tbuckley/cabot-search huggingface dataset:
Pharmacokinetic differences and ethnic variability in tolerance of cytotoxic drugs.
Authors: V. H. Phan, C. Tan, A. L. Sullivan, J. L. Vardy, A. Rittau, H. Xu, A. J. McLachlan, P. J. Beale, S. J. Clarke
Journal: Journal of Clinical Oncology (2010)

e13034 Background: Recent evidence shows an ethnic variability in tolerance of anticancer drugs among lung and breast cancer (LC and BC) patients. Pharmacogenetic differences in drug metabolizing enzymes have been proposed as the cause of these differences; however, they have not been associated with altered cytotoxic drug pharmacokinetics (PK). Other possible explanations include differences in dietary, concomitant medication, and inflammatory status. The aim of this study was to investigate interethnic differences in cytotoxic drug metabolism, inflammatory/nutritional status, genotype, and outcomes between Asian and Caucasian LC and BC patients. Here we present the PK data. Methods: Early BC patients receiving standard adjuvant anthracycline-based chemotherapy regimens and metastatic LC patients receiving palliative treatment with paclitaxel and carboplatin were recruited. Plasma samples were collected using a limited sampling strategy and concentrations were measured using HPLC for epirubicin and LC-MS for paclitaxel. Empiric Bayes estimates of clearance (CL) were obtained using a population PK analysis implemented in the NONMEM software. The toxicity profile after cycle 1 of chemotherapy was graded and correlated with the pharmacokinetics of anthracyclines (BC) and paclitaxel (LC). Results: Forty-two BC patients (30 Caucasians, 12 Asians) and 44 LC patients (33 Caucasian, 11 Asians) have been recruited. In BC, 11/12 (92%) Asians had grade IV neutropenia compared to 19/29 (66%) Caucasians (p=0.066). Asians had more severe anaemia and thrombocytopenia. In LC, there were no statistically significant ethnic differences in toxicity. PK analyses showed that paclitaxel CL in Asian LC patients (n=8, mean=11.0 L/h) was lower than in Caucasian patients (n=24, mean=13.4 L/h) (p=0.045). There was a trend for epirubicin CL to be lower in Asian patients (n=10, mean=78.0 L/h) compared to Caucasians (n=26, mean= 84.2 L/h). Conclusions: Preliminary data indicate Asian LC and BC patients have lower clearance of anthracyclines and paclitaxel, respectively, than Caucasians, which is likely to explain ethnic differences in toxicity. However, larger patient numbers are required to provide more conclusive results. No significant financial relationships to disclose.
Analysis of resilience and depression scores and their relation to quality of life in ambulatory lung cancer patients undergoing radiation therapy.
Authors: A. Armando, N. W. da Motta, R. C. Pinto, J. Matiello, D. L. Da Silva, A. F. Ferreira Filho
Journal: Journal of Clinical Oncology (2010)

e19578 Background: Resilience is a dynamic positive psychological characteristic that allow and help individuals and groups to maintain equilibrium amidst situations of stress and adversity. The way resilience of individual cancer patients correlates to their overall quality of life (QOL) is still little investigated and not completely understood. The main purpose of this study is to analyze resilience, QOL and depression scores as well as their correlations in a population of ambulatory lung cancer patients with ECOG PS 0-2 undergoing radiation therapy. Methods: From January 2009 we enrolled 30 consecutive ambulatory lung cancer patients referred to radiation treatment. On the moment of first nurse consultation, these patients completed the following questionnaires, all validated for Portuguese language of Brazil: A) the resilience scale of Wagnild and Young, B) the abbreviated World Health Organization quality-of-life scale(WHOQOL-bref), and C) the Beck Depression Inventory (BDI). Patients were considered depressed if they had a BDI score greater than 13. The study was approved by the Ethics Comitte and all patients signed the informed consent form. Results: The mean age of patients was 59 years (range 42-76) and 17 (57%) were men. The mean ECOG status was The treatment had curative intention in 15 patients (50%). Mean resilience score was 145 ± 25 (range 101-213. Mean BDI score was 11 ± 8 (range 0-41), with 8 patients (27%) classified as depressed. Mean WHOQOL-bref score was 87 ± 10 (range 70-110). We found a statistically positive correlation between resilience and QOL scores (r = 0.57, p = 0.001). BDI and QOL scores correlated negatively (r = −0.31, p = 0.09), but this correlation was of smaller magnitude when compared to the one between resilience and QOL scores. We found no statistical correlation between the total scores of resilience and the BDI (r = −0.03, Pp0.84). Conclusions: In our series, patients with higher resilience scores had better overall QOL as measured by the WHOQOL-bref scale. Strategies designed to enhance resilience in cancer patients have a clear potential role in improving their overall quality of life. No significant financial relationships to disclose.
Grading of neurotoxicity in cancer therapy.
Authors: A M Castellanos, W S Fields
Journal: Journal of Clinical Oncology (1986)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1986.4.8.1277 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3734850 Grading of neurotoxicity in cancer therapy. A M CastellanosxA M CastellanosSearch for articles by this author , W S FieldsxW S FieldsSearch for articles by this author https://doi.org/10.1200/JCO.1986.4.8.1277 PDF "Grading of neurotoxicity in cancer therapy.." Journal of Clinical Oncology, 4(8), pp. 1277–1278© 1986 by American Society of Clinical Oncology
Stereotactic radiosurgery for stage I NSCLC in medically inoperable patients: A prospective multicenter study.
Authors: A. Pennathur, R. I. Whyte, A. Zajac, D. G. Brachman, W. E. Gooding, N. A. Christie, H. C. Urschel, B. W. Loo, D. E. Heron, J. D. Luketich
Journal: Journal of Clinical Oncology (2010)

7080 Background: Surgical resection is the standard of care for patients with stage I non-small cell lung cancer (NSCLC). However, for high-risk patients stereotactic radiosurgery (SRS), offers an alternative option. Our objective was to prospectively evaluate SRS as definitive treatment for high risk patients with stage I NSCLC in a multi-institutional setting Methods: This is a prospective multicenter study (14 centers) to evaluate Cyberknife SRS for the treatment of stage I NSCLC in medically inoperable patients. Patients were accrued after evaluation by thoracic surgeons and oncologists. The tumor was stratified by location. A high biological effective dose (BED) was delivered (60 Gy) in three fractions to the 80% isodose line for peripheral lesions. We evaluated the initial response rate by the modified RECIST (Response Evaluation Criteria in Solid Tumors) criteria at 3-6 months. This modification incorporated imaging with Positron emission tomography (PET) scanning. We also evaluated time to progression and overall survival. Results: A total of 78 patients, 63 with stage IA, 15 with stage IB peripheral NSCLC underwent SRS. Seventy patients were evaluable for response. A complete response was observed in 11 patients (16%), partial response in 37 (53%), stable disease in 20 (28%), and progression in 2 patients (3%). The median follow-up was 11 months (range 0.1–49 months); the median overall survival was not reached. The probability of 2 year overall-survival for the entire group was 62% (95% CI 42%-77%). Overall survival did not differ by stage IA vs. IB (p=0.187). During follow-up with PET and/or CT, 18 patients had recurrence: only 1 local (5%), and 17 with regional or distant recurrence. Median recurrence-free survival (RFS) was 43 months. The probability of 2 year RFS was 54% (95% CI=33%-71%). Conclusions: Our preliminary results of the prospective multicenter study of SRS for high-risk patients with stage I peripheral NSCLC is promising compared to standard radiation. In particular, local control was good with a low local recurrence rate (5%), with this dose of 60 Gy in 3 fractions. Additional follow-up is needed, and is ongoing to fully evaluate the results of stereotactic radiosurgery for stage I NSCLC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Accuray
Fertility in male patients with Hodgkin's disease after therapy –results from the German Hodgkin Lymphoma Study Group (GHSG)
Authors: M. Sieniawski, A. Josting, K. Breuer, T. Sven, V. Diehl, A. Engert
Journal: Journal of Clinical Oncology (2004)

6547 Background: Treatment results in Hodgkin Disease (HD) have improved tremendously over the last two decades. Therefore long term sides effects of therapy are of growing importance. Infertility after therapy of HD is considered as a side effect of chemotherapy and radiotherapy. However patients with HD have increased risk for inadequate semen quality even prior to treatment. To investigate the influence of therapy on the fertility status in patients with HD we performed semen analysis before and after treatment. Methods: Semen quality was evaluated in patients with first diagnosis of HD enrolled into trials of the GHSG between 1988 and 2002. Patients had no history of chemotherapy or radiotherapy. All semen analyses were evaluated according to WHO-guidelines. Results: We included 111 male patients with a median age of 26 years (range 16–52 years). At first diagnosis 10 patients were in clinical stage (CS) I, 60 in CS II, 60 in CS III and 8 in CS IV; systemic symptoms were present in 52 patients. In 9 patients therapy regimens consisted only of chemotherapy, in 12 of radiotherapy and in 90 of combined modality. 71 patients underwent fertility screening before therapy; normospermia was diagnosed in 19 patients. All 111 patients underwent at least once a fertility screening after therapy; in 38 patients (34%) a recovery of spermatogenesis was observed (1st year: 18% (n=7); 2nd year: 24% (n=9); 3rd year: 26% (n=10); after 3rd year: 132% (n=12). From 12 patients treated with radiotherapy 11 (92%) recovered from azoospermia, from 9 patients treated only with chemotherapy only 1 patient recovered and from 90 patient treated with chemotherapy and radiotherapy recovered 26 (29%). Recovery rate from azoospermia was lower in patients treated with BEACOPP chemotherapy, with systemic symptoms and elevated BSG. Conclusions: We confirmed that HD patients had inadequate semen quality even prior to treatment. The majority of patients had azoospermia after treatment, but recovery of spermatogenesis was observed, in general after 2 years after the end of therapy. Patient treated only with radiotherapy recovered in higher frequency. No significant financial relationships to disclose.
In vivo brain energy metabolism in a rat model of chronic Hepatic Encephalopathy using 31P MRS
Authors: Cristina Cudalbu, Olivier Braissant, Arjun Jayaswal, Rolf Gruetter, Valerie A. Mclin
Journal: Hepatology (2013)

Keywords: CIBM-AIT Reference EPFL-CONF-199194View record in Web of Science Record created on 2014-06-02, modified on 2017-05-12
Pretreatment lab values to predict overall survival in patients with primary unresectable pancreatic adenocarcinoma treated with SBRT.
Authors: Muthuraman Alagappan, Erqi L. Pollom, Rie von Eyben, Pamela L. Kunz, George A. Fisher, James M. Ford, George A. Poultsides, Brendan C. Visser, Jeffrey A. Norton, Aya Kamaya, Laurie Ann Columbo, Albert Koong, Daniel Tandel Chang
Journal: Journal of Clinical Oncology (2015)

433 Background: This study investigates which pre-treatment hematologic and tumor marker values can predict for overall survival (OS) in patients with unresectable pancreatic adenocarcinoma treated with stereotactic body radiotherapy (SBRT) using data from the past 11 years from a single institution. Methods: Clinical data from 196 patients with primary unresectable pancreatic adenocarcinoma treated with SBRT at our institution from 2002 to 2013 was collected. Of these, 161 (82.1%) had locally advanced disease, 12 (6.1%) had borderline resectable disease, 21 (10.7%) were medically inoperable, and 2 (1.0%) had resectable disease but refused surgery. Prior to the start of treatment, lab values were collected for 191 of these patients including: hemoglobin, platelets, albumin, red blood cell (RBC) count, white blood cell (WBC) count, absolute lymphocyte count, absolute neutrophil count, and neutrophil to lymphocyte ratio (NLR). Additionally, tumor markers CA 19-9 and CEA were collected. Background clinical and demographic data was also available for the entire cohort. Results: The median follow-up for the entire cohort following SBRT was 7.7 months. Median OS from the start of treatment was 7.88 months (IQR 4.96-12.72). Prior radiation therapy (p = 0.0462), lower RBC (p = 0.0307), higher pre-treatment CEA (p = 0.0166), and higher NL ratio (p &lt; 0.0001) correlated with worse OS on univariate analysis. WBC, platelet counts, and CA 19-9 did not predict for OS on univariate analysis. On multivariate analysis, higher NL ratio (p = 0.0455) and higher CEA (p = 0.0148) were both correlated with decreased OS, while RBC and prior radiation therapy had no association. Conclusions: Review of pre-treatment hematologic and tumor marker values serves as a valuable predictor of overall survival in patients with unresectable pancreatic adenocarcinoma treated with SBRT. Higher pre-treatment NL ratio and CEA values are associated with poorer OS, which may help to stratify patients into different risk categories.
Efficacy and safety of bosutinib (BOS) for Philadelphia chromosome–positive (Ph+) leukemia in older versus younger patients (pts).
Authors: Tim H. Brummendorf, Carlo Gambacorti-Passerini, Philippe Schafhausen, Hanna Jean Khoury, Andreas Hochhaus, Thomas Kindler, Thomas Fischer, Nadine Besson, Eric Leip, Virginia Kelly, Jorge E. Cortes
Journal: Journal of Clinical Oncology (2012)

6511 Background: BOS is an oral dual Src/Abl kinase inhibitor with potent activity in Ph+ leukemia. Methods: Efficacy and safety of BOS 500 mg/d was evaluated in older (≥65 y; n = 119) and younger (&lt;65 y; n = 451) pts in 3 cohorts: chronic phase chronic myeloid leukemia (CP CML) after imatinib (IM; CP2L cohort; n = 287); CP CML after IM + dasatinib (DAS) and/or nilotinib (NIL; CP3L cohort; n = 119); and accelerated/blast phase (AP/BP) CML or acute lymphoblastic leukemia after IM ± DAS and/or NIL (ADV cohort; n = 164). Results: Baseline events (≥65 y vs &lt;65 y) included respiratory disorders (35% vs 13%), cardiac disorders (29% vs 9%), and diabetes (4% vs 4%). Median baseline medications were 3 (≥65 y) and 5 (&lt;65 y). Median BOS duration was 11 mo and median follow-up was 31 mo for all pts. 80% of ³65 y and 67% of &lt;65 y pts discontinued BOS, including 32% and 18% due to an adverse event (AE; most commonly thrombocytopenia [6% vs 3%]). Rates of response were similar or lower in older versus younger pts (Table). On-treatment transformation to AP/BP CML was similar between groups. Incidences of nonhematologic treatment-emergent AEs were generally similar between older and younger pts, notably (all grades/grade ≥3 for ≥65 y vs &lt;65 y): diarrhea (85%/9% vs 81%/8%), infection (56%/15% vs 49%/10%), and edema (8%/0% vs 4%/&lt;1%). Common grade ≥3 lab abnormalities (≥65 y vs &lt;65 y) were thrombocytopenia (35% vs 35%), neutropenia (21% vs 25%), and anemia (19% vs 19%). Conclusions: BOS demonstrated similar efficacy and acceptable safety in both older and younger pts across Ph+ leukemia cohorts. [Table: see text]
Invasive melanoma patients treated with Canvaxin specific active immunotherapy show serconversion for both IgG and IgM antibody responses to numerous protein and glycolipid tumor antigens
Authors: S. Kuhns, C. R. Ill, L. Zhang, D. Buckman, J. T. Nguyen, J. Thomas, D. van Epps, R. Essner, E. Hsueh, L. Foshag, M. Faries
Journal: Journal of Clinical Oncology (2005)

2574 Background: Although few nonsurgical treatment options offer significant benefit for patients with high-risk melanoma, extensive matched-pair control studies of phase II trials indicate that Canvaxin (C) immunotherapy can prolong survival (Ann. Surg. 236:438). C, a formulation of three live, replication-incompetent melanoma cell lines, was designed to induce a polyvalent immune response to multiple tumor antigens and thereby combat antigenic modulation by autologous tumor cells. We examined the nature, frequency, and magnitude of humoral immune responses to various tumor-associated antigens in patients receiving postoperative adjuvant C immunotherapy. Methods: Stage II, III and IV melanoma patients were enrolled in a randomized phase II trial of C immunotherapy after complete surgical resection. For the first 4 months, half of the patients received subcutaneous GM-CSF concurrent with each C dose and daily for the next four days. Each GM-CSF dose of 200 μg/m2 was administered evenly at four sites in the groin and axilla. Serum from 30 patients in this trial was collected immediately before the first dose of C and at 1, 2, 3, and 5 months. ELISA was used to evaluate each serum specimen for IgM and IgG antibody responses to ganglioside tumor antigens GD2, GD3, GM2, and GM3 and protein antigens gp100, MART-1 and MAGE-1. Results: All patients responded to at least one antigen, 84% responded to at least 3 antigens, and 50% responded to at least 5 antigens. Antiganglioside responses were more common than antiprotein responses. In general the patients who received C plus GM-CSF had stronger immune responses against 25.6% more antigens than those who received C alone. Only three patients showed no IgG responses; only one patient showed no IgM responses. Conclusions: C-induced antibody responses to numerous tumor antigens support the postoperative use of polyvalent live cells to trigger a broader, potentially more effective immune response. The scope of this response makes it more difficult for autologous tumor cells to escape immune attack by simultaneous modulation of multiple tumor antigens. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration CancerVax CancerVax
Effect of Celiprolol on Prevention of Cardiovascular Events in Vascular Ehlers-Danlos Syndrome
Authors: KT Ong, J Perdu, H Plauchu, Julie De Backer, Anne De Paepe, J Emmerich, X Jeunemaitre, D Germain, P Collignon, G Georgesco, E Bozec, JS Hulot, S Laurent, P Boutouyrie
Journal: Circulation (2009)
Primary prevention of bladder cancer: Does the public know the risk factors?
Authors: Erika L. Wood, Vishnukamal Golla, Rohit Goswamy, Bryan Fellman, Diana L Urbauer, Steven Canfield, Jay Bakul Shah
Journal: Journal of Clinical Oncology (2015)

366 Background: Smoking is the single most significant modifiable risk factor for bladder cancer, yet this is not well known outside of the medical community. Previous studies from tertiary referral centers have found that 36-58% of urology patients can identify smoking as a risk factor for bladder cancer. Since those patients may not be representative of the general population, we studied the knowledge base of bladder cancer risk factors among people encountered in the general waiting room of an urban county hospital. Methods: 215 participants over 18 years of age were recruited from the waiting room of an urban county hospital to participate in a brief survey on risk factors for various cancers. Fisher’s exact test and McNemar’s test were used to detect differences in knowledge between bladder cancer and other cancers. Results: The survey participant population was mostly female (65.6%), Hispanic (54%), and middle-aged (67% age 35-64). Most (54.8%) had an annual household income of less than $20,000, attained a high school education (49.1%) or below (24.1%), and 40.3% were current or former smokers. An overwhelming majority of participants chose smoking as a risk factor for lung cancer (92.2%), with 80.7% identifying smoking as the primary risk factor for lung cancer. In contrast, only 31.6% of participants chose smoking as a risk factor for bladder cancer with 7.4% selecting it as the primary risk factor for bladder cancer. Knowledge of smoking as a risk factor for bladder cancer was not impacted by education, income, smoking status, or personal/family history of cancer. Male gender and exposure to industrial chemicals were identified as risk factors for bladder cancer by a minority of patients (19.3% and 28.0%, respectively). Almost half of all participants surveyed (49.1%) incorrectly identified alcohol use as a risk factor for bladder cancer. Conclusions: Among participants of low socioeconomic status presenting to an urban county hospital, there is a concerning lack of knowledge about the major risk factors for bladder cancer. Given that smoking is a modifiable risk factor, future public education initiatives to prevent bladder cancer should focus on populations with low socioeconomic status as high-yield targets to affect change.
Abnormal Expression Of The Major Coxsackie-Adenovirus Receptor CAR On Immature Dysplastic CD105+ Erythroid Progenitor Cells In Patients With MDS and Related Bone Marrow Neoplasms
Authors: Sigrid Machherndl-Spandl, Susanne Suessner, Martin Danzer, Johannes Proell, Christian Gabriel, Jeroen Lauf, Gregor Eisenwort, Wolfgang R Sperr, Peter Valent, Hans-Ulrich Klein, Marie-Christine Bene, PharmSciD, Ulrich Germing, Uwe Platzbecker, Ansgar Weltermann, Otto Zach, Peter Bettelheim
Journal: Blood (2013)
Utility of photography to confirm skin lesion response assessed using a severity weighted assessment tool (SWAT) in cutaneous T-cell lymphoma (CTCL)
Authors: B. S. Mann, J. R. Johnson, K. He, R. Sridhara, A. T. Farrell, R. Dagher, R. Justice, R. Pazdur
Journal: Journal of Clinical Oncology (2007)

6579 Background: In Oct 2006, FDA approved vorinostat for treatment of cutaneous manifestations of CTCL–based on response rate and duration of response observed in CTCL skin lesions. Response was determined by change in SWAT score at follow up compared to the baseline score. SWAT Score: sum of % Body Surface Area weighted by factor 1, 2, or 4 for patch (no elevation from normal skin), plaque (&lt; 5 mm elevation) and tumor (= 5 mm elevation), respectively. All responses but one were partial. A partial response required = 50% reduction in whole body SWAT score lasting = 4 weeks. FDA also reviewed serial photographs of all patients (standard whole body views and close-ups of skin lesions), submitted as supportive evidence. Methods: An expert external reviewer, blind to SWAT scores, adjudicated responses by examining photographs and response determinations by photographs and by SWAT scores were compared. Results: Based on SWAT scores, skin lesions in 18 of 61 stage = IIB CTCL patients responded to vorinostat; there were 17 partial and 1 complete responses. Blinded reviewer adjudicated 4 photographs not evaluable (reasons: blurred image, color or light problem, wrong label), easily confirmed 7 responses, and called 7 responses equivocal. Responses seemed easier to determine in skin lesions with tumors or ulcers. Predominantly patch or plaque lesions were harder to evaluate: patches due to poor color reproduction and plaques due to inability to palpate. A response from plaque to patch morphology decreases SWAT score 50%, but the change may not manifest adequately in a photograph. Small sample size did not allow a reliable statistical analysis for correlation between different lesion types and ability to confirm objective responses (based on SWAT scores) by photography. Conclusions: Photography allows a limited evaluation of skin lesions in CTCL: inability to measure lesion thickness in photographs limits direct confirmation of SWAT scores. Photography complements SWAT evaluation: in half the cases in the vorinostat pivotal trial, a response by SWAT score was easily confirmed by the reviewer blind to SWAT scores. Further experience and technological advances in photography may reduce the number of not evaluable photographs. No significant financial relationships to disclose.