tbuckley/cabot-search huggingface dataset:
Efficacy of bolus and infusional 5-FU in elderly and non-elderly patients with metastatic colorectal cancer - a pooled analysis of clinical trials
Authors: G. Folprecht, D. Cunningham, B. Glimelius, F. Dicostanzo, J. Wils, W. Scheithauer, P. Rougier, E. Aranda, U. Pabst, C. H. Köhne
Journal: Journal of Clinical Oncology (2004)

8045 Background: Recently published population-based investigations showed elderly patients to be underrepresented in clinical trials and less often treated according the standard therapy, although they benefit to the same extent from adjuvant (radio-) chemotherapy as younger patients. No large series describes the influence of age on efficacy of chemotherapy in metastatic colorectal cancer. Methods: We carried out a retrospective analysis using source data of 3,825 patients who received 5-FU containing treatment in 22 European trials and identified 629 patients with an age of ≥ 70 years. Results: An equal overall survival was observed in elderly patients (10.8 months, 95 % CI 9.7–11.8) and in younger patients (11.3 months, 95 % CI 10.9–11.7, p = .31). Response rate did not differ between the age groups ≥ 70 and < 70 years (20.8 % and 17.6 %, p = .14). Progression free survival was marginally prolonged in elderly patients (5.5 months, 95 % CI 5.2–5.8 and 5.3 months, 95 % CI 5.1–5.5, p = .01). In both age groups, infusional 5-FU resulted in significantly increased response rates, overall survival and progression free survival compared to bolus 5-FU. The Cox- regression analysis showed no influence of age on OS. Conclusions: We conclude that "fit" elderly patients (fulfilling standard inclusion criteria of clinical trials) benefit to the same extent from palliative chemotherapy with 5-FU. Infusional 5-FU is more effective in elderly as in younger patients. Standardized palliative chemotherapy should generally be offered to elderly patients and they should not be excluded from clinical trials. No significant financial relationships to disclose.
Pharmacoeconomic analysis on high dose ifosfamide for metastatic osteosarcoma
Authors: A. A. Cardoso, C. G. Ferreira, R. Braun, G. Q. Mendes
Journal: Journal of Clinical Oncology (2004)

9043 Background: Metastatic osteosarcoma (OS) affects a young population and has a poor prognosis with 5-year survival < 15%. Ifosfamide (IFO) has shown high response rate as second-line chemotherapy (CT), but toxicity is high, as we previously reported, and overall survival is short. Overall, neither the role of second-line CT nor its cost-effectiveness have been established. At this end, new data may support the decision-making process. Methods: We reviewed the costs of the treatment of 27 patients with classic OS, treated with IFO for relapsed disease at INCA, from July 1999 to June 2002. The regimen used was IFO 12g/m2 (divided into 4 days), with Mesna and G-CSF. For cost analysis, the following parameters were included: in and outpatient visits, hospital admissions, CT (drugs, material, time and personnel), red cells and platelet transfusions, nephrologic support and blood tests. Results: Median age was 19.7 years. The response rate was 52% with median overall and 1-year survival of 10.3 months and 32.5%, respectively. The median number of cycles was 5.7; no treatment related death was observed. The total cost of treatment for this cohort was US$ 234,243 with a per patient cost US$ 8,675, excluding taxes. The distribution of costs was as follows: 80% related to CT costs (drugs + G-CSF + blood transfusion + antibiotics), 17% to hospital admissions and inpatient visits, 3% to other costs. Considering the median overall survival of 10.3 months, the cost per month of life was US$ 888. Conclusions: In our hands, IFO was an active agent, with symptom improvement and tumor reduction in more than half of the patients. Analyzing these numbers in light of few data comparing IFO vs best supportive care (except for Ferrari et al. who suggest a benefit for CT), the low median age of the patients and the global costs that are not prohibitive, we believe second-line high-dose IFO may have a cost-effectiveness that justifies its use. We emphasize though the need for more studies to determine the role of IFO in patients who are not candidates to salvage surgery, as well as strategies that minimize costs such as lower dose of IFO requiring thereby less G-CSF support and blood transfusions. No significant financial relationships to disclose.
XPD DNA Nucleotide Excision Repair (NER) Gene Polymorphisms Associated with DNA Repair Deficiency May Predict Better Treatment Outcomes in Secondary Acute Myeloid Leukemia (AML).
Authors: Nataliya Kuptsova-Clarkson, Christine Ambrosone, Joli Weiss, Maria R. Baer, Lara Sucheston, Gary Zirpoli, Kenneth Kopecky, Laurie Ann Ford, Javier Blanco, Meir Wetzler, Kirsten Moysich
Journal: Blood (2009)
439O Tracking spatiotemporal T790M heterogeneity in patients with EGFR-mutant advanced NSCLC after acquired resistance to EGFR TKIs
Authors: Y.-C. Zhang, C. Pi, E.-E. Ke, Z.-H. Chen, J. Su, Z.-Y. Dong, C.-R. Xu, H.-H. Yan, H.-Y. Tu, W.-Z. Zhong, X.-C. Zhang, J.-J. Yang, X.-N. Yang, Q. Zhou, Y.-L. Wu
Journal: Annals of Oncology (2016)
430P Comparison of multimodality therapy in clinical stage IIIAN2 non-small cell lung cancer: consecutive analysis of surgery, radiotherapy, chemotherapy and their combination
Authors: Y. Katsuya, H. Horinouchi, Y. Goto, S. Kanda, Y. Fujiwara, H. Nokihara, N. Yamamoto, K. Asakura, K. Nakagawa, H. Sakurai, S.-I. Watanabe, H. Igaki, Y. Itou, J. Itami, Y. Ohe
Journal: Annals of Oncology (2016)
NIMG-66. CLINICAL EXPERIENCES OF TUMOR TREATING FIELDS (TTFIELDS) IN PEDIATRIC PATIENTS WITH GBM
Authors: John Crawford, Girish Dhall, Ashley Margol, Marlon Saria, Santosh Kesari
Journal: Neuro-Oncology (2016)

Tumor Treatment Fields (TTFields) are an innovative therapeutic approach that is FDA-approved for glioblastoma (GBM) in adults older than 22 years. TTFields are delivered through a portable, non-invasive device (Optune®, Novocure, Inc, USA). We report clinical observations of treating 3 of 4 pediatric patients with TTFields. Patient 1, a 15-year-old girl, who was diagnosed with GBM in 1/2015, underwent a gross total resection followed by Temozolomide (TMZ) 75mg/m2 daily plus radiation therapy (RT). Upon completion of RT, she began monthly TMZ (200mg/m2 days 1-5) plus TTFields. She tolerated the TTFs well without toxicities. TTFields were continued for 4 months until disease progression. She died 2 months later. Patient 2, a 9-year-old boy, presented with GBM in March 2015. He underwent radiation therapy (RT) with concomitant daily TMZ (75mg/m2). Following RT, he received dose intense TMZ, daily everolimus, and TTFields. With disease progression in July 2015, he received Avastin 10mg/kg every 2 weeks plus stereotactic radiosurgery. He had no dose limiting toxicities during the duration of his therapy. One month later repeat MRI revealed non-enhancing infiltrative disease. All therapies were discontinued. He died 2 months later. Patient 3, a 4-year-old boy, presented in November 2013 with a large left frontal temporal contrast enhancing tumor. He underwent subtotal resection and high-dose chemotherapy with autologous stem cell rescue. He progressed while on chemotherapy necessitating focal photon RT with concomitant avastin, irinotecan, and vorinostat. In January 2015, he began TTF until March 2015 without dose limiting toxicity. He died 2 months later. These case studies of TTFs that pediatric patients with GBM are compliant with and tolerate 18 hours/daily TTFields therapy for up to 4 months without dose limiting toxicities. Further studies of TTFields in pediatric GBM patients are warranted.
Integrating health insurance assessments into oncology care.
Authors: Joanna Morales, Monica Bryant
Journal: Journal of Clinical Oncology (2016)

253 Background: Nearly 10% of the U.S. population lacks health insurance coverage. Healthcare professionals are often asked by their patients about health insurance options. The Patient Protection and Affordable Care Act (ACA) has brought new health care options and consumer protections for people coping with cancer. Unfortunately, there is a plethora of misinformation about these changes. Healthcare professionals are uniquely positioned to provide patients with accurate, quality information, improving patient quality of life. Methods: The presentation will cover the implementation of the ACA at the federal and state levels and the impact of the ACA on the cancer community. Attendees will learn about new consumer protections and health insurance options, and receive concrete tools to conduct clinical assessments that address access to health insurance coverage and the subsequent impact on psychosocial needs. Results: Our surveys have found that 75% of oncology healthcare professional respondents were asked for guidance on how healthcare reform might affect their patients. However, only 7% of those surveyed felt “very comfortable” answering questions about the ACA. Therefore, there is an obvious gap between the knowledge level of healthcare professionals and what they are being asked by their patients. Oncology healthcare provider attendees will gain a better understanding of health insurance options available to their patients. Attendees will receive practical tools to answer questions and provide appropriate resources, thereby alleviating anxiety, and improving quality of life for patients. Conclusions: In order to effectively navigate patients through the cancer care continuum, oncology healthcare providers must be armed with up-to-date knowledge about health insurance options and protections, and given concrete tools for conducting clinical assessments that address a broad spectrum of psychosocial needs.
393TiP A phase II trial of nedaplatin, 5-fluorouracil and docetaxel for induction chemotherapy with local advanced squamous cell carcinoma of the head and neck
Authors: S. Ueda, D. Nishikawa, K. Yane, Y. Akashi, T. Sakiyama, M. Terashima, T. Okabe, M. Yamaguchi, T. Matuura, K. Okajima
Journal: Annals of Oncology (2016)
Abstract 12942: Modified Glucose-Insulin-Potassium Regimen Provides Cardiac and Renal Protection With Improved Tissue Perfusion and Metabolism in Patients Undergoing Cardiopulmonary Bypass Surgery
Authors: Jia Li, Kun Zhao, Yue Zhang, Qin Cui, Rong Zhao, Jian Yang, Shiqiang Yu, Dinghua Yi, Feng Gao
Journal: Circulation (2015)

Background: Laboratory studies demonstrate glucose-insulin-potassium (GIK) as a potent cardioprotective intervention but clinical trials have yielded mixed results, presumably due to varying formulas and treatment timing of GIK. This study evaluated the effects of modified GIK given perioperatively in patients undergoing cardiopulmonary bypass (CPB) surgery. Methods and Results: In this prospective, randomized, double-blinded trial with 930 patients, 750 mL GIK (200 g/L glucose, 66.7 U/L insulin and 80 mmol/L KCl) or placebo treatment was administered intravenously at 1 mL/kg/h 10 min before anesthesia. The primary outcome was the incidence of major adverse cardiac events (MACE). No significant difference in mortality was observed between the two groups. GIK therapy reduced the incidence of MACE (OR, 0.57; 95% CI, 0.43-0.75; P&lt;0.001), enhanced cardiac function recovery with better glucose controlled without increasing perioperative blood glucose compared with placebo group. These benefits were associated with increased glucose uptake (9.5±4.6% vs. 5.6±2.6% in Placebo, P=0.005) and less lactate excretion (8.4 ± 9.2% vs. 33.4 ± 22.6% in Placebo, P&lt;0.001) evidenced by the difference between arterial and coronary sinus, more glycogen store analyzed by transmission electron micrograph, and increased phosphorylation of IRS-1 and Akt in the hearts of GIK-treated patients. Importantly, GIK therapy significantly reduced blood lactate at 1 h, 6 h and 12 h after operation compared with placebo group (all P&lt;0.001), indicating a enhanced tissue perfusion during CPB. Accordingly, patients treated with GIK had decreased markers of renal and hepatic injury, lower incidences of acute kidney injury and extended intensive care. Conclusions: Modified GIK regimen administrated perioperatively reduced the incidence of MACE and preserved cardiac and renal function in patients undergoing CPB surgery. These benefits were associated with activation of insulin signaling, improved myocardial metabolism and enhanced systemic tissue perfusion afforded by GIK. Clinical Trial Registration_URL: www.clinicaltrials.gov . Unique identifier: NCT01516138.
Is twice the duration of washout sufficient time between multiple breath nitrogen washout tests?
Authors: Kate M. Hardaker, Per Gustafsson, Peter Cooper, Dominic Fitzgerald, Hiran Selvadurai, Paul D. Robinson
Journal: European Respiratory Journal (2017)

Multiple breath washout (MBW) assesses both lung volume (functional residual capacity (FRC)) and ventilation inhomogeneity (lung clearance index (LCI)). The latter's insight into underlying lung pathology and response to intervention has triggered a recent MBW resurgence [1–4]. Validated commercial equipment has become available [5], increasing suitability for widespread use, and a European Respiratory Society/American Thoracic Society endorsed MBW consensus statement has been published to guide manufacturers and operators [6]. This document highlights the need for further evidence across several recommendation areas. In the May 2015 issue of this journal Salamon et al. [7] tackled one such important issue: what duration should be employed between two MBW tests within a testing session? Previous recommendations of gaps of ≥15 min in healthy and ≤60 min in obstructed patients [8] were shown to be too conservative . Using a gap of the previous washout duration led to 10% lower FRC values (p<0.001) but no effect was observed if this was doubled, in line with the recent consensus-based recommendation. [9]. The results presented here address two important limitations to the data presented by Salamon et al. [7], as acknowledged by the authors themselves, to further strengthen the recommendation's evidence base. First, in their paediatric cohort, an alternate, fixed-gap duration protocol was used (5 and 15 min), which translated to an excessive duration between tests (mean 2.6×). Secondly, LCI data was not reported, which may have compromised the ability to detect any detrimental effects. A wait time between MBNW tests of twice the washout duration has no detrimental effect on LCI and FRC outcomes <http://ow.ly/RF8y304V3PB>
Detection of NRAS, KRAS and BRAF mutations in FFPE derived DNA with a novel targeted resequencing-based diagnostics assay
Authors: C. Marques, K. Bettens, D. Goossens, L. Heyrman, C. Heusdens, S. Kupers, S. Berwouts, D. Van Barel, A. Rotthier, J. Del-Favero
Journal: Annals of Oncology (2016)
TMIC-07. DUAL INHIBITION OF ANG-2 AND VEGF RECEPTORS NORMALIZES TUMOR VASCULATURE AND PROLONGS SURVIVAL IN GLIOBLASTOMA BY ALTERING MACROPHAGES
Authors: Teresa Peterson, Nathaniel Kirkpatrick, Yuhui Huang, Christian Farrar, Koen Marjit, Jonas Kloepper, Meenal Datta, Zohreh Amoozgar, Giorgio Seano, Keehoon Jung, Walid Kamoun, Trupti Vardam, Matija Snuderl, Jermaine Goveia, Sampurna Chatterjee, Ana Batista, Alona Muzikansky, Ching Ching Leow, Lei Xu, Tracy Batchelor, Dan Duda, Dai Fukumura, Rakesh Jain
Journal: Neuro-Oncology (2016)

Glioblastomas (GBMs) rapidly become refractory to anti-VEGF therapies. We previously demonstrated that ectopic overexpression of angiopoietin-2 (Ang-2) compromises the benefits of anti- VEGF receptor (VEGFR) treatment in murine GBM models and that circulating Ang-2 levels in GBM patients rebound after an initial decrease following cediranib (a pan-VEGFR tyrosine kinase inhibitor) administration. Here we tested whether dual inhibition of VEGFR/Ang-2 could improve survival in two orthotopic models of GBM, Gl261 and U87. Dual therapy using cediranib and MEDI3617 (an anti–Ang-2–neutralizing antibody) improved survival over each therapy alone by delaying Gl261 growth and increasing U87 necrosis, effectively reducing viable tumor burden. Consistent with their vascular-modulating function, the dual therapies en-hanced morphological normalization of vessels. Dual therapy also led to changes in tumor-associated macrophages (TAMs). Inhibition of TAM recruitment using an anti–colony-stimulating factor-1 antibody compromised the survival benefit of dual therapy. Thus, dual inhibition of VEGFR/Ang-2 prolongs survival in preclinical GBM models by reducing tumor burden, improving normalization, and altering TAMs. This approach may represent a potential therapeutic strategy to overcome the limitations of anti-VEGFR mono- therapy in GBM patients by integrating the complementary effects of anti-Ang2 treatment on vessels and immune cells.
Everolimus and Mycophenolate as GvHD Prophylaxis Results In Improved Control of Advanced Disease and Reduced Bacterial and Fungal Infectious Complications After Allogeneic Stem Cell Transplantation
Authors: Reinhard E Marks, Hartmut Bertz, Ralph M. Waesch, Wolfgang Melchinger, Juergen Finke
Journal: Blood (2010)
Dose-dense adjuvant chemotherapy, treatment-induced amenorrhea and overall survival in premenopausal breast cancer patients: a pooled analysis of the MIG1 and GIM2 phase 3 studies
Authors: E. Blondeaux, M. Lambertini, M. Ceppi, F. Cognetti, G. Cavazzini, M. De Laurentiis, S. De Placido, A. Michelotti, G. Bisagni, A. Durando, E. Valle, T. Scotto, A. De Censi, A. Turletti, M. Benasso, S. Barni, F. Montemurro, F. Puglisi, C. Bighin, P. Bruzzi, L. Del Mastro
Journal: Annals of Oncology (2016)
GATA-3 Expression in Peripheral T-Cell Lymphomas (PTCL): Identification of a Cut-Off and Prognostic Value in PTCL-NOS Versus Others Hystotypes
Authors: Anna Dodero, Francesco Maura, Alessio Pellegrinelli, Antonello Cabras, Annalisa Chiappella, Domenico Novero, Federico Vittone, Francesco Zaja, Stefano Pizzolitto, Cristiana Carniti, Alessandra Cavane', Martina Pennisi, Umberto Vitolo, Niccolo' Bolli, Paolo Corradini
Journal: Blood (2015)
Synergistic Activity of Combinations of JAK2 Kinase Inhibitor with PI3K/mTOR, MEK or PIM Kinase Inhibitor Against Human Myeloproliferative Neoplasm Cells Expressing JAK2V617F
Authors: Warren Fiskus, Rekha Rao Manepalli, Ramesh Balusu, Kapil N. Bhalla
Journal: Blood (2010)
503O_PR CIC-rearranged sarcoma and BCOR-CCNB3 sarcoma: Clinical characteristics and treatment results of the newly-established “Ewing sarcoma-like” small round cell sarcomas
Authors: M. Endo, M. Sugawara, A. Yoshida, E. Kobayashi, T. Shimoi, M. Kodaira, M. Yunokawa, K. Yonemori, K. Tamura, S. Toki, T. Hirose, T. Uehara, T. Mori, K. Shimizu, Y. Tanzawa, F. Nakatani, H. Chuman, A. Kawai
Journal: Annals of Oncology (2016)
Lenalidomide Induced Myelosupression Is Potentially Associated with Renal Dysfunction in Treatment Naïve Myeloma (MM) Patients Receiving BiRD (Biaxin®/Revlimid®/Dexamethasone) Combination Therapy (Rx).
Authors: Ruben Niesvizky, D.S. Jayabalan, F. Zafar, P. Christos, R. Lent, R. Pearse, J. Tepler, S. Ely, T. Shore, J. Harpel, M. Schuster, K. Pekle, J.B. Jalbrzikowski, H.J. Cho, J. Leonard, M. Mazumdar, S. Chen-Kiang, M. Coleman
Journal: Blood (2006)
Central nervous system (CNS) disease during trastuzumab emtansine (T-DM1) for HER2 positive advanced breast cancer (ABC): A single institution experience
Authors: T. Irfan, N.M. Turner, S. Johnston, I. Smith, M. O'Brien, M. Parton, A. Ring, J. Noble, S. Stanway, N. Somaiah, K. Khabra, A. Okines
Journal: Annals of Oncology (2016)
High-Dose Imatinib Mesylate Treatment in Patients (Pts) with Previously Untreated Early Chronic Phase (CP) Chronic Myeloid Leukemia (CML).
Authors: Jorge Cortes, Moshe Talpaz, Susan O’Brien, Francis Giles, Mary Beth Rios, Laurie Levtak, Hagop Kantarjian
Journal: Blood (2004)
EXTH-60. RETINOBLASTOMA BINDING PROTEIN 4 (RBBP4) REGULATES MULTIPLE GENES CRITICAL FOR THERAPY RESPONSE IN GLIOBLASTOMA
Authors: Gaspar Kitange, Ann Mladek
Journal: Neuro-Oncology (2016)

Resistance to radiation and chemotherapy is one of the critical challenges in the treatment of patients with glioblastoma (GBM). We recently discovered that RBBP4 protein modulates TMZ sensitivity through epigenetic regulation of MGMT and RAD51 in GBM cells. To identify additional genes regulated by RBBP4, we conducted ChIP-sequencing (ChIP-seq) based on acetylated H3K9 (H3K9Ac) chromatin mark and RNA-sequencing (RNA-seq) in T98G cells expressing RBBP4- or control NT-shRNA. Analysis of ChIP- and RNA-seq revealed a dual role of RBBP4 in transcriptional regulation: 1065 genes were altered by silencing RBBP4 in T98G cells among which 671 (63%) were upregulated while 394 (37%) were down-regulated. Consistent with our initial findings, RNA-seq revealed that silencing RBBP4 in T98G suppresses the expression of MGMT and RAD51 and ChIP-seq demonstrated a decreased promoter H3K9Ac tags. RBBP4 silencing impacted mainly the expression of genes involved in the chromatin regulation. Interestingly, RNA- and ChIP-seq identified EYA1 and FIGNL1 as targets of regulation by RBBP4. While FIGNL1 protein recently was shown to play a role in DNA repair through a complex with RAD51, EYA1 protein is a phosphatase that dephosphorylates tyrosine 142 of histone H2AX, which is necessary for phosphorylation of H2AX (serine 139, γ-H2AX) in response to DNA damage. Lack of EYA1 in cells activates apoptosis instead of repairing the damaged DNA. Consistently, TMZ treatment induced accumulation of pH2AX-tyr142, which was accompanied with marked apoptosis as evidenced by cleaved PARP in RBBP4-silenced T98G cells. Importantly, silencing expression of RBBP4 significantly prolonged survival in orthotopic U251 and GBM43 xenografts. Together these findings suggest a possibility that RBBP4 is a “master regulator” of genes critical for therapy response, including MGMT and DNA repair genes RAD51, EYA1 and FIGNL1 in GBM. Therefore, RBBP4 is a potential target for designing strategies for sensitizing TMZ and other therapies in GBM.
Value in the Step 2 Clinical Skills Examination
Authors: Arjun Gupta, Ugis Gruntmanis
Journal: JAMA Internal Medicine (2017)

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Interferon-Related Gene Expression in Respiratory Syncytial Virus (RSV) Infected Pediatric Bronchial Epithelial Cells (BECs) Is Inversely Correlated with Lung Function
Authors: Andrew R. Parker, Matthew C. Altman, Elizabeth Whalen, Kira Misura, Michael Comeau, Tessa K. Kolstad, Stephen R. Reeves, Teal S. Hallstrand, Steven Ziegler, Jason S. Debley
Journal: Journal of Allergy and Clinical Immunology (2017)
Radium-223 (Ra-223) Re-treatment (Re-tx): First Experience From an International, Multicenter, Prospective Study in Patients (Pts) With Castration-Resistant Prostate Cancer and Bone Metastases (mCRPC)
Authors: G. Procopio, S. Severi, E. Verzoni, M. Sansovini, O. Sartor, D. Heinrich, N. Mariados, M.J. Méndez Vidal, D. Keizman, C. Thellenberg-Karlsson, A. Pe'er, S. J. Frank, K. Pulkkanen, J.M. Trigo Perez, L. T. Nordquist
Journal: Annals of Oncology (2016)