tbuckley/cabot-search huggingface dataset:
OS8.4 Impact of brain invasion assessment on outcome in intracranial grade II meningiomas
Authors: T Picart, C Dumot, F Ducray, A Durand, J Guyotat, M Berhouma, D Meyronet
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Brain invasion has already been identified as an independent criterion of meningioma recurrence by Jääskaläinen’s in 1986. While it was only suggested that meningiomas harbouring brain invasion could be staged as grade II in the 2007 WHO Classification of Tumours of the Central Nervous System, brain invasion was clearly listed as a grade II atypical meningioma criterion for the first time in the 2016 version. Since 2007, brain invasion has been carefully screened during the histopathological characterisation of meningiomas in our centre thanks to specific training of the neuropathology department staff. Furthermore, neurosurgeons are asked to provide well-preserved and grossly orientable tumours borders whenever possible. The aim of the present study was to compare the characteristics of patients diagnosed with grade II meningiomas before and after this change of practices. MATERIAL AND METHODS We retrospectively reviewed the characteristics of 125 patients with grade II meningiomas diagnosed between 2011 and 2014 (group A) and compared them to those of 166 patients with grade II meningiomas diagnosed between 1998 and 2005 (group B). RESULTS Tumour location and socio-demographic parameters were comparable in group A and B with a median age of 62 years in both groups (p=0.18). There were more de novo meningiomas in group A (84% vs 68.7%, p=0.004). Brain invasion was found in 59% in group A and 9% in group B (p=0.00001) while median Ki67 labelling was of 8.4% in group A and 10.5% in group B (p=0.04). Consistently, tumour borders were irregular in 52% in group A and 29% in group B (p=0.0002). Progression free survival was similar in the two groups (65 vs 66 months, p=0.92) but grade progression was more frequently observed in group B (18.9% vs 0%, p=0.006). In group A, meningiomas that were classified as grade II exclusively based on brain infiltration (n=33, group A-bi) had a similar progression rate compared to meningiomas with other criteria of atypia (27% vs 25%, p=0.98) and a similar time to progression (32 vs 32 months, p=0.74). The median time to progression of group A-bi meningiomas was also comparable to that of the other 258 pooled meningiomas (32 vs 40 months, p=0.40). CONCLUSION In accordance with the 2016 WHO Classification of Tumours of the Central Nervous System, the outcome of meningiomas defined as atypical solely based on brain infiltration seems to be comparable to that of meningiomas with other criteria of atypia. Appropriate coordination between neurosurgeons and neuropathologists is mandatory to optimally assess this criterion.
A phase I feasability study of concurrent fondaparinux (F) with carboplatin (Crb) and paclitaxel (P) for metastatic non-small cell lung cancer (NSCLC): An analysis of coagulation/angiogenic biomarker (CABM) kinetics.
Authors: David James Mooney, Debi Miley, Mary Jerome, Stefan C. Grant, Francisco Robert
Journal: Journal of Clinical Oncology (2013)

e19143 Background: There is an association between risk of thrombosis and metastatic cancer. Chemotherapy (C) also independently increases thrombotic risk. This increased risk is multifactorial, including endothelial damage and release of angiogenic cytokines. We hypothesized that adding anticoagulation to C may decrease thrombotic risk and also, potentially, have anti-tumor effect. Methods: The primary aim of this study was to determine the tolerability and safety (bleeding events) of the combination of F with 21-day cycle chemotherapy (Crb AUC 6 + P 200 mg/m 2 ) in two cohorts of untreated patients (pts) with stage IV NSCLC. The secondary objectives were to determine incidence of venous thrombosis (VT), changes in CABM parameters during treatment, and clinical efficacy endpoints. Two cohorts of pts received F from cycles 2-4 with Crb+P. Cohort A received 2.5 mg F daily from cycle 2-4. Cohort B received 7.5 mg of F on day 1, 2 of cycle 2-4 and 2.5 mg F on day 3-21. Results: Clinical data from 19 evaluable pts are as follows: median age 55 years, 63% male, and 32% adenocarcinoma. There was no major bleeding event (BE) in either cohort, and 5 pts had a minor BE. There was no VT. Median time to progression was 5 months (3.8-6.2 months), and overall survival was 10 months (4.3-15.6 months). Baseline values of sensitive markers of activated coagulation (D-Dimer, Thrombin Anti-Thrombin Complex) were above the normal range in most patients. These biomarkers tended to increase during the first cycle (without F); whereas the same markers decreased during the second cycle (with F). A reduction of the angiogenic biomarkers during therapy was observed with VEGF, TGF-β1, and Angiopoietin-1. Conclusions: Concurrent treatment with F and chemotherapy for metastatic NSCLC is feasible with no major bleeding and little minor bleeding. During chemotherapy, coagulant and angiogenic biomarkers tended to increase, perhaps suggesting an increase in thrombogenic state. When F was added, these markers trended downward, suggesting that the proangiogenic state associated with cancer may be significantly altered by anticoagulation. Clinical trial information: NCT00476216.
Pancreatic Ductal Adenocarcinoma—ESPAC…or It’s Back?
Authors: Maxwell Trudeau, Charles M. Vollmer
Journal: JAMA Surgery (2019)

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P04.19 Analysis of tumor immune microenvironment and immune checkpoint modulators across infantile and pediatric pilocytic astrocytomas to elucidate the role of immunotherapy in these tumors
Authors: K Kaur, V Suri, M C Sharma, A Garg, A Suri, C Sarkar
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Pilocytic astrocytomas are the most common central nervous system tumors in pediatric age-group. Although grade I, some of the cases show recurrence and progression, and few might not be amenable to surgery due to location or size, and hence have a less favorable prognosis. Drugs blocking immune check-point interactions such as those including programmed cell death ligand-1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are now in clinical use for certain tumors. We performed this study to understand the potential candidature of pilocytic astrocytomas in infants and children for immunotherapy by analyzing the expression of immune checkpoint proteins and immune infiltrate, and correlating with clinical details, wherever possible. MATERIALS AND METHODS Cases with adequate tissue (2010–2017) diagnosed in pediatric age-group (&lt;18 years) were retreived from the archives of Department of Pathology, AIIMS, New Delhi. Immunohistochemistry for PD-L1 (SP263, Ventana), CTLA-4, CD3, CD8, CD4 and CD68 was performed. Quantification of cytotoxic lymphocytes was done using digital imaging in the core of the tumor. RESULTS A total of 50 pilocytic astrocytomas were included, 14 of them were &lt;3 years (infants), while 36 were of pediatric age-group (3–18 years). Overall, male preponderance was noted. Cerebellum was the most common location, followed by 4th venrticle, optic pathway, hypothalamus, cerebrum and thalamus. Almost all CD3 lymphocytes were cytotoxic T-lymphocyes (CD8 positive, CTLs). Helper T-lymphocyte infiltration was not seen. Median CTL density/mm3 was 13/mm3(Range:1–85/mm3). CTLA-4 was positive in 4 cases, positivity ranged from 1–4 cells/lpf. PD-L1 was found to be positive in 7 cases, and the positivity ranged from 1+ to 2+ in 1 to 5% of tumor cells. A median TAM (tumor associated macrophages) density of 44/hpf (range: 1–98/hpf) was noted. There was no correlation of CTL density with PD-L1 or CTLA-4 expression, and neither with TAM density. On correlation with clinical parameters, a higher density of CTLs and TAMs was noted in infants, and a higher proportion of cases revealed PD-L1 positivity, though not statistically significant. There was no correlation of TILs or TAMs with the tumor location. CONCLUSION Immune check point blockade using PD-(L)1 or CTLA4 inhibitors may not be a potential therapeutic option for unresectable or recurrent pilocytic astrocytomas, as low positivity rate as well as extremely low percentage of tumor/ immune cells found to be positive. However, alternate forms of immunotherapy might be helpful as most of the cases showed immune infiltrates and a high density of tumor-associated macrophages (TAMs). Large scale studies with larger numbers and longer follow-up periods including in-vitro and clinical studies are warranted for decoding the tumor immunogram.
Small Bowel Adenocarcinoma, Version 1.2020, NCCN Clinical Practice Guidelines in Oncology
Authors: Al B. Benson, Alan P. Venook, Mahmoud M. Al-Hawary, Mustafa A. Arain, Yi-Jen Chen, Kristen K. Ciombor, Stacey A. Cohen, Harry S. Cooper, Dustin A. Deming, Ignacio Garrido-Laguna, Jean L. Grem, Sarah E. Hoffe, Joleen Hubbard, Steven Hunt, Ahmed Kamel, Natalie Kirilcuk, Smitha Krishnamurthi, Wells A. Messersmith, Jeffrey Meyerhardt, Eric D. Miller, Mary F. Mulcahy, Steven Nurkin, Michael J. Overman, Aparna Parikh, Hitendra Patel, Katrina S. Pedersen, Leonard B. Saltz, Charles Schneider, David Shibata, John M. Skibber, Constantinos T. Sofocleous, Elena M. Stoffel, Eden Stotsky-Himelfarb, Christopher G. Willett, Alyse Johnson-Chilla, Kristina M. Gregory, Lisa A. Gurski
Journal: Journal of the National Comprehensive Cancer Network (2019)

Small bowel adenocarcinoma (SBA) is a rare malignancy of the gastrointestinal tract that has increased in incidence across recent years. Often diagnosed at an advanced stage, outcomes for SBA are worse on average than for other related malignancies, including colorectal cancer. Due to the rarity of this disease, few studies have been done to direct optimal treatment, although recent data have shown that SBA responds to treatment differently than colorectal cancer, necessitating a separate approach to treatment. The NCCN Guidelines for Small Bowel Adenocarcinoma were created to establish an evidence-based standard of care for patients with SBA. These guidelines provide recommendations on the workup of suspected SBA, primary treatment options, adjuvant treatment, surveillance, and systemic therapy for metastatic disease. Additionally, principles of imaging and endoscopy, pathologic review, surgery, radiation therapy, and survivorship are described.
Incidence of venous thromboembolism in patients with hematologic malignancies related to upper extremity peripherally inserted central venous catheters.
Authors: Thomas A. Giever, Emily L. Richter, Kristine M. Broge, Patrick C. Foy, Linda S. Blust, Jeanne M. Palmer, Timothy S. Fenske, William S. Rilling, Parameswaran Hari, Ehab L. Atallah
Journal: Journal of Clinical Oncology (2013)

6586 Background: Central venous catheters (CVCs) are an integral part of management in patients with hematological malignancies (HMs). CVCs are not without risk however, including DVT which adds significant morbidity. Peripherally inserted central venous catheters (PICCs) via the brachiocephalic veins were the most common CVCs utilized at the Medical College of Wisconsin for patients with HMs. Recent evidence has indicated an increased risk of DVT in patients with PICCs. Methods: We retrospectively reviewed patients admitted to our institution from 2009-2011 with a HM and a CVC placed based upon CPT codes. A chart review was performed and those with a radiologic-confirmed DVT were identified. Results: From 2009-2011, 487 patients with HMs had 1091 CVCs placed. Diagnoses included lymphoproliferative disorders (35.8%), acute leukemia excluding APL (23.8%), APL (1.6%), plasma cell dyscrasias (34.6%), MDS (1.7%), CML (1.6%), and other diagnoses (0.7%). Of the CVCs placed 51% were in patients undergoing stem cell transplantation (HCT) and 49% were placed in non-HCT patients. A total of 91 DVTs were documented and confirmed. DVTs occurred in 85 of 728 PICCs (11.7%), 3 of 104 implanted ports (2.9%), 3 of 249 tunneled CVCs (1.2%), and 0 of 10 other CVCs. DVT rates were similar between HCT (47 of 556, 8.4%) and non-HCT (44 of 535, 8.2%) patients. The highest number of DVTs were associated with plasma cell dyscrasias (29 of 378, 7.7%) followed by lymphoproliferative disorders (28 of 391, 7.2%), acute leukemia (26 of 260, 10%), APL (3 of 18, 16.6%), MDS (3 of 19, 15.8%), and CML (2 of 17, 11.7%). Two DVTs occurred in the setting of warfarin therapy, 5 while on prophylactic and 9 while on therapeutic LMWH. The mean duration from line placement to DVT was 21 days (range 1-169). Using standard chi-squared evaluation, PICC lines were significantly more likely to be associated with DVTs than tunneled or implanted CVCs (p&lt;0.0001). Conclusions: Brachiocephalic PICC-lines are associated with a high incidence of DVT in patients with HMs compared to other CVCs. We have currently changed our practice to utilizing a tunneled internal jugular PICCs for central venous access.
P01.02 Serum-derived DNA methylation markers distinguish functional and invasiveness subtypes in patients harboring pituitary tumors
Authors: A V Castro, M Wells, K Asmaro, T S Sabedot, M S Mosella, T M Malta, K Nelson, J Snyder, A deCarvalho, A Mukherjee, D Chitale, A Robin, M Rosenblum, T Mikkelsen, L M Poisson, I Lee, T Walbert, A Bhan, S Kalkanis, J Rock, H Noushmehr
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Molecular profiling of circulating biomarkers released by tumors has a relevant clinical value in central nervous system (CNS) tumors, but its feasibility has not been investigated in pituitary tumors (PT) despite being the second common intraaxial tumors of the CNS (~15%). Although usually benign and slow-growing, they can be nonfunctioning and invade surrounding structures resulting in significant comorbidities. DNA methylation aberrations distinguish PT according to their functional status but their role in invasiveness is still unclear. Pre-surgical detection of clinically relevant molecular markers associated with tumor behavior can address current diagnostic and therapeutic challenges. We hypothesized that PT release cell-free DNA (cfDNA) into the bloodstream allowing for the profiling of epigenetic markers associated with relevant clinicopathological features. MATERIAL AND METHODS Genome-wide methylome profile of paired serum cfDNA (EPIC array) and tissue from 13 patients with pituitary macroadenomas (9 males; median age: 62; 9 NFPT, 6 invasive) and 3 controls serum (patients with epilepsy). RESULTS Unsupervised analysis of the serum methylome from patients harboring PT was distinct from controls and other diseases (hypopituitarism, glioma and colorectal cancer) and supervised analysis (Wilcoxon Rank-sum Test) identified significant differentially methylated probes (DMP) that segregated PT from control serum specimens. Nonfunctioning and invasive-specific DMPs identified in the serum also defined functional, and less prominently invasive status, in the tissue of an independent cohort of PT. CONCLUSION This is the first study to show the feasibility to profile the methylome in the serum of patients with PT using cfDNA. In addition, we identified unique methylation signatures that distinguished PT according to functional and invasiveness subtypes. These results underpin the potential role of methylation profile and liquid biopsy as a noninvasive approach to assess clinically relevant molecular features in the serum of patients harboring PT.
P12.07 Minimal bimodular G-quadruplex nano-construct as cryptic therapeutic DNA oligonucleotide to suppress glioblastoma cell functioning
Authors: A Kopylov, O Antipova, V Legatova, N Samoylenkova, E Savchenko, A Golovin, E Zavyalova, G Pavlova
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND G-quadruplex folding oligodeoxyribonucleotides (G4 ODNs) are considers to be potential anticancer agents, because G4 interferes with some functions of cell, like survival, proliferation, ets, by interacting with G4 binding regulatory proteins. There are some experimental data on anti-proliferative activities of G4: for telomerase complex, aptamers for STAT3, nucleolin, TOP1, SP1, VEGF, and SHP-2, but there is no molecular mechanism yet. Because ODNs are supposed to block regulatory proteins, like cryptic aptamers do, they could be potentially therapeutics, like monoclonal antibodies. The only current approach to find proper model for G4 plus reference cell line, is to screen sets of G4 for sets of cancer cell lines. To avoid selection from large number of G4 structures, we have initiated anti-proliferative study of minimal DNA nano-construct biHD1, built from two minimal active G4 15-mer, by testing 7 human cancer cell lines, including glioblastoma (GBM): U87 and primary cultures from GBM surgery samples. MATERIAL AND METHODS ODN were from Evrogen (Russia). ODN were folded: heated to 950C, slowly cooled to 250C. biHD1, GGTTGGTGTGGTTGG TGGTTGGTGTGGTTGG, and derivatives with G4 structure variations. CD in saline phosphate, pH 7.5; CHIRASCAN (UK) and MARK-5 (France); melting curves at 294 nm. 7 human cancer cell lines: colon, HCT116; prostate, PC3; lung, RL-67; breast adenocarcinoma, MCF7; melanoma, mS; HeLa; GBM, U87 and primary cultures from surgery samples; and human embryonic fibroblast, hEF, as control. MTT for cell viability by colorimetric measurements of metabolic activity (Tecan plate reader, Switzerland). ODN: 0.10 μM, 1.0 μM, 10 μM for 3 days. RESULTS biHD1 is dose-dependent toxic for several human cancer cell lines, most active for lung cancer RL-67 and GBM U87, survival at 10 μM ODN 35% and 45%, respectively. According to data for biHD1 derivatives with deviations from G4 conformation: length of linker joining modules, light distortions of loops, strong distortions of G4, freezing of G4 conformation, it is G4 fold which is responsible for toxicity for U87 cell line. CONCLUSION Cell survival after treatment with G4 minimal bimodular DNA oligonucleotide biHD1 and its derivatives have been tested for 7 human cancer cell lines, including CNS, U87. biHD1 is toxic for cancer cells, but not for embryonic fibroblast, as control; activity depends on G4 fold. Therefore, it is possible to manipulate with minimal G4 as module, and build G4 nano-construct being toxic for cancer cells, including GBM, U87. Research is supported by RFBR grants 17-00-00157, 18-29-01047
Perception and reaction of cancer patients to the diagnosis of cancer and their attitude towards disclosure of diagnosis: Local perspective from Saudi Arabia.
Authors: Ali Husain Aljubran, Ravichandran Kandasamy, Abdelmuniem Al-Dalee
Journal: Journal of Clinical Oncology (2012)

e19524 Background: Understanding the attitudes of cancer patients towards different cancer related issues is important for care delivery. However, in Saudi, there is yet no clear knowledge about the patient’s perception of cancer diagnosis or preferences regarding the disclosure of information. This study explored that area. Methods: The subjects were adult cancer patients who attended the outpatient clinics at King Faisal cancer center in Riyadh, Saudi Arabia. They completed a validated questionnaire of six sections. In this abstract, we present the data of the first three sections: The first section is about the sociodemographic characteristics, the second explores the patient’s perception and reaction to the diagnosis, and the third enquires about the patient’s preference regarding the disclosure of diagnosis. Estimated sample size: 225. Results: 234 patients participated. Age range: 15-86, median: 40.5 y. Males: 61.5%. 12.4% from suburban areas. 41.5% had higher than high school education. 76% had annual income &lt; $32,000. Regarding of what they thought to be the cause of their cancers, 42.4% thought that someone’s envy or eye of evil was the cause, and 11.7% thought it was environmental, while 44.2% could not attribute to any cause. About the disclosure of diagnosis, 34.5% were not the first to know about the diagnosis. However, 78% thought that no one should know about the diagnosis before the patient, but 33.5% agreed that family may know at the same time. For decision making, 40% wanted to take decision by themselves, while 52.4% wanted the family to participate in making decisions. Conclusions: In contrast to the public attitude regarding the disclosure of diagnosis, this study shows that majority of cancer patients believed that no one should know about the diagnosis before themselves. This result will help the current national debate. Also, it shows large proportion of patients believe of a metaphysical etiology for their diseases, which may affect their choices and directions. A similar study in the community is recommended to include patients who do not seek conventional treatments.