tbuckley/cabot-search huggingface dataset:
Use of polymorphisms in interleukin-1β (IL-1β) and IL-1 receptor antagonist (IL-1Ra) to predict tumor recurrence in stage II colon cancer
Authors: A. Pohl, G. Lurje, W. Zhang, D. Yang, A. E. Hendifar, P. C. Manegold, Y. Ning, S. Iqbal, A. B. El-Khoueiry, H. J. Lenz
Journal: Journal of Clinical Oncology (2008)

4138 Background: Identifying molecular markers for tumor recurrence is critical in successfully selecting patients with stage II colon cancer who are more likely to benefit from adjuvant chemotherapy. IL-1β and IL1-receptor antagonist (IL-1Ra) have been shown to play a critical role in the early initiation of tumor associated angiogenesis. In vitro and in vivo studies have shown that inhibition of the IL-1 receptor in IL-1β overexpressing tumors limits tumor angiogenesis and invasiveness. In this retrospective study, we tested whether 7 functionally significant polymorphisms within 5 genes (IL-1β, IL-1Ra, IL-8, CXCR1, CXCR2) in the chemokine family will predict the risk of tumor recurrence in stage II colon cancer patients treated with adjuvant chemotherapy. Methods: Between 1986 and 2007 blood specimens from 106 patients (median age of 60 years; range: 22–86) were obtained at the University of Southern California medical facilities. All patients were diagnosed with high-risk stage II colon cancer and were uniformly treated with 5-FU based adjuvant chemotherapy. The median follow-up was 4.4 years (range: 0.3–16.8). 31 of 106 patients (29.9%) developed tumor recurrence with a 3-year probability of 0.22 ± 0.04. Genomic DNA was extracted from peripheral blood and genotypes were determined using PCR-RFLP. Results: IL-1β +3954 T/T (median TTR: 1.5 years, p<0.001, log-rank test) and IL-1Ra 5 repeat polymorphism (median TTR: 0.8 years, p=0.031, log-rank test) were associated with an increased likelihood for tumor recurrence, compared to other genotype combinations of IL-1β (median TTR: 10.7 years) and IL-1Ra (median TTR: 10.7 years). In multivariate analysis, IL-1β +3954 T/T showed to be an independent prognostic factor for TTR (adjusted p=0.004). Conclusion: IL-1β C+3954T and IL-1Ra VNTR polymorphisms may serve as independent molecular markers for TTR in stage II colon. Early initiation of chemokine mediated angiogenesis seems to play a critical role in colon cancer tumor relapse. Therefore, targeting IL-1 receptor may be of clinical benefit for stage II colon cancer patients. Larger, prospective and biomarker embedded clinical trials are needed to validate these preliminary data. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb, Genentech™ BioOncology, ImClone Systems Incorporated, Merck, Pfizer Oncology, Response Genetics Genentech™ BioOncology, Merck, Pfizer Oncology, Roche, sanofi-aventis
Low frequency of altered biodistribution detected by Indium-111 imaging prior to yttrium-90 ibritumomab tiuxetan radioimmunotherapy: Imaging registry results
Authors: P. S. Conti, C. A. White, P. Pieslor, G. Menendez, V. D. Harrough, D. Matso, J. Aussie, T. Ryskamp, P. A. Foster
Journal: Journal of Clinical Oncology (2005)

6589 Background: Ibritumomab tiuxetan (Zevalin) therapy consists of a rituximab pre-dose followed by indium-111 ibritumomab tiuxetan (111In IT) for imaging on day 1 and yttrium 90 (90Y) IT for therapy on day 8. To verify expected biodistribution of the radiolabeled antibody, imaging scans are required at 2–24 and 48–72 hours after 111In IT. A third scan at 90–120 hours is optional. One of approximately 400 patients who received 111In IT imaging in clinical trials was ineligible for 90Y IT due to altered biodistribution. Biogen Idec established an imaging registry to monitor treatment decisions based on imaging results in the commercial setting. Methods: Data were collected on 953 of an estimated 1144–1192 patients receiving commercial 111In IT from March 2002 through March 2003. Results: Thirty-eight no-treatment decisions were made after 111In IT imaging (4% of cases captured); 16 for imaging reasons and 22 due to medical concerns. Twelve of the imaging cases met the criteria for altered biodistribution (1.3% incidence). Of these, 6 (0.63%) were suspected to be true altered biodistribution (4 prominent bone marrow, 1 pneumonia, 1 increased renal uptake), while 6 cases (0.63%) were associated with use of an unapproved radiolabeling procedure by 1 radiopharmacy. All cases of altered biodistribution appeared on scan 1. No-treatment decisions were made for medical reasons as follows: patients with a rapid change in clinical condition precluding treatment (n = 19), patients with a contraindication to IT detected after imaging (n = 2), and physician decision not to treat off label (n = 1). Conclusion: The reported rate of true altered biodistribution was <0.7% in a ibritumomab tiuxetan imaging registry that captured data for an estimated 80% of all patients treated commercially within 1 year of market launch. All cases of altered biodistribution were detected on the first scan. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration BioGen IDEC BioGen IDEC BioGen IDEC BioGen IDEC, Schering
Cardiovascular events in prostate cancer patients: A comparative analysis of German claims data.
Authors: Christoph Ruessel, Jochen Walker, Josephine Jacob, Michael Gedamke, Sebastian Vosgerau
Journal: Journal of Clinical Oncology (2016)

232 Background: In addition to the radical prostatectomy and radiotherapy, androgen deprivation therapies (ADT) have been established as a therapy option in patients with high-risk localized and metastatic prostate cancer (PCa). ADT was found to be associated with a higher risk for cardiovascular (CV) events. This retrospective claims-based study investigated whether CV event rates differ following initiation of ADT with gonadotropin-releasing hormone (GnRH) agonists or antagonists and PCa patients not treated with ADT. Methods: Analyses were based on claims data from the research database of the Health Risk Institute. Eligibility criteria included a PCa diagnosis between 2009 and 2013 and the initiation of ADT with GnRH agonists or antagonists or no ADT during follow up. Outcomes of interest included a composite endpoint of myocardial infarction (MI) or ischemic stroke (IS) as well as the occurrence of a CV event. The latter included MI, sequelae of cerebrovascular disease, IS, intracerebral hemorrhage, pulmonary embolism, phlebitis/thrombophlebitis, transient cerebral ischemic attacks and occlusion/stenosis of cerebral arteries. Results: ADT patients suffered from more comorbidities, were older, and were more likely to suffer from CV conditions than patients with no ADT during baseline. Patients treated with GnRH agonists and antagonists were comparable in terms of mean age and burden of comorbidities. The raw event rates for MI/IS and for CV events during follow up were higher in ADT patients than in patients without ADT (Table 1). Patients treated with GnRH agonists suffered more often from a CV event during follow-up than patients treated with antagonists. Conclusions: Our results indicate that ADT with GnRH antagonists is associated with fewer CV events in PCa patients than treatment with GnRH agonists. The results confirm findings from a pooled analysis of six phase III randomized controlled trials (Albertsen P. et al: Eur Urol 65 (2014) 565-573.). [Table: see text]
A new prognostic system for hepatocellular carcinoma: A retrospective study of 435 patients
Journal: Hepatology (1998)

The clinical outcome of cirrhotic patients with hepatocellular carcinoma (HCC) depends both on the residual liver function and tumor characteristics. However, the relative prognostic weight of these variables is not well defined. The aims of this study were to verify the value of known prognostic factors and to devise a prognostic index more sensitive than the commonly used Okuda stage. A retrospective analysis of the cases of HCC diagnosed at 16 Italian institutions from 1990 to 1992 was performed. Overall survival was the only end point used in the analysis. The Cox model, stratified by locoregional treatment, was used for multivariate analyses. The final model was derived from 10 randomly chosen training samples, and the prognostic validity of the Cancer of the Liver Italian Program (CLIP) score was assessed on the corresponding testing samples. Four hundred thirty-five cases of HCC were collected. As of January 1997, 313 patients (72%) were deceased. Overall median survival was 20 months. At multivariate analysis, independent predictive factors of survival were Child-Pugh stage, tumor morphology, α-fetoprotein (AFP), and portal vein thrombosis. A simple scoring system (CLIP score) was thus produced, assigning linear scores (0/1/2) to the covariates. Compared with Okuda stage, the CLIP score, structured as a six-category tool, has a greater discriminant ability, revealing a class of patients with an impressively more favorable prognosis and another class with a relatively shorter life expectancy. The CLIP score is a new prognostic system that accounts for both liver function and tumor characteristics. It is easy to calculate and appears to give more precise information than the Okuda stage.
Prospective analysis of association between use of statins or other lipid-lowering agents and melanoma risk in the Women’s Health Initiative.
Authors: D. B. Jagtap, C. A. Rosenberg, L. Martin, M. Pettinger, P. Greenland, J. D. Khandekar, R. Levy, D. Lane, M. S. Simon
Journal: Journal of Clinical Oncology (2011)

1586 Background: Melanoma is the most lethal form of skin cancer with an estimated 68,130 new cases diagnosed and 8700 deaths in 2010. The rapidly increasing incidence of melanoma and the high death rate associated with advanced or metastatic disease support the need to focus on prevention as a way to reduce both incidence and mortality. We utilized data from the Women’s Health Initiative (WHI) cohort to assess whether 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins) are associated with a decreased risk of melanoma. Methods: The study population consisted of 119,726 postmenopausal white women, in which 1,099 cases of malignant melanoma were identified over an average of 10.9 (S.D. 2.8) years of follow-up. All cases were confirmed by review of medical records and pathology reports. Information on statin use and duration was collected at baseline, and at select years during follow-up. Self- and interview-administered questionnaires were used to collect information on other risk factors. Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Analyses investigated the association of any statin use, type, potency, category and duration of use with melanoma. Results: Statins were used by 8,824 (7.4%) women. The annualized rate of melanoma was 0.09% among statin users and 0.08% among nonusers. The multivariable adjusted HR for statin users compared with nonusers was 1.09 (95% CI==0.86-1.40). There were no significant differences in risk based on type of statin, potency, category, or duration of use. There was no effect by tumor stage. Conclusions: There was no significant association of melanoma with use of statins among postmenopausal women in the WHI cohort.
Peripheral trafficking of bone marrow-derived stem cells in patients with different types of gastric neoplasms: Significance of complement and interleukins.
Authors: Wojciech Blogowski, Ewa Zuba-Surma, Marta Budkowska, Daria Salata, Maciej Tarnowski, Barbara Dolegowska, Teresa Starzynska
Journal: Journal of Clinical Oncology (2016)

49 Background: Increasing evidence suggests that gastric malignancy may be a stem cell disorder. Methods: Using FACS analysis supported by ImageStream technique verification, various populations of bone marrow-derived stem cells (BMSCs), such as Lin-CD45-CD133+CXCR4+ very small embryonic/epiblast-like stem cells (VSELs), CD45-STRO-1+CD105+ mesenchymal stem cells (MSCs), Lin-CD45+CD133+ hematopoietic stem/progenitor cells (HSPCs), and CD34 +/ KDR +/ CD31 +/ CD45- endothelial progenitor cells (EPCs) were enumerated and sorted from peripheral blood samples of patients with gastric cancer (n = 23) and other gastric tumors (GISTs, NENs, lymphomas; n = 15) and control patients (n = 15). RT-qPCR analysis for the expression of cancerous, embryonic, and tissue trans-differentiation markers (Oct-4, Nanog, TFF-1, TFF-2, Lgr-5, BMI-1) in circulating VSELs was employed. The plasma levels of stromal-derived factor-1 (SDF-1), complement-derived anaphylatoxins/molecules (C3a, C5a, C5b-9/MAC), and interleukins (IL-6, IL-8, IL-17 and IL-23) were measured. Results: Significantly lower numbers of circulating HSPCs, and intensified peripheral trafficking of both VSELs and MSCs was observed in patients with gastric cancer, but not in those with other types of gastric tumors. In gastric cancer patients, the circulating VSELs presented higher gene expression of Oct-4, Nanog, Lgr-5, BMI-1, and TFF-1/2. The abnormal balance in the peripheral trafficking of BMSCs in patients with gastric cancer was not associated with the clinical stage of the disease or with the systemic levels of stromal-derived factor-1 (SDF-1), but correlated with the levels of C5b-9/MAC, IL-6, IL-8 and IL-23. Conclusions: Abnormal peripheral trafficking of BMSCs occurs in patients with gastric cancer, but not in those with other types of gastric neoplasms. Selected interleukins and complement cascade-derived molecules, but not SDF-1, seem to be significant players associated with this phenomenon (POIG.01.01.02-00-109/09 and IP2014003273).
The usefulness of condom method EUS for esophageal mass evaluation.
Authors: Jeong Seop Moon, Sang Yong Seol, Pil Hun Song, Hyun Sung, Jeonghun Lee, Jae J Kim, Won Jae Yoon, Soo Hyung Ryu, You Sun Kim
Journal: Journal of Clinical Oncology (2016)

23 Background: The endoscopic ultrasonography (EUS) is positioned as the method of choice to evaluate the origin and depth of invasion for the esophageal mass. To overcome the disadvantages as aspiration resulting from water filling EUS and balloon rupture resulting from balloon EUS, we used condom method EUS for esophageal mass evaluation. Methods: We investigated retrospectively twenty six patients examined condom method EUS using high frequency ultrasound probes after diagnosed esophageal mass lesion including submucosal tumor by standard endoscopy between January 2007 and April 2015 at Seoul Paik Hospital, Seoul, Korea. We checked the originating layer, invasion depth and echogenicity of the mass and events complicated by procedure. Results: The condom method EUS provided high quality images without aeration and well-defined five layers of esophagus through 360 degrees. In all segments of esophagus; upper (n = 5), middle (n = 10), lower esophagus(n = 11), showed high resolution images without difference. Diagnosis were squamous cell cancer (n = 4), leiomyoma (n = 5), squamous intraepithelial neoplasia (n = 2), acanthosis (n = 2), inflammatory fibrinoid polyp (n = 1) and extrinsic compression (n = 1). Tumors were originated from mucosa (n = 5), muscularis mucosa (n = 10), submucosa (n = 3), mucosa invading into submucosa (n = 4), muscle propria (n = 3). One was diagnosed as outer compression. In esophageal cancer patients, by confirming the location and invasion of the tumor, we could make a decision the next step such as follow up, endoscopic removal or surgery. No complications had occurred in all cases, aspiration or balloon rupture. Conclusions: The condom method EUS is already known as a safe image diagnostic tool of high resolution. Simply to apply inexpensive latex condom filled with water can provide good EUS visual field and images of the esophageal mass lesions along the whole esophagus without aspiration risk.
Quality of care for comorbid conditions during the transition to survivorship.
Authors: C. F. Snyder, K. D. Frick, R. J. Herbert, A. L. Blackford, B. A. Neville, A. C. Wolff, M. A. Carducci, C. Earle
Journal: Journal of Clinical Oncology (2011)

9004 Background: Previous research has documented differences in the quality of preventive care received by cancer survivors vs. non-cancer controls. In this study, we expand on that research and assess the quality of chronic and acute comorbid condition care for cancer survivors vs. controls. Methods: We used SEER-Medicare to analyze breast, colorectal, and prostate cancer patients diagnosed with local/regional disease in 2004. Eligible patients were ≥66 at diagnosis, continuously enrolled in fee-for-service Medicare during the study period, and survived ≥3 years from diagnosis. Non-cancer controls were frequency matched to cases based on age, race, sex, region, and comorbidity. Quality of care was assessed during the initial transition to survivorship (defined as days 366-1095 from diagnosis) using 9 chronic disease quality indicators and 19 acute condition quality indicators from previous studies [Asch et al. 2000; Earle et al. 2004]. Logistic regression was used to compare care quality between cancer cases and controls, both overall and by cancer type, adjusting for sociodemographic characteristics. Results: 8,661 cancer cases (53% prostate, 22% breast, 26% colorectal) were matched with 17,322 controls. In analyses combining all three cancer types, cancer cases received better care on 2/9 chronic care indicators, with no differences on the other 7; however, cancer cases received worse care on 3/19 acute condition indicators, with no differences on the other 16. Colorectal cancer survivors received worse care than controls for both chronic (4/9 indicators) and acute conditions (3/19 indicators); prostate cancer survivors received better care than controls for chronic conditions (2/9 indicators) but worse care than controls for acute conditions (3/19 indicators). Breast cancer survivors received better care than controls for chronic conditions (2/9 indicators) and equivalent care for acute conditions (no differences). Conclusions: We found substantially different patterns in care quality for cancer survivors by cancer type. Further research should explore the factors associated with these differences in care quality to inform interventions to facilitate quality care for all cancer survivors.
Modifying Antigen-Encapsulating Liposomes with KALA Facilitates MHC Class I Antigen Presentation and Enhances Anti-tumor Effects
Authors: Naoya Miura, Hidetaka Akita, Naho Tateshita, Takashi Nakamura, Hideyoshi Harashima
Journal: Molecular Therapy (2017)

For a successful anti-cancer vaccine, antigen presentation on the major histocompatibility complex (MHC) class I is a requirement. To accomplish this, an antigen must be delivered to the cytoplasm by overcoming the endosome/lysosome. We previously reported that a lipid nanoparticle modified with a KALA peptide (WEAKLAKALAKALAKHLAKALAKALKA), an α-helical cationic peptide, permits the encapsulated pDNA to be efficiently delivered to the cytoplasm in bone marrow-derived dendritic cells (BMDCs). Herein, we report on the use of KALA-modified liposomes as an antigen carrier, in an attempt to induce potent antigen-specific cellular immunity. The subcutaneous injection of KALA-modified ovalbumin (OVA)-encapsulating liposomes (KALA-OVA-LPs) elicited a much more potent OVA-specific cytotoxic T lymphocyte activity and anti-tumor effect in comparison with particles that were modified with octa-arginine (R8), a cell-penetrating peptide (R8-OVA-LPs). In addition, the numbers of OVA-specific CD8+ T cells were increased by immunization the KALA-OVA-LPs. The treatment of BMDCs with KALA-OVA-LPs induced a substantial MHC class I antigen presentation. Furthermore, the acidic pH-dependent membrane destabilization activity of KALA-OVA-LPs strongly suggests that they are able to escape from endosomes/lysosomes and thereby deliver their cargos to the cytoplasm. Collectively, the KALA-modified liposome is a potential antigen delivery platform for use as a protein vaccine.
Correlation between plasma cytokine/angiogenic factors (C/AF) and signaling pathways activation from baseline tumor biopsy specimens in patients with advanced non small cell lung cancer (NSCLC): Preliminary analysis from the Biomarker-based Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) Clinical Study
Authors: H. T. Tran, E. S. Kim, J. J. Lee, R. S. Herbst, S. Liu, I. I. Wistuba, S. Yan, L. Mao, W. K. Hong, J. V. Heymach
Journal: Journal of Clinical Oncology (2008)

8010 Background: In the first phase of BATTLE clinical study, 72 pts with advanced, previously treated NSCLC were characterized into one of four biomarker groups (BGs) based on their pre-treatment tumor biomarker profile. BGs included the following: EGFR (mutation & gene copy number), angiogenesis (VEGF and VEGFR-2 by IHC), K-ras/B-raf mutations and RXR/Cyclin D-1 (IHC and gene copy number). We performed exploratory analysis of plasma levels of 59 C/AFs to investigate potential correlation with pathway activation from pretreatment tumor specimens. Methods: 62/72 pts consented to the optional blood collection for C/AF analysis. We used multiplex bead assays to measure 53 plasma C/AFs, including VEGF, basic FGF, HGF, E-selectin, MMP-9, multiple chemokines and interleukins (IL). Total and free IGF-1, IGFBP-3, osteopontin (OPN) and sVEGFR-1&2 were measured by ELISA. To evaluate the association between plasma C/AFs and pretreatment tumor markers, Wilcoxon test was performed. Results: A significantly higher score of association was observed with OPN (p=0.005), IL-2ra (p=0.012), IL6 (p= 0.026) and IL-7 (p=0.031) in patients in the EGFR positive group, compared to those patients who were negative for this marker group. Higher IGFBP-3 was significantly associated with K-ras/B-raf mutations (p=0.007) and IL-12 (p=0.021) was significantly higher in angiogenesis positive group. Additionally, MMP-9 (p=0.017) was significantly higher in patients with negative angiogenesis markers. Conclusions: Several plasma C/AFs are associated with specific tumor derived pathway activation. This preliminary exploratory analysis suggests that broad-based plasma profiling of cytokines and angiogenic factors may be feasible approach for identifying markers of activation of tumor signaling pathways. The BATTLE clinical study continues to accrual. (funding from Department of Defense - BATTLE grant W81XWH-06–1-0303) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca AstraZeneca, Genentech