tbuckley/cabot-search huggingface dataset:
Role of neutrophils in the early presymptomatic stages of doxorubicin cardiotoxicity in breast cancer.
Authors: Valentina K Todorova, Marjorie L Beggs, Eric R Siegel, Issam Makhoul, Jeanne Wei, V. Suzanne Klimberg
Journal: Journal of Clinical Oncology (2015)

98 Background: Doxorubicin (DOX) cardiotoxicity is cumulative-dose-dependent and begins with the first dose of chemotherapy. No biomarker for early presymptomatic detection of DOX cardiotoxicity has been validated. Our preliminary microarray-based study on DOX cardiotoxicity of breast cancer patients showed that neutrophil-associated inflammation was partly responsible for this side effect of DOX Based on our preliminary finding, the aim of this study was to examine the expression of the top dysregulated neutrophil-specific genes, including alpha-defensins, arginase, cathepsin G, elastase, haptoglobin, metalloprotease 9, cathelicidin 8 in the peripheral blood mononuclear cells (PBMCs) of breast cancer patients treated with DOX-based chemotherapy. Methods: Blood samples of 15 women treated for breast cancer with DOX-based chemotherapy were collected before the start and after the 1st cycle of chemotherapy. Cardiac function was assessed before the start and after the completion of chemotherapy. A decrease of left ventricle ejection fraction (LVEF) &gt; 10% or &lt; 55% was considered abnormal. PBMC gene expressions of the target genes were assessed by quantitative RT-PCR and normalized to 18S. Data were analyzed using 2-deltadelta CT method and compared between patients with abnormal versus those with normal LVEF. Results: A single dose of DOX-based chemotherapy induced significantly greater mRNA levels of the examined genes in PBMC of patients with subsequent abnormal decline of LVEF (n = 5) versus those patients who maintained a normal LVEF. The elevated neutrophil-associated transcripts in the early stages of DOX-based chemotherapy were independent of the neutrophil count. Conclusions: We have identified a set of transcripts in the early stages of DOX-based chemotherapy that can serve as biomarkers for prediction of later impairment of cardiac function in breast cancer patients. Biomarkers for early prediction of DOX-induced cardiotoxicity could allow individualization of chemotherapy and/or testing the effectiveness of cardio-preventive medication, and ultimately will help to reduce the incidence of the cardiotoxicity-associated morbidity and mortality in cancer survivors.
Survival according to residual disease after interval laparotomy in advanced epithelial ovarian cancer.
Authors: L. Bengrine-Lefevre, E. Viel, M. Brugirard, C. Tournigand, N. Perez-Staub, B. Chibaudel, L. Teixeira, H. Marijon, H. Gervais, M. L. Garcia, O. Bourges, F. Maindrault-Goebel, T. Andre, A. De Gramont
Journal: Journal of Clinical Oncology (2011)

e15521 Background: Interval or early debulking surgery has been evaluated in epithelial ovarian cancer with debatable results. One randomized trial achieved a 6 months survival benefit (Van der Burg, NEJM 1995) and another no benefit (Rose NEJM 2004). In these trials, results were not reported according to residual disease after interval laparotomy. The goal of the present study is to evaluate survival in patients who had no macroscopic residual tumor after interval laparotomy and to evaluate residual disease as an early endpoint that could challenge PFS or OS as endpoint in future trials. Methods: Survival was studied according to response and residual disease in patients with stage III-IV epithelial ovarian cancer who had macroscopic residual disease after initial laparotomy and were treated with 3-4 cycles of platinum-based chemotherapy and underwent interval laparotomy with the goal of removing all macroscopic disease Results: 222 patients had interval laparotomy: five had a pathological complete response to initial chemotherapy (2.3%), 29 a complete response with positive biopsies (13.1%), 146 (65.8%) a partial response, 24 (10.8%) a stable disease, 10 (4.5%) a progressive disease and 8 (3.6%) were not evaluable. Median survival was 61 months in 87 patients (39.2%) with no residual disease after interval laparotomy and 26 months in 135 patients (60.8%) with macroscopic residual disease after interval laparotomy. Probability of surviving 10 years was 27% (CI 19.3-34.3) in patients without residual disease and 0% in patients with RD. Conclusions: Stage III-IV ovarian cancer who had a no residual disease at interval laparotomy had a median survival in excess of 5 years. On the other hand, patients with residual disease at approximately 3 months may have no chance of cure. This finding could be useful in future trials aiming to improve the cure rate
Global evaluation of minimal residual disease in primary breast cancer patients
Authors: A. Lucci, S. Krishnamurthy, K. Mosalpuria, I. Bedrosian, F. Meric-Bernstam, J. M. Reuben, B. Singh, W. A. Woodward, M. Cristofanilli
Journal: Journal of Clinical Oncology (2008)

1020 Background: Disseminated tumor cells (DTCs) in bone marrow (BM) are correlated with worse outcome, yet there is little data on circulating tumor cells (CTCs) in operable patients. We hypothesized that a significant number of primary breast cancer patients have minimal residual disease (MRD= CTCs and/or DTCs) that correlates with primary tumor characteristics. Methods: We prospectively evaluated MRD in stage I-III patients. Bilateral anterior iliac crest BM aspirates (10ml each side) were processed by cytospin, Ficoll gradient, and ICC for cytokeratin (CK). Cells staining for CK (with malignant morphology) were DTC positive. CTCs were assessed using 30 ml of peripheral blood in a CellSearch system (Veridex, Warren, NJ), and were defined as ≥1 nucleated cell/10 ml lacking CD 45 but expressing CK 8, 18, or 19. Tumor characteristics compared with MRD included: T size, lymph node status, LVSI, ER, PgR, Her-2, and Ki-67. Patients who received chemotherapy prior to BM/ blood collection were included. Statistical analyses were performed using chi-square tests. Results: We enrolled 124 patients; two were lost to follow-up. BM was evaluable in 93/124 (75%), and blood in 106/124 (85%). Median follow-up is 18 mos. Table 1 shows clinicopathologic characteristics. Seventy-five percent (91/122) of patients received no systemic therapy prior to BM/blood collection. CTCs and DTCs were found in 36 %( 38/106) and 23 % (21/93) of patients respectively. Seventeen percent (18/106) had ≥ 2 CTCs, and 6% (6/106) had >5 CTCs. There was no statistically significant correlation between CTCs and DTCs. No tumor characteristics correlated with DTCs, but Her-2 positivity correlated with CTCs (p=0.02, OR= 4.2). There was no difference in rates of MRD in patients who received chemotherapy versus those who had not. Conclusions: CTCs and DTCs are found in a significant number of patients with primary breast cancer. No correlation existed between presence of CTCs and DTCs. Except for Her-2 and CTCs, primary tumor characteristics did not reliably predict presence of MRD. Patient Clinicopathologic Characteristics T1 31% (39/124) T2 43% (53/124) T3 8% (10/124) T4 18% (22/124) ER 61% (75/124) PgR 51% (63/124) Her2 15% (18/124) Ki-67, high 53% (27/51) Lymph Node Status 48% (57/118) LVSI 35%( 42/119) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Veridex
Abstract 12642: Nonspecific ST and T Wave Abnormalities on Resting Electrocardiography Predict Cardiovascular Events and Inducible Ischemia in Asymptomatic Diabetics in the Detection of Ischemia in Asymptomatic Diabetes Study
Authors: Henry Siu, Lawrence H Young, Alex Ryzhikov, Kimberly Hall, Silvio E Inzucchi, Frans J Wackers, Deborah A Chyun
Journal: Circulation (2010)

Background:  Nonspecific ST and T wave abnormalities (NSSTTA) on resting ECGs are associated with increased cardiovascular risk. Although NSSTTA are often neglected, they could potentially enhance cardiovascular risk stratification in patients with asymptomatic diabetes. We hypothesized that NSSTTA on resting ECGs can predict myocardial perfusion defects and cardiac events in asymptomatic diabetics.   Methods:  A post-hoc analysis of 1,123 patients with type 2 diabetes, free of symptoms of cardiac disease, in the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study. Patients were randomly assigned to screening (or no screening) with adenosine-stress myocardial perfusion imaging (MPI) and routine care by their primary provider. All patients received a resting 12-lead ECG; 4 patients were excluded in this analysis due to incomplete outcomes data. The Minnesota Code Manual of ECG Findings was utilized to determine the presence of NSSTTA. The primary cardiac events were myocardial infarction and cardiac death. The mean follow up was 4.8 years.   Results:  The prevalence of NSSTTA on baseline ECGs was 18.2% (204/1,119). Patients with NSSTTA versus those without NSSTTA had a higher incidence of abnormal stress MPI (31% vs. 20%, p = 0.03), more primary cardiac events (6.4% vs. 2.1%, p    Conclusions:  In the DIAD study, NSSTTA were associated with 1) more abnormal stress MPI, 2) an increased incidence of myocardial infarction and cardiac death, and 3) greater all-cause mortality, compared with those without NSSTTA. Patients with NSSTTA who were screened with MPI had improved cardiac outcomes. Thus, asymptomatic diabetics with NSSTTA constitute a higher risk sub-group. Prospective studies are needed to confirm that screening diabetic patients with NSSTTA improves cardiovascular outcomes. (ClinicalTrials.gov number, NCT00769275)
Post-treatment surveillance in locally advanced squamous cell carcinoma (SCCA) of the anal canal: A global subspecialist survey.
Authors: Cathy Eng, Richard A. Adams, Lisa A. Kachnic, Prajnan Das, Randy Devereux Ernst, Miguel A. Rodriguez-Bigas, Elisabeth Dupont, Al Bowen Benson
Journal: Journal of Clinical Oncology (2016)

573 Background: Squamous cell carcinoma of the anal canal will be diagnosed in 28,000 individuals globally. Considered a rare cancer, the incidence of anal carcinoma continues to rise annually. Majority of patients present with locally advanced disease in which concurrent chemoradiation (CRT) will be provided with curative intent. The Anal Cancer IRCI Working Group was created to pursue novel approaches to the diagnosis, treatment, and surveillance of patients. Yet, surveillance following completion of CRT is not well established and varies as per NCCN (v2.2015) and ESMO guidelines. Methods: A 22-question survey provided to anonymous international GI subspecialists in various fields. Questions pertained to timing and type of diagnostic imaging, surveillance interval, approach to detection of complete response (CR), and prevention of sexual dysfunction. Results: Survey distribution was initiated in March 2015 and still ongoing. Thus far, 96 physicians responded. Conclusions: Carcinoma of the anal canal continues to rise in incidence annually. Surveillance following completion of CRT is warranted; however, global variability in practice patterns for surveillance exists. As such, the IRCI Anal Cancer Working Group intends to provide an international consensus surveillance statement. [Table: see text]
Transplantation with Higher Dose of Natural Killer Cells Associated with Better Outcomes in Terms of Non-Relapse Mortality and Infectious Events after Allogeneic Peripheral Blood Stem Cell Transplantation from HLA-Matched Sibling Donors.
Authors: Sang Kyun Sohn, Dong Hwan Kim, Nan Young Lee, Jin Ho Baek, Jong Gwang Kim, Jang Soo Suh, Kun Soo Lee, Kyu Bo Lee, Ho Jin Shin, Joo Seop Chung
Journal: Blood (2004)
Use of clinical and treatment factors to predict survival outcome in nonmetastatic metaplastic breast cancer.
Authors: L. L. Lai, T. H. Luu, R. A. Nelson
Journal: Journal of Clinical Oncology (2011)

11 Background: Although metaplastic breast cancer (MBC) represents &lt; 1% of breast cancer, stem cell research has stimulated interest in the genetics and biology of MBC. Because prognostic clinical and treatment factors remain ill-defined for this rare breast cancer subtype, we queried a public cancer data registry to identify factors predictive of overall survival (OS) in MBC. Methods: Patients diagnosed with breast cancer from 2001-2008 were identified using the Surveillance, Epidemiology, and End Results (SEER) database. We included only patients with infiltrating ductal carcinoma (IDC) and MBC who had non-metastatic disease. Patients were evaluated by standard demographic, clinicopathologic, and treatment factors including age, race/ethnicity, extent of disease, tumor marker expression and treatment received. Differences between IDC and MBC were assessed using Chi-Square methods. OS across groups was measured using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazard and stepwise models were used to identify prognostic variables and to adjust for covariates. Median follow-up was 31 months. Results: Of the total 508,071 breast cancer cases, there were 1,246 (0.25%) patients with MBC and 392,809 (77%) with IDC. 5-yr OS for locoregional MBC and IDC was 67% and 84%, respectively (p&lt;0.0001). When compared with IDC, MBC patients were older, had larger ER/PR negative cancers, and were more likely to have nodal disease. Factors predictive of worse OS in MBC on multivariate analysis are listed below. Tumor grade, ER/PR expression, and type of surgery (partial v. total mastectomy) did not impact OS. Of the treatment factors, only radiation affected OS (p=0.0002). Conclusions: To our knowledge this is the largest report of clinical and treatment factors predictive of outcomes in patients with MBC. Studies integrating clinical factors with molecular data may advance therapy that is more specific for this rare breast cancer subtype. [Table: see text]
Melanoma as a subsequent neoplasm in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study.
Authors: A. S. Pappo, G. T. Armstrong, W. Liu, D. K. Srivastava, W. Leisenring, S. Hammond, M. Stovall, J. P. Neglia, L. L. Robison
Journal: Journal of Clinical Oncology (2011)

9510 Background: Survivors of childhood cancer are at increased risk of developing subsequent neoplasms. The incidence and clinical characteristics of subsequent melanoma has not been well described in survivors of childhood cancer. Methods: Analysis included 14,358 5-year survivors of childhood cancer diagnosed between 1970-1986. Cumulative incidence (CIN) of first occurrence of subsequent melanoma (invasive, ocular, or in situ) was estimated. The association of potential risk factors and CIN of melanoma were tested using cause specific hazards models with age as the time scale and censoring at time of death. Risks for subsequent malignant melanoma as compared to SEER data base (excluding in situ and ocular melanomas) were calculated using standardized incidence ratios (SIR) and excess absolute risk (EAR) per 1000 person years. Results: 55 survivors reported 61 malignant melanomas (invasive 50, in situ 9, and ocular 2). Median time to tumor development was 20.7 yrs (range 5.6-35.4yrs). Median age at diagnosis of first subsequent melanoma was 32yrs (10.9 – 49.0 yrs) and 28 were male. Initial diagnoses included leukemia (16), lymphoma (15), soft tissue and bone sarcoma (n=15), brain tumor (5), Wilms’ tumor (3), and neuroblastoma (1). At last contact, 82% of patients were alive. The CIN of first subsequent melanoma (excluding in-situ and ocular) at 36 yrs from initial cancer was 0.72% (95% CI 0.37-1.07). CIN point estimates by diagnosis ranged from 0.23% for brain tumors to 1.3% for soft tissue and bone sarcoma survivors. The SIR was 2.95 (95% CI 2.19 – 3.89), and EAR was 0.12 (95% CI 0.07 – 0.18) per 1000 person years. Occurrence of melanoma was not associated with age at primary cancer diagnosis, sex, race or family history of cancer. Conclusions: Although the incidence is low, survivors of childhood cancer are at increased risk for developing malignant melanoma. Continued surveillance and awareness of this risk is critical for early detection and treatment of this disease.
Impact of preoperative chemotherapy on overall survival for borderline resectable colorectal liver metastases
Authors: Akio Saiura, Yosuke Inoue, Yoshihiro Mise, Yu Takahashi, Takafumi Ichida, Takeaki Ishizawa
Journal: Journal of Clinical Oncology (2016)

365 Background: Treatment for borderline colorectal liver metastases (CLM) is often started with chemotherapy. However, the impact on overall survival (OS) is still unknown. Aims: The aim of this study is to analyze the impact of preoperative chemotherapy on the outcome for up-front resectable borderline CLMs (BLR-CLM). Methods: A retrospective review was performed of 169 patients who underwent liver resection of BLR-CLM among 510 patients underwent liver resection for CLM between 2005 and 2013. BLR-CRLM was defined as CRLM of four or more nodules or 5cm or larger nodule. Time to surgical failure (TSF) was defined as the time until unresectable relapse or death. OS, recurrence free survival (RFS) and TSF were compared between BLR-CLM treated with neoadjuvant chemotherapy (NAC) and up-front surgery (US). Results: After median follow-up period of 38 months, 5-year survival rate after liver resection of resectable cases (n = 263), BLR-CLM (n = 169), and initially unresectable CLM (n = 78) are 67.7%, 47.5% and 32.6%, respectively. For patients with BLR-CLM, 22 patients with early recurrence during or early after postoperative chemotherapy for the primary were excluded. In the remaining 147 patients, 75 patients were treated with NAC and 72 with US. Cumulative 5-year overall survival rates, progression free survival rates, and time-to surgical failure in NAC and US group are as follows: OS (60.1% vs 47.7%, p = 0.084), PFS (23.1% vs 15.5%, p &lt; 0.0001), TSF (38.0% vs 34.4%, p = 0.020). Conclusions: Preoperative chemotherapy for BLR-CLM could improve PFS and TSF. The impact on OS was still marginal. Prospective controlled study will be necessary.
Two decades of oncology randomized controlled trials: Factors associated with CONSORT clinical trial reporting checklist compliance.
Authors: G. Rodrigues, I. Arra, V. Velker, B. Rotenberg, T. Sexton
Journal: Journal of Clinical Oncology (2011)

6126 Background: The Consolidated Standards for Reporting Trials (CONSORT) checklist has been formulated to improve the reporting of randomized controlled trials (RCTs). The purpose of this investigation is to determine predictors of CONSORT checklist compliance in the oncology literature over the past two decades. Methods: Eight-hundred and fifty parallel two-arm RCTs assessing oncological interventions in adult breast, prostate, colorectal, and lung cancer between 1992-2010 were identified by a systematic search of the medical literature. Exclusion criteria included investigations reporting interim/secondary/long-term update analyses, pilot/phase 2 studies and studies not employing a parallel design. After full article review, 408 articles were eligible for inclusion into the CONSORT audit database. RCT descriptive variables including number of authors/study patients, 2009 journal impact factor/journal classification, type of cancer and therapeutic intervention, publication year, primary study country, and cooperative group involvement were captured for all trials. Compliance with the CONSORT checklist guidelines were assessed by two trained auditors in order to generate average and difference CONSORT checklist scores. Results: Mean average CONSORT score was 16.6 (SD 3, max 25) and median difference score was 2 (interquartile range 1-3). Kappa agreement for each individual CONSORT checklist item ranged from (0.02-0.92) with an overall two-way intraclass correlation coefficient of 0.71 (95%CI 0.61-0.78) for comparison of overall CONSORT score between raters. Recent year of publication, increasing author number, and higher impact factor were associated with higher average CONSORT scores (p<0.0001). Recent year of publication was the only factor associated with a decrease in the CONSORT difference score. Conclusions: In this largest known reported CONSORT compliance audit in the medical literature, improvements in RCT reporting has been observed over time in the cancer literature. Further work in the assessment of the reliability of individual CONSORT items is warranted given the observed kappa agreement heterogeneity.
Phase I study of ursodeoxycholic acid in combination with 5-fluorouracil, leucovorin, oxaliplatin, and bevacizumab for metastatic colorectal cancer.
Authors: Lily L. Lai, Ken Chiu, Vincent M. Chung, Dean Lim, Joseph Chao, Paul Henry Frankel, Stephen Shibata
Journal: Journal of Clinical Oncology (2012)

e14182 Background: Significant treatment advances have doubled the median survival in patients with metastatic colorectal cancer (mCRC). An emerging body of literature links cancer with aberrant metabolism. These findings suggest that treatment directed against CRC metabolism may add to improved survival outcomes. The bile acid, ursodeoxycholic acid (UDCA), lowers cholesterol and improves insulin sensitivity when used clinically. Moreover, UDCA protects against intestinal polyp development in animal and human studies. UDCA effects may be mediated through activation of FXR, since bile acids are the endogenous ligands for this nuclear receptor. FXR is a tumor suppressor in mouse models of colon cancer and a prognostic biomarker in patients with CRC. Activation of FXR with bile acids in mouse models suppresses intestinal tumorigenesis. We propose to determine the dose and safety of UDCA when added to standard therapy for mCRC. Methods: Trial Design: UDCA doses will be escalated using a 3+3 design which will stop at the MTD or at two levels above an Active Dose (AD), whichever is the lowest. The AD is defined as the dose that will activate FXR. After a 7 day run-in period of UDCA only, cytotoxic combination chemotherapy and antiangiogenic agent for mCRC will be given along with the UDCA. The use of a run-in period allows for metabolic studies to identify serum biomarkers of FXR activation and to determine an AD. Treatment or intervention planned: UDCA is given during a run-in period of 7 days. At the end of the run-in period, standard doses of 5-fluorouracil, leucovorin, oxaliplatin, and bevacizumab are added. Patients are treated until excessive toxicity, progression of disease, or surgical resection. Major eligibility criteria: Patients with mCRC are eligible. Patients with greater than 10% body weight loss within 6 months of entering the protocol, a diagnosis of diabetes and active diabetes treatment are excluded from the study. Results: Current enrollment: Cohorts 1, 2, 3 have been completed without DLT. Enrollment to Cohort 4 began in 12/2011. Conclusions: Continue dose escalation until MTD or 2 levels above AD.Clinical trial registry number: NCT00873275.