bluuebunny/crossref_metadata_2025_split huggingface dataset:
NCMP-21. REVERSIBLE MOTOR NEURON SYNDROME IN THE SETTING OF CANCER
Authors: Primdahl Ditte , Beinlich Brad , Albertson Megan 
Published: December 2020

Abstract
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 &gt; upper and right &gt; 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 &gt; 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 &gt; 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

Abstract

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

Abstract
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&lt; 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

Abstract

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&lt; 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

Abstract

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 &lt; 0.01), in an increase of facial nerve impairment (OR of 1.62, p &lt; 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

Abstract

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 &lt; 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 &lt; 0.05) and pediatricians (N=260, P &lt; 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

Abstract

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 &gt; 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

Abstract

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 &lt; 65 years. However, we did not find significant differences in compliance rate and gender variables between patients ≥ 65 years and &lt; 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

Abstract
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 &lt; 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&lt; 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

Abstract

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 = &lt; 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 = &lt; 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.