tbuckley/cabot-search huggingface dataset:
Recurrent glioblastoma versus late posttreatment changes: diagnostic accuracy of O-(2-[18F]fluoroethyl)-L-tyrosine positron emission tomography (18F-FET PET)
Authors: Asma Bashir, Sofie Mathilde Jacobsen, Otto Mølby Henriksen, Helle Broholm, Thomas Urup, Kirsten Grunnet, Vibeke Andrée Larsen, Søren Møller, Jane Skjøth-Rasmussen, Hans Skovgaard Poulsen, Ian Law
Journal: Neuro-Oncology (2019)

Abstract Background Diagnostic accuracy in previous studies of O-(2-[18F]-fluoroethyl)-L-tyrosine (18F-FET) PET in patients with suspected recurrent glioma may be influenced by prolonged dynamic PET acquisitions, heterogeneous populations, different non–standard-of-care therapies, and PET scans performed at different time points post radiotherapy. We investigated the diagnostic accuracy of a 20-minute 18F-FET PET scan in MRI-suspected recurrent glioblastoma 6 months after standard radiotherapy and its ability to prognosticate overall survival (OS). Methods In total, 146 glioblastoma patients with 168 18F-FET PET scans were reviewed retrospectively. Patients with MRI responses to bevacizumab or undergoing re-irradiation or immunotherapy after 18F-FET PET were excluded. Maximum and mean tumor-to-background ratios (TBRmax, TBRmean) and biological tumor volume (BTV) were recorded and verified by histopathology or clinical/radiological follow-up. Thresholds of 18F-FET parameters were determined by receiver operating characteristic (ROC) analysis. Prognostic factors were investigated in Cox proportional hazards models. Results Surgery was performed after 104 18F-FET PET scans, while clinical/radiological surveillance was used following 64, identifying 152 glioblastoma recurrences and 16 posttreatment changes. ROC analysis yielded thresholds of 2.0 for TBRmax, 1.8 for TBRmean, and 0.55 cm3 for BTV in differentiating recurrent glioblastoma from posttreatment changes with the best performance of TBRmax (sensitivity 99%, specificity 94%; P &amp;lt; 0.0001) followed by BTV (sensitivity 98%, specificity 94%; P &amp;lt; 0.0001). Using these thresholds, 166 18F-FET PET scans were correctly classified. Increasing BTV was associated with shorter OS (P &amp;lt; 0.0001). Conclusion A 20-minute 18F-FET PET scan is a powerful tool to distinguish posttreatment changes from recurrent glioblastoma 6-month postradiotherapy, and predicts OS.
Association of a School-Based, Asthma-Focused Telehealth Program With Emergency Department Visits Among Children Enrolled in South Carolina Medicaid
Authors: John Bian, Kathryn K. Cristaldi, Andrea P. Summer, Zemin Su, Justin Marsden, Patrick D. Mauldin, James T. McElligott
Journal: JAMA Pediatrics (2019)

Telehealth may improve access to care for populations in rural communities. However, little is known about the effectiveness of telehealth programs designed for children.To examine the associations of a school-based telehealth program in Williamsburg county (South Carolina) with all-cause emergency department (ED) visits made by children enrolled in Medicaid.This Medicaid claims data analysis was conducted in Williamsburg county and 4 surrounding counties in South Carolina and included children aged 3 to 17 years who were enrolled in Medicaid and living in any of the 5 counties from January 2012 to December 2017. Williamsburg served as the intervention and the 4 surrounding counties without a telehealth program as the control; 2012 to 2014 was designated as the preintervention period, whereas 2015 to 2017 served as the postintervention period. The study was designed with a difference-in-differences specification, in which the unit-of-analysis was a child-month, and a subsample included children with asthma. The data analysis was performed from July 2018 to February 2019.The school-based telehealth program implemented in Williamsburg county in 2015.The binary outcome was the status of at least 1 all-cause ED visit by a child in a given month.The full sample included 2 443 405 child-months from 23 198 children in Williamsburg county and 213 164 children in the control counties. The mean (SD) proportions of monthly ED visits in Williamsburg were 3.65% (0.10%) during the preintervention and 3.87% (0.11%) during the postintervention. The corresponding proportions of the 4 control counties were 3.37% preintervention (0.04%), and 3.56% postintervention (0.04%), respectively. The trends in the proportion were paralleled. In the asthma subsample, the proportions in Williamsburg were 3.16% (0.31%) during the preintervention and 3.38% (0.34%) during the postintervention, respectively. The proportions for the control counties were 3.02% preintervention (0.10%) and 3.90% postintervention (0.11%), respectively. There was an interaction of the proportions between the pre/postintervention period and the intervention/control counties in this subsample. The regression analysis of the full sample showed no association of the telehealth program with ED visits. The additional analysis of the asthma subsample showed that this program was associated with a reduction of 0.66 (95% CI, -1.16 to -0.17; P < .01) percentage point per 100 children per month in ED visits, representing an approximately 21% relative decrease.Although we found no association of this program with the ED visits of the overall studied population, this study suggests that telehealth with a focus on chronic pediatric diseases, such as asthma, may deliver substantial health benefits to rural and medically underserved communities.
ABI-009 (<i>nab</i>-sirolimus) in advanced malignant perivascular epithelioid cell tumors (PEComa): Preliminary efficacy, safety, and mutational status from AMPECT, an open label phase II registration trial.
Authors: Andrew J. Wagner, Vinod Ravi, Kristen N. Ganjoo, Brian Andrew Van Tine, Richard F. Riedel, Rashmi Chugh, Lee D. Cranmer, Erlinda Maria Gordon, Jason L. Hornick, David J. Kwiatkowski, Heng Du, Berta Grigorian, Anita N. Schmid, Shihe Hou, Katherine Harris, Neil Desai, Mark Andrew Dickson
Journal: Journal of Clinical Oncology (2019)

11005 Background: Malignant PEComa is a rare, aggressive sarcoma, with no approved treatment or prior clinical trials. Case reports suggest mTOR activation through mutations or deletions of TSC1 or TSC2 and activity of mTOR inhibitors in this disease. ABI-009 is an albumin-bound mTOR inhibitor with increased tumor uptake. The AMPECT trial is the first prospective study in malignant PEComa. Methods: Eligible patients (pts) with centrally confirmed PEComa receive ABI-009 (100 mg/m 2 IV, wkly, 2/3 wks) until progression or unacceptable toxicity. Primary endpoint: ORR by independent review (IR), assessed every 6 wks (RECIST v1.1). Secondary endpoints: duration of response (DOR), PFS6, PFS, and safety. Exploratory endpoints (EE): investigator-assessed (IA) outcomes and mutational status. Sample size: 30 efficacy-evaluable pts based on target ORR of 30% (primary analysis planned when all pts treated ≥6 mo). Results: EE and safety are reported (IR pending). As of Feb 12, 2019, enrollment is complete; 34 pts treated, 31 evaluable for efficacy, 42% (13/31) pts ongoing Rx. IA ORR is 42% PR (13/31, 95% CI: 24.5, 60.9), 35% SD (11/31), and 23% PD (7/31); 69% of PRs were reached at 1st restaging (wk 6); 69% PRs are ongoing, with 5 pts &gt;1yr and 2 pt &gt;2 yrs on Rx (all ongoing). Other IA outcomes: median DOR is not reached; PFS6 is 66%; median PFS is 8.9 mo (95% CI: 5.5, -). The most common (&gt;30%) nonhematologic treatment-related AEs (TRAEs) of any grade: mucositis (65%), fatigue (53%), nausea/weight loss (35% each), diarrhea (32%); the most common (&gt;15%) hematologic TRAEs: anemia (44%) and thrombocytopenia (18%). Pneumonitis (15%) was G1/G2. The most common (&gt;10%) G3 TRAEs: mucositis (18%), anemia (12%); No grade ≥4 TRAEs. TSC1 or TSC2 mutations occurred in 5 and 9 (no overlap) of 25 pts with known mutational status, respectively. PR was seen in 100% (9/9) pts with TSC2 mutation, 20% (1/5) pts with TSC1 mutation, and 9% (1/11) pts without mutation in TSC1 or TSC2, P &lt; 0.0001 (2x3 Fisher exact test). PR was significantly higher in pts with TSC2 mutations vs pts without mutation in TSC1 or TSC2, P = 0.0001 (Fisher exact test). Disease control (PR+SD) was seen in 93% (13/14) pts with TSC1 or TSC2 mutations vs 55% (6/11) pts without mutation in TSC1 or TSC2, P = NS. Conclusions: Preliminary IA outcomes showed that ABI-009 treatment of PEComa resulted in substantial and durable responses with manageable toxicities. TSC2 mutations were associated with IA response. Clinical trial information: NCT02494570.
Health-related quality of life and neurocognitive functioning with lomustine–temozolomide versus temozolomide in patients with newly diagnosed, MGMT-methylated glioblastoma (CeTeG/NOA-09): a randomised, multicentre, open-label, phase 3 trial
Authors: Johannes Weller, Theophilos Tzaridis, Frederic Mack, Joachim Peter Steinbach, Uwe Schlegel, Peter Hau, Dietmar Krex, Oliver Grauer, Roland Goldbrunner, Oliver Bähr, Martin Uhl, Clemens Seidel, Ghazaleh Tabatabai, Stefanie Brehmer, Lars Bullinger, Norbert Galldiks, Christina Schaub, Sied Kebir, Walter Stummer, Matthias Simon, Rolf Fimmers, Christoph Coch, Martin Glas, Ulrich Herrlinger, Niklas Schäfer
Journal: The Lancet Oncology (2019)
Postoperative Recurrence of Hepatocellular Carcinoma: The Importance of Distinguishing between Intrahepatic Metastasis and Multicentric Occurrence—Response
Authors: Sungwon Kim, Jaeseung Shin, Do Young Kim, Gi Hong Choi, Myeong-Jin Kim, Jin-Young Choi
Journal: Clinical Cancer Research (2019)

We thank Bai and Liang for their interest in our work and the valuable comments they have provided (1).Intrahepatic recurrence of hepatocellular carcinoma (HCC) may be caused by intrahepatic metastasis (IM) of the primary carcinoma or by de novo multicentric occurrence (MO). Although genetic or molecular studies can be used to definitively distinguish between the two, these techniques are not part of the standard evaluation process owing to their technical complexity. Several recent studies have reported that aggressive characteristics in primary tumors are associated with early recurrence within 2 years after surgery, whereas late recurrence (>2 years) is associated with underlying liver conditions, such as liver cirrhosis (2). In our study, we identified that radiomics with border extensions predicted both early (using 3-mm border extension) and late recurrence (using 3- and 5-mm border extensions) to a comparable level with the postoperative clinicopathologic model. Aggressive peritumoral morphologic characteristics, such as microvascular invasion for early recurrence and peritumoral cirrhotic parenchyma for late recurrence, could confer prognostic power to radiomics in these conditions. Interestingly, the prognostic power of radiomics for predicting late recurrence tended to increase with the widening of the border extension. In the absence of the border extension, the prognostic power of radiomics tended to be inferior to that of the clinicopathologic model. This suggests that the presence of cirrhosis in the peritumoral hepatic parenchyma included in the border extension may have affected the efficacy of radiomics for predicting late recurrence.In addition, the only known predictor of late recurrence of HCC is cirrhosis, and there may be morphologic differences between HCC arising in cirrhotic and noncirrhotic livers. HCC in noncirrhotic livers often presents at an advanced stage as a large-sized solitary or dominant mass with satellite nodules, unlike HCC in cirrhotic livers (3, 4). This tendency can be explained by either the inherent biological aggressiveness of noncirrhotic HCC or the typically delayed diagnosis (5). Radiomics may distinguish morphologic differences in primary HCCs depending on the presence of cirrhosis, which may be reflected in the prediction of late recurrence.However, the accuracy for distinguishing between IM and MO based on a 2-year cut-off value is limited, and an overlap is expected when using this cut-off value. Further research on radiomics for molecularly or genetically confirmed IM and MO are required. We believe that a radiomics study on the differential diagnosis between molecularly or genetically confirmed IM and MO is also needed.See the original Letter to the Editor, p. 5426No potential conflicts of interest were disclosed.
QOLP-04. CALCULATING THE NET CLINICAL BENEFIT IN BRAIN TUMOR TRIALS BY COMBINING SURVIVAL AND HEALTH-RELATED QUALITY OF LIFE DATA USING TWO METHODS: QUALITY ADJUSTED SURVIVAL EFFECT SIZES AND JOINT MODELLING
Authors: Marijke Coomans, Linda Dirven, Andrew Bottomley, Martin van den Bent, Jeff Sloan, Roger Stupp, Michael Weller, Jaap Reijneveld, Martin Taphoorn, Neil Aaronson, Brigitta Baumert, Alba Brandes, Olivier Chinot, Corneel Coens, Thierry Gorlia, Ulrich Herrlinger, Florence Keime-Guibert, Annika Malmström, Francesca Martinelli, Andrea Talacchi, Wolfgang Wick
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION The impact of treatment on both the quality and the quantity of life, i.e. the ‘net clinical benefit’, should be considered to facilitate shared decision making. Two methods that combine survival and health-related quality of life (HRQoL) data: Quality Adjusted Effect Sizes (QASES) and Joint Modelling (JM) were applied to gain insight in the net clinical benefit. METHODS The net clinical benefit in one RCT (EORTC 26951 comparing radiotherapy (RT) + PCV chemotherapy versus RT alone) was calculated as a proof of concept for other trials. With the QASES method, effect sizes for differences in survival and HRQoL between treatment arms were calculated. JM allows simultaneous modeling of a longitudinal outcome (HRQoL), and a time-to event outcome (survival). HRQoL scales/items that were selected for primary analysis in the main study were also selected for this analysis: fatigue, global health, social functioning, communication deficit, seizures, physical functioning, and nausea/vomiting. RESULTS 288/386 patients completed baseline HRQoL forms and were included in the analysis. Overall survival (OS) was significantly longer with combined treatment (42.3 vs. 30.6 months). The percentage of patients who experienced a clinically relevant deterioration (≥10 points) in nausea/vomiting, fatigue, social functioning and global health up to one year after treatment compared to baseline was larger in the RT+PCV arm. QASES corresponded to a reduction in the median OS difference from 9.7 months up till 5.5 months, given equal weights to OS and HRQoL. JM analyses resulted in a theoretical loss of treatment effect in OS of 2–6% when adjusting for HRQoL. CONCLUSION Both methods showed that adjusting for the impact of treatment on a relevant HRQoL parameter reduced the survival benefit in the experimental treatment arm compared to standard treatment arm. Applying these methods may facilitate communicating the impact of treatment to patients in clinical practice.
P11.13 Radiotherapy combined with a multimodal imaging approach in a glioblastoma preclinical model
Authors: D Salvatore, G Shaw, J Wright, I Teh, J Koch-Paszkowski, L Murray, A Scarsbrook, J Schneider, L Ottobrini, S Short
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Glioblastoma multiforme (GBM) carries a poor prognosis, partly due to biological and anatomical heterogeneity. Although radiotherapy (RT) is effective, high doses damage surrounding healthy tissues. Multimodal imaging with Magnetic Resonance (MRI) and Positron Emission Tomography (PET) may represent a useful approach for identifying GBM heterogeneity and visualising metabolic tumour properties. PET radiotracer [18F]-fluciclovine is preferentially accumulated in gliomas compared to healthy brain tissue via the cellular transport systems, LAT1 and ASCT2. In this study the effect of fractionated RT using multimodal imaging including [18F]-fluciclovine uptake and immunohistochemistry (IHC) in a GBM preclinical model will be validated. MATERIAL AND METHODS Two C57BL/6J mice cohorts were injected intracranially (i.c.) with murine CT2A-luc cells and subsequently submitted to multiparametric MRI and [18F]-fluciclovine PET imaging during hemi-brain RT (3Gy on 2 days/each week) for maximum 25 days after i.c. injection. Brains were collected for IHC characterization including LAT1 and ASCT2 staining. RESULTS Preliminary data showed that both MRI and PET were effective modalities to track tumour growth in this model. PET data revealed up to greater than 3-fold increase in SUVmax from regions of interest around the tumour site compared to healthy brain tissue. Time activity curves showed a steady increase in tumour uptake over 90 minutes. MRI showed a 25% increase in T2 values in tumours relative to unaffected contralateral regions. Confirmation of treatment response through matched imaging and IHC are ongoing, from which changes in glioma cell biology as well as amino acid transporter protein levels will be analysed. CONCLUSION These preliminary results show that multimodal imaging presents novel data in the assessment of treatment response in this model and will permit parallel IHC analyses to better define GBM tumour heterogeneity aligned with imaging changes. These data will also inform an on-going clinical study using the same imaging modalities. Work at authors’ labs are supported by an Investigator initiated project from Blue Earth Diagnostics (AS, SCS) and a University of Leeds Biswas studentship (SCS, DS). Daniela Salvatore is also supported by a Scholarship provided by Molecular and Translational Medicine Doctorate School of University of Milan (Italy).
P07.02 Enhanced glycolysis in glioblastomas is associated with tumor cells migration
Authors: M Ndiaye, C Rébé, A Ilie, L Ménégaut, T Pilot, F Ghiringhelli
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Glioblastoma is the most common primary brain tumor. Its prognosis remains poor even with the standard treatment - the Stupp protocol.The classic Warburg effect in cancers leads to increased glycolysis which causes acidification of the tumor environment. This phenomenon may favor migration of tumor cells as already reported in pancreatic ductal adenocarcinoma. We therefore hypothesized that enhanced glycolysis in glioblastomas could favor the tumor cell migration. MATERIAL AND METHODS We measured glycolysis by the extracellular acidification rate (ECAR) of several human glioblastomas cell lines (LN229, LN18, T98-G, U87-MG, U373-MG, U118-MG) with the Seahorse Analyzer. To confirm these results, we also measured the intracellular cAMP rates using the Cayman’s Elisa kit and we analyzed by RT-PCR the expression of the main genes coding for enzymes involved in glycolysis in these glioblastomas cell lines. Cell migration was measured with a scratch wound healing assay during 24 hours. RESULTS U118-MG was the glioblastoma cell line with the highest glycolysis rate, the highest production of cAMP and showed a strong expression of glycolysis-associated genes. LN229 was the glioblastoma cell line with the less important glycolysis rate, the lower production of cAMP and showed a weaker expression of glycolysis-associated genes. According to the scratch wound healing assay, U118-MG cells showed a more important migration than LN229 cells at 24 hours. CONCLUSION Glycolysis may be an attractive target to prevent effectively tumor cell migration in glioblastomas. Coupling the evaluation of glycolysis with histomolecular characterization of glioblastomas, could help to identify patients to whom adjuvant therapies that inhibit glycolysis such as fenofibrate could be proposed.
Proteomics: A panel of seven serum biomarkers as a promising diagnostic tool for breast cancer
Authors: R. Lastra, A. Monasterio, I. Alvarez-Busto, J. Mayordomo, J. Algorta, A. de Juan, I. Pericás, F. Garijo, J. Aberro, S. Fernandez, M. Martín
Journal: Journal of Clinical Oncology (2009)

e22019 Background: Conventionals serum biomarkets have a low sensibility in breast cancer diagnosis. Proteomic is a promising tool to identify new proteins profiles to be used in screening and early diagnosed. Methods: 1)Biomarker identification: Serum proteins from 114 women were separated and analysed by bidimensional gel electrophoresis; data from 72 patients (p) were compared with those from 42 control women to search for differentially expressed proteins. Several comparisons were performed between controls and p regarding clinical parameters such as histological type, tumour stage and lymph node affection (-/+). A total of 53 spots were found to be differentially expressed and identified by mass spectrometry (MS) as potential breast cancer biomarkers.2) Protein Chip development: A Protein Chip was developed with antibodies against six biomarkers and three control proteins (an antibody for the detection of a spiked control, for data normalization and two proteins as positive and negative controls). An antibody against CA15–3 antigen was also included as a reference breast tumour marker to be compared with our biomarker panel. 3) Clinical validation of the Protein Chip: A clinical validation study was carried out with 75 healthy women and 125 breast cancer p. After multivariate statistical analysis of the biomarker data, CA15–3 was discarded due to its low significance while a panel of 5 biomarkers was obtained as the best predictive model to discriminate p from healthy subjects. Results: 53 diferentially expressed proteins have been identified as potential breast cancer serum biomarkers after analysing 114 serum samples by 2DE Technology. A Protein Chip has been developed for the simultaneous detection of five serum biomarkers and three control proteins. After clinical validation with 200 p and healthy women, the sensitivity of the Protein Chip to detect breast cancer was 95% and its specificity was 27%. Conclusions: The high sensitivity of the Protein Chip suggests that it could be a valid tool to complement mammography (sensitivity &lt; 80%) in breast cancer screening programs, specially when its sensitivity tends to decrease, as it happens in young women and dense breast cases. Larger clinical validation trials are being developed. This work is supported by INDAS BIOTECH. No significant financial relationships to disclose.
Patient Satisfaction of Care in the Treatment of Vaso-Occlusive Crises: A Comparison of Emergency Department and Infusion Centers in the Escaped Study
Authors: Nebras Abu Al Hamayel, Jasmine Brooks, Hang Wang, Rebecca Seufert, Carlton Haywood, Ravi Varadhan, Mustapha Saheed, Jodi Segal, Chiung-Yu Huang, Joshua J. Field, Steven Frymark, Jane Little, Brandi Griffin, Nicole Arnold, Joseph Ryan Shows, Allie Piehet, Marc Proudford, Derek Robertson, Marcus Wallace, Adrienne Kincaid, Charles Green, Lorri Burgess, Sophie Lanzkron
Journal: Blood (2018)