tbuckley/cabot-search huggingface dataset:
Long term efficacy of nilotinib as front- and second-line therapy in Bosnia and Herzegovina: Real life experience.
Authors: Amina Kurtovic Kozaric, Erna Islamagic, Semir Beslija, Sabira Kurtovic, Lejla Mehinovic, Azra Hasic
Journal: Journal of Clinical Oncology (2017)

e18549 Background: In this study we examined the long-term real life clinical outcomes of patients receiving front- line nilotinib and patients who switched from branded or generic imatinib to nilotinib (second-line therapy) in Bosnia and Herzegovina. Methods: Patients in CML-CP (n = 70) who started their TKI treatment in period from June 2005 to August 2016 were included in this multicentre retrospective cohort study. Patients were categorized as: Group 1 (n = 31) contained patients receiving front-line nilotinib (300 mg twice daily) and Group 2 (n = 39) consisted of patients who started with front-line imatinib (Glivec or generic imatinib) and then were switched to nilotinib (400 mg or 600 mg twice daily). Nilotinib became available as front or second-line therapy in March 2011. Standard patients' variables were collected and disease progression was established as loss of CCyR and MMR. Survival probabilities were estimated with the Kaplan-Meier method and compared using the log-rank test. Results: Seventy patients (median age was 54.5 years; 61% was males) were enrolled in this study. The median follow-up was 39 months (range 3-51 months). Median wait period for therapy was 12 months (range 1-62) from diagnosis. In both studied groups, overall survival was 87% at 39 months. According to ITT principle, achievement of CCyR and MMR at 24 months on nilotinib therapy was higher in Group 1 compared to Group 2 (81% vs 67% and 74% vs 49%, respectively). Rate of death was similar in both studied groups (4/31 vs 5/39). In Group 2, five patients who had suboptimal response on front-line imatinib discontinued therapy (median period of 19.5 months) were switched when nilotinib became available. Interestingly, none of these patients died. Conclusions: Our results suggest that at 3 years, there was no difference in the overall suvival between studied groups. However, achievement of CCyR and MMR at 24 months was higher in patients on front-line nilotinib therapy. Patients who waited for therapy had optimal response regardless the wait period on nilotinib therapy.
P01.154 Volumetric response to TTFields in newly diagnosed GBM
Authors: J Kerschbaumer, C F Freyschlag, D Pinggera, C Thomé
Journal: Neuro-Oncology (2018)

Optune TTField treatment is an established, non-invasive therapy for patients with newly diagnosed or recurrent glioblastoma (GBM). Treatment efficacy was evaluated demonstrating significant improvement of both, overall and progression free survival. For analysis, the MacDonald criteria were used in clinical practice as well as in the EF-14 trial. We performed a 3D volumetric analysis of patients with newly diagnosed GBM who underwent resection and chemoradiation plus TTFields additionally. Between February 2016 and April 2017, 14 patients were initiated with TTField treatment. Seven patients with a treatment duration of more than 3 months were available for analysis of volumetric response rates (newly diagnosed GBM, device usage over 60%). Patients included were using the device between 3 and 14 months. A 80% cutoff in device usage was arbitrary set as this corresponds to the recommended daily usage of over 18 hours (= 75% ADU). Contrast enhancing tumor on T1 imaging (MPRAGE, 1mm slice thickness) was assessed by segmentation and volumetric analysis. The median age was 48 years (range 17–68 years) at the date of treatment initiation. Median preoperative tumor volume was 20.3 cc (range: 1.12–58.6cc), postoperative volume was 6.3 cc (range: 0–14.2cc) and volume at time of analysis was 1.2 cc (range: 0–7.1cc). Average device usage (ADU) of these patients was 89.5%. The median change of volume from postoperative to posttreatment volume was 4cc (range: 0–7.1cc) in patients with a median device usage of over 80%; whereas in patients with lesser than 80%, the mean volume change was 2.2cc (range 0–3.2cc). TTFields are generally accepted and efficacious for treatment of GBM. Our analysis showed that the combination of radiation, Temozolomide and TTFields lead to a reduction in contrast enhancing tumor volume. The effect seems to be related to treatment duration.
Patient predictive factors for clinical trial participation.
Authors: Adrianne Rose Mallen, Bernadette M. Boac, Sarah Todd, Sharon E. Robertson, Anjalika Gandhi, Michelle Kuznicki, Biwei Cao, Anthony Martin Magliocco, Robert Michael Wenham, Brooke Fridley, Hye Sook Chon
Journal: Journal of Clinical Oncology (2018)

6530 Background: Clinical trials (CT) in cancer research are considered the gold standard in evaluating efficacy of a new treatment and quite, literally, save lives. On average, only 3% of adult patients with cancer enroll in CT. Our primary aim was to assess patient predictive factors for CT participation. Our secondary aim was to assess overall survival for patients enrolled in CT versus no CT (NCT). Methods: A 14-year retrospective chart review was conducted for analysis of sociodemographic, clinicopathologic and treatment characteristics of 558 advanced stage epithelial ovarian cancer patients who were treated at a single-institution NCI-CCC at some point in their treatment course. Results: A total of 399/558 patients (71.5%) did not participate (NCT) versus 160/558 (28.5%) who did at some point in their treatment course (CT). Overall, 238/558 (43%) had CT discussion with their provider. The majority, 126/160 (78.75%) participated in CT at time of recurrence, 20/160 (12.5%) at time of adjuvant chemotherapy only and 14/160 (8.75%) for both adjuvant therapy and recurrence. Patients were well-matched in terms of disease characteristics. Younger age (58.04 in CT vs 63.07 in NCT, p < 0.0001), type of insurance (p < 0.0001), receipt of neoadjuvant chemo (p = 0.014), receipt of intraperitoneal chemo (p = 0.00024) and gynecologic oncologist as adjuvant chemo provider (p = 0.005) were also statistically significant patient factors associated with greater CT participation. Race (p = 0.02), educational level (p = 0.095), religion (p = 0.39), marital status (p = 0.66), distanced traveled for care (p = 0.99), debulking status (p = 0.72) and platinum sensitivity (p = 0.13) were not statistically significant patient factors. After adjusting for clinical factors associated with OS, women who participation in a clinical trial had significantly better OS (HR = 0.698, 95% CI (.544, 0.896), p = 0.005). Conclusions: Encouragement for clinical trials appears to be warranted. Improved survival was significant for CT patients and is further justification for offering the gold standard of treatment at our NCI-CCC. Understanding of patient predictive factors warrants further exploration so we can overcome barriers to patient enrollment in CT.
Abstract 17160: Mots-c: a Novel Mitochondrial-derived Peptide is Associated With Coronary Endothelial Function
Authors: Silvia Delrio, Junxiang Wan, Pinchas Cohen, Lilach O Lerman, Amir Lerman
Journal: Circulation (2016)

Introduction: Coronary endothelial dysfunction is the early stage of atherosclerosis and is associated with cardiovascular events. We previously demonstrated that the mitochondrial peptide (MDP) hu...
Gαi1 and Gαi3mediate VEGF-induced VEGFR2 endocytosis, signaling and angiogenesis
Authors: Jian Sun, Wei Huang, Shuo-fei Yang, Xiao-pei Zhang, Qing Yu, Zhi-qing Zhang, Jin Yao, Ke-ran Li, Qin Jiang, Cong Cao
Journal: Theranostics (2018)

VEGF binding to VEGFR2 leads to VEGFR2 endocytosis and downstream signaling activation to promote angiogenesis. Methods: Using genetic strategies, we tested the requirement of α subunits of heterotrimeric G proteins (Gαi1/3) in the process. Results: Gαi1/3 are located in the VEGFR2 endocytosis complex (VEGFR2-Ephrin-B2-Dab2-PAR-3), where they are required for VEGFR2 endocytosis and downstream signaling transduction. Gαi1/3 knockdown, knockout or dominant negative mutation inhibited VEGF-induced VEGFR2 endocytosis, and downstream Akt-mTOR and Erk-MAPK activation. Functional studies show that Gαi1/3 shRNA inhibited VEGF-induced proliferation, invasion, migration and vessel-like tube formation of HUVECs. In vivo, Gαi1/3 shRNA lentivirus inhibited alkali burn-induced neovascularization in mouse cornea. Further, oxygen-induced retinopathy (OIR)-induced retinal neovascularization was inhibited by intravitreal injection of Gαi1/3 shRNA lentivirus. Moreover, in vivo angiogenesis by alkali burn and OIR was significantly attenuated in Gαi1/3 double knockout mice. Significantly, Gαi1/3 proteins are upregulated in proliferative retinal tissues of proliferative diabetic retinopathy (PDR) patients. Conclusion: These results provide mechanistic insights into the critical role played by Gαi1/3 proteins in VEGF-induced VEGFR2 endocytosis, signaling and angiogenesis.
TCT-671 A Systematic Review and Meta-Analysis of Permanent Pacemaker Implantation and Paravalvular Leak Rates after Sutureless Aortic Valve Operations
Authors: Mohamad Lazkani, Charan Teja Reddy Yerasi, Sheena Prakash, Luke Seibolt, Ashish Pershad, Hao Fang
Journal: Journal of the American College of Cardiology (2018)
The quality of life (QoL) assessment of oxaliplatin-based preoperative chemotherapy for locally advanced gastric cancer: An integration analysis of two prospective phase I study.
Authors: Hironaga Satake, Akira Miki, Hisateru Yasui, Akihito Tsuji
Journal: Journal of Clinical Oncology (2017)

e18263 Background: Surgery with lymph node dissection is the primary treatment for patients with localized resectable gastric cancer. However, the prognosis of locally advanced gastric cancer is poor. One promising approach is neoadjuvant chemotherapy, however, the use of neoadjuvant chemotherapy consisting of oxaliplatin-based regimen for locally advanced gastric cancer has not been reported. Oxaliplatin-induced neurotoxicity may continue after the chemotherapy and interfere with patients’ daily activities. We conducted two prospective phase I study of oxaliplatin-based neoadjuvant chemotherapy for locally advanced gastric cancer and assessed the oxaliplatin-induced neuropathy using the FACT-Ga and FACT-GOG-Ntx assessments. Methods: We planned two cycles of oxaliplatin administration and evaluated oxaliplatin-induced neuropathy using the FACT-Ga and FACT-GOG-Ntx assessments. Patients with locally advanced gastric cancer received two cycles of neoadjuvant chemotherapy with oxaliplatin (100 or 130 mg/m 2 ) on day 1, as well as S-1 (80 mg/m 2 /day, b.i.d.) or capecitabine (2000 mg/m 2 /day, b.i.d.) for 14 days, repeated every 3 weeks. They then underwent gastrectomy with curative D2/3 lymph-node dissection followed by adjuvant S-1 (80 mg/m 2 /day, b.i.d.) for one year. QoL was assessed at baseline and during treatment. Results: Twelve patients were enrolled and fully assessed the QoL. All patients were chmo-naïve and had a good performance status: median age 70y, 67% male. The mean dose intensity of delivered during the neoadjuvant chemotherapy was 96.0% for oxaliplatin. Peripheral neuropathy was observed in all patients but with no functional disorders. Median time to QoL deterioration in FACT-G and FACT-GOG-NTx was 3 weeks. There were correlation between oxaliplatin administration and QoL deterioration by the repeated-measures ANOVA. Conclusions: FACT-GOG-Ntx showed that sensory neuropathy caused a deterioration in QoL immediately after the initiation of preoperative oxaliplatin-based chemotherapy, but that QoL recovered after the neo-adjuvant chemotherapy. Clinical trial information: UMIN000015950,UMIN000015181.
P01.133 Preoperative predictors of malignancy in non-enhancing glioma in the era of molecular classification
Authors: P Dao Trong, J Jesser, A von Deimling, S Kilian, C Herold-Mende, A Unterberg, C Jungk
Journal: Neuro-Oncology (2018)

The association of contrast enhancement with malignancy in glioma is widely accepted. A higher grade of uncertainty exists for preoperative grading of non-enhancing tumors. Prior studies point out, that contrast enhancement alone cannot be taken into account for grading glioma since up to 40% of high-grade tumors are reported to be non-enhancing. Here, we sought to reevaluate tumor grading of non-enhancing glioma with the new WHO classification of 2016 and analyzed clinical data and radiographic features (T2/FLAIR mismatch sign, subventricular zone involvement, tumor volume and growth) which might predict WHO grading, IDH mutation or progression free survival (PFS). Out of 626 glioma patients, 72 with non-enhancing glioma were identified who underwent first supratentorial surgery in our department from 2012 to 2017. Surgery included stereotaxic biopsy, open biopsy, subtotal and gross total resection. Median follow-up was 24.5 months (6–127 months). Histopathological and molecular examinations were performed by our senior neuropathologist in concordance with the new WHO classification of 2016. The “T2/FLAIR mismatch sign” and tumor involvement with the subventricular zone were evaluated by two independent investigators. Medical records of all patients were reviewed. The “Pignatti” risk score was calculated as previously described. 57% (41) of patients were IDHmut and 43% (31) IDHwt. 75% of the total study cohort (54 patients) in which preop-MRI suggested low grade glioma, were indeed classified grade III or IV and thus considered malignant. Involvement of the subventricular zone correlated with PFS (log-rank p= 0.02). Age significantly correlated with PFS (log-rank p= 0.01) and with tumor grade (log-regression p< 0.001). When applying the new WHO classification to the Pignatti risk score, no correlation in PFS and tumor grading could be seen. We could confirm that the T2/FLAIR mismatch sign is highly specific for IDH mutation (positive predictive value 96%; 95% CI: 83.30% - 99.92%). In this study, 75% of suspected non-enhancing low grade glioma were indeed grade III or IV according to the new WHO classification of 2016. We confirmed the T2/FLAIR-mismatch sign to be a highly specific marker for IDH mutation and found that involvement of the tumor with the subventricular zone was significantly correlated with a worse PFS. These results may help to improve preoperative patient counseling.
TCT-746 Can Cardiac MRI Viability Assessment Guide Revascularization Decisions in Patients with Ischemic Cardiomyopathy?
Authors: Demetrios Doukas, Jessica Marot, Katerina Porcaro, Lucas Burke, Nicholas Kassis, James Nguyen, Jane Cao, Mushabbar Syed, Verghese Mathew
Journal: Journal of the American College of Cardiology (2018)
Immune response, safety, and survival impact from CMB305 in NY-ESO-1+ recurrent soft tissue sarcomas (STS).
Authors: Neeta Somaiah, Sant P. Chawla, Matthew Stephen Block, John Charles Morris, Khanh Tu Do, Joseph W. Kim, Mihaela Druta, Kamalesh Kumar Sankhala, Patrick Hwu, Sacha Gnjatic, Hailing Lu, Richard T. Kenney, Gerry C. Bohac, Seth Pollack
Journal: Journal of Clinical Oncology (2017)

11006 Background: CMB305 is an active immunotherapy regimen designed to generate and expand anti-NY-ESO-1 T cells. It consists of LV305, a dendritic cell targeting lentiviral vector encoding NY-ESO-1, and a boost with G305, an NY-ESO-1 recombinant protein plus GLA-SE, a TLR-4 agonist. An LV305 phase 1 study demonstrated a 1-yr survival of 81% and induction of anti-NY-ESO-1 T cells in sarcoma patients (pts). This first-in-human study of CMB305 examined safety, immunogenicity, and efficacy in pts with NY-ESO-1 positive (+) solid tumors. Methods: Adults with previously treated NY-ESO-1 + sarcomas, NSCLC, ovarian cancer were enrolled in a 3+3 dose-escalation with an expansion phase 1 study. The CMB305 regimen included 4 intradermal injections of LV305 at 10 9 or 10 10 vector genomes, alternating with 3 intramuscular G305 injections at 250 µg for 3 months, then bimonthly G305 injections up to 1 yr. Results: As of 31Dec2016, 25 pts with STS (15 synovial (SS), 8 myxoid/round cell liposarcoma (MRCL), 2 other) were evaluable for safety; 23 SS/MRCL pts were evaluable for immune response (IR) and efficacy. All SS and MRCL pts received prior therapy for locally advanced/metastatic disease, 67% &gt; = 2 prior chemo regimens. No DLTs were observed; treatment related AEs were grade 1 and 2, except 1 pt with grade 3 SAE (prostatic pain). Of 11 SS/MRCL pts tested, 64% pts developed NY-ESO-1 specific T cells and 72% pts anti-NY-ESO-1 antibodies. T cell receptor sequencing indicated increased clonality, and antigen spreading after CMB305. Best response by immune related response criteria was stable disease in 8/15 (53%) SS pts and 6/8 (75%) MRCL pts. The 3 month PFS rate was 74% and 75% for SS and MRCL pts. Median survival has not been reached with 1-yr survival rate of 86% and 100% for SS and MRCL pts. Conclusions: CMB305 is safe, well tolerated, and demonstrates a survival rate that is favorable when compared with approved agents for recurrent STS. CMB305 resulted in a stronger and broader integrated IR than LV305, including antigen spreading. These data warrant further investigation of CMB305 as a monotherapy in a randomized clinical study in STS. A randomized study of CMB305 in combination with atezolizumab in SS/MRCL pts is ongoing. Clinical trial information: NCT02387125.
Epidemium: A multidisciplinary community to tackle cancer using big and open data.
Authors: Mehdi Benchoufi, Marc Fournier, David Magrez, Gaspard Macaux, Vanessa Barué, Alicia Mansilla Sanchez, Olivier de Fresnoye, Romain Fillaudeau, Ozanne Tauvel-Mocquet, Nassera Chalabi, Jean Frédéric Petit-Nivard, Leo Blondel, Marc Santolini, Béchir Ben Hadj Yahia
Journal: Journal of Clinical Oncology (2018)

e13604 Background: Cancer is a complex and polymorphic disease. Large open datasets are currently available, though unstructured and heterogeneous. As such, expertise from various fields is needed to curate and analyze these datasets. Epidemium was set up as an innovative multidisciplinary community-based program to tackle these challenges and offer a new approach to cancer epidemiology research using big data. Methods: Epidemium combines cancer knowledge and data science expertise with an open, inclusive and collaborative approach. It invites any willing participant to submit a project or to join an existing one, regardless of his background. To foster synergies within the open community, regular conferences, meetings, and data challenges were set up, combined with a dedicated web platform - built using open source software - hosting selected resources and open data sets (WHO, Roche, FAO, World Bank, ILO, etc.). A six-month community-oriented Challenge allowed teams to make contributions that were reviewed by an Independent Ethics Committee and a Scientific Committee. Results: As of June 2016, Epidemium had gathered 678 members with different backgrounds: 19% Health Professionals, 28% Computer Scientists, and 53% Data Scientists. 15 projects were submitted to the Challenge and 3 were awarded: Baseline, CancerViz, and ELSE, focusing respectively on risk and protective factors of cancer, distribution of cancer in time and space, and environmental changes and cancer. All contributions (3.600 on the wiki) were shared in open source. Conclusions: Epidemium provides a proof of concept showing that collective intelligence can be leveraged to tackle complex problems such as cancer epidemiology and big data management. The proposed framework accelerates research initiatives through interconnected tools, allowing real time analysis and collaboration within an open multidisciplinary ecosystem.
Randomized phase II study of cisplatin and etoposide versus temozolomide and capecitabine in patients (pts) with advanced G3 non-small cell gastroenteropancreatic neuroendocrine carcinomas (GEPNEC): A trial of the ECOG-ACRIN Cancer Research Group (EA2142).
Authors: Jennifer Rachel Eads, Paul J. Catalano, George A. Fisher, David S. Klimstra, Zheng Zhang, Daniel Rubin, Andrei Iagaru, Terence Z. Wong, Peter J. O'Dwyer
Journal: Journal of Clinical Oncology (2016)

TPS4149 Background: Poorly differentiated (G3) GEPNECs are rare tumors for which little prospective data are available. Historically these tumors have been treated akin to small cell lung cancer with platinum and etoposide based on histologic similarities. Emerging pathologic and clinical data suggest heterogeneity amongst G3 GEPNECs based on histology (small cell vs. non-small cell), Ki-67, response to therapy (platinum based vs. temozolomide based) and survival. Temozolomide based therapy appears the most promising alternative option. The proposed study will provide the first prospective data regarding the role of cisplatin and etoposide vs. temozolomide and capecitabine for G3 GEPNECs and their correlation with clinical parameters. Methods: This is a multi-center, randomized phase II trial. Pts with locally advanced/unresectable or metastatic G3 GEPNEC are randomized to receive capecitabine 750 mg/m2 PO every 12 hours days 1-14 and temozolomide 200 mg/m2 PO daily days 10-14 (Arm A) or cisplatin 25 mg/m2 IV daily days 1-3 and etoposide 100 mg/m2 IV daily days 1-3 (Arm B). Cycle length: 28 days (Arm A), 21 days (Arm B). Eligibility criteria include G3 non-small cell histology, Ki-67 proliferative index 20-100%, ≥ 10 mitotic figures per 10 high powered fields, measureable disease, no prior chemotherapy. Primary endpoint is progression free survival (PFS); secondary endpoints include response rate (RR), overall survival (OS) and toxicity. Tissue specimens will be collected for central pathology review with assessment of Ki-67 and its correlation with PFS, OS and response. CT, PET and octreoscan images will be banked. A total of 126 pts will be needed to accrue 120 eligible cases to detect an improvement in PFS from 6 months in the control arm (Arm B) to 10 months in the experimental arm (Arm A) with 90% power and a one-sided significance level of 0.10 using a log-rank test. Planned accrual is 4 pts per month over 30 months with an additional 12 months of follow-up. The trial was activated in November 2015. Clinical trial information: NCT02595424.
NK cells for PD-1/PD-L1 blockade immunotherapy: pinning down the NK cell
Authors: Cordelia Dunai, William J. Murphy
Journal: Journal of Clinical Investigation (2018)

In spite of a very robust body of literature and definitive data demonstrating the importance of the programmed cell death receptor-1 (PD-1) pathway in T cells and their function, the data on NK cell PD-1 expression have been highly variable and, particularly in the case of mouse NK cells, scarce. In this issue of the JCI, Hsu et al. present data demonstrating PD-1 expression on mouse NK cells only within tumors and show that PD-1 blockade elicits an antitumor NK cell-mediated response. This study indicates that, given the complexity of both the biology and study of NK cells, further work is needed to more clearly determine the role of the PD-1/PD-1 ligand (PD-L1) on NK cells.