tbuckley/cabot-search huggingface dataset:
P04.35 Preoperative tumor growth and microvessel density measurements in patients with glioblastoma
Authors: V E Mikkelsen, A Stensjøen, U S Granli, E M Berntsen, Ø Salvesen, O Solheim, S H Torp
Journal: Neuro-Oncology (2018)

Human glioblastomas (GBMs) are highly angiogenic tumors characterized by a rapid tumor growth. In radiological studies, the preoperative speed of growth of treatment-naïve human GBMs varies considerably among patients. Faster GBM growth has been related to increased angiogenesis and hypoxia in animal models; however, such links have been sparsely studied in human patients. We have therefore aimed to look for associations between microvessel density (MVD) counts by means of two endothelial markers and radiological speed of growth. In 102 patients with newly diagnosed GBMs, MVDs were counted using immunohistochemical staining of von Willebrand factor (vWF, factor VIII), a pan-endothelial marker, and CD105 (endoglin), a marker of proliferating endothelial cells. Radiological speed of growth was estimated from preoperative tumor volumes on two contrast-enhanced T1-weighted MRI scans taken ≥14 days apart. Because speed of growth has previously been shown to be highly associated with initial tumor volume, an expected Gompertzian growth curve fitted from the volume data and the interval between the scans was used to dichotomize the patients into two groups; tumors with a larger or smaller volume increase than expected from the curve (i. e. faster or slower growing tumors, respectively). These groups were assessed for associations with the MVDs using Mann-Whitney U tests and a multivariable binary logistic regression analysis, which included histopathological features previously found to independently predict faster GBM growth. CD105-MVD was the only marker significantly associated with faster growth in a univariable analysis (P = 0.049). However, when corrected for the presence of thromboses and high cellular density in a multivariable model, CD105-MVD was no longer significant. In this model, thromboses and high cellular density were significant independent predictors of faster growth with OR 4.2 (95% CI 1.2–14.3, P = 0.021) and OR 2.6 (95% CI 1.0–6.5, P = 0.048), respectively. Our results show that vWF-MVD and CD105-MVD are not independently associated with faster GBM growth, suggesting faster GBM growth is also driven by angiogenesis-independent processes.
P05.63 The best treatment for Vestibular Schwannoma: Systematic Review of Clinical Trials and Case Series
Authors: T L B Nghia, M N Y, M E Morra, N L Vuong, N M Tin, D Karam, M A Refaey, K Shahin, A L Soliman, N T Huy
Journal: Neuro-Oncology (2018)

Vestibular Schwannoma (VS) causes loss of hearing, loss of balance, tinnitus and even may lead to facial numbness. Various treatment choices have been increasing such as surgery, fractionated stereotactic radiotherapy (FSRT), Gamma Knife radiosurgery (GKRS), single fraction linac stereotactic radiosurgery (SFSRT) and conservative treatment. However, there is no conclusive evidence about the best treatment of VS. In this study, we aimed to systematically review and meta-analyze all possible strategies for management of VS. We conducted a systematic electronic search in 13 electronic databases; PubMed, ScienceDirect, WHO Global Health Library, Virtual Health Library (VHL), Scopus, The Institute of Science Index (ISI), Google Scholar, Clinical trials, Controlled Trials (MRCT), Cochrane, System for Information on Grey Literature in Europe (SIGLE), EMBASE, New York Academy of Medicine Grey Literature Report (NYAM) database for relevant studies. Original studies and case series reporting treatment of VS were included. Meta-analysis with random effects models was performed for the outcomes of tumor size reduction, increase in hearing capability, and complications. We included 48 studies including 3531 participants. The pooled proportions and 95% confidence intervals (95%-CIs) for tumor size reduction using FSRT and GKRS were 0.34 (0.20; 0.51) and 0.53 (0.40; 0.65), respectively. The proportions and 95%-CÍs of increase in hearing capability using surgery, FSRT, and GKRS were 0.11 (0.0; 0.91); 0.08 (0.05; 0.11), and 0.08 (0.05; 0.13), respectively. The pooled proportions of complications of surgery, FSRT, GKRS, and SFSRT were 0.18 (0.10; 0.30); 0.15 (0.08; 0.24); 0.21 (0.14; 0.30); and 0.32 (0.12; 0.24), respectively. Our study highlights the efficacy and safety of different treatments for VS such as surgery, FSRT, GKRS, and SFSRT. However, there are no controlled trials to compare these different remedies. Future large scale randomized controlled trials are needed to clarify.
Abstract 14718: Mutations in the Gene Encoding Ribonucleic Binding Motif Protein 20 (RBM20) Are Frequent Causes of Dilated Cardiomyopathy in Denmark
Authors: Thomas M Hey, Mads M Aagaard, Maria Harbo, Torsten B Rasmussen, Tenna Gadgaard, Trine Madsen, Jacob E Møller, Henning Mølgaard, Hans Eiskjær, Jens Mogensen
Journal: Circulation (2016)

Background: Dilated cardiomyopathy (DCM) is a hereditary cardiac condition characterized by unexplained heart failure with reduced ejection fraction. So far more than 100 DCM genes have been report...
Safety and efficacy of lanreotide depot/autogel (LAN) in patients with lung NETs: The randomized, double-blind, placebo (PBO)-controlled phase III SPINET study.
Authors: Diane Lauren Reidy, Matthew H. Kulke, Edward M. Wolin, Simron Singh, Diego Ferone, Beloo Mirakhur, Christine Massien, Aude Houchard, Martyn E. Caplin, Eric Baudin
Journal: Journal of Clinical Oncology (2016)

TPS8580 Background: In the CLARINET study (NCT00353496), LAN was associated with significantly prolonged progression-free survival (PFS) in patients with metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) of grade 1 or 2 (Ki-67 < 10%). Limited options are available for the treatment of patients with advanced lung NETs. The aim of the SPINET study is to evaluate the safety and antitumor efficacy of LAN 120 mg vs. PBO in these patients. Methods: SPINET is an international, multicenter, randomized, double-blind, PBO-controlled phase III study. Main inclusion criteria: adult patients with well-differentiated typical or atypical, metastatic and/or unresectable lung NETs, positive somatostatin-receptor imaging ( ≥ grade 2 Krenning scale), ≤ 1 course of chemotherapy, ECOG PS 0-1. A total of 216 patients will be enrolled from 80 sites across the USA, Canada, and Europe. Patients will be randomized 2:1 to receive either LAN (120 mg every 28 days) + best supportive care (BSC) or PBO + BSC, until progressive disease (PD)/death or unacceptable toxicity. Patients receiving PBO who experience PD may opt to receive LAN 120 mg in an open-label extension phase. All patients who experience PD will be followed to document survival, quality of life (QoL), and subsequent anticancer treatments. The primary endpoint, PFS (time from randomization to progressive disease [PD]/death), will be assessed based on central review using RECIST v1.1. Main secondary endpoints include PFS according to local review, objective response rates, overall survival, changes in plasma chromogranin (CgA) levels, LAN pharmacokinetics, QoL, and safety. This trial is active and registered with the EU Clinical Trials Register (EudraCT:2015-004992-62). Clinical trial information: 2015-004992-62.
P04.90 Observational prospective multi-centric study of delta radiomics Features Analysis for the prediction of patients outcomes in GLIoblastoma multifome: GLI.F.A. Project
Authors: M Lupattelli, S Chiesa, F Beghella Bartoli, I Palumbo, R Gatta, R Tarducci, N Dinapoli, M Balducci, C Aristei, V Valentini
Journal: Neuro-Oncology (2018)

Despite decades of research, glioblastoma (GBM) remains the most malignant primary brain tumor. Different investigations have focused on the GBM’s heterogeneous features to develop an individualized patient management. A multi-institutional study, the GLI.F.A. (Glioblastoma: advanced Imaging Features Analysis) Project, was performed for a comprehensive analysis of GBM heterogeneity in order to create a multidimensional map for predictive models (PM) and decision support systems (DSS) in GBM. Adult patient with newly diagnosed GBM, that undergo to surgery and chemo-radiotherapy according to EORTC 26981-22981-NCIC trial, were analyzed in this first phase of the study. Gross Tumor Volume (GTV) was contoured in the T1 post contrast and T2-FLAIR weighted images. A brain ontology and a platform for sharing and combining multiple datasets (SPIDER BOA System for Patient Individual Data Entry and Recording Beyond Ontology Awareness) were created in order to standardize data collection. Preoperative MRI features were extracted by the MODDICOM software. Wilcoxon Mann Whitney test, Log-rank test for Kaplan-Meier curves were utilized to evaluate the significance of the radiomic features on the T2-Flair and T1 images. The main outcomes we considered were overall survival, progression free survival and response to radio-chemotherapy (RTCT). The median value of the features was used to categorize the continue variables. Twenty-seven patients, treated from July 2014 to February 2018, were enrolled in this study. Median age was 61 years (range 45–75) and 20 patients are still alive. The MODDICOM software analyzed 94 image features. Significant features divided by MRI sequence and outcomes are reported in Tab1. The first order features, describing the statistical characteristics of images, resulted significant for OS on the T2-weighted MRI and for response to RTCT on the T1 weighted MRI; the second order features, describing the spatial correlation between images voxels, showed the most significant result for OS and PFS on contrast-enhanced T1. This preliminary univariate analysis suggests that the radiomic features relates to survival and clinical outcomes and that is possible to stratify patients according MR based quantitative imaging. A higher number of patients, multivariate analysis and external validation are next steps for getting reliable predictive models.
Potential life-years lost: The impact of the cancer drug regulatory process in Canada.
Authors: Joanna Gotfrit, John Shin, Ranjeeta Mallick, David J. Stewart, Paul Wheatley-Price
Journal: Journal of Clinical Oncology (2018)

6515 Background: Canada has an established publicly-funded healthcare system but a complex drug approval and funding process. After proof of efficacy (POE; key publication/presentation), before becoming publicly accessible each drug undergoes a Health Canada approval process, a health technology assessment (HTA), a pricing negotiation and finally individual provincial funding agreements. We quantified potential life-years lost due to delays in this process. Methods: We analyzed drugs for advanced lung, breast and colorectal cancer that underwent the HTA process between 2011-2017. Life-years lost were calculated by: (documented PFS/OS improvement) x (number of eligible patients) x (time from POE to first public funding). For conservative calculation, we assumed all eligible patients in Canada had access at the time of first public funding, while in reality provinces fund at different time-points. Results: We analyzed 21 drugs. Of these, 15 have been funded publicly. See Table 1 for time delays and life-years lost for select publicly funded drugs. The time from POE to first public funding ranged from 1.2-7.5 years (median 2.1 years). Total progression-free life-years lost from POE to first public funding were 36,854 (lung 9,015; breast 4,134; colorectal 23,706 years). Total overall life-years lost from POE to first public funding were 48,366 (lung 32,388; breast 5,823; colorectal 10,155 years). Conclusions: The number of potential life-years lost during the drug regulatory and funding process in Canada is substantial. Recognizing that inter-provincial differences exist and that eligible patients may not all receive a given drug, if even a fraction does so, the impact of delays remains substantive. Other countries with similar systems likely experience similar delays. Collaborative national initiatives are required to address this major barrier to treatment access. Tumour Site Drug Name Indication Time from efficacy to first public funding (years) Progression-free life-years lost Overall life-years lost Lung Pembrolizumab 1st line, expressing PD-L1 > 50% 1.2 2240 8229 Breast Pertuzumab Her2/neu(+), in combination with a taxane/trastuzumab 1.9 1001 2494 Colorectal Cetuximab 1st line, KRAS wild type 6.4 4352 10154
Impact of prior systemic therapy on lymphocytic infiltration in surgically resected breast cancer brain metastases.
Authors: Andrew Bacotti, Rui Wang, Allison Mary Deal, Grace Prince, Megan Jean McKee, Stergios J. Moschos, Edi Brogi, Aki Morikawa, Carey K. Anders, Andrew David Seidman
Journal: Journal of Clinical Oncology (2018)

2063 Background: Tumor infiltrating lymphocytes (TILs) have been positively correlated with response to systemic therapy and for triple negative and HER2+ subtypes and clinical outcomes in early breast cancer (BC) (Denkert C et al., Lancet Oncol 2018). Less is known about TILs in metastatic sites (Cimino-Mathews A et al., Hum Pathol 2016; Ogiya R et al., Cancer Sci 2016), particularly brain (BM), where unique immune regulation governs stromal composition (Duchnowska R et al., Breast Can Res 2016; Harter PN et al., Oncotarget 2015). Reactive glial cells actively participate in cytokine-mediated T cell stimulation (Fitzgerald DP et al., Clin Exp Met 2008). The impact of prior medical therapy (chemotherapy, endocrine therapy, and HER2-targeted therapy) on the presence of TILs and gliosis in human BCBMs has not been previously reported. Methods: In order to determine the impact of prior medical therapy on the presence of TILs and other histopathologic variables, we examined prior treatment data for 133 patients who underwent craniotomy for resection of BMs from the electronic medical record. We examined the relationship between prior systemic therapy exposure and the histologic features of gliosis, necrosis, hemorrhage, and lymphocyte infiltration (LI) assessed by hematoxylin and eosin stain in BCBMs resected at subsequent craniotomy in uni- and multivariate analyses (Prince G et al. Proc ASCO 2017, abstract 2072). Results: Complete treatment data were available for 122 patients. 36 of 114 patients (31.6%) who had received prior systemic treatment had BCBM LI while BCBM LI was observed in 6 of 8 patients (75%) who had not received systemic treatment {significant by Fisher’s exact test p = 0.02}. There were no statistically significant relationships between prior systemic therapy and the three other histologic variables examined. Conclusions: This observation suggests that systemic therapy may interfere with the immune response to BCBMs. This motivates clinical investigation of strategies to enhance LI for therapeutic benefit to improve outcomes for patients with BCBMs. Analysis of these tissue samples to address the potential significance of the pattern of LI as well as relevant biomarkers is ongoing.
Are signatures of radiosensitivity ready for routine clinical use? A pragmatic comparison of clinical, pathological, and gene signature predictors of outcome in oropharynx head and neck cancers.
Authors: Andrew Dhawan, Jacob Gardinier Scott, Purnima Sundaresan, Michael Veness, Sandro Porceddu, Eric Hau, Verity Ahern, Adrian L. Harris, Francesca Meteora Buffa, Harriet E. Gee
Journal: Journal of Clinical Oncology (2018)

e18046 Background: To determine abilities and limitations of accepted clinico-pathological predictors of outcome in oropharynx cancer (OPC) in relation to currently-available gene expression signatures, to identify low-risk OPC patients. Methods: Using the Cancer Genome Atlas (TCGA) OPC dataset (N = 114), available clinico-pathological parameters were used to translate staging from AJCC version 7 (AJCC 7) to the newly-released AJCC 8, and patients were risk-stratified using a clinical algorithm developed by Ang et al. Literature review identified 15 mRNA expression signatures applicable to OPC encompassing radiosensitivity, HPV status, hypoxia, and microsatellite instability. We quality tested these signatures using the sigQC methodology, and used for signature refinement. We examined signatures and clinico-pathological variables as predictors of survival in univariate and multivariate analyses. Results: AJCC 7 Stage was not predictive of recurrence-free survival (RFS) or overall survival (OS). AJCC 8 more evenly staged cases and significantly predicted RFS and OS. Gene signature quality was highly variable, and refinement improved performance. Among gene signatures and clinico-pathological variables in multivariate analysis, TP53 mutation status remained the strongest predictor of OS, especially for HPV-negative tumours, which showed enrichment for TP53 mutations. Among HPV-positive cases, signatures for radiosensitivity, hypoxia, and microsatellite instability revealed significant biological heterogeneity. Thus, a subset of signatures may apply to stratify patients clinically into 'very low risk' and 'low risk' groups. Conclusions: Significant heterogeneity exists in OPC, especially among HPV-positive cases. As a result, current prognostic biomarkers may not adequately identify patients for treatment de-escalation. While some gene signatures may be near routine clinical use, our work shows that quality control, refinement, and validation on independent data is paramount to ascertaining their true predictive ability and reproducibility.
Impact of metastasectomy in the multimodality approach for <i>BRAF</i><i><sup>V600E</sup></i> metastatic colorectal cancer (mCRC): The Mayo Clinic experience.
Authors: Benny Johnson, Zhaohui Jin, Mark J. Truty, Rory L. Smoot, Michael L. Kendrick, David M. Nagorney, Axel Grothey
Journal: Journal of Clinical Oncology (2017)

e15045 Background: BRAF V600E mutations are present in 7% of mCRC patients (pts) and portend a poor prognosis. Data guiding initial treatment decisions are limited. This study investigates the management approach and clinical impact of utilizing metastasectomy for pts with BRAF V600E mCRC. Methods: By using prospective clinical and molecular data from Mayo Clinic, pts with BRAF V600E mCRC were analyzed for clinical characteristics, treatment and survival outcomes. Statistical analyses utilized Kaplan-Meier method, Log-rank test, and Cox proportional hazards models. Results: 164 pts with BRAF V600E mCRC were identified between 6/1999-8/2015. Complete follow up data were available for 52 pts. Median age of 65 years, 61% female, ECOG PS ≤ 1, 71% of pts had right sided tumors and 28% presented with liver limited metastasis. Only 7% (4/52) received FOLFOXIRI/BEV (average of 8 cycles). Peripheral neuropathy, pending BRAF status , and prior progression on FOLFOX, were the most common reasons documented for avoiding FOLFOXIRI/BEV. FOLFOX/BEV was the most common 1 st line regimen used (32% of pts). Median overall survival (mOS) for all 52 pts was 25 months (mo) with median progression free survival (PFS) of 9.3 mo, reflecting worse survival when compared to BRAF wild-type control patients treated at Mayo Clinic (249 pts, mOS: 43 mo). With median follow up of 18.3 mo, 21 pts who underwent metastasectomy had improved OS (29.1mo vs. 22.7mo, HR = 0.33; CI: 0.12-0.78; p = 0.01) and PFS (13.6mo vs. 6.2mo, HR = 0.53, CI: 0.28-0.97; p = 0.03) when compared to the non-metastasectomy cohort, respectively. In multivariate analysis, metastasectomy remained statistically significant for improved survival outcomes (HR 0.52; 95% CI 0.07-1.02; p = 0.02). Median relapse-free survival after metastasectomy was 9.7 mo (95% CI, 5.5 mo-19.5 mo). Only 2 pts remain disease free at the time of last follow up, with 1 pt without recurrent disease for greater than 2 years (28.9 mo). Conclusions: The use of multimodality therapy incorporating metastasectomy for BRAF V600E mCRC is a critical component for enhanced survival outcomes.
The volume-outcome relationship in emergent vs. non-emergent admissions for acute leukemia in Medicare beneficiaries aged 65 and older.
Authors: Michael P Thompson, Teresa M Waters, Erin Kaplan, Caitlin N McKillop, Michael Gary Martin
Journal: Journal of Clinical Oncology (2016)

e18109 Background: Compared to hospitals that rarely treat acute leukemia, hospitals treating higher volumes of acute leukemia may be better equipped to treat emergent admissions, potentially improving patient outcomes. Methods: We used 2013 claims data from 10,101 Medicare beneficiaries aged 65 and older receiving acute leukemia care in 2,045 hospitals to rank-order facilities by increasing annual case volume. Hospitals were categorized as very high volume (N = 38), high (N = 109), and low volume (N = 1,898). We used hierarchical logistic regression models to estimate odds of 30-day post-discharge mortality in patients treated in very high and high hospital volume to patients treated in low volume hospitals, adjusting for patient factors. We then examined the volume-outcome relationship in emergent and non-emergent admissions separately. Results: The median case volume for very high, high, and low volume hospitals was 46, 17, and 2, respectively. As hospital volume decreased, the proportion of emergent admissions increased significantly (p < 0.001): very high volume – 39.9%, high volume – 43.9%, and low volume – 62.1%. Patients treated in very high (OR = 0.66; 95% CI: 0.57, 0.75; p < 0.001) and high volume (OR = 0.87; 95% CI: 0.77, 0.98, p < 0.05) hospitals had reduced likelihood of 30-day post-discharge mortality, compared to low volume hospitals. When treated in very high volume hospitals, both emergent (OR = 0.65, 95% CI: 0.55, 0.83; p < 0.001) and non-emergent (OR = 0.65, 95% CI: 0.55, 0.78; p < 0.001) patients had reduced likelihood of mortality, compared to those treated in low volume hospitals. However, when treated in high volume hospitals, only non-emergent patients enjoyed reduced likelihood of mortality (OR = 0.80, 95% CI: 0.68, 0.95, p < 0.05), while emergent patients failed to show any benefit over low volume hospitals (OR = 0.95; 95% CI: 0.80, 1.12, p > 0.05). Conclusions: Only when treated in very high volume hospitals do emergent admissions for acute leukemia in Medicare beneficiaries aged 65 and older have reduced 30-day post-discharge mortality. Future research should seek to understand the clinical benefit observed in very high volume hospitals for emergent admissions.