tbuckley/cabot-search huggingface dataset:
Clinical Impact of Stereotyped Antigen Receptors in Chronic Lymphocytic Leukemia
Authors: Panagiotis Baliakas, Anastasia Hadzidimitriou, Lesley-Ann Sutton, Evangelia Minga, Andreas Agathangelidis, Athina Tsanousa, Lydia Scarfo, Zadie Davis, Joy Yan, Tait D. Shanafelt, Karla Plevova, Yorick Sandberg, Fie Juhl Vojdeman, Myriam Boudjoghra, Tatiana Tzenou, Maria Chatzouli, Charles C. Chu, Silvio Veronese, Anne Catherine Gardiner, Larry Mansouri, Karin E Smedby, Lone Pedersen, Denis Moreno, Kirsten van Lom, Veronique Giudicelli, Hana Francova, Florence Nguyen-Khac, Panagiotis Panagiotidis, Gunnar Juliusson, Lefteris Angelis, Achilles Anagnostopoulos, Marie-Paule Lefranc, Monica Facco, Livio Trentin, Mark Catherwood, Marco Montillo, Christian H Geisler, Anton W Langerak, Sarka Pospisilova, Nicholas Chiorazzi, David Oscier, Diane F. Jelinek, Nikos Darzentas, Chrysoula Belessi, Frederic Davi, Richard Rosenquist, Paolo Ghia, Kostas Stamatopoulos
Journal: Blood (2014)
Barriers for accrual to clinical trials in adult patients (pts) with thoracic malignancies
Authors: M. Q. Baggstrom, E. Gilstrap, A. Skelton, A. Viswanathan, D. Morgensztern, P. A. Nations, D. Foersterling, R. Govindan
Journal: Journal of Clinical Oncology (2006)

6058 Background: Despite recent advances in the treatment of pts with thoracic malignancies, the outcome continues to be poor. Only about 3% of all adult oncology pts enroll in clinical trials compared to approximately 50% of pediatric pts. The proportion of adult pts enrolled in clinical trials is low, even in tertiary cancer centers. It is critical to understand the barriers for accrual to clinical trials. Methods: We reviewed the outpatient charts of all pts with thoracic malignancies (non-small cell lung cancer [NSCLC], small cell lung cancer, and esophageal cancer) referred to the thoracic medical oncology group at our institution from 11/1/2004 to 10/31/2005. Available and appropriate clinical trials are presented to the pts routinely and reasons for non-enrollment are documented. We collected information on histology, stage, performance status (PS) and co-morbid conditions. Appropriate studies at the time of initial consultation were noted from database. Results: Of 284 consecutive patient charts reviewed, 13 pts (4.6%) did not require therapy, 6 pts (2.1%) were deemed to have a non-thoracic primary on review, and 15 pts (5.3%) had already initiated therapy at the time of consultation. Of the remaining 250 evaluable pts, 88 pts (35.2%) were not enrolled because of lack of available appropriate clinical trials at the time of initial consultation. The most common categories were adjuvant therapy for early stage NSCLC and advanced esophageal cancer. Twenty-one pts (8.4%) enrolled onto a clinical trial. The most common reasons for not participating in a clinical trial include: ineligibility due to PS (28 pts, 11.2%), geographic issues (23 pts, 9.2%), patient refusal (16 pts, 6.4%) and co-morbid conditions (9 pts, 3.6%). Ten pts (4.0%) were lost to follow up. Conclusions: 1. Lack of appropriate and available clinical trials and poor PS are the two most common reasons for lack of patient enrollment in clinical trials at our institution. 2. It is critical to develop innovative clinical trials for pts with advanced esophageal cancer, adjuvant therapy in early stage NSCLC, and poor PS. 3. More work is needed to understand patient perception about clinical trials. [Table: see text]
Faces of lung cancer: A multi-media intervention to increase clinical trial accrual
Authors: G. P. Quinn, S. T. Vadaparampil, G. Bepler
Journal: Journal of Clinical Oncology (2008)

17536 Background: Lung cancer patients report stigma associated with their disease and believe most cancer related materials are not specifically for lung cancer, but rather for breast or prostate. Furthermore, despite the abundance of lung related clinical trials (CT), less than 3% of all eligible patients are on a trial. Formative research with this patient population revealed myths and misperceptions associated with CT. The purpose of the project was to identify cognitive barriers to CT participation among newly diagnosed lung cancer patients and to develop and evaluate media materials designed to increase awareness and reduce misperceptions related to CTs. Methods: In-depth interviews were conducted with 26 lung cancer patients who were either new patients (n=16) or existing patients (n=10) to assess and compare awareness of and barriers to CTs. Results: Results showed that regardless of patient status, there were similar myths associated with clinical trials (CT) including the belief that: CTs were a last resort; being offered a CT implied there was no hope for the patient; patients on CT were treated as “guinea pigs”; there was stigma of lung cancer related to smoking; no one they knew had ever been on a trial. Based on these results and media preferences expressed by patients, we created Faces of Lung Cancer, a multi-media intervention to increase awareness of CTs and reduce misperceptions. Faces of Lung Cancer includes: a website (www.facesoflungcancer.com), book, brochure, and framed exhibit of photos and essays of lung cancer patients of all ages and races who participated in a CT, along with health care professionals who assist with CTs. Conclusion: On-going evaluations indicate all forms of the media have increased awareness and reduced myths. Respondents agreed lung cancer patients and their loved ones would benefit from the project (M = 4.80, SD = 0.41), the essays were easy to read (M = 4.84, SD = 0.37), Faces of Lung Cancer photo essay is a powerful tool for communicating important information (M = 4.80, SD = 0.41) No significant financial relationships to disclose.
Screening with prostate specific antigen and metastatic prostate cancer risk: A population-based case-control study
Authors: J. A. Kopec, V. Goel, P. S. Bunting, J. Neuman, E. C. Sayre, P. Warde, P. E. Levers, N. Fleshner
Journal: Journal of Clinical Oncology (2004)

4651 Background: Screening of asymptomatic men with the prostate specific antigen (PSA) is a highly controversial issue. There is little evidence to date that such screening is effective in reducing mortality from prostate cancer. We conducted a population-based case-control study to determine if screening with PSA reduces the risk of metastatic prostate cancer. Methods: The study was carried out in Metropolitan Toronto and five surrounding counties in Ontario, Canada. Cases were men diagnosed with metastatic prostate cancer between August 1, 1999 and May 31, 2002. Controls were randomly sampled from the source population and matched to cases for age, area of residence, and observation time. Medical records and a self-administered questionnaire were used to collect the data. We obtained information on PSA testing, digital rectal exams, symptoms, comorbidity, use of health services, as well as known and suspected risk factors for prostate cancer. Analyses were performed on 236 cases and 462 controls. Results: After adjustment for observation time, the frequency of screening among asymptomatic men was 24.6% in the cases and 33.1% in the controls (odds ratio 0.66, 95% confidence interval 0.47 to 0.92). Self-reported screening was also significantly less frequent among the cases (odds ratio 0.48, 0.34 to 0.67). No significant confounding was found in multiple logistic regression analyses. Secondary analyses including symptomatic and asymptomatic men showed that the cases generally had fewer symptoms and fewer PSA tests than the controls, except for the last year before the diagnosis of prostate cancer. In symptomatic men, the association between PSA testing and metastatic prostate cancer was not significant. Conclusions: The results suggest that screening of asymptomatic men with PSA may substantially reduce the risk of metastatic prostate cancer. Further research is needed to confirm these results in a randomized trial and to assess the economic and quality of life aspects of PSA screening. No significant financial relationships to disclose.
Socioeconomic and racial disparities in the selection and outcomes of a chest-wall boost in post-mastectomy radiation therapy.
Authors: Clayton Burnett Hess, Kari Fish, Megan Eileen Daly, Jyoti Mayadev
Journal: Journal of Clinical Oncology (2013)

14 Background: We investigated socioeconomic and racial disparities in the selection and outcomes of patients from the California Cancer Registry receiving post-mastectomy radiation therapy (PMRT) with or without a chest-wall boost (CWB). Methods: Records of 5,586 women with invasive breast cancer, diagnosed from 2005-2009, treated with PMRT were reviewed and stratified based on treatment with (n=2,482 [44%]) or without (n=3,104 [56%]) a CWB. Race and socioeconomic status (SES) between the cohorts were analyzed. Bivariate analyses of the impact of race and socio-demographic factors on breast cancer-specific survival (BCS) and overall survival (OS) were performed using the Kaplan-Meier method. Adjusting for potential confounders, we used multivariate proportional hazards models to identify predictors of BCS and OS, reported as hazard ratios (HR) with 95% confidence intervals (CI). Results: The majority of PMRT patients were white (58%), compared to Hispanic (20%), Asian/Pacific-Islander (15%), and black (6%). Most were of high SES (50%), compared to middle (21%) or low (29%). Non-white patients were more frequently of low SES (59% vs. 40%). Hispanic frequency (61%) of advanced-stage (3-4) disease was the highest of all races. Low SES was also associated with higher stage (37% vs. 60%) compared to high SES, which comparatively presented with lower-stage (1-2) disease (42% vs. 57%, p=0.0187). Low-SES patients were more likely to receive a CWB (31 vs. 26%) while high-SES patients were less likely (48% vs. 53%, p&lt;0.0001). White women were more likely to be treated without a CWB (60 vs. 57%), while Hispanic women were less likely (23% vs. 18%, p=0.0003). Women not treated with a CWB with low SES had a lower BCS (HR 1.541 p=0.0114) and OS (HR 1.794. p=&lt;0.001) compared to women of high SES. Black women not treated a CWB had lower OS (HR 1.712, p=0.0249) compared to similarly-treated white women. Conclusions: Low SES and Hispanic race were associated with advanced stage, and more commonly treated with a CWB. Low-SES and black women treated without a CWB had lower OS, while the former also had lower BCS. These findings suggest that economic and racial health-care disparities contribute to worse outcomes.
LX1032: A potential new therapy for carcinoid syndrome (CS)
Authors: C. Pappas, A. Turnage, K. S. Frazier, Q. Liu, P. Brown
Journal: Journal of Clinical Oncology (2009)

e14555 Background: Patients with metastatic CS experience a variety of symptoms due to increased serotonin (5-HT) produced by metastatic GI tumor cells. The enzyme tryptophan hydroxylase (TPH) catalyzes the rate-limiting step in the synthesis of 5-HT. Reducing 5-HT synthesis by TPH inhibition represents a new mechanism for potentially managing symptoms associated with CS. LX1032 is a novel, orally bioavailable TPH inhibitor designed to afford systemic exposure without affecting 5-HT synthesis in the CNS. Preclinical studies of LX1032 in multiple species confirmed systemic inhibition of 5-HT synthesis without changes in brain 5-HT levels. Methods: Single (n=47 subjects) and multiple (n=40 subjects) ascending dose studies with LX1032 were completed in normal volunteers; 24-hr urinary 5-HIAA and blood 5-HT were measured as biomarkers of 5-HT metabolism. Results: LX1032 produced a significant dose-dependent reduction in urinary 5-HIAA and blood 5-HT levels, with maximal reductions observed at doses at or above 500 mg, once daily, in the 14 day multiple ascending dose (MAD) study; the mean change from baseline in blood 5-HT was -30% for the 1500 mg (500 mg TID) dose group. Single doses up to 500 mg were well tolerated with no evidence of dose limiting toxicity or tolerability; GI related adverse events (nausea, emesis, and diarrhea) started to emerge at the 1,000 mg dose level and became dose-limiting at the 1,500 mg single dose level. Multiple doses were well tolerated at all dose levels up to 1.500 mg (500 mg TID). Adverse events (AEs) were mild to moderate and no serious AEs occurred; a dose-dependent, mild increase in hepatic transaminase levels was observed in the MAD study. Conclusions: Inhibiting TPH, and thereby reducing peripheral 5-HT production, represents a potential new approach for managing symptoms in CS patients. LX1032 is a novel, orally bioavailable TPH inhibitor that significantly reduced 5-HT production at well tolerated dose levels. The favorable safety profile and observed decrease in urinary 5-HIAA and blood 5-HT levels indicate that LX1032 could be used to lower 5-HT as a potential new approach for managing hyperserotoninemia-related complications of CS, and support studies of the compound in CS patients. [Table: see text]
Characterisation and Prognostic Significance of WT-1 Gene Expression in Acute Myeloid Leukemia (AML).
Authors: Steven W. Lane, Russell Saal, Suzanne Negus, Peter Mollee, M. Mather, Devinder Gill, Anthony K. Mills, Robert J. Bird, Matthew J. Hourigan, Mark Jones, Paula Marlton
Journal: Blood (2006)
Compliance with oral topotecan in patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC)
Authors: J. R. Eckardt, R. Ramlau, R. Gervais, F. Shepherd, M. O’Brien, T. Ciuleanu, B. Dharan, P. Wissel, G. Ross
Journal: Journal of Clinical Oncology (2006)

7092 Background: Compliance with chemotherapy can affect treatment efficacy and patient safety. Selecting an oral chemotherapy regimen with good tolerability in appropriate patients is important. To determine general level of compliance of oral topotecan, a retrospective analysis was conducted on 3 international open-label, multicenter, 2-arm randomized, phase III studies of patients with NSCLC and SCLC. Methods: Patients were randomized to receive oral topotecan d1–5 q21d as follows: Study 387 (Ramlau et al, Proc ASCO, 2005) 2.3 mg/m 2 /d second-line vs IV docetaxel for NSCLC; Study 389 (Eckardt et al, Proc ASCO, 2005) 1.7 mg/m 2 /d first-line with cisplatin vs etoposide/cisplatin for extensive-disease SCLC; and Study 478 (O’Brien et al, Lung Cancer 2005) 2.3 mg/m 2 /d second-line vs best supportive care for SCLC. Oral topotecan was administered to the patient in the clinic on day 1 of each course and the patient was responsible for self-administering the oral capsules the remaining 4 days of dosing. Patient compliance was defined as 100x(sum of number of caps taken across courses)/(sum of number of caps dispensed across courses), where number of caps taken = number of caps dispensed-number of caps returned. Results: Accrual per arm was (387), 414 patients; (389) 389; (478) 71. In the treated population for all three groups, adherence to oral topotecan was high, with &gt;90% of patients recording at least 90% overall compliance (Table). Mean age (% ≥65 years/%PS 2) was (387) 58.8 years (29.2%/14%), (389) 59.7 (32.6%/13%), and (478) 59.8 (33.8%/27%). Median oral topotecan dose intensity (% target) for each course was (387) 87%, (389) 95%, and (478) 98%. The most common reason for dose reductions or delays was hematological toxicity. Conclusions: Oral topotecan can be administered on an outpatient basis with a high degree of patient compliance in the treated population, which included those ≥65 years and those with poor PS. [Table: see text] [Table: see text]
Abstract 145: Mitophagy Protects Against Statin-Induced Cell Death in Muscle Cells
Authors: Allen Andres, Mridula Ramesh, Genaro Hernandez, Michael Gurney, Phyllis-Jean Linton, Moutusee Islam, Roberta Gottlieb
Journal: Circulation Research (2014)

Statins are a family of cholesterol lowering drugs associated with undisputable cardiovascular benefits. However, their use is associated with the risk of developing skeletal muscle myopathy which remains a significant barrier to maximizing the efficacy of statin therapy. Many recognize that the instances of statin-associated myopathy reported grossly underestimate the actual frequency of these events. Statin myopathy is a major reason for why many patients are unable to comply with their prescribed statin treatments. Identifying and understanding the molecular events involved in the development of statin-induced myopathy will pave the way to mitigating the unwanted effect of statin-myopathy. We have identified that statins induce mitochondrial loss in both C2C12 myotubes, and in gastrocnemius muscle of mice evidenced by loss of mitochondrial markers Tom70 and Cox4 by western blot analysis. C2C12 myotubes were treated with 2μM simvastatin for 24 hours, and wild-type C57BL/6 mice were given a daily i.p. dose of 20mg/kg simvastatin for 2 weeks. Pretreatment of C2C12 cells with 100nM bafilomycin for 2 hours before statin treatment attenuated autophagic flux, and prevents the observed loss of mitochondria through Tom70 and Cox4 mitochondrial markers. Thus, the loss of mitochondria is attributable to autophagy (mitophagy). Statin treatment increases the expression of Bnip3 and p62/SQSTM1 (sequestosome 1) which have been identified as important facilitators of mitophagy. We found increased Bnip3 dimerization via western blot under non-reducing conditions which implies increased activity. Furthermore, we observed increased mitochondrial translocation of p62/SQSTM1. Based on our findings, we hypothesized that statin-induced mitophagy may play a key role in the development of muscle myopathy. To investigate the role of mitophagy in statin myopathy, we silenced p62/SQSTM1 via RNAi prior to statin treatment. Surprisingly, reducing mitophagic flux via p62/SQSTM1 silencing resulted in increased destruction of myotubes. This was associated with increased levels of cytosolic cytochrome c. Our data combined suggests that mitophagy protects against statin-mediated cell death by sequestering and eliminating decrepit mitochondria via autophagy.
Platinum compounds (PLcs) added to standard adjuvant or neoadjuvant regimen of biweekly doxorubicin plus cyclophosphamide (AC), followed by weekly paclitaxel (wP) in triple-negative (TN), HER2-neu-positive (HER2+), or locally advanced breast cancer (LABC): Preliminary results of a prospective, phase II, nonrandomized study.
Authors: M. Vassilaki, A. Sioulas, M. Tsantekidou, A. Klitsa, N. Desses, C. Georgakopoulos, P. Thomou, G. Xepapadakis
Journal: Journal of Clinical Oncology (2010)

e11006 Background: PLcs are active in TN locally advanced and metastatic breast cancer. This study aims to assess efficacy and safety resulting from the addition of cisplatin or carboplatin to a standard regimen in the adjuvant or neoadjuvant treatment of high-risk early-stage or LABC. Methods: 29 eligible patients (pts) were enrolled in this study between 2005-2009. Median age was 53 years (range 34-76). 6 pts were stage I, 3 IIA, 4 IIB, 10 IIIA and 6 IIIC. 8 pts had TN and 13 HER2+ tumors. Pts with stage I disease were TN- and/or BRCA1-positive. Treatment plan consisted of 4 AC (60/600 mg/m2) biweekly followed by either 12 wP 70 mg/m2 plus weekly cisplatin (wCDDP) 25 mg/m2 or 12 wP 70 mg/m2 plus carboplatin AUC5 every 3 weeks. IV bisphosphonates to be given monthly, in both regimens. Results: A total of 26 eligible for analysis pts (3 ongoing, 2 adjuvant and 1 neoadjuvant) completed 4 AC followed by wP plus either wCDDP (18 pts) or carboplatin (8 pts). 208 cycles of wCDDP and 40 cycles of carboplatin every 3 weeks were administered. All pts remain disease free. 3 evaluable pts who underwent neoadjuvant chemotherapy achieved pathologic complete response (pCR) in breast and lymph node specimens. Current median survival is 16.5 months (range 6-54). Both regimens were well tolerated with manageable toxicities. One week interval and dose reduction was necessary for few pts, mainly for neurotoxicity. Conclusions: PLcs added to the adjuvant and neoadjuvant treatment of pts with TN, HER2+ or LABC demonstrated to be active and safe. Data from large, randomized trials with longer follow-up period are warranted to elucidate this issue. No significant financial relationships to disclose.
Vascular thromboembolic events in patients (pts) with advanced urothelial cancer (UC) treated with carboplatin/gemcitabine alone or in combination with bevacizumab
Authors: A. B. Apolo, A. M. Regazzi, M. I. Milowsky, D. F. Bajorin
Journal: Journal of Clinical Oncology (2009)

5074 Background: Vascular thromboembolic events (VTE) occur in 13% of UC pts treated with cisplatin-based therapy ( J Urol 160:2021, 1998). Carboplatin-based therapy is used in UC pts intolerant of cisplatin but the frequency of VTE is unknown. Bevacizumab added to chemotherapy increases VTE in non-small cell lung cancer (NSCLC; 5% vs 3%) (Oncologist 12:713, 2007), breast cancer (7.4% vs 5.5%) and colorectal cancer (19% vs 16%) (JAMA. 2008;300:2288). This study evaluated VTE in UC pts treated with carboplatin/gemcitabine alone or with bevacizumab. Methods: Pts with advanced UC treated on a Memorial Sloan-Kettering Cancer Center protocol from June 2006 to September 2008 were analyzed prospectively. Therapy included &gt; 3 cycles of bevacizumab (15 mg/kg on day 1) plus carboplatin (AUC 5 or 4.5 on day 1) and gemcitabine (1000 mg/m2 on days 1,8) every 21 days. Evaluation for VTE on a contemporary UC control group of pts receiving carboplatin plus gemcitabine alone during the exact same time period was conducted retrospectively. VTE were defined as pulmonary embolism (PE), deep venous thrombosis (DVT), myocardial infarctions (MI) and cerebral vascular accidents (CVA). Pts with simultaneous PE and DVT were considered to have one VTE. Results: 89 pts were evaluated. Of the 25 pts treated with bevacizumab plus chemotherapy, 4 pts (16.0%; 95% CI 5–36%) had a VTE of which there were 2 PE alone, 1 DVT alone, and 1 DVT and PE. No MI was observed in bevacizumab-treated pts. Of the 64 contemporary control pts treated with gemcitabine plus carboplatin alone, there were 11 pts (17%; 95% CI 9–29%) who had a VTE of which there were 4 PE alone, 4 DVT alone, 2 DVT and PE, and 1 MI. No CVA were seen in either group. Conclusions: Pts with advanced UC receiving carboplatin plus gemcitabine have a very high rate of VTE (17%). The VTE incidence is similar to colon cancer (16%) and greater than NSCLC (3%) and breast cancer (5.5%). The VTE rate is similar for both cisplatin and carboplatin, suggesting that it is intrinsic to the UC disease state. In this study, the addition of bevacizumab to carboplatin/gemcitabine was not associated with an increase in VTE over that seen for carboplatin/gemcitabine alone. No significant financial relationships to disclose.