tbuckley/cabot-search huggingface dataset:
CMET-12. TUMOR CELL DETECTION BY IMMUNOFLOW CYTOMETRY AND BRAF MUTATION ANALYSIS IN CEREBROSPINAL FLUID OF MELANOMA PATIENTS WITH SUSPECTED LEPTOMENINGEAL METASTASES
Authors: Mark van Bussel, Dick Pluim, Bojana Milojkovic-Kerklaan, Daan van den Broek, Jos Beijnen, Willem Boogerd, Jan Schellens, Emilie Le Rhun, Dieta Brandsma
Journal: Neuro-Oncology (2017)

Approximately five percent of melanoma patients develop leptomeningeal metastases (LM). Diagnosis of LM can be made on clinical symptoms and typical contrast enhancement of the leptomeninges on MRI brain or spine and/or CSF cytology. However, MRI has a sensitivity of 76% and a specificity of 77%. Sensitivity of CSF cytology is also low: 55% at first analysis, increasing to 80% upon second sampling. To improve CSF diagnostics in melanoma patients suspected of LM, we developed a MCSP (Melanoma-associated Chondroitin Sulfate Proteoglycan)-based immunoflow cytometry assay and compared its diagnostic value with CSF cytology.To determine driver mutation status, BRAFV600E mutation analysis in cell-free CSF was performed. We included 24 melanoma patients with a clinical suspicion of LM but a non-confirmatory MRI and a subcohort of 5 patients with radiologically proven LM. BRAFV600E mutation in the primary melanoma was determined as part of routine clinical care and BRAF-mutations in ctDNA in cell-free CSF were determined using digital droplet PCR. Cytology had a sensitivity of 70% (95% CI 35–92%) and a specificity of 100% (95% CI 70–100%). At a cut-off value of >0.4 tumor cells/mL the MCSP-based immunoflow cytometry assay had a sensitivity of 100% (66%-100%) and a specificity of 100%(70–100%). We identified BRAFV600E mutations in ctDNA in cell-free CSF in 6 of the 7 BRAF-positive patients with LM. No BRAF-mutation was identified in the absence of LM or in the absence of a BRAF-mutation in the primary tumor. Melanoma cells in CSF can be identified in patients with LM with a negative CSF cytology using the MCSP-based immunoflow cytometry assay. BRAF mutations can be detected in cell-free CSF of BRAFV600E positive patients with LM. Both assays are promising tools to improve the CSF diagnostics in melanoma patients suspected for LM.
P3.16-033 Significance of Spread through Air Spaces in Resected Pathological Stage I Lung Adenocarcinoma
Authors: G. Toyokawa, Y. Yamada, T. Tagawa, F. Kinoshita, Y. Kozuma, T. Matsubara, N. Haratake, S. Takamori, T. Akamine, K. Takada, F. Hirai, Y. Oda, Y. Maehara
Journal: Journal of Thoracic Oncology (2017)
PALL-06. ADVANCE CARE PLANNING IN GLIOBLASTOMA PATIENTS: PHASE I OF A FEASIBILITY STUDY
Authors: Lara Fritz, Linda Dirven, Jaap C Reijneveld, Johan A F Koekkoek, Hanneke Zwinkels, Anne M Stiggelbout, H Roeline W Pasman, Martin J B Taphoorn
Journal: Neuro-Oncology (2017)

Although Advance Care Planning (ACP) has shown to improve outcomes in other patient groups, including patient/family satisfaction and the quality of end of life (EOL) care, it is unknown if implementation of an ACP program would be feasible in daily clinical practice for glioblastoma patients. In phase I of this feasibility study, we aimed to assess possible barriers and facilitators for participation and implementation, the preferred content of the ACP program, and the best time to introduce such a program in the disease trajectory. A focus group with health care professionals (HCPs) was conducted as well as individual semi-structured interviews with patients and proxies (of both living and deceased patients), which were thematically analyzed. Barriers for participation were that the program would be confronting or exhausting, while facilitators included access to information and finding peace. All predefined topics were considered relevant by participants, but should not be discussed too early, especially topics with respect to EOL care. New topics included proxies’ needs and financial issues. The optimal time to introduce varied; HCPs and proxies of deceased patients indicated that the program should be implemented soon after diagnosis. Living patients and their proxies indicated that the program could be initiated soon after diagnosis, but that topics about the EOL phase should be postponed until the EOL phase has started. The positive results of phase I are currently used to develop an ACP program specifically for GBM patients, which will subsequently be evaluated in a longitudinal prospective study. The results suggest to offer the program soon after diagnosis, but patients and proxies should choose themselves which topics they want to discuss. The program itself, as well as its impact on several outcomes (e.g. health-related quality of life, satisfaction with care and quality of EOL care) will be evaluated.
P2.10-006 Prognostic Factors of Mortality and Recurrence of Malignant Pleural Effusion in High-Risk Tumors According to the LENT Score Study
Authors: F. Abrão, M. Oliveira, G. Viana, I. Abreu, R. Younes, C. Marciano
Journal: Journal of Thoracic Oncology (2017)
P3.03-017 Blood Samples NGS for Baseline Molecular Signature of Anotinib Treated Advanced NSCLC Patients in ALTER0303 Trial
Authors: B. Han, Y. Zhao, K. Li, J. Wang, Q. Wang, L. Zhang, J. Shi, Z. Wang, J. He, Y. Shi, Y. Cheng, W. Chen, X. Wang, Y. Luo, K. Nan
Journal: Journal of Thoracic Oncology (2017)
OA 02.03 Prophylactic Irradiation of Tracts (PIT) in Patients with Pleural Mesothelioma: Results of a Multicenter Phase III Trial
Authors: N. Bayman, W. Appel, L. Ashcroft, D. Baldwin, A. Bates, L. Darlison, J. Edwards, V. Ezhil, D. Gilligan, M. Hatton, T. Mansy, M. Peake, L. Pemberton, R. Rintoul, D. Ryder, P. Taylor, C. Faivre-Finn
Journal: Journal of Thoracic Oncology (2017)
TMIC-45. DIFFUSION OF D-2-HYDROXYGLUTARATE FROM IDH1 MUTANT GLIOMAS IN THE BRAIN
Authors: Craig Horbinski, Grant Hartung, Benjamin Liu, Snezana Mirkov, Kevin Tangen, Dusten Unruh, Jann Sarkaria, Andreas Linninger
Journal: Neuro-Oncology (2017)

Approximately 20-30% of diffusely infiltrative gliomas in adults contain a point mutation in isocitrate dehydrogenase 1 (IDH1mut), which leads to production of D-2-hydroxyglutarate (D2HG). Production of D2HG is so efficient that D2HG concentrations often reach 30 mM within IDH1mut gliomas. Yet, while up to 100 µM D2HG can be detected in the circulating cerebrospinal fluid of IDH1mut glioma patients, the amount of D2HG to which nonneoplastic cells are exposed within and surrounding an IDH1mut glioma is unknown and difficult to measure directly in patients or animal models. Thus, to date, the majority of research on D2HG has focused on its effects inside tumor cells, with very little known about its role in the tumor microenvironment. Liquid chromatography-mass spectrometry (LC-MS) analysis indicates that patient-derived IDH1mut glioma cells release approximately 3.7-6.7 pg D2HG per cell per week in culture. Extrapolating this to an average-sized tumor (30 ml glioma volume and 1x108 cells/ml tumor, the latter based on a previously published estimate of tumor cell density), the rate of D2HG release by an IDH1mut glioma (SA) is calculated to be 3.2-5.8x10-12 moles/ml/sec. Mathematical models of D2HG production and diffusion around an IDH1mut glioma were independently generated based on intracerebral fluid dynamics and previously reported D2HG concentrations in the cerebrospinal fluid. These models estimate an SA of 2.9-17.0x10-12 moles/ml/sec, in good agreement with the LC-MS data generated from in vitro models. In even the most conservative of these diffusion models, the extracellular concentration of D2HG exceeds 3 mM within a 2 cm radius from the center of an IDH1mut glioma. This has profound implications for understanding how D2HG may alter the microenvironmental landscape in IDH1mut gliomas.
GENE-60. INTEGRATED GENOMIC AND EPIGENOMIC ANALYSIS FOR HEMANGIOBLASTOMAS OF THE CENTRAL NERVOUS SYSTEM
Authors: Shunsaku Takayanagi, Akitake Mukasa, Masashi Nomura, Shota Tanaka, Hirofumi Nakatomi, Keisuke Ueki, Kohichi Ichimura, Hiroyuki Aburatani, Nobuhito Saito
Journal: Neuro-Oncology (2017)

Hemangioblastomas (HBs) are benign central nervous system (CNS) neoplasms that present as sporadic, isolated lesions or as a subset of CNS lesions in von Hippel-Lindau (VHL) disease. VHL disease caused by a germline mutation of VHL on chromosome 3 predisposes individuals to multi-organ tumors, including clear cell renal cell carcinomas (ccRCCs), as well as HBs. HBs have not been analyzed in detail regarding genetic and epigenetic alterations as much as ccRCCs. Genetic and epigenetic alterations were comprehensively analyzed in 11 VHL disease-related HBs and 21 sporadic ones. Using direct sequencing, target deep sequencing, multiplex ligation-dependent probe amplification assays, VHL alterations were detected in 100% and 62% of VHL-related and sporadic HBs, respectively. Using data from single nucleotide polymorphism arrays, the almost similar ratios of VHL-related and sporadic HBs were found loss of heterogyzosity (LOH) on chromosome 3 (64% and 57%, respectively). VHL premotor hypermethylation was detected only in sporadic HBs (33%). The rate of biallelic VHL inactivation among VHL-related and sporadic HBs was 64% and 52%, respectively. No significant mutation of PBRM1,BAP1,SETD2, which are novel candidate genes that may be causative for ccRCCs, was detected in HBs by using target deep sequencing. No HB of CIMP (CpG island methylator phenotype), which was known to be detected in a subset of ccRCCs, was detected by using an Illumina Infinium 450K methylation chip. Although biallelic inactivation of VHL is a dominant mechanism in the pathogenesis of HBs, as well as ccRCCs, other unknown mechanisms different from ccRCCs may also be involved in the pathogenesis of HBs.
GMC to push for erasure of paediatrician convicted of manslaughter
Authors: Clare Dyer
Journal: BMJ (2017)

The General Medical Council is to press ahead with an appeal in the High Court against what it considers a too lenient regulatory sanction on a paediatrician convicted of gross negligence manslaughter, despite a letter signed by more than 100 doctors urging the GMC to reconsider.

Last June a medical practitioners tribunal found that Hadiza Bawa-Garba’s failings were a causative factor in the death of 6 year old Jack Adcock from sepsis. But the tribunal decided not to accede to the GMC’s call to strike her off the UK medical register.

Instead, the tribunal opted for a 12 month suspension from the register, citing “multiple systemic failures,” her unblemished record before and since, and evidence from colleagues and consultants that she was …
MA 09.09 Isotoxic Dose-Escalated Radiotherapy (RT) in Non-Small Cell Lung Cancer (NSCLC) with Deep Inspiration Breath Hold (DIBH)
Authors: H. Bainbridge, A. Dunlop, D. Mcquaid, R. Colgan, S. Popat, N. Yousaf, J. Bhosle, M. O’Brien, M. Ahmed, I. Locke, F. Mcdonald
Journal: Journal of Thoracic Oncology (2017)
Abstract 19076: Long-Term Vascular Response to Cobalt-Chromium Everolimus-Eluting Stent: Five-Year Follow-Up Optical Coherence Tomography Study
Authors: Shoichi Kuramitsu, Shinjo Sonoda, Hiroyuki Jinnouchi, Yoshitaka Muraoka, Shinichi Shirai, Kenji Ando
Journal: Circulation (2016)

Introduction:  The cobalt-chromium everolimus-eluting stent (CoCr-EES) have shown the improved safety and efficacy compared with first-generation drug-eluting stents. However, the long-term vascular response to CoCr-EES has not been fully evaluated.   Hypothesis:  We sought to assess the vascular response to CoCr-EES at 5 years after stent implantation using optical coherence tomography (OCT).   Methods:  From April 2015 and January 2016, a total of 24 patient (28 lesions) treated only with CoCr-EES and without any treated-vessel related events during the 5 years after the procedure were prospectively enrolled at 2 Japanese institutions. Quantitative parameters and qualitative characteristics of the neointima were evaluated. In addition, to assess whether the lesion complexity affects the long-term vascular response to CoCr-EES, we compared the OCT findings between lesions with type C of the AHA/ACC classification and those with non-type C.   Results:  A total of 5738 struts in 35 CoCr-EESs were analyzed. Uncovered and malapposed struts were found in 62 (1.1%) and 38 (0.66%) out of 5738 struts, respectively. Cross-sectional qualitative analysis of the neointima tissue showed that the frequency of lipid-laden neointima was 24 out of 621 cross-sections (3.9%). Compared with non-type C lesions, the frequency of malapposed struts was significantly higher in type C lesions (0.92% vs. 0.19%, p  0.99). No significant difference in the frequency of lipid-laden neointima was found between the type C and non-type C lesions (2.8% vs. 5.7%, p=0.09)   Conclusions:  CoCr-EES shows an excellent vascular response at 5-year follow-up. The lesion complexity might have little influence on long-term vascular response to CoCr-EES in stable patients.
NCOG-09. COMPREHENSIVE ASSESSMENT OF LONG-TERM SOCIAL COGNITION (THEORY OF MIND) OUTCOMES IN GLIOMA PATIENTS FOLLOWING STANDARD-OF-CARE TREATMENT
Authors: Taylor Sutcliffe, Olivia Bjorkquist, Kateryna Skirnyk, Matthew Tate
Journal: Neuro-Oncology (2017)

Gliomas and their treatment have been shown to impact patients' behavioral and emotional regulation and personality, which can affect social relationships and overall quality of life. Theory of Mind (ToM), an important component of social cognition, is the ability to attribute mental states (thoughts, beliefs, intentions) to oneself and others. Prior data suggest the right frontal cortex is critically involved in ToM performance, although much of these data are based on a single measure, Reading the Mind in the Eyes. In this study, to more comprehensively assess social cognition and identify critical aspects of ToM impaired in this population, six validated ToM tasks were administered to glioma patients postoperatively (n=10) and to matched normal subjects (n=5). Tasks assessed multiple ToM domains, including mental state attribution (Reading the Mind in the Eyes, Reading the Mind in the Voice), intention attribution (Comic Strip, Picture Sequencing), and understanding of social motivations (Happé's Stories) and complex social situations (Faux Pas). Glioma patients' performance on Picture Sequencing was poorer than that of matched controls (88.9% vs. 97.1%, p<0.05), though there was no difference in their performance on other tasks compared to controls. Additionally, performance of patients with left-sided tumors was inferior to that of patients with right-sided tumors on Picture Sequencing (83.9% vs. 92.9%, p<0.05) and Happé's Stories (88.9% vs. 97.1%, p<0.05). Overall, our preliminary data indicate subtle deficits in intention attribution in glioma patients, suggesting intention attribution is most impaired in this population and that Picture Sequencing might be the most sensitive task for detecting these deficits. Glioma patients performed strongly overall despite surgery and chemoradiotherapy, suggesting significant plasticity of ToM networks. We anticipate that, with increased power, our study will reveal greater social cognition deficits in glioma patients, which will allow us to investigate relationships between task performance, tumor characteristics, and functional outcomes.
P1.01-016 Next-Generation Sequencing Shows Mechanisms of Intrinsic Resistance in ALK-Positive NSCLC Patients Treated with Crizotinib
Authors: B. Solomon, J. Soria, F. Blackhall, A. Shaw, D.R. Camidge, D. Kim, T. Mok, J. Fernandez-Banet, Z. Kan, S. Li, Y. Liu, S. Ho
Journal: Journal of Thoracic Oncology (2017)
Fast Setting Silk Fibroin Bioink for Bioprinting of Patient‐Specific Memory‐Shape Implants
Authors: João B. Costa, Joana Silva‐Correia, Joaquim M. Oliveira, Rui L. Reis
Journal: Advanced Healthcare Materials (2017)

Abstract The pursuit for the “perfect” biomimetic and personalized implant for musculoskeletal tissue regeneration remains a big challenge. 3D printing technology that makes use of a novel and promising biomaterials can be part of the solution. In this study, a fast setting enzymatic‐crosslinked silk fibroin (SF) bioink for 3D bioprinting is developed. Their properties are fine‐tuned and different structures with good resolution, reproducibility, and reliability can be fabricated. Many potential applications exist for the SF bioinks including 3D bioprinted scaffolds and patient‐specific implants exhibiting unique characteristics such as good mechanical properties, memory‐shape feature, suitable degradation, and tunable pore architecture and morphology.
MNGI-12. A RETROSPECTIVE INTERVENTIONAL COHORT STUDY TO ASSESS THE EFFICACY AND SAFETY OF SANDOSTATIN LAR (OCTREOTIDE ACETATE) FOR THE TREATMENT OF MENINGIOMAS IN ADULT PATIENTS
Authors: Emely Nguyen, Beverly Fu, Manisha Dandekar, Jose Carrillo, Xiao-Tang Kong, Gilbert Cadena, Frank PK Hsu, John Billimek, Daniela Bota
Journal: Neuro-Oncology (2017)

Meningioma is the most common primary intracranial tumor in adults. Thorough majority of tumors are slow growing, many patients fail first-line treatments with surgery and/or radiation. Others are poor surgical candidates for definitive surgical resection due to their age, tumor location or associated medical comorbidities. Few targeted therapies and biologics for meningioma are studied, and they have limited efficacy. This study aims to assess the efficacy and safety of Sandostatin LAR as a potential treatment for recurrent, treatment resistant meningiomas. The retrospective chart review included patients over 18 years of age and diagnosed with meningioma who were administered Sandostatin LAR from 01/01/2010 until 06/01/2017 at the University of California, Irvine (UCI). The primary endpoints were overall survival (OS) and progression-free survival (PFS). The secondary endpoint was assessing safety. There were 47 patients included in the chart review. The mean age was 64 years old and 69.6% were female. The mean KPS score was 80 (60-100). The majority of patients were diagnosed with WHO grade 1 meningioma (73.3%) compared to WHO grade 2 (11.1%) and WHO grade 3 (15.6%). Of the 47 patients, 14 experienced disease progression and 6 died. The mean overall survival times for grade 1, 2, and 3 were 4.5, 2.3, and 0.91 years respectively. Median time to progression for grade 1, 2, and 3 were 3.1, 2.3, and 0.20 years respectively. The most common AE was diarrhea which occurred in 19 out of 47 patients. Overall, Sandostatin LAR was well tolerated. This is the largest reported cohort of meningioma patients treated with Sandostatin LAR and it suggests that Sandostatin LAR can be an effective, well tolerated treatment for these patients.
ACTR-47. COMBINED TREATMENT WITH HYPOFRACTIONATED RADIOTHERAPY AND TEMOZOLOMIDE BENEFITS OVER SINGLE TREATMENT IN ELDERLY PATIENTS WITH METHYLATED BUT NOT UNMETHYLATED MGMT GLIOBLASTOMA
Authors: Motoo Nagane, Yuki Yamagishi, Keiichi Kobayashi, Kuniaki Saito, Daisuke Shimada, Satoshi Kume, Shohei Iijima, Nobuyoshi Sasaki, Yoshiaki Shiokawa
Journal: Neuro-Oncology (2017)

Recent results from several phase III randomized trials for elderly patients with glioblastoma (GBM) led us to choose treatment regimens by era according to what were thought to be standard of care at that time. Here we compare retrospectively the outcome of the regimens selected to evaluate optimal therapeutic options for the intractable disease. Sixty-three patients (female: 32) with histologically confirmed GBM at age of 71 or older receiving postoperative adjuvant therapy since 2000 were eligible. Treatment principles were as follows: Era A (-2006): radiotherapy (RT) 60 Gy; B (2007–2008): RT (60 Gy) plus temozolomide (TMZ); C (2009–2013): RT plus TMZ (60 Gy for age 71–75; 40 Gy for age 76 or older); D (2013-): RT 40 Gy (unmethylated MGMT) or TMZ (methylated MGMT). mOS/mPFS were 14.9 m/5.6 m. mOS by treatment era was as follows: A 5.5 m, B 16.8 m, C 16.9 m, D 12.5 m (p=0.049). Combination of RT plus TMZ yielded significantly better OS (p=0.037) and PFS (p=0.003) than other treatments, which was more prominent in methylated MGMT cases (OS: p=0.005, PFS: p<0.001), but not in unmethylated MGMT. Multivariate analysis showed KPS, EOR, and RT/TMZ combination as significant prognosticators for OS. Furthermore, in 50 patients treated with RT, TMZ, or both, combined RT/TMZ lead to better outcome. Of note, those with methylated MGMT had significantly longer PFS by RT/TMZ than TMZ alone. RT plus TMZ is recommended for elderly GBM patients especially if MGMT is methylated.
P3.03-025 Tumor Biomarkers for the Routine Care of Advanced Non-Small-Cell Lung Cancer: A Decade of Experience in Implementing Predictive Genomic Events
Authors: D. Rangachari, P. Vanderlaan, X. Le, A. Majid, M. Parikh, S. Gangadharan, M. Kent, M. Huberman, S. Kobayashi, D. Costa
Journal: Journal of Thoracic Oncology (2017)
RARE-04. SYNCHRONOUS CENTRAL NERVOUS SYSTEM (CNS) ATYPICAL TERATOID/ RHABDOID TUMOR (AT/RT) AND A MALIGNANT RHABDOID TUMOR OF THE KIDNEY- CASE REPORT OF A LONG-TERM SURVIVOR AND A REVIEW OF THE LITERATURE
Authors: Mohammad H Abu Arja, Priyal Patel, Jeffery Auletta, Erin Meyer, Mark Ranalli, Diana Osorio, Pournima Navalkele, Summit Shah, Jonathan L Finlay, Suzanne Conley, Jennifer Aldrink, Jonathan Pindrik, Mohamed AbdelBaki
Journal: Neuro-Oncology (2017)

Central nervous system (CNS) atypical teratoid/rhabdoid tumor (AT/RT) with synchronous or metachronous extra-CNS tumors are extremely rare in children. The majority have a germline mutation in the SMARCB1 gene and a very poor outcome. We report one of longest surviving cases in the literature for a child diagnosed with a metastatic CNS AT/RT and a synchronous malignant rhabdoid tumor (MRT) of the kidney. We also conducted an extensive literature review for patients diagnosed with CNS AT/RT and synchronous or metachronous extra-CNS primary tumors. A seven-week old female was diagnosed with a posterior fossa AT/RT with spinal metastasis and a synchronous MRT of the right kidney. The patient was treated using an intensive multimodality approach combining surgical resection, intra-thecal chemotherapy, and high-dose chemotherapy (HDCT) with autologous hematopoietic stem cell support (AHSCS). She is currently 24 months of age without any evidence of disease. Our literature review identified 27 children diagnosed with a CNS AT/RT and extra-CNS tumors. The median age at presentation was 4.1 months with 19 patients presenting in the first six months of age. The most common site of extra-CNS disease was the kidney. Germline mutation in SMARCB1 gene was reported in 74.1% of the patients. The median survival time was 5.6 months, with only two patients surviving more than 24 months. The use of irradiation was avoided in our patient and in one of the two other surviving patients. Children with CNS AT/RT with synchronous or metachronous extra- CNS tumors have a dismal prognosis. The rarity of the tumor and lack of a standard treatment approach have contributed to the reported poor outcomes. An aggressive multimodal treatment approach including maximal surgical resection, intra-thecal chemotherapy and HDCT with AHSCS may improve the outcomes for this patient population without the need for radiation therapy.