tbuckley/cabot-search huggingface dataset:
Serum Amyloid A (SAA), C-reactive protein (CRP) and IL-6 as prognostic indicators in Renal Cell Carcinoma and Prostate Cancer
Authors: M. Mata, T. Lohr, M. Lakshminarayanan, K. H. Lo, U. Prabhakar
Journal: Journal of Clinical Oncology (2004)

9711 Background: IL-6, CRP and SAA are three biomarkers whose expressions have been shown to correlate with prognosis in select tumor models. We have evaluated these three biomarkers and their potential use as prognostic indicators in renal cell carcinoma (RCC) and prostate cancer in a retrospective study. Methods: Serum samples from patients with RCC or prostate cancer were obtained from IMPATH-BCP, Inc. (New York, NY). Healthy control subjects were also included. Serum levels of IL-6, CRP and SAA were measured using commercially available ELISA kits. Summary statistics were calculated and associations between variables were evaluated using linear regression analysis and Pearson correlation coefficient. Results: Serum levels of IL-6 (range <0.78 - 175 pg/mL), CRP (range 0.74 - 144.98 μg/mL) and SAA (<9.40 - 1530.84 ng/mL) were measured. All three biomarkers were found to be significantly higher in patients with RCC, while only SAA and CRP were found to be significantly higher in PC patients when compared to normal donors. Significant correlations between IL-6, CRP, and SAA were revealed by statistical analysis of the RCC serum data (IL-6/CRP r2=0.752; SAA/CRP r2=0.596; SAA/IL-6 r2=0.635). Correlation of these markers with patient survival (defined as the number of days between date of diagnosis and date of death) was found using Pearson correlation coefficients for RCC data analysis (IL-6 -0.4151, p=0.0063; CRP –0.4129, p=0.0059; SAA –0.3793, p=0.0158). In prostate cancer patients, no correlations between PSA and SAA, or CRP and IL-6 were found. Additionally, no significant correlation was observed between the investigated markers and survival (IL-6 0.0996, p=0.4650; CRP −0.0354, p=0.8219; SAA –0.0670, p=0.6207). Conclusions: Based on these results, it appears that there may be mild to moderate association between survival time and the inflammatory markers in RCC but not in PC. However, other clinical variables may affect these conclusions in these heterogeneous populations. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Centocor, Inc. Centocor, Inc. Centocor, Inc.
Non‐invasive measurement of right atrial pressure by near‐infrared spectroscopy: preliminary experience. A report from the <scp>SICA‐HF</scp> study
Authors: Pierpaolo Pellicori, Andrew L. Clark, Anna Kallvikbacka‐Bennett, Jufen Zhang, Alessia Urbinati, Luca Monzo, Riet Dierckx, Stefan D. Anker, John G.F. Cleland
Journal: European Journal of Heart Failure (2017)
Former football club doctors must compensate player for kidney failures, German court rules
Authors: Ned Stafford
Journal: BMJ (2017)

Two doctors who worked on behalf of the German Bundesliga football club Werder Bremen contributed to the kidney problems of Ivan Klasnic, a former Croatia international player who underwent two kidney transplants in 2007 and now requires a third, a German court has ruled.

In the ruling issued on 31 March 2017, Bremen District Court, where Klasnic filed a civil malpractice lawsuit in 2008, awarded him €100 000 (£85 600; $106 700) as compensation for pain and suffering.

Gotz Dimanski, who was Werder Bremen’s team doctor in 2007, and Manju Guha, a cardiologist who was responsible for annual routine internal examinations at the time, were ordered to pay for Klasnic’s past and future medical costs, as well as damages for loss of income, …
Two phase I studies of prime-boost vaccinations with vaccinia-fowlpox vaccines expressing CEA, MUC-1, and TRICOM costimulatory molecules (B7.1/ICAM-1/LFA-3) in patients with advanced pancreatic cancer
Authors: T. Schuetz, J. Marshall, H. L. Kaufman, H. Safran, D. Panicali
Journal: Journal of Clinical Oncology (2004)

2564 Background: Recombinant pox viruses have been developed as therapeutic anti-tumor vaccines. Previous studies have demonstrated a correlation between the generation of T-cell immunity by these vaccines and overall survival (OS). We report the results of two Phase I studies of vaccines targeting MUC-1 and CEA. Methods: The first study tested an earlier generation of the vaccines. The second study tested recombinant vaccinia and fowlpox viruses co-expressing CEA, MUC-1, and the TRICOM genes (PANVAC-VF). Safety was the primary objective of both studies. Twenty-two patients with advanced pancreatic cancer (Stage III or IV) were enrolled (20 with metastatic disease; all had received prior therapy). Patients received a ‘prime’ dose of vaccinia on Day 0, followed by ‘boost’ doses of fowlpox on Days 14, 28, and 42; all vaccinations were followed by local GM-CSF (100 μg) for 4 days. Patients who were clinically stable were able to continue vaccinations monthly. Safety parameters evaluated included vital signs, physical examination, laboratory tests, and adverse events (AEs). All patients were followed for survival. Results: The most common AE related to the vaccines was grade 1 injection site reaction, which included erythema, swelling, pruritis, blister, induration, and pain. Other common AEs were fatigue, anorexia, nausea, vomiting, fever, headache, and myalgia. There was one grade 3 fever. No serious adverse events related to vaccine occurred. Six of the 12 patients enrolled in the first study have died. However, the median OS cannot yet be calculated and currently is at least 7.3 months. Conclusions: All of the patients in the first study had metastatic disease at baseline and all had failed first-line chemotherapy. Historical control data suggest that the expected median OS in this patient population is approximately 3 months. Although the sample size is small and the analysis is limited by comparison to historical controls, these data suggest that vaccination has improved median OS in this patient population. A randomized trial is planned for early 2004. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Therion Biologics Roche; Therion Biolgoics Therion Biolgoics
Storage of Radium in War-time
Authors: G. F. Stebbing
Journal: BMJ (1939)

RADIUM is not only a valuable but also a very dangerous substance. If, during an air raid, any quantity of radium was dispersed by violence, the buildings in which it was dispersed, as well as a considerable area surrounding the buildings, would be for many years to come a menace to any people who inhabited them. One-hundredth of a milligram would probably be fatal if inhaled.
A natural language processing algorithm to measure quality prostate cancer care.
Authors: Tina Hernandez-Boussard, Panagiotis Kourdis, Rajendra Dulal, Michelle Ferrari, Solomon Henry, Tina Seto, Kathryn McDonald, Douglas W. Blayney, James D. Brooks
Journal: Journal of Clinical Oncology (2017)

232 Background: Electronic health records (EHRs) are a widely adopted but underutilized source of data for systematic assessment of healthcare quality. Barriers for use of this data source include its vast complexity, lack of structure, and the lack of use of standardized vocabulary and terminology by clinicians. This project aims to develop generalizable algorithms to extract useful knowledge regarding prostate cancer quality metrics from EHRs. Methods: We used EHR ICD-9/10 codes to identify prostate cancer patients receiving care at our academic medical center. Patients were confirmed in the California Cancer Registry (CCR), which provided data on tumor characteristics, treatment data, treatment outcomes and survival. We focused on three potential pretreatment process quality measures, which included documentation within 6 months prior to initial treatment of prostate-specific antigen (PSA), digital rectal exam (DRE) performance, and Gleason score. Each quality metric was defined using target terms and concepts to extract from the EHRs. Terms were mapped to a standardized medical vocabulary or ontology, enabling us to represent the metric elements by a concept domain and its permissible values. The structured representation of the quality metric included rules that accounted for the temporal order of the metric components. Our algorithms used natural language processing for free text annotation and negation, to ensure terms such as ‘DRE deferred’ are appropriately categorized. Results: We identified 2,123 patients receiving prostate cancer treatment between 2008-2016, of whom 1413 (67%) were matched in the CCR. We compared accuracy of our data mining algorithm, a random sample of manual chart review, and the CCR. (See Table.) Conclusions: EHR systems can be used to assess and report quality metrics systematically, efficiently, and with high accuracy. The development of such systems can improve and reduce the burden of quality reporting and potentially reduce costs of measuring quality metrics through automation. [Table: see text]
NY-ESO-1 specific CD4<sup>+</sup> T<sub>helper</sub>1 cells for immunotherapy of cancer.
Authors: Simone Kayser, Cristina Boß, Michael Schumm, Judith Feucht, Stefan Stevanovic, Peter Lang, Rupert Handgretinger, Claus Garbe, Martin Röcken, Tobias Feuchtinger
Journal: Journal of Clinical Oncology (2014)

3071 Background: NY-ESO-1 is an attractive target for adoptive T cell transfer (ACT) as it is expressed on a variety of tumors, but not in normal tissue except germline cells. Immune attack against cancer is mediated by cell lysis or induction of growth arrest through paralysis directly in tumor cells. The latter can be achieved by CD4+, IFN-γ-producing Thelper1 (Th1) cells. Translation of this immune mediated mechanisms into clinical application has been limited by complex in vitro protocols and regulatory hurdles. Methods: We established a short protocol according to good manufacturing practice (GMP) to generate NY-ESO-1 specific T cells with focus on Th1 cells. After presensitization with overlapping NY-ESO-1-peptides, IL-2 and IL-7, T cells were enriched based on IFN-γ capture technique. Cells were expanded using autologous feeder cells and IL-2, IL-7 and IL-15 and T-cell specificity and function was analyzed. Results: Large numbers of specific NY-ESO-1 CD4+ T cells with a Th1 cytokine profile and lower numbers of cytokine secreting CD8+ T cells could be generated with a sustained expansion potential. Manufactured CD4+ T cells show strong specific responses with IFN-γ+, TNF-α+ and IL-2+ and induce growth arrest and apoptosis in tumor cells. The T-cell products did not include alloreactive or regulatory T cells. Specificity was confirmed with a new identified MHC class II matched NY-ESO-1 derived peptide and recognition of processed NY-ESO-1 Protein was demonstrated. Conclusions: Adoptive T-cell transfer by a novel cancer treatment-approach with tumor-antigen specific CD4+ Th1 lymphocytes can be performed to boost anti-cancer immunity and is feasible with T cells from healthy allogeneic donors as well as with autologous T cells from cancer patients. The T-cell generation process was approved by the regulatory authorities. Due to the frequent expression of NY-ESO-1 in tumors the therapy is applicable to a large patient collective in different cancer entities.
A phase II randomized open-label study of MM-121, a fully human monoclonal antibody targeting ErbB3, in combination with weekly paclitaxel versus weekly paclitaxel in patients with platinum-resistant/refractory ovarian cancers.
Authors: Joyce Liu, Isabelle Laure Ray-Coquard, Frédéric Selle, Andres Poveda, David Cibula, Hal W. Hirte, Francesco Raspagliesi, Laurence Gladieff, Philipp Harter, Ilaria Schiavetto, Isabelle Marie Tabah-Fisch, Gavin MacBeath, Akos Gabor Czibere, R. Wendel Naumann, Robert L. Coleman, Ignace Vergote, Eric Pujade-Lauraine
Journal: Journal of Clinical Oncology (2014)

5519 Background: Heregulin induced activation of ErbB3 has been implicated as a mechanism of resistance to many targeted and cytotoxic therapies such as paclitaxel in preclinical models. MM-121 is a monoclonal antibody designed to interfere with this mechanism of resistance. Methods: This was a global, open-label, randomized Phase II study of MM-121 in patients with platinum resistant ovarian cancer. Patients were randomized (Ratio 2:1) to receive MM-121 plus paclitaxel (M+P) or paclitaxel alone (P). The primary objective was to compare progression-free survival (PFS) between the groups. Pretreatment fresh biopsies obtained from all patients were analyzed to assess a pre-specified set of mechanistically-linked biomarkers (BM): heregulin (HRG), betacellulin, EGFR, ErbB2, and ErbB3. Results: 223 patients (140 (M+P), 83 (P)) were included in the efficacy analyses. Baseline demographics and disease characteristics were balanced. Most patients (80.3%) had received 2 or more prior platinum-based regimens. Median PFS was analyzed after 171 events (115 (M+P), 56 (P)) and was 3.75 months (M+P) and 3.68 months (P) with a stratified hazard ratio (HR) of 1.027 [95% CI 0.741 - 1.425]. Two biomarkers based on pre-clinical predictions were used to identify a subset of BM positive patients (34%: 57/169 patients with BM available). In this BM positive group the HR for PFS was 0.37 [0.2 - 0.8] and the HR in the BM negative group was 1.54 [1.0 - 2.4]. The overall safety profile was consistent with expected adverse events (AEs), with the exception of an increase in the pulmonary embolism rate (5.0% (M+P) vs. 1.2% (P)). However, the overall rate of venous thromboembolic events was comparable (5.7% (M+P) vs. 7.5% (P)). Most AEs were reported as mild to moderate in severity and included diarrhea, vomiting, stomatitis, and mucosal inflammation. Conclusions: A signal of benefit was observed in a biomarker positive subpopulation, althoughthe study regimen was not effective at prolonging PFS in the overall study population. Any further development of MM-121 in ovarian cancer should focus on biomarker-selected patients. Clinical trial information: NCT01447706.
Metformin enhances the activity of rituximab in B-cell lymphoma pre-clinical models.
Authors: Priyank P. Patel, Juan J Gu, Cory Mavis, Myron Stefan Czuczman, Francisco J. Hernandez-Ilizaliturri
Journal: Journal of Clinical Oncology (2015)

e19513 Background: The Warburg effect is primarily observed in rapidly growing tumors including aggressive B-cell lymphomas and is thought to be a consequence of the progression to cancer rather than the cause of it and altering the glucose metabolism in cancer cells appears to be an attractive strategy in cancer medicine. Retrospective studies have shown survival benefit in solid tumors and diffuse large B-cell lymphoma cohorts who were on metformin for type-2 diabetes. In an attempt to characterize the mechanism by which metformin affects the biology of B-cell lymphoma, we studied its effect on rituximab activity. Methods: A panel of B-cell lymphoma cells was exposed to metformin +/- rituximab or isotype control, changes in cell cycle distribution or induction of apoptosis was determined by flow cytometry. Antibody-dependent cellular cytotoxicity (ADCC) and complement mediated cytotoxicity (CMC) assays were performed to demonstrate changes in sensitivity to rituximab following metformin exposure. For in vivo studies, SCID mice were inoculated via tail vein injection (iv) with Raji cells (day 0) and assigned to observation, rituximab (at 10mg/kg/dose on days +3,7,10 and 14), metformin (at 2mg/ml in drinking water) or metformin and rituximab. Differences in survival (measured at the time for limb paralysis development) were evaluated by log-rank test between treatment arms. Results: In vitro exposure to metformin resulted in S/G1 cell cycle arrest and induction of apoptosis in a dose-dependent manner. Metformin enhanced the anti-proliferative effects of mAbs targeting CD20. Moreover, pre-incubation of lymphoma cells enhanced rituximab-mediated CMC. In vivo, significant improvement in survival was observed in metformin + rituximab arm (mean survival not reached at 69+/- 5.3 days) compared to rituximab (mean survival 57.1 +/- 4.2 days) (p = 0.05). Conclusions: Our data suggests that metformin inhibits the proliferation of B-cell lymphoma cell lines and enhances the anti-tumor activity of rituximab. Our finding highlights a potential role for metformin in the treatment of B-cell malignancies.
The Quality Oncology Practice Initiative program: Experience in Spain.
Authors: Carlos Camps, Eduardo Diaz Rubio, Rafael Lopez, Alfredo Carrato, Pedro Gascon, Feyjoo Margarita, Vicente Guillem
Journal: Journal of Clinical Oncology (2017)

214 Background: Patient care quality is a discipline that is being considered highly important in today’s healthcare. Quality Oncology Practice Initiative (QOPI) is a referral worldwide in terms of quality for oncology practices. The ECO Foundation is a platform of experts representing the major Spanish hospitals involved in the treatment of cancer patients. ECO reached an agreement with QOPI in order to involve Spanish hospitals in the participation of the QOPI program. Methods: Two rounds of data collection were carried out (Fall 2015 and Spring 2016). Practices had to registered on-line and submit data into the platform provided by QOPI. ECO Foundation offers all centres the support of a CRO. 11 Spanish hospitals have participated in the first round and 6 in the second. 4 of them have participated in both rounds. Core and Lung Cancer modules were completed. Results: For the Fall 2015 round, 686 charts were included. In Spring 2016 334 charts were collected. For the first round, highest scores were: Pathology report confirming malignancy, Plan of care for pain, Effectiveness of narcotic, Patient consent, Tobacco cessation counselling, Patient emotional well-being assessed and in the 9 items of the lung cancer module. Lowest scores were: Pain addressed, Smoking status use, Smoking use cessation counselling, Smoking use cessation administered and Height, Weight, and BSA documented. For the Spring 2016 round, the results were similar, but for the items with the highest scores were now included: Chemotherapy intent discussion, Patient consents for chemotherapy, Smoking status documented, Height, Weight, and BSA documented. In Fall 2015, 7 out of 11 practices obtained a global score of over 70%, and in 2016, 3 out of 6. Regarding the 4 hospitals that repeated in both stages,3 reported an improvement of the global scoring in 2016. Conclusions: These preliminary results are a good starting point for the continued implementation of the QOPI program in Spain. Thus providing a well-structured approach to analyse cancer care in Spain, offering training programs for quality improvement in oncology practices. ECO Foundation will continue pursuing excellence and quality in Spain with future activities like the certification programs and training seminars.
Understanding the patient experience of cancer treatment in Ontario, Canada: A qualitative study.
Authors: Erica Bridge, Lesley Gotlib Conn, Suman Dhanju, Simron Singh, Lesley Moody
Journal: Journal of Clinical Oncology (2017)

225 Background: In cancer care, patient experience is most often measured quantitatively. However, this approach has limitations in understanding the entire patient experience. Qualitative methods provide an opportunity to understand self reported and more complex issues most important to patients and their family members. This qualitative study explores the patient experience of outpatient cancer treatment throughout Ontario, Canada. Methods: Qualitative content analysis was done by two researchers using data from the annual Ambulatory Oncology Patient Satisfaction Survey (AOPSS) from 2013-15. The AOPSS is a retrospective, paper-based, mailed survey, designed to capture the experiences of patients who are currently receiving cancer treatment or who have received cancer treatment within the previous six months. Patients surveyed were asked “Is there anything else you would like to tell us about your cancer care services?” The National Research Corporation of Canada’s eight dimensions of patient-centred care was used to guide the analysis. Results: 5,391 patients responded to the open-ended question. Demographic information includes: gender, age, education level and disease site. 7,328 coded responses were generated, of which 3,658 (49.9%) were related to eight dimensions of patient-centred care with accompanying sub-dimensions: patients’ preferences (23.5%): dignity and respect; preferences and decision-making; care provider behaviours; emotional support (21.5%): caring, compassion and comfort; anxiety and stress; resources; and sensitive diagnosis; coordination of care (15.8%): care provider and treatment coordination; wait times; information and education (15.7%): patient-care provider communication; information needs; care provider knowledge and skills; access (9.4%): centre location; transportation and accommodation; system; parking; continuity and transition (8.1%): centre personnel; continuity between departments; continuity in the community; discharge; physical comfort (5.1%): environment; pain management and family and friends (0.8%). Conclusions: Qualitative analysis is an effective tool to capture patient experience on a population level.
Community-Based Practice Variations in Topical Treatment of Actinic Keratoses
Authors: Molly Storer, Zheng Zhu, Monika Sokil, Margaret Ford, Romain Neugebauer, Maryam M. Asgari
Journal: JAMA Dermatology (2017)

This data analysis uses data from a large community-based population and examines how variations in fluorouracil and imiquimod prescription patterns for treatment of actinic keratoses are influenced by patient age, sex, anatomic site, and prescriber type.
Evaluation of invasion patterns and their correlation with integrin alphavbeta expression in brain metastases of solid cancers.
Authors: Anna Sophie Berghoff, Orsolya Rajky, Frank Winkler, Michael Weller, Christoph Zielinski, Jens Schittenhelm, Matthias Preusser
Journal: Journal of Clinical Oncology (2013)

2059 Background: Understanding the pathobiology of brain metastases (BM) could guide the establishment of new targeted therapies. Methods: We collected 57 autopsy specimens of BM (primary tumor: 27 lung cancer, 6 breast cancer, 8 melanoma, 1 kidney cancer, 2 colorectal cancer, 13 other) and histologically evaluated the patterns of invasion into the surrounding brain parenchyma. Expression of the following integrins was evaluated using immunohistochemistry: with novel antibodies for αv subunit, αvβ3, αvβ5, αvβ6 and αvβ8 integrin. Results: We observed three main invasion patterns: well-demarcated (29/57, 51%), vascular co-option (10/57, 18%) and diffuse infiltration (18/57, 32%). There was no association of invasion pattern with primary tumor type, although vascular co-option was most common in melanomas (4/10, 40%). αv subunit expression was lowest in the vascular co-option group (p = 0.05, t-test). αvβ6 levels were higher in the well-demarcated group than in the vascular co-option group (p = 0.025; t-test) and were higher in lung cancer BM than in melanoma BM (0.01, t-test). αvβ3 and αvβ5 were frequently expressed in tumoral (αvβ3: 30/57, 53%; αvβ5: 55/57, 97%) and peritumoral (αvβ3: 29/57, 51%, αvβ5: 54/57 (95%) vascular structures and 27/57 (47%) specimens showed avb5 and 6/57 (11%) αvβ3 expression on tumor cells. Prior radio- or chemotherapy did not correlate with invasion pattern or integrin expression. Conclusions: We delineate three distinct invasion patterns of BM into the brain parenchyma: well-demarcated growth, vascular co-option and diffuse infiltration. Integrin expression is frequent on tumor and vascular cells in BM and associated with distinct invasion patterns. Anti-integrin therapy could be a valid treatment option in patients with BM.