tbuckley/cabot-search huggingface dataset:
Progression-free survival as surrogate endpoint of overall survival in patients with advanced/recurrent gastric cancer: Individual patient data analysis on 4,102 patients from 20 randomized trials.
Authors: K. Shitara, T. Burzykowski
Journal: Journal of Clinical Oncology (2011)

4095 Background: New developed agents for advanced gastric carcinoma (AGC) are expected to prolong survival with acceptable toxicity. Overall survival (OS) can be observed only after prolonged follow-up, and any potential effect of first-line therapies on OS may be confounded by subsequent therapy. Using the strength of the meta-analysis approach, the GASTRIC group investigated whether progression-free survival (PFS) could be considered a valid surrogate for OS to assess the benefits of first-line therapies for patients with AGC. Methods: Individual patient data were collected on 4,102 patients in 20 randomized trials. Surrogacy was assessed through the correlation between the endpoints as well as through the correlation between the treatment effects on the endpoints. For this latter analysis, we relied on the comparison between the experimental arms of the trials included in the meta-analysis and their corresponding control arms. We defined as “experimental” the treatment arms that contained more drugs (e.g., triple combinations as compared with double combinations, regardless of the drugs involved in the respective regimens) or that contained newer agents when the same number of drugs was tested. Sensitivity analyses are carried out on trials completed before and after 1991 and on patients with evaluable clinical responses. Results: PFS (rank correlation coefficient, 0.834; 95% CI, 0.833 to 0.835) was strongly associated with OS at the individual level. However, log hazard ratio of PFS was only moderately correlated with log hazard ratio of OS. Trial-level R² adjusted for the estimation errors in the treatment effect was estimated to 0.57 (95% CI= -0.05, 1.19), but the confidence limits were too wide to be informative. Conclusions: This study shows that PFS in AGC is strongly correlated with OS at the individual level. However, treatment effects on PFS are only moderately correlated with treatment effects on OS. Further research is needed to clarify the surrogacy of PFS for OS or the role of PFS as the true end point in future randomized trials of chemotherapy for AGC.
Predictor c: A tissue-based IVD predicting progression of disease in colorectal cancer UICC stages II or III.
Authors: H. Adams, B. Hinzmann, T. Mayr, I. Klaman, A. Rosenthal
Journal: Journal of Clinical Oncology (2010)

3612 Background: We discovered a prognostic gene signature (Predictor-C) containing 32 Affymetrix probesets in a cohort of 55 pts with colorectal cancer (CRC) UICC stage I or stage II. From all pts snap-frozen tumor samples and a minimum follow-up of 5 years were available. Predictor-C discriminates between pts with high risk vs. low risk of progression of disease. We now report on a performance evaluation of Predictor-C in an independent set of CRC pts with UICC stage II or stage III disease. Methods: We tested the hypothesis that the lower one-sided 95% exact confidence limit of the correct classification rate (CCR) of Predictor- C in the validation set is higher than 0.55 with a power of > 0.85, given the true CCR is 0.68. For this hypothesis test, data from 164 pts would be required. We selected 164 pts from a total of 393 pts who were recruited into an international multicenter study of CRC. Pts were operated on between 1990 and 2000 in Denmark, Finland, Germany, Austria, Netherlands and Canada. For all 393 pts frozen CRC tissue, Affymetrix array data (U133 Plus 2.0, U133A) and a follow-up of five years were available. The validation set is comprised of 90 pts with stage II and 74 pts with stage III. Seventy-two pts suffered from a progression of disease, while 92 pts had no propgression. Results: Applying Predictor-C to the validation set revealed a CCR of 0.63 (95% exact confidence limits [CI]: 0.555-0.708), a sensitivity of 0.64 (95% CI: 0.517-0.749), a specificity of 0.63 (95% CI: 0.523-0.729), a positive predictive value (PPV) of 0.58 (95% CI: 0.459-0.685), and a negative predictive value of 0.69 (95% CI: 0.580-0.787). The point estimate for progression-free survival at 5 years after surgery for pts classified as low-risk is 0.62 (95% CI: 0.458-0.789), and for pts classified as high-risk this estimate is 0.45 (95% CI: 0.332-0.564). The baseline characteristics of these 164 pts were representative for the whole population of CRC patients diagnosed with UICC stage II or stage III, in almost all aspects. Conclusions: Predictor-C was successfully validated in an independent set of pts with UICC stage II or UICC stage III. The clinical utility of Predictor-C lies in its PPV of 58% justifying the adjuvant treatment of the high-risk group. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Signature Diagnostics AG Signature Diagnostics AG Signature Diagnostics AG
Role of obesity in a randomized placebo-controlled, double-blind trial of difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas.
Authors: B. S. Lin, J. A. Zell, N. Madson, C. E. McLaren, E. W. Gerner, F. L. Meyskens
Journal: Journal of Clinical Oncology (2011)

374 Background: Chemoprevention with difluoromethylornithine (DFMO) plus sulindac markedly reduces risk of recurrence in colorectal adenoma (CRA) patients. Obesity is associated with risk of CRA and colorectal cancer (CRC). This study investigates how obesity influences CRA characteristics at baseline and risk of recurrence after treatment with DFMO plus sulindac vs. placebo. Methods: Our analysis included subjects enrolled in a phase III CRA prevention clinical trial investigating DFMO plus sulindac vs. placebo. Patients were classified by obesity (BMI &gt; 30 kg/m 2 ) status at baseline. Pearson's χ 2 statistic or Fisher's exact test and Mann-Whitney U test were used to compare baseline characteristics with regard to obesity status. Log-binomial regression analysis was used to determine the relative risk of metachronous adenoma, adenoma with advanced histology, or multiple adenomas, adjusted for covariates. Results: At baseline, obesity was associated with increased adenoma number (p =0.017), size (p =0.003), advanced histology (p =0.042), high-risk adenomas (p =0.0002), and distal adenomas (p =0.038). Obesity did not modify adenoma recurrence after treatment with DFMO plus sulindac or placebo (p =0.80). Conclusions: Our results provide supporting evidence for the association of obesity with high-risk adenoma features at baseline; however, obesity does not substantially modify CRA risk reduction after treatment with DFMO plus sulindac vs. placebo. [Table: see text] [Table: see text]
The impact of bevacizumab usage on patients who were curative resected for liver-confined metastases from colorectal cancer.
Authors: N. Turan, D. Koca, F. Dane, N. Özdemir, B. B. Oven Ustaalioglu, I. Oztop, A. Ulas, V. Berk, M. Kucukoner, O. Balakan, M. A. Ozturk, M. Benekli, M. Gumus, U. Yilmaz, S. Ozkan, S. Buyukberber
Journal: Journal of Clinical Oncology (2011)

e14120 Background: We investigate whether there have been differences in disease-free survival (DFS) and overall survival (OS) among patients who were treated with different cytotoxic regimens (fluoropyrimidines alone or irinotecan or oxaliplatin based) with or without bevacizumab after complete resection of liver-confined metastases from colorectal cancer (CRC). Methods: Between May 2000 and July 2010, a total of 166 patients who underwent liver resection with curative intent from CRC were retrospectively analyzed. Results: Of the 166 patients, 70 were treated with oxaliplatin based regimens, 71 were irinotecan based and 25 were treated with fluoropyrimidines alone. With respect to bevacizumab usage, 72 were treated with cytotoxic regimens plus bevacizumab (BEV) while 94 were treated with cytotoxic regimens alone (NoBEV). After metastasectomy, the median follow-up time was 21 months, and the median OS and DFS were 54 months and 13 months, respectively. In the univariate analysis, no significant differences were found between BEV and NoBEV groups with respect to DFS (p:0.52) and OS (p:0.56). No statistical differences were found in most of baseline characteristics (age, gender, number and diameter of the largest liver lesions, surgical margins status, colon or rectum primary, prior adjuvant chemotherapy, metachronous or synchronous metastases, stage of the primary tumor) between BEV and NoBEV groups in exception that the type of cytotoxic regimens combined with bevacizumab. The majority of cytotoxic regimens used with BEV group were irinotecan based while the majority of which were oxaliplatin based regimens in NoBEV group. Conclusions: Adding bevacizumab to cytotoxic regimens has no impact on clinical outcomes with respect to DFS and OS after complete resection of liver-confined metastases for CRC.
Phase I study evaluating the pharmacokinetics (PK) of components of S-1 in patients with impaired hepatic function.
Authors: D. Mahalingam, J. Sarantopoulos, M. S. Gordon, N. B. Pandya, B. R. Tan, A. C. Mita, C. Zergebel, K. Saito, C. H. Takimoto, M. W. Saif
Journal: Journal of Clinical Oncology (2011)

2612 Background: S‐1 is a new oral fluoropyrimidine that combines tegafur (FT), a prodrug of 5-FU, with two modulators, gimeracil (CDHP), and oteracil (Oxo). CDHP inhibits 5-FU degradation by DPD inhibition, and Oxo inhibits 5-FU phosphorylation in the GI tract. CDHP and Oxo are mainly renally excreted, however, FT is metabolized in the liver. Hepatic impairment (HI) could influence both the conversion process of FT to 5‐FU by CYP2A6 and the catabolism of 5-FU by DPD. Methods: Patients (pts) with advanced solid tumors, ECOG ≤2, adequate renal and heme function were stratified into 4 HI cohorts: normal, mild, moderate, and severe, using NCI ODWG Criteria. Six pt cohorts received the same dose of S-1, 30 mg/m2 PO BID for 14 days followed by 7-day off period in 21 day cycles. Blood PK and urine analysis of S-1 components, metabolites (5-FU, FBAL, CA, uracil) were performed during cycle 1. Objectives were to provide a recommended dose (RD) and characterize safety, for different HI cohorts. Results: 27 pts received S-1, 5 pts required 1 dose reduction. Median age was 55 (25-72), 14 pts were male. The majority of pts had GI tumors. HI cohorts(pt #): normal(6), mild(8), moderate(7), severe(6). Most common treatment-emergent AEs reported over all cycles for all pts: nausea (52%), diarrhea (37%), vomiting (37%), fatigue (33%), stomatitis (22%), and rash (15%). 1 grade 3 HFS in mild cohort. 1 pt in the mild HI cohort experienced 1 DLT – grade 3 elevated ALT on day21 which resolved after 8 days. After single and multiple doses of S-1, there was considerable variability in plasma PK data with no trends observed in the magnitude of PK parameters as a function of HI. No effect of HI on FT, Oxo, or FBAL for AUC or Cmax following single- or multiple-dose administration was observed. No accumulation of S-1 components or metabolites. SD was seen in 11 pts (CRC, gastric, appendix, lung and melanoma) and 1 PR (pancreas) in the mild HI cohort. Conclusions: S-1 was generally well tolerated in this pt population with a safety profile consistent with previous reports. Clinical and PK results suggest that RD for S-1 for pts with mild, moderate, or severe HI is 30 mg/m2 BID for 14 days followed by a 7-day off period. Dose adjustment based on severity of HI is not warranted.
CYC065, a Potent Derivative of Seliciclib Is Active In Multiple Myeloma In Preclinical Studies
Authors: Samantha Pozzi, Diana Cirstea, Loredana Santo, Doris M Nabikejje, Kishan Patel, Kathryn M Luly, Gaurav Gharti-Chhetry, Sonia Vallet, Homare Eda, Teru Hideshima, Simon R Green, Kenneth C. Anderson, David T. Scadden, Noopur Raje
Journal: Blood (2010)
Emerging Roles of Wisp-1 and SFRP4 in Proliferation and Differentiation Potential of Wharton's Jelly Mesenchymal Stem/Stromal Cells
Authors: Aristea Batsali, Charalampos Pontikoglou, Emmanuel Agrafiotis, Elisavet Kouvidi, Irene Mavroudi, Athina Damianaki, Maria-Christina Kastrinaki, Helen Papadaki
Journal: Blood (2014)
Extended Follow-up of the International Randomized Phase 3 First-Line Indolent Trial (FIT) Shows Durable Benefit of 90 Y-Ibritumomab Tiuxetan (Zevalin®) Consolidation of First Remission in Advanced Stage Follicular Non-Hodgkin’s Lymphoma.
Authors: Franck Morschhauser, Angelika Bischof-Delaloye, Ama Z S Rohatiner, Gilles Andre Salles, Jens Kuhlmann, Willem JL Van Putten, John Radford, Pierre Soubeyran, Achiel Van Hoof, Anton Hagenbeek
Journal: Blood (2008)
Factors associated with on-time regular screening among the Korean population eligible to be screened for gastric cancer: A nationwide retrospective cohort study based on National Cancer Screening Program (NCSP) data.
Authors: M. Hahm, K. S. Choi, H. Lee, J. K. Jun, E. Park
Journal: Journal of Clinical Oncology (2011)

1558 Background: Regular screening for early detection can decrease cancer mortality. Our aim was to identify factors associated with recurrent screening among all people eligible to be screened for gastric cancer. Methods: The study population was derived from National Cancer Screening Program data maintained by the National Health Insurance Corporation. The study population was restricted to persons among the NCSP-recommended invited population who were screened for gastric cancer in 2005 and 2006. We identified whether these people attended the gastric-cancer screening program again after 2 years. Finally, 4,060,257 participants were selected as study subjects. Logistic regression was used to identify factors associated with rescreening behavior. Results: 59.4% of baseline participants attended a subsequent screening program 2 years later. NHI beneficiaries with a premium over 50% were significantly more likely to be rescreened than were those on medical aid (OR = 2.14, CI = 2.12–2.16). Subjects who experienced a ‘true negative’ result at baseline screening were more likely to be screened again (OR = 1.03, CI = 1.02–1.04). People who had an upper gastrointestinal series at the baseline test were more likely to be rescreened than those who had an endoscopy. In addition, experience with a previous opportunity to be screened and prior gastric-cancer screening attendance were correlated with rescreening (p < 0.05). Conclusions: The study results highlight that income level affected the rescreening rate despite full support by the NCSP for low-income people. Furthermore, continuous exposure to the screening program under the NCSP increased the rescreening rate.
Clinical trial participation among patients with advanced cancer: What characteristics most influence enrollment?
Authors: R. Jimenez, B. Zhang, M. E. Nilsson, S. Joffe, C. Lathan, H. G. Prigerson
Journal: Journal of Clinical Oncology (2011)

9073 Background: Studies using administrative data report that patients belonging to racial/ethnic minority groups are less likely to be enrolled in clinical trials. We studied a cohort of terminally ill cancer patients to determine: a) if the observed lower rate of racial/ethnic minority trial enrollment was accounted for by psychosocial confounding factors, and b) the factors most associated with clinical trial enrollment. Methods: Coping with Cancer (CwC) is an NCI/NIMH-funded multi-site, prospective longitudinal study of patients with advanced cancer. Baseline interviews with 358 patients captured clinical trial enrollment as well as patients’ medical status and psycho-social characteristics. Logistic regression models estimated associations between enrollment and select baseline characteristics. Stepwise, backward and subset model selection procedures were applied to identify confounding variables. Baseline characteristics significant at α= 0.05 were retained in the final model. Results: At baseline, a median of 4.4 months prior to death, 35 of 358 patients (9.8%) reported being enrolled in a trial. In unadjusted analyses, race/ethnicity, health insurance coverage, performance status, recruitment from Yale Cancer Center, having pancreatic or lung cancer, preferring life-extending care, not having discussed end-of-life care and not wanting to discuss life-expectancy with their physician were associated (p<0.05) with enrollment. In multivariate analysis, patients not reporting an end-of-life discussion (AOR, 0.18; 95%CI 0.04-0.72), not wanting to discuss life-expectancy (AOR, 0.31; 95%CI 0.04-0.83), and those receiving care at Yale (AOR, 12.26; 95%CI 1.09-4.84) were more likely than other patients to be trial enrollees. Conclusions: Patient race/ethnicity was not associated with clinical trial enrollment after adjustment for psychosocial covariates. Patients endorsing less engagement in discussions about end-of-life planning were more likely to be enrolled in a clinical trial.
Efficacy of darbepoetin alfa in colorectal cancer patients: Data from the CHOICE study.
Authors: S. Van Belle, K. Urbanski, H. Orfeuvre, P. Foucher, T. Wheeler, B. Pujol
Journal: Journal of Clinical Oncology (2011)

552 Background: To evaluate adherence to hemoglobin (Hb) values recommended by the updated European (EU) product label for darbepoetin alfa (DA) and describe hematological response in patients (pts) receiving DA for the treatment of chemotherapy-induced anemia in clinical practice. Data of colorectal cancer (CRC) pts are reported. Methods: A prospective, multicenter, observational study assessed DA use in CRC, breast, ovarian and lung cancer pts in 11 EU countries. Data (such as Hb levels and need for red blood cell (RBC) transfusions) were extracted from medical records on an electronic case report form. Results: This interim analysis included 1,290 pts. 192 pts had CRC: 1% had stage I, 6% stage II, 18% stage III and 75% stage IV cancer. The most-used chemotherapy regimens were 5-fluoruracil or capecitabine (33%), ironotecan- (27%) and oxaliplatin-based (24%). Baseline (BL) Hb values were available for 189 pts; the mean (standard deviation, SD) Hb value at BL was 9.8 (0.8) g/dL; 60% of CRC pts had BL Hb values of &lt;10 g/dL and 90% values of &lt;11 g/dL. Of the 119 pts still on study at week (wk) 9, 60% (95% CI: 51, 68) achieved a Hb level of 10-12 g/dL at wk 9 (primary outcome measure). With increasing BL Hb values, more pts achieved Hb ≥10 g/dL (see table). The mean (SD) Hb at the end of treatment period (EOTP) was 11.0 (1.5) g/dL. The Kaplan-Meier (K-M) % of pts with Hb levels ≥10 g/dL at EOTP was 91% (only pts with BL Hb &lt;10 g/dL included). The K-M % of pts with Hb levels &gt;13 g/dL at EOTP was 10% for pts with BL Hb &lt;10 g/dL. Of pts in the study for ≥29 days after start of DA, the K-M % of pts needing RBC transfusions after wk 5 was 21% at EOTP. No treatment-related adverse drug reactions were reported. Conclusions: Most CRC pts were treated in accordance with the EU product label. The high K-M % of pts with Hb values ≥10 g/dL suggests DA is effective. Hb levels &gt;13 g/dL were rare for pts with BL Hb &lt;10 g/dL. Sponsored by Amgen (Europe) GmbH. [Table: see text] [Table: see text]
The SH2-B Adaptor Protein Negatively Regulates EPO-Dependent Signalling Via Interaction with Erythropoietin Receptor Ptyr-343
Authors: Mojib Javadi Javed, Edda Tschirch, Bryan K Beattie, Natalie Stickle, Kai Huang, Robert Jaster, Christin Carter-Su, Dwayne Barber
Journal: Blood (2008)
Gene expression profiles involved in survival and progression pathways modulated by oligoelements and lachesis muta venom in MDA-MB-231 breast cancer cells using expression macroarray analysis
Authors: E. J. Crescenti, V. Medina, M. Croci, R. Bergoc, F. Sanchez-Jimenez, E. Rivera
Journal: Journal of Clinical Oncology (2008)

22192 Background: We have previously reported that the combination of oligoelements (Se, Zn, Mn) plus Lachesis muta venom (O-LM) significantly inhibits proliferation of malignant human cell lines including breast cancer cells like MCF-7 and MDA-MB-231. The effect of O-LM was associated with an induction of cell cycle arrest, differentiation and apoptosis. Furthermore, O-LM increased survival of animals with experimental tumors by additionally producing an up-regulation of innate and T-cell mediated immunity (ASCO Proceedings 2006, 2007). In the present work we analyzed the gene expression profiles using PCR array analysis and identified several genes in the angiogenic and survival pathways that are modulated by O-LM in MDA-MB-231 cells. Methods: The amount of cDNA was determined using cDNA GEarray (SuperArray Biosciences). After subtracting the background, the signal intensity of each single spot was normalized to that of the ribosomal protein L13a. Similar results were obtained with other housekeeping genes (β-actin, GAPDH). Results were expressed as the mean ± SEM of the expression ratios of O-LM-treated vs. untreated cells from triplicates Results: O-LM markedly up- regulated expression of genes related to growth inhibition and apoptosis as INFα,γ; IL-8, TNFα (5, 6, 3, 6.3-fold, respectively). Conversely, O-LM increased expression of genes linked to migration and angiogenesis like EDG1; EFNA2; ETS-1; FGF1,6; FGFR1, VEGFB; GRO1; ITGB3; MMP2, MMP9, HIF1A, MDK, (5, 5.3, 5.8, 4, 6, 3.2, 1.5, 2.1, 6, 5.9, 4.7, 3.2, 4.5-fold) while decreased the expression of TGFB1;TGFR2;TIMP-1. By using different techniques like RT-PCR, Western blot, among others we further confirmed the effect of O-LM on gene expression profile of the breast cancer cells. Conclusions: The therapeutic action of O-LM is based on its ability of targeting simultaneously multiple pathways involved in cancer development and progression. Present study clearly demonstrates the capacity of O-LM to modulate the expression of different genes related to angiogenic and survival pathways that are correlated with the mediated signaling processes previously reported. No significant financial relationships to disclose.
Efficacy and safety of endoscopic submucosal dissection for superficial squamous esophageal neoplasia: A systematic review and meta-analysis of the literature.
Authors: Joon Sung Kim, Byung-Wook Kim, Jeong-Seon Ji, Bo-In Lee, Hwang Choi
Journal: Journal of Clinical Oncology (2013)

127 Background: The number of ESD candidates with esophageal neoplasia has increased with the recent development of endoscopy. Increasing number of studies has recently reported the application of endoscopic submucosal dissection (ESD) for treatment of esophageal lesions. However, most of these series were retrospective and single center studies that included only a relatively small number of cases. The aim of this systematic review and meta-analysis was to assess the efficacy and safety of ESD for esophageal lesions. Methods: Comprehensive literature searches were performed on studies that reported ESD for the removal of esophageal dysplasia or esophageal squamous cell carcinoma. MEDLINE, EMBASE and the Cochrane Library were searched using the primary keywords “endoscopic submucosal dissection”, “esophagus” and “esophageal”. Statistical analyses were executed by the aid of Comprehensive Meta-analysis software version 2. Results: A total of 17 studies were identified. Meta-analysis revealed pooled estimates of complete cure en bloc resection as 89.7% (95%CI 85%-93%; I 2 =54.6%) and pooled estimates of en bloc resection as 96% (95%CI;93%-98%; I 2 =21.2). The pooled estimates of complications of ESD such as bleeding, perforation and stenosis were 2%, 5%, 12%, respectively. Subgroup analysis was performed by grouping studies into two groups. Complete cure en bloc resection was 92.4% for studies from Japan and 81.6% for studies from other countries than Japan. Conclusions: ESD appeared to be an extremely effective technique to achieve complete cure en bloc resection of superficial squamous esophageal neoplasia. The very low rate of complications also shows the potential safety of this approach. However, the resection rates were statistically different for studies from Japan and for studies from other countries. Standardization of techniques and equipment may be needed before ESD can be widely accepted for treatment of superficial squamous esophageal neoplasms.