tbuckley/cabot-search huggingface dataset:
Prevalence of Informal Caregiving in States Participating in the US Patient Protection and Affordable Care Act Balancing Incentive Program, 2011-2018
Authors: Rebecca Anastos-Wallen, Rachel M. Werner, Paula Chatterjee
Journal: JAMA Network Open (2020)

<h3>Importance</h3> The Balancing Incentives Program (BIP), established under the 2010 Patient Protection and Affordable Care Act provided federal funding for states to shift long-term care out of institutional settings and into the home. However, the association of its implementation with informal caregiving is not known. <h3>Objective</h3> To evaluate the association between BIP participation and the prevalence and frequency of informal caregiving and socioeconomic disparities among caregivers. <h3>Design, Setting, and Participants</h3> The cohort study included respondents to the 2011-2018 American Time Use Survey in BIP-adopting states and non–BIP-adopting states. <h3>Exposure</h3> Living in a state that had implemented the BIP after program implementation had begun (April 2012 to April 2018). <h3>Main Outcomes and Measures</h3> Prevalence of caregiving among all respondents, frequency of caregiving, and minutes of daily sleep, a marker of well-being. Differences-in-differences (DID) regression analysis was used to compare these outcomes between BIP-adopting states and non–BIP-adopting states. <h3>Results</h3> The study included 38 343 respondents in BIP-adopting states (median age, 47 years [interquartile range (IQR), 31-61 years]; 51.9% women), of whom 7428 were caregivers (median age, 51 years [IQR, 37-61 years]; 55.6% women), and 26 437 respondents in non–BIP-adopting states (median age, 48 years [IQR, 32-62 years]; 52.7% women), of whom 5527 were caregivers (median age, 52 years [IQR, 38-62 years]; 57.9% women). There was no change in the prevalence of caregiving between BIP-adopting and non–BIP-adopting states after program implementation (DID, 0.00%; 95% CI, −0.01% to 0.01%). Caregivers in BIP-adopting states were more likely to provide daily care after implementation (DID, 3.2%; 95% CI, 0.3%-6.0%;<i>P</i> = .03) and report increased time sleeping (DID, 15.6 minutes; 95% CI, 4.9-26.2 minutes;<i>P</i> = .005) compared with caregivers in non–BIP-adopting states. This association was more pronounced among caregivers with more education (DID, 25.1 minutes; 95% CI, 6.5-43.8 minutes;<i>P</i> = .01) and higher annual family income (DID, 16.9 minutes; 95% CI, 5.9-27.9 minutes;<i>P</i> = .004) compared with caregivers in non–BIP-adopting states who had the same education and income levels, respectively. <h3>Conclusions and Relevance</h3> In this cohort study, the BIP was associated with increased daily caregiving and improved caregiver well-being. However, it may have disproportionately benefited caregivers of higher socioeconomic status, potentially exacerbating disparities in caregiver stress. Future policies should aim to mitigate this unintended consequence.
CTNI-06. SINGLE-CENTER REAL-WORLD ANALYSIS ON CEREBROSPINAL FLUID IN PATIENTS WITH LEPTOMENINGEAL METASTASES OF NON-SMALL CELL LUNG CANCER
Authors: Junjie Zhen, Lei Wen, Shaoqun Li, Mingyao Lai, Zhaoming Zhou, Changguo Shan, Linbo Cai
Journal: Neuro-Oncology (2020)

Abstract OBJECTIVE To investigate the clinical values of real-world cerebrospinal fluid (CSF) examination in the diagnosis and prognosis of leptomeningeal metastases (LM) in the patients with non-small cell lung cancer (NSCLC). METHODS The clinical manifestations of patients diagnosed with NSCLC-LM in Guangdong Sanjiu Brain Hospital from 2010 until 2019 and the results from the routine, biochemical and cytologic examinations of their CSF were analyzed retrospectively. Moreover, the effects of different indicators on the prognosis of patients were determined by survival analysis. RESULTS Fifty-eight of the 80 patients underwent CSF examination, and the median values of the initial CSF pressure measured by lumbar puncture was 255mmH2O (60-350mmH2O). Tumor cells were found by the cytologic examination of CSF in 56 of the 58 cases (96.6%). The median levels of protein, glucose, chloride, lactate dehydrogenase (LDH) and carcinoembryonic antigen (CEA) in CSF were 0.4g/L (0–8.3g/L), 2.7mmol/L (0–11.9mmol/L), 120.7mmol/L (0–140.5mmol/L), 21.3U/L (0–221.5U/L) and 31.4ng/ml (0–784.2ng/ml), respectively. Sixteen patients underwent gene detection, and the results showed that there were 4 cases of wild type and 12 cases of mutation type. The survival analysis revealed that the median overall survival (mOS) after being diagnosed with LM, patients in LDH≤37U/L group and those in LDH &amp;gt;37U/L group were 8.0 months, 23.7 months and 4.6 months (P=0.039), respectively, which indicated that the LDH level in CSF was the independent prognostic factor for the survival. CONCLUSION Using the cytologic examination of CSF in patients with LM to detect tumor cells is conducive to the early diagnosis of LM. The high CSF pressure in patients with LM is one of the reasons for the neurologic signs and symptoms. The gene mutations found in the CSF in some patients can be used to guide the further systematic treatment. The LDH level in CSF is the independent prognostic factor affecting the survival.
QOL-09. WHOLE-BRAIN WHITE MATTER NETWORK CONNECTIVITY IS DISRUPTED BY PEDIATRIC BRAIN TUMOR TREATMENT
Authors: Adeoye Oyefiade, Kiran Beera, Iska Moxon-Emre, Jovanka Skocic, Ute Bartels, Suzanne Laughlin, Vijay Ramaswamy, Donald Mabbott
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Treatments for pediatric brain tumors (PBT) are neurotoxic and lead to long-term deficits that are driven by the perturbation of underlying white matter (WM). It is unclear if and how treatment may impair WM connectivity across the entire brain. METHODS Magnetic resonance images from 41 PBT survivors (mean age: 13.19 years, 53% M) and 41 typically developing (TD) children (mean age: 13.32 years, 51% M) were analyzed. Image reconstruction, segmentation, and node parcellation were completed in FreeSurfer. DTI maps and probabilistic streamline generation were completed in MRtrix3. Connectivity matrices were based on the number of streamlines connecting two nodes and the mean DTI (FA) index across streamlines. We used graph theoretical analyses to define structural differences between groups, and random forest (RF) analyses to identify hubs that reliably classify PBT and TD children. RESULTS For survivors treated with radiation, betweeness centrality was greater in the left insular (p &amp;lt; 0.000) but smaller in the right pallidum (p &amp;lt; 0.05). For survivors treated without radiation (surgery-only), betweeness centrality was smaller in the right interparietal sulcus (p &amp;lt; 0.05). RF analyses showed that differences in WM connectivity from the right pallidum to other parts of the brain reliably classified PBT survivors from TD children (classification accuracy = 77%). CONCLUSIONS The left insular, right pallidum, and right inter-parietal sulcus are structurally perturbed hubs in PBT survivors. WM connectivity from the right pallidum is vulnerable to the long-term effects of treatment for PBT.
RONC-04. RE-IRRADIATION AFTER TREATMENT OF MEDULLOBLASTOMA; RELAPSED CASES AND SECOND CANCER CASES
Authors: Toshinori Soejima, Nobutoshi Fukumitsu, Yusuke Demizu, Masayuki Mima, Takeshi Suzuki, Atsufumi Kawamura, Yoshiyuki Kosaka
Journal: Neuro-Oncology (2020)

Abstract PURPOSE Late complications such as brainstem necrosis are great concern of re-irradiation for brain tumor. Proton beam therapy can reduce radiation dose of organs at risk such as brainstem, so is expected to reduce late complications. PATIENTS AND METHODS Patients with medulloblastoma treated with re-irradiation from January 2015 to February 2019 at the Kobe Children’s Hospital and the Kobe Proton Center were reviewed. There were three cases of relapsed medulloblastoma and three cases of second cancer (glioblastomas). RESULTS In relapsed cases, all three cases treated with 12 Gy in 8 fractions cranio-spinal irradiation followed by gamma knife radiosurgery (one) or 28.8 Gy (RBE) in 16 fractions of proton beam therapy (two). Follow-up periods were 8 to 19 months (median 12 months) and all three cases survived without relapse. In second cancer cases, all three cases were treated with 40.05 Gy per 15 fractions of radiation therapy (2 cases were treated with photon and one case with proton). However, all cases relapsed and two cases died of disease. CONCLUSION Twelve Gy in 8 fractions cranio-spinal irradiation followed by 28.8 Gy (RBE) in 16 fractions of proton beam therapy is thought to be useful for the relapsed case. Re-irradiation for second cancer was disappointing and further study is warranted.
COVD-16. THE COVID-19 PANDEMIC FROM A NEURO-ONCOLOGY PERSPECTIVE: STRATEGIES, PROTOCOLS, AND LESSON LEARNED
Authors: John Burke, Manish Aghi, Andrew Chan, Praveen Mummaneni, Mitchel Berger
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION The COVID-19 pandemic has had an incalculable impact on our national healthcare system, and elective surgical procedures have been particularly affected. Given that brain tumors often straddle the line between elective and emergent procedures, the pandemic has presented unique challenges to the neuro-oncology community. Here, we present our institutional protocols to (1) maintain an active outpatient neuro-oncology practice, (2) triage surgical cases under limited operating room availability, and (3) safely resume research efforts. METHODS Given the rapidly evolving nature of the pandemic, we based the development of our protocols on the Delphi system to achieve consensus across a multi-disciplinary panel of experts. Specifically, we used this system to develop (1) a standardized physical examination that could be implemented over tele-medicine and (2) a triage system for surgical cases. Research efforts were largely suspended in the early days of the pandemic, however protocols for enrollment in clinical trials as well as the resumption of benchwork were also developed. RESULTS From the COVID-19 shelter-in-place order (March, 2020) through May 2020, our department performed 96 surgeries for the resection of brain tumors compared to 127 such surgeries from the three months prior. During this time, using a modified Delphi procedure, we developed detailed protocols to triage tumor cases. Implementation of telemedicine outpatient visits allowed the continuation of the neuro-oncology clinic and, ultimately, the resumption of clinical trials. CONCLUSIONS The protocols presented here offer several strategies to continue neuro-oncological care during the pandemic, including the surgical treatment of brain tumors. As we prepare for future outbreaks, these treatment algorithms will help ensure that patients with brain tumors receive the highest level of care independent of COVID-19.
Population-based Screening for Hereditary Colorectal Cancer Variants in Japan
Authors: Masashi Fujita, Xiaoxi Liu, Yusuke Iwasaki, Chikashi Terao, Keijiro Mizukami, Eiryo Kawakami, Sadaaki Takata, Chihiro Inai, Tomomi Aoi, Misaki Mizukoshi, Kazuhiro Maejima, Makoto Hirata, Yoshinori Murakami, Yoichiro Kamatani, Michiaki Kubo, Kiwamu Akagi, Koichi Matsuda, Hidewaki Nakagawa, Yukihide Momozawa
Journal: Clinical Gastroenterology and Hepatology (2020)
HGG-57. WHOLE-GENOME SEQUENCING, METHYLATION ANALYSIS, AND SINGLE-CELL RNA-SEQ DEFINE UNIQUE CHARACTERISTICS OF PEDIATRIC TREATMENT-INDUCED HIGH-GRADE GLIOMA AND SUGGEST ONCOGENIC MECHANISMS
Authors: John Lucas, John DeSisto, Ke Xu, Andrew Donson, Tong Lin, Bridget Sanford, Gang Wu, Quynh Tran, Dale Hedges, Chih-Yang Hsu, Gregory Armstrong, Michael Arnold, Smita Bhatia, Patrick Flannery, Rakeb Lemma, Lakotah Hardie, Ulrich Schuller, Lindsey Hoffman, Kathleen Dorris, Jean Levy, Todd Hankinson, Michael Handler, Arthur Liu, Nicholas Foreman, Rajeev Vibhakar, Kenneth Jones, Sariah Allen, Jinghui Zhang, Suzanne Baker, Thomas Merchant, Brent Orr, Adam Green
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Pediatric treatment-induced high-grade glioma (TIHGG) is among the most severe late effects observed in childhood cancer survivors and is uniformly fatal. We previously showed that TIHGG are divergent from de novo pediatric high-grade glioma (pHGG) and cluster into two gene expression subgroups, one stemlike and the other inflammatory. Here we systematically compared TIHGG molecular profiles to pHGG and evaluated expression and single cell sequencing profiles in order to identify oncogenic mechanisms and the cellular basis for the observed TIHGG gene expression subgroups. MATERIALS/ METHODS 450/850K methylation and mutational signature analysis was conducted in 36 TIHGG samples. Resultant data were analyzed for the presence of chromothripsis, distinct molecular alterations, and mutational signatures in a subset of 10 samples with whole genome sequencing data. Five TIHGGs underwent single-cell RNA-Seq analysis (scRNAseq). RESULTS 26/36 TIHGG clustered with the pedRTK1 methylation class. TIHGG were characterized by an increased frequency of chromothripsis relative to pHGG (67% vs. 31%, p=0.036). FISH and WGS revealed frequent PDGFRA amplification secondary to enrichment in ecDNA. TIHGG were enriched for COSMIC mutational signatures 5 and 19 (p=0.0003) relative to pHGG. scRNAseq data showed that TIHGG tumors are composed of stem-like, neuronal, and inflammatory cell populations which may contribute to the previously described dominant expression profiles. CONCLUSIONS TIHGG represents a distinct molecular subtype of pHGG. Chromothripsis, leading to enriched expression of genes in extrachromosomal DNA, likely contribute to TIHGG oncogenesis. The dominant cell type (stem-like vs. inflammatory) may define the expression subgroup derived from bulk RNA-seq in heterogeneous tumors.
CSIG-09. ATRX DEFICIENCY IN GLIOMA IMPACTS TRANSCRIPTIONAL PROFILES AND THE IMMUNE MICROENVIRONMENT IN VIVO
Authors: David Irvin, Hannah Roberts, Vladislav Sharin, Ahsan Farooqi, Sharvari Dharmaiah, Christian Alvarez, Jason Huse
Journal: Neuro-Oncology (2020)

Abstract Current treatment for diffuse astrocytoma fails to address its underlying molecular mechanisms leading to inevitable disease progression and eventual patient death. Genomic studies have implicated ATRX alterations as critical to low grade glioma biology. Our lab has previously shown in vitro that ATRX influences glioma motility, cellular differentiation state, and epigenetic programming, however, the influence of ATRX alterations in vivo remains unclear. Here, we leveraged an RCAS/tva mouse tumor model to probe the role of ATRX deficiency in glioma. Atrx deficient murine tumors exhibited lower histopathological grade and were associated with longer survival than Atrx-intact counterparts, and syngeneic allografts of cell lines derived from primary tumors mirrored the differential degrees of aggressiveness seen in primary tumors. Tumor-derived Atrx-deficient cell lines showed increased susceptibility to G-quadruplex stabilizing compounds, pointing to increased replication stress and recapitulating a key phenotype of ATRX-mutant gliomas in humans. Transcriptional profiling revealed enrichments in MYC target genes, E2F targets as well as G2/M checkpoint pathways in Atrx-intact tumors and cells, and enrichment in RAS signaling in Atrx-deficient tumors and cells. Finally, Atrx deficient murine gliomas displayed increased levels of NK cells, a phenotype recapitulated in ATRX-mutant human gliomas, and primary Atrx-deficient glioma lines exhibited increased levels of NK cell-attracting cytokines. These latter findings suggest that ATRX deficiency could influence interactions between glioma cells and their immune microenvironment by way of phenotypically relevant molecular mechanisms.
Simultaneous epigenetic perturbation and genome imaging reveal distinct roles of H3K9me3 in chromatin architecture and transcription
Authors: Ying Feng, Yao Wang, Xiangnan Wang, Xiaohui He, Chen Yang, Ardalan Naseri, Thoru Pederson, Jing Zheng, Shaojie Zhang, Xiao Xiao, Wei Xie, Hanhui Ma
Journal: Genome biology (2020)

Abstract Introduction Despite the long-observed correlation between H3K9me3, chromatin architecture, and transcriptional repression, how H3K9me3 regulates genome higher-order organization and transcriptional activity in living cells remains unclear. Result Here, we develop EpiGo (Epigenetic perturbation induced Genome organization)-KRAB to introduce H3K9me3 at hundreds of loci spanning megabases on human chromosome 19 and simultaneously track genome organization. EpiGo-KRAB is sufficient to induce genomic clustering and de novo heterochromatin-like domain formation, which requires SETDB1, a methyltransferase of H3K9me3. Unexpectedly, EpiGo-KRAB-induced heterochromatin-like domain does not result in widespread gene repression except a small set of genes with concurrent loss of H3K4me3 and H3K27ac. Ectopic H3K9me3 appears to spread in inactive regions but is largely restricted from transcriptional initiation sites in active regions. Finally, Hi-C analysis showed that EpiGo-KRAB reshapes existing compartments mainly at compartment boundaries. Conclusions These results reveal the role of H3K9me3 in genome organization could be partially separated from its function in gene repression.
LGG-30. TRAMETINIB-ASSOCIATED HYPONATREMIA IN A CHILD WITH LOW GRADE GLIOMA IS NOT SEEN FOLLOWING TREATMENT WITH ALTERNATIVE MEK INHIBITOR
Authors: Margot A Lazow, Sarah A Lawson, Ralph Salloum, Trent R Hummel, Natasha Pillay Smiley, Mariko D DeWire-Schottmiller, Maryam Fouladi, Peter M de Blank
Journal: Neuro-Oncology (2020)

Abstract Molecularly targeted therapy with MEK inhibitors is increasingly being incorporated into the treatment of pediatric low-grade gliomas (LGGs). Trametinib is an orally available MEK1/2 inhibitor that has demonstrated tumor control in LGGs with BRAF alterations. Safe expansion of MEK inhibitor therapy within the pediatric patient population demands adequate understanding of and surveillance for potential MEK-inhibitor specific toxicities, especially among young children. Hyponatremia has been reported in adult patients receiving BRAF/MEK inhibitor combination treatment as well as in two pediatric patients with known diabetes insipidus treated with trametinib monotherapy. To our knowledge, single-agent trametinib has not previously been reported to be associated with hyponatremia in children in the absence of an underlying endocrinopathy. We present a case of hyponatremia associated with trametinib use in an infant with progressive LGG without known endocrine dysfunction, which recurred after significant dose reduction. Therapy with an alternative MEK1/2 inhibitor, binimetinib, provided excellent tumor response without hyponatremia. Hyponatremia is a rare but serious side effect of trametinib, even without underlying pituitary dysfunction. Infants and patients lacking the ability to quickly regulate fluid intake in response to osmolality changes are at particular risk of suffering severe consequences from hyponatremia and should be monitored closely with initiation of trametinib. Switching to a different drug within the same class may offer an alternative to significant dose reduction or discontinuation due to this toxicity.
NCOG-59. PROGRESSION-FREE SURVIVAL AS A PRIMARY OUTCOME MEASURE TO COMPARE CONSOLIDATIVE STRATEGIES IN RELAPSED/REFRACTORY PRIMARY CNS LYMPHOMA
Authors: Alipi Bonm, Alec Gibson, Leona Holmberg, Marco Mielcarec, Tresa McGranahan, Lynne Taylor, Jerome Graber
Journal: Neuro-Oncology (2020)

Abstract Relapsed or refractory primary CNS non-Hodgkin’s lymphoma (rrPCNSL) is a rare and challenging malignancy for which better evidence is needed to guide management. We present a retrospective cohort of 70 consecutive patients with rrPCNSL treated at the University of Washington between 2000-2020. HIV positive and secondary CNS lymphoma patients were excluded. During a median follow-up of 19.8 months, median overall survival (OS) was 18.30 months and median progression-free survival (PFS) was 12.67 months. At all stages of disease (diagnosis, first relapse, multiple relapses), PFS was an excellent predictor of OS. There was a small effect of age &amp;lt; 70 on PFS after initial diagnosis (PFS1), but no effect on PFS after first (PFS2) or subsequent (PFS3+) relapses. There was no effect of age &amp;lt; 60 on PFS1, PFS2, or PFS3+. Patients reinduced with high-dose methotrexate-based (HD-MTX) regimens had an overall response rate (ORR) of 86.7% and median PFS 17.2 months. For patients who responded to reinduction therapy, those consolidated with autologous stem cell transplant (ASCT) had median PFS of 30.3 months (n=11) compared with 12.1 months for other consolidation strategies (n=9), and 9.0 months for no consolidation (n=20). Although patients receiving ASCT were younger, KPS, sex, and the median number of recurrences were similar between consolidation groups. We conclude that PFS is a useful endpoint for rrPCNSL which predicts OS and is not associated with age. Using PFS as an endpoint, we did not detect a benefit to any consolidation strategy other than ASCT.
EPEN-51. CHILDHOOD INTRACRANIAL EPENDYMOMA: A MULTI-CENTER RETROSPECTIVE ANALYSIS
Authors: Emily Owens Pickle, Ana Aguilar-Bonilla, Bertha Ben Khallouq, Stacie Stapleton, Eric Sandler, Anne-Marie Langevin, Jamie Libes, Iftikhar Hanif, Amy Smith
Journal: Neuro-Oncology (2020)

Abstract Ependymoma is a heterogeneous disease which is resistant to improvement. Current challenges are the unreliability of histologic classification, the uncertain role of adjuvant chemotherapy, and a lack of clinical trials integrating molecular and clinical diagnostics into risk-guided therapy. Ependymoma can show surprising latency, reoccurring many years after the original diagnosis. In this study, we performed a retrospective analysis of ependymoma cases treated at six centers over a period of 12 years. A total of 73 cases were submitted from six sites; 68 cases were retained for review. Median age at diagnosis was 4.1 years and gender was reported as male (50%) and female (50%). Histologic grade was reported as Grade II (49%) and Grade III (50%)(not reported: 1). Anatomic location reported as supratentorial (27%) and infratentorial (73%). Metastatic disease was reported in 9% of patients. At diagnosis, gross total resection was achieved in 59% of cases. Twenty-eight percent of patients have died, 59% of patients are alive (with and without disease), and 13% of patients are lost to follow-up. Maximal safe surgical resection is currently the best predictor of long-term survival but was achieved in only 60% of cases. Biology-based therapy will be the next step towards improving the prognosis of pediatric ependymoma.