tbuckley/cabot-search huggingface dataset:
Prognostic value of CA27.29 trend during adjuvant chemotherapy and until 2 years thereafter in patients with primary breast cancer.
Authors: B. K. Rack, P. G. M. Hepp, U. Andergassen, J. K. Neugebauer, J. Salmen, G. Heinrich, J. Schreier, A. Hoenig, D. Finas, T. Zwingers, R. Kreienberg, M. W. Beckmann, W. Lichtenegger, H. L. Sommer, K. Friese, W. Janni
Journal: Journal of Clinical Oncology (2011)

10589 Background: Several trials have shown that the use of tumor markers (TM) can lead to an early diagnosis of tumor recurrence in breast cancer. While TM are frequently used in routine clinical practice, it is still unclear whether the prognosis of breast cancer patients can be improved by early treatment induction. Methods: The SUCCESS Trial compares FEC-docetaxel (Doc) vs. FEC-Doc-Gemcitabine (Doc-G) regime and two vs. five year treatment with Zoledronat in patients with primary breast cancer (N+ or high risk). CA27.29 has been measured before and after chemotherapy and at 2 years with the ST AIA-PACK Ca27.29 reagent using MUC-1 for AIA-600II (Tosoh Bioscience, Tessenderlo, Belgium). The course of Ca27.29 from pre-chemotherapy baseline to 2 years was evaluated in this analysis. Results: CA27.29 data is available of 3,202 patients before and 2,015 pts 2 years after chemotherapy. 20.2% of pts had increasing (>=1 U/ml), 59.7% had decreasing, 20.1% had stable CA27.29 levels from before CHT to 2 years thereafter. For a difference >=5 U/ml 6.1% of pts had increasing values, 23.5% had decreasing, 70.4% had stable CA27.29 levels from before CHT to 2 years. Patients with increasing CA27.29 levels from before CHT to 2 years after CHT had a sig worse DFS (HR 1.016; [95%CI 1.011-1.021] for >=1 U/ml each p<0.001) and OS (HR 1.02; [95%CI 1.004-1.037] p<0.001) than patients with stable or decreasing levels. Between those with stable and decreasing levels there was no significant difference in terms of prognosis [figure Kaplan-Meier DFS]. Patients with an increase >=5 U/ml had an 81% increased risk for recurrence (HR=1.810 (CI: 1.111-2.948). In the multivariate analysis taking into account tumor size, nodal status, grading, age, hormonal and HER2/neu receptor status increasing CA27.29 levels were an independent prognostic marker. Conclusions: A small increase of the tumor marker CA27.29 compared to pre-chemotherapy baseline was associated with a worse prognosis. Therefore, changes in TM values compared to baseline in the individual patient could result in a more accurate and clinically relevant interpretation of tumor markers.
Potential pitfalls of binary reporting metrics using a QOPI end-of-life (EOL) sample.
Authors: Constance Barysauskas, Carole Kathleen Dalby, Paul J. Catalano, Joseph O. Jacobson
Journal: Journal of Clinical Oncology (2014)

261 Background: Practice accountability through measurement is emergent in the United States. The National Quality Forum has adopted several EOL metrics as national standards. Care at EOL is highly variable due to patient and family preference, symptom management, and psychosocial care. We hypothesize binary measures with fixed cut-points limit the understanding of EOL practice thus reducing opportunities for care improvement. Methods: We previously demonstrated limitations of the QOPI sampling methodology among all patients at Dana-Farber Cancer Institute Satellites following the QOPI sampling strategy between July 1, 2012 and December 31, 2012. Using the same population, we examined the distribution of chemotherapy administration in the last two weeks of life. We compared our QOPI EOL data (A) with simulated scenarios modeled via log-normal distributions (B, C, D, E). The binary metric was held constant at the observed proportion to illustrate potential variability in other statistical metrics. Results: A total of 193 patients received chemotherapy before death. Chemotherapy administration in the last two weeks of life was measured at 11%, with a mean of 84 days (inter-quartile range, IQR: 92 days). Different distributions were generated by varying the mean and SD as demonstrated in the table below. Conclusions: As our simulated scenarios show, practices disseminating the same binary metric may stem from very different distributions. We have identified two limitations of binary reporting metrics with fixed cut-points. First, binary metrics risk misrepresenting actual delivered care as substantially different practice patterns can result in the same binary result. Second, binary metrics greatly limit the ability to learn from actual practice patterns. Quality improvement projects may be wrongly prioritized based on the national standards and project focus may be misaligned with practice need. EOL care is multifaceted and nuanced; binary metrics are convenient, but may be misleading to practice accountability and limit opportunities for practice improvement. [Table: see text]
Exploratory analysis of the visceral disease (VD) patient subset in COU-AA-301, a phase III study of abiraterone acetate (AA) in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Oscar B. Goodman, Thomas W. Flaig, Arturo Molina, Peter Mulders, Henrik Suttmann, Jinhui Li, Thian San Kheoh, Johann Sebastian De Bono, Howard I. Scher
Journal: Journal of Clinical Oncology (2013)

14 Background: VD is a negative prognostic factor in mCRPC patients (pts) and may be less responsive to hormonal therapy. AA, a selective androgen biosynthesis inhibitor, inhibits androgen synthesis from adrenal and intratumoral sources. Improved overall survival (OS) with AA vs prednisone (P) was demonstrated in a randomized trial of pts with mCRPC post-docetaxel (D). Here we further assess the effect of AA on OS and other clinical outcomes in post-D mCRPC pts with VD (liver or lung, but not nodal-only metastases). Methods: In COU-AA-301, pts with mCRPC previously treated with D were randomized 2:1 to AA (1000 mg) + P (5 mg BID) (n=797) or placebo + P (n=398). The primary end point was OS. Data shown herein represent the updated analysis (775 events) of patients with (n=352) or without (n=843) VD. Results: The OS benefit of AA was similarly improved in patients with VD (4.6 m) and without VD (4.8 m) (Table). Treatment with AA led to significant 40% and 32% reductions in the risk of radiographic progression or death in patients with VD or without VD, respectively. Soft-tissue objective response rates were superior with AA in both groups. PSA response rates (50% reduction) were significantly improved by AA in both groups. Grade 3/4 adverse events (AEs) were similar in both groups. Hypertension, hypokalemia, and LFT abnormalities were observed with AA in pts with and without VD. Conclusions: AA has substantial anti-tumor activity and provides clinical benefit including improvements in OS and rPFS in post-D mCRPC pts with VD indicating it is a therapeutically active treatment option for CRPC pts. Safety/tolerability of AA in pts with VD was similar to that reported previously in mCRPC. Clinical trial information: NCT00638690. [Table: see text]
Abstract 12014: Modified HASBLED Bleeding Risk Score in Dialysis Patients With Atrial Fibrillation
Authors: Michele Murphy, William Maddox, Stan Nahman, Matthew Diamond, Robert Sorrentino, Avirup Guha, Jennifer Waller
Journal: Circulation (2015)

Introduction: Hemodialysis patients (HD pts) with atrial fibrillation (AF) have increased risk of stroke. The HASBLED (Hypertension (HTN), Abnl Renal/Liver Function, Stroke, Bleeding Hx, Labile INR, Elderly, Drugs/Alcohol) risk score predicts bleeding in the general AF population. It is unknown whether the HASBLED score can be applied to HD pts who are at additional bleeding risk due to uremic platelet dysfunction and the regular use of heparin. Hypothesis: To address this question, we queried the United States Renal Data System (USRDS) for bleeding events in HD pts with AF, and correlated those events with a modified HASBLED (mHASBLED) score. Methods: All incident HD pts with AF from the USRDS for 2006-2010 were queried for major bleeding events and mHASBLED parameters using ICD-9 diagnosis codes and data from CMS form 2728. For mHASBLED, the HTN parameter was defined as "HTN as the cause of renal failure", and labile INR as &gt; 16 INRs/yr, but all other parameters could be derived from the dataset. Logistic regression (LR) analysis was used to estimate the odds ratio (OR) for the mHASBLED score to predict major bleeding events. Results: 74,631 HD pts had AF, and 9.8% had a major bleeding event (GI bleeding and hemorrhagic stroke). By univariate analysis, those who bled were more likely to be elderly, have an underlying cause of renal disease due to HTN, prior bleeding event, hepatitis C, labile INR, and be on oral anticoagulants. By LR, variables with the greatest impact on bleeding were HTN as a cause of underlying renal disease, prior bleeding history, and labile INR (OR of 1.10, 2.20 and 2.24, respectively). The OR for bleeding events increased by 1.28 for each unit increase in mHASBLED. Older age, prior stroke, abnormal renal or liver function, and drug use had the least effect. Note that the lowest possible score in this cohort is 1, given that all patients had renal failure. Conclusions: In HD pts with AF, the mHASBLED predicts major bleeding events. The universal presence of renal disease, and the lack of specific clinical data from the USRDS may limit the clinical precision of a given score, however mHASBLED may remain a useful indicator of bleeding risk in this population.
PD-1/PD-L1 expression and molecular associations in HPB malignancies.
Authors: Kabir Mody, Rebecca Feldman, Sandeep K. Reddy, Gina A Reynolds, Jessica M McMillan, Elizabeth Johnson
Journal: Journal of Clinical Oncology (2016)

289 Background: Cholangiocarcinoma (CC), hepatocellular carcinoma (HCC), and pancreatic ductal adenocarcinoma (PDAC) are all devastating malignancies. Limited data exists about PD-1 and PDL1 expression in these cancers. We assessed expression of PD1/PDL1 in a large cohort of patients with hepato-pancreatico-biliary (HPB) cancers and explored the existence of accompanying genomic mutations associated with expression of PD-1/PD-L1. Methods: 524 patients with HPB cancers (354 PDAC, 58 HCC, 54 intrahepatic (ICC), 18 extrahepatic (ECC), and 40 gallbladder (GBC)) were included in the study and tumors tested centrally at a CLIA lab (Caris Life Sciences, Phoenix, AZ). Tests included one or more of the following: gene sequencing (next generation sequencing, Illumina TruSeq), protein expression (immunohistochemistry [IHC]) and gene amplification). PD-1 (SP142 antibody) and PD-L1 (MRQ-22 antibody) status was tested in all samples. Two-tailed Fisher's exact test was performed to test where proportions of positive results were different by subgroup (p²0.05). Results: Among those with PDAC, HCC, ICC, ECC, and GBC, rates of PD1 expression on tumor infiltrating lymphocytes (TILs) and PD-L1 expression on tumor cells is detailed in the Table. In PD-1+, compared with PD-1- HPB cancers, mutations in the following were more prevalent, though not statistically significant: BRCA2, ATM, CTNNB1, and PIK3CA. Among all theranostic biomarkers tested, TOP2A expression (IHC) was significantly increased in PD-L1+ versus PD-L1- tumors (82% vs 60%; p=0.0083). Conclusions: HPB tumors express PD-L1 at a frequency of 4-18%, and PD-1 at a frequency of 29-45%. A statistically significant association of mutations with PD-1+ or PD-L1+ tumors was not identified in this group of tumors. PD-L1 expression associates with TOP2a expression, a marker of proliferation and also anthracycline sensitivity. Further evaluation of this correlation and PDL1/PD-1 + anthracycline combination therapy may be warranted. [Table: see text]
Utilization of adjuvant therapy in Medicaid and uninsured seminoma patients: Results from the National Cancer Database.
Authors: Jonathan J. Paly, Chun Chieh Lin, Phillip John Gray, Ahmedin Jemal, Jason Alexander Efstathiou
Journal: Journal of Clinical Oncology (2014)

388 Background: Seminoma is the most common testicular cancer, and cancer specific survival approaches 100% if diagnosed and treated early. Following orchiectomy, several adjuvant therapy options exist for patients with stage 1A/B and 2A/B disease. As the Affordable Care Act’s (ACA) individual insurance mandate and expansion of Medicaid coverage will begin in 2014, we sought to understand whether differences exist in receipt of adjuvant therapy between uninsured and Medicaid patients in order to predict possible treatment patterns after the ACA takes effect. Methods: Uninsured and Medicaid patients diagnosed with seminoma from 1998-2010 in the National Cancer Data Base were identified. Multivariate logistic regressions were used to assess the relationship between uninsured status vs. Medicaid and receipt of adjuvant therapy. Results: Of 41,745 seminoma patients, 5,895 (14%) patients were on Medicaid or uninsured. Compared to Medicaid patients, uninsured patients were more likely to be younger (&lt;29 years old), Hispanic, live in the South, treated in community hospitals, reside in areas with higher education levels, and present with stage IA/B disease (66.5% vs 59.4%, p &lt; 0.01). After controlling for sociodemographic and clinical characteristics, uninsured stage IA/B patients had a 16% decreased likelihood of receiving adjuvant radiation or chemotherapy than Medicaid patients (p&lt;0.05). In addition, stage 1A/B patients who were Hispanic, aged 50 or more, diagnosed in 2006-2010, treated in low-volume-case facilities or had tumor size &lt; 4cm were less likely to receive adjuvant therapy. No treatment differences by insurance were seen in stage IIA/B patients. Conclusions: Our analysis suggests a modest association between the decision to seek optional adjuvant therapy and uninsured vs. Medicaid status in patients with stage IA/B seminoma. Given that national recommendations support surveillance, it will be increasingly important to counsel newly insured patients on the benefits of post-orchiectomy surveillance for early stage disease. In addition, no difference in management was identified for CS 2A/B patients suggesting that required therapy was not modified or avoided in the uninsured.
Incorporating gold nanoclusters and target-directed liposomes as a synergistic amplified colorimetric sensor for HER2-positive breast cancer cell detection
Authors: Yu Tao, Mingqiang Li, Bumjun Kim, Debra T. Auguste
Journal: Theranostics (2017)

Breast cancer is the second leading cause of cancer-related mortality in women.Successful development of sensitive nanoprobes for breast cancer cell detection is of great importance for breast cancer diagnosis and symptomatic treatment.Herein, inspired by the intrinsic peroxidase property of gold nanoclusters, high loading, and targeting ability of ErbB2/Her2 antibody functionalized liposomes, we report that gold nanoclusters-loaded, target-directed, functionalized liposomes can serve as a robust sensing platform for amplified colorimetric detection of HER2-positive breast cancer cells.This approach allows HER2-positive breast cancer cell identification at high sensitivity with high selectivity.In addition, the colorimetric "readout" offers extra advantages in terms of low-cost, portability, and easy-to-use applications.The practicality of this platform was further proved by successful detection of HER2-positive breast cancer cells in human serum samples and in breast cancer tissue, which indicated our proposed method has potential for application in cancer theranostics.
Financial toxicity in thyroid cancer: An analysis from the North American Thyroid Cancer Survivorship study.
Authors: Jonas A. De Souza, Raymon Grogan, Brisa Aschebrook-Kilfoy
Journal: Journal of Clinical Oncology (2016)

17 Background: Financial toxicity (FTox) has been associated with worse health-related quality-of-life (HRQoL), compliance, and even survival in cancer patients (pts). Measuring FTox and understanding its predictors are of paramount importance when planning intervention strategies, the value of care, and healthcare policies. We report FTox and its predictors in a large cohort of thyroid cancer pts and survivors. Methods: Pts with thyroid cancer were surveyed in the North American Thyroid Cancer Survivorship Study. FTox was assessed by the previously validated COmprehensive Score for financial Toxicity (COST), as well as by questions related to financial distress (out-of-pocket costs, loss of income and bankruptcy). Data on sociodemographics, income, type of disease, length of diagnosis (LOD), and prior therapies were collected. Predictors of FTox were assessed in multivariate analyses, controlling for potential confounders, such as HRQoL (as measured by the thyroid cancer-specific City of Hope instrument), type of treatment received, and LOD. Results: 591 pts with thyroid cancer within the past 6 years were surveyed in 2 countries: 553 (93.5%) in the United States (U.S.), and 38 (6.5%) in Canada. Most were women (n = 518 pts, 88%). The median LOD was 857 days (range 105-2176 days), and 430 pts (72.8%) had papillary thyroid cancer. There were 61 pts (10.3%) with Stage IV, and 11 (1.9%) were on tyrosine kinase inhibitors. Overall, 234 pts (39.5%) stated that their out-of-pocket costs were higher than previously thought; 207 pts (35%) felt their disease resulted in loss of income; 44 pts (7.4%) were unable to meet their monthly expenses; and 7 pts (1.2%) declared bankruptcy after diagnosis. The median COST value was 24 (range 0-44). In multivariate analyses, the independent predictors of worse FTox were lower income (p &lt; 0.001), female gender (p = 0.01), lower educational level (p = 0.002), healthcare delivery in the U.S., (p = 0.002), and worse HRQoL (p &lt; 0.001). Conclusions: A significant proportion of thyroid cancer pts experience FTox. We identified pts characteristics (gender, education, income), as well as geographical differences (healthcare delivery in the U.S.) as predictors of FTox.
Radioprotective effects of cimetidine on rats irradiated by long-term, low-dose-rate neutrons and 60Co γ-rays
Authors: Ding-Wen Jiang, Qing-Rong Wang, Xian-Rong Shen, Ying He, Tian-Tian Qian, Qiong Liu, Deng-Yong Hou, Yu-Ming Liu, Wei Chen, Xin Ren, Ke-Xian Li
Journal: Military Medical Research (2017)

Cimetidine, an antagonist of histamine type II receptors, has shown protective effects against γ-rays or neutrons. However, there have been no reports on the effects of cimetidine against neutrons combined with γ-rays. This study was carried out to evaluate the protective effects of cimetidine on rats exposed to long-term, low-dose-rate neutron and γ-ray combined irradiation (n-γ LDR). Fifty male Sprague-Dawley (SD) rats were randomly divided into 5 groups: the normal control group, radiation model group, 20 mg/(kg · d) cimetidine group, 80 mg/(kg · d) cimetidine group and 160 mg/(kg · d) cimetidine group (10 rats per group). Except for the normal control group, 40 rats were simultaneously exposed to fission neutrons (252Cf, 0.085 mGy/h) for 22 h every day and γ-rays (60Co, 0.097 Gy/h) for 1.03 h once every three days, and the cimetidine groups were administered intragastrically with cimetidine at doses of 20, 80 and 160 mg/kg each day. Peripheral blood WBC of the rats was counted the day following exposure to γ-rays. The rats were anesthetized and sacrificed on the day following exposure to 252Cf for 28 days. The spleen, thymus, testicle, liver and intestinal tract indexes were evaluated. The DNA content of bone marrow cells and concanavalin A (ConA)-induced lymphocyte proliferation were measured. The frequency of micronuclei in polychromatic erythrocytes (fMNPCEs), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) in the serum and liver tissues were detected. The peripheral blood WBC in the cimetidine groups was increased significantly on the 8th day and the 26th day compared with those in the radiation model group. The spleen, thymus and testicle indexes of the cimetidine groups were higher than those of the radiation model group. The DNA content of bone marrow cells and lymphocyte proliferation in the cimetidine groups were increased significantly, and fMNPCE was reduced 1.41-1.77 fold in cimetidine treated groups. The activities of SOD and GSH-Px in the cimetidine groups were increased significantly, and the content of MDA in the cimetidine groups was decreased significantly. The results suggested that cimetidine alleviated damage induced by long-term, low-dose-rate neutron and γ combined irradiation via antioxidation and immunomodulation. Cimetidine might be useful as a potent radioprotector for radiotherapy patients as well as for occupational exposure workers.
Pharmacokinetics (PK) and pharmacodynamics (PD) of PD 0325901, a second generation MEK inhibitor after multiple oral doses of PD 0325901 to advanced cancer patients
Authors: S. S. Menon, L. R. Whitfield, S. Sadis, M. B. Meyer, J. Leopold, P. M. Lorusso, S. Krishnamurthi, J. R. Rinehart, L. Nabell, G. Croghan
Journal: Journal of Clinical Oncology (2005)

3066 Background: PD 0325901 is a potent and selective inhibitor of MEK1/2, (MAPK/ERK/KINASE) being developed for treatment of cancer. Methods: This first-in-human trial employed an open-label, dose-escalating design where patients received 21-day courses of oral PD 0325901 (QD or BID) every 4 weeks. Doses ranged from 1 mg QD to > 20 mg BID. The PK of PD 0325901 and it's metabolite PD 0315209 were assessed on Day 1 (Cycles 1&2) and on Day 21. The effect of food on the PK of PD 0325901 was evaluated in a limited number of patients (Day 1 of Cycles 1 & 2). PD markers of MEK1/2 activity (pERK) and cell proliferation (Ki67) were assessed by quantitative immunohistochemistry in tumor biopsies obtained at baseline and on Day 15 (2–4 hours after dosing). Dose escalation and additional PK and PD assessments continue. Results: PD 0325901 and PD 0315209 Cmax and AUC on Days 1 and 21 generally increased with dose over the dose range studied. PD 0325901 was rapidly absorbed under fasting conditions with peak plasma concentrations occurring approximately 1 hour after dosing. Food prolonged Tmax 4-fold, decreased Cmax modestly, and had a variable effect on AUC. The mean metabolite to parent AUC ratios ranged from 0.4 to 1.8. Steady-state average plasma concentrations predicted necessary for near maximal pERK suppression in preclinical xenograft models were, on average, achieved at doses ≥ 15 mg BID. However, strong tumor pERK suppression was observed at much lower doses (average 84% decline over the dose range of 2 mg BID to 30 mg BID). Ki67 was also markedly affected over this dose range (average 60% decline). Conclusions: PD 0325901 Cmax and AUC generally increased with dose over the dose range studied. PD 0325901 strongly suppressed pERK levels in tumors at relatively low dose levels. PD 0325901 is a good candidate to evaluate MEK1/2 as a therapeutic target in cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer