tbuckley/cabot-search huggingface dataset:
Absolute PSA value after androgen deprivation (AD) is a strong independent predictor of survival in new metastatic (D2) prostate cancer (PCa): Data from Southwest Oncology Group Trial 9346 (INT-0162)
Authors: M. Hussain, C. M. Tangen, P. F. Schellhammer, E. D. Crawford, C. S. Higano, G. Wilding, A. Akdas, E. J. Small, B. Donnelly, D. Raghavan
Journal: Journal of Clinical Oncology (2006)

4517 Background: PSA is a biomarker for monitoring disease activity in PCa. It is not well established if absolute PSA values achieved after AD is prognostic in patients (pts) with new D2 PCa. Methods: Hormone naive D2 pts with baseline PSA ≥ 5ng/mL are treated with 7 months (ms) AD induction. Pts achieving PSA-n (PSA ≤ 4.0 ng/ml that is stable or declining on ms 6 and 7) are randomized to continuous vs. intermittent AD on month 8. To be eligible for this analysis (approved by Data Safety Monitoring Committee), pts had to have a prestudy PSA with at least 2 subsequent PSAs during induction and be registered at least 1 year prior to analysis date. Survival was defined from 8 months to death due to any cause. Associations were evaluated by proportional hazards regression models. P≤0.05 was statistically significant. Results: Of the first 1,395 registered pts, 1345 were eligible for this analysis. Median age was 70 years, median baseline PSA 76.1 ng/mL, 38% had bone pain (BP) and 47 % had Gleason sum (GS) &gt; 7. Median number of on-study PSAs during induction was 5 (range: 2 -18). Of the 1,345 pts, 1134 achieved PSA-n with 965 maintaining PSA-n at end of induction. Of those achieving PSA-n, 604 (45% of all pts) had an undetectable PSA (PSA-u, ≤ 0.2 ng/mL) at end of induction. In multivariate analysis, 4 significant independent risk factors were associated with post-induction survival: Performance status, GS, BP, and being randomized. After adjustment for these factors, pts who had a PSA-n at the end of induction but not PSA-u had less than half the risk of death (RoD) as those who did not have PSA-n (HR: 0.41; 95% CI 0.32, 0.54, p &lt; 0.001), and pts with PSA-u had about one-quarter the RoD as pts with no PSA-n (HR: 0.26; 95% CI 0.20, 0.35, p &lt; 0.001). After adjustment for covariates, pts with PSA-u had significantly better survival than those with only PSA-n at end of induction (p &lt; 0.001). The median overall survival was 13 ms for the 383 not normalized (95% CI: 11 to 16 ms), 44 ms for the 360 pts normalized but not undetectable (95% CI: 39 to 55 ms), and 75 ms for the 602 pts with PSA-u (95% CI: 62, 91 ms). Conclusion: Achieving a PSA-n or PSA-u after 7 ms of AD is a strong predictor of survival and should be used to tailor future trial design in new D2 pts. [Table: see text]
Human papilloma virus (HPV): Burden of the disease in cervical cancer in the Extended Middle East and North Africa (EMENA). A comprehensive review
Authors: M. A. Seoud, K. M. Seoud, S. Lindely, S. Anis
Journal: Journal of Clinical Oncology (2009)

e16577 Background: Cervical cancer is less common in the EMENA than in the rest of the world. The purpose of this paper is to review the prevalence of HPV in the general population (GP), in cervical intraepithelial neoplasia (CIN) and in cervical cancer (CCA) in the EMENA. Methods: We performed an extensive literature search (English and French literature). Data extracted included information on the method of HPV detection and HPV type-specific data, age, and the histology of the CCA when available. Results: In North Africa (Algeria, Morocco, and Egypt): The prevalence of HPV varied from 5%-12% in the low-risk GP and to 20%-49% in the high-risk GP such as prostitutes. In CIN it varied from 25%-90% (HPV 16 in 40%-100%). In CCA HPV was present in 61%-98% of cases (HPV 16 in 50%-73%). In the Middle East (Jordan, Lebanon, and Israel): The prevalence of HPV was 1.8%-13% in the low-risk GP, in CIN it was 32%-88% (HPV 16 in 10%-30%), and in CCA it varied from 45%-78% (HPV 16 in 31–67%). In the gulf countries (UAE): HPV was found in 4%-11% of the low-risk GP and 20%-30% in the high GP. HPV was present in 37% in LSIL and 67% in HSIL. In CCA, High-risk HPV was present in 87% of specimen in one study. In Turkey, Iran, and Pakistan: HPV was present in 1.5%-13% in the low-risk GP, and up to 42.9% in patients with abnormal smears. In CIN HPV was found in 50% to 100% (HPV 16 in up to 76%). In CCA, HPV was detected in 60%-100% (HPV 16 in 27%-95%). In the GP the age range was 30–50 years, while in CIN it was 30–60 years, and in CCA it was 30–70 years. The studies were varied with small number of patients and varied detection methods that are difficult to compare. Most were PCR, few were Hybrid Capture (I or II). Conclusions: Although the studies on the prevalence of HPV in the EMENA region are not abundant, but there is enough data to suggest that the prevalence of HPV is around 5%-12% in the GP, 30%-80% in CIN and 60%-90% in cervical cancer with HPV 16 as the most predominant type. [Table: see text]
Amelioration of polycystic kidney disease by modification of dietary protein intake in the rat.
Authors: M R Ogborn, S Sareen
Journal: Journal of the American Society of Nephrology (1995)

Polycystic kidney disease is the most common potentially lethal single- gene inherited disease in man. There is no specific therapy. Previous studies in the pcy mouse model of polycystic kidney disease have shown amelioration of cystic change by reduction in dietary protein intake. The Han:SPRD-cy rat is a model of autosomal dominant polycystic kidney disease that closely resembles human disease in its histology and clinical course. We compared the morphometric assessment of cystic change and standard laboratory measures of renal function in heterozygous Han: SPRD-cy rats that received isocaloric diets containing either 8% or 20% protein as casein. This level of dietary protein restriction was associated with a significant reduction of mean body weight in the 8% protein group (358 g) compared with 20% protein (490 g; P = 0.027). Mean renal volume, adjusted for the difference in body weight, was significantly lower in the 8% protein group (6.2 mL/kg) compared with the 20% protein group (11.6 mL/kg; P = 0.016). The major component in this reduction was a reduction in total cyst volume to a mean 0.47 mL in the 8% protein group from 2.68 mL in the 20% protein group (P < 0.0001). All 8% protein diet animals survived to 6 months of age, but 3 of 11 20% protein diet animals died between 5 and 6 months of age. Mean serum creatinine and urea levels were significantly lower in the 8% protein group (118 mmol/L and 15.6 mmol/L) compared with the 20% protein group (272 mmol/L, P = 0.0033, and 81.5 mmol/L, P = 0.0002, respectively). Dietary protein restriction is a potent method for modifying the course of polycystic kidney disease in the Han:SPRD-cy/+ rat. These findings emphasize the potential for diet to alter the physiology of the renal tubulointerstitium.
Risk of local-regional and distant recurrence in triple-negative T1N0 breast cancer
Authors: J. A. Malmgren, M. K. Atwood, H. G. Kaplan
Journal: Journal of Clinical Oncology (2008)

609 Background: Triple-negative (TN) breast cancer (BC) has a high recurrence rate but effectiveness of current treatments is not well documented. Methods: From a prospective cohort of primary breast cancer registry patients at our institution (1999–2004), we identified a subset of TNM stage I (T1N0) BC. Estrogen (ER) and progesterone receptor (PR)/HER2/neu (HER2) negative (TN) patients (N=91) were compared to ER+/PR+/HER2- (HR+/HER2-) patients (N=770). Diagnosis and treatment variables were chart abstracted and vital and disease status was updated annually including local, regional or distant recurrence (endpoint). Length of follow-up was at least 2 years, average = 4.62 years. Pearson chi-square testing was used for bivariate evaluation of outcomes. Relapse-free survival (RFS) using any recurrence as the endpoint was evaluated using the Kaplan-Meier procedure. Results: Average patient age was 59 years (range 23–88). TN patients were more likely to receive adriamycin/cytoxan/taxane combination adjuvant chemotherapy, 25% vs. 8% (chi-square = 20.97, p =0.013). The rate of any recurrence was 9.9% in the TN group vs. 1.3% in the HR+/HER2 group (chi-square = 27.84, p<0.001) and distant recurrence was 6.6% vs. 1.0% (chi-square = 31.10, p<0.001). Of the 9 recurrences in the TN group three were local/regional and six were distant and the distribution by T stage was 0% in TN T1a (0/5), 15.4% in TN T1b (2/13), and 9.6% in TN T1c (7/73). Among the HR+/HER2- patients there were no recurrences in the T1a or T1b group and 10 in the T1c group (n=430, 2.3%). For adjuvant chemotherapy treated women the recurrence rate was 9.4% among TN patients and 1.3% among HR+/HER2- patients (Pearson chi-square = 8.27, p = 0.004). Distant metastases sites were as follows: TN; bone (3), lung (2), distant nodes (1), (n=6, 6.6%), and HR+/HER2-; bone (6), liver (1), simultaneous bone and liver (1), (n=8, 1.0%). Among all T1N0 patients, five-year RFS was 99% in the HR+/HER2- group and 88% in the TN group (log-rank test = 30.29, p<0.001). Conclusions: Overall and among adjuvant chemotherapy treated patients, TN patients had significantly worse outcomes compared to HR+/HER2- breast cancer patients. Treatment agents and modalities specifically designed for the triple-negative subgroup need to be identified and tested to equilibrate outcomes. No significant financial relationships to disclose.
A phase I dose-escalation study of INCB028060, an inhibitor of c-MET receptor tyrosine kinase, in patients with advanced solid tumors.
Authors: R. C. Donehower, A. Scardina, M. Hill, J. Bowman, R. C. Newton, X. Liu, P. Scherle, Q. Wang, S. Diamond, J. Boer, F. Lee, T. Gau, H. A. Burris, J. C. Bendell, S. F. Jones, J. R. Infante
Journal: Journal of Clinical Oncology (2011)

3091 Background: INCB028060 is a potent and selective inhibitor of c-MET receptor tyrosine kinase (RTK). This first-in-human study aims to determine the maximum tolerated dose (MTD), pharmacokinetics (PK), pharmacodynamics (PD), and potential efficacy of INCB028060. Methods: In a standard 3+3 escalation, patients (pts) age =18 years with advanced solid tumors are treated with INCB028060 orally once (QD) or twice daily on a continuous 28-day schedule. C-MET inhibition is evaluated by adding c-MET overexpressing SNU-5 human gastric cancer cells to pts whole blood and then analyzing for inhibition of phospho-c-MET by ELISA. Results: At this time 17 pts have been treated across dose levels of 10, 20, 50, and 70 mg/once daily. Median age is 63 years, median ECOG PS is 0, and the most common tumor types are colorectal (4), NSCLC (3), and prostate/HCC/cholangiocarcinoma (2 each). One pt with breast cancer and diffuse liver metastases treated at 50 mg QD developed grade 3 AST elevation on C1D22, having had grade 2 AST at baseline; the AST continued to rise once treatment was discontinued. The MTD has not been reached and no other grade 3/4 adverse events (AEs) noted. CTC grade 1-2 AEs considered possibly treatment-related have included mild tremor, fatigue, nausea, diarrhea, indigestion, headache, and agitation. The Cmax and AUC values of INCB028060 have been dose-proportional, with a mean half-life of 6.8 hours. For the 70 mg QD cohort, INCB028060 mean plasma concentrations exceeded IC90 for ∼17 h of the day. At the 70 mg dose level on day 15, the oral CL was 35.2 (+/- 11.5) L/h and renal clearance was negligible. Dose-dependent reductions in phospho-c-MET levels have been detected on day 15 (pre-dose) by whole blood-based PD analysis, with mean inhibition of 41.3%, 45.7%, 67.5% and 69% at 10, 20, 50 and 70 mg/day, respectively. Conclusions: Thus far, toxicity has been manageable with INCB028060. The PK profile is favorable and supports exploration of a BID schedule. Dose-dependent decreases in phospho-c-MET are promising.
Evaluation of renal function and carboplatin clearance in Japanese cancer patients
Authors: T. Shimokata, Y. Yasuda, A. Hamada, K. Kawada, Y. Hasagawa, Y. Ando
Journal: Journal of Clinical Oncology (2009)

2556 Background: There is a close relationship between carboplatin clearance and glomerular filtration rate (GFR). Calvert developed the following formula for the dosing of carboplatin: dose (mg) = target area under the concentration versus time curve (AUC, mg ml -1 min) × [GFR (ml min -1 ) + 25]. However, this formula has not been evaluated in Japanese population. In this study, we prospectively evaluated renal function and carboplatin clearance in Japanese cancer patients. Methods: GFR was measured by inulin clearance before chemotherapy. The dose of carboplatin was determined by Calvert's formula using adjusted 24-h creatinine clearance (Ccr) by adding 0.2 (mg dl -1 ) to serum creatinine. A pharmacokinetic study was performed during the first cycle of the chemotherapy. Blood samples were obtained at 10 points within 24 hours. The observed AUC of carboplatin and the observed carboplatin clearance were calculated. Results: Inulin clearance was estimated in 28 cancer patients. Estimation of renal function with adjusted 24-h Ccr and estimated GFR equation (eGFR) were unbiased [mean prediction error (MPE) = -2.3%, 5.2% respectively] and acceptably precise [root mean squared error (RMSE) = 23.7%, 25.7% respectively], whereas non-adjusted Ccr and the Cockcroft-Gault equation overestimated GFR (MPE = 24.2%, 12.5% and RMSE = 37.2%, 32.7% respectively). Observed carboplatin clearance was proportional to GFR in range of renal function in this study (r = 0.903) and we verified the linearity. Non-renal clearance of carboplatin in Japanese cancer patients was 5.6 (ml min -1 ). Conclusions: 24-h Ccr adjusted by adding 0.2 (mg dl -1 ) to serum creatinine and eGFR were useful in assessing renal function for carboplatin dosing. It was suggested that non-renal clearance of carboplatin in Japanese cancer patients was less than 25 (ml min -1 ). No significant financial relationships to disclose.
P-glycoprotein expression at diagnosis may not be a primary mechanism of therapeutic failure in childhood rhabdomyosarcoma.
Authors: J F Kuttesch, D M Parham, X Luo, W H Meyer, L Bowman, D N Shapiro, A S Pappo, W M Crist, W T Beck, P J Houghton
Journal: Journal of Clinical Oncology (1996)

PURPOSE To evaluate the prognostic significance of tumor cell P-glycoprotein (Pgp) expression at diagnosis in children with rhabdomyosarcoma. PATIENTS AND METHODS A panel of three anti-Pgp monoclonal antibodies (mAb) (C219, C494, and JSB-1) that recognize different Pgp epitopes was used to measure Pgp expression in rhabdomyosarcoma specimens obtained at diagnosis from 76 patients treated at St Jude Children's Research Hospital from 1969 to 1991. Two separate experiments using different immunohistochemical methods (immune alkaline phosphatase and immunoperoxidase) were performed to evaluate Pgp expression. The immunostaining was graded using a semiquantitative scale corresponding to the percentage of tumor cells with detectable staining. The influence of Pgp expression on outcome was assessed by the Kaplan-Meier method and Cox regression analysis with stepwise selection. The relationship between Pgp expression and clinical features was assessed using the Mantel-Haenszel method. RESULTS Pgp expression at diagnosis did not predict worse overall survival or progression-free survival when tested in either experiment with C219, C494, or JSB-1 separately. No association was shown between Pgp expression and clinical features (clinical group, primary site, or histology) or response. However, in the immune alkaline phosphatase experiment, patients whose tumors had more than 10% tumor cell staining with all three mAbs had a significantly higher rate of estimated 5-year survival (78% +/- 10%) than did all other patients (38% +/- 8%; P = .025). In this instance, Pgp expression had independent prognostic value after adjusting for clinical group. CONCLUSION We found no strong association between Pgp expression at diagnosis and clinical features or extent of disease in pediatric rhabdomyosarcoma. Depending on the criteria used to define it, high Pgp expression at diagnosis does not predict poor outcome. Although a large prospective study is needed to provide definitive conclusions, our findings suggest that Pgp-mediated multidrug resistance may not be a primary mechanism of therapeutic failure in rhabdomyosarcoma.
Two Patients With Sarcoma
Authors: Gerard C. Blobe, Michelle Mantel, Milos Janicek, George D. Demetri
Journal: Journal of Clinical Oncology (2000)

Article Tools Two Patients With Sarcoma Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.11.2343 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10829056 Two Patients With Sarcoma Gerard C. BlobexGerard C. BlobeSearch for articles by this author , Michelle MantelxMichelle MantelSearch for articles by this author , Milos JanicekxMilos JanicekSearch for articles by this author , George D. DemetrixGeorge D. DemetriSearch for articles by this author Show More Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA https://doi.org/10.1200/JCO.2000.18.11.2343 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical Oncology
Nitric oxide and asymmetric dimethylarginine and CD 40 ligand levels in malignancy associated thrombosis and their modulation by anticoagulants
Authors: D. Hoppensteadt, D. Fareed, O. Iqbal, A. Lale, J. Fareed
Journal: Journal of Clinical Oncology (2007)

17049 Background: Cancer associated thrombotic complications are primarily due to endothelial dysfunction and upregulation of inflammatory processes. Nitric oxide (NO) represents one of the major endothelial derived vasoactive mediators. Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of NO synthase which inhibits NO production at pathophysiologic levels. CD 40 ligand (CD 40L) is also upregulated in cancer. Methods: To test the hypothesis that endothelial dysfunction in cancer patients may result in increased ADMA levels, plasma samples were retrospectively analyzed from an open label, multidose, active comparator designed study in which all patients (n=110) were initially treated with low molecular weight heparin, enoxaparin (E) at 1–1.5 mg/kg sc for 5 days and further subdivided into group E which continued to receive E and warfarin (W) group which was given oral anticoagulants for a period of up to 12 weeks. Baseline blood samples (BL), 5 days post E (IPE) and 4–6 week samples from the E and W were analyzed for ADMA and CD 40L levels by ELISA methods. NO levels were measured using a chromogenic method. Results: The baseline levels of NO, ADMA and CD 40L levels were markedly elevated in cancer patients. The E treated group showed a marked decrease in the ADMA and CD 40L levels which persisted throughout the treatment period. However, in the W converted group the ADMA and CD 40L levels rebounded to an increased level indicating that E differentially regulated ADMA in these patients. The down regulation pattern of NO was similar for both E and W. Conclusions: These results suggest that patients with cancer and thrombosis exhibit simultaneous upregulation of ADMA, CD 40L and NO. While E and W show a differential regulation of ADMA and CD 40L, both result in a downregulation of NO. The fact that E regulates ADMA is highly suggestive of its role in iNOS regulation which may be involved in the inflammatory response in cancer patients. [Table: see text] No significant financial relationships to disclose.
More "alcopops" have come on market since study was done
Authors: M.-A. McKibben
Journal: BMJ (1996)

EDITOR,—Neil McKeganey and colleagues' survey of the drinking patterns of schoolchildren in Dundee highlights concerns that the alcohol industry's development of designer drinks such as white ciders and fruit wines is exacerbating an already worrying level of drinking among under 18 year olds.1 From 1990 to 1994 the number of regular drinkers among the 11–15 age group rose considerably (from 13% to 17% in England, 15% to 19% in Wales, and …
Central venous access in the pediatric cancer patient—Problems unique to developing countries: 5-year experience at a regional cancer center in Western India
Authors: R. Pandey, A. A. Patel, S. A. Shah, K. M. Patel, P. M. Shah, S. N. Shukla, B. J. Parikh, A. S. Anand, S. S. Talati, H. P. Panchal
Journal: Journal of Clinical Oncology (2006)

9049 Background: Central venous catheter (CVC) is required in the pediatric cancer patient for chemotherapy administration and supportive care. This study was carried out to review our experience with CVC, with special reference to issues unique to developing countries. Methods: 178 children who underwent 181 CVC insertions at our institute between January 2001 and October 2005 were retrospectively analysed for demographics, diagnosis, type of CVC, infective and non infective complications. Continuous data were assessed using the t test or the Wilcoxon rank sum test and categorical data by the chi square test or the Fisher’s exact test. Results: Median age was 6.5 years (0.6–13 yr). Commonest diagnosis was acute lymphoid leukemia (ALL) (n=60). CVC used were Hickman (n=162), subcutaneous ports (n=9) and peripherally inserted central catheters (n=10). Patients with hickman catheters had 164 insertions for 162 patients with a total of 14,090 catheter days, an average of 86.9 days/catheter. There were 5.36 culture positive infections /1000 catheter days. The commonest isolate was Coagulase negative S. Aureus (CNS) (44/80 cases). CVC infection with CNS was associated with higher risk of recurrent infections (OR=3.5 {95%CI=2.12–8.23} p=0.01). Patients having recurrent CVC infections received antibiotics for a median of 9.4 days as against a median of 10 days for those with non-recurrent infections (p=0.01, Wilcoxon rank sum). In 58 ALL patients, early (within 15 days of induction) insertion of CVC was associated with increased risk of culture positive infection as against late (after 15 days of induction) insertion (OR=2.3, 95%CI=1.0–5.2, p=0.05). Other complications were thrombosis (n=3), exit-site infection (n=5), tunnel infection (n=3), catheter fracture (n=1) and dislodgement (n=3). Conclusions: As most patients do not afford port, Hickman is the most preferred CVC in pediatric oncology in a developing country. Most patients are of low literacy and poor socioeconomic status. This is reflected in significantly high rates of CVC infection. Communication between the inserting doctor, nursing staff and proper counseling of the patient is the key to reduce complications No significant financial relationships to disclose.