bluuebunny/crossref_metadata_2025_split huggingface dataset:
PATH-25. EXPERIENCE WITH AN RNA FUSION TRANSCRIPT PANEL FOR DETECTION OF POTENTIAL THERAPEUTIC TARGETS IN GLIOMAS
Authors: Kothari Shawn , Bagley Stephen , Desai Arati , Morrisette Jennifer , Sussman Robyn , MacLean Nasrallah 
Published: December 2020

Abstract
Next-generation sequencing to identify fusion proteins is increasingly employed across oncology to identify therapeutic targets.1 The clinical relevance of detecting fusion transcripts is well described in the pediatric glioma population, but similar reports for adult patients are scant.2 The University of Pennsylvania Health System (UPHS) has implemented routine use of an RNA fusion transcript panel (ArcherDX, Boulder, CO) on resected brain tumors since August 2017. Here we report the results of this analysis for adult patients with gliomas and highlight potentially targetable fusions. Over the period of August 2017 through December 2019, fusion analysis was performed on resected gliomas of over 200 patients. Ninety-seven patients were found to have a detected fusion protein. Eighty-three of the 97 patients (86%) had glioblastoma and 14 (14%) had lower grade gliomas. A total of 26 unique fusions were found. The most common (n=55) was EGFRvIII. NTRK fusions were of special interest as FDA-approved agents are available for patients harboring this genetic alteration.3 We identified 8 patients (8%) with NTRK fusions including ARHGEFF2:NTRK1, BNA: NTRK1, BCR: NTRK2, PDE5A/NTRK2, SKAP2/NTRK2, and STRN: NTRK2. Several of these patients went on to receive TRK kinase inhibitors with clinical benefit. Of the 97 patients with a detected fusion, 24 (25%) were found to have a potentially targetable fusion other than EGFRvIII, with inhibitors available in clinical trials or as off-label therapy. These fusions included BRAF (n=5; BRAF: LHFPL3, KIAA1549:BRAF), FGFR (n=9; FGFR3:BRAP, FGFR3:RENBP, FGFR3:TACC3), MET (n=7; CAPZA2-MET, KLF12:MET, PTPRZ1:MET, ST7:MET), and ROS1 (n=3; DLL: ROS1, GOPC: ROS1). In sum, routine clinical use of an RNA-based fusion transcript panel for adult patients with glioma may allow for detection of therapeutically targetable alterations in a meaningful proportion of cases. Prospective trials are needed to determine whether targeting specific fusions is beneficial for adult patients with glioma.
PATH-28. EXTENT AND PROGNOSTIC VALUE OF MGMT PROMOTOR METHYLATION DEPEND ON IDH MUTATION AND 1p19q CO-DELETION IN GLIOMA WHO GRADE II
Authors: Karschnia Philipp , Teske Nico , Siller Sebastian , Dorostkar Mario M , Weller Jonathan , Herms Jochen , Baehring Joachim M , von Baumgarten Louisa , Tonn Joerg-Christian , Thon Niklas 
Published: December 2020

Abstract

INTRODUCTION
Methylation of the promotor region of the O6-methylguanin-DNA-methyltransferase (MGMT) gene is associated with increased survival in low- and high-grade glioma. It is unknown whether this association also applies to the 2016 WHO categories of glioma WHO grade II.

MATERIAL AND METHODS
We retrospectively searched the institutional database of the Center for Neuro-Oncology for patients with glioma WHO grade II. Patients were assigned to one of three groups according to the 2016 WHO classification system: 1. 1p19q co-deleted oligodendroglioma, IDH mutant; 2. 1p19q non-codeleted astrocytoma, IDH mutant; 3. 1p19q non-codeleted astrocytoma, IDH wild-type. MGMT methylation status was analysed using Sanger sequencing of the CpG sites 74-98 within the MGMT promotor region. The total number of methylated CpG sites was calculated for each patient.

RESULTS
155 patients with glioma WHO grade II were encountered, including 81 1p19q co-deleted, IDH mutant oligodendrogliomas; 54 IDH mutant astrocytomas; and 20 IDH wild-type astrocytomas. The mean number of methylated CpG sites among oligodendrogliomas was significantly higher when compared to IDH mutant astrocytomas (18.9 ± 0.4 vs. 16.3 ± 0.6; p = 0.001). In turn, the number of methylated CpG sites among IDH mutant astrocytomas was higher when compared to IDH wild-type astrocytomas (16.3 ± 0.6 vs. 12.3 ± 1.9; p = 0.007). Median follow-up was estimated at 35 months. Median time to malignant progression was 87 months for all patients, and median overall survival was not reached. In the entire cohort, a larger number of methylated CpG sites was prognostic of overall survival and time to malignant progression. When analysed separately for the three WHO subgroups, a similar association was only retained in IDH wild-type astrocytoma.

CONCLUSION
In our series of WHO II gliomas, MGMT promotor methylation appeared strongly associated with 1p19q codeletion and IDH mutations. MGMT promotor methylation was only prognostic in IDH wild-type astrocytoma.
PATH-31. ARTIFICIAL INTELLIGENCE IN GLIOMA PATHOLOGY IMAGE ANALYSIS FOR RISK PREDICTION
Authors: Chunduru Pranathi , Phillips Joanna , Molinaro Annette 
Published: December 2020

Abstract
Pathological evaluation of tumor tissue images stained with hematoxylin and eosin (H&E) is pivotal in diagnosis and predictive of outcome, yet only a small fraction of the rich phenotypic information on the slide is currently used for clinical care. In this study, we developed a computational approach based on deep learning to predict overall survival within distinct molecular subtypes of glioma patients and to extract prognostic biomarkers from microscopic images of tissue biopsies. Whole-slide images from 766 unique patients [IDH: 336 IDH-wildtype, 364 IDH-mutant, 1p/19q: 142 1p/19q-codeleted, 620 1p/19q-non-codeleted] were obtained from The Cancer Genome Atlas (TCGA). Sub-images that were free of artifacts and that contained viable tumor with descriptive histologic characteristics were extracted, which were used for training and testing the deep neural-network. Our unified survival deep learning framework (SDL) uses a residual CNN network integrated with a traditional survival model to predict patient risk from digitized whole-slide images. We employed statistical sampling techniques and randomized transformation of images to address challenges in learning from histology images. Univariable and multivariable Cox proportional-hazards regression models were used to evaluate the significance of predicted patient risk with and without controlling for known prognostic factors. The integrated SDL framework showed substantial prognostic power achieving a median c-index of 0.79 [95 % CI 0.77 - 0.81]. In multivariable Cox regression analysis, SDL risk was significantly associated with overall survival (hazard ratio of 1.65, 95% CI 1.49-1.83, p &lt; 0.001) after adjusting for age, grade, IDH status, ATRX status, 1p19q codeletion and CDKN2A/2B status. Only IDH-status and age were also significant in the multivariable model. Preliminary findings highlight the emerging role of AI in precision medicine and suggest the utility for computational analysis of tumor tissue images for objective and accurate prediction of outcome for glioma patients and also for risk stratification for targeted clinical therapy.
PATH-33. EPIGENOMIC ANALYSIS OF SPINAL EPENDYMOMA
Authors: Yamazawa Erika , Tanaka Shota , Genta Nagae , Hiroko Meguro , Umeda Takayoshi , Hana Taijun , Takami Toshihiro , Nakanishi Yuta , Taniguchi Makoto , Takai Keisuke , Komori Takashi , Ichimura Kouichi , Fukuoka Kohei , Takayanagi Shunsaku , Aburatani Hiroyuki , Saito Nobuhito 
Published: December 2020

Abstract

BACKGROUND
Ependymomas commonly occur in the fourth ventricle and the spinal cord. Gross total resection, age and WHO grade are known prognostic factors. Ependymomas are currently classified into 9 distinct subgroups by DNA methylation profile analysis. Spinal cord ependymoma is distinct from other subgroups. To investigate heterogeneity within spinal cord ependymoma, we examined DNA methylation profiles.

MATERIALS AND METHODS
We used Infinium MethylationEPIC array (illumina) to obtain DNA methylation data from frozen specimens of spinal ependymoma resected at the University of Tokyo, Osaka City University, and Tokyo Metropolitan Neurological Hospital. Japan Pediatric Molecular Neuro-Oncology Group provided methylation data for 11 reported cases. Cluster analysis was performed using Cluster3.0.

RESULTS
We analyzed 34 patients, 21 male and 13 female, aged from 18 to 76 years (median 50.5 years), including 2 cases with neurofibromatosis type 2. WHO grade was grade_3 in 2 cases and grade_2 in others. Clustering of the DNA methylation data showed that WHO grade_3 cases tended to be classified into a subgroup distinct from other cases.

CONCLUSION
This is the largest DNA methylation profiling study on spinal cord ependymoma to date. The study may suggest a new subgroup correlated with higher WHO grade.
PATH-34. GENETIC PROFILING OF AGGRESSIVE MENINGIOMAS REVEAL DIVERSE SPECTRUM OF ACCOMPANYING ALTERATIONS BEYOND NF2 INACTIVATION
Authors: Schulte Jessica , Magill Stephen , Nguyen Minh , Bush Nancy Ann Oberheim , Villanueva-Meyer Javier , Theodosopoulos Philip , McDermott Michael , Butowski Nicholas , Bollen Andrew , Tihan Tarik , Lee Julieann , Pekmezci Melike , Perry Arie , Raleigh David , Solomon David 
Published: December 2020

Abstract

BACKGROUND
Meningiomas are the most common primary central nervous system tumor in adults. The majority are clinically indolent and WHO grade I. However, 20-30% are WHO grade II and 1-3% are WHO grade III, which have shorter progression-free (PFS) and overall survival. A subset of grade I meningiomas also follow an aggressive course, requiring serial resection and/or radiotherapy, similar to high-grade meningiomas. The objective of this study was to characterize the genetic alterations in meningiomas with an aggressive clinical course.

METHODS
Targeted next-generation sequencing (NGS) of 40 aggressive meningiomas was performed using the UCSF500 cancer panel, which assesses ~500 cancer-related genes. Information on patient demographics, tumor histopathology, and treatment history was also collected.

RESULTS
Meningiomas analyzed included 15 (38%) WHO grade I, 11 (28%) WHO grade II, and 13 (33%) WHO grade III. At the time of genetic profiling, 71% of patients had received prior treatment (68% surgery, 48% fractionated radiotherapy, 23% radiosurgery). The most commonly altered gene was NF2, with 71% of tumors demonstrating biallelic inactivation. Other common alterations included biallelic CDKN2A/B deletion (15%) and TERT amplification or promoter mutation (13%). Other recurrent alterations involved SUFU (8%), and ARID1A, ATM, BAP1, DMD, KDM6A, and PTEN (each 5%). Genes which are commonly altered in indolent WHO grade I meningiomas, such as AKT1, KLF4, PIK3CA, SMO, and TRAF7, were intact in this cohort.

CONCLUSIONS
The additional genetic alterations beyond NF2 inactivation that drive aggressive meningiomas are diverse and include homozygous deletion of CDKN2A (negative regulator of cyclin-dependent kinases 4/6), inactivating mutations in SUFU (a negative regulator of Hedgehog signaling), homozygous deletion of PTEN (a negative regulator of mTOR signaling), and mutations/deletions in epigenetic regulatory factors (e.g. ARID1A, KDM6A). Clinical trials are needed to assess the efficacy of therapeutics targeting these specific pathways in patients with meningiomas refractory to conventional treatments.
QOLP-07. HEALTH-RELATED QUALITY OF LIFE AND SYMPTOM BURDEN IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA TREATED WITH BEVACIZUMAB BEYOND PROGRESSION: A PROSPECTIVE TRIAL
Authors: Tanaka Shota , Narita Yoshitaka , Mukasa Akitake , Nagane Motoo , Aoki Tomokazu , Wakabayashi Toshihiko , Uzuka Takeo , Nakamura Hideo , Arakawa Yoshiki , Suehiro Satoshi , Nakada Mitsutoshi , Morita Satoshi , Kato Mamoru , Ichimura Kouichi , Nishikawa Ryo 
Published: December 2020

Abstract

BACKGROUND
In BIOMARK trial, patients with newly diagnosed glioblastoma were treated with standard chemoradiotherapy combined with first-line bevacizumab; a subset of patients continued bevacizumab beyond progression (BBP). Neurocognitive function (NCF), symptom burden, and health-related quality of life (HRQoL) were examined as secondary endpoints.

PATIENTS AND METHODS
In the primary protocol, newly diagnosed glioblastoma patients aged 20-75 received standard 6-week radiotherapy combined with temozolomide and bevacizumab followed by 4-week cycles of temozolomide plus bevacizumab, and then 2-3-week cycles of bevacizumab monotherapy. Upon recurrence, patients were subjected to the secondary protocol with 2-3-week cycles of bevacizumab monotherapy with or without other chemotherapeutic agents. NCF tests (Hopkins verbal learning test-revised, trail making test, and controlled oral word association), EORTC QLQ-C30/BN20, and MDASI-BT were completed by the patients. Time to deterioration (TTD) was defined as the time from randomization until a pre-specified change from baseline without further improvement or death. The Kaplan-Meier method and the log-rank test were used to assess TTD for each subscale of the above tests.

RESULTS
Overall, 94 patients were enrolled in the study. Analyses were based on the full analysis set cohort (N=90), excluding non-glioblastoma diagnosis by central review. The median overall survival (OS) and progression-free survival (PFS) were 25.0 and 14.9 months, respectively. Baseline HRQoL and symptom burden subscales (emotional functioning, symptom severity score, affective factor, and focal factor) were significantly associated with PFS. The median TTD was 8.7, 7.5, 8.1 months for global health status/QoL, symptom severity score, interference score, respectively. Among patients who experienced recurrence, disease progression was apparently preceded by deterioration in terms of symptom burden.

CONCLUSIONS
Detailed analysis of HRQoL and symptom burden may aid care of glioblastoma patients throughout the disease trajectory.
QOLP-11. QUALITY OF END-OF-LIFE CARE IN PATIENTS WITH HIGH GRADE GLIOMAS
Authors: Ou Alexander , Harrison Rebecca , Liu Diane , Naqvi Mujtaba , Naqvi Syed Mussadiq , O’Brien Barbara , Weathers Shiao-Pei , de Groot John , Bruera Eduardo 
Published: December 2020

Abstract

BACKGROUND
Patients with high-grade gliomas (HGG) face unique challenges toward the end of life (EoL), given their aggressive disease trajectory and progressive neurologic deterioration. The discipline of supportive care (SC) has been beneficial in improving quality of EoL care in patients with non-CNS cancers, however data on its contribution to EoL care in patients with HGG is lacking.

METHODS
We retrospectively reviewed charts of MDA patients from 2010-2017 to compare the demographic factors and clinical and quantitative EoL outcomes between patients with HGG--who were either referred (n=54) or not referred (n=85) to SC--and patients with non-CNS cancers who were referred to SC (n=72). A composite score for poor EoL quality outcomes was used with the following variables: death in hospital, chemotherapy within 14d of death, ≥2 hospitalizations, ≥2 ER visits, ICU admission and &gt;14 days hospitalization within the last 30 days of life. Patients were eligible for SC based on poor/declining performance status, &lt; 6 month prognosis, or recurrent GBM.

RESULTS
Patients with HGG had similar EoL quality regardless of SC referral, and these patients in general had better EoL quality than patients with non-CNS cancers (p=0.005). EoL quality was significantly worse in HGG patients who received late versus early SC referrals (p=0.0066). Both weakness (OR=1.27, p=0.0289) and number of disease progressions (OR=2.618, p=0.001) at the time of eligibility for SC were predictive of poorer quality of EOL. The majority of HGG patients (61.2%) eligible for SC were not referred.

CONCLUSIONS
EoL outcomes in patients with malignant gliomas are overall better than those of patients with non-CNS cancer, however certain clinical features and later SC referral remain significantly associated with poorer EoL quality. Our data suggest that the role of SC in improving EoL outcomes in our patient population warrants further evaluation.
QOLP-12. EMBEDDING OUTPATIENT PALLIATIVE CARE INTO NEURO-ONCOLOGY CLINIC – RESULTS FROM A ONE YEAR PILOT
Authors: Taylor Jennie , Rabow Michael , Chang Susan , Butowski Nicholas , Clarke Jennifer , Page Margaretta , Rossi Rosemary , Shibley W Patrick , Calton Brook 
Published: December 2020

Abstract

BACKGROUND
Glioblastoma (GBM) patients fall within NCCN and ASCO guidelines for early palliative care (PC). However, data suggests they are less likely than systemic cancers to be referred to PC and often later in their illness. This results in potential missed opportunities, both for improving symptom control and earlier completion of important tasks, like advance care planning. Data on how to best incorporate comprehensive PC into routine neuro-oncology (NO) patient care is needed.

METHODS
We piloted a program embedding a PC physician into UCSF’s NO clinic one half-day per week. NO physicians were encouraged to refer GBM patients within 3 months of diagnosis and other patients with PC needs. PC visits were offered in-person, by telemedicine, or at home. PC physician and NO social worker made joint visits when possible; chaplaincy support was available by telemedicine. Data was collected using Palliative Care Quality Network (PCQN) database and patient satisfaction survey.

RESULTS
To date, 37 patients have been referred resulting in 103 visits (average 2.8 visits/person): 25% in-person; 68% telemedicine; 6% at home. PC physician and NO social worker met jointly with 46% visits. Median age was 58 years, 41% female, 81% non-Hispanic white, 84% GBM, median 9 months from diagnosis, and 73% receiving first line treatment. Interventions addressed across visits: 94% non-pain symptoms, 76% psychosocial needs; 71% pain; and 70% GOC. Results from satisfaction survey demonstrated 79% would recommend seeing PC embedded in NO to others and highest benefits were attention to practical considerations to staying healthy at home, discussing preferences for future medical care, and help with coping.

CONCLUSIONS
Embedding PC into NO clinics is a unique model for addressing symptoms and GOC early, is well received by patients and caregivers, and provides opportunities for collaboration and PC physicians to specialize in caring for needs of NO patients.
QOLP-14. FROM SYMPTOMS TO RADIOTHERAPY: A QUALITATIVE ASSESSMENT OF PATIENT EXPERIENCE IN NEWLY DIAGNOSED HIGH-GRADE GLIOMA
Authors: Chainey Jonathan , Kim Michael , Chan Vivien Ka-Ying , Au Karolyn 
Published: December 2020

Abstract

INTRODUCTION
Considering the poor prognosis of high-grade gliomas, past studies focusing on the felt experience and supportive care needs of patients concentrated on the end-of-life period. Little is known on these subjects during the initial acute portion of the patient’s journey, from symptom onset, through surgery, to chemoradiation. This period is one of substantial anxiety for patients and their caregivers, and one during which they struggle to comprehend a large amount of information and navigate a complex situation.

METHODS
Adult patients with a new histopathological diagnosis of high-grade glioma who underwent radiotherapy participated in a semi-structured, face-to-face interview. Different segments of the patient’s journey were explored, with a focus on patient’s emotions, interactions with healthcare providers, satisfaction during the process and access to supports. Descriptive thematic analysis in the tradition of grounded theory was performed.

RESULTS
Fifteen patients (7 males, age 34-71 years) were interviewed, and four themes emerged from the analysis. First, information conveyed by the medical team was frequently disconnected from patients’ understanding regarding diagnosis and treatment. Second, specific events created a lasting impression that the medical system, and at times medical care providers, lacked empathy. Third, patients’ perceptions of shortcomings within the medical system led to decreased trust, particularly regarding the follow-up process. Finally, although respondents identified multiple inadequacies during their journey, they nonetheless acknowledged the great support and quality of services they received.

CONCLUSION
This study provides insight into patients’ experiences and perceived shortcomings of the medical system, from the time of presentation until the end of radiotherapy treatment in patients with new diagnosis of high-grade glioma. These findings should influence clinicians’ attitudes and guide systematic changes including delivery of information and the referral process.
QOLP-16. EFFICACY OF SCRAMBLER THERAPY (CALMARE®) FOR THE TREATMENT OF CHRONIC CHEMOTHERAPY-INDUCED PERIPHERAL NEUROPATHY
Authors: Prakash Neal , Tran Rachel , Strain Elizabeth 
Published: December 2020

Abstract

BACKGROUND
Chemotherapy-induced peripheral neuropathy (CIPN) is a common and serious consequence of cancer treatment that, for up to 30% of patients, persists beyond six months of completing chemotherapy. Scrambler therapy (ST) is a therapeutic modality with emerging evidence supporting its ability to diminish CIPN symptoms.

METHODS
Data was from a convenience sample of 24 CIPN patients (with symptoms between 1-240 months after platinum-based, taxane, or combination chemotherapy) completing 10 sessions of ST using the Calmare® device in the City of Hope Outpatient Physical Therapy Department. Patients were treated for ~45 minutes per session over 10 sessions. Patients received a standardized assessment pre- and post ST that included: EORTC chemotherapy-induced peripheral neuropathy questionnaire (QLQ-CIPN20), mono-filament testing, pain intensity numerical rating scale, numbness scale, extensor hallicus longus strength, Timed Up and Go, Romberg, and single leg balance.

RESULTS
Regardless of length of symptoms, significant changes were seen in post-treatment assessment of quality of life as measured by the QLQ-CIPN-20 and numbness scale. Post-treatment QLQ-CIPN-20 total scores decreased by an average of 7.1 points (n= 24, p&lt; .01). Numbness in the left lower extremity decreased by an average of 1 point of the 0-4 point scale (n=24, p=.0007) and 1.09 points on the right lower extremity (n=24, p &lt; .0004). There was a trend towards improvements in pain, monofilament testing, single leg balance, and Romberg test, though they did not reach a level of significance. Surprisingly, only 3 of 24 patients reported pain related to their CIPN at the start of treatment.

CONCLUSION
For patients with CIPN, scrambler therapy improves numbness and improves quality of life measures. This suggests an important role for this treatment modality in cancer patients suffering from this debilitating condition.