tbuckley/cabot-search huggingface dataset:
Extranodal NHL- A retrospective review of clinico-pathologic features and outcome and comparison with nodal NHL. Single institution experience years: 1988–2004
Authors: A. Lal, S. Adil, N. Masood
Journal: Journal of Clinical Oncology (2006)

17542 Background: Non-Hodgkin’s lymphoma (NHL) arising in an extra nodal (EN) site is not uncommon and its natural history and treatment is clearly characterized in the literature. Data on EN-NHL and comparison with N-NHL with relation to survival and prognostic factors is scarce in our part of the world. The primary objective of this study was to analyze the anatomic distribution, clinical features and outcome of DLBCL patients according to the primary site with applicability of International Prognostic Index (IPI). Methods: From 1988 to 2004, 557 patients were analyzed for the clinico-pathologic characteristics, treatment outcome and prognostic factors affecting overall survival. Results: Median age was 48.7 ± 15.3 years ; the M: F ratio was 2:1. The distribution according to the primary site was: lymph node, 322 cases (58%) of these 145 cases (44%) stage IV, 76 cases (23%) Stage III, 60 cases (18%) stage II and 47 cases(15%) stage I ; and EN sites, 235 (42%), including GIT (44%) followed by upper aerodigestive tract (19%), bones (08%), spine (05%), and 3% each as breast, CNS, testis,lungs. The median survival rate was 4.8 and 6.3 years in NL and ENL respectively vary according to primary site/stage of the lymphoma. In the univariate analysis age less than 60 years, early stage I-II, extra nodal involvement primarily gastric or bone, 0–1 extra nodal site, 0–1 PS, lack of B symptoms, normal LDH level has been associated with good prognosis. In the multivariate analysis age, PS, stage and level of LDH were the main variables to predict OS; no nodal or extranodal site maintained their prognostic value. Conclusion: Our data correspond with series from west increasing incidence extranodal lymphoma due to improved diagnostic techniques and superior results with chemotherapy by preserving the organ. Few patients with bowel obstruction or cord compression lymphoma required surgery for diagnosis or relief of symptoms. There is significant difference from western data in histologies DLBC-NHL is the most common histologies in our study. Overall survival patients with EN-NHL were similar to nodal NH-Lymphoma but largely depended on IPI. No significant financial relationships to disclose.
CMET-39. INTRA-CSF LIPOSOMAL CYTARABINE PLUS SYSTEMIC THERAPY AS INITIAL TREATMENT OF BREAST CANCER LEPTOMENINGEAL METASTASIS: A RANDOMISED, OPEN-LABEL TRIAL
Authors: Emilie Le Rhun, Audrey Mailliez, Jennifer Wallet, Isabelle Rodrigues, Thomas Boulanger, Isabelle Desmoulins, Jérôme Barrière, Michel Fabbro, Sophie Taillibert, Charles Andre, Marie Cecile Le Deley, Michael Weller, Jacques Bonneterre
Journal: Neuro-Oncology (2018)

Intra-cerebrospinal fluid (CSF) therapy for the treatment of leptomeningeal metastasis (LM). remains controversial. DEPOSEIN (NCT01645839) was a multicenter randomized open-label study exploring the efficacy of liposomal cytarabine added to standard-of-care systemic therapy for the treatment of LM from breast cancer. Inclusion was based on the identification of tumor cells in the CSF or typical clinical and magnetic resonance imaging (MRI) signs of LM. Patients were randomly assigned to receive systemic therapy alone (arm A) or in combination with intra-CSF liposomal cytarabine (arm B). Neurological and patient-reported outcomes (PRO) were performed monthly, cerebrospinal MRI every 2 months. The primary endpoint was progression-free survival in the leptomeningeal compartment (LM-PFS); 66 events were required to ensure 80% power for a hazard ratio of 0.5 (two-sided alpha=5%). Thirty-seven patients were assigned to arm A, 36 patients to arm B. Baseline characteristics were similar between arms. The median number of liposomal cytarabine injections in arm B was 5 (range 1–20). Focal radiotherapy was performed in 6 (16%) and 5 (14%) patients in arms A and B, respectively. Serious adverse events were reported in 20 and 27 patients in arms A and B. In the intent-to-treat population, median LM-PFS locally assessed was 2.0 months (95% confidence interval (CI) 1.3 2.7) in arm A versus 4.3 months (95% CI 2.3 5.7) in arm B (HR=0.57, 95% CI 0.35 0.92, p=0.02). Sixty-eight patients have died. Median OS was 4.0 months (95% CI 2.2–6.5) in arm A versus 7.3 months (95%CI 3.9–12.6) in arm B (HR=0.80, 95% CI 0.50–1.29, p=0.35). Centrally reviewed LM-PFS and PRO will also be reported. CONCLUSIONS: The addition of liposomal cytarabine to systemic therapy may improve LM-related PFS but may not significantly improve survival. PRO will be essential to determine a possible clinical benefit from intrathecal chemotherapy.
SURG-01. AN INTRAOPERATIVE RAMAN SPECTROSCOPIC PROBE FOR GLIOMA SURGERY: INDICATIONS, SAFETY, AND FUTURE DIRECTIONS
Authors: Thomas Noh, Laila Poisson, Michelle Brusatori, Ana deCarvalho, Gregory Auner, Steven Kalkanis
Journal: Neuro-Oncology (2018)

Raman spectroscopy is a tool that utilizes a non-contact label-free modality of optical imaging that measures inelastic scattered photon shifts to give a unique biochemical signature. There is established work showing that these unique fingerprints can differentiate a glioma from necrosis and normal brain. The ability to instantly characterize these organic tissues intraoperatively, then, can help guide a surgeon’s resection. The goal of the present study is to review the Raman work that has been performed to date, its demonstrated safety in a rat model and the indications for use of this operative tool. We review the fundamental principles of Raman spectroscopy, some contemporary data, and show its effectiveness as an intraoperative probe. Because the probe uses a 100mW 785nM laser wavelength, we also determined the threshold at which it causes damage to cortical grey matter in a rat model. Raman spectroscopy has a high sensitivity and specificity (>97%) when discriminating between grey matter, necrosis and GBM. A discriminant function analysis, supervised classification algorithm, is used for spectral identification to allow relevant spectral interpretation and allows for tailoring to which Raman peaks are significant for diagnosis. In regards to safety, animal experiments showed no damage seen at 10 seconds/250mW and estimated damage to occur at 60 seconds/250mW. We also present an intraoperative workflow of how this tool could be used in the operating room. A Raman spectrographic probe is a safe and powerful tool that can provide live intraoperative diagnosis and identify tissue margins. Further work is being done to identify clinical outcomes, the unique fingerprints of other pathological tissues and further differentiate gliomas based on molecular markers like IDH-1.
RTHP-27. PATTERNS OF FAILURE AFTER STEREOTACTIC RADIOSURGERY FOR RECURRENT HIGH-GRADE GLIOMA: A SINGLE INSTITUTION EXPERIENCE OF 10 YEARS
Authors: Chibawanye Ene, Meghan Macomber, Eric Holland, Daniel Silbergeld, Lia Halasz
Journal: Neuro-Oncology (2018)

Stereotactic radiosurgery (SRS) is a treatment modality that is frequently used as salvage therapy for small nodular recurrent high grade gliomas (HGG). Due to the infiltrative nature of HGG, it is unclear if this highly focused technique provides a durable local control benefit. Objective To determine how demographic or clinical factors influence the pattern of failure following SRS for recurrent high grade gliomas. We retrospectively reviewed clinical, radiographic and follow-up information for 47 consecutive patients receiving SRS for recurrent HGG at our institution between June 2006 and July 2016. All patients initially presented with a HGG (WHO Grade III and IV). Following SRS for recurrence, all patients experienced treatment failure, and we evaluated patterns of local, regional, and distant failure in relation to the SRS 50% isodose line. Most patients with recurrent HGG developed in-field treatment failure following SRS (N = 40; 85%). Higher SRS doses were associated with longer time-to-failure (HR = 0.80 per 1Gy increase; 95% CI 0.67–0.96; P = .016). There was a statistically significant increase in distant versus in-field failure among older patients (P=.035). This effect was independent of bevacizumab use (OR = 0.54, P =1.0). CONCLUSIONS: Based on our experience, the majority of treatment failures after SRS for recurrent HGG were in-field. Older patients, however, presented with more distant failures. Our results indicate that higher SRS doses delivered to a larger area as fractioned or unfractioned regimen may prolong time-to-failure, especially in the older population.
STEM-23. miR-486-5p REGULATES TUMOR SUPPRESSOR NETWORKS AND ITS INHIBITION REDUCES TUMOR VOLUME AND SENSITIZES TO RADIATION TREATMENT IN A PDX MOUSE MODEL OF GBM
Authors: Ivan Kotchetkov, Hernando Lopez-Berotni, Nicole Michelson, Yuan Rui, Bachchu Lal, Yunqing Li, Jordan Green, John Laterra
Journal: Neuro-Oncology (2018)

Glioblastoma multiforme (GBM) is a heterogeneous malignancy that contains a subpopulation of tumor cells with stem-like features. These GBM stem cells (GSCs) have the ability to self-renew and establish tumors. As such, they are thought to disproportionately contribute to re-growth and resistance to therapy, and targeting mechanisms that underlie stemness may lead to development of more effective treatments. Work from the Laterra lab has shown that the transcription factors (TFs) Oct4 and Sox2 drive GBM cells toward a stem-like phenotype, in part by regulating subsets of microRNAs (miRNAs). One commonly overlooked mechanism by which these TFs can promote tumorigenesis is by inhibiting repressors of cell stemness and tumor propagation through miRNAs. This study demonstrates that miR-486-5p is induced by Sox2 12-fold and regulates GSC self-renewal as measured by limiting dilution and sphere formation assays by inhibiting tumor suppressors PTEN and FOXO1 in established glioma cell lines and patient-derived neurospheres. Inhibition of endogenous miR-486-5p in these lines leads to cell death. Furthermore, in vivo delivery of miR-486-5p inhibitor via a novel nanoparticle complex to pre-established patient-derived GBM xenografts (PDX) in mice decreases tumor volume by 61% (p < 0.001) and sensitizes to the effects of ionizing radiation 9-fold (p < 0.001). Thus, the Sox2:miR-486-5p axis offers a promising translational target for therapies aimed at depleting GBMs of stem-like cells in combination with standard therapies.
HOUT-29. HEALTHCARE COSTS FOR HIGH-GRADE GLIOMAS: A POPULATION-BASED STUDY
Authors: Yang Liu, Evan Tyler, Martin Lustick, David Klein, Kevin Walter
Journal: Neuro-Oncology (2018)

Clinical management of patients with high-grade gliomas (HGGs) is very challenging both clinically and financially. As costs of cancer care in the US are expected to increase and oncology care is switching from volume-based to value-based pattern, efforts are needed to establish effective and efficient management of patients with HGGs. However, relevant data are limited. In this study, we retrospectively identified 88 primary HGGs patients diagnosed and treated at our institution between January 1, 2011 and February 28, 2017 and linked patient clinical information from electronic health record with all insurance claims data (all paid) from Excellus BCBS. Among these patients, the median age at diagnosis was 59 years and the majority of the patients were white (94.3%) with GBM (80.7%). Total median healthcare costs for clinical management of HGGs were $184,159.83 (95% CI: $151,214.98, $222.431.36). The largest component of healthcare costs was outpatient service, followed by inpatient costs. When we examined costs by service type, we found the leading cost was radiology service, followed by inpatient surgical, prescription drugs, inpatient medical and outpatient pharmacy. Compared with patients under non-commercial insurance, patients under commercial insurance had longer survival time (median: 411 days vs. 358 days, p = 0.563), higher healthcare costs in total ($235,732.85 vs. $142,134.07, p < 0.001), and in each phase of clinical care. We further observed a U-shaped curve healthcare costs pattern, i.e., healthcare costs were high in the phase of initial care (3-month after diagnosis) and 9-month after initial diagnosis with relative low between these two phases. Generalized linear model showed patients with commercial insurance, better Karnofsky Performance Status, longer survival time had higher healthcare costs. Our real-world study demonstrated that healthcare costs for patients with HGGs were substantial and such high healthcare costs were positively associated with patient survival and commercial insurance.
Abstract IA20: Immunotherapy: Biomarkers and checkpoint blockade in NSCLC
Authors: David P. Carbone, Michael Sharpnack, Kai He
Journal: Clinical Cancer Research (2018)

Abstract Immunotherapy approaches targeting the PD-1 pathway have shown some clinical benefits in a fraction of patients with lung cancer, but expression of PD-L1 has proved to be an imperfect biomarker of efficacy. Recent studies have shown that tumor mutation burden (TMB) is also correlated with outcome and that it appears to be independent of PD-L1. TMB, however, only indirectly measures the number of neoantigenic peptides presented on tumor cell surface class I MHC, and predicted MHC matches may be an even better predictor of benefit. In addition, mutations in genes such as LKB1 may modulate the immune response, and mutations in the antigen presentation pathway may block it altogether. Mutations in DNA repair pathway genes may increase the number of potential neoantigens. Analysis of non-PD-1 pathway immunomodulators, immune cell infiltration, microenvironmental and microbiomic context, together with in-depth analysis of tumor somatic genomics, could lead to better patient selection for immunotherapy. Citation Format: David P. Carbone, Michael Sharpnack, Kai He. Immunotherapy: Biomarkers and checkpoint blockade in NSCLC [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr IA20.
QOLP-24. ATTITUDES TOWARD FERTILITY AND FERTILITY PRESERVATION IN WOMEN WITH GLIOMA
Authors: Rachel Stiner, Jennifer Clarke, Nikita Sinha, Jessica Chan, Joseph Letourneau, Erin Niemasik, Jane Rabbitt, Susan Chang, Nicholas Butowski, Michael Prados, Mitchell Rosen
Journal: Neuro-Oncology (2018)

No studies have examined the fertility priorities of women undergoing treatment for glioma. Glioma patients frequently undergo chemotherapy as part of their treatment, however it is unknown whether patients are aware of the possible effects of treatment on their fertility. Our objective was to assess the fertility priorities of glioma patients and ascertain whether female glioma patients are being effectively counseled on the effects of chemotherapy on fertility prior to beginning treatment. The sample was composed of female patients from the Neuro-oncology clinic of the University of California, San Francisco. Participants completed a cross-sectional survey between October 2010 and December 2013 exploring their attitudes toward fertility and their experience with fertility counseling prior to chemotherapy initiation. Seventy-two women completed the survey. Analysis of the survey results showed that 30% of women receiving chemotherapy reported having a discussion regarding fertility preservation prior to beginning treatment. Of those who reported having this discussion, 80% were aware that chemotherapy could negatively affect their fertility. Many women reported that while fertility preservation was not important to them at the time of diagnosis, it was a priority for them at the time of survey completion. Although interest in having children tended to decrease after cancer treatment, the majority of respondents reported desiring a child after treatment. CONCLUSIONS: The data obtained in this study suggest a lack of understanding of reproductive priorities which may be addressed with a more comprehensive fertility discussion prior to beginning treatment.
CADD-10. 2-HYDROXYOLEIC ACID, A NOVEL MEMBRANE LIPID REGULATOR, DEMONSTRATES CLINICAL ACTIVITY IN HIGH-GRADE GLIOMA
Authors: Derek Hanson, Pablo Escriba, Antione Perier, Vicenc Tur
Journal: Neuro-Oncology (2018)

2-hydroxyoleic acid (2OHOA) is the first potential anti-cancer drug to act by modification of cell membrane lipid content. Through its unique mechanism, 2OHOA targets the membrane lipid composition and organization of cancer cells, altering downstream signaling cascades that promote tumor cell proliferation. Cancer cells demonstrate an abnormal membrane lipid microdomain phenotype rich in phosphatidylethanolamine (PE) and phosphatidylcholine (PC) and relatively sphingomyelin-poor when compared to non-malignant cells. Through its direct activity on sphingomyelin synthase 1, 2OHOA is able to alter the lipid membrane composition of cancer cells and restore the membrane to a normal sphingomyelin-rich phenotype. Ras is only able to propagate its signal cascade when located near the cell membrane and demonstrates an affinity for PE/PC microdomains. 2OHOA exposure results in replacement of PC and PE domains with sphingomyelin, thereby displacing Ras from the cell membrane to the cytoplasm where it is inert. Thus through normalization of the lipid membrane composition, 2OHOA is able to effectively downregulate the Ras signaling cascade, resulting in decreased tumor cell proliferation. A European phase I/IIa trial of 2OHOA in adult patients with high-grade glioma and other advanced solid tumors has recently been completed. The results are promising with five refractory malignant glioma patients demonstrating objective clinical benefit by RANO criteria for six or more months, including one glioblastoma patient with a sustained partial response (93% regression from baseline) of the primary lesion for over thirty-three months of therapy. The drug has been very well-tolerated in adult patients with minimal toxicity. A European phase IIb trial for adult patients with newly diagnosed high-grade glioma combining 2OHOA with standard therapy (radiotherapy and temozolomide) is being planned. A pediatric phase I trial of 2OHOA for children with high-grade glioma and other advanced solid tumors is due to open in the United States in 2018.
Peripheral Blood DNA Methylation as Potential Biomarker of Malignant Pleural Mesothelioma in Asbestos-Exposed Subjects
Authors: Simonetta Guarrera, Clara Viberti, Giovanni Cugliari, Alessandra Allione, Elisabetta Casalone, Marta Betti, Daniela Ferrante, Anna Aspesi, Caterina Casadio, Federica Grosso, Roberta Libener, Ezio Piccolini, Dario Mirabelli, Irma Dianzani, Corrado Magnani, Giuseppe Matullo
Journal: Journal of Thoracic Oncology (2018)
Protein kinase C binding protein 1 inhibits hypoxia-inducible factor-1 in the heart
Authors: Kathryn J Schunke, Chad B Walton, David R Veal, Chrisy T Mafnas, Cynthia D Anderson, Allison L Williams, Ralph V Shohet
Journal: Cardiovascular Research (2018)

Hypoxia-inducible factor-1 alpha (HIF-1α) is a key transcription factor responsible for the induction of genes that facilitate adaptation to hypoxia. To study HIF-1 signalling in the heart, we developed a mouse model in which an oxygen-stable form of HIF-1α can be inducibly expressed in cardiac myocytes, under the regulation of tetracycline.
Abstract 11961: Impact of Left Ventricular Systolic Stress on Contractility in Hypertension Assessed by One-beat Three-dimensional Speckle Tracking Echocardiography With High Volume Rates
Authors: Itta Kawamura, Masanori Kawasaki, Ryuhei Tanaka, Rina Otake, Yoshie Nakano, Nozomi Nomura, Hidemaro Sato, Hirotaka Miwa, Shingo Minatoguchi, Koji Ono, Maki Saeki, Maki Nagaya, Noriaki Sato, Takashi Yoshizane, Kunihiko Tsuchiya, Shinji Tomita, Hitoshi Matsuo, Toshiyuki Noda, Sachiro Watanabe, Shinya Minatoguchi
Journal: Circulation (2015)

Background: Left ventricular hypertrophy (LVH) is known as compensative mechanism of LV against pressure overload to reduce LV stress and maintain systolic performance. However, the relationship between LV systolic stress and strain or torsion that reflects contractility assessed by 3-dimensional speckle tracking echocardiography with high volume rates (3D-STE) has not been examined. We sought to evaluate the impact of LV systolic stress on LV contractility in hypertension (HTN). Methods: A total of 162 subjects {131 HTN patients and 31 controls (age 65±12)} were enrolled. HTN were divided into 3 groups: 47 HTN patients without LVH (age 67±12), 47 HTN patients with LVH (age 70±11) and 37 patients with hypertensive heart failure (HHF) (age 74±15). We examined LV longitudinal, circumferential and radial peak strain, LV strain rate at systole (SR) and LV torsion by 3D-STE with 70-80vps. LV systolic stress was calculated as LV end systolic radius x systolic blood pressure / thickness. Results: LV strain and SR in 3 directions and torsion decreased in HHF (longitudinal strain; control: -19±3, HTN without LVH: -18±4, HTN with LVH: -17±4, HHF: -13±4*. Torsion; 1.4±0.2, 1.4±0.3, 1.5±0.3, 1.2±0.2* °/cm, *p&lt;0.05 vs control) associated with increased systolic stress (129±24, 141±36, 143±40, 164±51* mmHg). There was correlation between LV systolic stress and longitudinal, radial and circumferential peak strain (r=0.18, p=0.024, r=-0.22, p=0.005 and r=0.18, p=0.021, respectively) and between LV stress and LV radial SR (r=-0.1.9, p=0.018) in total subjects. There was not a significant correlation between LV systolic stress and strain or SR in 3 directions in controls. Significant correlation was found between LV stress and circumferential strain or torsion in HHF (r=0.43, r=-0.34, p&lt;0.05), but not between LV stress and longitudinal or radial strain in HHF. Conclusion: Reduction of LV contractility assessed by LV strain, SR-S and torsion was associated with LV stress. In HHF only circumferential strain and torsion were decreased associated with increased LV stress, suggesting that the beginning of reduction in circumferential strain and torsion after deterioration of longitudinal and radial contractility due to increased systolic stress may be responsible for HHF.
NIMG-80. A RADIOMIC SIGNATURE AS A NON-INVASIVE PREDICTOR OF PROGRESSION-FREE SURVIVAL IN PATIENTS WITH LOWER-GRADE GLIOMAS
Authors: Yinyan Wang, Xing Liu, Yiming Li, Zhiyan Sun
Journal: Neuro-Oncology (2018)

The aim of this study was to develop a radiomics signature for prediction of progression-free survival (PFS) in lower-grade gliomas and to investigate the genetic background behind the radiomics signature. In this retrospective study, training (n = 216) and validation (n = 84) cohorts were collected from the Cancer Genome Atlas and Chinese Glioma Genome Atlas, respectively. For each patient, a total of 431 radiomics features were extracted from preoperative T2-weighted magnetic resonance images. A radiomics signature was generated in the training cohort, and its prognostic value was evaluated in both the training and validation cohorts. The genetic characteristics of the group with high-risk scores were identified by radiogenomic analysis, and a nomogram was established for prediction of PFS. There was a significant association between the radiomics signature (including 9 screened radiomics features) and PFS, which was independent of other clinicopathologic factors in both the training (P < 0.001, multivariate Cox regression) and validation (P = 0.025, multivariate Cox regression) cohorts. Radiogenomic analysis revealed that the radiomics signature was associated with the immune response, programmed cell death, cell proliferation, and vasculature development. A nomogram established using the radiomics signature and clinicopathologic risk factors demonstrated high accuracy and good calibration for prediction of PFS in both the training (C-index, 0.69) and validation (C-index, 0.87) cohorts. CONCLUSIONS: PFS can be predicted non-invasively in patients with LGGs by a group of radiomics features that could reflect the biological processes of these tumors.