tbuckley/cabot-search huggingface dataset:
Higher peripheral lymphocyte count to predict survival in triple-negative breast cancer (TNBC).
Authors: Anosheh Afghahi, Joseph Rigdon, Natasha Purington, Manisha Desai, Emma Pierson, Maya Mathur, Caroline A. Thompson, Christina Curtis, Robert B. West, Kathleen C. Horst, Scarlett Lin Gomez, James M. Ford, George W. Sledge, Allison W. Kurian
Journal: Journal of Clinical Oncology (2016)

1010 Background: A rich lymphocytic infiltrate in pre-treatment tumor biopsies predicts better overall survival (OS) in TNBC. We investigated whether peripheral lymphocyte count is similarly associated with OS in TNBC, and assessed other prognostic factors including race/ethnicity, treatment, and germline BRCA1 and BRCA2 (BRCA1/2) mutation status. Methods: Diagnostic and treatment data from electronic medical records of two California medical centers were linked on the patient level with demographic, staging and survival data from the California Cancer Registry. Cox and logistic regression models were used to evaluate associations between absolute lymphocyte count (ALC) and OS. The former used the lowest ALC value (minALC) since TNBC diagnosis (dx); the latter used ALC over time since dx. Models were adjusted for total white blood cell count (WBC), absolute neutrophil count (ANC), age, race, socioeconomic status (SES), stage, chemotherapy (CT), radiotherapy (RT) and BRCA1/2 mutations. Results: 1480 Stage I-III TNBC patients (pts) were treated at one or both centers from 2000-2014; 1130 (76.4%) pts had CT and 797 (53.9%) RT. Of 788 pts with ALC data, 496 (62.9%) were lymphopenic (minALC < 1.0 K/uL). On multivariable analysis (MVA), higher ALC, but not WBC or ANC, predicted OS; this association increased over time (odds ratio [OR] of ALC, at dx: 0.34, 95% confidence interval [CI] 0.23-0.49; at 5 years post-dx: 0.18, CI 0.12-0.28). Other predictors of OS were CT and RT use and high SES, with a trend toward better OS with a BRCA1/2 mutation (Table). Probability of 5-year OS on MVA was 85% for pts who were ever lymphopenic, versus 96% for pts who were not. Conclusions: Higher ALC strongly predicted better 5-year OS (96%, versus 85% with minALC < 1.0) in TNBC; this association increased over time, suggesting that higher ALC may enhance the curative potential of early treatment. Future studies should examine the role of peripheral and tumor lymphocytes in TNBC, and of moderating genetic factors. MVA of association between minALC and OS. Characteristics Hazard Ratio (95% CI) Age 1.01 (1.00, 1.02) SES 0.82 (0.71, 0.93) BRCA1/2 Mutation 0.67 (0.33, 1.33) CT Use 0.52 (0.33, 0.81) RT Use 0.66 (0.47, 0.92) minALC 0.22 (0.14, 0.34)
Maximizing Benefits and Minimizing Harms of Lung Cancer Screening
Authors: Jason N. Mansoori, Nathaniel Little, Stephen P. Malkoski
Journal: JAMA Internal Medicine (2017)

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Expression of metabolic enzymes as predictors of prognosis in patients with aggressive primary brain cancers.
Authors: Kenneth A. Schwartz, Mary Noel, Mohammed Shaik, Howard Chang, L. Karl Olson
Journal: Journal of Clinical Oncology (2017)

e13529 Background: Aggressive primary brain cancers like glioblastoma multiforme (GBM) are metabolically active tumors. We hypothesis that abnormalexpression of metabolic enzymes may be useful in predicting survival. Methods: 60 patients (45 with GBM, 11 with anaplastic gliomas and 4 with gliosarcoma) were evaluated using Immunohistochemistry (IHC) to measure the relative expression of metabolic enzymes known to be predictors of prognosis including hexokinase-II (HK2) and mutated isocitrate dehydrogenase-1 (IDH1-R132H) as well as several ketolytic enzymes including cytosolic type 2 (R)-beta-hydroxybutyrate dehydrogenase (BDH2)..The tumors were graded based on the percentage of immunoreactive tumor cells: Positive (≥20%), Negative ( &lt; 20%). Survival was calculated using Kaplan Meier (KM), and an age adjusted hazard ratio (aHR) for death was obtained using cox proportional analysis for enzyme expression. Significance p ≤0.05. Results: Demographics for 60 patients; 19 females and 41 males, median age 62 years, and median survival for all the patients 5.9 months. Univariate analysis showed positive HK2 and negative BDH2 expression had decreased survival with (HR of 1.8 p = 0.06 and 2.6 p = 0.01), respectively. In a multivariate analysis after adjusting to age, histology and other enzyme expression, positive HK2 and negative BDH2 expression were statistically associated with decreased survival (aHR of 11.3 p = 0.001 and 32.6, p = 0.0004), respectively. The group with favorable prognosis (negative HK2 and positive BDH2 expression) (n = 36) had a median survival of 9.7 months (95% CI 4.2 -13.5) whereas the group with non-favorable prognosis (neither a negative HK2 nor a positive BDH, n = 24) had a median survival of 3.1 months (95% CI 1.8 – 5.8). Because only 3 patients had GBM that were positive for the IDH1-R132H mutant protein, IDH1-R132H was not used as a statistically valid predictor in this study. Conclusions: Our current result confirms the poor prognosis associated with positive expression of HK2, and suggests that negative IHC expression of BDH2 may be a new indicator of poor prognosis for patients with aggressive primary brain cancers.
Review: Compared with systolic BP target of &lt; 160 mm Hg, targeting &lt; 120 is more effective; &lt; 130 balances benefits and harms
Authors: Raj Padwal
Journal: Annals of Internal Medicine (2017)

Source Citation Bangalore S, Toklu B, Gianos E, et al. Optimal systolic blood pressure target after SPRINT: insights from a network meta-analysis of randomized trials. Am J Med. 2017;130:707-19. 28109971
Abstract 1161: AAV-2-mediated Nerve Growth Factor Gene Transfer Prevents the Development of Experimental Diabetic Cardiomyopathy in Mice
Authors: Marco Meloni, Andrea Caporali, Lorena Zentilin, Paolo Madeddu, Mauro Giacca, Costanza Emanueli
Journal: Circulation (2009)

Diabetes mellitus (DM) can cause cardiac dysfunction and heart failure independently of other risk factors like hypertension and myocardial infarction. The neurotrophin nerve growth factor (NGF) ex...
Risk-adapted screening in bladder cancer with the open-access tool RiskCheck Bladder Cancer: Proof of principle by the health service research foundation IQUO.
Authors: Goetz Geiges, Frank Koenig, Gerson Lüdecke
Journal: Journal of Clinical Oncology (2013)

1571 Background: The open-access questionnaire RiskCheck Bladder Cancer (RCBC) was proven in daily routine work from German urologists organized in the health services research foundation IQUO on asymptomatic patients to identify BC risk exposure and its relation to detectable tumors. Methods: The open-access RCBC questionnaire checked asymptomatic patients for their BC risk exposure in relation to personal-, smoking-, occupation- and medical induced risk. This resulted in a risk stratification with low- intermediate- and high risk. The intermediate and high risk subjects were checked for tumor presence by routine diagnostics. IBM-SPSS 20 was used for descriptive statistics and effectiveness was proven by classification tree analysis and cross-table analysis with Chi-square test. Results: Out of 303 checked asymptomatic persons 274 (90.4%) were negative for tumor and 29 (9.6%) had a detectable tumor. In the group of NED 176 (68.1%) persons were classified as low risk, and 98 (16.2%) with tumor risk. Out of the 29 detected tumors 20 were at intermediate or high risk (68.9%). This resulted in an over all detection rate of 6.6% and focused on the risk population of 16.9%. The RCBC risk assessment was significant (p &lt; 0.01). Sensitivity 69.0%, specificity 64.2%, NPV 95.1%, PPV 16.9%, false positive cases 35.8%, false negative cases 31.0%, accuracy 64.7%. Compared to the common incidence (35/100,000) this is an increase in effectiveness of 188.6 in the screened population and 482.8 in relation to the risk population alone. Conclusions: Preventive medical care becomes effective because RCBC is able to condense a population with focusing investigations on people living under risk. A reasonable preventive care by a yearly recall control in urological offices for the risk population (32.3%) can be organized. In consequence the assessment is work effective, aim achieving and in result cost effective. The questionnaire RCBC integrates evidence based bladder cancer inductors, is easy in use and as a open-access tool available in 10 languages via internet to all medical services. www.riskcheck-bladder-cancer.info.
Single-institute retrospective review of pregnancy-associated breast cancer patients and similar cohort of nonpregnant breast cancer patients with regard to age and year of diagnosis for their outcome, prognosis, and overall survival.
Authors: Kausar Suleman
Journal: Journal of Clinical Oncology (2014)

e11563 Background: In this paper we intended to review the data of PABC Single Institute experience and outcome, and to compare those seen in a matched group for age and year of diagnosis. Methods: The data of all patients with PABC and similar cohort of non-pregnant breast cancer patients retrospectively reviewed. Group 1 is PABC and Group 2 is matched control without pregnancy during time period of 2001 to 2010. Stage 1 and 2 patients were classified as Early Stage, Stage 3 and 4 patients were classified as Advanced Stage patients. Her-2 was considered positive if +3 or FISH amplified. 110 patients in Group 1 and 114 patients in Group II were identified. Statistical analysis is intended to test the hypothesis that pregnant breast cancer women have different outcomes in comparison to the non-pregnant breast cancer women. Statistical analysis was conducted using SAS 9.3 and R-2.14.1 Results: In both groups, patient age ranged between 20 to 45, and they were all diagnosed at the same time interval. The median follow up is 34 months PABC and 54 months in Group 2. Group 1 has more triple negative, as 23%, versus 15% (26 versus 17 patients). Early Stage was more common in Group 2 than Group 1, 57 versus 36 patients. Group 1 had more Advanced Stage patients as 62, compared to only 42 in Group 2. ER+PR+ tumor is more in Group2 vs Group 1, 56 vs 41 patients. Her-2 positive patients were fairly same 40 versus 36 patients in. Overall there was a statistical significance of triple negative and advanced stage to be common in Group 1 versus Group 2. In pregnant patients there was 5 year survival rate 65% compared to non pregnant match group of 82% with p value of0.002 and DFS was also 47.5% vs 65.4% p value .002. Conclusions: Our conclusion is pregnancy associated breast cancer is diagnosed at a more advance stage, more aggressive, they were more triple negative and associated with worse DFS and overall survival. Their mortality rate is twice the mortality rate of non pregnant matched group and relapse rate 68% increased compare to match group.
Abstract 98: Tenascin-C as a Novel Biomarker for Predicting Therapeutic Effect in Kawasaki Disease
Authors: Yoshiaki Okuma, Kyoko Imanaka-Yoshida, Michiaki Hiroe, Takeji Matsushita, Jun Abe, Fukiko Ichida, Tsutomu Saji, Kei Takahashi, Isao Shiraishi, Kenji Suda, Atsuhito Takeda, Yoshihide Mitani, Yukako Yoshikane
Journal: Circulation (2015)

Background: In acute stage of Kawasaki disease (KD), patients who are unresponsive to initial therapy are immediately administered additional therapy to prevent the development of coronary artery abnormalities (CAAs). Although failure to respond is defined as persistent or recrudescent fever after treatment, it is difficult to recognize the presence of fever because steroids are administered with intravenous immunoglobulin (IVIG) in severe KD patients in Japan. In addition, inflammatory markers such as CRP usually decrease after initial therapy in patients who are unresponsive to initial therapy and there is no biomarker for monitoring treatment effect. Tenascin-C (TN-C) is an extracellular matrix protein specifically upregulated in response to tissue injury and inflammation. Methods: We recruited 174 patients (male 102, female 72) from August 2011 to April 2014, from fourteen institutions in Japan. Serum levels of TN-C (sTN-C) were examined using ELISA before and after initial treatment. The initial treatments consisted of: 30 aspirin only, 111 IVIG + aspirin, and 33 IVIG + aspirin + prednisolone. We compared patients who responded to initial therapy (R group; n = 134) with those who did not respond (NR group; n = 40) regarding patient profile and laboratory data. Results: Patients in NR group had higher % neutrophil (p = 0.004), CRP (p = 0.012) and sTN-C (p = 0.049) than in R group before treatment. After initial therapy, WBC, % neutrophil and CRP significantly decreased in both groups (p &lt; 0.001), but sTN-C did not significantly decrease in NR group (p = 0.485). When sTN-C after initial therapy was used to predict unresponsiveness of initial therapy, sensitivity, specificity and AUC were 85%, 55%, and 0.745 respectively. Especially in patients who were administered steroids with IVIG as initial therapy, the accuracy of predictive model using sTN-C after initial therapy was high (AUC 0.812, sensitivity 71%, specificity 81%). The incidence of CAAs tends to be higher in NR group than in R group (12.5 vs. 3.7 %, p = 0.051). Conclusions: TN-C is a potential biomarker in predicting the need for additional therapy. Especially in KD patients who are treated by steroids with IVIG, TN-C may be useful.
Phase I trial of a dual TOR kinase and DNA-PK inhibitor (CC-115) in advanced solid and hematologic cancers.
Authors: Pamela N. Munster, Amit Mahipal, John J. Nemunaitis, Monica M. Mita, Luis G. Paz-Ares, Christophe Massard, Tom Mikkelsen, Cristina Cruz, Dana E. Rathkopf, George R. Blumenschein, Manuel Hidalgo, David C. Smith, Barbara Eichhorst, Timothy Francis Cloughesy, Brett Garrick, Torsten Trowe, Ellen Filvaroff, Kristen Hege, Johanna C. Bendell
Journal: Journal of Clinical Oncology (2016)

2505 Background: CC-115 is a potent inhibitor of DNA-PK and TOR kinase (DNA-PKi/TORKi) with broad pre-clinical anti-tumor activity. Methods: Subjects with relapsed/refractory advanced solid and hematologic cancers enrolled in a first-in-human Phase 1a/b study of CC-115 given orally once or twice daily until disease progression in dose escalation and expansion cohorts. Results: 44 subjects evaluated across 10 dose escalation cohorts (0.5 – 40 mg) established 10 mg twice-daily (BID) as the recommended dose for cohort expansion in 62 additional subjects with glioblastoma multiforme (GBM: 14), head and neck squamous carcinoma (HNSCC: 18), chronic lymphocytic leukemia (CLL: 8), and ETS-overexpressing tumors (castration-resistant prostate cancer [CRPC: 12] and Ewing's sarcoma [ES: 10]). The most common (> 20%) expansion phase related adverse events were fatigue (37%), nausea (31%), decreased appetite (29%), and hyperglycemia (24%). Linear, dose proportional exposure was observed with a terminal half life of 4 to 8 hrs (mean steady state Cmax 75 ng/mL, AUC0-24 776 ngxhr/mL at 10mg BID). Gastric pH-altering drugs and food did not impact PK. Plasma accumulation was minimal, renal clearance was negligible and brain penetration was confirmed in resected GBM (tumor/plasma ratio 0.7). Inhibition of TORC1 (pS6, p4EBP1) and TORC2 (pAKT) biomarkers in blood cells was exposure-dependent and consistently achieved with 10 mg BID dosing. DNA-PK inhibition was demonstrated ex vivo in circulating CLL cells from one subject dosed with CC-115. Tumor responses during dose escalation included 1 complete response (endometrial; >3yr), 1 partial response (melanoma), and stable disease (SD) in 18 (41%) subjects. In the efficacy-evaluable expansion cohorts, SD was observed in CRPC (64%), HNSCC (53%), GBM (non-progression 21%), and ES (22%). One PR, and 3 PR with lymphocytosis (IWCLL), were seen in CLL. Conclusions: CC-115 was well tolerated with toxicities comparable with approved mTOR inhibitors. Evidence of TORC1/TORC2/DNA-PK pathway inhibition was observed as well as preliminary signals of broad anti-tumor activity. Phase 2 trials combining CC-115 with androgen deprivation in CRPC and radiation in GBM are planned. Clinical trial information: NCT01353625.
Seeking Convergence to advance Biomaterials Science and Translation by Chinese Association for Biomaterials
Authors: Guigen Zhang, Jian Yang, Bingyun Li, Kelvin Yeung, Yi Hong
Journal: Bioactive Materials (2017)

The Chinese Association for Biomaterials (CAB) organized a CAB Day Symposium with a theme of "Seeking Convergence to Advance Biomaterials Science and Translation."Image 1.
Disease-free (DFS) and overall survival (OS) at 3.4 years (yrs) for neoadjuvant bevacizumab (Bev) added to docetaxel followed by fluorouracil, epirubicin and cyclophosphamide (D-FEC), for women with HER2 negative early breast cancer: The ARTemis trial.
Authors: Helena Margaret Earl, Louise Hiller, Janet Dunn, Clare Blenkinsop, Louise Grybowicz, Anne-Laure Vallier, Jean Abraham, Luke Hughes-Davies, Karen McAdam, Stephen Chan, Rizvana Ahmad, Tamas Hickish, Stephen Houston, Daniel Rea, John Bartlett, Carlos Caldas, David A. Cameron, Elena Provenzano, Jeremy Thomas, Larry Hayward
Journal: Journal of Clinical Oncology (2016)

1014 Background: ARTemis compared the addition of Bev to neoadjuvant D-FEC in HER2 negative breast cancer. Improved pathological complete response (pCR) with Bev has been reported previously. Methods: We enrolled women ≥ 18 yrs with radiological tumour size > 20mm, ± axillary involvement, at 66 centres in the UK. Patients (pts) were randomly assigned to 3 cycles of D (100 mg/m² every [q] 21 days [d]) followed by 3 cycles of F (500mg/m2), E (100mg/m2) and C (500 mg/m²) q 21d (D-FEC), ± 4 cycles Bev (15mg/kg) (Bev+D-FEC). We present the DFS and OS results, analysed by intention-to-treat. pCR is defined by report review; analysis by central pathology review will be available at the time of presentation. Results: Between May'09 and Jan'13, we randomised 800 pts; 401 to D-FEC and 399 to Bev+D-FEC. Median follow-up was 3.4 yrs (IQR 2.5–4.4). 131 deaths and 183 DFS events have occurred. Both OS and DFS were similar across treatments (3-yr OS: Bev+D-FEC 85%, D-FEC 87%; hazard ratio (HR) 0.80 (95%CI 0.57-1.12) p = 0.19. 3-yr DFS: Bev+D-FEC 77%, D-FEC 80%; HR 0.86 (95%CI 0.64-1.14) p = 0.29). pCR was associated with improved OS in D-FEC pts (3-yr OS: pCR 96%, non-pCR 84%; log-rank p = 0.01) but not with Bev+D-FEC (3-yr OS: pCR 87%, non-pCR 83%; log-rank p = 0.71). Similarly pCR predicted for improved DFS with D-FEC (3-yr DFS: pCR 97%, non-pCR 76%; log-rank p = 0.0006), but not with Bev+D-FEC (3-yr DFS: pCR 84%, non-pCR 74%; log-rank p = 0.19). There was borderline heterogeneity in the effect of the addition of Bev between pCR and non-pCR groups in terms of OS (p = 0.07), and significant heterogeneity in terms of DFS (p = 0.02). Conclusions: Although Bev+D-FEC produced significantly higher pCR rates when added to chemotherapy in the ARTemis trial, OS and DFS were not improved. Moreover pCR achieved by Bev+D-FEC does not appear to be associated with the improved OS and DFS which is seen with pCR achieved by D-FEC. This data suggests that micro-metastatic breast cancer may be angiogenesis-independent and hence not altered by neoadjuvant Bev treatment. Clinical trial information: ISRCTN 68502941.
Use of a nanotechnology-based system for the prospective characterization of circulating tumor cells in head and neck cancer patients.
Authors: Joseph Michael Caster, Michael Joseph Eblan, Ja Hye Myung, Kyle Wang, Seungpyo Hong, Bhishamjit S. Chera, Andrew Wang
Journal: Journal of Clinical Oncology (2016)

11536 Background: Circulating tumor cells (CTCs) are an important biomarker in cancer and there is significant interest in developing new technologies to adequately assess CTCs to enable personalized treatment. Limited data exists for CTCs in patients with head and neck cancers (HNC) who may benefit from risk-based treatment. The purpose of this prospective, correlative study is to investigate the clinical significance of CTCs, as measured by a highly sensitive CTC capture technology UiChip, in HNC patients undergoing definitive radiation treatment (RT). Methods: Non-metastatic HNC patients undergoing definitive RT (+/- chemotherapy) were eligible. Peripheral blood was collected at up to 7 time points: prior to starting RT, first week, mid-point, end of treatment, and every 4 to 12 weeks post RT. CTCs were quantified using UiChip. The primary endpoint was changes in CTCs pre- and post- RT. Results: 35 patients are included in this analysis. CTCs were detected in all patients pre-RT. There was no association between pre-RT CTCs and T or N stage. Among 25 patients with sequential CTC measurements, the median CTC count (CTCs/mL) significantly decreased from 71 (range, 7-849) before RT to 32 (2-209) at completion of RT and 27 (2-78) at 4 to 12 weeks post-treatment. Ten patients had locally persistent disease and/or distant metastasis at a median follow-up of 10.6 months (range, 3.7-17). CTCs declined throughout the treatment course in patients with complete responses, in contrast to an elevation in CTCs at mid or post-RT in the 5 patients with pathologic residual disease and/or distant failures with 3 months of their last CTC measurement (Table). Conclusions: We demonstrated that the UiChip can capture CTCs in a diverse population of HNC patients. Our pilot data suggests that individual patient CTC changes with treatment may be a predictive biomarker for clinical outcomes. Median CTC/mL peripheral blood (median % of baseline). Pre-RT Mid-RT Post-RT Number (%) in Complete Responders to RT (N=20) 76 37 (38%) 26 (18%) IQR (%) 39-125 21-81 (13-102%) 8-52 (12-44%) Number (%) in Partial Responders to RT (N=5) 42 66 (133%) 23 (55%) IQR (%) 36-303 27-120 (31-211%) 22-57 (42-71%) IQR: Interquartile Range