tbuckley/cabot-search huggingface dataset:
Randomized trial of short-course versus long-course radiotherapy for palliation of painful vertebral bone metastases: A retrospective analysis of RTOG 97–14
Authors: D. D. Howell, J. L. James, W. F. Hartsell, M. Suntharalingam, M. Machtay, J. H. Suh, W. F. Demas, H. M. Sandler, L. A. Kachnic, L. B. Berk
Journal: Journal of Clinical Oncology (2009)

9521 Background: RTOG 97–14 [Hartsell et al, breast/prostate cancer patients (pts) with painful bone metastases randomized to 8 Gy/1 fraction or 30 Gy/10 fractions], revealed no difference in pain relief or narcotic use 3 months post randomization. The 8 Gy regimen resulted in fewer acute toxicities, but higher rates of retreatment for recurrent pain. Single 8 Gy fractions for painful vertebral bone mets have not been well accepted, possibly due to provider concerns about efficacy and toxicity. The present study evaluates treatment differences in the subset of pts treated specifically for painful vertebral bone mets (PVBM). Methods: PVBM were treated to the cervical, thoracic, and/or lumbar spine. Chi-square test was used to evaluate population differences between PVBM and non-PVBM. Amongst PVBM, differences in retreatment rates (cumulative incidence method, Gray's test) and in pain relief/BPI worst pain score, narcotic use, and toxicity 3 months post randomization (chi-square test) were evaluated. Results: Of 909 eligible pts, 235 (26%) were PVBM. PVBM and non-PVBM pts differed in % of males [55% vs. 47%,p=0.03] and pts with multiple painful sites [57% vs. 38%,p&lt;0.01]. Amongst PVBM, more 30 Gy pts had multiple sites treated [65% vs. 49%, p=0.02]. T [10% vs. 20%, p=0.01] here was no statistically significant difference (8 vs. 30 Gy) in pain relief [70% vs. 62%, p=0.59] or narcotic use [27% vs. 24%, p=0.76] at 3 months. There were significant differences in acute grade 2–4 toxicityand acute grade 2–4 GI toxicity [6% vs. 14%, p=0.01] at 3 months, lower toxicity seen in 8 Gy. Late toxicity was rare, with 1 grade 3 CNS event (8 Gy) and 1 grade 4 lung event (30 Gy). 8 Gy showed significantly higher 3-year retreatment rates [15% vs. 5%, p=0.01]. Conclusions: Although a clinically different pt population, the results for PVBM are comparable to those of the entire study population. Both 8 Gy/1 fraction and 30 Gy/10 fractions resulted in comparable pain relief and narcotic use at 3 months. Both were well tolerated with few adverse effects. 8 Gy had less acute toxicity, and a higher need for retreatment than 30 Gy. This may have implications for future research comparing single fraction conventional radiation therapy with stereotactic spine radiosurgery. No significant financial relationships to disclose.
Non-metastatic Ewing's family tumors: High-dose chemotherapy with stem cell rescue in poor responder patients. Preliminary results of the Italian/Scandinavian ISG/SSG III protocol
Authors: S. Ferrari, T. Alvegard, R. Luksch, A. Tienghi, K. S. Hall, G. Bernini, A. Brach del Prever, P. Picci, G. Bacci, S. Smeland
Journal: Journal of Clinical Oncology (2007)

10014 Background: Poor response to induction chemotherapy negatively affects prognosis for Ewing's sarcoma (ES) patients. To improve outcome, high-dose chemotherapy (HDCT) with stem cell rescue was added to conventional chemotherapy in patients poor responders after induction treatment. Methods: Non-metastatic ES patients aged &lt;= 40 years were eligible. All patients received VAC (vincristin 2 mg-doxorubicin 80 mg/m 2 -cyclofosfamide 1,200 mg/m 2 ) weeks 0 and 6, IVAc (ifosfamide 9g/m 2 -vincristin 2 mg-actinomycin 2 mg) week 3 and IE (ifosfamide 9g/m 2 -etoposide 450 mg/m 2 ) week 9 as induction therapy. Poor response was histologically defined as persistence of microfoci of viable tumor cells and radiologically as persistence of soft tissue mass. As maintenance treatment good responders (GR) received three cycles of VAC-IVAc-IE. Poor responders (PR) received VAC (weeks 13,19), IE (week 22), CE (mobilizing cycle, cyclophoshamide 4g/m 2 , etoposide 600 mg/m 2 , week 16) and HDCT with BuMel (busulfan 4 mg/kg × 4 days orally and melphalan 140 mg/m 2 with stem cell support week 25). Results: Starting from 1999, 296 patients were enrolled with a median age of 15 years (3–40). 54 % of the tumors were located to the extremities and 46% in the axial skeleton. 274 patients underwent local treatment: surgery in 222 (81%) patients (with post operative Rxt in 70), RxT alone in 52 (19%). 10 patients progressed during treatment. No toxic deaths were recorded. Response evalutation was available for 262 patients: 135 (52%) were PR. 116 of them completed protocol treatment and 19 did not receive HDCT (5 poor harvest, 5 medical contraindication, 9 refusal).With a median follow-up of 37 months (1–89) 5-year overall and event-free survival were 74 % and 65.5% respectively. 5-year event-free survival was 71% (95% CI 62–81%) for GR, 68% (95% CI 58–78%) for PR treated with HDCT and 35% (95% CI 10–60%) for PR who did not receive HDCT. Conclusions: The preliminary survival data show for PR similar outcome as for GR. The treatment including HDCT is feasible with no toxic death recorded. Longer follow-up will confirm its efficacy. No significant financial relationships to disclose.
FRI0069 Comorbidity in Early Rheumatoid Arthritis - Which is the Role of Inflammation?
Authors: L. Innala, C. Sjöberg, E. Berglin, S. Magnusson, B. Möller, S. Rantapää-Dahlqvist, T. Smedby, A. Södergren, S. Wållberg-Jonsson
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Patients with rheumatoid arthritis (RA) suffer from comorbidities that contribute to a shortened lifespan. Inflammation is of importance for the development of cardiovascular disease, but little is known on its relationship with other comorbidities in RA. <h3>Objectives</h3> To examine the prevalence of comorbidities in early RA and the role of inflammation in this context. <h3>Methods</h3> All patients with early RA (symptom duration &lt;12 months) in Northern Sweden are since 1995 included in a prospective study on co-morbidities. By now 950 patients have been included. At the time of this compilation, 715 patients were followed-up of whom 498 had been ill for ≥5 years. Data on comorbidities, disease activity, x-ray (hands/feet), laboratory samples (autoantibodies, inflammatory variables) and pharmacological therapy were collected in record studies and further validated using a questionnaire at RA onset (T0) and after 5 years of disease (T5). <h3>Results</h3> 53% had one or more comorbidities at RA onset. By then, the most common comorbidities were hypertension (26.3%), obstructive pulmonary disease (13.9%), diabetes (8.0%), hypothyroidism (6.3%) and malignancy (5.0%). After 5 years, 41% had developed at least one new comorbidity; most common were hypertension (15.1%), malignancy (7.8%), stroke/TIA (5.1%), myocardial infarction (4.3%) and osteoporosis (3.7%). Univariate regression analyses showed that age (p&lt;0.001), ESR (p&lt;0.01), extra-articular RA (p&lt;0.01), corticosteroids (p&lt;0.001) were associated with a new comorbidity during 5 years. Female gender and biologics reduced this risk (p&lt;0.01 for both). In a multiple regression model adjusted for age, sex, smoking and corticosteroids, ESR were associated with a new comorbidity at follow-up. In a similar model, the relationship between ESR and endocrine comorbidity approached significance (p=0,10). <h3>Conclusions</h3> There was substantial comorbidity among RA patients already at disease onset and considerable new comorbidity during the first five years of disease. Measures of disease activity were associated with occurrence of comorbidity. <h3>References</h3> Innala et al. Arthritis Res Ther 2011; 13: R131, Charlson et al. J Chron Dis, 1987; 40: 373-383, 25: 469-483, Norton et al. Rheumatol. 2013;52:99-110. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4651
Tridimensional Personality Questionnaire scores of sons of alcoholic and nonalcoholic fathers
Authors: M A Schuckit, M Irwin, H I Mahler
Journal: American Journal of Psychiatry (1990)

The authors studied 33 men whose fathers had severe alcohol-related problems and 33 subjects with no family history of alcoholism. The former supplied information about the course of their fathers' alcohol problems; all 66 men answered questions about their own drinking and drug use and completed the Tridimensional Personality Questionnaire. There were no significant relationships between any of the 18 questionnaire scores and a subject's quantity/frequency of drinking or his family history of alcoholism. There was only one significant correlation between the alcoholic fathers' type 2 characteristics, according to the type 1/type 2 theory, and the sons' questionnaire scores. The relevance of these findings to the theory is discussed.
Transcriptional profiles of triple receptor-negative breast cancer: Are Caucasian, Hispanic, and African-American women different?
Authors: W. Dean-Colomb, K. Yan, C. Liedtke, W. F. Symmans, F. A. Holmes, J. O'Shaughnessy, L. Asmar, G. N. Hortobagyi, L. Pusztai, A. M. Gonzalez-Angulo US Oncology
Journal: Journal of Clinical Oncology (2008)

22014 Background: 24% of breast cancers occur in African-American women (AAW), but they account for 33% of the deaths annually. Triple receptor-negative breast cancer (TNBC) is more common in AAW. The goal of this study was to see if the transcriptional profiles of TNBC in AAW were different from the profiles of other ethnicities. Methods: Transcriptional profiling was performed using Affymetrix U133 gene chips on pretreatment fine needle aspiration specimens from patients who participated in a series of pharmacogenomic neoadjuvant chemotherapy studies at MDACC and USO. Patients with TNBC, defined by routine clinical assays (IHC and/or FISH), were selected for further analysis. Supervised hierarchical clustering was performed to determine clusters by ethnicity and unequal variance t-test was used to examine differences in gene expression between TNBC in AAW compared with others. False discovery rate was assessed by beta uniform mixture analysis of the p values from the t-statistics. Results: Four hundred and twenty-one gene expression profiles were examined which included 98 tumors that were TNBC. Of these, 19 belonged to AAW, 23 to Hispanic women and 56 to Caucasian women. There were no differences in patient and tumor characteristics or pathologic response rates by ethnicity. There was no clustering of gene expression data by ethnicity. There were no genes differentially expressed in TNBC in AAW compared to other women after the adjustment for multiple comparisons. Conclusion: The transcriptional profiles of AAW women with TNBC were similar to that of women of other ethnicities. No significant financial relationships to disclose.
Support groups whose members have themselves had breast cancer are helpful
Authors: H. Caulton
Journal: BMJ (1996)

EDITOR,—Although all support groups have a useful role, it is a pity that the support group used in June M C McArdle and colleagues' study was not one whose members have all had breast cancer themselves and are specifically dedicated to supporting patients with breast cancer.1 Members of such support groups can therefore truly empathise with the patients …
Abstract 11253: Inhibition of Dipeptidyl Peptidase IV Improves Left Ventricular Compliance in Obese Diabetic Mice
Authors: Anne-Sophie Hervent, Nazha Hamdani, Veerle Matheeussen, Marc Demolder, Ingrid De Meester, Walter Paulus, Gilles De Keulenaer
Journal: Circulation (2012)

INTRODUCTION: Diabetes cardiomyopathy (DCMP) is a leading cause of cardiac morbidity and mortality. DCMP is characterized by left ventricular (LV) hypertrophy and fibrosis, and by LV diastolic dysf...
Abstract 17785: Discordance Between Reversal of Hemodynamic and Diastolic Parameters Post Aortic Valve Replacement with Preserved Ejection Fraction
Authors: Daniel Marrero, Monica Sanchez-Ross, Valentin Suma, Bani M Azari, Sameh Mohareb, Amit K Correa, Amgad N Makaryus, Suraj Sookhu, Daniel Swistel, Sandhya Balaram, Farooq A Chaudhry
Journal: Circulation (2012)
The quantification of the catalytic subunit of telomerase in plasma is a prognostic factor in advanced non-small cell lung cancer (NSCLC) patients
Authors: R. Sirera, C. Camps, L. Llobat, A. Berrocal, R. M. Bremnes, A. Blasco, A. Juarez, M. Taron, J. J. Sanchez, R. Rosell
Journal: Journal of Clinical Oncology (2006)

7052 Background: Qualitative and quantitative analysis of circulating DNA in blood is a promising non-invasive diagnostic and prognostic tool. Our aim was to study the association between the free amount in plasma of the catalytic subunit of telomerase (hTERT) and several clinical variables in advanced NSCLC patients. Methods: We examined 451 NSCLC patients in stage IIIB and IV, treated with cisplatin and docetaxel. Blood samples were collected before chemotherapy, and circulating DNA was extracted from the serum using commercial adsorption columns. The amount of free hTERT in plasma was quantified by using RT-PCR. Results: Median age was 61 years [35–82] and 84% were males. 99% had performance status 0–1. 84% were in stage IV and 16% in stage IIIB. The histological subtypes were: 32% squamous cell carcinoma, 50% adenocarcinoma, 14% anaplastic large cell, and 4% undifferentiated. 41% of the patients received second line chemotherapy. 1% achieved complete response (CR), 36% partial response (PR), 35% had stable disease (SD) and 28% progressive disease (PD). Median hTERT value was 4856 ng/ml; for patients in IIIB was 4847 ng/ml [263–964826] and 4886 ng/ml [67–4373520] in stage IV (p = 0.75). There was not association between hTERT values and response to therapy, 20588 ng/ml [122–317251] in the CR+PR group vs 50204 ng/ml [67–4373520] in the SD+PD group (p = 0.09). hTERT values were not related with the localization of the metastasis. Dividing the cohort in two sets according to hTERT median we found two significantly different groups in terms of Overall Survival (OS) and Time To Progression (TTP). Patients with hTERT &lt;4856 ng/ml had a median TTP of 5.3 months (m) [4.4–6.1] while for hTERT &gt;4856 ng/ml was 4.1 m [3.5–4.6], (p = 0.0009). OS when hTERT &lt;4856 ng/ml was 10.1m [4.9–11.3] and for hTERT &gt;4856 ng/ml was 8.4 m [7.2–9.5], (p = 0.01). In the multivariate analysis, hTERT was an independent predictive variable for TTP (HR 1.39, CI 95% 1.1–1.7, p = 0.002) and OS (HR 1.27, CI 95% 1.1–1.6, p = 0.04). Conclusions: In advanced NSCLC patients, the quantification of free circulating hTERT in plasma is an affordable and valuable prognostic marker. High plasma hTERT levels are a poor prognostic indicator for TTP and OS. No significant financial relationships to disclose.
Burnout in the practice of oncology: Results of a follow-up survey
Authors: D. A. Whippen, E. L. Zuckerman, J. W. Andersen, D. Y. Kamin, J. C. Holland
Journal: Journal of Clinical Oncology (2004)

6053 Purpose: Stress burnout among oncologists is a continuing concern, particularly as professional, economic, and political challenges have intensified over the past decade. In a 1991 study of ASCO members [SurveyI], 56% of respondents reported feeling burnout in their professional lives. SurveyII (2002) addressed whether the prevalence and scope of burnout among oncologists had changed in the intervening decade. Methods: The 1991 survey instrument was used. Additional questions from the Maslach Burnout Inventory (Maslach & Jackson, 1981) were added to enrich the burnout measure. The web-based survey was sent to 16,635 ASCO members. Results: 1,299 (12.8%) surveys were completed. SurveyII respondents were comparable to ASCO membership in sex and age ratios. 57% SurveyII respondents had >10 years in practice since their training vs 17% in SurveyI. 34% of SurveyII respondents reported burnout in their professional lives (vs 56% in SurveyI). The most often cited reasons for burnout continue to be lack of personal or vacation time (40% SurveyII vs 57% SurveyI) and exposure to fatal illness (31% SurveyII vs 53% SurveyI). Frustration with limited therapeutic success diminished over the decade (22% SurveyII vs 45% SurveyI), and the sense of frustration or failure also dropped (38% Survey II vs 56% SurveyI). Ways to alleviate stress differed slightly, with fewer SurveyII respondents choosing sabbaticals (25% vs 44%) and more personal or vacation time (46% vs 69%). A third in both surveys recommended a smaller patient load to alleviate burnout. Over half said that burnout affected their personal lives and over one-third said it affected patient care. In SurveyII, 40% said they never considered a change in job or career, and 22% considered a change a few times per year. Conclusions: Burnout continues to be reported by over one third of oncologists surveyed. The reduced sense of failure and frustration may account for the reduction in burnout from 12 years ago. More than one-third still report symptoms affecting their personal well-being and patient care. These data suggest that ASCO's programs should address burnout. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Foundation
Second-Line Treatment of Advanced Gastric Cancer: Where Do We Stand?
Authors: Amit Mahipal, Minsig Choi, Richard Kim
Journal: Journal of the National Comprehensive Cancer Network (2015)

Gastric cancer is a leading cause of cancer death and is associated with poor prognosis. The treatment of advanced gastric cancer is changing with the development of novel agents. Until recently, no standard treatment was available for patients with advanced gastric cancer in the second-line setting. Single-agent chemotherapy with docetaxel or irinotecan has been shown to improve survival and quality of life in patients whose disease has progressed while on prior chemotherapy. Combination chemotherapy is associated with a modest benefit at the expense of increased toxicity. Recently, ramucirumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF) receptor-2, has been approved for the treatment of refractory advanced gastric cancer as a single agent or in combination with paclitaxel. Apatinib, a small molecule tyrosine kinase inhibitor targeting VEGF, has demonstrated activity in Asian populations whose disease has progressed on 2 lines of therapy. However, much work is still needed, including the development of biomarkers that could predict response to therapy.
Abstract LB-032: Soluble E-cadherin as a microenvironmental factor that enhances tumor progression
Authors: Pratima Patil, Robert W. Mason, Julia D' Ambrosio, Ayyappan K. Rajasekaran
Journal: Cancer Research (2015)

Abstract During malignant transformation of epithelial cells, their well-organized architecture is disrupted. A key event observed during epithelial cancer progression is down regulation of E-cadherin (E-cad), a central adherens junction protein that plays a crucial role in directing cell polarity, epithelial architecture and cell-cell adhesion. One mechanism by which tumor cells downregulate E-cad is by the proteolytic cleavage of its extracellular domain by proteases such as the matrix metalloproteinases (MMPs). This proteolytic cleavage results in the shedding of the E-cad ectodomain as an 80 kDa fragment known as soluble E-cadherin (sE-cad). Elevated levels of sE-cad are found in the serum and urine of cancer patients. In tumor cells physiological consequences include enhanced tumor cell migration and invasion, induction of MMP secretion, and increased cell signaling; all of which ultimately result in tumor progression. sE-cad also causes morphological changes in epithelial cells, including disruption of the adherens junction. However, the influence of elevated sE-cad levels on normal tissue architecture is not well understood. Specifically, the mechanism by which sE-cad in the tumor microenvironment interacts with cellular E-cad in normal epithelium is yet to be elucidated. We used a three-dimensional (3D) cell-culture system to determine the effects of sE-cad on normal epithelial cyst morphology. In this study, we show that recombinant, purified sE-cad can induce lumen-filling in normal non-tumorigenic Madin-Darby canine kidney (MDCK) epithelial cysts. The acinar luminal filling and multiple lumen formation induced by purified sE-cad represent changes in epithelial tissue structure that are characteristic of premalignant lesions reported in human epithelial glandular tumors. We further demonstrate that co-culturing of tumor cells with epithelial MDCK cysts results in disruption of 3D epithelial architecture and filling up of the hollow lumen. Our results also show that tumor cell-induced lumen filling is trigged by sE-cad shedding, with a concomitant increase in MMP-9. Using an inhibitor of MMP-9, we provide evidence that MMP-9 is crucial for lumen filling. Together, these novel findings indicate that invasive carcinoma cells can induce structural alterations in adjacent normal epithelium, and that elevated sE-cad levels disrupt epithelial architecture and activate signaling pathways in normal epithelial cells. Citation Format: Pratima Patil, Robert W. Mason, Julia D' Ambrosio, Ayyappan K. Rajasekaran. Soluble E-cadherin as a microenvironmental factor that enhances tumor progression. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-032. doi:10.1158/1538-7445.AM2015-LB-032
Kinetic Modeling and Constrained Reconstruction of Hyperpolarized [1-13C]-Pyruvate Offers Improved Metabolic Imaging of Tumors
Authors: James A. Bankson, Christopher M. Walker, Marc S. Ramirez, Wolfgang Stefan, David Fuentes, Matthew E. Merritt, Jaehyuk Lee, Vlad C. Sandulache, Yunyun Chen, Liem Phan, Ping-Chieh Chou, Arvind Rao, Sai-Ching J. Yeung, Mong-Hong Lee, Dawid Schellingerhout, Charles A. Conrad, Craig Malloy, A. Dean Sherry, Stephen Y. Lai, John D. Hazle
Journal: Cancer Research (2015)

Hyperpolarized [1-(13)C]-pyruvate has shown tremendous promise as an agent for imaging tumor metabolism with unprecedented sensitivity and specificity. Imaging hyperpolarized substrates by magnetic resonance is unlike traditional MRI because signals are highly transient and their spatial distribution varies continuously over their observable lifetime. Therefore, new imaging approaches are needed to ensure optimal measurement under these circumstances. Constrained reconstruction algorithms can integrate prior information, including biophysical models of the substrate/target interaction, to reduce the amount of data that is required for image analysis and reconstruction. In this study, we show that metabolic MRI with hyperpolarized pyruvate is biased by tumor perfusion and present a new pharmacokinetic model for hyperpolarized substrates that accounts for these effects. The suitability of this model is confirmed by statistical comparison with alternates using data from 55 dynamic spectroscopic measurements in normal animals and murine models of anaplastic thyroid cancer, glioblastoma, and triple-negative breast cancer. The kinetic model was then integrated into a constrained reconstruction algorithm and feasibility was tested using significantly undersampled imaging data from tumor-bearing animals. Compared with naïve image reconstruction, this approach requires far fewer signal-depleting excitations and focuses analysis and reconstruction on new information that is uniquely available from hyperpolarized pyruvate and its metabolites, thus improving the reproducibility and accuracy of metabolic imaging measurements.