tbuckley/cabot-search huggingface dataset:
Newly Discovered Polymorphism in the CD34+ Stem Cell Specific AC133-P1 Promoter Linked to Leukemias.
Authors: Sergey V. Shmelkov, Ryan St.Clair, Lin Jun, Agata Calderone, Matthias A. Karajannis, Kristian K. Jensen, Lauren M. Young, Kathryn Walsh, Koji Shido, David Jin, Fan Zhang, Joseph Cheng, George Lam, Rafael Tejada, Scott T. Avecilla, Loic Vincent, Hans-Georg Kopp, Gal Akiri, David Lyden, Shahin Rafii
Journal: Blood (2004)
Synergistic Effect of Quinacrine with Chemotherapeutics or TRAIL in Hematopoietic Malignant Cells
Authors: Wenge Wang, Amriti R. Lulla, Liz J. Hernandez-Borrero, David T. Dicker, Emmanuel K. Teye, Mala K. Talekar, Nathan G. Dolloff, Jeffrey J. Pu, Wafik S. El-Deiry
Journal: Blood (2014)
Health-related quality of life (HRQoL) in newly diagnosed patients (pts) with chronic phase chronic myelogenous leukemia (CP CML) treated with bosutinib (BOS) or imatinib (IM).
Authors: J. H. Lipton, P. C. Trask, D. Cella, L. Duvillie, C. Powell, M. V. Ramanan, Z. Maslyak, D. Kim
Journal: Journal of Clinical Oncology (2011)

6612 Background: BOS, a dual Src/Abl kinase inhibitor, demonstrated significantly higher response rates versus IM in evaluable pts with CP CML in a phase 3, open-label study. Given the length of time a pt may receive 1st-line treatment for CP CML (>8 yrs), understanding the impact on HRQoL is important, as pts may not present with significant symptom burden. The effect of BOS and IM on HRQoL was an exploratory endpoint. Methods: Pts with newly diagnosed CP CML were randomized 1:1 to BOS or IM. HRQoL was measured using the 44-item Functional Assessment of Cancer Therapy–Leukemia (FACT-Leu). The FACT-Leu is rated on a scale of 0-4 and consists of the Physical Well-being (PWB), Social/Family Well-being (SFWB), Emotional Well-being (EWB), Functional Well-being (FWB), Leukemia Subscale (LeuS), Treatment Outcome Index (TOI), FACT-G Total, and FACT-Leu Total scores; higher scores reflect better HRQoL. Minimal important differences (MID) on the scales range from 2-12 points. The FACT-Leu was completed at baseline (BL), every 3 mo on study, and at treatment completion. Paired t-tests and repeated measures mixed-effects models were used to assess within and between-group differences. Results: Of 250 and 252 pts randomized to BOS and IM, respectively, BL HRQoL data was available for 233 and 235 pts; median follow-up times were 16.0 and 16.5 mo; 71% and 80% of pts remain on treatment. No differences between groups were observed at BL or over the first 12 mo of therapy; however, the study was not powered to detect between-group differences. At 3 mo, significant improvements from BL for BOS and IM pts were observed in EWB (P <0.05 and P <0.001, respectively) and LeuS (P <0.01 and P <0.001); IM pts also reported significant improvements on the FACT-G Total (P <0.05), TOI (P <0.001), and FACT-Leu (P <0.001). At 12 mo, trends noted at 3 mo were evident at the same or greater level of significance, except EWB for BOS pts. None of the changes exceeded the MID. Conclusions: These early HRQoL data suggest both BOS and IM increase several aspects of HRQoL in newly diagnosed CP CML pts. This finding is important given the reported efficacy and manageable, but distinct, safety profiles of BOS and IM.
Using the ALBI grade as a prognostic marker for radioembolization of hepatocellular carcinoma.
Authors: Homan Mohammadi, Yazan Abuodeh, Will Jin, Jessica M. Frakes, Mark Friedman, Benjamin Biebel, Junsung Choi, Ghassan El-Haddad, Bela Kis, Jennifer Sweeney, Richard D. Kim, Jose Mario Pimiento, Mokenge Peter Malafa, Daniel A. Anaya, Sarah E. Hoffe
Journal: Journal of Clinical Oncology (2016)

366 Background: The Childs-Pugh class (C-P) is a commonly used scoring system to measure liver function in patients with hepatocellular carcinoma (HCC). While originally developed for patients undergoing esophageal resection for varices in the setting of cirrhosis and portal hypertension, it is now a widely accepted measure of liver function. The Albumin-Bilirubin (ALBI) grading system is a model developed in 2015 to assess liver function that has eliminated the subjective measures present in C-P. We correlate the ALBI grading system and C-P classes to overall survival in our HCC patients receiving radioembolization. Methods: With IRB approval, we retrospectively evaluated patients who received radioembolization for HCC between 2009-2014. We evaluated the albumin and bilirubin levels in our patients prior to receiving their first radioembolization (n = 121). The ALBI grades were calculated from these data with the formula (log10 bilirubin x 0.66) + (albumin x -0.085) and separated into grades based on the thresholds set in the original manuscript. These grades were then correlated to outcomes using Mantel-Cox Log analysis. The statistical comparisons were duplicated with C-P classes. Results: Median survival for C-P class A and B were 13.1 and 8.4 months (p &lt; 0.0005), respectively while median survival for ALBI grades 1 and 2 were 20.9 and 11.0 months (p &lt; 0.0005), respectively. Our C-P class A patient group was re-stratified using the ALBI formula and found to have two cohorts of patients with statistically significant differences in survival. The median survival between ALBI grades 1 and 2 within this patient group was 20.9 and 11.0 months (p = 0.002), respectively. Too few C-P class C or ALBI grade 3 patients were within our dataset for statistically significant results. Conclusions: We demonstrated that the ALBI grading system is a more sensitive marker of liver function than the C-P classes in the setting of mild to moderate dysfunction. Using the ALBI grade, we identified a subset of patients that have significantly better outcomes from radioembolization for HCC within C-P class A.
The effect of obesity on operating room (OR) utilization in breast surgery.
Authors: Julie Dunderdale, Borko Jovanovic, Swati Kulkarni
Journal: Journal of Clinical Oncology (2016)

36 Background: More than one-third of adults in the United States are obese. Studies have shown that obesity-related comorbidities increase health care costs, but the effect of obesity on operating room utilization has not been completely evaluated. The purpose of our study was to examine how operative time (OPT) for common procedures in breast surgery is affected by patient weight. We expected that weight affected OPT more so for extensive procedures, such as axillary lymph node dissection (ALND) and mastectomy, than for minimally invasive procedures, such as lumpectomy and sentinel lymph node biopsy (SLNB). Methods: OPT and weight for ten breast surgeries were analyzed from the American College of Surgeons 2010 National Surgical Quality Improvement Project database. Only women were included, and those who underwent additional procedures or had incomplete data were excluded. Patients were divided into three groups based on their weight (&lt;135 lbs, 135-199 lbs, and ≥200 lbs). Using the two-sample t-test, OPT for the procedures was compared among the lowest and highest weight categories. We specifically looked at lumpectomy, lumpectomy plus SLNB, ALND, mastectomy, and modified radical mastectomy (MRM). Results: In all, 16,077 patients were included in the analysis. When the lowest and highest weight groups (&lt;135 lbs and ≥200 lbs) were compared for all procedures, a significant difference of 13 min was seen (p&lt;0.0001). For these same groups, a significant, but not relevant for scheduling, difference in OPT was noted for lumpectomy alone (37 vs. 41 min, p&lt;0.0001) and lumpectomy plus SLNB (71 vs. 80 min, p&lt;0.0001). However, weight affected ALND and mastectomy more drastically. The difference for lumpectomy plus ALND was 22 min (93 vs. 115 min, p=0.0004), while the differences for simple mastectomy and mastectomy plus SLNB were 24 min (89 vs. 113 min, p&lt;0.0001) and 23 min (102 vs. 125 min, p&lt;0.0001), respectively. In addition, the difference for MRM was 22 min (104 vs. 126 min, p&lt;0.0001). Conclusions: Patient weight does significantly affect OPT for lumpectomy and SLNB, but the difference is much greater for ALND, mastectomy, and MRM. Therefore, when scheduling more extensive procedures for obese patients, additional time should be allotted to improve OR utilization.
Flavopiridol Administered as a Pharmacologically-Derived Schedule Demonstrates Marked Clinical Activity in Refractory, Genetically High Risk, Chronic Lymphocytic Leukemia (CLL).
Authors: John C. Byrd, Thomas S. Lin, James T. Dalton, Di Wu, Beth Fischer, Mollie E. Moran, Kristie A. Blum, Roshini S. Shank, David M. Lucas, Margaret S. Lucas, Jose-Ramon Suarez, Michael R. Grever
Journal: Blood (2004)
Role of biliary CEACAM6 as a biomarker for cholangiocarcinoma.
Authors: John B. Rose, Camilo Correa-Gallego, James Nelson, Adnan Alseidi, Scott Helton, Peter J. Allen, Michael D'Angelica, Ronald P. DeMatteo, Yuman Fong, T. Peter Kingham, Kris Kowdley, William R. Jarnagin, Flavio G. Rocha
Journal: Journal of Clinical Oncology (2013)

177 Background: Distinguishing bile duct carcinoma from other diagnoses is often difficult using endoscopic or percutaneous techniques. The cell surface protein CEACAM6 is over-expressed in many gastrointestinal cancers and may be selectively elevated in biliary adenocarcinoma. The aim of the present study is to determine if CEACAM6 can be detected in the bile of patients with biliary cancer and can serve as a diagnostic biomarker for cholangiocarcinoma. Methods: Bile duct and gallbladder bile from patients with benign biliary disease and cholangiocarcinoma (hilar, intrahepatic and distal) was collected at the time of index operation. The concentration of CEACAM6 was quantified by sandwich enzyme-linked immunosorbent assay (ELISA) and correlated to pathologic diagnosis. Diagnostic capability of CEACAM6 was evaluated by Wilcoxon rank-sum, logistic regression, and receiver operating characterisitic (ROC) curve analysis. Results: Bile from 73 patients was analyzed: 40 with benign disease and 33 with cholangiocarcinoma. Patients in the benign cohort were younger, predominantly female, and had lower mean biliary CEACAM6 levels than patients in the malignant cohort (102 ng/ml vs. 239 ng/ml; p=0.0006). Logistic regression analysis determined CEACAM6 to be a positive predictor of extrahepatic but not intrahepatic cholangiocarcinoma (p=0.0015). ROC curve with a CEACAM6 level &gt;22.1 ng/ml was associated with 85% sensitivity, 73% specificity, and a likelihood ratio of 3.15 (AUC 0.82) for extrahepatic cholangiocarcinoma. Conclusions: CEACAM6 levels in bile can predict patients with extrahepatic cholangiocarcinoma with acceptable accuracy. Further investigation is warranted in a larger cohort of patients prior to clinical application.
Impact of diabetes on clinicopathologic and genetic features of colorectal cancer formation.
Authors: Hui-li Wong, Robert N. Jorissen, Oliver Sieber, Lara Rachel Lipton, Jayesh Desai, Jeanne Tie, Suzanne Kosmider, Susie Bae, Ian Jones, Matthew Croxford, Malcolm Steel, Andrew Bui, Peter Gibbs
Journal: Journal of Clinical Oncology (2013)

426 Background: Diabetes mellitus is reported to increase the risk of colorectal cancer (CRC) development and has been associated with poor tumour-specific outcomes. Here we assessed the impact of diabetes on the clinicopathologic features and tumour mutation profiles of CRC. Methods: Analysis of a prospective series of patients diagnosed with CRC between January 2000 and December 2010. Fresh-frozen and formalin-fixed, paraffin-embedded tumour specimens were retrieved and genomic DNA extracted for analysis of microsatellite instability (MSI), CpG island methylator phenotype (CIMP) and mutations in BRAF, KRAS, PIK3CA, TP53 and APC genes. Propensity-score matching and logistic regression were used to estimate the association of diabetes with tumour molecular profile, controlling for age, sex, tumour stage, body mass index (BMI), smoking and socio-economic status. Results: Of the 1,348 patients assessed, 288 (21.4%) had a history of diabetes mellitus. Compared to patients without diabetes, diabetics were more likely to be older (age &gt; 70 yrs: 56% vs 47%, p = 0.006), male (57% vs 47%, p = 0.002) and have a higher BMI (BMI &gt; 25: 82% vs 65%, p &lt; 0.0001). There were no statistically significant differences in tumour site, differentiation or lymphovascular invasion. Propensity scores were used to match 260 diabetic patients to an equal number of nondiabetics. In multivariate regression analysis, diabetes was associated with BRAF-mutated tumours (OR 2.81, 95% CI 1.16-7.59, p = 0.029) and showed a trend towards MSI-high tumours (OR 1.54, 95% CI 0.91-2.63, p = 0.110). Results are shown in the Table. Survival analysis is planned. Conclusions: CRC patients with diabetes are older, more likely male and have higher BMI than non-diabetics. In this preliminary analysis, an association between diabetes and BRAF-mutant CRC was found, and may explain reported differences in outcomes for diabetic CRC patients. [Table: see text]
Influence of age and socioeconomic status (SES) on testicular cancer (TC) specific mortality: A population-based study of 27,948 patients.
Authors: S. D. Fossa, L. B. Travis, L. Chen, M. Cvancarova
Journal: Journal of Clinical Oncology (2010)

4578 Background: Age ≥ 40 years at diagnosis and low SES may be associated with increased TC-specific mortality. Methods: Cumulative 10-yr TC-specific mortality adjusted for competing risk was calculated for men reported to the SEER Program (1978-2006) with histologically confirmed seminoma (16,007) or nonseminoma (11,887) at age 15+ years. SES was calculated as tertiles of distribution of “% of men 25+ yr with < high school education” for pt's residence county (T1:lowest; T3: highest). Multivariate Cox regression included extent of disease (localized; metastatic), post-orchiectomy surgery (RPLND-recorded since 1998), radiotherapy (RAD), marital status (married; single) and race (white; non-white), but not chemotherapy (not available). Overall survival of 5-yr TC survivors was compared with rates for men in the general population (controls). Results: Cumulative 10-yr mortality for seminoma pts diagnosed < 40 and 40+ yr were 1.4% (95% CI 1.2-1.7) and 2.3% (95% CI 1.9-2.7), respectively. For nonseminoma pts, corresponding figures were 6.1% (95% CI 5.5-6.5) and 9.1% (95% CI 7.6-11.0). For seminoma pts, mortality risk decreased with improving SES: 2.3% (95% CI 1.9-2.7), 1.5% (95% CI 1.2-1.7), and 1.6 % (95% CI 1.2-1.9), T1 given first. Similar significant differences were observed for nonseminoma [8.6, 6.6, and 4.0, respectively].In Cox analyses, age and SES were significantly associated with unfavorable mortality for nonseminoma pts along with being single, non-white, having metastatic disease, and no record of post-orchiectomy treatment. For seminoma pts, the same variables, except race and SES, were significant. After 25-30 yrs follow-up, small significant differences in overall survival were observed between 5-yr TC survivors and controls. Conclusions: Medical parameters, age 40+ and single status are significantly associated with unfavorable TC-specific mortality. Low SES and being non-white further worsens the prognosis of nonseminoma pts. After up to 3 decades of follow-up, 5-yr TC survivors display significantly lower overall survival than the age-matched male general population. No significant financial relationships to disclose.
Patient-reported outcomes from POINTBREAK: The randomized, open-label, phase III study of pemetrexed (pem) + carboplatin (cb) + bevacizumab (bev) followed by maintenance pem + bev versus paclitaxel (pac) + cb + bev followed by maintenance bev in patients with stage IIIb or IV nonsquamous non-small cell lung cancer (NS-NSCLC).
Authors: David R. Spigel, Jyoti D. Patel, Craig H. Reynolds, Edward B. Garon, Robert C. Hermann, Ramaswamy Govindan, Mark Olsen, Katherine B. Winfree, Jingyi Liu, Susan C. Guba, Mark A. Socinski, Philip Bonomi
Journal: Journal of Clinical Oncology (2012)

53 Background: Treatment (tx) impact on pt quality of life (QoL) informs pt and physician choices in the management of NSCLC. QoL, a secondary endpoint of POINTBREAK, was assessed using the patient-reported Functional Assessment of Cancer Therapy General (FACT-G), Lung (FACT-L), and Neurotoxicity (FACT&amp;GOG-Ntx). Methods: Pts with previously untreated stage IIIB/IV NS-NSCLC and ECOG performance status 0-1 were randomized to receive induction Pem+Cb+Bev or Pac+Cb+Bev for up to 4 cycles. Pts without progressive disease received maintenance Pem+Bev (Pem Arm) or Bev (Pac Arm). Pts completed the FACT-G [physical, emotional, functional, and social well-being subscales (SS)], FACT-L (FACT-G + lung cancer SS), and FACT&amp;GOG-Ntx (FACT-G + Ntx SS) at each visit. SS score and total score (TS) were calculated for each instrument. Tx group differences were analyzed using Linear Mixed Effects model. Toxicity was investigator assessed using CTCAE and was compared with Fisher’s exact test. Results: The primary endpoint of superior OS for the Pem arm was not met and is reported elsewhere. Pt overall compliance on the FACT was 91.2% (Pem Arm) and 90.0% (Pac Arm). For both the FACT-G and FACT-L TS, no overall significant change from baseline difference was observed between the Pem and Pac Arms. No overall differences were seen in SS scores except for Ntx. Pts on the Pem Arm had significantly less change from baseline in Ntx SS score and Ntx TS than pts in the Pac Arm at cycle 2 (p&lt;0.001), and this significant tx effect persisted through induction and the six cycles of maintenance considered in the analysis. Significantly fewer pts on the Pem Arm experienced investigator assessed Grade 3/4 sensory neuropathy compared to the Pac Arm (0.0% vs. 4.1%, p&lt;.00001). Conclusions: Based on the FACT results, pts on the Pem and Pac Arms reported similar changes in QoL except for less change from baseline in Ntx on the Pem Arm. Patient-reported Ntx is consistent with the clinically-measured drug-related Grade 3/4 sensory neuropathy.
Correlation between HER2 status and central nervous system (CNS) involvement in metastatic castration-resistant prostate cancer (mCRPC).
Authors: A. Gernone, A. Pagliarulo, S. Trabucco, V. Pagliarulo
Journal: Journal of Clinical Oncology (2011)

e15190 Background: The incidence of CNS metastases, including parenchyma and leptomeninges, in prostate cancer is very low. Prostate cancer mainly metastasizes to bones. HER-2/neu is a proto-oncogene that encodes a transmembrane receptor belonging to the family of epidermal growth factor receptors. The purpose of this retrospective study was to evaluate the relation between HER-2 status in primary cancer tissues and risk of CNS metastases in pts with mCRPC. Methods: From 2003 to 2010, 130 pts with mCRPC were treated with 3weekly docetaxel chemotherapy 75 mg/mq. All pts had bone metastases. The median age was 66 (41-88), median baseline PSA: 110 ng/ml (range 5-1100), median ECOG Performance Status: 1 (range 0-2). The data on 130 pts, who underwent diagnostic biopsy or potentially curative resection with lymphoadenopathy, were reviewed. Tissue blocks from primary prostate cancer tissues were obtained. Grade 3 of the HER-2 by immunohistochemical (IHC) staining was defined as a positive result or gene amplification by fluorescence in situ hybridization (FISH). 10 (7.7%) out of these 130 pts were diagnosed with CNS metastases by using magnetic resonance imaging. Results: CNS metastases were observed in HER-2 positive pts. 6/10 pts presented parenchymal metastases: 4 pts were asymptomatic, 3 pts underwent metastasectomy and all of them received palliative whole-brain RT. 4/10 pts presented leptomeningeal metastases with neurological symptoms and 2 of them received palliative whole-brain RT. The median time from prostate cancer diagnosis to the date of diagnosis of CNS metastases was 6 years (range 1-8). The median time from first cycle of docetaxel to the date of diagnosis of CNS metastases was 3 years (range 1.5-4). Conclusions: These preliminary data demonstrated that HER-2 expression confers an increased risk of CNS metastases in mCRPC and constitutes a therapeutic challenge. The apparent increase of CNS presentation may be related to the effectiveness of systemic therapy.
A model for coordinated delivery of individualized complementary and integrative medicine care for cancer survivors.
Authors: Michelle Niesley, Kathryn Doran, Nhu Huynh, Marie Winters
Journal: Journal of Clinical Oncology (2016)

e286 Background: Cancer survivors may experience both physical and psychosocial sequelae as a result of cancer treatment. Many patients consult either their oncologist or primary care physician for lifestyle interventions to address survivorship issues. While studies demonstrate complementary and integrative medicine (CIM) therapies may reduce the risk of both all-cause mortality and cancer-specific mortality by 50% (Frenkel M et al. Curr Oncol Rep. 2015 May;17(5):445), the most effective method to ensure compliance with individualized dietary counseling, exercise, or nutritional supplement information to the patient is unknown. Here we present a multidisciplinary survivorship care model to increase compliance with CIM practices that positively impact survivorship outcomes. Methods: Each Patient Empowered Care (PEC) team at our hospital consists of a medical oncologist, naturopathic doctor, nurse care manager, and a nutritionist, who discuss the assessment and plan for each patient they will see that day. Additional integrative services include chiropractic care, acupuncture, and Oncology Rehab (physical, occupational, speech, and massage therapy). Naturopathic doctors recommend nutritional supplements specific to both the patient’s oncology regimen and other comorbidities, and also ensure these supplements do not interfere with metabolism of other active medications. Oncology Rehab encourages exercise via our Motion for Life program, where physical fitness programs are tailored to the patient’s individual needs. The Nutrition program provides individualized coaching and nutritional management. Patients continue CIM therapies long after oncology care has concluded. Results: Patients satisfaction and outcomes are improved by facilitating compliance with individualized lifestyle recommendations. Conclusions: This model increases compliance with CIM recommendations by facilitating transparent communication among PEC team members, while providing the patient with a single facility that individualizes their wellness regimen.