bluuebunny/crossref_metadata_2025 huggingface dataset:
NCMP-20. A RETROSPECTIVE SINGLE-CENTER EXPERIENCE WITH NONBACTERIAL THROMBOTIC ENDOCARDITIS AND STROKE - OUTCOMES, ANTICOAGULATION STRATEGIES, AND INCORPORATION OF NEXT-GENERATION SEQUENCING DAT
Authors: Aaroe Ashley , Alfaro-Munoz Kristin , Bornstein Charles , Kell Trey , Camp Samuel , Chen Merry , Woodman Karin , Tummala Sudhakar , Kleiman Anne , de Groot John , Loghin Monica
Published: December 2020

BACKGROUND

Acute ischemic stroke is a common neurologic complication of cancer and contributes to worse prognosis. Hypercoagulable state is an important stroke mechanism in cancer. Nonbacterial thrombotic endocarditis (NBTE) represents an extreme manifestation of such hypercoagulability. Evidence comparing LMHW to unfractionated heparin or direct oral anticoagulants (DOACs) for secondary stroke prevention is lacking in cancer patients. It is also unknown whether certain tumor mutations are associated with increased risk of NBTE.

METHODS

We reviewed clinical documents at MD Anderson Cancer Center using a RichSearch Natural Language Processing application to search for terms related to marantic endocarditis. Each patient was assessed for documentation of both valvular thickening or vegetations on echocardiogram, and negative blood cultures. Targeted next generation sequencing (NGS) information was interrogated using the PROACTIVE database.

RESULTS

100 patient records were reviewed and of these 41 patients were determined to have likely NBTE based on the above criteria. 12 patients had recurrent strokes despite anticoagulation, two of whom had two recurrent strokes despite different anticoagulation strategies (4 strokes through therapeutic dose LMWH, 4 through rivaroxaban, 3 through apixaban, 1 through fondaparinux). The most common primary malignancies were non-small cell lung cancer (n=14) and pancreatic cancer (n=11). NGS data was available for 13 patients, and the most common mutations were KRAS (n=8), TP53 (n=7), EGFR (n=4), and BRAF (n=2)

CONCLUSIONS

NBTE is an important stroke mechanism in cancer, and the optimal secondary prevention strategy is unknown. These results confirm that NBTE is common in NSCLC and pancreatic cancer. These cancer types commonly harbor mutations such as KRAS, TP53 and EGFR, and work is ongoing to clarify how such mutations might contribute to hypercoagulability. Recurrent stroke is possible with all anticoagulation strategies. Further analysis of outcomes, serum biomarkers (ex. D-dimer), and comorbid medical diagnoses known to confer increased cardiovascular risk is underway.
NCMP-21. REVERSIBLE MOTOR NEURON SYNDROME IN THE SETTING OF CANCER
Authors: Primdahl Ditte , Beinlich Brad , Albertson Megan
Published: December 2020

60 year old female was admitted with difficulty swallowing, slurred speech and gait instability resulting in multiple falls worsening over 2-3 weeks. Her exam revealed subtle spastic dysarthric speech, spasticity in all four extremities (lower > upper and right > left), hyperreflexia, and bilateral Babinksi and Hoffman signs consistent with pure upper motor neuron syndrome. An MRI brain and total spine were without evidence of neurological pathology but revealed an incidental finding of lymphadenopathy concerning for neoplastic process. Her symptoms continued to worsen over the next few weeks and she developed severe, nearly continuous, extensor spasms of BLE (right > left) with stimulus sensitivity causing inability to walk. She was started on baclofen, tizanidine and diazepam for spasticity with only mild improvement. An MRI cervical spine was repeated (please see below) and revealed hyperintense T2 signal in lateral corticospinal tract (right > left) without enhancement and no cord compression. Given strong clinical concern for paraneoplastic process patient received 0.4 g/kg IVIG for 5 days and concurrent 1000 mg methylprednisolone for 3 days with dramatic improvement within days. Cervical lymph node biopsy lead to diagnosis of nodal marginal zone lymphoma. A CT abdomen revealed an ovarian mass concerning for teratoma vs dermoid cyst (pending resection and final pathology). She was treated with weekly boosters of IVIG and IV methylprednisolone and was started on Rituximab for her Lymphoma. When seen in clinic a month post discharge nearly all of her symptoms had resolved. Neurological exam showed subtle residual spasticity making this presentation most consistent with a reversible pure upper motor neuron syndrome.
NCOG-02. PROGNOSTIC VALIDATION OF THE EANO ESMO CLASSIFICATION OF LEPTOMENINGEAL METASTASIS
Authors: Le Rhun Emilie , Devos Patrick , Weller Johannes , Seystahl Katharina , Mo Francesca , Compter Annette , Berghoff Anna Sophie , Jongen Joost , Wolpert Fabian , Rudà Roberta , Brandsma Dieta , Preusser Matthias , van den Bent Martin , Herrlinger Ulrich , Weller Michael
Published: December 2020

BACKGROUND

The EANO ESMO guidelines have proposed a classification of leptomeningeal metastases (LM) based on clinical (typical/atypical), cytological (positive/negative/equivocal) and MRI (A linear, B nodular, C linear and nodular, D normal or hydrocephalus only) presentation. Type I LM is defined by the presence of tumor cells in the cerebrospinal fluid (CSF) (confirmed LM) whereas type II LM is defined by typical clinical and MRI signs (probable or possible LM). Here we explored the clinical utility of these EANO ESMO LM subtypes for choice of treatment and outcome.

PATIENTS AND METHODS

We retrospectively assembled data from 254 patients with newly diagnosed LM from different solid tumors, including as main primary tumors breast cancer (n=98, 45%), lung cancer (n=65, 25.5%) and melanoma (n=51, 13.5%). Survival curves were estimated using the Kaplan-Meier method and compared by Log-rank test.

RESULTS

Median age at LM diagnosis was 56.5 years (range 20-82 years). Typical clinical LM symptoms or signs were noted in 225 patients (88.5%); only 13 patients (5%) were clinically asymptomatic. The most common MRI subtype was A seen in 117 patients (46%). Types B (n=33, 13%), C (n=54, 21%) and D (n=50, 19.5%) were less common. Tumor cells in the CSF were observed in 186 patients (73%) whereas the CSF was equivocal in 24 (9.5%) and negative in 44 (17.5%) patients. Patients with confirmed LM had inferior outcome than patients with probable or possible LM (p=0.0063). Type I patients had inferior outcome than type II patients (p=0.0019). Nodular disease was a negative prognostic factor in type II LM, but not in type I LM (p=0.0138).

CONCLUSION

The EANO ESMO LM subtypes are highly prognostic and should be considered for stratification and overall design of clinical trials.
NCOG-07. FEATURES OF EPILEPTOGENIC BRAIN METASTASES AND THEIR TREATMENT
Authors: Musgrave Nicholas , Huntoon Kristin , Wang Joshua , Hardesty Douglas , Prevedello Daniel , Lonser Russell , Elder Bradley
Published: December 2020

Patients with brain metastases (BM) may experience seizures at diagnosis or during their treatment. Seizures are associated with decreased overall survival (OS) and poorer quality of life. Therapeutic options may include surgical resection of epileptogenic BM. This study evaluated features of epileptogenic BM and whether surgical resection of these tumors improved seizure control and OS. A retrospective single-center review between 2006-2016 identified 1581 patients with BM. Data analyzed included demographics, primary cancer, systemic treatments, radiographic features of BM, BM treatment modalities, anti-epileptic drugs (AEDs), and seizure characteristics before and after intervention for BM. Chi-squared tests were used for categorical variables. Kaplan-Meier curves and Breslow values were used to assess OS following seizure. Of 1581 patients with BM, 136 (9%) experienced one or more seizures. Seizure was the presenting symptom of BM in 74 (54.4%) patients. Melanoma metastases were most epileptogenic, causing seizure in 38 of 216 (17.6%) patients (p< 0.001). Frontal lobe metastases were most common in patients with seizures (100, 73.5% p=0.033). After median follow-up of 23 months, 48 of 80 (60%) surgical patients were seizure free compared with 27 of 56 (48.2%) non-surgical patients. OS from first seizure was improved in surgical patients versus non-surgical patients (735±133 vs 447±74 days, p=0.043). Frontal lobe tumor resection (n=61) conferred improved survival compared with non-frontal lobe tumor resections (n=19) (698±323 vs 344±132 days, p=0.044). Variables such as demographics, number of BM, tumor histology, and dose of AED were not significantly different between surgical and non-surgical groups. Seizures due to BM cause significant morbidity and mortality. Frontal lobe location and melanoma histology increase seizure risk. Resection of BM was associated with improved seizure control and prolonged OS from the time of first seizure. Further studies should delineate the impact of surgery and determine if a specific constellation of variables warrants prophylactic AEDs.
NCOG-09. EFFICACY OF HER2-TARGETED ANTIBODY THERAPY IN HER2-POSITIVE BREAST CANCER BRAIN METASTASES: A NATIONAL ANALYSIS
Authors: Hulsbergen Alexander , Broekman Marike , Smith Timothy , Aizer Ayal A , Iorgulescu Bryan
Published: December 2020

BACKGROUND

Breast cancer brain metastases (BCBM) commonly develop in human epidermal growth factor 2-positive (HER2+) breast cancer, but BCBM patients are underrepresented in clinical trials, leading to a lack of knowledge on the efficacy of HER2-targeted therapy in this population.

METHODS

We analyzed clinical characteristics and outcomes of HER2+BCBM patients from the National Cancer Database 2010–2016, comprising 70% of newly-diagnosed cancers in the U.S, to assess overall survival (OS) associated with HER2-targeted monoclonal antibody therapy (HER2-mab; i.e. trastuzumab, pertuzumab, and trastuzumab emtansine; encoded as of 2013). Survival was estimated with Kaplan-Meier techniques and compared with landmark analysis and Cox regression. The landmark timepoint was selected at which 75% of HER2-mab patients received HER2-mab, which was within 58 days of diagnosis.

RESULTS

1,059 HER2+BCBM patients were identified, 717 (67.7%) patients were estrogen receptor negative (ER-) and 342 (32.3%) were ER+. Median follow-up was 12.0 months, at the end of which 73.8% of patients were deceased. Median OS was 12.2 and 22.1 months for ER- and ER+ patients, respectively. Following FDA approvals of pertuzumab (2012) and ado-trastuzumab emtansine (2013), HER2-mab usage for HER2+BCBM patients rose from 53.6% in 2013 to 71.7% in 2016. 420 BCBM patients had complete data for landmark analyses: 70.0% (n=294) received HER2-mab and 30.0% (n=126) did not, in which HER2-mab was associated with significantly improved OS in both ER- (median 22.2 months, 95%CI: 18.2-25.4; vs. 9.5 mos, 95%CI: 6.3-10.7; p=0.0001) and ER+ (median 25.7 months, 95%CI: 21.4-not reached; vs. 19.6 months, 95%CI: 11.1-35.2; p=0.02) patients. In multivariable Cox landmark analysis adjusted for ER status, age at diagnosis, extracranial disease, chemotherapy, radiotherapy, and metastasectomy; HER2-mab demonstrated significantly improved OS (hazard ratio 0.59 vs. no HER2-mab, 95%CI: 0.44-0.77; p< 0.001).

CONCLUSIONS

In this large national study, HER2-mab was associated with substantially improved overall survival in HER2+ BCBM patients.
NCOG-12. STEREOTACTIC RADIOSURGERY FOR VESTIBULAR SCHWANNOMAS IN NEUROFIBROMATOSIS TYPE 2 PATIENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Tosi Umberto , Maayan Omri , An Anjile , Lavieri Miguel , Guadix Sergio , DeRosa Antonio , Christos Paul , Pannullo Susan , Stieg Philip , Brandmaier Andrew , Knisely Jonathan , Ramakrishna Rohan
Published: December 2020

BACKGROUND

One of the hallmarks of neurofibromatosis type 2 (NF2) is the presence of bilateral vestibular schwannomas (VSs) that result in progressive hearing loss and compression of nearby brainstem structures causing cranial nerve palsies. Treatment of these tumors remains challenging, as both surgical removal and expectant management can result in symptom progression. Stereotactic radiosurgery (SRS) has recently been investigated for the management of NF2-associated VSs; however, the role, promises, and pitfalls of this treatment modality remain unclear.

METHODS

Ovid MEDLINE, EMBASE, Web of Science, and Cochrane Reviews were searched for studies assessing SRS outcome in NF2-associated VSs only. Primary endpoints included tumor control, serviceable hearing, presence of tinnitus, and cranial nerve V and VII symptoms.

RESULTS

A total of 16 studies (589 patients harboring 750 tumors) was included in this analysis. Clinical tumor control was achieved in 88% of cases (95% CI: 80%-95%); salvage surgery was needed in 8% (95% CI: 4%-13%) of cases. Treatment resulted in a worsening of pre-treatment serviceable hearing (OR of 0.26, p < 0.01), in an increase of facial nerve impairment (OR of 1.62, p < 0.01), and showed a trend for increase trigeminal nerve impairment as well (OR of 1.42, p = 0.07). The incidence of vestibular symptoms and hydrocephalus requiring shunting could not be assessed since these measures were not reported consistently.

CONCLUSIONS

The treatment of NF2-associated VS continues to pose a challenge, as current SRS regimens result in impaired hearing and worse cranial nerve comorbidities, despite achieving high tumor control. It remains unclear if these findings have to be intended as treatment complications or, rather, continuous disease progression despite tumor control.
NCOG-13. THE IMPACT OF CME ON THE KNOWLEDGE OF NEUROFIBROMATOSIS TYPE 1-RELATED TUMORS
Authors: Worst Michelle , Parikh Kinjal , Caracio Rich , Fagerlie Sara
Published: December 2020

BACKGROUND

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic condition characterized by a wide spectrum of clinical findings. Patients with NF1 develop benign and malignant tumors along the nerves of the skin, brain, and other body parts. Due to the unique presentation of each patient, clinicians are challenged to stay current with emerging data and how best to integrate new agents into multidisciplinary treatment paradigms. The objective of this study was to assess changes in neurologists’ and pediatricians’ knowledge and confidence through participation in education regarding NF1 treatment.

METHODS

The educational activity consisted of a 30-minute online enduring, 1 faculty, chapterized summary of a live symposium. Educational effect was assessed with a repeated pairs pre-/post-assessment study with a 3-item, multiple choice, knowledge questionnaire and one confidence assessment question. For all questions, each participant served as his/her own control. Pre- and post-assessment scores were compared to determine relative changes in the proportion of correct responses. A chi-square test assessed statistical significance at the P < 0.05 level. The activity launched 23rd December 2019; data were collected until 2nd April 2020.

RESULTS

Overall, statistically significant improvements were seen after education for neurologists (N=171, P < 0.05) and pediatricians (N=260, P < 0.01). The relative improvement in correct answers was 26% for neurologists and 48% for pediatricians (percent of total correct responses pre-/post-assessment were 27%/34% and 23%/34%, respectively). Following the activity, 16% of neurologists and 22% of pediatricians had a measurable increase in confidence regarding their understanding of multidisciplinary management of NF1.

CONCLUSIONS

Participation in an online, 30-minute enduring CME intervention resulted in statistically significant improvements in knowledge and confidence of neurologists and pediatricians, that result in improvements in clinical care. Continued educational activities are paramount to address residual gaps and further increase clinicians’ confidence in this clinical setting.
NCOG-24. WAKE FOREST NCORP RESEARCH BASE FEASIBILITY STUDY OF RAMIPRIL FOR PREVENTING COGNITIVE DECLINE IN GLIOBLASTOMA PATIENTS RECEIVING BRAIN RADIOTHERAPY (WF-1801)
Authors: Cramer Christina , Page Brandi , Wefel Jeffrey S , Dressler Emily , Ip Edward , Rapp Steve , Shaw Edward , Weaver Kathryn , Lesser Glenn , Chan Michael
Published: December 2020

INTRODUCTION

Chronic neuro-inflammation after brain radiotherapy (RT) contributes to radiation-induced cognitive decline (RICD). The renin angiotensin system (RAS) may mediate this inflammatory cascade after RT. Ramipril is an angiotensin-converting enzyme inhibitor used to treat hypertension and has good blood-brain barrier penetration. By blocking RAS activation, ramipril reduces neuro-inflammation and preclinical data show that ramipril administration during RT can prevent RICD.

METHODS

WF-1801 is an ongoing feasibility study that will enroll a total of 75 patients. Patients ≥ 18 with newly diagnosed and pathologically confirmed GBM who will receive chemoradiation are eligible. All participants take ramipril daily during RT and for 4 months thereafter. Ramipril is titrated from 1.25mg to 5mg daily over 3 weeks. A cognitive battery that includes the Hopkins Verbal Learning Test-Revised (HVLT-R), Trail Making Test (TMT), and Controlled Oral Word Association test (COWA) is administered at baseline, end of RT, and 1-month and 4-months post-RT. The co-primary endpoints are retention rate (with retention defined as compliance with > 75% of drug therapy doses) and neurocognitive function at 1-month post-RT. To estimate the effect of ramipril on cognitive function, performance on the cognitive battery will be compared to a historical control (cognitive data from the control arm of RTOG 0825). ApoE genotyping is being performed as a correlative study.

RESULTS

31 of a planned 75 participants have been enrolled over 14 months. 20 of 31 (64.5%) are male. 21 (67.7%) are between the age of 40-64. 20 (95.6%) are white and 29 (93.6%) are not Hispanic or Latino.

CONCLUSION

Despite a pause in accrual due to COVID-19, we are easily meeting planned accrual goals. Community oncology-based clinical trials of interventions to prevent cognitive toxicity appear to be feasible. GBM patients seem eager to enroll in studies seeking to prevent cognitive decline. Supported by NCI grant UG1CA189824.
NCOG-26. IMPACT OF GENDER ON TUMOR TREATING FIELDS COMPLIANCE IN PATIENTS WITH GLIOBLASTOMA
Authors: Karpf Lauren , Chawla Sanjeev , Desiderio Lisa , Mohan Suyash
Published: December 2020

BACKGROUND

Tumor treating fields (TTFields) has emerged as a novel antimitotic modality to treat glioblastoma (GBM). Recently, a positive association was reported between TTFields dose at the tumor bed and survival outcomes in GBM patients. Dose density depends upon power density and compliance rate (cumulative amount of time TTFields therapy is delivered to the patient). Increased compliance with TTFields has been proposed as an independent prognostic factor for improved clinical benefits. There is evidence that females tend to respond better than males to standard therapy. However, the impact of gender and age on TTFields compliance is not fully understood in GBM patients.

OBJECTIVE

To investigate potential interactions amongst age, gender and TTFields compliance in GBM patients.

METHODS

A cohort of 16 patients (males =9; females=7; mean-age=60.8±7.6years) with newly diagnosed and recurrent GBM receiving TTFields were analyzed retrospectively. Device usage time was collected from internal log files in each case. The mean duration of TTFields therapy in patients was 4 months. Chi-square and independent sample T-tests were performed to evaluate differences in compliance rates based on patient age and gender and to examine gender-age relationships. Additionally, Pearson correlation analyses were performed to determine associations between gender and compliance rates. The probability (p) value of 0.05 was considered significant.

RESULTS

A trend (p=0.067) towards greater TTFields compliance was observed in females (80.1±0.11%) versus males (63.0±0.22%). Additionally, there was a strong positive correlation (R=0.73; p=0.058) between age and compliance rates for female patients. There were 6 patients ≥ 65 years and 10 patients < 65 years. However, we did not find significant differences in compliance rate and gender variables between patients ≥ 65 years and < 65 years of age.

CONCLUSIONS

Our results demonstrate gender influences TTFields compliance amongst GBM patients. However, future studies with larger cohorts are warranted to validate these findings.
NCOG-27. INCREASED OVERALL SURVIVAL AMONG RACIAL MINORITIES AND SUBOPTIMAL USE OF STANDARD OF CARE TREATMENT IN GLIOBLASTOMA MULTIFORME
Authors: Boisclair Stephanie , Samuels Shenae , Khunger Arjun , Wietecha Delia A , Cohen Alejandro Lopez , King Kelly , Sareli Candice , Jacques Jessica , Salzberg Mathew , Vulfovich Michel , Hunis Brian , Raez Luis E , Hussein Atif M
Published: December 2020

Glioblastoma Multiforme (GBM) is the most common primary central nervous system (CNS) tumor and is always considered grade IV given its aggressive nature and poor overall survival (OS). Despite advancements in surgical techniques and cancer therapies, GBM treatment has remained the same since 2005: total resection followed by temozolomide and radiation. We hypothesized that OS has increased over the years and is similar among all races/ethnic groups without reduction of mortality based upon treatment facility. METHODS: The National Cancer Database from 2004-2016 was utilized to obtain demographic, tumor and treatment factors of GBM (excluding gliosarcomas). Multivariate Weibull regression model was used to evaluate prognostic factors for OS in months(m). RESULTS: A total of 119,496 patients were identified. There was a significant difference(P=0.000) in OS for patients diagnosed in 2012-2016 (10.2m) compared to 2008-2011 (9.2m) and 2004-2007 (8.1m). Among racial groups, the highest incidence was among whites (91.8%) whom also had the lowest OS (9.0m), followed by Blacks (10.5m), Hispanics (11.7m) and Asians (12.9m)(P=0.000). Patients with unilateral tumors (72.1%) and tumor size < 3cm (18.3%) had an increased OS (9.8m-10.2m and 11.2m, respectively) compared with patients having bilateral tumors or larger size ≥ 3cm (OS of 4.8m and 8.9m, respectively)(P=0.000). Increasing age (HR=1.03) and comorbidity score ≥ 3 (HR=1.40) were independent predictors of death (P=0.000), while female sex (HR=0.88), Asian ethnicity (HR=0.75) and treatment at an academic/research facility (HR=0.86) were independent predictors of survival(P< 0.01). Only 60.1% of patients (n=59,112) received ideal treatment (surgery, chemotherapy and radiation), while only 3.2% of all GBM patients received palliative care. DISCUSSION: Decreased OS was found among white race, large and bilateral tumors. Despite a statistically significant, although minimal, increase in OS since 2004-2007, there is notable underutilization of ideal treatment and palliative care. Further studies should focus on access inequalities and limitations to treatment.
NCOG-28. SURGERY FOR RECURRENT GBM IMPROVES SURVIVAL INDEPENDENT OF PROGNOSTIC FACTORS
Authors: Voisin Mathew , Zadeh Gelareh
Published: December 2020

BACKGROUND

The survival benefit of surgery for recurrent GBM in the current literature is variable, and often attributed to improvements in surgical technique over time. Studies examining outcomes over prolonged periods are lacking. The primary objective of our study was to determine if surgery for recurrent GBM confers a survival benefit compared to patients not undergoing repeat surgery. The secondary objective of our study was to investigate the effect of known prognostic factors on survival for patients undergoing repeat surgery for GBM.

METHODS

We analyzed our brain tumour biobank database from 1992 to 2018 for all adult patients that underwent repeat surgery for primary recurrent GBM. This cohort was compared to publicly available data from The Cancer Genome Atlas (TCGA). Survival and prognostic factors were compared within and between groups using Kaplan-Meier survival curves and Cox proportional hazards models.

RESULTS

A total of 676 patients were included (surgery cohort = 91, non-surgery cohort = 585). The surgery group had a lower age at diagnosis (50.6 vs 58.2 years old, p = < 0.001) and higher Karnofsky Performance Status (KPS) (81.4 vs 77.5, p = 0.002) at diagnosis than the non-surgery group. Other known prognostic factors including IDH status and MGMT methylation status were balanced between groups. Overall median survival was higher in the surgery group than the non-surgery group (30.6 months vs 13.9 months, p = < 0.0001). Within the surgery group, prognostic factors including age, sex, KPS, IDH status, MGMT status, extent of resection by surgeon, tumour location, and time to recurrence were not associated with additional survival benefit.

CONCLUSIONS

Patients that undergo surgery for recurrent GBM are of younger age and lower KPS at time of initial diagnosis. In patients that undergo repeat surgery, known patient and tumour prognostic factors are not associated with additional survival benefit.
NCOG-30. ADJUVANT VERSUS SALVAGE MANAGEMENT FOR IDH-MUTANT LOW GRADE GLIOMA
Authors: Tom Martin , Park Deborah , Tewari Surabhi , Wei Wei , Chao Samuel , Yu Jennifer , Suh John , Ahluwalia Manmeet , Peereboom David , Stevens Glen , Fallah Jaleh , Prayson Richard , Barnett Gene , Angelov Lilyana , Mohammadi Alireza , Murphy Erin
Published: December 2020

PURPOSE

Timing of postoperative treatment in low-grade glioma (LGG) remains controversial. We sought to evaluate outcomes between adjuvant versus salvage management among patients with IDH-mutant molecularly-defined LGG.

METHODS

We analyzed a single-institutional database of adults diagnosed with LGG (grade II) with an IDH-mutation and either 1p19q-codeletion (oligodendroglioma) or 1p19q-intact (astrocytoma). Cox multivariable analysis (MVA) accounting for age, sex, and extent-of-resection, was used to compare adjuvant versus salvage approaches on overall survival (OS), progression free survival (PFS), next-intervention free survival (NIFS, defined as intervention subsequent to either adjuvant or salvage treatment), and malignant-transformation free survival (MTFS). Adjuvant treatment was defined as immediate postoperative treatment with radiotherapy (RT) and/or temozolomide (TMZ) prior to progression. Salvage management was defined as postoperative observation followed by surgery or RT and/or TMZ at progression.

RESULTS

Of 162 patients with oligodendroglioma, median follow-up was 8.5 years (range, 0.03-25.7). Adjuvant treatment was given to 97 (59.9%) patients, with 65 (40.1%) undergoing a salvage approach. On MVA, adjuvant treatment was not associated with OS, PFS, NIFS, or MTFS (p > 0.05 each). Among 82 patients with astrocytoma, median follow-up was 6.1 years (range, 0.5–25.7), and adjuvant treatment was administered to 41 (50.0%) patients, while 41 (50.0%) received salvage management. On MVA, adjuvant treatment was associated with improved PFS (HR 0.42, 95% CI 0.24-0.73, p < 0.001) and NIFS (HR 0.35, 95% CI 0.18–0.65, p < 0.001), but was not associated with OS or MTFS (p > 0.05 each).

CONCLUSIONS

Among grade II, IDH-mutant oligodendrogliomas, initial postoperative observation followed by salvage treatment at progression may be appropriate, as immediate adjuvant therapy was not associated improved outcomes. However, a more individualized postoperative management approach is required for grade II, IDH-mutant astrocytomas, as adjuvant treatment was associated with improved PFS and NIFS, but not OS. Further validation and prospective studies are required.
NCOG-31. DEVELOPMENT AND EVALUATION OF PROGNOSTIC MODELS TO PREDICT SURVIVAL OF PATIENTS WITH GLIOBLASTOMA MULTIFORME
Authors: Lin John , Mai Michelle , Paracha Saba
Published: December 2020

Glioblastoma multiforme (GBM), the most common form of glioma, is a malignant tumor with a high risk of mortality. By providing accurate survival estimates, prognostic models have been identified as promising tools in clinical decision support. In this study, we produced and validated two machine learning-based models to predict survival time for GBM patients. Publicly available clinical and genomic data from The Cancer Genome Atlas (TCGA) and Broad Institute GDAC Firehouse were obtained through cBioPortal. Random forest and multivariate regression models were created to predict survival. Predictive accuracy was assessed and compared through mean absolute error (MAE) and root mean square error (RMSE) calculations. 619 GBM patients were included in the dataset. There were 381 (62.9%) cases of recurrence/progression and 53 (8.7%) cases of disease-free survival. The MAE and RMSE values were 0.553 and 0.887 years respectively for the random forest regression model, and they were 1.756 and 2.451 years respectively for the multivariate regression model. Both models accurately predicted overall survival. Comparison of models through MAE, RMSE, and visual analysis produced higher accuracy values for random forest than multivariate linear regression. Further investigation on feature selection and model optimization may improve predictive power. These findings suggest that using machine learning in GBM prognostic modeling will improve clinical decision support. *Co-first authors.
NCOG-32. THE SAFETY AND EFFICACY OF DEXAMETHASONE IN THE MANAGEMENT OF GLIOMA PATIENTS
Authors: Medikonda Ravi , Patel Kisha , Saleh Laura , Srivastava Siddhartha , Jackson Christina , Mohan Aditya , Weingart Jon , Bettegowda Chetan , Gallia Gary , Brem Henry , Lim Michael
Published: December 2020

Dexamethasone is routinely administered to glioma patients for the management of cerebral edema. Dexamethasone is associated with significant side effects including hyperglycemia, increased risk of infection, and impaired anti-tumor immune response. Despite these risks, there are no standardized guidelines for the effective use of dexamethasone in managing glioma. In this single-institution retrospective cohort study, we evaluate the effect of dexamethasone in glioma patients undergoing surgical resection on post-operative complications and overall survival. 436 patients met the inclusion criteria for this study. 46% of patients received pre-operative dexamethasone, and 90% of patients received post-operative dexamethasone. Pre-operative dexamethasone usage did not significantly affect the immediate post-operative T2 flair volume (p=0.53), however it was associated with a higher incidence of post-operative wound infection (4.0% vs 0%, p=0.002) and post-operative hyperglycemia ((p=0.02). Administration of dexamethasone in the post-operative setting did not affect the incidence of post-operative wound infection (p = 0.38) or hyperglycemia (p=0.18). It also did not affect the 3-month T2 flair volume (p=0.87). On cox proportional hazards analysis, pre-operative dexamethasone was associated with a greater hazard of death (HR=1.48; p=0.01), and post-operative dexamethasone was associated with a lower hazard of death (HR=0.20; p=0.04) after adjusting for several possible confounders. Our findings demonstrate significant differences in the safety and efficacy of pre-operative and post-operative dexamethasone in glioma patients. Routine use of pre-operative dexamethasone appears to increase the risk of post-operative complications and negatively impact survival, whereas post-operative dexamethasone improves survival and was not associated with a higher risk of steroid-related post-operative complications. These findings reaffirm a role for dexamethasone in managing cerebral edema in glioma patients, but also highlight the potential for serious negative consequences with dexamethasone use. This study provides a rationale for re-evaluating the role of dexamethasone, particularly in the pre-operative period.
NCOG-34. AN ASSESSMENT OF OVERALL SURVIVAL AND PALLIATIVE CARE USE AMONG PATIENTS WITH GLIOSARCOMA DIAGNOSED OVER A TWELVE-YEAR SPAN
Authors: Boisclair Stephanie , Samuels Shenae , Raez Luis E , Wietecha Delia A , Cohen Alejandro Lopez , Khunger Arjun , King Kelly , Sareli Candice , Adames Jorges , Jacques Jessica , Salzberg Mathew , Hunis Brian , Vulfovich Michel , Hussein Atif M
Published: December 2020

Gliosarcoma (GS), a rare variant of glioblastoma, accounts for less than 5% of CNS tumors. Due to its low incidence and prevalence, very few comprehensive, large-scale studies are reported in the literature that describe prognostic elements and treatment outcomes. The objective of the study was to examine patient and treatment characteristics to identify significant predictors of survival. METHODS: Data on patients with GS, diagnosed between 2004-2016, was extracted from the National Cancer Database (NCDB). Univariate analysis and a multivariate Weibull regression model was used to determine prognostic factors of survival (months). Kaplan-Meier (KM) method with log-rank test was used to compare and estimate overall survival rates between various groups. RESULTS: There was a total of 2,656 GS patients identified in the NCDB between the years of 2004-2016 with median age of 62 years old. In multivariable Weibull regression model, increasing age (HR=1.04, p=0.000) and increasing comorbidities were independent predictors of increased hazard of death. Having 3 or more comorbidities had the strongest association with increased hazard of death (HR=1.44; P=0.001). The OS has minimally improved over the period of 2004-2016; median OS was highest among those diagnosed between 2012 and 2016 at 11.4 months followed by an OS of 10.6 months between 2004 and 2007, and 9.1 months between 2008 and 2011 (P=0.001). Although current clinical guidelines recommend chemotherapy and radiation within 30 days of surgery, there was no statistically significant difference in median OS between patients who had chemotherapy initiated within 30 days, between 30 and 60 days or later than 60 days (P=0.109). There is also no statistically significant difference in OS for time of radiation initiation categories (P=0.752). In a disease with such low OS and limited treatment options, palliative care use was found in only 45 (1.7%) patients.
NCOG-38. CLINICAL CHARACTERISTICS OF LOW GRADE GLIOMA PATIENTS WITH NON-CANONICAL IDH1 AND IDH2 MUTATIONS
Authors: Peters Katherine , Lipp Eric , Broadwater Gloria , Herndon James , Johnson Margaret , Randazzo Dina , Desjardins Annick , Friedman Henry , Ashley David , Affronti Mary
Published: December 2020

BACKGROUND

Low grade gliomas (LGGs) develop in young adults and represent 10-15% of all glial tumors. While LGG patients can have longer survival than higher grade tumors, progression, transformation, and ultimately mortality occurs. Mutations in Isocitrate dehydrogenase 1/2 (IDH1/IDH2) are prevalent in LGG and are responsible for gliomagenesis. The classic IDH1 mutation is located at 132 codon and represented as p.Arg132His, but there are non-canonical IDH1 and IDH2 mutations. We sought to compare clinical characteristics of LGG patients with classic IDH1 p.Arg132His mutation to LGG patients with non-canonical IDH1 and IDH2 mutations.

METHODS

We queried an IRB-approved registry retrospectively from 12/2004- 9/2019. We included IDH1/IDH2 mutant LGG (WHO grade II) and known IDH1 and IDH2 targeted mutation analysis using standard PCR followed by DNA sequencing to detect point mutations in IDH1/IDH2 genes. We obtained available clinical and histopathological data. We estimated progression-free survival (PFS), time to transformation (TT), and overall survival (OS) using Kaplan-Meier methods.

RESULTS

We identified 267 LGG patients with median follow-up of 9.1 yrs (95%CI 8.4-9.9 yrs). Classic IDH1 p.Arg132His mutation occurred in 223 (83.9%) patients. IDH2 mutations occurred in 14 (5.2%) patients. Non-canonical IDH1 mutations were in 30 (11.2%) patients and included the following mutations: p.Arg132Cys (13), p.Arg132Gly (10), p.Arg132Ser (4), p.Arg132Leu (1), p.Arg119Gln (1), and p.Arg172Met (1). Initial presentation, OS, and TT did not differ between IDH1/IDH2 groups. PFS differed significantly between groups with improved median PFS in IDH2 mutant LGG (5.4 yrs; 95%CI 3.5-25.2) versus classic IDH1 mutant LGG (4.1 yrs; 95%CI 3.7-4.9 yrs) and non-canonical IDH1 mutant LGG (2.6 yrs; 95%CI 2.1-4.8) (log-rank p=0.019). Notably, non-canonical mutations were more common in astrocytoma (22/30; 73.3%) than other LGG histologies (p=0.018).

CONCLUSIONS

In this cohort, LGG patients with non-canonical mutations have a shorter time to progression than patients with classic p.Arg132His mutation and IDH2 mutations.
NCOG-40. IMPLEMENTING RANO CRITERIA IN A RESOURCE-LIMITED SETTING AND ITS ASSOCIATION WITH OVERALL SURVIVAL OF GLIOMA PATIENTS: EXPERIENCE FROM A NATIONAL CANCER CENTER IN INDONESIA
Authors: Ghazali Malueka Rusdy , Sofyan Henry , Aninditha Tiara , Andriani Rini
Published: December 2020

INTRODUCTION

Gliomas are one of the most common central nervous system tumors in adults. The Response Assessment Criteria in Neuro-Oncology (RANO) was developed to standardize the radiographic parameters used to assess therapeutic outcomes in glioma patients. A previous study has shown an association between therapeutic response based on RANO criteria and overall survival in glioma patients. However, the feasibility of applying RANO criteria in settings with limited resources has never been reported. This study aims to assess the feasibility of applying RANO criteria in clinical settings in Indonesia. This study also wants to see the role of the RANO criteria as a prognostic factor for gliomas in Indonesia.

METHOD

Data of glioma patients were retrospectively collected from Dharmais Cancer Hospital in Jakarta, Indonesia. Dharmais Cancer Hospital is the highest referral hospital for brain tumors in the country. Clinical and demographic data were collected from the medical record.

RESULTS

From 138 identified glioma patients from 2017 to May 2020, only 34 patients can be assessed using RANO criteria. The majority of the patients do not have post-surgical MRI that can be used as a baseline. Among 34 included patients, 38.2% were categorized as responsive, 23.5% as stable disease and 38.2% were categorized as progressive. Kaplan-Meier analysis showed that the median overall survival in the progressive group is significantly shorter than the median survival of responsive/stable group (21.2 vs. 57.5 months respectively, p=0.001). Multivariate cox regression analysis was performed to see the association of RANO criteria and other confounding variables (sex, age, glioma grade, glioma location, and therapy) with overall survival. The result showed that RANO progression was significantly associated with decreased survival (HR 18.38, p=0.045).

CONCLUSION

This retrospective analysis demonstrates the feasibility of applying RANO criteria in Indonesia and its association with overall survival.
NCOG-41. FUNCTIONAL OUTCOME FOLLOWING NON-DOMINANT HEMISPHERIC GLIOMA SURGERY FROM THE ASPECT OF INDEPENDENCE LEVEL, COGNITIVE FUNCTION AND RETURN TO SOCIAL LIVES
Authors: Nakajima Riho , Kinoshita Masashi , Okita Hirokazu , Nakada Mitsutoshi
Published: December 2020

BACKGROUND

Functional outcome has been paid much attention in surgery for eloquent area or dominant hemisphere. Little is known about functional outcome following surgery for non-dominant hemispheric gliomas, although some resent reports revealed the importance of right cerebral hemisphere on glioma surgery. Here, we investigated functional outcome of right cerebral hemispheric gliomas from the aspect of independence level, cognitive function, and return to social lives.

METHODS

Totally 82 patients with right cerebral hemispheric gliomas who underwent surgery for resection in Kanazawa university hospital were studied. Patients were divided into two groups, WHO grade II/III and IV. Karnofsky Performance Status (KPS), Mini-mental state examination (MMSE), and whether or not to return to work at pre-operation and chronic phase were evaluated. To reveal responsible region for decline of each index, the voxel-based lesion symptom (VLSM) analyses were performed.

RESULTS

MMSE; no difference was found through postoperative course in grade II/III, whereas postoperative score of grade IV was declined significantly compared with pre-operation (25.1 and 21.9 point; p=0.048). KPS; preoperative independence level was maintained until chronic phase in grade II/III (94.7 and 89.5). While, in grade IV, postoperative KPS was declined significantly than that of pre-operation (82.0 and 70.0, p=0.007). Results of the VLSM analysis revealed that patients who resected temporo-parietal junction in grade IV showed significantly low KPS score. Return to social lives; Reintegration ratio of working population was 71% and 35% for grade II/III and IV, respectively. Of these, as for grade II/III gliomas, the cingulate cortex and medial orbito-frontal cortex relate to return to social lives.

CONCLUSIONS

Functional outcome following surgery depends on tumor grade and resected region in right cerebral hemispheric gliomas.
NCOG-44. NEUROLOGIC ASSESSMENT IN NEURO-ONCOLOGY (NANO) SCALE IN A PHASE II STUDY OF PEMBROLIZUMAB OR PEMBROLIZUMAB PLUS BEVACIZUMAB IN PATIENTS WITH RECURRENT GLIOBLASTOMA
Authors: Nayak Lakshmi , Molinaro Annette , Peters Katherine , Clarke Jennifer , Jordan Justin , de Groot John , Nghiemphu Phioanh , Kaley Thomas , Colman Howard , McCluskey Christine , Gaffey Sarah , Smith Timothy , Cote David , Severgnini Mariano , Yearley Jennifer , Zhao Qing , Blumenschein Wendy , Duda Gabriel , Muzikansky Alona , Jain Rakesh , Wen Patrick , Reardon David
Published: December 2020

PURPOSE

The neurologic assessment in neuro-oncology (NANO) scale was developed as a standardized metric to objectively measure neurologic function in brain tumor patients to complement radiographic assessment in defining overall outcome. A multicenter, phase 2 study of pembrolizumab with or without bevacizumab in patients with recurrent glioblastoma incorporated the NANO scale as an exploratory endpoint.

METHODS

Neurologic examination was evaluated at baseline and MRI assessments using the NANO scale until patients came off study. Statistical descriptive data analysis was performed using R (version 3.4.3). Correlation analysis utilized Fisher’s exact test.

RESULTS

NANO compliance rate was 94% in 80 patients accrued on the study. Of the 80 patients, 7 were missing NANO at baseline visit and were excluded from analysis for NANO response criteria. Fifteen patients did not have end of treatment NANO evaluation. Of 73 patients, 35 (48%) had a normal neurologic examination at baseline by NANO. Strength and language accounted for the majority of changes in neurologic function over the course of study treatment. Eighteen patients (25%) had neurologic progression by NANO, of whom 2 did not have concurrent radiographic progression. Three patients (pembrolizumab plus bevacizumab cohort) had a neurologic response associated with stable disease on MRI. NANO assessment prior to initiation of cycle 3 correlated with RANO response (p=0.011), change in KPS (p=0.002) and dexamethasone requirement (p=0.007) while those with NANO progression at this assessment had worse overall survival (291 vs 324 days), but this trend did not achieve statistical significance (p=0.2).

CONCLUSIONS

Evaluation of neurologic function by NANO scale was feasible in a multicenter prospective study in patients with GBM with a high compliance rate. The NANO scale objectively tracked stable neurologic function in most patients throughout the trial period and was associated with a trend for survival.
NCOG-54. SAFETY OF TRANSSPHENOIDAL SURGERY FOR NONFUNCTIONING PITUITARY ADENOMA IN ELDERLY 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

Life expectancy has increased over the past century, shifting the demographic distribution towards older age groups. Elderly patients comprise up to 14% of patients with pituitary tumors, with most lesions being nonfunctioning adenomas (NFPAs). Here, we compare clinical and surgical outcomes and post-operative complications between non-elderly adult (age ≥ 18 years and ≤ 65 years) and elderly (age > 65 years) NFPA patients.

METHODS

Retrospective review of 908 patients undergoing transsphenoidal surgery for NFPA at a single institution from 2007-2019.

RESULTS

Elderly patients represented 32.4% of patients. Both groups were similar in gender (57.3% vs 60.5% male;P=0.4), tumor size (2.56 vs 2.46 cm;P=0.2), and cavernous sinus invasion (35.8% vs 33.7%;P=0.6). Regarding post-operative outcomes, length of stay (1 vs 2 days; P=0.5), extent of resection (59.8% vs 64.8% GTR;P=0.2), CSF leak requiring surgical revision (4.3% vs 1.4%;P=0.06), 30-day readmission (8.1% vs 7.3%;P=0.7), infection (3.1% vs 2.0%;P=0.5), and new hypopituitarism (13.9% vs 12.0%;P=0.3) were similar between both groups. Elderly patients were less likely to have adjuvant radiation (8.7% vs 16.3%;P=0.009), future re-operation (3.8% vs 9.5%;P=0.003), and post-operative diabetes insipidus (DI) (3.7% vs 9.4%;P=0.002), and more likely to have post-operative hyponatremia (26.7% vs 16.4%;P< 0.001) and new cranial nerve deficit (1.9% vs 0.0%;P=0.01). Elderly patients’ post-operative sodium peaked and troughed on POD3 (mean=138.7 mEq/L) and POD9 (mean=130.8 mEq/L), respectively, compared to non-elderly patients (peak POD2 mean=139.9 mEq/L, trough POD8 mean=131.3 mEq/L).

CONCLUSION

Our analysis revealed that elderly patients experienced more post-operative hyponatremia, while non-elderly patients experienced more post-operative DI. Elderly patients also experience later peak and trough in serum sodium, suggesting age-related differences in stalk-related morbidities of NFPA resection. Overall, our results show that transsphenoidal surgery for NFPA in elderly patients is safe with low complication rates. We hope our results will guide discussions with elderly patients regarding possible risks and outcomes.
NCOG-59. PROGRESSION-FREE SURVIVAL AS A PRIMARY OUTCOME MEASURE TO COMPARE CONSOLIDATIVE STRATEGIES IN RELAPSED/REFRACTORY PRIMARY CNS LYMPHOMA
Authors: Bonm Alipi , Gibson Alec , Holmberg Leona , Mielcarec Marco , McGranahan Tresa , Taylor Lynne , Graber Jerome
Published: December 2020

Relapsed or refractory primary CNS non-Hodgkin’s lymphoma (rrPCNSL) is a rare and challenging malignancy for which better evidence is needed to guide management. We present a retrospective cohort of 70 consecutive patients with rrPCNSL treated at the University of Washington between 2000-2020. HIV positive and secondary CNS lymphoma patients were excluded. During a median follow-up of 19.8 months, median overall survival (OS) was 18.30 months and median progression-free survival (PFS) was 12.67 months. At all stages of disease (diagnosis, first relapse, multiple relapses), PFS was an excellent predictor of OS. There was a small effect of age < 70 on PFS after initial diagnosis (PFS1), but no effect on PFS after first (PFS2) or subsequent (PFS3+) relapses. There was no effect of age < 60 on PFS1, PFS2, or PFS3+. Patients reinduced with high-dose methotrexate-based (HD-MTX) regimens had an overall response rate (ORR) of 86.7% and median PFS 17.2 months. For patients who responded to reinduction therapy, those consolidated with autologous stem cell transplant (ASCT) had median PFS of 30.3 months (n=11) compared with 12.1 months for other consolidation strategies (n=9), and 9.0 months for no consolidation (n=20). Although patients receiving ASCT were younger, KPS, sex, and the median number of recurrences were similar between consolidation groups. We conclude that PFS is a useful endpoint for rrPCNSL which predicts OS and is not associated with age. Using PFS as an endpoint, we did not detect a benefit to any consolidation strategy other than ASCT.