tbuckley/cabot-search huggingface dataset:
MNGI-21. OPTIMISING PATIENT SELECTION FOR ANTIEPILEPTIC DRUG THERAPY IN MENINGIOMA SURGERY
Authors: Abdurrahman Islim, Arousa Ali, Ananyo Bagchi, Mohammad Ahmad, Samantha Mills, Emmanuel Chavredakis, Andrew Brodbelt, Michael Jenkinson
Journal: Neuro-Oncology (2018)

Epilepsy is a major cause of morbidity and mortality in meningioma patients. The aims of this study were to determine which factors predispose meningioma patients to developing perioperative seizures and to understand the impact of antiepileptic drugs. Patients treated for a histologically-confirmed intracranial meningioma at the authors institution between 2010 and 2015 were retrospectively examined. Clinical and imaging data were assessed. Multivariate analysis was performed using binary logistic regression. The effect of antiepileptic treatment was assessed using survival analysis. Two hundred and eighty-three patients met the selection criteria; seizures were present in 68 (24%) preoperatively and in 48 patients (17%) following surgery. Of the 68 with preoperative seizures, 19 continued to have them, whereas de-novo seizures arose postoperatively in 29 seizure-naïve patients. Risk factors of postoperative seizures were convexity location (OR=2.05 [95% CI=1.07–3.98], p=0.030), fronto-parietal location (OR=4.42 [95% CI= 1.49–13.16], p=0.007) and preoperative seizures (OR=2.65 [95% CI=1.37–5.24], p=0.005). The two locations, in addition to the presence of midline shift on preoperative imaging (OR=4.15 [95% CI=1.54–11.24], p=0.005), were significantly correlated with postoperative seizures in seizure-naïve patients. Antiepileptic treatment in patients with those risk factors reduced the possibility of seizures at any time point within the 1st year postoperatively by approximately 40%, although this did not meet statistical significance. Prophylactic antiepileptic treatment might be warranted in seizure-naïve meningioma patients with 1 risk factor. High-quality randomised controlled trials are required to verify those factors and to define the role of antiepileptics in meningioma practice.
NIMG-61. MANAGEMENT OF INTRAOPERATIVE MRI AND NEURONAVIGATION SYSTEM WITH PET FOR MALIGNANT GLIOMAS MANAGEMENT OF INTRAOPERATIVE MRI AND NEURONAVIGATION SYSTEM WITH PET FOR MALIGNANT GLIOMAS
Authors: Keisuke Miyake, Daisuke Ogawa, Masaki Okada, Tetsuhiro Hatakeyama, Takashi Tamiya
Journal: Neuro-Oncology (2018)

Image-guided surgery, such as neuronavigation systems with magnetic resonance imaging (MRI) have become standard techniques for glioma surgeries. However, MRI is limited by correct metabolism of glioma cells. Positron-emission tomography (PET) uses radiotracers to achieve metabolic and molecular imaging, but can only be evaluated preoperatively. We compared the utility of intraoperative real-time MRI (IoMRI) and multiple PET studies (methionine [MET], fluorothymidine [FLT], and fluoromisonidazole [FMISO]) for malignant glioma surgery. Between January 2016 and May 2018, 39 patients with gliomas underwent IoMRI, whereas 19 (excluding biopsy cases) underwent multiple PET studies for tumor removal. Of these 19 patients, 12 had recurrence and 7 did not. Excision rate and residual region by IoMRI and PET studies were compared. The respective excision rates in the recurrent and nonrecurrent groups were 91.9% (80.499) and 97.7% (92.7100) with IoMRI, 92.3% (79.297.1) and 99.4% (98.3100) with MET, 94.5% (84.597.5) and 99.2% (97.5100) with FLT, and 95.9% (90.298.3) and 98.7% (93.5100) with FMISO. In the recurrent group, the residual volume of each PET tracer was significantly larger than that of IoMRI. All recurrences wherein accumulation areas of each PET tracer remained in the IoMRI excision areas were detected. Recurrence was observed from these sites, particularly the residual region overlapping residual accumulations of MET and FLT. CONCLUSIONS: Fusion of IoMRI images with preoperative multiple PET images during navigation remains challenging. When accumulation areas of more than two PET tracers, particularly MET and FLT, overlap with the residual IoMRI region, considering tumor removal becomes important.
RTHP-24. CLINICAL FEATURES OF BASAL GANGLIA GERM CELL TUMORS AND ITS CLINICAL OUTCOMES
Authors: Lin Bo Cai, Mingyao Lai
Journal: Neuro-Oncology (2018)

To provide a basis for standardizing the diagnosis and treatment of basal ganglia germ cell tumors (GCTs) by summarizing the clinical features and sharing our clinical experiences. Of 320 patients with intracranial GCTs treated in our hospital from 2005 to 2017, 37 developed basal ganglia GCTs, including 34 male and 3 female, with a median age of 12 years. The symptoms included extremity weakness, headache, precocious puberty, diabetes insipidus and hypoevolutism. The lesions predominately located in left basal ganglia. Two patient was diagnosed as having spinal metastasis. Positive serum tumor markers was found in 22 cases. Tumor markers detection for 15 cases of cerebrospinal fluid showed 7 of -HCG (+) and 1 of -HCG (+) and AFP (+). Seventeen patients were pathologically diagnosed as GCTs (n=13), yolk sac tumor (n=2), embryonal carcinoma (n=1) and immature teratoma (n=1); 17 were diagnosed with tumor markers; and 3 received diagnostic radiotherapy. Surgery was conducted in 17 cases. Thirty-six patients received whole CNS radiotherapy and local radiotherapy, and the other 1 underwent chemotherapy. Adjuvant chemotherapy included BEP in 22 cases and EP in 8 cases. Tumor markers, imaging features and survival time were evaluated. Due to incomplete imaging data, 4 of 37 cases weren’t evaluated. Of 33 cases, CR was achieved in 16 cases; PR in 13; SD in 1; and PD in 3. After being followed-up to October 2017, 27 patients were alive, 7 were lost and 3 died. The 5-year progression-free survival rate was 88.8%. Basal ganglia GCTs is common in male, frequently involving left basal ganglia, with good prognosis. Chemoradiotherapy are suggested for patients with -HCG and/or AFP (+). For those with -HCG and/or AFP (-), pathologic diagnosis should be performed before chemoradiotherapy, and diagnostic radiotherapy is not recommended for its high risk.
Abstract P161: Self-Management Resources in Heart Failure: A Prospective Community Study
Authors: Matteo Fabbri, Sheila Manemann, Cynthia Boyd, Jennifer Wolff, Alanna Chamberlain, Susan Weston, Kathleen Yost, Lila Finney Rutten, Joan Griffin, Jill Killian, Veronique Roger
Journal: Circulation (2018)

Introduction: Little is known about the characteristics and resources that enable patients with heart failure (HF) to engage in effective self-management. To address this gap in knowledge, we measured personal and health care resources for self-management and examined associations with mortality among patients with HF. Methods: We surveyed 5543 residents of 11 counties in Southeast Minnesota with a first-ever code for HF [International Classification of Disease, Ninth Revision code 428 or Tenth Revision code I50] between 1/1/2013 and 3/31/2016. Self-management resources were measured with the health care and personal subscales of the Chronic Illness Resources Survey (CIRS), both of which included 3 questions on a 5-point scale. The responses were averaged and participants were categorized as low if the mean score was below the median of the distribution (range from 1 to 5). The survey was returned by 2866 participants (response rate 52%) and those with complete data on the main items of interest were retained for analysis (N=2212). Cox proportional hazards regression was used to determine the association between each subscale and mortality. Results: Among 2212 participants (mean age 72.8 years, 54.1% men) the median health care score was 4, while the personal score was 3. Those with low health care resources were older and less educated than those with a higher score (p&lt;0.05), while those with low personal resources had less comorbidities and lower education attainment compared to those with a higher score (p&lt;0.05). After a mean (SD) follow-up of 1.3 ± 0.6 years, 207 deaths occurred. Low levels of both self-management resources were associated with an increased risk of death compared with patients with high levels (Table). Conclusions: Having limited self-management resources is associated with an increased risk of mortality among patients with HF. Thus, interventions aimed at supporting self-management among patients with HF may improve outcomes.
ACTR-67. A PHASE I STUDY OF CONVECTION-ENHANCED DELIVERY OF LIPOSOMAL-IRINOTECAN (ONIVYDE) USING REAL-TIME IMAGING WITH GADOLINIUM IN PATIENTS WITH RECURRENT HIGH GRADE GLIOMAS: RESULTS THUS FAR
Authors: Karishma Kumar, Susan Chang, Nancy Ann Oberheim-Bush, Jennifer Clarke, Jennie Taylor, Margaretta Page, Katherine Chang, Lisa Guthrie, Amanda Lawrence, Chelsea Lindahl, Courtney Miyamoto, Ute Vogrinec, Nicholas Butowski
Journal: Neuro-Oncology (2018)

Chemotherapy for high grade gliomas (HGG) is limited by the blood-brain-barrier (BBB). Convection enhanced delivery (CED) improves chemotherapy delivery by utilizing fluid convection obviating the challenges of crossing the BBB while minimizing systemic toxicity. CED of nanoliposomal-irinotecan (Onivyde) showed to be a superior delivery route for anti-tumor activity in animal models. An advance of this trial is the development and use of real time CED, which utilizes MRI to visualize the CED process with the aid of co-convected contrast agents, monitoring delivery into the brain and affording for corrective action. This is a 3 + 3 single dose escalation trial with 2 cohorts: 20mg/ml and 40mg/ml. Onivyde and GAD were co-infused via the same catheters in a one-time delivery. The total volume of infusate, and consequently total dose, were personalized based on the patient's tumor volume, and ranged from 20–680 mg of Onivyde, given via up to 4 catheters. Tumor diameters were allowed to be 1 – 4 cm, with injection volumes ranging from 2 – 17 mL of infusate. 10 patients have been treated on this protocol, all in under 5 hours. There were 7 GBs, 2 anaplastic astrocytomas, and 1 oligoastrocytoma. Seven patients lived over a year after treatment, which is remarkable since median survival rates for multiply recurrent: GBs = 8 months, AAs = 11 months. Utilizing imaging software, we correlated pre-infusion modeling of the drug distribution with post-infusion imaging. A number of technical challenges were overcome by real time monitoring; the total volume of distribution (Vd), and the Vd to volume infused (Vi) ratio for each infusion was ~2. Image-guided distribution allows for safe real-time placement and adjustment of CED cannula of Onivyde into patient's brains. Such methods allow for maximum tumor coverage and warrant further studies with repeat dosing.
RARE-27. CHIMERIC SPINAL CORD GLIOPROLIFERATIVE LESION FOLLOWING INTRATHECAL FETAL STEM CELL INFUSION
Authors: Douglas Ney, Vera Fridman, Mark Ewalt, B K Kleinschmidt-DeMasters
Journal: Neuro-Oncology (2018)

Commercial stem cell therapy is available in select practices, particularly at non-U.S. sites, and is increasingly sought as a therapy by patients who are willing to travel for off-label treatment. To date, two cases of a spinal cord “glioneuronal lesion” or “glioproliferative lesion” have been reported. We report the third case, which by microdissection showed the glioproliferative spinal cord lesion to have mixed host/donor origin. CASE: A 73- year-old man presented with 3–4 years of progressive lower extremity weakness; he received intrathecal stem cell therapy (at least partly fetal in origin) in Russia, 7/2016. Symptoms began about 1 month after infusion. At presentation to our clinic in 11/17, neuroimaging showed nerve root enlargement with mild enhancement and clumping of nerve roots. Cerebrospinal fluid demonstrated significant elevation of protein (>1500mg/dL) and low glucose (32mg/dL). Multiple CSF samples were negative for malignancy or clonality. Extensive laboratory work-up for malignancy and inflammatory processes was negative. However, PET-CT showed intense uptake along the nerve roots of the cauda equina. Nerve root biopsy on 1/4/2018 showed a glioproliferative lesion with moderate cell density and cytological atypia associated with mononuclear inflammation. Microdissection of the inflammatory element showed only host cells while alleles from two different individuals, one the recipient, were identified in the glioproliferative cord process. With progressive symptomatology, the patient received 2 cycles of high dose methotrexate. Follow-up PET-CT showed progression and he was referred for radiation therapy. This case with identification of chimeric origin for the glioproliferative, but not inflammatory, component of the lesion builds on the two previously-reported cases and underscores the need for greater awareness of potential complications of commercial stem cell therapy.
RARE-24. OBJECTIVE RESPONSE AND CLINICAL BENEFIT IN RECURRENT EPENDYMOMA IN ADULTS: FINAL REPORT OF CERN 08-02: A PHASE II STUDY OF DOSE-DENSE TEMOZOLOMIDE AND LAPATINIB
Authors: Terri Armstrong, Ying Yuan, Jimin Wu, Tito Mendoza, Elizabeth Vera, Antonio Omuro, Frank Lieberman, H Robins, Elizabeth Gerstner, Jing Wu, Patrick Wen, Tom Mikkelsen, Kenneth Aldape, Mark Gilbert
Journal: Neuro-Oncology (2018)

Ependymoma is a rare tumor for which the role of chemotherapy has not been established either for newly diagnosed or recurrent disease. We report on the first prospective adult clinical trial of chemotherapy for recurrent ependymoma. Adult (> 18 years) were treated with dose-dense temozolomide (125–150 mg/m2, 7days on/7days off) and daily lapatinib (1250 mg/day). Efficacy was based on serial imaging of either brain or spine using MRI. Clinical benefit was evaluated using longitudinal assessment of symptom burden (MDASI-BT/MDASI-Spine) and performance status. Primary endpoint was progression free survival. Additional endpoints included 12-month PFS rate, objective response and clinical benefit (KPS and changes in proportion of moderate-severe disease-related symptom burden through cycle 6). 50 patients were treated with this regimen. Median age = 43.5, median KPS = 90, median number of prior relapse = 2. By tumor grade: III n = 19, II n = 16, I n = 8. 25 patients had spinal cord, 15 had supratentorial and 8 had infratentorial tumors. Treatment was well tolerated with a 10% Grade 3–4 myelotoxicity rate. Median PFS = 0.65 years (95%CI 0.46, 1.02). 1-year PFS=38%, with 1 complete and 4 partial responses. KPS improved in all but 1 patient and MDASI measures were completed on 86% of cases with reduction in moderate-severe pain in 53% and 71% of brain and spine patients respectively. Patients with spine tumors reported improvement in numbness (57%), weakness (24%), fatigue (23%)and autonomic dysfunction (bladder control (73%), sexual function (9%), and bowel function (36%)). CONCLUSIONS: These results demonstrate evidence of clinical activity, including objective responses and a nearly 40% stable disease rate at one year, with improvement in disease-related symptoms. This combination regimen was well tolerated and should be considered as a standard salvage regimen for adult patients with recurrent ependymoma.
QOLP-10. THE IMPACT OF VARIOUS FACTORS ON HEALTH-RELATED QUALITY OF LIFE (hrQOL) IN PATIENTS UNDERGOING INTRACRANIAL RADIOTHERAPY
Authors: Jeffrey Burkeen, Euyhyun Lee, Tonya Pan, Carrie McDonald, Jona Hattangadi-Gluth
Journal: Neuro-Oncology (2018)

PURPOSE: Treatment of brain tumors significantly impacts health-related quality of life (hrQOL). In this prospective longitudinal study of hrQOL in patients receiving intracranial radiotherapy (RT) we sought to better understand the factors impacting patient hrQOL following brain RT. Data was collected prospectively at our institution from 2013–2017. Prior to RT, patients completed a core overall hrQOL tool (EORTC QLQ C-15-PAL) and a brain tumor-specific module (QLQ-BN20), repeating these questionnaires one month post-treatment and every 3-months until patient death or study withdrawal. Baseline patient data collected included age, gender, KPS, tumor type (primary or metastasis), histology, and RT treatment type. Statistical analyses using R software package included linear regression modeling for continuous hrQOL outcomes and proportional odds modeling for ordinal hrQOL outcomes. Two hundred twenty one patients (51% male, 49% female) completed baseline surveys. The majority of patients had brain metastases (57%) while 43% had a primary brain tumor (13% WHO grade I-II, 26% WHO grade III-IV, and 4% benign/other). Global hrQOL was significantly affected by tumor type, histology, and RT treatment type one month post-RT, with metastatic patients 41% less likely to give a higher score than primary brain tumor patients (p=0.031), WHO grade I-II patients 8 times more likely to give a higher score than those with brain metastases (p=0.017), and patients receiving SRS or WBRT 75–81% less likely to give a higher score than those receiving partial brain RT (p=0.039). Other hrQOL measures impacted by various clinical and treatment factors included future uncertainty, emotional and physical functioning, fatigue, motor dysfunction, and nausea and vomiting. CONCLUSIONS: We demonstrated significant longitudinal overall and brain tumor-specific hrQOL differences due to such factors as tumor type, disease histology, and treatment type following intracranial RT. This knowledge may help better predict certain hrQOL outcomes and guide patient care following intracranial RT.
GENE-23. PREVIOUSLY IDENTIFIED COMMON GLIOMA RISK SNPs ARE ASSOCIATED WITH FAMILIAL GLIOMA
Authors: Quinn Ostrom, Georgina Armstrong, Christopher Amos, Jonine Bernstein, Elizabeth Claus, Jeanette Eckel-Passow, Dora Il’yasova, Christoffer Johansen, Daniel Lachance, Rose Lai, Ryan Merrell, Sara Olson, Joellen Schildkraut, Sanjay Shete, Richard Houlston, Robert Jenkins, Margaret Wrensch, Beatrice Melin, Jill Barnholtz-Sloan, Melissa Bondy
Journal: Neuro-Oncology (2018)

Approximately 5% of gliomas occur in individuals with a family history of glioma, and first-degree relatives of brain tumor cases have a two-fold increase in risk of brain tumor. Family-based studies have had little success in identifying high penetrance risk variants. Recent somatic characterization has shown that tumors from familial cases are indistinguishable from sporadic cases, suggesting that familial cases may arise through similar mechanisms of gliomagenesis, and therefore may be associated with common variants as well as rare mutations. In this analysis, we assessed whether previously identified common risk variants are associated with familial glioma. Data were obtained from the Glioma International Case Control (GICC) Study for 447 familial cases and 3,286 controls. We assessed 25 risk loci previously identified by glioma GWAS, and odds ratios (OR) and 95% confidence intervals (95%CI) were calculated using an additive genetic logistic regression model adjusted for age, sex, and the first principal component. Results were considered significant at p TERT, EGFR, CCDC26, CDKN2B, TP53, and RTEL1. The strongest association was at rs55705857 (CCDC26, OR=2.5, p=1.14x10-14). These SNPs were further examined using a case-only approach comparing familial to non-familial cases, and there was no significant difference in allele frequencies by family history status. In this analysis we identified a significant association between familial glioma and six common risk variants previously identified by glioma GWAS. This provides further evidence of shared pathways of genetic risk and gliomagenesis between familial and non-familial glioma. Further exploration is necessary to determine the overall contribution of common genetic variation to risk of familial glioma.
HOUT-11. ECONOMIC IMPACT OF SODIUM THIOSULFATE ON CISPLATIN-INDUCED HEARING LOSS
Authors: Rongwei (Rochelle) Fu, Kristin Knight, David Freyer, Nancy Doolittle, Penelope Brock, Edward Neweult
Journal: Neuro-Oncology (2018)

BACKGROUND. Cisplatin-induced hearing loss (CIHL) develops in majority of children receiving cisplatin chemotherapy. Recently two phase-3 clinical trials demonstrated effectiveness of sodium thiosulfate (STS) in preventing CIHL. This study quantifies the potential economic impact of STS on cisplatin-treated children with hepatoblastoma (HB) in US. METHODS. We used an incidence-based approach to model CIHL cost for standard risk HB patients 19 yrs. Input data included: 1) estimates of incidence and survival, and age distribution of HB in US; 2) incidence of CIHL and effectiveness of STS; 3) lifelong health care and education cost and lost productivity (up to 65 yrs). Market cost of STS is unknown and not included but expected to be a small part of lifelong cost. When estimating the total and reduced costs, costs of CIHL were calculated by age and degree of CIHL severity (none, mild, severe), and the uncertainty in the input estimates were incorporated through Monte Carlo simulation. RESULTS. For a child diagnosed with HB at 1yr old and developed severe CIHL, the estimated lifelong cost is $825K ($347K health care and education cost; $478K lost productivity). Given an incidence of 0.13 cases per 100,000 in US, the annual cost of CIHL is estimated to be $16.7 million (95% CI 15.5–17.8). Assuming that all new HB patients receive STS and CIHL is reduced from 70% to 30%, the annual reduced cost in the US would be $1.81million (95% CI 1.29–2.34) after 5 years, $3.60million (95% CI 2.87–4.37) and $6.96million (95% CI 5.98–8.03), respectively, after 10 and 20 years. CONCLUSION. STS treatment could potentially lead to significant reduction in CIHL-related cost to society. Further analyses will evaluate the economic impact of STS on all childhood solid tumors, and include STS cost. Such economic impact will help inform the future clinical role of STS.
NCMP-27. QUALITY OF LIFE IN LONG-TERM SURVIVORS OF PEDIATRIC CANCER: THE IMPACT OF HEARING LOSS
Authors: Kristin Knight, Rongwei (Rochelle) Fu, Nancy Doolittle, David Cahana, Amy Huddleston, Heather Leon, Susan Lindemulder, Sara Walker, Jeff Wong, Edward Neweult
Journal: Neuro-Oncology (2018)

Cisplatin chemotherapy causes irreversible hearing loss (HL) in approximately 50% of children and adolescents. We examined the association between cisplatin-induced HL and health-related quality of life (HRQOL) in a cohort of childhood cancer survivors. Participants were ≤18 years at time of treatment, received a cumulative cisplatin dose ≥200 mg/m2, and had at least one year between treatment completion and study enrollment. HL was graded using the International Society of Pediatric Oncology Ototoxicity Scale. HRQOL was assessed with self- and parent-reported versions of the Pediatric QOL Inventory (PedsQL). A questionnaire was developed for survivors and parents to assess the use of hearing technology, communication difficulties, and educational needs. Data were analyzed using linear regression and Fisher’s exact test. Data from 66 patients (36 M/30 F) are summarized. The median age at diagnosis was 8.8 years (range 1 month-18 years), and the age range at the time of study enrollment was 3.6–35.1 years. The average time since treatment completion was 9 years (range 1.5–22 years). Diagnoses included medulloblastoma (39%), osteosarcoma (27%), neuroblastoma (14%), hepatoblastoma (8%) and other (12%). At the end of treatment 27% had no HL while 38% had mild HL and 35% had severe HL. Self- and parent-reported HRQOLs were strongly associated (P < 0.0001) and there were no differences in HRQOL among HL groups. However, survivors with severe HL more frequently reported speech and language delay (p<.01), learning disability (p<.05), limitation in activities (p<.01), and need for special education (p<.01). CONCLUSIONS: In this large cohort of long-term childhood cancer survivors, severe HL was significantly associated with communication and learning difficulties and need for educational supports, but not with HRQOL as measured by the PedsQL.