tbuckley/cabot-search huggingface dataset:
PSA decline does not correlate with overall survival in clinical trials with docetaxel for androgen independent prostate cancer (AIPC)
Authors: O. Smaletz, F. R. Moreira, S. D. Simon, A. Katz, R. C. Gansl, J. Tabacof
Journal: Journal of Clinical Oncology (2005)

4673 Background: Since uncontrolled trials have shown an association between a decline in PSA levels of 50% or greater and survival, some investigators advocate that the rate of PSA decline in a phase II trial can guide the selection of agents for further testing and phase III trials. This approach may not be valid with docetaxel-based regimens. Methods: A computer-based search of the PubMed database was performed of all published clinical trials of docetaxel-based regimens in patients with AIPC between 1999 and November 2004. Trials were eligible for analysis if they accrued only patients with metastatic AIPC for first line chemotherapy with a docetaxel-based regimen and they reported median overall survival. We sought to define the correlation between PSA decline and median overall survival in clinical trials with docetaxel-based regimens. Analyses were done for the whole group and for two subgroups: every 3-weeks and weekly regimens. Weighted linear regression was used to assess this relationship. Results: A total of 19 published trials were retrieved, and 9 (7 phase II and 2 phase III) trials are eligible for analysis, for a total of 1330 patients and a median of 47 patients (range, 25–338) accrued for each study/arm of treatment. There are 5 regimens in the every 3-weeks group and 6 regimens in the weekly regimen group (two trials had two different treatment arms). The median > 50% PSA reduction reported was 50% (range, 37%–81%). The median median-overall survival time reported in the clinical trials was 18.9 months (range, 9.75–28.9). Correlation for the whole group, for the every 3-weeks group and the weekly regimens group were weak [respectively, R2=1.2% (p=0.746); R2=0.8 (p=0.89); R2= 5% (p=0.67)]. Conclusions: PSA decline of 50% or greater does not correlate with overall survival in clinical trials with docetaxel-based regimens in AIPC. Hence, a higher rate of PSA decline in a phase II trial should not guide the selection of a new docetaxel-based regimen as the experimental arm for future phase III trials. No significant financial relationships to disclose.
Outcome of patients with right heart thrombi: the Right Heart Thrombi European Registry
Authors: Marcin Koć, Maciej Kostrubiec, Waldemar Elikowski, Nicolas Meneveau, Mareike Lankeit, Stefano Grifoni, Agnieszka Kuch-Wocial, Antoniu Petris, Beata Zaborska, Branislav S. Stefanović, Thomas Hugues, Adam Torbicki, Stavros Konstantinides, Piotr Pruszczyk
Journal: European Respiratory Journal (2016)

Our aim was the assessment of the prognostic significance of right heart thrombi (RiHT) and their characteristics in pulmonary embolism in relation to established prognostic factors. 138 patients (69 females) aged (mean± sd ) 62±19 years with RiHT were included into a multicenter registry. A control group of 276 patients without RiHT was created by propensity scoring from a cohort of 963 contemporary patients. The primary end-point was 30-day pulmonary embolism-related mortality; the secondary end-point included 30-day all-cause mortality. In RiHT patients, pulmonary embolism mortality was higher in 31 patients with systolic blood pressure &lt;90 mmHg than in 107 normotensives (42% versus 12%, p=0.0002) and was higher in the 83 normotensives with right ventricular dysfunction (RVD) than in the 24 normotensives without RVD (16% versus 0%, p=0.038). In multivariable analysis the simplified Pulmonary Embolism Severity Index predicted mortality (hazard ratio 2.43, 95% CI 1.58–3.73; p&lt;0.0001), while RiHT characteristics did not. Patients with RiHT had higher pulmonary embolism mortality than controls (19% versus 8%, p=0.003), especially normotensive patients with RVD (16% versus 7%, p=0.02). 30-day mortality in patients with RiHT is related to haemodynamic consequences of pulmonary embolism and not to RiHT characteristics. However, patients with RiHT and pulmonary embolism resulting in RVD seem to have worse prognosis than propensity score-matched controls.
Hereditary cancer risk notification and testing: how interested is the general population?
Authors: M A Andrykowski, R Lightner, J L Studts, R K Munn
Journal: Journal of Clinical Oncology (1997)

Great interest in predictive testing for hereditary cancer syndromes has been reported. Prior research has focused on testing for specific hereditary syndromes and/or among individuals at high risk for positive carrier status. Given anticipated expansion of both the range of hereditary syndromes for which testing will be available, as well as the clinical settings in which testing will occur, assessment of interest in hereditary cancer risk testing and notification in the general public is warranted.As part of an annual statewide telephone survey, adults' (N = 654) interest in hereditary cancer risk testing and notification was assessed.Interest in both risk testing (82%) and risk notification (87%) was high. Logistic regression analyses indicated that disinterest in risk notification was associated with female sex, performance of fewer health protective behaviors, and better perceptions of personal health. Disinterest in risk testing was associated with these same variables as well as older age, less concern over developing cancer, and a more extensive history of cancer in first degree relatives.In the absence of risk-reducing behaviors with demonstrable efficacy, hereditary risk testing programs may have difficulty attracting the interest of those at greatest risk for carrier status. In contrast, many individuals at low risk for positive carrier status might seek testing, perhaps as a means of seeking reassurance regarding their low hereditary risk.
Abstract 9346: Imbalance Between Plasma Serotonin and Sphingosine 1-Phosphate is a Novel Therapeutic Target of Statins in Patients with Early Atherosclerosis
Authors: Tomonori Sugiura, Yasuaki Dohi, Sumiyo Yamashita, Nobuyuki Ohte, Chieko Mori, Yuji Hirowatari, Ryunosuke Ohkawa, Yuko Mishima, Yutaka Yatomi, Genjiro Kimura, Satoshi Fujii
Journal: Circulation (2010)

Background: Serotonin derived from enterochromaffin cells is incorporated to platelets and modulates vascular tone. Conversely, sphingosine 1-phosphate (S1P) is a potent bioactive lipid responsible...
Proton pump inhibition prevents gastrointestinal bleeding in ultramarathon runners: a randomised, double blinded, placebo controlled study * Commentary * Commentary * Commentary
Authors: M Thalmann, G H Sodeck, S Kavouras, A Matalas, K Skenderi, N Yannikouris, H Domanovits
Journal: British Journal of Sports Medicine (2006)

Background: Ultra-endurance running is emerging as a popular sport in Western industrialised countries. Gastrointestinal bleeding has been reported to be an adverse effect in these runners. Objective: To see if the oral administration of a proton pump inhibitor would reduce the incidence of gastrointestinal bleeding in an ultramarathon. Methods: In a randomised, double blinded, placebo controlled study, a prophylactic regimen of three days of an oral proton pump inhibitor (pantoprazole 20 mg) was tested in healthy athletes participating in the Spartathlon ultramarathon. The incidence of gastrointestinal bleeding was assessed by a stool guaiac test. Results: Results were obtained for 70 healthy volunteers. The data for 20 of 35 runners in the intervention group and 17 of 35 runners in the placebo group were entered into the final analysis. At the end of the ultramarathon, two subjects in the intervention group and 12 in the placebo group had positive stool guaiac tests (risk difference 0.86; 95% confidence interval 0.45 to 0.96; p = 0.001). Conclusion: A short prophylactic regimen of oral proton pump inhibition can successfully decrease the incidence of gastrointestinal bleeding in participants in an ultramarathon.
A phase I study of veliparib (ABT-888) in combination with low-dose fractionated whole abdominal radiation therapy (LDFWAR) in patients with advanced solid malignancies and peritoneal carcinomatosis.
Authors: Kim Anna Reiss, Joseph M. Herman, Marianna Zahurak, Anthony M. Brade, Laura A. Dawson, Angela Scardina, Caitlin Joffe, Emily Petito, Amy Hacker-Prietz, Alice P. Chen, Sarah Madhu Temkin, Naomi Horiba, Lillian L. Siu, Nilofer Saba Azad
Journal: Journal of Clinical Oncology (2014)

4139 Background: The combination of low-dose radiation therapy with poly (ADP-ribose) polymerase (PARP) inhibition has been shown to enhance anti-tumor efficacy through potentiating DNA damage in tumor cells. In this phase I study, we combined low dose fractionated whole abdominal radiation (LDFWAR) with escalating doses of veliparib (ABT-888), an orally available, small molecule PARP inhibitor, in patients (pts) with peritoneal carcinomatosis from advanced solid tumor malignancies. Methods: Pts were treated with escalating doses of veliparib, starting at 40mg PO BID on days 5-21 of the first 28-day cycle and on days 1-21 of the subsequent 2 cycles. LDFWAR consisted of 21.6Gy in 36 fractions, 0.6 Gy twice daily on days 1 and 5 for weeks 1-3 of each cycle. Circulating tumor cells (CTCs) were serially collected. Quality of life (QoL) was assessed using the EORTC-QLQ-C30 questionnaire. Results: 22 pts were treated. Treatment-related gr3 and 4 toxicites included lymphopenia (68%), anemia (9%), thrombocytopenia (14%), neutropenia (4%), leukopenia (9%), ascites (4%), vomiting (4%) and dyspnea (4%). Of 21 pts evaluable for response, disease stabilization (≥24 wks) was observed in 7 (33%) patients. Median progression free survival (PFS) was 4.7 months and overall survival (OS) was 15.5 months. In the subset of 8 ovarian and fallopian cancers (OV), median PFS was 6.9 months and OS was 17.6 months compared to PFS 2.9 months and OS 13.4 months in others. QoL data assessed at baseline and after cycle 2 showed no significant worsening with dose escalation. Pts with OV had better QoL over time than those with other cancers. Lower baseline CTCs trended towards improved OS. Conclusions: The combination of veliparib and LDFWAR is a well-tolerated regimen that results in remarkable disease stability in a refractory, pretreated pt population with advanced solid tumors and carcinomatosis, particularly in the OV subpopulation. Clinical trial information: NCT01264432. Durable disease stability (≥24wk) No. pts (%) PFS median, months (95% CI) OS median, months (95% CI) All patients (n=21) 7/21 (33) 4.6 15.5 Ovarian (n=8) 4/7 (57) 6.9 17.6 Non-ovarian (n=13) 3/14 (21) 2.9 13.4
Random assignment multicenter phase II study of modified docetaxel, cisplatin, fluorouracil (mDCF) versus DCF with growth factor support (GCSF) in metastatic gastroesophageal adenocarcinoma (GE).
Authors: M. A. Shah, S. Shibata, R. G. Stoller, M. Kemeny, P. S. Ritch, S. S. Krishnamurthi, Y. B. Su, Y. Y. Janjigian, M. Capanu, D. P. Kelsen
Journal: Journal of Clinical Oncology (2010)

4014 Background: DCF is a standard first-line treatment for metastatic GE; however 80% experience grade 3-4 non-heme toxicity, and 30% febrile/neutropenia. We developed a modified DCF regimen with a goal to minimize toxicity without compromising efficacy. We report the initial results of an MSKCC Gastric Cancer Consortium random assignment phase II study evaluating mDCF and parent DCF with GCSF in advanced GE. Methods: Previously untreated metastatic GE patients were randomly assigned to Arm A, mDCF(D 40mg/m2, FU 400mg/m2, L 400mg/m2, FU 1000 mg/m2/day x2, C 40mg/m2 day 3 q14 days without GCSF) or Arm B, DCF(D 75 mg/m2, C 75 mg/m2, FU 750 mg/m2/d x5, with prophylactic GCSF q3 weeks). The primary endpoint is 6-month PFS, with 43% 6-month PFS as DCF historical control. Target accrual is 54 patients in each arm, with type I and II error at 0.1. An early stopping rule for toxicity is employed. Results: 72 evaluable patients from 10 centers have enrolled (Arm A, n=41; Arm B, n=31): median age 56 (31-76), KPS 90% (70-100%), M:F 60:17. Grade 3/4 attributable adverse events in the first 3-months for the first 30 patients in each arm are provided: Arm A—Any (57%), neutropenia (39%), febrile/neutropenia (6%), nausea/vomiting/dehydration (3%). Arm B—Any (73%), neutropenia (40%), febrile/neutropenia (17%), nausea/vomiting (20%). Toxicity-related hospitalizations: Arm A (30%, n=9), Arm B (53%, n=16). Arm B has met the early stopping rule for toxicity. Efficacy is shown in the Table. Conclusions: In this random assignment trial, despite the use of prophylactic GCSF, standard DCF is associated with unacceptable toxicity. Without compromising efficacy (median OS 15.1 months), modified DCF appears considerably more tolerable. Modified DCF is an appropriate three-drug regimen for further development in GE, including incorporation of targeted agents. Arm A—mDCF (n=41) Arm B—parent DCF+G (n=31) Liver/peritoneal disease 88% 88% Response rate 52% (33-71%) 34% (17-52 %) 6-month PFS (95%CI) 57% (37-73%) 57% (36-73 %) Time to treatment failure (median, range) 8.6 mo (5-14 mo) 7.1 mo (4-13 mo) Overall survival, median (95% CI) 15.1 mo (9-25 mo) 12.6 mo (8-18 mo) Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis
Expression of the retinoblastoma-related gene Rb2/p130 correlates with clinical outcome in endometrial cancer.
Authors: T Susini, F Baldi, C M Howard, A Baldi, G Taddei, D Massi, S Rapi, L Savino, G Massi, A Giordano
Journal: Journal of Clinical Oncology (1998)

PURPOSE The retinoblastoma gene is the prototype of tumor-suppressor genes and has been shown to be involved in the pathogenesis and progression of several human malignancies. In this study, we determined the relation between the expression of a newly discovered retinoblastoma-related gene Rb2/p130 and outcome in patients with endometrial carcinoma. PATIENTS AND METHODS pRb2/p130 expression was determined immunohistochemically in specimens of endometrial carcinoma (stages I to IV) from 100 patients who underwent surgery as the first treatment. The pRb2/p130 status was analyzed in relation to the length of disease-free survival and disease-specific survival. RESULTS Decreased levels of pRb2/p130 in endometrial cancer cells was significantly associated with a decreased probability of remaining disease-free after treatment (P = .003) and with decreased probability of survival (P &lt; .0001). In a multivariate analysis, pRb2/p130 status (P = .004), tumor stage (P = .009), and ploidy status (P = .02) were independent predictors of clinical outcome. The risk of dying of disease was increased substantially (risk ratio, 4.91; 95% confidence interval, 1.66 to 14.54) among patients with decreased levels of pRb2/p130 in tumor cells. CONCLUSION In patients with endometrial carcinoma who did not receive radiotherapy or chemotherapy before surgery, the presence of decreased levels of pRb2/p130 in tumor cells is associated with a significantly increased risk of recurrence and death of disease, independent of tumor stage and ploidy status.
The impact of ”laying on of hands” on well being in patients with advanced cancer
Authors: G. Pohl, H. Seemann, N. Zojer, C. Ochsner, C. Luhan, M. Schemper, H. Heinzl, H. Ludwig
Journal: Journal of Clinical Oncology (2006)

18566 Background: To determine whether the impact of “laying on of hands” on well being of patients with advanced cancer is more efficient when performed by a person with “healing powers” as compared to an actor. Methods: A total of 80 patients was registered to participate in a randomized, single-blind phase III trial to evaluate the difference in efficacy of “laying on of hands” by either a “healer” or a sham person (actor). Both arms were designed to consist of a total of 40 patients, divided into 5 groups including 8 patients each. Each patient should receive treatment for 5 minutes, 3 times a week. A “Well-being scale” was used to measure differences in treatment outcomes. The primary and secondary endpoint evaluated the difference in the total sum score of the “Well-being scale” between the two arms on day 10 or day 5, respectively. Results: The first run was unblinded by the “healer”. Hence, only the second run was available for comparison. There was no significant difference in sum-score values between the “healer” and the actor (p = 0.34) with regard to the primary endpoint or the secondary endpoint (p = 0.94). After the second run, the “healer” quit and a major protocol violation occurred. Despite this major obstacle, the study was completed by the actor as a descriptive, explorative study. There was a significant decrease in total sum score values after each single treatment (day 1, 3 and 5, p &lt; 0.0001, respectively) for all patients. In addition, a significant improvement in symptoms could be found on day 5 (p &lt; 0.001) after treatment and day 10 (p = 0.0002) as compared to day 1 before treatment. Conclusions: “Laying on of hands” resulted in a significant improvement of cancer or cancer-therapy associated symptoms. The magnitude of improvement obtained was similar when “treatment” was provided by a self declared “healer” or an actor, although the comparison was hampered by protocol vialotions by the “healer”. No significant financial relationships to disclose.
Phase III trial of thoracic irradiation with or without cisplatin for locally advanced unresectable non-small-cell lung cancer: a Hoosier Oncology Group protocol.
Authors: C Blanke, R Ansari, R Mantravadi, R Gonin, R Tokars, W Fisher, K Pennington, T O'Connor, S Rynard, M Miller
Journal: Journal of Clinical Oncology (1995)

PURPOSE Here we report the results of a phase III study, to evaluate whether the addition of cisplatin to radiation therapy (XRT) would improve progression-free survival or overall survival for patients with locally advanced unresectable non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Two hundred forty patients with biopsy-proven unresectable NSCLC without distant metastases or lower-stage medically inoperable patients were randomized to one of two treatment arms. Arm A consisted of thoracic XRT alone, 60 to 65 Gy total tumor dose in daily fractions of 1.80 to 2.00 Gy; and arm B consisted of identical XRT with the addition of cisplatin 70 mg/m2 every 3 weeks for three cycles beginning on the first day of irradiation. RESULTS Two hundred fifteen patients were eligible and assessable. The overall response rate was 50% on the combination arm versus 38% on the XRT-alone arm (P = .076). The median progression-free survival time was 23 versus 22 weeks, respectively (P = .0537). The median survival time was 43 weeks on the combination arm versus 46 weeks on the XRT arm (Poverall = .3469). The 1-, 2-, and 5-year survival rates were 43%, 18%, and 5% on the combination arm versus 45% 13%, and 2% on the XRT arm, respectively. CONCLUSION Cisplatin, administered every 3 weeks, does not significantly improve response rate, progression-free survival, or overall survival when added to thoracic XRT for locally advanced unresectable NSCLC.
An Integrated Analysis of Heterogeneous Drug Responses in Acute Myeloid Leukemia That Enables the Discovery of Predictive Biomarkers
Authors: Weihsu C. Chen, Julie S. Yuan, Yan Xing, Amanda Mitchell, Nathan Mbong, Andreea C. Popescu, Jessica McLeod, Gitte Gerhard, James A. Kennedy, Goce Bogdanoski, Stevan Lauriault, Sofie Perdu, Yulia Merkulova, Mark D. Minden, Donna E. Hogge, Cynthia Guidos, John E. Dick, Jean C.Y. Wang
Journal: Cancer Research (2016)

Abstract Many promising new cancer drugs proceed through preclinical testing and early-phase trials only to fail in late-stage clinical testing. Thus, improved models that better predict survival outcomes and enable the development of biomarkers are needed to identify patients most likely to respond to and benefit from therapy. Here, we describe a comprehensive approach in which we incorporated biobanking, xenografting, and multiplexed phospho-flow (PF) cytometric profiling to study drug response and identify predictive biomarkers in acute myeloid leukemia (AML) patients. To test the efficacy of our approach, we evaluated the investigational JAK2 inhibitor fedratinib (FED) in 64 patient samples. FED robustly reduced leukemia in mouse xenograft models in 59% of cases and was also effective in limiting the protumorigenic activity of leukemia stem cells as shown by serial transplantation assays. In parallel, PF profiling identified FED-mediated reduction in phospho-STAT5 (pSTAT5) levels as a predictive biomarker of in vivo drug response with high specificity (92%) and strong positive predictive value (93%). Unexpectedly, another JAK inhibitor, ruxolitinib (RUX), was ineffective in 8 of 10 FED-responsive samples. Notably, this outcome could be predicted by the status of pSTAT5 signaling, which was unaffected by RUX treatment. Consistent with this observed discrepancy, PF analysis revealed that FED exerted its effects through multiple JAK2-independent mechanisms. Collectively, this work establishes an integrated approach for testing novel anticancer agents that captures the inherent variability of response caused by disease heterogeneity and in parallel, facilitates the identification of predictive biomarkers that can help stratify patients into appropriate clinical trials. Cancer Res; 76(5); 1214–24. ©2016 AACR.
Incidence and survival among female breast cancer patients in the United States: An analysis from national registry data 2000-2009.
Authors: Huan Huang, Kathy Lang, Madhav Namjoshi, Victoria Federico, Joseph Menzin
Journal: Journal of Clinical Oncology (2012)

41 Background: This study evaluated incidence and survival among breast cancer (BC) patients in the United States during 2000-2009, by cancer stage. Methods: The Surveillance, Epidemiology, and End Results (SEER) Program SEER*Stat Database was used for this analysis. SEER is an epidemiologic surveillance system consisting of population-based tumor registries designed to track cancer incidence and survival in the US. The registries routinely collect information on incident cancer cases in areas that represent approximately 25% of the US population. We evaluated age-adjusted (to the 2000 US standard population) incidence (number of cases per 100,000 population), and survival among newly diagnosed female breast cancer patients during 2000-2009, by cancer stage (localized, regional, distant and unknown/unstaged). Results: A total of 547,086 cases of female BC were reported to SEER during 2000-2009. Localized BC (average incidence rate during 2000-2009 of 77.6 cases per 100,000 population) was the most common stage among newly diagnosed patients, followed by regional (39.7), distant (6.2), and unknown/unstaged BC (3.2). Incidence rates decreased for regional (average annual change -1.3%), localized (average annual change -0.2%), and unknown/unstaged (average annual change -7.2%) BC and increased for distant BC (1.4%). One-year (five-year) survival rates averaged over 2000-2009 (2000-2005 for five-year) were 100% (97%) for localized BC, 98% (82%) for regional BC, 65% (22%) for distant BC, and 80% (55%) for unknown/unstaged BC. Both one-year and five-year survival rates were steady during this period. Conclusions: Based on US population-based registry data, the incidence and survival for breast cancer were relatively steady for localized, regional and distant BC over the most recently-available 10-year period. There is considerable room to improve survival rates for patients with regional and distant BC. Further studies evaluating the survival experience of later-stage BC patients based on other key factors, such as age, race, treatment patterns, and tumor characteristics (e.g., ER/HER2 status) are warranted.