bluuebunny/crossref_metadata_2025 huggingface dataset:
NCMP-25. CLINICAL FEATURES, NEUROLOGIC RECOVERY, AND RISK PREDICTION OF POST-OPERATIVE POSTERIOR FOSSA SYNDROME: A PROSPECTIVE STUDY
Authors: Khan Raja B , Patay Zoltan , Kilmo Paul , Huang Jie , Onar-Thomas Arzu , Kumar Rahul , Boop Frederick A , Raches Darcy , Conklin Heather , Sharma Richa , Simmons Andrea , Sadighi Zsila , Gajjar Amar
Published: December 2020

INTRODUCTION

Posterior fossa syndrome (PFS) is a known consequence of medulloblastoma resection. Our aim was to clinically define PFS, its evolution over time, and ascertain risk factors for its development and poor recovery.

METHODS

Children with medulloblastoma treated at St Jude Children’s Research Hospital from 6/2013-7/2019 received standardized neurological examinations, before and periodically after radiation therapy. Most (98.3%) were enrolled on the ongoing multi-institutional protocol (SJMB12; NCT 01878617).

RESULTS

Sixty (34%) of 178 evaluated children had PFS. Forty (23%) had complete mutism (PFS1) and 20 (11%) had diminished speech (PFS2). All children with PFS had severe ataxia and 42.5% of PFS1 had movement disorders. By multivariable analysis, younger age (p=0.0005) and surgery in a low-volume surgery center (p=0.0146) increased PFS risk, while SHH tumors had reduced risk (p=0.0025). Speech and gait returned in PFS1/PFS2 children at a median of 2.3/0.7 and 2.1/1.5 months respectively, however, 12 (44.4%) of 27 PFS1 children with 12 months of follow-up were non-ambulatory at one-year. Movement disorder (p= 0.037) and high ataxia score (p< 0.0001) were associated with delayed speech recovery. Older age (p= 0.0147) and high ataxia score (p< 0.0001) were association with delayed gait return. Symptoms improved in all children but no child with PFS had normal neurologic examination at a median of 23 months after surgery.

CONCLUSION

Categorizing PFS in to types 1 and 2 has prognostic relevance. Almost half of the children with PFS1 remained non-ambulatory at 12-month follow-up. Surgical experience was a major modifiable contributor to the development of PFS.
NCOG-01. STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASES AT THE GUY’S CANCER CENTER, LONDON: AN AUDIT FOR THE FIRST 17 MONTHS
Authors: Bhadra Kallol , Al-Salihi Omar , Hassan Sheila , Swampillai Angela , Blythe Kirsty , Forner Samantha , Sisodia Caroline , Brazil Lucy
Published: December 2020

INTRODUCTION

Stereotactic radiosurgery (SRS) commenced at Guy’s Cancer Hospital in August 2017. We report our first seventeen months’ data (August 2017 to December 2018) for brain metastases SRS.

METHOD

Patients referred via Neuro Oncology MDT were assessed for suitability for SRS via clinical review and 1mm-slice MRI. Treatment was planned on Eclipse v15.6 and delivered using Truebeam STx Linac(FFF) and Align RT v5.1 for matching. Dose prescription, according to departmental protocol, was set at 100% isodose, ranging from 18Gy to 25Gy, with fractionation varying from single to five fractions depending on factors including size, volume and locations. Post-treatment, patients were discharged back to their primary treating team for 3-monthly MRI.

RESULTS

Between Aug-17 to Dec-18, 70 patients with brain metastases were treated with a total of 122 lesions. Mean age was 66 years (range 37-93) and Median follow-up 9 months. Primary tumour sites mainly included lung 34(48.5%), breast 16(22.8%) and melanoma 17(24.3%). Brain-only metastases, including small volume primary with brain metastases were found in 85.4% cases, whilst visceral disease with brain metastases were found in 14.5% patients. Out of 122 lesions, the majority were treated in the primary setting; 95(77.8%) vs 27(22.1%) in the adjuvant setting. At 9-months follow up, local failure rate was in 26(21.3%) sites and 17 new sites in distant brain appeared. 31(44.2%) patients received no systemic therapy after SRS, whilst immunotherapy was received by 14(20%), with the remaining receiving hormones or chemotherapy. Median Overall Survival was 9.2 months (95% CI: 4.5-13.8) and Median progression-free survival was 5.9 months (95% CI: 7.0-10.4).

CONCLUSION

Overall Survival results were encouraging with initial auditing proving SRS as effective approach. Local control rates correlate well with randomized control trials results for SRS in brain metastases.
NCOG-04. PRETREATMENT VOLUME OF MR-DETERMINED WHITE MATTER INJURY (WMI) PREDICTS NEUROCOGNITIVE DECLINE AFTER HIPPOCAMPAL AVOIDANT (HA) WBRT+MEMANTINE FOR BRAIN METASTASES: SECONDARY ANALYSIS OF NRG ONCOLOGYCC001
Authors: Bovi Joseph , Pugh Stephanie , Brown Paul , Gondi Vinai , Wefel Jeffrey S , Tome Wolfgang A , Gilbert Mark , Robinson Cliff , Benzinger Tammie L S , Sabsevitz David , Lee Karen , Paulson Eric , Kundapur Vijayananda , Roberge David , Kaufman Isaac , Shah Sunjay A , Usuki Kenneth Y , Stea Baldassarre D , Yoon Harold A , DeMora Lyudmila , Mehta Minesh , Kachnik Lisa
Published: December 2020

PURPOSE

Previous secondary analysis of NRG/RTOG 0933 provided hypothesis-generating data supporting a relationship between larger volumes of MR-determined pre-treatment WMI and developing neurocognitive decline following HA-WBRT. The current study examines the relationship between pre-treatment WMI and neurocognitive function (NCF) following WBRT+memantine +/-HA in a substantially larger cohort.

METHODS

NCF testing was performed at baseline,2,4,6,and 12 months post-WBRT, and included Hopkins Verbal Learning Test–Revised (HVLT-R), Trail Making Test (TMT) Parts A and B, and Controlled Oral Word Association (COWA). Pre-treatment WMI was measured by FLAIR volume corrected for whole brain volume and corrected for the FLAIR volume associated with metastases (FLAIR/(whole brain volume – metastasis FLAIR volume). Pearson correlation coefficients were used to assess association between pre-treatment WMI and change from baseline for each standardized NCF score.

RESULTS

Of 518 randomized patients, 442 (217,WBRT+Memantine; 225,HA-WBRT+Memantine) had WMI data and were included. In the entire cohort, mean FLAIR volume was 9.3cc (0.1-68.2cc), mean metastases FLAIR volume was 61.5cc (0-423.5cc), mean Whole Brain volume was 1336.4cc (949.4-2397.8cc). At 2 months, there were no significant correlations between neurocognitive test change scores and pre-treatment WMI volume. However, at 4 months, both HVLT-R Total Recall and TMT Part B change score and pre-treatment WMI volume were significantly negatively correlated on the HA-WBRT+Memantine arm (ρ=-0.22 p=0.042 and ρ=-0.27, p=0.013). At 12 months, both TMT Part A and TMT Part B change scores and pre-treatment WMI volume were significantly negatively correlated on the HA-WBRT+Memantine arm (ρ=-0.30, p=0.046 and ρ=-0.53, p< 0.001).

CONCLUSIONS

Pre-treatment WMI volume was a significant imaging-biomarker predictor of post-treatment neurocognitive decline at 4-and 12-months following HA-WBRT+Memantine. This suggests patients with greater pre-treatment WMI were more susceptible to neurocognitive decline, specifically when undergoing HA-WBRT, but not following standard WBRT. Dose heterogeneity inherent to HA-WBRT delivery may contribute to these findings and are hypothesis generating.
NCOG-06. A NOVEL ONLINE CALCULATOR PREDICTING SHORT-TERM POSTOPERATIVE OUTCOMES IN METASTATIC BRAIN CANCER PATIENTS
Authors: Khalafallah Adham , Jimenez Adrian , Patel Palak , Huq Sakibul , Azmeh Omar , Mukherjee Debraj
Published: December 2020

BACKGROUND

Establishing predictors of hospital length of stay (LOS), discharge deposition, and total hospital charges is essential to providing high-quality, value-based care. Though previous research has investigated these outcomes for patients with metastatic brain tumors, there are currently no tools that synthesize such research findings and allow for prediction of these outcomes on a patient-by-patient basis.

OBJECTIVE

We sought to develop a prediction calculator that uses patient demographic and clinical information to predict extended hospital length of stay, nonroutine discharge disposition, and high total hospital charges for patients with metastatic brain tumors.

METHODS

Patients undergoing surgery for metastatic brain tumors at a single academic institution were analyzed (2017-2019). Multivariate logistic regression was used to identify independent predictors of extended LOS (> 8 days), nonroutine discharge, and high total hospital charges (> $45,660.00). p < 0.05 was considered statistically significant. C-statistics and the Hosmer-Lemeshow test were used to assess model discrimination and calibration, respectively.

RESULTS

A total of 222 patients were included in our analysis, with a mean age of 62.2 years. The majority of patients were male (52.7%) and Caucasian (76.6%). Our models predicting extended LOS, nonroutine discharge, and high hospital charges had optimism-corrected c-statistics > 0.7, and all three models demonstrated adequate calibration (p > 0.05). The final models are available as an online calculator (https://neurooncsurgery.shinyapps.io/mets_brain_cancer_calculator/).

CONCLUSIONS

Our models predicting postoperative outcomes allow for individualized risk-estimation for patients following surgery for metastatic brain cancer. Our results may be useful in helping clinicians to provide high-value care and to ensure optimal patient outcomes
NCOG-14. PSYCHOSOCIAL OUTCOMES IN CHILDREN WITH NEUROFIBROMATOSIS TYPE 1 AND PLEXIFORM NEUROFIBROMAS
Authors: Puccetti Diane , Mission Paige , Damodharan Shawn
Published: December 2020

OBJECTIVE

This case series seeks to examine neurocognitive outcomes, social-emotional functioning, and family burden in young children diagnosed with Neurofibromatosis, type 1 (NF1) with early growing plexiform neurofibromas (PNFs).

BACKGROUND

Neurofibromatosis, type 1 (NF1) is a common predisposing chronic disease arising in early childhood, with an incidence of approximately 1:3000. Though NF1 displays a wide range of phenotypic variability, the primary feature of the disease is peripheral nerve sheath tumors called neurofibromas. Less is well known regarding the broader neurocognitive and social-emotional profile in presentations with more complex tumor growths, namely PNFs, which are present in at least half of the NF1-affected population.

METHODS

Participants with NF1 and PNFs (n=2) aged 6-7years completed comprehensive neuropsychological evaluations and parents completed measures of quality of life, social-emotional/behavioral functioning of child, parental stress, family adaptability, and family cohesion.

RESULTS

Outcomes suggest broad neurocognitive dysfunction (e.g., executive functioning deficits, attention problems, visual-motor delays, and poor motor coordination), social-emotional challenges (e.g., symptoms of anxiety and depression, and poor social skills), and familial distress.

CONCLUSIONS

Findings indicate the value of early and frequent monitoring of children with PNFs in medical systems and multi-disciplinary teams, and the importance of early intervention for both children and families.
NCOG-18. IS THE RANO CRITERIA FOR LOW-GRADE GLIOMA RELIABLE IN THE CLINICAL SETTING? – A RELIABILITY STUDY
Authors: Horta Erika , Zhou Yueren , Poisson Laila M , Griffith Brent , Stone Michael , Snyder James , Walbert Tobias
Published: December 2020

INTRODUCTION

Magnetic resonance imaging (MRI) is a fundamental component of longitudinal neuro-oncology evaluation and decision-making. The Response Assessment in Neuro-Oncology criteria for low-grade gliomas (RANOLGG) was designed as an outcome measure for clinical trials. Thus, this project intends to study the reliability of RANOLGG in the clinic setting.

METHODS

21 pairs of brain MRIs, that averaged three years apart, were selected from 21 patients with tissue diagnosis of WHO grade 2 gliomas. Two neuro-oncologists and two neuro-radiologists reviewed and independently scored the MRI pairs according to RANOLGG categories of progressive disease, stable disease, minor response, partial response, and complete response. Kappa-Fleiss (KF) was used to evaluate agreement among reviewers.

RESULTS

Reviewers awarded identical scores in only 33% of MRI pairs and there was a complete disagreement in one MRI pair. Overall reliability of the criteria in the clinical setting is moderate (KF = 0.44). Agreement between neuroradiologists (KF = 0.51) and between neuro-oncologists (KF = 0.48) were similar. Interpretation of post-contrast T1-weighted images had a better agreement (KF = 0.31) than T2/FLAIR-weighted images which had a poor agreement (KF = -0.02). Classification of progression versus non-progression had only a moderate agreement (KF= 0.49). History of radiation therapy or chemotherapy did not influence the criteria reliability (fisher exact text, p = 0.58, p =0.27, respectively).

CONCLUSION

RANOLGG reliability in the clinical setting is moderate, therefore it should be used cautiously for clinical decision-making. Other tools that can support the neuro-oncologist in the follow-up of patients with low-grade glioma are additional MRI sequences other than T2/FLAIR and contrast – weighted images, computer-aided diagnosis such as volumetrics, spectroscopy, positron emission tomography, and multidisciplinary tumor boards. Likewise, when image criteria for low-grade gliomas are designed, T2/FLAIR should be used guardedly, due to low interpretation agreement.
NCOG-19. BEVACIZUMAB IN REAL LIFE PATIENTS WITH RECURRENT GLIOBLASTOMA: BENEFIT OR FUTILITY?
Authors: Smolenschi Cristina , Colomba Emeline , Rassy Elie , Lezghed Naima , Kettab Mohamed , Louvel Guillaume , Garcia Gabriel , Cheaib Bianca , Bockel Sophie , Pallud Johan , Dezamis Edouard , Copaciu Razvan , Knafo Steven , Ammari Samy , Dhermain Frederic , Domont Julien , Martanovschi Larisa , Mahmoud Fekih , Dumont Sarah
Published: December 2020

Angiogenesis represents a hallmark of glioblastoma but most trials disappointed and failed to change the poor outcome of this disease. However, Bevacizumab (Bev) is widely used in clinical practice by expert oncologists due to experience or efficacy in real life.We retrospectively reviewed the use of Bev and its benefit in terms of Time to treatment failure (TTF), Overall Survival(OS), Objective Response Rate (ORR) and clinical benefit. METHODS: We analyzed two hundred and two patients treated at Gustave Roussy Cancer Campus with Bev until definitive failure for recurrent glioblastoma between 2006 and 2016. Patients were treated with Bev alone or in association with radiotherapy, temozolomide, lomustine or irinotecan. RESULTS: The median duration of Bev treatment until definitive failure was 6 months. The median TTF was 7.27 months(95%CI 6.30-8.24) and the median OS from diagnosis was 22.43 months(95%CI 19.68-25.18). Two patients were still alive without active treatment at the end of study. A hundred and fourteen (56%) patients experienced symptom amelioration and seventy-five (37%) improved their Performance Status. Fifty percent of patients exhibited Partial and Complete Response on MRI, as best radiological response, within 1.6 months. No patient had anaphylactic reaction. Grade 1-2 hypertension(HT)(17%) and grade 1(10%) proteinuria were most common. Six patients presented lethal toxicity: 4 with GI perforation, 1 p with cerebral hemorrhage and 1 p with arterial bleeding. HT was correlated with treatment response in 67% of patients. A neutrophil count superior to 6000/mm³ was associated with longer TTF(mTTF 8.23m(95%CI 6.64-9.82). CONCLUSION: This retrospective study reports a substantial clinical benefit of Bev in patients with recurrent glioblastoma with an acceptable toxicity profile. As the panel of therapeutic option is still very limited in these tumors, this work supports the maintained use of Bev as a therapeutic option.
NCOG-20. AWAKE SURGERY FOR RIGHT FRONTAL LOBE GLIOMA CAN IMPROVE THE RESECTION RATE AND PRESERVE HIGHER COGNITIVE FUNCTIONS
Authors: Nakada Mitsutoshi , Nakajima Riho , Kinoshita Masashi
Published: December 2020

OBJECTIVE

Awake surgery is the standard treatment to preserve motor and language functions. The aim of this study is to evaluate the awake surgery for the patients with right frontal lobe (RFL) glioma on resection rate and preservation of higher cognitive functions.

METHODS

Out of the 139 cases that underwent awake surgery at our hospital between 2013 and 2019, 34 cases (mean age: 47.8 years) of RFL glioma were included in this study. The WHO classification was grade II, III, and IV for 15, 13, and 6 cases, respectively. We evaluated visual spatial cognition (VSC), spatial working memory (SWM), and social cognition (SC) before and after the surgery. These relevant areas were mapped intraoperatively. We did not map these areas in the cases in which the task could not be accomplished. Therefore, each function was divided into an intraoperative evaluation group (EG) and a non-evaluation group (NEG), and the resection rate and functional outcomes were compared.

RESULTS

The removal rate was significantly higher in the EG group for VSC and SC than that in the NEG (p= 0.0078 and 0.0024, respectively). The chronic disability rate of VSC was significantly lower in the EG than that in the NEG (5.6% vs. 31.3%, p= 0.043). None of the patients had postoperative disability of SWM in the EG which is significantly lower than that in the NEG (16.7%, p= 0.049). SC tended to have a lower disability rate (20.0%) in the EG compared to that in the NEG (45.8%). The probability that the posterior deep part of the middle frontal gyrus, which is the relevant area of VSC, was resected higher in the NEG (p= 0.0052).

CONCLUSIONS

We scientifically verified that the awake surgery for RFL glioma contributes to the improvement of resection rate and the preservation of higher cognitive functions.
NCOG-39. PROGRESSION-FREE AND SURVIVAL RATE OF CHEMOTHERAPY IN PEDIATRICS WITH OPTIC PATHWAY GLIOMAS: A SYSTEMATIC REVIEW
Authors: Pangaribuan Vega , Kurniawan Jemmy , Widyandana Doni
Published: December 2020

BACKGROUND

Optic pathway gliomas (OPG) are typically astrocytic neoplasms that represent 3-5% of all pediatric brain tumors. The prognosis of these tumors has often been poor. Total surgical resection of OPG is not amenable, thus the role of surgery remains limited. Chemotherapy can be considered as the main modality of treatment; it is also able to postpone the use of radiotherapy which may harm the brain growth in children.

METHODS

We conducted the PRISMA-guided systematic literature search from 6 electronic databases to identify studies reporting outcomes of chemotherapy in OPG patients. The inclusion criteria are literature reporting the survival outcomes of chemotherapy in OPG patients with minimum subjects of 10 patients and aged below 22 years old.

RESULTS

A total of 48 out of 557 studies were assessed for its full paper eligibility. Thus, we found 10 studies comprising of 451 patients that met the inclusion criteria for analysis. From 8 different regimens of chemotherapy that were reported, the most commonly used regimens are Carboplastin ± Vincristine. The 3-year, 5-year, and 10-year progression-free survival (PFS) rates were ranged from 23-70%, 34-73%, and 47.1% respectively. The 3-year, 5-year, and 10-year overall survival (OS) rate has a range of 91-95%, 70.1-97%, and 61.3%-62.3% respectively. In detail, we found that 1 study with Cisplatin with Etoposide regimens reported 0% of the 5-year PFS rate, therefore it was excluded from the analysis. There are 2 studies that reported a high rate of 5-year radiotherapy free survival with chemotherapy, ranging from 61-82%.

CONCLUSION

This systematic review showed that chemotherapy in patients with OPG leads to an unsatisfactory 5-year PFS rate (34-73%), however it is able to provide a high 5-year OS (91-95%). In the absence of good quality control for these studies, future prospective clinical trials with adjusted confounding factors are urgently needed.
NCOG-56. THE NATURAL COURSE OF ATYPICAL MENINGIOMA AFTER GROSS TOTAL RESECTION WITHOUT ADJUVANT TREATMENT
Authors: Jun Yoo Hee , Kim Jeong Hoon
Published: December 2020

Atypical meningioma represent more aggressive clinical behaviors than WHO grade I meningiomas. In this study, We research natural course of atypical meningioma after gross total resection without adjuvant treatment. MATERIAL AND METHODS: We retrospectively reviewed the records of patients with histopathologically diagnosed atypical meningiomas between June 1990 and December 2015 at Asan Medical Center, Korea. Patients treated with Simpson grade I, II resection were included. Patients variably underwent adjuvant radiation therapy according to each surgeon’s preferences. RESULTS: In this study, 117 patients were enrolled and the average follow-up was 43 months (range 3~228 months). In Simpson grade I tumor resection group, recurrence was confirmed in 10 out of 63 patients without adjuvant treatment, and 1 out of 13 patients with adjuvant radiation treatment. There were 12 recurrence cases in Simpson grade II tumor resection and no adjuvant treatment group, of the total 32 cases. There was 4 recurrence case of total 8 cases of Simpson grade II tumor resection with adjuvant radiation treatment group. In groups with no adjuvant treatment, Simpson grade I resection group had a better prognosis on 5-year PFS (82.9% vs 54.9%, p=0.005) compared to Simpson grade II resection group. DISCUSSION: The results of this study show that there is a significant difference in 5-year PFS between the Simpson grade I and II groups without adjuvant treatment, commonly referred to as the gross total resection group. Although this study report adjuvant RT is not superior to observation, more intensive post-operative imaging surveillance protocols would be considered in Simpson grade II resection group without adjuvant treatment. CONCLUSION: The natural course of atypical meningioma after gross total resection without adjuvant treatment signified Simpson grade I and II resection show significant different prognosis.
NCOG-57. NEUROPSYCHOLOGICAL FUNCTION IN MENINGEAL MELANOCYTOMA: A CASE REPORT
Authors: Baughman Brandon , Pebley Kinsey , Pandey Manjari , Ballo Matthew , Michael Madison
Published: December 2020

Meningeal melanocytomas are rare tumors derived from leptomeningeal melanocytes. The aggressive subtype is considered a rare variant of malignant melanoma, carrying a poor prognosis. To date, the extant literature is void of any studies that have systematically assessed cognition or neuropsychological function in these patients. We present a case report of a 61-year-old male, right-hand dominant, Caucasian male with 16 years of formal education. He has an unremarkable medical history, and his presenting symptom were syncopal episodes. An extensive work-up revealed a complex pineal region mass. Serum markers (CEA, AFP, and beta HcG) were negative. The patient continued to deteriorate neurologically and underwent a gross total resection of the mass. At the time of resection, there was evidence of definitive leptomeningeal dissemination. Because of the leptomeningeal spread, he underwent whole brain radiation therapy with a boost to the cerebellum and surgical site. He subsequently required implantation of a ventriculoperitoneal shunt for treatment of communicating hydrocephalus. Prior to WBRT, the patient underwent comprehensive neuropsychological testing. According to the patient and his spouse, they estimated functioning at approximately 50% of normal cognition, with precipitous decline noted prior to resection of the lesion. At the time of the exam, he was dependent in essentially all instrumental activities of daily living. The examination identified a pattern consistent with diffuse subcortical involvement, characterized by impairments in cognitive processing speed, attention, working memory and executive function. Conversely, the patient demonstrated no amnesia or higher cortical dysfunction. Moreover, mood, anxiety, or other psychopathology failed to account for his cognitive impairment. In our review, this is the first case in the literature of a patient with meningeal melanocytoma (with leptomeningeal spread) who has been comprehensively assessed neuropsychologically. Conceptualizations, treatment, and prognosis will be discussed.
NCOG-58. IMPACT OF TIME FROM PRESENTATION TO TREATMENT INITIATION ON CLINICAL OUTCOMES IN CENTRAL NERVOUS SYSTEM LYMPHOMA
Authors: Barbaro Marissa , Pan Peter , Torres Sara , Thakur Kiran , Welch Mary
Published: December 2020

OBJECTIVE

To examine impact of time from presentation to treatment initiation (TPT) on clinical outcomes in a cohort of patients with central nervous system lymphoma (CNSL).

INTRODUCTION

Earlier work in our population found that multifocal disease, cerebrospinal fluid (CSF) sampling, and use of immunomodulatory therapies were associated with longer TPT in CNSL, but impact on clinical outcomes was not assessed.

METHODS

We retrospectively reviewed records of patients who were diagnosed with CNSL from 2010-2018 and treated at Columbia University Irving Medical Center (CUIMC). Regression models were applied to examine the impact of age, gender, response to methotrexate (MTX), use of radiation, and TPT >/= 30 days on survival 1 year from diagnosis (one-year survival), overall survival (OS), and functional independence (FI, defined as Karnofsky Performance Status (KPS) > 70).

RESULTS

There were sixty-nine patients (51% men; median age at diagnosis 70 years, range 21-90). Median TPT was 24 days (range 7-372). TPT was < 30 days in 59 (85%) and >/= 30 days in 10 (15%). One-year survival was 77%, and FI rate was 78%. Negative prognostic factors for OS were age > 65 years (HR 5.34, CI 1.20-24.30, p=0.03) and absence of complete response to MTX (HR 2.40, CI 0.87-6.69, p=0.09). Only complete response to MTX predicted both FI (OR 4.71, CI 1.17-19.02, p=0.03) and one-year survival (OR 6.77, CI 1.98-23.13, p=0.002). Notably, OS was numerically improved among patients with TPT >/= 30 days vs. < 30 days (HR 0.31, p=0.27), though this did not meet statistical significance.

CONCLUSIONS

Longer TPT has been associated with worse outcomes in systemic lymphoma, but such a correlation has not always been observed in brain cancers such as glioblastoma. We found no negative impact of longer TPT on survival or FI.
NCOG-60. MALIGNANT MELANOMA IN NEUROCUTANEOUS MELANOCYTOSIS: A RETROSPECTIVE CASE SERIES (2000-2020)
Authors: Elmore Kevin , Sener Ugur , Ennin Elsie , Suser Stephanie , Marghoob Ashfaq , Haque Sofia , Khakoo Yasmin
Published: December 2020

Neurocutaneous melanocytosis (NCM) is a rare neurocutaneous syndrome which typically develops in children with large congenital melanocytic nevi (LCMN) and excessive melanocyte proliferation in the leptomeninges and brain parenchyma. Malignant melanoma develops in an estimated 2.3% of patients with LCMN and 40-60% of patients with NCM. NCM-associated melanomas frequently harbor NRAS mutations with no well-established role for targeted therapy. In a retrospective, single-institution study, we reviewed eleven patients with NCM-associated CNS melanoma evaluated at Memorial Sloan Kettering Cancer Center from June 2000 to January 2020. Five patients had previously identified focal melanocytosis prior to developing melanoma. In this subgroup, the median time from identification of focal melanocytosis to melanoma diagnosis was 80 months (range: 18-200). Median age at melanoma diagnosis was 9.9 years (range: 1.1-25.3). Presentation at the time of diagnosis with CNS melanoma included headache (45%), focal deficits (45%), and seizure (18%). Eight patients had hydrocephalus (73%). Five patients presented with a focal mass (45%) and six patients had focal or diffuse leptomeningeal disease without a mass (55%). Leptomeningeal spread eventually developed in all patients. Where molecular testing was available, three melanomas had NRAS mutations and none were associated with BRAF mutations. Seven patients were treated with cancer-directed therapy including temozolomide, trametinib, ipilimumab, and nivolumab, with each therapy being administered to two patients. Radiation therapy was used in three patients, including whole brain radiation therapy and stereotactic radiosurgery. Median survival from melanoma diagnosis was 9.1 months (range: 1-60.4). The longest surviving patient was initially diagnosed with cutaneous melanoma, surviving 60.4 months after diagnosis with cutaneous melanoma and 22.7 months after diagnosis with CNS melanoma. Prognosis remains guarded in patients with NCM-associated melanoma, and further investigation is warranted to identify effective management strategies.
NCOG-64. INCIDENCE OF EARLY OCULAR COMPLICATIONS AFTER PROTON RADIATION FOR CHILDHOOD BRAIN TUMORS
Authors: Bavle Abhishek , Confer Michael , Simpson Hilarie , Gavula Theresa , Gross Naina , Lim Maria , McNall-Knapp Rene , Collinge Janine
Published: December 2020

OBJECTIVES

To determine the incidence, timing and risk factors of ocular complications after proton radiation (RT) in childhood brain tumor patients, to better inform screening for these complications.

METHODS

We performed a single-institution retrospective review of children treated with proton RT for brain tumors, with ophthalmology data available. Data abstracted included demographics, radiation details and ocular complications (cataract, dry eyes, retinal changes).

RESULTS

We treated 81 children with brain tumors, with protons, from 2010-18. Forty three patients with ophthalmology data available, were included in the study, with a median age of 8.3 years (y) (0.8 – 20.6y) (13 craniospinal irradiation/CSI, 27 involved-field radiation/IFRT, 3 whole ventricle). Median follow-up from end of radiation to last eye exam was 2.1y (0.2 – 7.2y). The incidence of ocular complications was 21% (9/43 patients) overall, and 62% (8/13) after CSI. Bilateral cataracts were detected at a median of 3.2y post-radiation, with incidence of 14% (6/43) overall and 38% (5/13) after CSI. Three patients underwent lens replacement. Dry eyes developed in 23% (3/13) of patients during or soon after CSI (0.04 and 0.7y post-RT). One patient with craniopharyngioma developed retinal scarring and cataracts, 2.2y and 3.5y, after IFRT. The median radiation dose to the lenses, for patients with cataract, was 26.02 Gy RBE (4 patients: 19.41 – 31.54). For 3 patients with dry eyes, the median dose (Gy RBE) was 27.93 (11.98 – 28.71) to lenses, 36.96 (25.12 – 47.49) to lacrimal glands and 30.78 (25.08 – 36.49) to corneas (mean doses to bilateral ocular structures).

CONCLUSIONS

Children are at risk for cataract and dry eyes after cranial protons, especially CSI, and need ophthalmology follow-up. Larger studies are needed to validate these findings and identify risk-mitigation strategies, with longer follow-up to determine the incidence of ocular complications, and functional outcomes, after cranial proton radiation.
NCOG-68. COMPARING COGNITIVE PROFILES OF PERSONS WITH BRAIN AND NON-BRAIN METASTATIC CANCER
Authors: Willhelm Gabrielle , Del Bene Victor , Aita Stephen , Gammon Meredith , Gerstenecker Adam , Fiveash John , Marotta Dario , Triebel Kristen
Published: December 2020

OBJECTIVE

Cognitive impairment in primary cancer and brain metastatic (BM) cancer has been well-documented. However, to date, there are no neuropsychological studies comparing the cognitive profiles of people with BM and non-brain metastatic cancer (NBM). The present study addressed this gap in the literature by comparing the cognitive profiles of participants with BM and NBM.

METHOD

The study sample consisted of 61 BM, 40 NBM, and 37 healthy control (HC) participants. All participants completed the same neuropsychological battery, including tests of processing speed, attention, working memory, expressive language, auditory-verbal memory, and executive functioning.

RESULTS

Both clinical groups showed reduced processing speed, verbal learning/memory, and executive functions. BM participants performed below HC participants across all neuropsychological tests, while NBM participants performed below control participants on tests of processing speed and executive functioning. The clinical groups differed in semantic verbal fluency (NBM > BM). Fifty-seven percent of BM participants had ≥ 3 impaired scores (i.e., ≤ 5th percentile), and 25% of NBM participants had the same level of cognitive impairment.

CONCLUSION

Over half of BM participants were cognitively impaired on at least three neuropsychological tests, and 25% of NBM participants also demonstrated this same level of cognitive impairment. In the BM group, the elevated rate of cognitive dysfunction is likely due to the greater neurologic disease burden posed by brain metastases, while in the NBM group, the cognitive deficits are possibly due to systemic illness and treatment effects.
NCOG-70. RELIABILITY AND VALIDITY OF A NEW SELF-REPORT INDEX OF COGNITIVE CONCERNS IN BRAIN TUMOR PATIENTS
Authors: Zarrella Giuliana , Perez Alice , Dietrich Jorg , Parsons Michael
Published: December 2020

INTRODUCTION

Subjective cognitive dysfunction is an important outcome measure in neuro-oncology and may provide additional information beyond performance-based neuropsychological testing. The Functional Assessment of Cancer Therapy-Brain (FACT-Br) is a frequently used quality of life (QoL) measure that includes indices of physical, emotional, social, and neurologic aspects of disease, but does not measure cognitive concerns. This study seeks to develop and validate an index of self-reported cognition derived from existing items on the FACT-Br.

METHODS

145 patients (Mage=51.08, Medu=15.63) with heterogeneous brain tumor diagnoses completed neuropsychological evaluation including cognitive testing and self-report measures. Nine FACT-Br items regarding cognition were combined to form the Cognitive Index (CI). Reliability of the CI was measured with Cronbach’s alpha. Concurrent validity was assessed by correlating the CI with the Patient-Reported Outcomes Measurement Information System (PROMIS) Cognitive Abilities-8 or PROMIS Cognitive Concerns-8. Discriminant validity was assessed by correlation of the CI with other FACT-Br indices and the Beck Depression and Anxiety Inventories (BDI, BAI).

RESULTS

Internal consistency within the CI was high (Cronbach’s a 0.864). The CI correlated strongly with the PROMIS-Abilities (r =.680; p< 0.001) and PROMIS-Concerns (r=.780; p< 0.001) indicating high convergent validity. Moderate correlations were observed between the CI and the physical and functional subscales of the FACT (r=.453 and .555), whereas correlations with the social and emotional functioning subscales were weaker (r=.381 and .325). The FACT-Br-CI correlated strongly with BDI (r=-.622) and more weakly with the BAI (r=-.344). Consistent with prior literature, the CI showed modest correlations with neuropsychological measures, including verbal memory encoding (r=.300), verbal fluency (r=.252) and a composite measure of cognition (r=.249; all p’s< .01).

CONCLUSIONS

The FACT-Br-CI is a reliable and valid measure of self-reported cognition. Studies that include the FACT-Br could be retrospectively analyzed to assess self-reported cognitive outcomes, enriching the information gained from prior research.
NCOG-72. DIFFERENTIAL EFFECTS OF SURGERY AND CHEMOTHERAPY ON CHILDREN WITH POSTERIOR FOSSA BRAIN TUMORS
Authors: Dhanani Sofia , O’Neil Sharon , Tanedo Jeffrey , Malvar Jemily , Tamrazi Benita , Finlay Jonathan , Trane Francesca , Rajagopalan Vidya , Lepore Natasha , Nelson Mary Baron
Published: December 2020

BACKGROUND

Few neuroimaging studies of children with brain tumors treated with chemotherapy without radiation exist, and the neuropsychological effects of chemotherapy remain unclear. We aimed to differentiate the effects of surgery and chemotherapy on brain microstructure and cognition.

METHODS

Twenty-eight children with a history of posterior fossa tumor (17 treated with surgery alone; 11 treated with surgery + chemotherapy), and 21 sibling controls (n= 49) underwent diffusion tensor imaging (DTI) and neuropsychological assessment a mean of 4.5 (surgery group) to 9 years (surgery + chemotherapy group) after treatment. Psychometric measures focused on general intelligence, executive functions, processing speed, learning and memory, and social-emotional functioning. Age at diagnosis and time since diagnosis were covariates in the analyses. Group differences in DTI findings and psychometric scores, and correlations between psychometric scores and DTI results were examined.

RESULTS

Mean fractional anisotropy (FA) in the prefrontal cortex, white matter tracts, hippocampus, putamen, globus pallidus, thalamus, and pons were significantly (z≥ 2SD) lower in children treated with surgery + chemotherapy compared to those treated with surgery alone. In neuropsychological evaluation, the patient groups differed only in receptive vocabulary (p= 0.05), with children treated with surgery + chemotherapy scoring lower. Both patient groups scored lower than healthy sibling controls on measures of visuoconstructional reasoning (p= 0.02) and delayed visual (p= 0.02) and spatial memory (p= 0.01). Lower FA in the uncinate fasciculus and higher FA in the right thalamus associated with higher scores on general intelligence (p= 0.003, p= 0.002), and higher FA in the right thalamus associated with higher scores on spatial learning (p= 0.01) and memory (p= 0.01) in children treated with surgery + chemotherapy.

CONCLUSIONS

Chemotherapy is associated with injury to the microstructure of white and gray matter and neuropsychological deficits not seen in children with posterior fossa tumors treated with surgery alone.
NCOG-73. EFFECT OF TIME TO DIAGNOSIS IN CHILDREN WITH MALIGNANT CENTRAL NERVOUS SYSTEM TUMORS ON SURVIVAL OUTCOMES AND DISEASE-ASSOCIATED MORBIDITY: AN INSTITUTIONAL COHORT STUDY
Authors: Ronsley Rebecca , Irvine Mike , Kang Mehima , Goldman Ran , Cheng Sylvia
Published: December 2020

OBJECTIVE

To determine the impact of time to diagnosis on disease related morbidity and mortality.

METHODS

This is a retrospective review of all diagnoses of malignant CNS tumors in children presenting to BC Children’s Hospital (BCCH) from 2000-2019. Analyses were conducted to assess the relationship between time to diagnosis and overall survival as well as long-term morbidity; stratified by tumor type, age and presence of metastatic disease.

RESULTS

From 2000-2019, there were 116 children diagnosed with malignant CNS tumors at BCCH (mean age 9.5 years, 67% male). Tumors included medulloblastoma (27, 23.3%), ependymoma (14, 12.1%), high grade gliomas (19, 16.4%), CNS germ cell tumors (40, 34.4%), and other embryonal CNS tumors (16, 13.8%). Median time to diagnosis from first symptom onset was 63 days (IQR 26.5 – 237.5 days). 18% had metastatic disease. Within this cohort, 3-year EFS was 57%, and 5-year overall survival was 78.4%. 64% of patients were alive with no evidence of disease at median follow up from treatment completion of 4.31 years (IQR 1.77 – 6.15 years). Long-term morbidity included panhypopituitarism (20.7%), vision loss(22.4%), hearing loss(30.2%), learning disability(17.2%) and cognitive impairment (19.8%). In a cox proportional hazards model, overall survival was associated with time to diagnosis(estimate 0.0271;SE=1.6500;p=0.028), high grade glioma(estimate 8.3200; SE=0.6650; p=0.001), age at diagnosis(estimate 0.8590; SE=0.0532; p=0.004), relapse (estimate 4.9600; SE=0.6100; p=0.009) and metastatic disease (estimate 9.1700; SE=0.5660; p< 0.001). Vision loss was also significantly correlated with time to diagnosis (estimate 0.542; SE=0.2940; p=0.038).

CONCLUSION

Median time to diagnosis is associated with overall survival and long-term morbidity in pediatric patients treated for malignant CNS tumors. These data highlight that knowledge translation to the public, primary care and emergency room professionals should be a priority in order to promote early connection with medical care and mitigate morbidity and mortality in those with pediatric CNS tumors.
NCOG-75. ESTIMATED PHYSICIAN COST OF A NEURO-ONCOLOGY MULTIDISCIPLINARY TEAM (MDT) TUMOR BOARD MEETING AT A SINGLE ACADEMIC CENTER
Authors: Schroeder Brett , Graber Jerome , Cuevas Emmanuel
Published: December 2020

BACKGROUND

Multidisciplinary teams (MDTs) to improve coordination across disciplines have become commonplace in oncology. Quantifying the impact of MDTs is challenging, and they carry significant costs. Weekly neuro-oncology tumor boards are attended by neuro-oncologists, neurosurgeons, radiation-oncologists, neuro-radiologists, neuro-pathologists, and support staff including mid-level practitioners, research coordinators, social workers, nurses and trainees. Our aim was to estimate costs associated with neuro-oncology MDTs.

METHODS

The estimated physician cost of MDT meetings were calculated from reported salaries of each physician specialty. Annual salaries from the Doximity 2019 Physician Compensation Report (PCR) included data for 4 neurosurgeons, 4 radiation-oncologists, 2 radiologists, 2 oncologists, and 2 neurologists. Medscape 2019 PCR data was compiled for 4 general surgeons, 2 radiologists, 2 oncologists, 2 pathologists, and 2 neurologists. The Physician Wages Across Specialties by Leigh in 2011 (JAMA) was utilized for 4 neurosurgeons, 4 radiation oncologists, 2 oncologists, and 2 neurologists. Annual salary data was divided by annual hours per specialty as reported by the Annual Work Hours Across Specialties, 2011. These values were then applied to an MDT for one patient, one hour, weekly, and annually.

RESULTS

The Doximity 2019 PCR yielded a per meeting cost of $2,520.84, and an annual cost of $131,083.68. The Medscape 2019 PCR produced a cost of $1,570.60 weekly, and $81,671.20 annually. JAMA data estimated a per meeting cost of $1,448.06, and $75.299.12. The mean per meeting and annual costs were $1846.50, and $96,018.00, respectively. With 6-10 cases per MDT, the mean costs per patient were $184.65 to $307.75.

CONCLUSIONS

Costs of MDT are not negligible. The impact of MDTs on patient outcomes are harder to quantify, but evidence exists that organized MDTs improve patient prognosis, and unorganized MDTs may negatively affect prognosis. Processes to streamline MDTs could help answer outcomes research questions, improve efficiency, and generate clinically relevant performance metrics.
NIMG-03. DEEP LEARNING SURVIVAL ANALYSIS FOR MULTIPLE BRAIN METASTASES
Authors: Chang Enoch , Joel Marina , Chang Hannah , Du Justin , Yu James , An Yi , Hansen James , Omuro Antonio , Chiang Veronica , Aneja Sanjay
Published: December 2020

PURPOSE

Deep learning survival models show promise for outcome prediction by leveraging the ability to model non-linear relationships between pixel-level imaging predictors and survival data. We hypothesized that a deep learning survival model derived from quantitative imaging predictors would be more effective than traditional models of survival in patients with brain metastases.

METHODS

We analyzed 831 patients with 3596 total brain metastases treated with primary stereotactic radiosurgery at our institution between 2000-2018. The primary outcome of interest was overall survival following treatment. 851 3D radiomic features were extracted from T1 post contrast MRI images of each brain metastasis and aggregated per patient. Minimum redundancy maximum relevance was used for dimensionality reduction. Relevant features were trained on DeepSurv (Cox proportional hazard neural network architecture) to model overall survival. The disease-specific Graded Prognostic Assessment which uses age, Karnofsky performance status, presence of extracranial metastases, number of brain metastases, and disease-specific molecular characteristics was used as our traditional model. Discriminatory ability between models was assessed with concordance indices (c-index) using 100 bootstrapped samples of 415 patients and evaluated for statistical significance in difference with the 2-sample t-test.

RESULTS

Median overall survival was 13 months, median age was 63 years, and the most common primary sites were NSCLC (38.5%), melanoma (18.9%), breast (14.9%), SCLC (7.2%), renal (5.3%), and GI (4.7%). The deep learning model using radiomic imaging features (c-index: 0.848, 95% CI [0.811, 0.877]) had superior discriminatory ability compared to the GPA (c-index: 0.380, 95% CI [0.356, 0.403]). Performance was significantly improved with p< 0.001 on the 2-sample t-test.

CONCLUSIONS

A deep learning model using quantitative radiomic imaging features performed better than a traditional linear model using clinical predictors at modeling survival in patients with multiple brain metastases. This represents a promising method to improve prognostication for patients diagnosed with brain metastases.
NIMG-04. MRI EVALUATION OF THE EFFECT OF WHOLE BRAIN RADIOTHERAPY ON BRAIN METASTASIS
Authors: Crowe William , Zhao Dawen , Zhang Zhongwei , Wang Lulu , Bourland John
Published: December 2020

Poor prognosis of breast cancer brain metastasis partially results from the inability of therapeutics to penetrate the Blood-Brain-Barrier (BBB). Whole Brain Radiotherapy (WBRT) is standard-of-care for brain metastasis, however the early effects of fractionated WBRT on brain metastases have not been evaluated. Here, we applied longitudinal MRI to study WBRT’s effect on tumor volume, BBB permeability, and tumor-cell killing using anatomic, Dynamic Contrast Enhanced (DCE), and Diffusion-weighted (DW) MRI, evaluating tumor volume, permeability, and cytotoxic effect, respectively. The BCBM mouse model was established with left ventricle MDA-MB231-Br cell injection. MRI occurred before and 24h after 3 daily fractionated 4Gy WBRT (2.4Gy/min) or sham irradiation. In addition to anatomic MRI, DW MRI measured tissue ADC to study cytotoxic effect, and DCE MRI measured BBB permeability, quantified as the permeability variable Ktrans. Before treatment, T2-weighted images revealed hyperintense multifocal lesions in brains, and many had intact BBB indicated by no T1-w contrast-enhancement. WBRT tumors were smaller than sham irradiated tumors after 3 days (p< 0.05), while no difference in the number of new lesions was observed. DW MRI demonstrated increased ADC in WBRT tumors (p< 0.05), correlating well with elevated Caspase-3 staining of apoptotic cells. T1-w contrast enhanced images of tumors after treatment revealed no differences in the population of contrast-enhanced tumors between the WBRT and sham radiation groups. However, quantitative DCE MRI showed higher Ktrans in WBRT treated tumors relative to sham treated lesions, and an increase in Ktrans of WBRT tumors (p< 0.05), despite high permeability heterogeneity both inter- and intra-tumorally, indicating remaining impermeable BBB. In addition to monitoring tumor volume, longitudinal MRI provided non-invasive assessments of temporal and spatial changes in cellularity and vascular permeability of brain metastasis in response to WBRT, which may prove to be useful for defining an ideal treatment window for potential combination BCBM treatments.