tbuckley/cabot-search huggingface dataset:
Intravenous vs. intra-arterial methotrexate-based chemotherapy regimens for newly diagnosed primary central nervous system lymphoma.
Authors: Nancy Diane Doolittle, Agnieszka Korfel, Rochelle Fu, Peter Martus, Patrick Roth, Michael Weller, Gustavo Mendez, Alp Ozpinar, Prakash Ambady, Edward A. Neuwelt
Journal: Journal of Clinical Oncology (2016)

e13505 Background: High-dose (HD) methotrexate (MTX) is currently the most beneficial drug for newly diagnosed primary central nervous system lymphoma, however approximately 50% of patients relapse within two yrs of diagnosis. Older age is a negative prognostic marker. It has not been possible to conduct a randomized trial comparing MTX-based intravenous (iv) vs. intra-arterial (ia) regimens. Thus we compared efficacy from two first-line MTX-based regimens: HD MTX (iv, 4gr/m2) (Thiel, Lancet Oncol 2010) and MTX (ia, 3.5gr/m2) with enhanced delivery (Angelov, JCO 2009). Both reported acceptable toxicities. Methods: We obtained Institutional Review Board approval. Patients who received first-line WBRT or rituximab were not included. Separate analysis was conducted for patients < 65 yrs and ≥ 65 yrs. Results: Baseline age and KPS were similar between iv and ia patients in both age groups. The average number of MTX courses was 4.0 (iv) and 7.5 (ia). Univariately, the ia group had significantly higher complete response rate (CRR) and progression free survival (PFS) than iv group, but significance was borderline regarding overall survival (OS) for both age groups. After adjusting for patient characteristics, only CRR and PFS remained significantly higher in the ia patients < 65yrs. Conclusions: These results provide historical comparisons prior to the addition of rituximab to MTX regimens. Data suggest improved CRR and PFS associated with enhanced delivery in patients < 65 yrs. Both regimens and age groups show promising CRR however rapid recurrence is the challenge. Many groups including us, report increased OS with the addition of first-line rituximab. Maintenance immunotherapy may have a role in prolonging CR and OS, and is being tested in a randomized study. Age < 65 yrs Age ≥ 65 IV IA P value* IV IA P value* N 217 69 188 33 CRR 35% 59% < 0.001 0.006 27% 58% < 0.001 0.0562 Median PFS (mo) (95% CI) 5.2 (3.3-7.1) 17.5 (8.5-44.2) < 0.001 0.004 3.0 (2.6-3.8) 12.4 (4.2-16.2) 0.008 0.118 Median OS (mo) (95%CI) 26.2 (19.0-36.2) 45.0 (21.1-71.9) 0.054 0.295 8.3 (5.7-12.9) 14.5 (6.8-30.7) 0.059 0.334 *Top and bottom P-values are from univariate and multivariate analyses, separately
Use of serum uPA change to predict PFS and overall survival in first-line trastuzumab-treated breast cancer.
Authors: H. Y. Hou, U. Anyanwu, N. Jamshidi, K. Leitzel, S. M. Ali, W. Köstler, E. Fuchs, P. Hamer, W. P. Carney, A. Lipton
Journal: Journal of Clinical Oncology (2010)

1050 Background: About half of patients with HER2-positive breast cancer will respond to first-line trastuzumab-containing therapy, but of these most will progress within a year with acquired resistance. Since trastuzumab treatment is now used in the HER2-positive adjuvant breast cancer setting, trastuzumab resistance will continue to be a recurring clinical problem, and better predictive and prognostic biomarkers are urgently needed. Methods: Serum TIMP-1, uPA, and carbonic anhydrase 9 (CA9) were measured using ELISA in 60 patients with metastatic breast cancer before starting first-line trastuzumab-containing therapy, and at the closest 1 month post-trastuzumab blood draw. The TIMP-1, uPA, and CA9 ELISAs were from Oncogene Science/Siemens Healthcare Diagnostics, Cambridge, MA. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox modeling. Results: When serum biomarker change (pretreatment to 1 month post-trastuzumab treatment) was analyzed on a continuous basis, change in serum TIMP- 1 and CA 9 were not significant for PFS or OS. However the change in serum uPA was a significant predictive factor for PFS to first-line trastuzumab treatment (HR=1.0176, p=0.006) and for OS (HR=1.0167, p=0.027): declining serum uPA predicted for increased survival, and increasing serum uPA predicted for decreased survival. Using cutpoint analysis, patients who achieved a 25% decline in serum uPA levels (14/60, 23%) had a longer PFS (median 1331 days) compared to those patients who did not (median 364 days) (HR 4.6) (p=0.004). In similar fashion, patients who achieved the 25% decline in serum uPA levels had a longer OS (median 2,130 days) compared to those patients who did not (median 1,079 days) (HR 4.3) (p=0.017). Conclusions: The change in serum uPA level from pretreatment to 1 month post-trastuzumab treatment predicted PFS and overall survival in patients with metastatic breast cancer treated with first-line trastuzumab-containing therapy. These serum biomarkers deserve further study in larger trials of HER2-targeted breast cancer treatment. Supported by a grant from Komen for the Cure. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Oncogene Science/Siemens Healthcare Diagnostics Oncogene Science Oncogene Science/Siemens Healthcare Diagnostics Oncogene Science/Siemens Healthcare Diagnostics
Cost-Effectiveness Analysis of Elective Neck Dissection in Patients With Clinically Node-Negative Oral Cavity Cancer
Authors: Joseph R. Acevedo, Katherine E. Fero, Bayard Wilson, Assuntina G. Sacco, Loren K. Mell, Charles S. Coffey, James D. Murphy
Journal: Journal of Clinical Oncology (2016)

Purpose Recently, a large randomized trial found a survival advantage among patients who received elective neck dissection in conjunction with primary surgery for clinically node-negative oral cavity cancer compared with those receiving primary surgery alone. However, elective neck dissection comes with greater upfront cost and patient morbidity. We present a cost-effectiveness analysis of elective neck dissection for the initial surgical management of early-stage oral cavity cancer. Methods We constructed a Markov model to simulate primary, adjuvant, and salvage therapy; disease recurrence; and survival in patients with T1/T2 clinically node-negative oral cavity squamous cell carcinoma. Transition probabilities were derived from clinical trial data; costs (in 2015 US dollars) and health utilities were estimated from the literature. Incremental cost-effectiveness ratios, expressed as dollar per quality-adjusted life-year (QALY), were calculated with incremental cost-effectiveness ratios less than $100,000/QALY considered cost effective. We conducted one-way and probabilistic sensitivity analyses to examine model uncertainty. Results Our base-case model found that over a lifetime the addition of elective neck dissection to primary surgery reduced overall costs by $6,000 and improved effectiveness by 0.42 QALYs compared with primary surgery alone. The decrease in overall cost despite the added neck dissection was a result of less use of salvage therapy. On one-way sensitivity analysis, the model was most sensitive to assumptions about disease recurrence, survival, and the health utility reduction from a neck dissection. Probabilistic sensitivity analysis found that treatment with elective neck dissection was cost effective 76% of the time at a willingness-to-pay threshold of $100,000/QALY. Conclusion Our study found that the addition of elective neck dissection reduces costs and improves health outcomes, making this a cost-effective treatment strategy for patients with early-stage oral cavity cancer.
Correlation of messenger RNA expression patterns of ERCC1, TS, EGFR, and VEGFR2 with KRAS and BRAF mutational status in advanced colorectal cancer: Implications for targeted therapies.
Authors: Martin K. H. Maus, Craig Stephens, Stephanie H. Astrow, Peter Philipp Grimminger, Dongyun Yang, Fotios Loupakis, Jack Hsiang, Gary Zeger, Xu Huang, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2013)

383 Background: Gene expression levels of ERCC1, TS, EGFR and VEGFR2 may have predictive value for the personalized use of standard chemotherapeutics as well as agents targeting the EGFR and VEGF pathways and the efficacy of EGFR directed monoclonal antibodies like panitumumab and cetuximab has been confirmed to be dependent on wt KRAS and wt BRAF in patients with advanced colorectal cancer. We investigated the correlations between KRAS/BRAF mutational status and the mRNA expression levels of these genes. Methods: Formalin-fixed paraffin-embedded tumor specimens from 600 patients with advanced colorectal adenocarcinoma were microdissected and DNA and RNA was extracted. Specifically designed primers and probes were used to detect 7 different base substitutions in codon 12 and 13 of KRAS, V600E mutations in BRAF and the expression levels of ERCC1, TS, EGFR and VEGFR2 by RT-PCR. Results: Mt KRAS tumors had significantly lower TS and EGFR gene expression levels compared with wt KRAS (p&lt;0,001), whereas mt BRAF tumors showed significantly increased TS and EGFR mRNA levels compared to wt BRAF (p&lt;0,001). Mt BRAF tumors showed significantly higher mRNA levels than mt KRAS tumors (p&lt;0,001). ERCC1 and VEGFR2 mRNA levels were significantly down-regulated in mt KRAS specimen (p&lt;0,001), but showed no significant correlation with BRAF mutational status. Conclusions: KRAS and BRAF mutations are associated with opposite mRNA expression levels for TS and EGFR. Recently, resistance to BRAF inhibition in mt BRAF colorectal tumors has been shown in preclinical models to be associated with up-regulation of EGFR. Our data suggests that BRAF mutants are associated with high EGFR levels at the time of diagnosis, and not necessarily part of an acquired mechanism of resistance. Significantly lower mRNA expression levels of VEGFR2 in mt KRAS tumors may explain lower response to angiogenesis inhibition seen in the TML study.
Targeted Nanomaterials: Overcoming Instability of Antibody-Nanomaterial Conjugates: Next Generation Targeted Nanomedicines Using Bispecific Antibodies (Adv. Healthcare Mater. 16/2016)
Authors: Christopher B. Howard, Nicholas Fletcher, Zachary H. Houston, Adrian V. Fuchs, Nathan R. B. Boase, Joshua D. Simpson, Lyndon J. Raftery, Tim Ruder, Martina L. Jones, Christopher J. de Bakker, Stephen M. Mahler, Kristofer J. Thurecht
Journal: Advanced Healthcare Materials (2016)

Christopher B. Howard, and co-workers report the generation of targeted nanomaterials for cancer theranostics by mixing of hyperbranched polyethylene glycol polymers with bispecific antibodies (BsAbs) on page 2055. The cover represents a facile method to generate actively targeted nanomaterials using polymeric nanomaterials, coupled to a BsAb with dual specificity for polymer and cancer targets such as Epidermal Growth Factor Receptor. The image captures effective tethering of the BsAb (yellow-red) to polymeric nanomaterials (blue), creating a bio-nanomaterial that targets cancer cells. Cover design by Sumukh Kumble.
Cognitive impairment associated with chemotherapy for breast cancer: An exploratory case-control study
Authors: C. M. Booth, J. Vardy, A. Crawley, S. Rourke, G. Pond, L. Wagner, I. F. Tannock
Journal: Journal of Clinical Oncology (2006)

8501 Background: There is evidence that some women suffer cognitive impairment after adjuvant chemotherapy (CT) for breast cancer and it may be sustained. We report a case-control study to explore underlying mechanisms with blood tests and functional imaging. Methods: Women diagnosed with breast cancer within 5 years were recruited to 3 groups of 20. Cases (group A) had received CT and self-reported cognitive dysfunction on a prototype FACT-COG questionnaire. There were 2 groups of controls: group B had received CT but did not report cognitive problems; group C had breast cancer but did not receive CT. Comprehensive tests of cognitive function (2.5 hr) were performed. Blood tests evaluated sex hormones, coagulation factors, 10 cytokines, and apolipoprotein genotype. Functional MRI (fMRI) scans were performed while subjects performed a mental task. Results: Currently, 60 women have completed FACT-COG, 39 have undergone neuropsychological assessment and 31 have completed fMRI; testing and analysis will be complete by May 2006. Median time from diagnosis was 2 years. There was increased self-report of cognitive impairment in CT vs non-CT patients (p&lt;0.0001). Formal cognitive testing disclosed more impairment in group C (no CT) as compared to groups A and B: 29% vs 0% by classical tests (p=0.046), and 61% vs 47% and 25% (p=0.38) by computerized testing. This may be due to slight imbalance of demographic factors. Decreased activation in fMRI was seen in frontal areas and right parahippocampus of women who self-reported greater cognitive impairment (p&lt;0.0005), while separate frontal areas show increased activity in women with greater objective cognitive impairment (p&lt;0.0005). Patients who received CT reported more fatigue than non-CT patients (p=0.027). There was an association between fatigue and self-reported cognitive impairment (p=0.004) and anxiety and depression (General Health Questionnaire) (p=0.009), but not with objective cognitive testing. As yet there is no significant correlation between symptoms and cytokine levels. Conclusions: Self-reported cognitive impairment is associated with prior chemotherapy and changes in fMRI but not with formal cognitive testing. The larger sample size is required to confirm these changes and explore possible mechanisms. No significant financial relationships to disclose.
Initial Remission Duration Is the Most Important Predictor of Outcome Following FLAG-Amsacrine Salvage of AML in First Relapse,
Authors: Chun Yew Fong, George Grigoriadis, Jay Hocking, Philip Campbell, Anthony P. Schwarer, Patricia A. Walker, Sharon Avery, Sushrut S. Patil, Hatem H. Salem, Andrew Spencer, Andrew H Wei
Journal: Blood (2011)
Skin Lesions and Recurrent Fever in Acute Myeloid Leukemia Patient Treated With Allogeneic Stem Cell Transplant
Authors: Seongseok Yun, Nicole D. Vincelette
Journal: JAMA Oncology (2016)

A 69-year-old man with a history of relapsed acute myeloid leukemia monocytic type presented with intermittent fever and fatigue 2 months after allogeneic stem cell transplantation; home medications included acyclovir, fluconazole, and cyclosporine. What is your diagnosis?
Stable Long-Term Risk of Leukemia in Patients with Severe Congenital Neutropenia Maintained On G-CSF Therapy.
Authors: Philip S. Rosenberg, Cornelia Zeidler, Audrey Anna Bolyard, Blanche P. Alter, Mary Ann Bonilla, Yigal Dror, Sally E Kinsey, Daniel C. Link, Akiko Shimamura, Peter E. Newburger, Laurence A. Boxer, Karl Welte, David C. Dale
Journal: Blood (2009)
Mechanistic Rationale for Inhibition of Poly(ADP-Ribose) Polymerase in ETS Gene Fusion-Positive Prostate Cancer
Authors: J. Chad Brenner, Bushra Ateeq, Yong Li, Anastasia K. Yocum, Qi Cao, Irfan A. Asangani, Sonam Patel, Xiaoju Wang, Hallie Liang, Jindan Yu, Nallasivam Palanisamy, Javed Siddiqui, Wei Yan, Xuhong Cao, Rohit Mehra, Aaron Sabolch, Venkatesha Basrur, Robert J. Lonigro, Jun Yang, Scott A. Tomlins, Christopher A. Maher, Kojo S.J. Elenitoba-Johnson, Maha Hussain, Nora M. Navone, Kenneth J. Pienta, Sooryanarayana Varambally, Felix Y. Feng, Arul M. Chinnaiyan
Journal: Cancer Cell (2013)
Low Rate of Dysplasia Detection in Mucosa Surrounding Dysplastic Lesions in Patients Undergoing Surveillance for Inflammatory Bowel Diseases
Authors: Joren R. ten Hove, Erik Mooiweer, Evelien Dekker, Andrea E. van der Meulen-de Jong, G. Johan A. Offerhaus, Cyriel Y. Ponsioen, Peter D. Siersema, Bas Oldenburg
Journal: Clinical Gastroenterology and Hepatology (2016)
70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer
Authors: Fatima Cardoso, Laura J. van’t Veer, Jan Bogaerts, Leen Slaets, Giuseppe Viale, Suzette Delaloge, Jean-Yves Pierga, Etienne Brain, Sylvain Causeret, Mauro DeLorenzi, Annuska M. Glas, Vassilis Golfinopoulos, Theodora Goulioti, Susan Knox, Erika Matos, Bart Meulemans, Peter A. Neijenhuis, Ulrike Nitz, Rodolfo Passalacqua, Peter Ravdin, Isabel T. Rubio, Mahasti Saghatchian, Tineke J. Smilde, Christos Sotiriou, Lisette Stork, Carolyn Straehle, Geraldine Thomas, Alastair M. Thompson, Jacobus M. van der Hoeven, Peter Vuylsteke, René Bernards, Konstantinos Tryfonidis, Emiel Rutgers, Martine Piccart
Journal: New England Journal of Medicine (2016)

The 70-gene signature test (MammaPrint) has been shown to improve prediction of clinical outcome in women with early-stage breast cancer. We sought to provide prospective evidence of the clinical utility of the addition of the 70-gene signature to standard clinical–pathological criteria in selecting patients for adjuvant chemotherapy.
A case report of Grover’s disease from immunotherapy-a skin toxicity induced by inhibition of CTLA-4 but not PD-1
Authors: Marc Uemura, Faisal Faˈak, Cara Haymaker, Natalie McQuail, Elizabeth Sirmans, Courtney W. Hudgens, Lydia Barbara, Chantale Bernatchez, Jonathan L. Curry, Patrick Hwu, Michael T. Tetzlaff, Adi Diab
Journal: Journal for ImmunoTherapy of Cancer (2016)

Immune related adverse events (irAEs) are common side effects of checkpoint inhibitory (CPI) therapies targeting CTLA-4 and PD-1/PD-L1. Grover's disease is an uncommon dermatologic condition with unclear pathogenesis previously reported as an irAE with ipilimumab.We report an additional case of ipilimumab-induced Grover's disease. Interestingly, this dermatologic side effect did not appear with use of anti-PD-1 therapy in our patient. Immune analysis was performed and suggests a possible role of Th2 cells in its patholgenesis.This case suggests that Grover's disease is an irAE induced by Ipilimumab. Our immune analysis suggests that Th2 cells may be pathogenic mediators which warrants further study.
Abstract B36: Interrogating cellular metabolism to improve therapy for EGFR mutant NSCLC
Authors: Chun-Te Chiang, Chi-Li Chiu, Cosimo Arnesano, Scott E. Fraser, David B. Agus, Dan L. Ruderman, Shannon M. Mumenthaler
Journal: Cancer Research (2016)

Abstract Tyrosine kinase inhibitors (TKIs) that target the EGFR are the standard of care for patients with EGFR mutant non-small lung cancer (NSCLC). However, TKIs are not curative; most patients with EGFR-mutant NSCLC treated with EGFR TKIs develop resistance within 9 to 14 months. The tumor microenvironment is thought to influence the fitness of cancer cells and drive the evolution of a tumor, but the effect of altered environmental conditions on oncogenic signaling and therapeutic response is not well understood. In the present study, we used the Operetta® High Content Imaging System to track cell dynamics over time and found that microenvironmental stress, specifically nutrient starvation, had a differential effect on growth rates of TKIs sensitive and resistant cells. Furthermore, we discovered that TKIs sensitive and resistant cells have differential metabolic signaling in response to this microenvironmental stress. To further interrogate cellular metabolism in TKIs sensitive and resistant cells, we utilized fluorescence lifetime imaging microscopy (FLIM), a state-of-the-art live-cell imaging technique to measure the autofluorescence lifetime of metabolic coenzyme NADH, the principle electron acceptor in glycolysis and electron donor in oxidative phosphorylation. Taken together, our data suggest that TKIs sensitive and resistant cells have adopted different metabolic strategies to cope with stressful environmental conditions, and interrogating tumor metabolic adaptations would inform the design of new therapeutic strategies to delay or prevent the outgrowth of resistant clones during treatment of EGFR mutant NSCLC. Citation Format: Chun-Te Chiang, Chi-Li Chiu, Cosimo Arnesano, Scott E. Fraser, David B. Agus, Dan L. Ruderman, Shannon M. Mumenthaler. Interrogating cellular metabolism to improve therapy for EGFR mutant NSCLC. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr B36.
Polymeric hepatitis C virus non-structural protein 5A nanocapsules induce intrahepatic antigen-specific immune responses
Authors: Michael Fichter, Keti Piradashvili, Anette Pietrzak-Nguyen, Leah Pretsch, Gabor Kuhn, Susanne Strand, Markus Knuf, Fred Zepp, Frederik R. Wurm, Volker Mailänder, Katharina Landfester, Stephan Gehring
Journal: Biomaterials (2016)
Evaluation of a system-level organizational approach to person-centered care education and implementation toolkit.
Authors: Lesley Moody, Hannah Shamji, Esther Green, Laura Macdougall, Naomi Peek, Simron Singh
Journal: Journal of Clinical Oncology (2014)

67 Background: Cancer Care Ontario (CCO) is an Ontario government agency which drives quality and improvement in the delivery of care and the patient experience for the Ontario cancer system. Person-Centred Care (PCC) has been identified as a goal from the recent Institute of Medicine (IOM) report and as a corporate strategic priority at CCO. As an initial step in a province-wide PCC strategy, CCO is developing and internally disseminating a patient engagement toolkit and eLearning module with expansion to regional cancer programs. Methods: The PCC eLearning module defines the care approach and explains the corporate goals and objectives of practicing PCC at CCO. Pre- and post-evaluation metrics are embedded to measure module impact on a rating scale with respect to: (1) understanding of PCC; (2) willingness to include the patient voice in CCO work; and (3) understanding of the role of patients who serve as advisors at CCO. The Patient Engagement Toolkit was developed as a step-by-step guide on why and how to engage Patients and Family Advisors (PFAs) in different organizational contexts. To test effectiveness and impact, we piloted the toolkit in 6 interactive sessions across 7 departments with 184 CCO employees over 2 months (Clinical Program and Quality Initiatives, Regional Program, Communication, Finance/Procurement/Facilities, HR, Business Analyst/Project Management Office). We are taking a comprehensive mixed methods evaluation approach with online surveys and key informant interviews to identify uptake and barriers. Results: Preliminary findings suggest considerable increase in the understanding of PCC and the role of PFAs at CCO, with 138 current instances of patient engagement in 1 quarter. After an introduction to the toolkit, many employees (86.7%) understood the value of engaging PFAs and most (63.7%) felt willing to start. Conclusions: Initial program evaluation demonstrates an increase in the understanding and implementation of direct (e.g., joining committees/working groups) and indirect PFA engagement (e.g., speaking at events/in focus groups) across CCO departments. Further evaluation of the toolkit at a provincial level is needed.
Predictive values of activity of daily livings score for the identification of worse performance status
Authors: Yuki Kataoka, Sawako Hosokawa, Nobuko Maehashi, Mariko Shinomiya, Shimada Masatoshi, Junichi Nikaido, Reika Horiguchi, Katsuya Hirano, Kazuo Endo, Masataka Hirabayashi
Journal: Annals of Oncology (2015)
Intracranial Pressure Rescued by Decompressive Surgery after Traumatic Brain Injury
Authors: Lori A. Shutter, Shelly D. Timmons
Journal: New England Journal of Medicine (2016)

Hutchinson et al.1 report in the Journal the results of the Randomised Evaluation of Surgery with Craniectomy for Uncontrollable Elevation of Intracranial Pressure (RESCUEicp) trial, which compared decompressive craniectomy with continued medical management for refractory elevation of intracranial pressure after severe traumatic brain injury. Urgent treatment of patients with such an injury focuses on minimizing secondary brain injury, particularly from increased intracranial pressure. When common medical interventions fail to control intracranial pressure, decompressive craniectomy to prevent herniation may be considered. This surgery addresses a physiological problem (refractory elevation of intracranial pressure) and has a proven benefit in the management of . . .