tbuckley/cabot-search huggingface dataset:
Retrospective study of phase I clinical trials participation in patients at least 65 years of age at Karmanos Cancer Institute (KCI), Wayne State University, Detroit, Michigan
Authors: P. Vishnu, P. Jasti, L. Ding, L. K. Heilbrun, R. Venkatramanamoorthy, P. M. LoRusso, E. I. Heath
Journal: Journal of Clinical Oncology (2009)

e20626 Background: It is important to increase our understanding of recruitment barriers in the elderly population to improve their participation in clinical trials. The primary objective of this study was to describe the demographics, treatment, toxicity, and overall survival (OS) of all patients ≥ 65 years who presented to the Phase I clinical trials service at KCI between 1995–2005. Methods: Patient demographics, co-morbidities, tumor type, reason not enrolled on a Phase 1 clinical trial, toxicities, and OS were obtained by retrospective chart reviews. The patients were divided into 3 mutually exclusive groups: patients considered but not enrolled (PC), enrolled but not treated (PE), and treated (PT). OS was compared across these three groups. Results: 216 patients met the study criteria. Of these, there were 114 PC, 7 PE, and 95 PT. Lack of enrollment was due to ineligibility (30%), loss to follow-up (12%), refusal (8%), or no trial available (2%). Median age was 71 years, 63% were males and 87% were Caucasian. 59% had performance status (PS) 1; 16% had PS 2. 66% of patients had a history of cardiovascular disease but renal, liver, hematological diseases were found in less than 7% of patients at baseline. Colorectal (27%), lung (15%) and prostate (8%) were the 3 most common cancers. 54% received a cytotoxic agent, 62% a biologic agent, and 17% combination therapy. The 3 most common Grade 3–4 toxicities were: 15% leucopenia, 11% electrolyte abnormalities, and 4% anemia. The median OS for PC, PE, and PT was 3.9 mos, 2.2 mos, and 8.4 mos, respectively (p &lt; 0.001 between any pair). However, PS 0–1 patients comprised 47%, 75%, and 73% of those 3 patient subgroups, respectively. Conclusions: More than half of the elderly patients initially considered for Phase 1 clinical trials at KCI were not enrolled due to ineligibility, refusal, or lost to follow up. Phase I chemotherapy appears feasible in patients age ≥ 65 years old. OS was significantly longer for patients treated on Phase I trials compared to those who were not, although that may be confounded by PS differences. More detailed OS comparisons will be presented. No significant financial relationships to disclose.
Guideline-discordant androgen deprivation therapy (ADT) use in localized prostate cancer (CaP) and cost implications: A population-based study.
Authors: Adam Rea Kuykendal, Laura H Hendrix, Ramzi George Salloum, Paul Alphonso Godley, Ronald C. Chen
Journal: Journal of Clinical Oncology (2012)

4647 Background: ADT use in localized CaP has increased overall survival and is recommended by National Comprehensive Cancer Network (NCCN) guidelines in certain clinical situations. However, ADT may cause harm and is without benefit in other situations. Prior studies showed a decline in “inappropriate” ADT use coinciding with Medicare reimbursement changes in 2004-2005. This study examines recent trends in ADT use and quantifies the cost of guideline-discordant ADT. Methods: Patients in the Surveillance Epidemiology and End Results (SEER)-Medicare database diagnosed with non-metastatic CaP between 2004 and 2007, ages 66-80 were included for analysis. PSA, Gleason score and clinical stage were used to define D’Amico risk categories. Logistic regression was used to examine factors associated with guideline-discordant ADT use. Annual direct cost was estimated using the current Medicare reimbursement amount for ADT. Results: Of 24,280 men included, 13% received guideline-discordant ADT. Discordant use declined from 15% in 2004 to 11% in 2007. In low-risk patients, 15% received discordant ADT, mostly due to simultaneous ADT with radiation. Discordant use was seen in 7% of intermediate and 16% of high-risk patients, mostly from ADT monotherapy. African American (AA) (p&lt;.001), older patients (p&lt;.001) and those with more comorbidities (p&lt;.001) were more likely to receive discordant ADT (Table). The estimated annual direct cost to Medicare from discordant ADT is $43,500,000. Conclusions: Approximately one in eight patients received ADT discordant with published guidelines, with AA and elderly patients disproportionately affected. Elimination of discordant use would result in substantial savings in healthcare costs. [Table: see text]
Patients with breast cancer feel empowered by their participation in online support groups
Authors: W. M. Smit, C. F. van Uden-Kraan, C. H. Drossaert, E. R. Seydel, E. Taal, M. A. van de Laar
Journal: Journal of Clinical Oncology (2007)

19544 Background: People often join support groups when they find themselves in stressful circumstances such as serious health conditions. With the increase in the availability and popularity of the Internet, the opportunity to join support groups online has arisen. Ever since the rise of online support groups, much is expected of the potential empowering effect of taking part in these groups for patients. However, thus far, there is no direct evidence. Therefore the purpose of this study was to explore if and how people with breast cancer feel empowered by their participation in online support groups and which processes that take place in online support groups contribute to these outcomes. Methods: We have sent a posting with a link to an online survey to 7 online support groups for patients with breast cancer. In total 214 participants responded to the request to fill in the survey. Results: The majority of the respondents were women (n=211). The mean age of the respondents was 46 years (SD 8.9 years). The respondents were diagnosed 3 years ago on average, with a range of 0 to 15 years. The respondents felt empowered in several ways by their participation. First of all, most respondents (74%) felt better informed. They indicated that as a result of their participation, they had received adequate information to deal with their disease (60%). Additionally, most participants felt more confident in the relation with their physician. The participants indicated that they knew better which questions to ask their physician (69%) and that they felt better prepared for a consult with their physician (61%). For some of the respondents, participation in an online support group enabled easier acceptation of the disease (48%) and helped them to “open up” about their disease (49%). The main processes that contributed to these outcomes were: exchanging information, comparing with other participants and encountering social support. Conclusions: This study suggests that participation in online support groups can make a valuable contribution to the emergence of empowered patients, who set their own health agendas and who take control of their own health status, as is deemed necessary in the current transformation towards a modern health care consumer model. No significant financial relationships to disclose.
Myocardial MMP-2 contributes to SERCA2a proteolysis during cardiac ischaemia–reperfusion injury
Authors: Andrej Roczkowsky, Brandon Y H Chan, Tim Y T Lee, Zabed Mahmud, Bridgette Hartley, Olivier Julien, Gareth Armanious, Howard S Young, Richard Schulz
Journal: Cardiovascular Research (2019)

Matrix metalloproteinase-2 (MMP-2) is a zinc-dependent protease which contributes to cardiac contractile dysfunction when activated during myocardial ischaemia-reperfusion (IR) injury. MMP-2 is localized to several subcellular sites inside cardiac myocytes; however, its role in the sarcoplasmic reticulum (SR) is unknown. The Ca2+ ATPase SERCA2a, which pumps cytosolic Ca2+ into the SR to facilitate muscle relaxation, is degraded in cardiac IR injury; however, the protease responsible for this is unclear. We hypothesized that MMP-2 contributes to cardiac contractile dysfunction by proteolyzing SERCA2a, thereby impairing its activity in IR injury.Isolated rat hearts were subjected to IR injury in the presence or absence of the selective MMP inhibitor ARP-100, or perfused aerobically as a control. Inhibition of MMP activity with ARP-100 significantly improved the recovery of cardiac mechanical function and prevented the increase of a 70 kDa SERCA2a degradation fragment following IR injury, although 110 kDa SERCA2a and phospholamban levels appeared unchanged. Electrophoresis of IR heart samples followed by LC-MS/MS confirmed the presence of a SERCA2a fragment of ∼70 kDa. MMP-2 activity co-purified with SR-enriched microsomes prepared from the isolated rat hearts. Endogenous SERCA2a in SR-enriched microsomes was proteolyzed to ∼70 kDa products when incubated in vitro with exogenous MMP-2. MMP-2 also cleaved purified porcine SERCA2a in vitro. SERCA activity in SR-enriched microsomes was decreased by IR injury; however, this was not prevented with ARP-100.This study shows that MMP-2 activity is found in SR-enriched microsomes from heart muscle and that SERCA2a is proteolyzed by MMP-2. The cardioprotective actions of MMP inhibition in myocardial IR injury may include the prevention of SERCA2a degradation.
Clozapine and Evidence-Based Psychopharmacology for Schizophrenia
Authors: T. Scott Stroup
Journal: JAMA Psychiatry (2019)

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Hepatic arterial infusion (HAI) of oxaliplatin in advanced hepatocellular cancer (HCC): A phase I study
Authors: R. Rathore, D. Iannitti, G. Soares, H. Wanebo, C. Maia-Aucna, H. Safran
Journal: Journal of Clinical Oncology (2006)

14010 Background: We performed this phase I study is to evaluate the feasibility and determine the Maximally Tolerated Dose of HAI-oxaliplatin given every 3 weeks in advanced HCC. Methods: Patients (pts) with unresectable or recurrent HCC were eligible for therapy on this protocol. HAI-oxaliplatin was administered over 2 hours via a percutaneously placed hepatic arterial catheter or a surgically inserted hepatic arterial infusion pump. Therapy was continued until disease progression or excessive toxicity not amenable to appropriate modifications. Restaging was performed after every 2 cycles. Dose escalation levels for HAI-oxaliplatin are 90 mg/m 2 , 110 mg/m 2 , 130 mg/m 2 and 150 mg/m 2 given every 3 weeks. Results: A total of 16 patients have been enrolled and toxicity data are available for all patients. Median age was 61 yrs (range 47–84 yrs), there were 15 men and 1 woman. The stage distribution is: stage II-3 pts, stage III- 7 pts, stage IV- 6 pts. Prior therapies including chemoembolization (CE) in 3 pts, radiofrequency ablation (RFA) in 3 pts, and both RFA and CE in 1 pt. A total of 37 cycles (range 1–3) have been delivered. Levels 1 and 3 had to be expanded to 6 pts each due to major toxicity in 2 pts at each level. Level 2 was expanded as 1 pt was non-compliant. Major toxicities are shown below. One patient developed embolic bowel ischemia after his HAI procedure. There was one episode each of duodenal perforation and duodenal ulceration. Traditional grade 3/4 hematologic and gastrointestinal toxicities were infrequent. Among 13 pts receiving at least 2 cycles, 3 pts had partial responses (PR) and 4 pts had stable disease (SD). Greater than 50% reduction in AFP was seen in the 3 pts with PR and 2 pts with SD. Conclusions: HAI-oxaliplatin is feasible, well tolerable, and demonstrates activity in this population of pts with advanced HCC. [Table: see text] No significant financial relationships to disclose.
Tolerogenic signaling of alveolar macrophages induces lung adaptation to oxidative injury
Authors: Benoit Allard, Alice Panariti, Erwan Pernet, Jeffrey Downey, Satoshi Ano, Marieme Dembele, Emily Nakada, Utako Fujii, Toby K McGovern, William S Powell, Maziar Divangahi, James G Martin
Journal: Journal of Allergy and Clinical Immunology (2019)
Development and validation of the hand-foot reaction and quality of life (HF-QoL) questionnaire for oncology.
Authors: Roger T. Anderson, Karen N. Keating, Helen A Doll
Journal: Journal of Clinical Oncology (2013)

e20537 Background: Skin toxicity (hand-foot syndrome and hand-foot skin reaction, HFS/R) related to antineoplastic therapy is a significant issue in oncology practice with potentially large impacts on health-related quality of life (HRQL). Methods: A brief, patient self-reported questionnaire, The Hand-Foot Quality of Life (HF-QoL), was developed to measure HFS/R symptoms associated with cancer therapeutic agents and their effect on daily activities. The validity and reliability of the HF-QoL was tested in a phase 2b trial of sorafenib in 223 patients with locally advanced or metastatic breast cancer. Other measures completed included a patient rating of condition severity, the FACT-B, and the clinician-rated NCI-CTCAE [version 3.0] grading for rash. Psychometric properties tested included factor loadings, internal consistency, construct and discriminant validity, and responsiveness. The minimal clinically important difference (MCID) was estimated. Results: The final HF-QoL instrument comprises a 20-item Symptom rating scale and an 18-item Daily Activities scale. Each scale demonstrated excellent measurement properties and strongly discriminated between NCI-CTCAE grade and patient-rated condition severity with moderate to large effect sizes (&gt;0·50 standard deviation). The Daily Activities domain had excellent internal consistency (Cronbach’s alpha 0·96) and was correlated with FACT-B, FACT-G (both r=-0·53) and Symptom scores (r=0·82). Both HF-QoL scores increased notably and linearly with increasing patient-rated condition severity (p&lt;0·001). The MCIDs were estimated as 4 units for Daily Activities and 6 units for Symptoms means. Conclusions: The HF-QoL is a valid and reliable measure of symptoms associated with HFS/R and its effects on daily activities in this population of patients with advanced breast cancer. The HF-QoL is thus suitable for assessing HRQL impairment associated with HFS/R with cancer chemotherapeutic agents.
Gemcitabine and plasmacytic non-Hodgkin lymphoma response.
Authors: Ahmad Jajeh
Journal: Journal of Clinical Oncology (2013)

e19537 Background: Lymphomas are highly sensitive to chemotherapy. Gemcitabine is an active agent in non-Hodgkin lymphomas NHL. It is a diflourinated analogue of deoxycytadine which acts as antimetabolite. It is cell cycle specific and blocks cells in the G1/S interface. Gemcitabine is a better substrate for transport into cells. Active phosphorylated form is more readly and is excreted more slowly than other drugs. It inhibit DNA synthesis via depletion of cellular deoxynucleotide pools and by way of masked DNA chain termination. Gemcitabine seem to work it best on indolent and plasmacytoid low grade and intermediate NHL. Gemcitabine is also an active agent in Hodgkin lymphoma, Diffuse large B Cell NHL and T cell lymphomas. Methods: Retrospective reviews of patients with B cell NHL treated with gemcitabine as a single agent or in combination was carried out in one single institution over the last 13 years. Reveiw of biopsy reports and histology with immunostaining and flowcytometry done. This include CD20, CD10, BCL2, BCL6, MUM1, CD5, and cyclin D1. Clinical correlation with outcome CR, PR and Overall survival was done. Results: Forty patients with B cell lymphoproliferative disorders NHL were identified; five with mantle cell, ten with marginal zone and plasmacytoid morphology, fifteen with Diffuse Large B Cell Lymphoma DLBCLand ten with other low grade morphology. No correlation with germinal type versus post germinal (activated type) found in term of response. Plasmacytoid/ marginal zone type and mantle cell seem to have the best significant durable response when compared to DLBCL and other low grade NHL. Of note most patients received gemcitabine after failure to rituximab-CHOP and as salvage therapy in post second- and third-line failure. Conclusions: Gemcitabine may have more durable activity if used as a first-line combination therapy. Larger group of patients analysis needed to see if this agent has more activities in germinal than activated type of DLBCL. Plasmacytoid NHL seem to have more rapid and durable respone in our analysis.
Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass
Authors: Eric M. Graham, Reneé H. Martin, Jason R. Buckley, Sinai C. Zyblewski, Minoo N. Kavarana, Scott M. Bradley, Bahaaldin Alsoufi, William T. Mahle, Marc Hassid, Andrew M. Atz
Journal: Journal of the American College of Cardiology (2019)
Prediction of short-term outcome in terminally ill cancer patients
Authors: J. Durand, S. Pourchet, F. Goldwasser
Journal: Journal of Clinical Oncology (2007)

19572 Background: Oncologists tend to overestimate survival of advanced cancer patients (pts) emphasizing the need for objective prognostic models to prevent futility. Methods: From January 2004 to May 2006, a prospective unicenter study was done in terminally ill cancer pts referred to a palliative care unit. Evaluation at admission included physical examination and the following routine blood tests : total blood count, hemostasis (Prothrombin Time (PT), activated Partial Thromboplastin Time (aPTT)), inflammatory and nutritional proteins (fibrinogen, ferritin, PINI = [alpha-1 acid glycoprotein x C-reactive protein (CRP)] / [albumin x prealbumin]), serum lipids (total and HDL cholesterol), biochemistry (urea, serum creatinine, calcium, total bilirubin, B12 vitamin) and liver enzymes (AST, ALT, LDH). Fatal outcome within the first 48 hours and lack of blood tests were exclusion criteria. A multivariate analysis according to a logistic regression was used to estimate the probability of fatal outcome within 2 weeks (wks) based on baseline patients characteristics. Results: 285 consecutive pts were hospitalized; 246 were evaluable : 133 men and 113 women (median age : 64 years; range: 18–94). Primary tumor was gynecological (18.3%), gastro-intestinal (16.3%), pulmonary (13.4%), hepatic or biliary (13.8%), urological (11.8%), head and neck (9.3%), haematological (3.3%) or others (13.8%). In univariate analysis, survival ≤ 2 wks correlated with male gender (p&lt;0.001), Karnofsky Index (KI) (p&lt;0.001), leucocytes (WBC) (p&lt;0.001), aPTT (p=0.04), Urea (p=0.011), Total bilirubin (p=0.004), AST (p&lt;0.001), LDH (p=0.008), albumin (p=0.042), prealbumin (p=0.004), CRP (p=0.028), ferritin (p=0.007), B12 vitamin (p=0.042) and PINI (p=0.001). In multivariate analysis, male gender (p=0.034), cutaneous metastases (p=0.012), KI ≤ 20% (p=0.002), WBC &gt; 7.5G/l (p=0.012), fibrinogen &gt; 6.5 g/l (p=0.021), LDH &gt; 2N (p=0.035) and PINI &gt; 20 (p=0.007) were predictive. A mathematical model was built to estimate the probability of fatal outcome within 2 wks. Conclusions: We created a tool which may help physicians to better estimate survival of terminally ill cancer pts and to prevent unnecessary overtreatment. Our score needs prospective validation in a multicenter study. No significant financial relationships to disclose.
Anti-androgen resistance in prostate cancer cells induced by IL-1β.
Authors: Xinhua Zhu, Julia Staverosky, Susan Logan
Journal: Journal of Clinical Oncology (2013)

e16057 Background: Chronic inflammation has been linked to cancer initiation and progression in a variety of tissues. The impact of acute and chronic inflammatory signaling on androgen receptor (AR) function has not been widely studied. We employed IL-1β, one of important cytokines responsible for inflammation to treat LNCaP, which is both androgen- and bicalutamide-sensitive prostate cells. Methods: To mimic the effects of inflammation on AR function, we treated the LNCaP prostate cancer cell line either acutely or chronically with IL-1β. AR protein and mRNA expression levels were examined over time course of IL-1β stimulation in either the presence or absence of the synthetic androgen, R1881. The population of cells chronically treated with IL-1β are called LNCaP-CI. Chromatin immunoprecipitation was used to measure the active epigenetic marks H3K4 dimethylation on the enhancer of M phase genes such as CDC20, CDK1 and UBE2C. mRNA level of AR, CDC20, CDK1 and UBE2C was done with quantitative PCR. Results: Acute IL-1β treatment inhibits the transcription of the AR gene itself, resulting in the reduction of AR protein levels. In cells subjected to chronic IL-1β stimulation, the transcription of the AR gene is restored within a few cell passages, and the cells acquire the ability to grow in the presence of the anti-androgen, bicalutamide. Using chromatin immunoprecipitation, we found that acquired bicalutamide resistance in chronic IL-1β treatment correlates with increased selective active epigenetic mark H3K4me2 occupancy on the M-phase gene enhancer of UBE2C, CDC20 and CDK1 through AR recruitment and subsequent up-regulation of the M-phase genesin LNCaP-CI cells. Conclusions: Bicalutamide resistance induced by IL-1β recapitulates the biological properties of LNCaP-abl (CRPC cells) and CRPC clinical cases through upregulation of M-phase genes, suggesting that chronic inflammation, induced by IL-1β characterizes the development of CRPC from androgen-dependent prostate cancer transformation. The data will lead to further investigation of identifying potential therapeutic targets in IL-1β pathway to prevent the process of this lethal transformation.