1.26, p = < 0.0001), with 12 patients (52%) suffering severe debility (n=2) or death (n=10). CONCLUSION: Bevacizumab associated intracerebral hemorrhages remain uncommon events, similar to the baseline rate of spontaneous hemorrhage associated with malignant glioma. We observed a trend towards significance with higher doses per infusion associated with an increased rate of intracerebral hemorrhage. The combination of anticoagulation and BEV appears to confer a greater risk of hemorrhage than BEV alone.
NCOG-03. FACTORS ASSOCIATED WITH ADJACENT LEVEL TUMOR PROGRESSION IN PATIENTS RECEIVING SEPARATION SURGERY FOLLOWED BY SPINE STEREOTACTIC RADIOSURGERY FOR METASTATIC EPIDURAL SPINAL CORD COMPRESSION
Authors: Chakravarthy Vikram , Khan Hammad , Srivatsa Shaarada , Knusel Konrad , Emch Todd , Krishnaney Ajit
Published: December 2020

INTRODUCTION

Separation surgery followed by spine stereotactic radiosurgery (SSRS) has been shown to achieve favorable rates of local tumor control and patient-reported outcomes in patients with metastatic epidural spinal cord compression (MESCC). If left untreated, MESCC causes severe pain, progressive neurological impairment, and eventual paraplegia with a median survival of 3-6 months. The present study aimed to identify factors associated with adjacent level progression and examine its impact on overall survival (OS) in this population.

METHODS

This study included 39 patients who received separation surgery followed by SSRS for MESCC. Preoperative, postoperative, and post-SSRS MRIs were used to measure amount of epidural disease, amount of local bone marrow involvement, and adjacent level epidural (AEP) and osseous (AOP) progression. Factors associated with AEP and AOP were examined using the log-rank test and cox proportional hazards modeling.

RESULTS

Median OS in our cohort was 14.7 mo (2.07-96.3). AEP and AOP were observed in 4/39 (10.3%) and 16/39 (41.0%) patients at a mean of 6.1±5.4 mo and 5.3±5.3 mo post-SSRS, respectively. AEP (7.52 vs. 17.1 mo, p = 0.014) and AOP (13.0 vs. 17.1 mo, p = 0.047) were each significantly associated with decreased OS. Factors associated with AEP included primary tumor histology, low-dose hypofractionated SSRS, increased time from surgery to SSRS, and greater amount of local epidural disease preoperatively (p < 0.05). Factors associated with AOP included greater amount of local bone marrow infiltration by tumor pre- and postoperatively and greater amount of local epidural disease postoperatively (p < 0.05). Primary tumor histology and increased time from surgery to SSRS were associated with AOP by trend (p < 0.10).

CONCLUSION

This study identifies factors associated with adjacent level progression and shows that AEP and AOP are associated with shorter OS in patients receiving separation surgery followed by SSRS for MESCC.
NCOG-05. MANAGEMENT OF BRAIN METASTASIS IN TRIPLE NEGATIVE BREAST CANCER
Authors: Medikonda Ravi , Srivastava Siddhartha , Kim Timothy , Xia Yuanxuan , Patel Mira , Jackson Christopher , Theodros Debebe , Kim Jennifer , Kleinberg Lawrence , Redmond Kristin , Weingart Jon , Mukherjee Debraj , Bettegowda Chetan , Gallia Gary , Brem Henry , Lim Michael
Published: December 2020

Brain metastasis is common in patients with breast cancer, and those with triple negative status have an even higher risk. Stereotactic radiosurgery (SRS) is preferred to whole brain radiation therapy (WBRT) in most patients. However, triple negative status is currently not considered when determining optimal radiation therapy. Given the aggressive nature of triple negative breast cancer, we evaluated a role for WBRT for all patients in this cohort. We conducted a single-institution retrospective cohort study to determine whether triple negative patients with brain metastases have a higher burden of intracranial disease and whether type of initial radiation therapy affects overall survival for this cohort of patients. 85 patients met the inclusion criteria for this study. 25% of patients had triple negative breast cancer, of which 91% received SRS and 53% of patients received WBRT. The average number of new brain metastases from time of initial brain imaging to radiation therapy was 0.67 (St.Dev:1.1) in the non-triple negative status patients and 2.6 (St. Dev:3.7) in the triple negative status patients (p=0.001). Using a cox proportional hazards model, it was found that whole brain radiotherapy does not significantly affect overall survival in patients with triple negative breast cancer (p = 0.96). Our findings highlight the highly aggressive intracranial nature of triple negative breast cancer. Indeed, the rate of increase in brain metastases is significantly higher for triple negative patients compared to non-triple negative patients. As a result, we evaluated whether triple negative patients would benefit from whole brain radiation regardless of findings on initial brain imaging. Despite 53% of patients receiving WBRT, our investigation found that there is no additional benefit to WBRT in triple negative breast cancer patients. These results suggest a need to re-evaluate the role of WBRT in the management of triple negative breast cancer.
NCOG-10. ASSESSMENT OF SURVIVAL AND SAFETY FOLLOWING INTRATHECAL CHEMOTHERAPY VIA OMMAYA RESERVOIR FOR LEPTOMENINGEAL DISEASE
Authors: Shah Shiv , Butterfield Richard , Bendok Bernard , Lyons Mark , Ariete John , Yancey Eric , Mrugala Maciej
Published: December 2020

INTRODUCTION

Leptomeningeal disease (LMD) is an aggressive, late-stage complication of systemic cancers that maintains a poor prognosis with an average survival of 3-6 months. Ommaya reservoirs (OR) are an accessible alternative to serial lumbar punctures for the delivery of intrathecal chemotherapy in the treatment of LMD. However, widespread use of OR has been limited by reports of complications, limited physicians trained in their use, and the stigma of brain surgery. Here, we assess survival and complication rates for patients who received intrathecal chemotherapy through OR for LMD treatment.

METHODS

After IRB approval, chart review of patients who received at least one administration of intrathecal chemotherapy through OR for LMD treatment between 2017- 2020 at Mayo Clinic in Phoenix, Arizona was conducted. Charts were reviewed for demographics, treatment type, complications, and outcomes.

RESULTS

A total of 10 patients were included. The median overall survival from date of first OR injection was 110.5 days (95% CI: 64 – not estimable). The median time to progression from the first injection was 55.5 days (95% CI: 45 – 753). A total of 82 OR injections were conducted for an average of approximately 8 injections per patient. Two patients (20%) experienced mild adverse events – grade 2 or lower by Common Terminology Criteria for Adverse Events with a single injection. The majority of injections involved no adverse events with the overall risk of any complication at 2.4%. None of the patients experienced infection, a commonly reported complication of OR use.

CONCLUSIONS

Our results support the inclusion of intrathecal chemotherapy via OR into the treatment paradigm in patients with leptomeningeal malignancies. This approach is feasible, safe, and median survival is comparable with data reported in published series. The overall complication rate in patients receiving intrathecal chemotherapy through OR is very low including the risk of infection.
NCOG-23. PATTERNS OF DISTRESS IN OLDER PATIENTS WITH GLIOBLASTOMA: A FOLLOW-UP TO A SINGLE INSTITUTION CROSS-SECTIONAL STUDY OF DISTRESS IN PRIMARY BRAIN TUMOR PATIENTS
Authors: Johnson Margaret , Herndon James , Lipp Eric , Affronti Mary , Desjardins Annick , Bhattacharya Manisha , Friedman Henry , Ashley David , Peters Katherine , Randazzo Dina
Published: December 2020

INTRODUCTION

We previously reported to SNO, high levels of psychosocial distress in adult patients with primary brain tumors (PBTs), particularly during the first 6 months following diagnosis. The purpose of this follow-up study was to identify patterns of distress among older (≥ 65 years) patients with glioblastoma (GBM) compared to their younger (ages 18-64) counterparts.

METHODS

In our initial cross-sectional study, we collected the National Comprehensive Cancer Network’s Distress Thermometer (NCCN-DT) and problem list from adult patients with PBTs (WHO grades I-IV) seen at our institution between December 2013 and February 2016. We performed subsequent analyses on a subset of patients with GBM.

RESULTS

We identified 343 patients with GBM from the original dataset, of which 23.0% (n= 78) were ≥ 65 years old. The proportion of patients ≥ 65 years old with elevated distress (i.e. DT ≥ 4) was greater than the proportion of younger patients reporting elevated distress (47.4% vs 30.6%; p= 0.0068). Elevated distress was significantly greater during the first 6 months post diagnosis for all ages (p= 0.008). In subgroup analyses, a decrease in distress beyond 6 months was seen in younger patients (45.7% vs 27.4%; p= 0.021), but not in older patients. In older patients, a greater number of problems were selected on the NCCN DT and problem list tool: emotional and physical concerns were reported more frequently compared to their younger counterparts. Older patients were more likely to report difficulty with “bathing” and “getting around” (p= 0.009, p< 0.001, respectively). There were no differences in older versus younger GBM patients with regard to housing, transportation, treatment decisions, depression, fatigue, or memory.

CONCLUSIONS

In contrast to their younger counterparts, older patients with GBM experienced elevated levels of distress and a greater absolute number of specific psychosocial problems, mostly related to emotional and physical concerns.
NCOG-25. EFFICACY OF ANTICONVULSANT THERAPY IN GLIOMA PATIENTS
Authors: Medikonda Ravi , Patel Kisha , Saleh Laura , Srivastava Siddhartha , Jackson Christina , Mohan Aditya , Shah Pavan , Weingart Jon , Bettegowda Chetan , Gallia Gary , Brem Henry , Lim Michael
Published: December 2020

Gliomas account for 30% of primary brain tumors and can frequently present with seizures. There are few guidelines for usage of anticonvulsant therapy in glioma patients. Some clinicians utilize anticonvulsant therapy in all glioma patients as a means of prophylaxis, whereas other clinicians prescribe anticonvulsant therapy only in patients that experience seizures. In this single-institution retrospective cohort study, we evaluate the effect of commonly prescribed anticonvulsant levetiracetam on incidence of post-operative seizures and overall survival in primary glioma patients. 436 patients met the inclusion criteria for this study. 35% of patients presented with a pre-operative seizure and 63% of patients received pre-operative Levetiracetam. The incidence of a seizure within 1 year of tumor resection was 31%. On multivariate logistic regression analysis of patient pre-operative clinical and imaging characteristics, it was found that only a pre-operative seizure (p = 0.02) significantly increased the odds of a post-operative seizure within 1 year of tumor resection. Neither pre-operative levetiracetam (p = 0.31), intra-operative levetiracetam (p = 0.59), or post-operative levetiracetam (p = 0.75) significantly reduced the odds of a post-operative seizure. Using a cox proportional hazards model, pre-operative levetiracetam (p = 0.11), intra-operative levetiracetam (p = 0.34), and post-operative levetiracetam (p = 0.88) do not significantly affect overall survival. Our findings reveal that glioma patients are often prescribed anticonvulsant medication regardless of whether they have had a pre-operative seizure. Most patients also receive anti-convulsant medication in the peri-operative and post-operative setting regardless of whether they have had pre-operative or immediate post-operative seizures. Use of pre-operative or intra-operative levetiracetam as a prophylactic measure does not impact the incidence of post-operative seizures. Furthermore, anti-convulsant therapies do not demonstrate a survival benefit in our study. These results provide a rationale for re-evaluating the use of anti-convulsant medications in glioma patients that do not have seizure symptoms.
NCOG-33. HEMATOLOGIC PREDICTORS OF OUTCOMES IN GLIOBLASTOMA TREATED WITH SURGERY AND CHEMORADIATION
Authors: Damico Nicholas , Elder Theresa , Kharouta Michael , Sloan Anthony , Kerstetter-Fogle Amber , Harris Peggy , Kumar Aryavarta , Mansur David , Machtay Mitchell , Bhatt Aashish , Buerki Robin , Sloan Andrew E , Choi Serah
Published: December 2020

BACKGROUND

There are conflicting reports regarding the prognostic value of platelet and other blood counts in glioblastoma. However, few series have looked at all hematologic parameters simultaneously.

METHODS

We performed a retrospective chart review of patients diagnosed with supratentorial glioblastoma from 2014-2019 who started conventional chemoradiation following initial surgical biopsy and/or resection. Hematologic parameters were collected at baseline, in the preoperative and postoperative periods and at the initiation and completion of chemoradiation. This included platelet counts, hemoglobin levels, white blood cell counts (WBC), neutrophil and lymphocyte counts with neutrophil:lymphocyte (NLR) and platelet:lymphocyte ratios (PLR) calculated at each time point. Cox regression was performed to assess the association between each hematologic parameter and both overall survival (OS) and progression free survival (PFS). A multivariate Cox proportional hazards model adjusted for all hematologic parameters, age, sex, race and KPS was generated for each time point. All hematologic parameters were modeled as continuous variables.

RESULTS

A total of 58 patients met inclusion criteria. 18 were female and 40 male. The median age was 59.5 (range 43-82). Median follow up for all patients was 15.3 months. A total of 52 patients completed radiation therapy and 18 completed 6 cycles of adjuvant chemotherapy. Hemoglobin and neutrophil counts at the conclusion of chemoradiation were associated with OS and PFS on univariate and multivariate analyses. The HR for OS were 0.74 (95% CI 0.5807-0.9313) and 1.28 (1.143-1.441) respectively. The HR for PFS were 0.70 (0.5531-0.8881) and 1.16 (1.05-1.271) respectively. Postoperative lymphocyte and platelet counts at initiation of chemoradiation were both associated with OS with unadjusted HR of 3.2 (1.037-9.960) and HR of 0.99 (0.9898-0.9999) respectively, which remained significant on multivariate analysis. However, neither were associated with PFS.

CONCLUSION

Several hematologic parameters are associated with glioblastoma outcomes in these initial analyses. Further analyses with additional patients are ongoing.
NCOG-35. PREDICTORS OF POSTOPERATIVE SEIZURES IN PATIENTS WITH GLIOBLASTOMA MULTIFORME
Authors: Zhang Yue , Dincer Alper , Feld Noah , Carr Matthew , Zhang Lily , Opalak Charles , Rock Andrew , Broaddus William
Published: December 2020

INTRODUCTION

Seizures are a major cause of morbidity in patients with GBM, resulting in neurocognitive deficits and reduced QOL. There are limited studies on the predictors of postoperative seizures in these patients. Furthermore, there is no consensus among neurosurgeons on the timing of perioperative use of antiepileptic drugs (AEDs). The objective of this study is to determine patient- and tumor-related factors associated with postoperative seizures in GBM patients who undergo surgical resection.

METHODS

Our patient data registry was queried for adult patients treated for GBM at VCU from 2005 to 2014. Univariate and multivariable logistic regression analyses were performed to identify patient and tumor factors associated with postoperative seizure within a 12 month period. Cox proportional hazards regression analysis was used to evaluate the overall risk of postoperative seizure.

RESULTS

146 patients met the criteria for the study. Of these, 39 patients (27%) experienced a postoperative seizure within 12 months. On univariate analysis, factors significantly associated with postoperative seizure within 12-months included percent (%) of FLAIR volume resected (OR: .81; CI: 0.65-0.99; p=.046), history of AED use (OR: 2.51; CI: 1.20-5.25; p = 0.015), and history of seizure (OR: 2.26, CI: 1.07-4.76; p=0.033). On multivariate analysis, % FLAIR resection maintained significance. (OR of 0.79; CI: .63-.99; p = 0.044). The increased overall risk of postoperative seizure was associated with preoperative seizure < 30 days before surgery. (HR:6.65, CI: 1.02-43.36, p=0.048).

DISCUSSION

Our study found that the increased extent of resection of FLAIR volume correlates with decreased odds of seizure occurrence in the 12-month postoperative period. Epileptogenesis of GBM seizures within this time period may be due to tumor-related edema or infiltrative tumor cells. Evaluation of FLAIR imaging postoperatively may be a useful clinical tool to guide AED management in high-risk patients.
NCOG-36. FIRST HEALTH UTILITIES OF GLIOBLASTOMA PATIENTS USING TTFIELDS TREATMENT
Authors: Chavez Gordon , Proescholdt Christina
Published: December 2020

BACKGROUND

Despite the importance of Health State Utilities for health policy and medical decision making, there are no publications that provide high quality utility values estimated from glioblastoma multiforme (GBM) patients. Published health economic evaluations for GBM treatments rely on utilities determined by Garside et al. (2007), which used the standard gamble method in healthy panel members of the UK National Health System. There are no published utilities for GBM estimated from a general population sample, and there are no utility estimates whatsoever for Tumor Treating Fields (TTFields) users.

METHODS

We designed a study to remedy this major deficit by eliciting utilities directly from GBM patients using the EuroQol 5-Dimension (EQ-5D) survey. The EQ-5D is a widely used and NICE-recommended tool for the estimation of health state utilities. The survey is composed of a questionnaire that asks patients to specify their health state along 5 dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Statistical models provided by EuroQol’s network of researchers convert this data into health state utility estimates.

RESULTS

The EQ-5D questionnaire is administered to active patients using TTFields treatment during the study duration, allowing the elicitation of health preference measures for different glioblastoma health states based on: progression status (progressed vs. non-progressed), current treatments (TTFields only vs. TTFields + others) and time-from-diagnosis (0-12 months vs. > 12 months)

CONCLUSION

These results are important for understanding the patient preferences using TTFields treatment and communicating these preferences to decision makers. This study is the first to provide direct, high quality utility measures in glioblastoma patients using TTFields treatment.
NCOG-45. FIRST-LINE ANTIEPILEPTIC DRUG TREATMENT IN GLIOMA PATIENTS WITH EPILEPSY: LEVETIRACETAM VERSUS VALPROIC ACID
Authors: van der Meer Pim , Dirven Linda , Fiocco Marta , Vos Maaike , Kouwenhoven Mathilde , van den Bent Martin , Taphoorn Martin , Koekkoek Johan
Published: December 2020

BACKGROUND

Levetiracetam and valproic acid are two of the most commonly prescribed antiepileptic drugs (AEDs) in patients with a glioma and epilepsy. This study aimed at estimating the cumulative incidence of treatment failure of first-line monotherapy levetiracetam versus valproic acid in glioma patients with epilepsy.

METHODS

In this retrospective observational study, a competing risk model was used to estimate the cumulative incidence of treatment failure, from AED treatment initiation, for the two AEDs with death as competing event. Patients were matched on baseline covariates potentially related to treatment assignment and/or outcomes of interest according to the nearest neighbour propensity score matching technique. Secondary outcomes were the cumulative incidence of recurrent seizure, from AED treatment initiation (estimated with a competing risk model), and severity of adverse effects. Maximum duration of follow-up was 36 months.

RESULTS

In total, 776 patients using levetiracetam and 659 using valproic were identified. Matching resulted in two equal groups of 429 patients, with similar covariate distribution. The cumulative incidence of treatment failure (any reason) at 12 months for levetiracetam and valproic acid was equal to 33% (95%CI=29-38%) versus 50% (95%CI=45-55%), respectively (p< 0.001). The cumulative incidence of treatment failure due to uncontrolled seizures was significantly lower for levetiracetam compared to valproic acid (12 months: 16% [95%CI=12-19%] versus 28% [95%CI=23-32%]; p< 0.001), but no differences were found for treatment failure due to adverse effects (12 months: 14% [95%CI=11-18%] versus 15% [95%CI=11-18%]; p=0.636). The cumulative incidence of recurrent seizure of levetiracetam was significantly lower compared to valproic acid (12 months: 54% [95%CI=49-59%] versus 67% [95%CI=62-71%]; p< 0.001). No significant differences were found for level of toxicity.

CONCLUSION

Our results suggest that levetiracetam has superior efficacy compared to valproic acid, while showing a similar level of toxicity. Therefore, levetiracetam seems the preferred choice for first-line AED treatment in glioma patients.
NCOG-47. CAN YOUNG CHILDREN WITH RELAPSED MEDULLOBLASTOMA BE SALVAGED AFTER INITIAL IRRADIATION-SPARING APPROACHES?
Authors: Erker Craig , Larouche Valérie , Aguilera Dolly , Margol Ashley , Cacciotti Chantel , Perreault Sébastien , Cohen Kenneth J , AbdelBaki Mohamed , Hukin Juliette , Rassekh Shahrad Rod , Eisenstat David D , Wilson Beverly , Hoppman Anna L , Dhall Girish , Holly Taylor , Knipstein Jeffrey , Sandler Eric S , Klawinski Darren , Dorris Kathleen , Fay-McClymont Taryn B , Salloum Ralph , Harrod Virginia L , Crooks Bruce , Ramaswamy Vijay , Finlay Jonathan , Bouffet Eric , Lafay-Cousin Lucie
Published: December 2020

INTRODUCTION

Irradiation-sparing approaches are used in young children with medulloblastoma (MB) given the vulnerability of the developing brain to neurocognitive impairment. Limited data are available following relapse for these patients. We aimed to describe the management and outcomes of young children with MB who relapsed after initial treatment without craniospinal irradiation (CSI).

METHODS

International retrospective study including patients with MB diagnosed between 1995-2017, ≤ 72 months old, initially treated without CSI, who subsequently relapsed.

RESULTS

Data are available for 66 patients. The median age at initial diagnosis was 27 months (range, 6-72). At diagnosis, 27 patients had metastatic disease. Initial therapy included conventional chemotherapy or with high-dose chemotherapy (HDC) in 30 and 36 patients, respectively. Eight (12.1%) received upfront focal irradiation. Molecular subgrouping was available for 27 (41%) patients. Ten were SHH, five group 3, six group 4 and six others were non-WNT/non-SHH. The median time from initial diagnosis to relapse was 13 months (range, 3-63). Relapse was local, disseminated, or combined in 39%, 32%, and 29%, respectively. The median time to death from relapse was 18 months. Curative intent therapy was given in 53 patients with irradiation (81%), conventional chemotherapy without HDC (40%), and HDC (25%). For patients who received irradiation, 85% received CSI (median dose 33 Gy, 18-41.4) and 15% focal irradiation. Ten patients received chemotherapy without salvage irradiation. The median follow-up time was 44 months (range, 4-255), 33 (62%) patients who underwent curative-intent therapy were alive, including 8/10 SHH, 2/3 group 3, 2/6 group 4, and 4/5 non-WNT/non-SHH. Three of four patients with SHH and treated without salvage radiotherapy are survivors. The 5-year OS for curative intent was 70%.

CONCLUSION

A substantial proportion of young children who relapse following irradiation-sparing strategies can be salvaged. A proportion of children with SHH MB can be salvaged without salvage radiotherapy.
NCOG-48. TRANSFORMATION FROM LOW GRADE MENINGIOMA AND PROGNOSTIC FACTORS FOR SHORTER TIME TO RECURRENCE OF WHO GRADE III MENINGIOMA DIAGNOSIS
Authors: Chew Jessica , Chen William , Susko Matthew S , Vasudevan Harish N , Braunstein Steve , Magill Stephen , Raleigh David
Published: December 2020

BACKGROUND

WHO grade III meningiomas are rare, and clinical outcomes data are limited. To address this problem, we analyzed a single institution retrospective cohort of patients with WHO grade III meningiomas.

METHODS

Patients who underwent resection of WHO grade III meningiomas between 1983 and 2019 with available follow-up data were included. Treatment, local recurrence, and overall survival rates were obtained. Kaplan-Meier analysis, log rank tests, and Student’s t tests were used for statistical analyses.

RESULTS

Ninety consecutive patients met inclusion criteria. Median follow-up was 3.2 years (IQR: 1.2-7.9), median age was 58 years (IQR: 46-67). Twenty-three patients (26%) underwent resection alone, and 58 (64%) underwent resection with adjuvant radiotherapy. Fifty-one patients developed local recurrences, with median time to recurrence of 1.0 year (IQR: 0.6-2.9) and higher MIB-1 labeling index for tumors that recurred within 1 year (25% versus 17%, p=0.04). There was a median of 2 recurrences per patient (IQR: 1-3), with a median of 2 resections and 2 radiotherapy courses for initial and salvage treatments. Thirty-nine patients with recurrences died, with median overall survival of 3.7 years (IQR: 1.8-8.8). Thirty-seven patients (41%) had prior low grade meningioma diagnoses with subsequent transformation to grade III, including 6 (7%) with grade I, 16 (18%) with grade II, and 15 (17%) with unknown grade. There was a median of 1 low grade recurrence per patient (IQR: 0-3) before transformation to grade III, which occurred a median of 4.3 years (IQR: 2.4-9.9) after initial diagnosis. Prior low grade diagnosis was associated with shorter time to recurrence of WHO grade III meningioma (p=0.01), and worse overall survival (p=0.03).

CONCLUSION

Patients with WHO grade III meningioma have poor outcomes despite aggressive multimodal therapy, and there is an urgent, unmet need for new high grade meningioma treatments.
NCOG-49. COMBINED NECROSIS AND BRAIN INVASION PREDICT RADIO-RESISTANCE AND TUMOR RECURRENCE IN ATYPICAL MENINGIOMA
Authors: Emili Garcia-Segura Monica , Erickson Anders , Jairath Rishi , Munoz David , Das Sunit
Published: December 2020

BACKGROUND

Meningiomas are the most common tumors in the central nervous system, with variable recurrence rates depending on WHO grading. Atypical (WHO grade II) meningioma has a higher recurrence rate than benign meningioma (WHO grade I). The efficacy of adjuvant radiotherapy (RT) to improve tumor control has been questioned.

METHODS

This cohort study retrospectively reviewed all patients at St. Michaels Hospital Tumor Patient Database with a diagnosis of atypical meningioma (AM) who underwent surgical resection between 1995 and 2015. Patient and tumor characteristics such as location, neuropathological diagnosis, resection extent, RT and time to reoccurrence or progression were recorded. Resection extent was defined by Simpson Grading Scale as either Gross Total (GTR) or Subtotal (STR) resection. Cox univariate regression and Kaplan-Meier survival analysis were employed to identify risk factors for recurrence and radio-resistance.

RESULTS

In our cohort of 181 patients, the combination of necrosis and brain invasion was associated with an increased reoccurrence risk (HR= 4.560, P=0.001) and the lowest progression-free survival relative to other histopathological predictors. This trend was maintained after GTR (P=0.001), whereas necrosis alone and combined necrosis and brain invasion were both associated with low progression-free survival in STR (P=0.001). Radiotherapy was associated with decreased progression-free survival (P=0.001), especially in patients who received GTR (P=0.001). This trend was maintained in patients with necrosis alone (P=0.002) but especially in patients with combined necrosis and brain invasion (P=0.001).

CONCLUSION

Combined necrosis and brain invasion is a strong predictor of tumor recurrence and radio-resistance in AM, regardless of extent of resection or RT.
NCOG-50. CLINICAL AND GENOMIC FACTORS ASSOCIATED WITH SEIZURES IN MENINGIOMAS
Authors: Gupte Trisha , Jin Lan , Li Chang , Yalcin Kanat , Youngblood Mark , Miyagishima Danielle , Mishra Ketu , Fulbright Robert , Erson-omay Zeynep , Gunel Murat , Moliterno Jennifer
Published: December 2020

Clinical and genomic sequencing data of 394 patients surgically treated for meningioma were reviewed to better understand the relationship between seizures and meningiomas. Correlations of clinical and genomic variables and occurrence of preoperative (PRESZ) and postoperative (POSTSZ) seizures were analyzed. 17% of patients presented with PRESZ and used AEDs preoperatively for 46.5 months on average as they were more likely to be treated in the setting of a recurrent tumor (p = 0.042). PRESZ patients were at higher risk for worse progression free survival (HR 2.68, 95% CI 1.30-5.50) and were also more likely to have meningiomas with an NF2-mutation (p = 0.032), higher grade (p = 0.030) and brain invasion (p = 0.009). On multivariate analysis, edema (OR 3.11, 95% CI 1.46-6.65; p = 0.003) and atypical histology (OR 2.00, 95% CI 1.03-3.90; p = 0.041) were positive predictors of PRESZ, while genomic subgroup was not, such that the effect of NF2 mutation was indirectly mediated through atypical histology and edema (p = 0.012). Seizure freedom was achieved in 83.3% of the cohort. 20% of all seizure-free patients were able to discontinue AED use postoperatively and they were more likely to have undergone a GTR (p = 0.031). Edema (OR 13.69, 95% CI 1.19-14.88; p = 0.026), recurrent tumors (OR 7.41, 95% CI 1.27-8.68; p = 0.015), and postoperative radiation (OR 6.37, 95% CI 1.16-7.53; p = 0.023) were significant predictors of POSTSZ. Hedgehog-pathway mutated tumors were associated with POSTSZ in Grade I meningiomas (p = 0.026). While NF2-mutated tumors are significantly associated with PRESZ, this appears due to corresponding edema and atypical histology. Patients who undergo radiation and/or suffer recurrence are at risk for POSTSZ, irrespective of extent of resection. PRESZ may portend a more potentially aggressive molecular entity and challenging clinical course with higher recurrence risk.
NCOG-51. CORRELATION BETWEEN TUMOR VOLUME AND SERUM PROLACTIN AND IMPACT OF TUMOR CELLULAR DENSITY ON PROLACTINOMA SURGICAL OUTCOMES IN A COHORT OF 181 PATIENTS
Authors: Pereira Matheus , Oh Taemin , Joshi Rushikesh , Haddad Alexander , Pereira Kaitlyn , Osorio Robert , Donohue Kevin , Peeran Zain , Sudhir Sweta , Jain Saket , Beniwal Angad , Gurrola José , El-Sayed Ivan , Blevins Lewis , Theodosopoulos Philip , Kunwar Sandeep , Aghi Manish
Published: December 2020

INTRODUCTION

Prolactinomas are common pituitary adenomas managed medically or surgically.

METHODS

Reviewed 181 prolactinomas resected transsphenoidally 2012-2019. Tumor volumes were quantified using BrainLab Smartbrush. Pearson correlation analysis and linear regression were used to identify associations between tumor volumes and serum prolactin. Tumor density was defined as serum prolactin divided by tumor volume.

RESULTS

Mean tumor volume was 6.33cm3 and mean pre-op prolactin was 803.4ug/L, with men having larger (12.11 vs 2.93cm3;p< 0.001) and women having denser (173.9 vs 107.6ug/L/cm3;p=0.011) prolactinomas. Pearson correlation (R=0.688;p< 0.001) and linear regression revealed a strong association between pre-op volume and prolactin levels, with 96.9g/L increase in prolactin/cm3 increase in volume (p< 0.001); this holds true for men (R=0.584;p< 0.001) and women (R=0.939;p< 0.001), with women demonstrating greater prolactin/cm3 tumor density (186.5 vs 75.0ug/L;p< 0.001). MiB index did not correlate with pre-op volume (p=0.449) or pre-op prolactin (p=0.452). Logistic regression showed decreased biochemical remission with increasing pre-op volume (OR=0.891;p< 0.001). Increased MiB index (p=0.971) and p53 (p=0.525) staining did not affect remission rates. Positive PIT-1 staining was associated with higher remission rates (OR=2.508;p=0.005). Patients without remission had denser tumors (149.9 vs. 100.6ug/L/cm3;p=0.013), with Pearson correlation yielding R=0.736 between pre-op volume and pre-op prolactin (p< 0.001), and R=0.476 between residual volume and post-op prolactin (p< 0.001). Patients without remission exhibited 142.9ug/L increase in prolactin/cm3 of pre-op volume (p< 0.001), higher than the 58.9ug/L increase in prolactin/cm3 in patients with remission (p< 0.001). Patients without remission had residual tumors with 68.4ug/L increase in prolactin/cm3 of remaining volume after resection (p< 0.001).

CONCLUSION

Our analysis revealed significant correlation between prolactinoma volume and serum prolactin levels. Patients without remission had greater tumor cellular density than those with remission. The volume-prolactin correlation persisted post-operatively, although surgery reduced tumor density. These results could identify prolactinomas for which surgery could achieve biochemical remission.
NCOG-55. HARMONIZING LANGUAGE TO MAXIMIZE IMPACT: AN UPDATE ON COMMON DATA ELEMENTS FOR MENINGIOMA AND REVIEW OF CLINICAL TRIALS IN MENINGIOMA
Authors: Wang Justin , Nassiri Farshad , Au Karolyn , Drummond Kate , Jenkinson Michael , Santarius Thomas , Barnholtz-Sloan Jill S , Jungk Christine , DiMeco Francesco , Galanis Evanthia , Saladino Andrea , Zhou Yueren , Suppiah Suganth , Badhiwala Jetan , Aldape Kenneth , Poisson Laila M , Zadeh Gelareh
Published: December 2020

BACKGROUND

With increasing studies reporting on the molecular profiling of meningiomas, there is a need to harmonize language used to capture clinical data across centers to ensure that molecular alterations are appropriately linked to clinical variables of interest. Here the International Consortium on Meningiomas presents a final set of core and supplemental meningioma-specific Common Data Elements (CDEs) to facilitate comparative and pooled analyses.

METHODS

The generation of CDEs followed the four-phase process similar to other National Institute of Neurological Disorders and Stroke (NINDS) CDE projects: development/discovery based on data from published and ongoing meningioma trials, internal validation, external validation including presentation of our data form at the Society for Neuro-Oncology previously, and distribution.

RESULTS

We developed a set of CDEs organized into patient- and tumor-level modules. In total, the Consortium identified 16 core CDEs (9 patient-level and 7-tumour-level) e.g. age at index surgery, diagnosis of neurofibromatosis, prior chemotherapy or radiation, tumor location, extent of resection, recurrence, etc. An additional 15 supplemental CDEs were defined and described (8 patient-level and 7 tumour-level) e.g. race, cause of death, multiple tumors, tumor size, Simpson grade, second intervention, etc. These CDES are now made publicly available for dissemination and adoption. We also present a narrative review and analysis of recent and ongoing meningioma trials.

CONCLUSIONS

These CDEs provide a framework for discussion in the neuro-oncology community that will facilitating data sharing for collaborative research projects and aid in developing a common language for comparative and pooled analyses. The CDEs are intended to be dynamic parameters that evolve with time and The Consortium welcomes international feedback for further refinement and implementation of these CDEs.
NCOG-62. CNS SARCOMA IN A TODDLER WITH NOVEL BALANCED TRANSLOCATION OF t(8;11)(q13;q13)
Authors: Patil Prabhumallikarjun
Published: December 2020

A CASE REPORT

A 23-month-old boy was noted to have a brain tumor after being evaluated for chronic global developmental delay. The initial neurological exam was concerning for left leg circumduction and drag. Further investigation with MRI demonstrated a 7 x 9.3 x 7.4 cm supratentorial cystic encapsulated mass identified in the right lateral ventricle with heterogeneously enhancing mural nodule measuring 0.9 x 2.7 x 3.3 cm in diameter. Capsular enhancement was also noted after contrast administration. No diffusion restriction was seen. Mass effect on septum pellucidum was seen along with an increase in size of the left lateral ventricle. Following which the patient underwent right posterior parietal craniotomy and gross total resection of the tumor. Pathology report based on the cellular appearance, cell density, presence of necrosis, and the proliferative activity classified the tumor as likely intermediate grade undifferentiated sarcoma, mostly mesenchymal in origin. Tumor cytogenetics showed balanced translocation (8;11) (q13; q13) in all metaphase cells. Cytogenetics performed on the blood sample showed normal karyotype, suggesting that the translocation seen in tumor cells was somatic in nature rather and not a germline mutation. As the radiological signs and the long clinical course of the disease (evidenced by global developmental delay noted more than a year prior to a presentation and no signs of disseminated disease) suggested it to be a low-grade tumor a decision was made not to treat aggressively with further chemo and radiotherapy. However, the pathology of the tumor was suggestive of a primary malignant undifferentiated sarcoma of the brain. The patient continued to do well with no signs of recurrence on MRI and/or clinical picture for 4 years after the initial surgery.

DISCUSSION

Primary CNS sarcoma is rare. Balanced translocation (8;11) (q13; q13) has not been described in the literature before.