tbuckley/cabot-search huggingface dataset:
Recombinant erythropoietin (Epo)/darbepoetin (Darb) associated venous thromboembolism (VTE) in the oncology setting: Findings from the Research on Adverse Drug Events And Reports (RADAR) project
Authors: K. Gleason, C. Tigue, P. Yarnold, J. McKoy, C. Angelotta, D. Courtney, B. Edwards, J. Bohlius, C. Bennett
Journal: Journal of Clinical Oncology (2007)

2552 Background: Cancer patients are at increased risk for VTE as compared to the general population, making VTE as a sADR difficult to detect in the oncology setting. In 2004, two phase III trials identified higher mortality rates among epo-treated cancer patients who were receiving chemotherapy in “off-label” settings- with these studies identifying higher VTE rates in the treatment arms. We reviewed data on epo/darb-associated VTE in the oncology setting. Methods: Data sources were meta-analyses and the FDA’s MedWatch database. Results: Since 1996, only 259 VTE reports (darb: n=30, epo: n=229) of VTE in the setting of chemotherapy and epo/darb were reported to MedWatch. Meta-analyses findings are tabulated below: Conclusions: In 2004, package inserts for Epo/Darb were revised, identifying increased risks of VTE with these agents in the oncology setting. Identification of this adverse drug reaction thirteen years after Epo received FDA approval for this indication (and had been prescribed to &gt; 500,000 cancer patients) illustrates difficulties inherent with current pharmacovigilance efforts. [Table: see text] No significant financial relationships to disclose.
Bendamustine Versus Chlorambucil as First-Line Treatment in B Cell Chronic Lymphocytic Leukemia: An Updated Analysis from An International Phase III Study.
Authors: Wolfgang Ulrich Knauf, Toshko Lissitchkov, Ali Aldaoud, Anna Liberati, Javier Loscertales, Roul Herbrecht, Gunnar Juliusson, Gerhard Postner, Liana Gercheva, Stefan Goranov, Martin Becker, Klaus Hoeffken, Francoise Huguet, Robert Foa, Karlheinz Merkle, Marco Montillo
Journal: Blood (2008)
Ewing's sarcoma in bones of the hands and feet: a clinicopathologic study and review of the literature.
Authors: S K Shirley, F B Askin, L A Gilula, T J Vietti, P R Thomas, G P Siegal, W R Reinus, J M Kissane, M E Nesbit
Journal: Journal of Clinical Oncology (1985)

Review of current data from the Intergroup Ewing's Sarcoma Study (IESS) shows that Ewing's sarcoma (ES) is rare in bones of the hands and feet. Only 12 of 377 evaluable patients in the first two IESS studies had a primary tumor in these small, distal bones. The age distribution was typical for that seen in patients with ES at other sites. Males were affected twice as often as females, and tumors in the bones of the feet were much more common than those in the hands. All signs and symptoms were local in distribution. As in other sites, the dominant histologic pattern was categorized as diffuse. With the exception of those patients with lesions in the calcaneus, the prognosis for disease-free survival was excellent. A literature review of cases of ES reported in bones of the hands and feet showed generally comparable results.
Time trends in the use of adjuvant chemotherapy (CTX) and outcomes in women with T1N0 breast cancer (BC) in the National Comprehensive Cancer Network (NCCN).
Authors: Ines Maria Vaz Duarte Luis, Rebecca A Ottesen, Melissa E Hughes, Rizvan Mamet, Harold J. Burstein, Stephen B. Edge, Ana M. Gonzalez-Angulo, Sara H. Javid, Beverly Moy, Hope S. Rugo, Richard L. Theriault, Jane C. Weeks, Nancy U. Lin
Journal: Journal of Clinical Oncology (2013)

1006 Background: The role of adjuvant CTX in women with small BC is controversial. Here we analyze time trends of CTX use and outcomes in women with T1N0 BC treated at NCCN cancer centers. Methods: 8917 women were identified who received surgery or systemic therapy at an NCCN center with T1a, T1b or T1c N0 M0 BC between 2000-09. Tumors were grouped by biologic subgroups by hormone receptor (HR) and HER2 status and T subgroups (T1a, T1b, T1c). Primary endpoints were receipt of adjuvant CTX (± trastuzumab) and BC specific survival (BCSS). Chi-square, Cochran Armitage trend, Kaplan Meier estimates, log-rank test and Cox hazard proportional regression were used for analysis. In this report we focus on T1a/b results (N=4113). Results: Median follow up time was 5.5 years (range, 0.7-12.7). CTX use differed according to biologic and T subgroups, with significant changes over time (Table). In 2009, more than 50% of patients (pts) with HER2+ and HR-2- T1a/b breast cancers received CTX (± trastuzumab). The table lists use of CTX by year and subset and the 5 year BCSS for pts treated and not treated with CTX. Conclusions: A high proportion of pts with HER2+ and HR-HER2- T1N0 breast cancers received adjuvant CTX, with a sharp increase in use of CTX among HER2+ over the past decade. Use of CTX is higher in T1b compared to T1a tumors. In this study, women with T1a and T1b tumors have an excellent prognosis without CTX at 5 Yr. Careful examination of cutoffs for absolute benefit sufficient to recommend CTX is warranted. [Table: see text]
Pathologic node involvement as a prognostic factor in HER2-amplified primary breast cancer (BC) patients (pts) treated without trastuzumab
Authors: S. Chabaud, O. Tredan, I. Treilleux, V. Bourdes, T. Gargi, D. Pérol, T. Bachelot
Journal: Journal of Clinical Oncology (2008)

11537 Background: Current management of BC pts with HER2 overexpression includes chemotherapy and trastuzumab treatment. In order to assess the potential individual benefit of this treatment we analyzed outcome data and prognostic factors in a prospectively characterized cohort of HER2 positive BC pts treated before the trastuzumab era. Methods: Medical records from 103 HER2 positive BC pts treated between 1996 and 2005 according to our standard institutional protocols without adjuvant trastuzumab were analyzed. Clinicopathologic variables such as age, menopausal status, clinical stage, pathologic tumor size (pTS), histologic grade (HG), ER and PR status, lymphovascular invasion (LVI) and axillary lymph node (ALN) status were extracted from the institutional database that has been prospectively collected since 1996. Variables with a 0.15 significance level in univariate analysis were entered in a multivariate Cox model. A backward stepwise procedure discriminated non-influential variables at 0.05 level. Results: Median follow-up was 3.5 years (ys) (95%CI, 3.0–3.8) and median age was 55 ys (range: 33–91). pTS was >20 mm for 63% of tumors; 89% were ductal carcinoma, 34% were grade 2 and 62% grade 3; 49% had LVI, and 37% were ER negative; 37% had micrometastatic ALN, 48% had macrometastatic ALN and 34% had ≥ 3 ALN+. Sixty percent received chemotherapy and 65% received hormone therapy. The relapse rate was 38%, 31 pts died and median progression-free survival (PFS) was 5.3 ys (95%CI, 2.9–7.2). HG is not a prognostic factor by univariate analysis. Only macrometastatic ALN (HR=3.0; 95%CI, 1.1–8.3; p=.034) are the only independent predictors for PFS by multivariate analysis. Five-ys PFS rate was 90% (95%CI, 60–98%) for N0 pts with pTS ≤ 10 mm. Conclusions: For pts with HER2 positive breast cancer, the usual clinicopathologic features may not be appropriated to predict outcomes. Further biological characterizations may allow for better pts selection. No significant financial relationships to disclose.
Correlation of insulin-like growth factor 1 (IGF-1) expression and clinical outcome in K-RAS wild-type colorectal cancer patients treated with cetuximab-irinotecan
Authors: M. Scartozzi, I. Bearzi, A. Mandolesi, F. Loupakis, A. Zaniboni, R. Berardi, C. Pierantoni, G. Masi, A. Falcone, S. Cascinu
Journal: Journal of Clinical Oncology (2009)

4017 Background: K-RAS wild type colorectal tumors show an improved response rate to anti-EGFR monoclonal antibodies. Nevertheless 70% to 40% of these patients still does not seem to benefit from this therapeutic approach. Recent data suggested that in presence of IGF-1 system altered activation colorectal cancer cells may escape anti-EGFR mediated cell death. The interaction between IGF-1 expression and K-RAS mutational analysis was tested in order to verify the ability of IGF-1 to identify a sub-group of patients more likely to benefit from EGFR-targeted antibodies treatment. Methods: IGF-1 expression and K-RAS mutational status was assessed in advanced colorectal cancer patients receiving irinotecan/cetuximab. Results: Sixty-two patients were analyzed. IGF-1 was negative in 21 patients (34%). and overexpressed in the remaining 41 cases (66%). In IGF-1 negative and IGF-1 positive tumors we observed progressive disease in 6 (29%) and 26 (63%) patients respectively (p = 0.01). Median time to progression was 7.7 months in patients showing IGF-1 negative tumors and 2.3 months for IGF-1 expressing tumors (p = 0.005). Among K-RAS wild type patients, IGF-1 negative and positive tumors showed a partial response to cetuximab-irinotecan in 7 (50%) and 1 (5%) cases respectively (p = 0.004). Median time to progression in IGF-1 negative tumors was 11 months and 3.2 months in IGF-1 positive colorectal cancers (p = 0.03). Conclusions: IGF-1 proved to be a reliable predictive factor for resistance to anti-EGFR monoclonal antibodies in K-RAS wild type colorectal cancer. Combined IGF-1 and K-RAS analysis may represent an effective strategy for a better selection of responding colorectal tumors in this setting. No significant financial relationships to disclose.
Clinical and Molecular Features Of Young Patients With Myelodisplastic Syndromes (MDS)
Authors: Bilori Bilori, Hideki Makishima, Bartlomiej P Przychodzen, Mohamed Ashkar, Rohan Garje, Swapna Thota, Brittney Dienes, Kathryn M Guinta, Ramon V. Tiu, Mikkael A. Sekeres, Jaroslaw P. Maciejewski
Journal: Blood (2013)
ErbB3 protein expression in serous ovarian carcinomas of elderly women
Authors: M. S. Hirsch, J. Liu, R. Drapkin, H. Lee, U. A. Matulonis
Journal: Journal of Clinical Oncology (2007)

16026 Background: Ovarian carcinoma is the leading cause of death due to gynecologic malignancies, and older age at the time of diagnosis has been suggested to correlate with poorer outcome. Recent studies suggest that expression of ErbB3, a member of the epidermal growth factor receptor family, is associated with decreased survival. The goal of this study was to examine ErbB3 protein expression with a tissue microarray (TMA) comprised of advanced papillary serous (PS) ovarian carcinomas, and to correlate results with clinical information to evaluate for expression differences in younger and older women. Methods: A high density TMA (with 4 cores per primary tumor) was constructed by retrospective review of PS ovarian carcinoma cases seen between 1999 and 2005. Patients were divided into 2 cohorts based on age (=65 and =55 at diagnosis). Only cases of stage III or IV disease were included, and patients with BRCA mutations were excluded. Clinical data were obtained by chart and database review. TMA sections were immunostained for ErbB3, and expression was correlated with age, stage, and overall survival. Results: 136 primary tumors were available: 72 in the =65 group, 64 in the =55 group. Tumors from the =65 cohort were significantly less likely to express ErbB3 (16.7%) when compared to the ≤55 cohort (51.6%) (p&lt;0.0001). Patients whose tumors expressed ErbB3 had decreased median survival (33.6 months) compared to ErbB3 negative cases (47.3 months), but these results were not statistically significant (p=0.10). ErbB3 expression correlated in a borderline significant manner with stage (dichotomized as IIIa/IIIb vs. IIIc/IV) at the time of diagnosis (stage IIIa/b 11.8%+ vs. stage IIIc/IV 36.1%+; p=0.055). Multivariate analysis with respect to age, stage, and ErbB3 status did not reveal ErbB3 to be a statistically significant predictor of poor outcome in this data set. Conclusions: These results demonstrate that PS ovarian carcinomas in patients aged =65 at the time of diagnosis are significantly less likely to express ErbB3 than those ≤55. Correlation between ErbB3 expression and more advanced stage at the time of diagnosis bordered on significance. There was a non-significant trend towards decreased overall survival in both univariate and multivariate analyses in patients whose tumors exhibited ErbB3 expression. No significant financial relationships to disclose.
The Survivin Suppressant YM155 (Sepantronium Bromide) Has Potent Pre-Clinical Activity Against Pediatric Acute Myeloid Leukemia
Authors: Erica B. Little, Amanda M. Smith, Andjelija Zivanovic, Alfred K.S. Liu, Shannon Waldron, Wendy J. Ingram, Andrew R. Hallahan, Andrew S. Moore
Journal: Blood (2013)
Dexamethasone (DM) for cancer-related fatigue: A double-blinded, randomized, placebo-controlled trial.
Authors: Sriram Yennurajalingam, Susan Frisbee-Hume, Marvin Omar Delgado-Guay, Janet Bull, Alexandria T. Phan, Nizar M. Tannir, Jennifer Keating Litton, J. Lynn Palmer, Akhila Sunkepally Reddy, David Hui, Shalini Dalal, Lisa Massie, Saroj Vadhan-Raj, Suresh K. Reddy, James M. Reuben, Eduardo Bruera
Journal: Journal of Clinical Oncology (2012)

9002 Background: Cancer-related-fatigue (CRF) is the most common and distressing symptoms in patients with advanced cancer. Currently, there is no standard treatment for CRF. Although corticosteroids have been used in the treatment of CRF, there are no well-powered placebo-controlled trials that used a validated CRF outcome measure. The primary objective of this prospective, randomized, double-blind, placebo-controlled study is to compare the effect of DM versus placebo on CRF. Methods: Advanced cancer patients with fatigue ≥ 4/10 on the Edmonton Symptom Assessment Scale (ESAS) and at least 2 other CRF-related symptoms (pain, nausea, appetite, depression, anxiety or sleep disturbance ≥ 4/10), normal cognition, no infections and hemoglobin ≥ 9 g/L were eligible for enrollment. Patients were randomized to either receive dexamethasone 4 mg orally twice a day for 15 days (primary end point) or matching placebo. The primary outcome was the day 15 change in Functional Assessment of Chronic Illness-Fatigue (FACIT-F) subscale scores. Differences in the group means (normal distribution) were analyzed using the two-sample t-test. Results: In 83 evaluable patients (43 DM and 40 placebo), median age was 60 years, 61% were white, and 53% were female. There was no difference in the demographics and fatigue (FACIT-F subscale) between DM and placebo groups except for sex (p=0.02). The mean (SD) FACIT-F subscores at baseline and at day 15 for DM were 18 (11) and 27 (11) (p&lt;0.001) and for placebo were 21 (9) and 24 (12) (p=0.06), respectively. Mean improvement in FACIT-F subscale was significantly higher in the DM group compared to placebo (9.6 (11) vs. 3.1 (9.7), p=0.005). We found a significant difference in ESAS physical distress (p=0.02), but no differences in ESAS overall symptom distress (p=0.11) and ESAS psychological distress (P=0.88) between DM and placebo. There were insignificantly higher numbers of grade ≥3 toxicities in patients who received DM than in patients who received placebo (20/42 vs. 18/47, p=0.37). Conclusions: Dexamethasone was more effective than placebo in reducing CRF in patients with advanced cancer. Long-term safety studies are needed.
P3.04 Genome Wide Proteomics Using Peptide High Resolution Isoelectric Focusing Hirief-Ms Allows Detection New Human Gene Models
Authors: J. Lehtiö, M. Branca, H. Johansson, M. Orre, V. Granholm, J. Forshed, M. Perez-Bercoff, L. Käll
Journal: Annals of Oncology (2012)
Identical-Twin Transplants for B-Cell Chronic Lymphocytic Leukemia (B-CLL).
Authors: Steven Pavletic, Guimei Zhou, Kathleen Sobocinski, Kristine Doney, John DiPersio, Walter Feremans, Letizia Foroni, H. Grant Prentice, Charles LeMaistre, Giuseppe Bandini, Augustin Ferrant, Niels Jacobsen, Issa Khouri, Robert Peter Gale, Sergio Giralt, Emilio Montserrat, John Chan, Christopher Bredeson
Journal: Blood (2004)
Oral S-1 and carboplatin plus bevacizumab with maintenance S-1 and bevacizumab for chemo-naive patients (Pts) with advanced non-squamous non-small cell lung cancer (NSCLC).
Authors: Hiroyasu Kaneda, Yoshiko Urata, Isamu Okamoto, Yoshihiro Hattori, Keiko Okuno, Temiko Shimada, Masayuki Takeda, Takayasu Kurata, Masaki Miyazaki, Masaaki Terashima, Kaoru Tanaka, Hidemi Kiyota, Hidetoshi Hayashi, Toshihiro Kudo, Takafumi Okabe, Koichi Azuma, Satoshi Morita, Kazuhiko Nakagawa, Shunichi Negoro, Miyako Satouchi
Journal: Journal of Clinical Oncology (2012)

e18060 Background: Our previous phase III trial has demonstrated that S-1 in combination with carboplatin has promising activity as well as superior toxicity profile compared with carboplatin/paclitaxel for the first-line treatment of advanced NSCLC (JCO vol28, 2010). This study evaluated the efficacy and safety of new combination of S-1 and carboplatin plus bevasizumab (Cb/S1/Bev) followed by continuation maintenance of S-1 and bevacizumab (S1/Bev) in chemo-naïve Pts with advanced non-squamous NSCLC. Methods: Pts receive carboplatin AUC 5 and bevacizumab 15 mg/kg on day 1 plus oral S-1 (40 mg/m 2 b.i.d. ) on days 1 to 14. Treatment is repeated every 21 days up to 6 cycles. For the patients with SD or PR, S-1 combined with bevacizumab are continued every 21 days until disease progression or toxicity. Primary endpoint of this study was overall response rate (ORR). Results: Between April 2010 to October 2011, 48 patients were enrolled. Median age was 65 years (range=F35-77), male/female=33/15, PS 0/1=15/33, adeno/non-adeno=42/6. Median cycles of Cb/S1/Bev treatment were 4 (range=1-6), and 59% (n= 28) of Pts shifted to maintenance therapy. Among Pts who shifted to maintenance phase, median cycles treated with S1/Bev were 3.5 (range=1-10). Grade 3/4 toxicities included: neutropenia (23.4%/4.3%), anemia (4.3%/6.4%), thrombocytopenia (6.4%/6.4%) and hypertension (8.3%/0%). No treatment related death was occurred. Forty-six pts were evaluable for response. ORR was 50 % and disease control rate was 78 %, with a median time to progression of 7.4 months (95% CI: 3.9-10.8). Conclusions: Treatment with S-1 and carboplatin plus bevacizumab with maintenance S-1 and bevacizumab in pts with advanced non-squamous NSCLC is feasible with an acceptable toxicity profile. The encouraging activity justifies further development of this new regimen.
<i>BRCA1</i> and <i>BRCA2</i> mutation carrier predictions using the BRCAPRO model in clinic-based minority families enrolled in the Breast Cancer Family Registry (B-CFR)
Authors: D. Huo, R. T. Senie, M. B. Terry, M. B. Daly, S. S. Buys, O. I. Olopade
Journal: Journal of Clinical Oncology (2007)

21037 Background: BRCA mutation prediction models, such as BRCAPRO, are used in cancer risk clinics, but they were developed based on mutation rates and penetrance observed in individuals of Ashkenazi Jewish and European ancestry. Furthermore, in clinical counseling it is not always clear whether to test additional family members for BRCA mutations after the proband tests negative. The aim of this study is to evaluate the performance of the BRCAPRO model among clinic-based minority families and to evaluate the clinical utility of testing additional family members in high risk families. Methods: A total of 314 families with at least one member having been tested for BRCA mutations were enrolled through the B-CFR. Families of Ashkenazi Jewish ancestry were excluded. Using the BRCAPRO model with default penetrance and allele frequency for non-Ashkenazi Jewish populations, the predicted likelihood of carrying either a BRCA1 or BRCA2 mutations was generated. Sensitivity, specificity, and area under the receiver operating characteristic curves (AUC) were calculated. Results: There were 55 African American, 181 Hispanic, 42 Asian American and 36 other minority families. The AUC was 0.771 (95% confidence interval, CI: 0.720–0.816) for all minorities combined. At a predicted probability of 10%, the sensitivity for identifying mutation carriers was 65% and the specificity was 76%. The performance was marginally significantly better for Hispanic families than the other minority groups (p=0.07). In 228 families (73%), multiple individuals were tested for BRCA mutations. After taking into account the mutation status of family members, the performance of the BRCAPRO model was improved: the AUC increased to 0.862 (95% CI: 0.820–0.899) and the specificity at the 10% threshold increased to 83%, while the sensitivity remained the same. Conclusions: The data support the use of BRCAPRO in pretest prediction of BRCA1/2 mutations for minority families in high risk clinic settings. Mutation status of family members provides additional predictive value, which may help counselors decide whether to offer other family members the test when one member has already tested negative, given a positive family history of breast and ovarian cancer. No significant financial relationships to disclose.
Nonmetastatic, high-risk prostate cancer patients with biochemical relapse after local treatment: A prospective, randomized phase III study comparing hormonal therapy ± docetaxel—An analysis of final safety results.
Authors: S. Oudard, I. Latorzeff, P. Beuzeboc, A. Caty, E. Sevin, R. Delva, F. Rolland, L. Mourey, F. Priou, S. Culine
Journal: Journal of Clinical Oncology (2010)

4685 Background: More than 75% of high risk prostate cancer (PC) patients (pts) will undergo PSA recurrence within 2 years after local treatment. Docetaxel (D) is indicated for metastatic castrated-refractory PC. D activity in high risk patients was investigated. Methods: A multicenter, randomized phase 3 study was designed to compare HT (triptorelin, every 3 months for 1 year) to HT+D (70 mg/m2 Q3W, 6 cycles) in non-metastatic PC pts at high risk of systemic recurrence after radical prostatectomy (RP) and/or radiotherapy (RT). Inclusion criteria were at least 1 of the following: Gleason ≥ 8, PSA-DT ≤ 6 months, positive surgical margins, PSA velocity > 0.75 ng/mL/year, pathological pelvic lymph nodes, time from initial treatment to inclusion ≤ 12 months. Within maximum 90 days before inclusion, at least 3 consecutive progressive PSA > 0.2 ng/mL (RP) or >1 ng/mL (RT). Primary endpoint was PSA Progression Free Survival; secondary endpoints were PSA response, time to clinical progression, overall survival and safety (NCI-CTC 2.0). Results: 254 patients were included, 127 pts in both arm (A: HT+D and B: HT). For A and B arms, median age at inclusion was 64 and 66 years, delay from initial diagnosis to study entry 34 and 33 months, ECOG=0 95.5% and 93.6% and Gleason score ≥ 8 31% and 25%, respectively. In arm A, the most commonly observed grade 3-4 toxicities were: neutropenia (47.5%), febrile neutropenia (7.3%), thrombocytopenia (2.5%) and anemia (<1%), 17.1% received growth factors. Grade 1-2 toxicities were: asthenia (73.8%), hair loss (49.2%), nausea (28.7%), vomiting (10.6%), constipation (17.1%), diarrhea (31.9%), edema (24.6%), nail changes (38.5%) and sensory neuropathy (7.3%). Hormone-therapy related toxicities in both arms were comparable and essentially grade 2 hot flushes and depression. Conclusions: Final safety analysis exhibited mainly hematological toxicity due to D. These results suggest favorable safety of D in early stage PC patients. In June 2010, 140 patients will have completed the follow-up period and preliminary results on biological and clinical efficacy will be available. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer, sanofi-aventis Pfizer, sanofi-aventis