tbuckley/cabot-search huggingface dataset:
CCL5 deficiency promotes liver repair by improving inflammation resolution and liver regeneration through M2 macrophage polarization
Authors: Meng Li, Xuehua Sun, Jie Zhao, Lei Xia, Jichang Li, Min Xu, Bingrui Wang, Han Guo, Chang Yu, Yueqiu Gao, Hailong Wu, Xiaoni Kong, Qiang Xia
Journal: Cellular and Molecular Immunology (2019)
P14.66 TTFields dose distribution and tumor growth patterns confirm clinical activity of TTFields: MRI analysis of the randomized phase 3 EF-14 trial
Authors: S Kebir, M T Ballo, S Jeyapalan, S A Toms, A Hottinger, E Pollom, M Glas
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND The randomized phase 3 EF-14 trial showed that the addition of tumor treating fields (TTFields) to temozolomide (TMZ) treatment improved survival in newly diagnosed glioblastoma patients over TMZ alone. As TTFields delivery is designed to optimize dose at the tumor bed, we hypothesized that tumor recurrence is likely to occur in distant sites and we investigated the pattern of tumor growth at relapse in due consideration of TTFields dose intensity distribution. METHODS Patients on therapy for more than 2 months who exhibited radiological progression were included in the study (treatment: N=280/466, control: N=122/229) Contrast-enhanced T1-weighted scans at baseline and at relapse served for segmentation of enhancing tumor and necrosis. Lesions outside a proximal boundary zone of 20mm surrounding lesions identified at baseline were defined as distal. In addition, infratentorial progression was assessed. Moreover, we identified patients treated with TTFields with sufficient MRI data for dose calculations and radiographically confirmed tumor relapse (N=225/466). TTFields intensity distributions were computed in a finite element method applied in a realistic head model with virtual transducer arrays. TTFields dose density (mW/cm3) was defined as TTFields power loss density multiplied by average patient compliance during the first 6 months of therapy. At baseline, regions of residual tumor and regions of normal brain were identified to calculate TTFields dose within each of these regions and noted its relationship with subsequent recurrence. RESULTS Distal progressions were more common in the TTFields arm (18% vs. 8%). Infratentorial progression was seen in 4% of the treatment arm vs. 0 patients in the control. Lesions at progression were more distant from the original lesion in the TTFields arm (57.0 + 26.2 mm vs. 46.6 + 14.8 mm). Local tumors grew at a significantly lower pace in the TTFields arm as compared to the control arm (3.6 + 14.5 ml vs. 8.3 + 17.9 ml). The average dose density in areas of enhancing tumor that regressed to normal was higher than in the areas of normal brain that progressed to enhancing tumor (0.84 mW/cm3 vs. 0.75 mW/cm3). Regardless of the expansion margin used for analysis, TTFields dose density in areas of normal brain that remained normal at the time of progression was higher than in the areas that progressed to enhancing tumor. CONCLUSIONS TTFields appear to induce distant tumor growth pattern and are associated with a lower tumor growth rate. In addition, the importance of dose density at the tumor bed is stressed as higher dose densities were seen in areas of normal brain that remain normal at the time of progression providing further rationale for carefully planning array placement to maximize delivery to areas at higher risk of recurrence. Taken together, these findings confirm the clinical activity of TTFields.
OS3.4 Karnofsky and WHO performance scores of brain tumour patients may limit inclusion in protocols though they depend on clinician status
Authors: D Frappaz, L Taillandier, A Bonneville Levard, J Sorre, D Ricard, S Carrie, C Schiffler, M Weller
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Inclusion criteria for oncological protocols often use the Karnofsky performance score (KPS) &gt;=70 or the WHO performance score (PS) 0–2 as a cut-off value. Inclusion of neuro-oncology patients may be hampered, when general condition is preserved, while performance is decreased due to physical handicap. The goal of this study is to compare the KPS and PS assessments according to the status of the clinician. MATERIAL AND METHODS A cross-sectional survey was conducted through ANOCEF and EANO networks. Clinicians evaluated KPS and PS in 6 clinical situations concerning neuro oncology patients (from youngest and fittest to oldest, crippled with comorbidities). RESULTS The rate of PS &lt;70 or PS&gt; 2 increased significantly from case 1 to 6. Sex or nationality of the clinicians had no impact when adjusting on clinician characteristics. Conversely, speciality (residents/general practitioner vs neurosurgeons vs neurologists vs oncologists), impacted KPS or PS evaluations (p&lt;.0001 and p=0.0046, respectively). Residents or general practitioner estimate KPS much lower than the others specialities. Neurosurgeons estimate PS more severely. Clinicians who were not used to including patients in clinical trials proposed lower KPS scores (p = 0.0008). This tendancy was not shown on PS. Eldest physicians significantly rated more severely than the youngest (p = 0.0459 and p &lt;.0001 for KPS and PS, respectively). In a multivariate analysis, age and speciality were correlated with KPS and PS rating even if adjusted on cases. Discordant decision for protocol inclusion (i:e: (KPS) &gt;=70 vs PS 0–2) showed little discrepancy in case 1 (2.3%), while discrepancy increased to respectively 16, 46, 39, 33 and 43% for cases 2 to 6: in nearly all cases, the KPS would have denied access to a trial, while WHO Ps would have allowed CONCLUSION Rating of KP and PS is subjective in neuro oncology patients: influenced by speciality, age and inclusion habit (for KPS) of clinicians, PS 0–2 allows usually more inclusion than KPS&gt;=70 in more severely disabled patients. A Neuro oncology specific KPS and/or PS definition is warranted to allow more widely inclusion of patients with exclusive neurologic handicap.
PD-1 Expression in Chronic Lymphocytic Leukemia and Large B-Cell Richter Transformation (DLBCL-RT): A Distinguishing Feature for DLBCL-RT and Promising Surrogate Marker for Clonal Relatedness
Authors: Rong He, Wei Ding, David Viswanatha, Dong Chen, Min Shi, Daniel L. Van Dyke, Linda N Dao, Sameer A. Parikh, Tait D Shanafelt, Timothy G. Call, Stephen M Ansell, Jose F. Leis, Ming Mai, Curtis A. Hanson, Karen L Rech
Journal: Blood (2017)
P14.93 The utility of the brain 18-FDG-PET and perfusion magnetic resonance imaging in the radionecrosis differential diagnosis
Authors: N Mongay, N Vidal, A Lucas, M Macià, G Plans, A Fernandez-Coello, C Majos, L Rodriguez-Bel, M Alemany, J Bruna
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Radiation-induced necrosis (RDN) is a side effect observed in patients who underwent stereotactic radiosurgery (SRS) alone or combined with whole brain radiotherapy (WBRT) as treatment for their brain tumors. Nowadays, RDN diagnosis and differentiation from tumor progression using the standard imaging techniques represents a challenge, and histological diagnosis still is the gold standard.Our aim is to assess the positive and negative predictive values (PPV, NPV) of FDG-PET and perfusion magnetic resonance imaging (MRI) in RDN diagnosis. MATERIAL AND METHODS From our Pathology department database, all patients with RDN or mixed (tumor plus RDN) brain lesions diagnosis during last 5 years were reviewed. Demographic, clinical and oncologic treatment characteristics were recorded. MRI and FDG-PET images at the suspicion (clinical or radiological) of progression or RDN were registered and compared with the definite diagnosis provided by the tissue sample analysis. Sensitivity, specificity, as such as PPV and NPV for perfusion MRI sequences and FDG-PET image analysis were calculated. RESULTS 162 patients underwent SRS+/- WBRT in a 5 year period. During follow-up, 11 patients had surgery-confirmed RDN. There are 11 patients (3 women) with 12 lesions, 3 from a breast cancer, 6 from a lung tumor, 1 from a melanoma, 1 atypical meningioma and 1 glioblastoma. 9 of them were treated with both SRS and WBRT, and the 3 others with WBRT alone. The mean age was 65.36 (range: 44–77) years. The median time between the completion of radiation therapy and the suspicion of RDN was 19.7 (range: 3–34) months. With the evolution, it was observed an evident increase in the size of surronding oedema (2–6 times) by FLAIR RMI. We estimate a PPV 0.40 and NPV 0.80 for perfusion MRI, and PPV 0.25 and NPV 0.75 for FDG-PET, respectively. CONCLUSION The diagnostic performance of both techniques in our series is low and similar to published data; therefore its results must be carefully interpreted in each case. It is peremptory to implement new diagnostic tools in the standard of care with better diagnostic outcomes.
Functional peptide presentation on different hydrogen bonding biomaterials using supramolecular additives
Authors: Ronald C. van Gaal, Antonetta B.C. Buskermolen, Bastiaan D. Ippel, Peter-Paul K.H. Fransen, Sabrina Zaccaria, Carlijn V.C. Bouten, Patricia Y.W. Dankers
Journal: Biomaterials (2019)
Results of a phase II study assessing efficacy and tolerance of fluorouracil (FU), leucovorin, irinotecan, and bevacizumab (FOLFIRI + B) in first-line metastatic colorectal cancer (MCRC): The Omega Trial (NTC 00467142).
Authors: Jacques Robert, Yves Becouarn, Laurent Cany, Marina Pulido, Jérôme Dauba, Richard Beyssac, Dominique Bechade, Caroline Lalet, Simone Mathoulin-Pelissier, Rene Brunet, Marianne Fonck
Journal: Journal of Clinical Oncology (2012)

e14023 Background: This phase II study evaluates efficacy and tolerance of FOLFIRI +B in first-line MCRC treatment and assesses several genetic polymorphisms as potential markers of treatment activity or toxicity. Methods: Adult patients (pts) with histologically-proven, non-resectable MCRC, ECOG≤2, were included in this two-stage Simon’s design requiring 61 evaluable pts. 14-day cycles consisted of B (5mg/kg), irinotecan (180mg/m²), bolus FU (400mg/m²) and leucovorin (400mg/m²) followed by a 46-hour infusion of FU (2400mg/m²). UGT1A1, thymidylate synthase and VEGFA promoter SNPs were assessed. Primary endpoint was response rate according to RECIST criteria. Results: Sixty-two pts (25 male) from 7 centers were enrolled between Jan07 – Aug09. Median age: 68 years (1 st -3 rd quartile : 60.4-75.4]); ECOG 0-1 (95.2%); primary tumor location was colon (85.4%) or rectum (14.6%). Principal MCRC locations were: liver (54 pts), lung (28 pts) or peritoneum (17 pts). All pts were evaluable for toxicity. 1058 cycles were administered, median of 13 (range 3-62). Grade 3/4 toxicities were: neutropenia 19.4%; no febrile neutropenia; diarrhea 11.3%; nausea-vomiting 1.6%. No hypertension, thrombotic events, proteinuria or gastrointestinal perforation were observed. 59/62 pts were evaluable for efficacy with 28 pts in PR (47.5%; 95%CI 34.3-60.9), 20 with SD (33.9%) and 11 in PD (18.6%). Median response duration: 9.5 months (range 2.7-20); median time to progression: 10.3 months (range 8.8-11.7); median overall survival (OS) 25.7 months (range 20.2-29.7). 11/59 unresectable pts could finally be resected. To date, three VEGFA polymorphisms have been identified and associations with OS tested. The common genotype of rs25648 is associated with better OS (HR: 0.277; 95%CI: 0.12-0.64). Conclusions: FOLFIRI +B has a good safety profile, is active, with a long median OS leading to resect 18.6% of initially unresectable pts. Genetic polymorphism rs25648 has currently been identified as a marker of better OS, and further analyses for potential UGT1A1 and thymidylate synthase markers are underway.
A correlative analysis of biochemical and radiologic hepatic disease in metastatic pancreatic adenocarcinoma (PA).
Authors: Deaglan Joseph McHugh, MinYuen Teo, Nataliya Rozumna-Martynyuk, Raymond S. McDermott
Journal: Journal of Clinical Oncology (2013)

e15163 Background: The liver is the most common site of distant metastases (mets) in patients with PA. We aimed to study radiomorphology of PA-related liver mets and its correlation with the degree of biochemical hepatic dysfunction. The impact of liver failure on patient mortality was also assessed. Methods: Using National Cancer Institute-Organ Dysfunction Working Group guidelines, patients were stratified into 4 groups A (Normal), B (Mild), C (Moderate), D (severe) based on serum bilirubin and aspartate transaminase levels. Two sets of results were recorded for each patient - at diagnosis (baseline) and the the last available prior to death. CT scan at diagnosis were used to measure both the number and diameter of two largest lesions for each patients’ liver mets. Results: 58 patients with metastatic PA were identified. 5 of these patients were excluded from this study as their imaging was not available. 34 (59%) had hepatic mets. Of 34 patients, 47.1% (n=16) had diffuse mets. 23.5% (n=8) had 6-10 liver mets. 20.6% (n=7) had 2-5 liver mets. 8.8% (n=3) had a solitary metastasis. Four of these patients were excluded as they were still alive at the time of the biochemical analysis. Of 31 patients at baseline: 25.8% (n=8), 35.5% (n=7), 22.6% (n=7), 16.1% (n=5) of patients had group A, B, C and D hepatic dysfunction respectively. The median time between last liver function testing and death was 10 days (range 0-114 days). Prior to death, 16.1% (n=5), 35.5% (n=11), 6.5% (n=2), 41.9% (n=13) of patients had group A, B, C and D dysfunction respectively. Of the 13 patients with severe hepatic dysfunction prior to death, 7 had no radiographic evidence of extrinsic obstruction. No difference in number of liver mets were seen between groups A and B when compared to C and D. However, groups C+D had higher mean size, 2.8 x 2.3 vs. 2.4 x 1.8 cm (p=0.047). No survival difference was noted (4.6 vs 2.5 months, p=0.425). Conclusions: The majority of patients had diffuse liver mets at diagnosis. There was no significant correlation between the radiological burden of hepatic disease and the degree of hepatic impairment at diagnosis. PA-related liver mets was the likeliest cause of death in up to 22.6% of patients.
OS7.1 Impact of the addition of Rituximab to standard therapy with high dose methotrexate on health-related quality of life in primary central nervous system lymphoma patients
Authors: M van der Meulen, L Dirven, K Bakunina, M J B Taphoorn, M J van den Bent, S Issa, J K Doorduijn, J E C Bromberg
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Data on the impact of treatment with Rituximab on health-related quality of life (HRQoL) in primary central nervous system lymphoma (PCNSL) patients are scarce. To determine the net clinical benefit of a new treatment, analyzing the effect on HRQoL is warranted. MATERIAL AND METHODS Patients from a phase III trial (HOVON 105/ ALLG NHL 24), randomized to standard chemotherapy with or without Rituximab, were asked to fill in the EORTC QLQ-C30 and QLQ-BN20 questionnaires before and during treatment, and up to 2 years follow-up or progression. Five predetermined scales were selected for primary analyses: global health status (GH), role (RF) and social functioning (SF), fatigue (FA), and motor dysfunction (MD). A difference ≥10 points was defined as clinically relevant. Cross-sectional analyses were performed comparing changes in HRQoL scores from baseline between the two arms at 12 and 24 months after treatment. Effect of whole brain radiotherapy (WBRT) was analyzed in irradiated patients only. Differences in HRQoL over time between the treatment arms, i.e. the primary outcome, were assessed using linear mixed models (LMM). RESULTS 175/199 patients completed at least one HRQoL questionnaire, and compliance was &gt;60% at all evaluation points. Median age was 61 (IQR 55–66), 74% had a WHO performance score &lt;2, and 38% received WBRT, similar to the total trial population. HRQoL scores on all five scales were significantly and to a clinically relevant extent improved at 12 and 24 months follow-up when compared to baseline in both arms (range: 11.6–42.4), except for FA and MD at 12 months (both -7.2). Differences in HRQoL changes from baseline to 12 and 24 months between the two arms were not statistically significant (range: 3.6–10.9). In the irradiated patients (n=52), HRQoL scores remained stable up to 24 months compared to shortly after WBRT for GH, SF, FA and MD (range -8.1 - 7.6). A clinically relevant and statically significant improvement was seen in RF for both arms at 12 and 24 months compared to ‘after WBRT’(range: +16.7 - +22.2). After correction for multiple testing, LMM analyses showed no statistically significant and clinically relevant differences between the arms for any of the scales over time (range: -3.8 to +4.0). CONCLUSION Treatment resulted in improved HRQoL, but the addition of Rituximab to standard chemotherapy did not further impact HRQoL over time. WBRT did not result in deterioration of HRQoL up to 2 years of follow-up.
Edmonton Symptom Assessment Scale and Clinical Characteristics Associated With Cannabinoid Use in Oncology Supportive Care Outpatients
Authors: Young D. Chang, Jae-Woo Jung, Ritika Oberoi-Jassal, Jongphil Kim, Sahana Rajasekhara, Meghan Haas, Joshua Smith, Vijay Desai, Kristine A. Donovan, Diane Portman
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: Information about the frequency of cannabinoid use and the clinical characteristics of its users in oncology supportive care is limited. This study explored associations between cannabinoid use and cancer-related clinical characteristics in a cancer population. Patients and Methods: This retrospective review included 332 patients who had a urine drug test (UDT) for tetrahydrocannabinol (THC) together with completion of an Edmonton Symptom Assessment Scale (ESAS) and cannabinoid history questionnaire on the same day that urine was obtained during 1 year in the supportive care clinic. Results: The frequency of positive results for THC in a UDT was 22.9% (n=76). Significant statistical differences were seen between THC-positive and THC-negative patients for age (median of 52 [lower quartile, 44; upper quartile, 56] vs 58 [48; 67] years; P &lt;.001), male sex (53.9% vs 39.5%; P =.034), and past or current cannabinoid use (65.8% vs 26.2%; P &lt;.001). Statistical significance was observed in ESAS items between the THC-positive and THC-negative groups for pain (7 [lower quartile, 5; upper quartile; 8] vs 5 [3; 7]; P =.001), nausea (1 [0; 3] vs 0 [0; 3]; P =.049), appetite (4 [2; 7] vs 3 [0; 5.75]; P =.015), overall well-being (5.5 [4; 7] vs 5 [3; 6]; P =.002), spiritual well-being (5 [2; 6] vs 3 [1; 3]; P =.015), insomnia (7 [5; 9] vs 4 [2; 7]; P &lt;.001), and total ESAS (52 [34; 66] vs 44 [29; 54]; P =.001). Among patients who reported current or past cannabinoid use, THC-positive patients had higher total scores and scores for pain, appetite, overall well-being, spiritual well-being, and insomnia than THC-negative patients. Conclusions: Patients with cancer receiving outpatient supportive care who had positive UDT results for THC had higher symptom severity scores for pain, nausea, appetite, overall and spiritual well-being, and insomnia compared with their THC-negative counterparts. These results highlight potential opportunities to improve palliative care.
Stereotactic Body Radiotherapy (Cyberknife) for Early Stage Hepatocellular Carcinoma: A Single Center Experience of 43 Patients and 58 Lesions
Authors: Zixiang Lim, Hendrick Tan, Julian Soares, Michael Christopher Wallace, Leon A. Adams, George Garas, Gerry C. MacQuillan, Jonathan Tibbals, Shaun Samuelson, John Ferguson, Colin Tang, Gary P. Jeffrey
Journal: Hepatology (2018)
P14.109 Standard error of measurement (SEM) and intraclass coefficient (ICC) in volumetric assessment of postoperative residual tumor volume in glioblastoma
Authors: G Hallaert, H Pinson, D Van Roost, J Kalala, V Vandriessche, T Boterberg
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Residual contrast-enhancing tumor volume (RTV) is an important parameter in glioblastoma (GBM) treatment. MR imaging within 48hrs after surgery is the preferred imaging modality but is prone to variability because of different interpretation by different raters. Variability can be statistically assessed using agreement and reliability parameters. The former are underreported in medical literature and are often mixed up with the latter. But agreement parameters are to be preferred in assessment of the level of agreement between repeated measurements. A typical agreement parameter is the standard error of measurement (SEM), which is expressed in the same unit as the original variable. Reliability parameters on the other hand relate the measurement error to the variability between study objects. A typical and well-known reliability parameter is the intraclass coefficient (ICC), expressed on a scale from 0 to 1. We investigated both SEM and ICC between and within raters concerning RTV in GBM. MATERIAL AND METHODS Ten cases were randomly selected from a glioblastoma database. Three observers (a neuroradiologist, NR; a neurosurgeon, NS; a junior neurosurgical trainee, JNT) performed two sessions of volumetric assessment of RTV, blinded for each others results and independently from each other. At least 2 months passed in between sessions. Volumetric assessment was performed using Magnetisation Prepared-Rapid Echo Gradient (MPRAGE) 0.9mm images in standard neuronavigation software (Medtronic Inc, Louisville, CO, USA), in comparison with other images when deemed necessary by the individual rater. Semi-automated segmentation was applied, meaning that the rater used automated segmentation technique on each slice, but adjusted according to his of her own judgement (segmentational growing around the region of interest). Volumes were expressed in mL. Statistical analysis was performed using R software (version 3.4.3 (30-11-2017); Attached packages: psych foreign pander date knitr) to calculate ICCs. SEMs were manually calculated using the formulae by De Vet et al. RESULTS Intrarater ICC agreement was 0.96 (0.87–0.99), 1 (0.98–1) and 0.77 (0.34–0.94) for NS, NR and JNT resp. SEM agreement was 0.87mL, 0.25mL and 2.67mL resp. Interrater variability was as follows: NS-NR 0.89 (0.65–0.97) ICC and 1.42mL SEM; NS-JNT 0.93 (0.77–0.98) ICC and 1.52mL SEM; NR-JNT 0.74 (0.28–0.93) ICC and 2.81mL SEM. CONCLUSION Agreement on postoperative residual contrast-enchancing tumor volume in GBM was high between neurosurgeon and neuroradiologist, with SEM 1.42mL. SEM probably reflects the differences in interpretation, especially of areas with blood products on postoperative MR imaging. Both intrarater and interrater agreement was highest for more experienced raters.