tbuckley/cabot-search huggingface dataset:
Searching for circulating proteins as new biomarkers/potential therapeutic targets in advanced pancreatic cancer patients.
Authors: Roberto A. Pazo Cid, Julian Pardo, Ana Nuno-Alves, Ibón Gurruchaga, Maria Alvarez, Mª Irene Torres, Ana Comin, Mª Pilar Felices, Javier Martínez-Lite, Antonio Anton
Journal: Journal of Clinical Oncology (2018)

e16219 Background: Ca19.9 is the only validated biomarker in pancreatic cancer. Novel biomarkers are needed. Methods: Plasma samples from ECOG 0-1 metastatic pancreatic cancer patients (n = 20) were colected prospectively before (basal time, Bt) and after one cycle (1Ct) of first-line nab-paclitaxel plus gemcitabine therapy (AG). A 440 protein multiplex ELISA array was run in the 40 plasma samples. The cohort was followed up for a median of 12 months (m) for progression free survival (PFS), overall survival (OS) and overall response rate (ORR). Survival curves estimated using Kaplan-Meier were compared with log-rank tests. Results: Median PFS 9,2m (95% CI 3.2-14.5) and OS 13.5m (95% CI 4.4-20.5); ORR: CR/PR/SD/PD 0/8/11/1. At Bt: Proteins predictive for both PFS and OS: IL18Rb, CCL13 (MCP), Decorin, Pepsinogen and CXCL5 (ENA78); Proteins predictive for ORR: FcgRIIBC, IL15R, Lipocalin2, ESAM, Activin A, WIF1, Galectin 1 and TECK; Proteins predictive only for PFS: IL17F, CCL17, Adipsin, CRP, MMP2, Chemerin, Thrombomodulin, Transferrin, CA9, Eotaxin, IL5 ans IL10; Proteins predictive only for OS: NRG1b1, ICAM2 (CD102), DLK1, Lox1, CXCL14, CHI3L1, P-cadherin, IL32a and FGF7. At 1Ct: only IL18Rb was predictive for both PFS and OS; only FcgRIIBC and IL15R were predictive for ORR. Conclusions: Higher plasma levels of IL18Rb are strong predictors of better survival. Higher plasma levels of FcgRIIBC and/or lower plasma levels of IL15R are key factors of response to AG. These proteins deserve further evaluation both as biomarkers and as potential therapeutic targets. IL18Rb plasma levels OS Bt (m) p = 0.049 OS 1Ct (m) p = 0.021 PFS Bt (m) p = 0.004 PFS 1Ct (m) p < 0.001 < Median 9.8 (7.08-11.8) 9.0 (5.58-12.4) 7.1 (4.46-9.73) 5.8 (4.46-9.73) > Median 17.8 (10.4-25,06) 17.8 (10.4-25,06) 11.8 (9.3-14.3) 13.1 (9.3-14.3 PD (n = 8) SD p-value Test X SD X SD FcgRIIBC Bt 1610.69 848.21 736.02 541.11 0.014 Student t FcgRIIBC 1Ct 254.07 404.16 -155.53 466,32 0.041 UMannW IL15R Bt 1.63 4.60 16.87 21.25 0.030 UMannW IL15R 1Ct -1,28 3.62 13.78 21.28 0.031 UMannW
PET scan metabolic activity and programmed cell death-ligand 1 expression in lung cancer patients: Is there a correlation?
Authors: Heather Katz, Raj Singh, Hayden Ansinelli, Christopher Blackwell, Mohamed Farouq Alsharedi
Journal: Journal of Clinical Oncology (2018)

e21199 Background: Lung Cancer is the leading cause of cancer related death. Checkpoint inhibitors have changed the treatment algorithm for Non-Small Cell Lung Cancer (NSCLC). Checking PD-L1 by immunohistochemistry is now standard of care however maybe unobtainable due to limited tissue biopsy. Positron emission tomography (PET)/computed tomography (CT) using F-18 fluorodeoxyglucose (FDG) is also ordered as part of the workup. After review of the medical literature and current limited data, we aim to determine if metabolic activity on PET scan correlates with PD-L1 expression and can serve as a predictor of PD-L1 status. Methods: A retrospective chart review was performed from January 2016 to June 2017 at the Edwards Comprehensive Cancer Center in Huntington, WV. Fifty lung cancer patients were checked for PD-L1. Exclusion criteria included no PET scan, PET scan without SUVmax or inadequate PD-L1 sampling. Thirty-three charts were reviewed for age, gender, histology, smoking history, PD-L1 status, PET maximum SUV and presence of brain metastasis. Results: There was a homogenous group of patients: all were caucasian, average age was 68.7, gender distribution was 54.5% male and 45.5% female. Most patients had NSCLC (96.9%); Most smoked (93.9%); Only 9% had brain metastasis. PD-L1 expression: 36.4% had PD-L1 0%, 60.6% had PD-L1 < 50% and 3% had PD-L1 > 50%. PET CT scan Mean SUVmax was 12.18. Statistical analysis after adjusting for age, gender, PD-L1 expression indicated no correlation between PDL1 and PET SUVmax (Spearman Correlation p = 0.679). Conclusions: Although this small single institution study did not yield a correlation between PET maximum SUV and PD-L1 status, further studies are needed to assess whether there is an association between PET/CT SUV and PD-L1 to determine if metabolic activity on PET scan can be used to predict PD-L1 expression.
MSNCs and MgO-MSNCs as drug delivery systems to control the adsorption kinetics and release rate of indometacin
Authors: Xin Zheng, Shuang Feng, Xiudan Wang, Zhenning Shi, Yuling Mao, Qinfu Zhao, Siling Wang
Journal: Asian Journal of Pharmaceutical Sciences (2018)

Mesoporous silica cocoon materials (MSNCs) and MgO doped mesoporous silica cocoons (MgO-MSNCs) with the cocoon-like hierarchical morphology and different alkalinities were synthesized as carriers for acidic drugs. Indomethacin (IMC) was selected as a model drug and loaded into carriers. All materials and the drug-loaded samples were characterized by nitrogen adsorption, FTIR spectroscopy, transmission electron microscopy (TEM), powder X-Ray diffraction (XRD) and differential scanning calorimetry (DSC). The effect of the Mg/Si molar ratio on the kinetics and equilibrium of IMC adsorption on MgO-MSNCs was thoroughly examined, and it was found that the increase in the Mg/Si molar ratio resulted in an increasing IMC adsorption rate due to the increased affinity between alkaline MgO-MSNCs and weak acid IMC. The adsorption kinetics fitted a pseudo second-order model well. The Freundlich isotherm showed a better fit, indicating that the coverage of IMC on the surface of MgO-MSNCs was heterogeneous. The maximum adsorption capacity of adsorbent was calculated by the Langmuir isotherm equation. The Temkin equation provided further support that the IMC adsorption on MgO-MSNCs was dominated by a chemisorption process. MgO-MSNCs also have the advantage of allowing an adjustment of the drug release rate of weak acid drug. The cytotoxicity assay indicated good biocompatibility of MgO-MSNCs. Our research on MgO-MSNCs carriers demonstrated their potential therapeutic benefit for safe and effective management of IMC adsorption and in vitro release.
An intervention study to reduce black-white treatment disparities in early stage non-small cell lung cancer.
Authors: Paul R. Walker, Sam Cykert, Lloyd Edwards, Rohan Arya, Peggye Dilworth-Anderson
Journal: Journal of Clinical Oncology (2017)

6560 Background: Racial disparities in the treatment of non-small lung cancer (NSCLC) continue to exist leading to poorer outcomes in African-Americans (AA) compared to Caucasians (C). Our previous multi-institutional prospective cohort study of 386 patients identified a surgical rate in early stage NSCLC of 66% C but only 55% AA (p = 0.05; OR 0.75; 95% CI 0.57-0.99). (Cykert et al JAMA 2010) A 3 year retrospective chart review of all patients with early stage NSCLC at the 3 academic institutions involved in this current intervention study identified 714 patients with early stage NSCLC. Baseline surgical rates 69% for C and 66% for AA. Combined stereotactic body radiation therapy (SBRT) with surgery C 80% and AA 76%. Controlling for co-morbidities, COPD, age and other demographic data, the OR for surgery AA compared to C 0.64 (95% CI 0.43-0.96) and for combined surgery or SBRT AA compared to C 0.61 (95% CI 0.43-0.96). Methods: Patients with a stage I or II NSCLC were identified and randomized to each institution’s standard of care approach or to an ‘intervention’ component utilizing a trained navigator to enhance patient communication and treatment understanding. Results: 244 patients were prospectively recruited into this intervention study. Mean age 65.7 years; 54% women; 89 (34%) AA. The intervention group showed an overall surgical rate of 74% (74.8% C, 71.4% AA; p = 0.6). Combined treatment of either surgery or SBRT increased an ablative treatment to 91.9% for C and 94.1% AA patients (p = 0.5). Logistic regression was performed comparing the intervention group to the baseline group. Results showed that overall treatment improved for both C and AA, the surgical and overall treatment disparity between C and AA was no longer present, while age, COPD, and clinical stage remained significant predictors of treatment. Conclusions: A multifaceted intervention designed to enhance patient communication and treatment understanding removed the surgical and overall early lung cancer treatment disparity between AA and C. Clinical trial information: NCT01687738.
The role of microphthalmia transcription factor (Mitf) in prediction of distant metastases in cutaneous melanoma.
Authors: Rand Naffouje, George I. Salti
Journal: Journal of Clinical Oncology (2016)

9564 Background: Microphthalmia Transcription Factor (Mitf) plays a central role in melanocyte maturation and differentiation, as well as tumorigenesis. We previously proved that Mitf expression of < 50% (Mitf < 50) in primary melanoma can serve as a predictor of lymphatic dissemination. In this prospective study we aim to further assess the value of Mitf expression in the primary tumor, and whether it can serve as a predictor of hematogenous spread, hence a predictor of distant metastatic formation in cutaneous melanoma. Methods: This is a prospective study including 171 patients diagnosed with primary cutaneous melanoma. All patients underwent resection of the primary tumor with either lymph node biopsies or dissections. Mitf expression in the primary melanoma was assessed via immunohistochemistry. Disease Free Survival (DFS) and Overall Survival (OS) curves were generated using the Kaplan-Meier method. Mitf < 50 was tested as an independent factor against age, location, histology, and thickness in a multivariate logistic regression model to predict distant metastasis. Results: 100 patients had Mitf < 50 (58.5%) whereas 71 had Mitf ≥ 50 (41.5%). Patients with Mitf < 50 had a significantly higher rate of distant metastases compared to those who had Mitf ≥ 50 (42% vs. 11.3%; p < 0.0001), and significantly shorter DFS (25.8±20.4 vs. 39.3±29.5 months; p < 0.0001) and OS (32.2±22.2 vs. 41.0±31.1 months; p = 0.042). In a multivariate logistic regression analysis, Mitf < 50 was shown to be a significant predictor of distant metastatic disease, along with thickness and dysplastic pathology. Conclusions: Mitf < 50 in primary melanoma can serve as a predictor of hematogenous spread. The high expression of this molecular marker in the primary tumor is validated to be a favorable prognosticator of DFS and OS.
Gender differences and trends in suicide risk among cancer survivors.
Authors: Nosayaba Osazuwa-Peters, Eric Adjei Boakye, Matthew C Simpson, Longwen Zhao, Kahee A. Mohammed, Travis M Loux, Mark Alex Varvares, Mario Schootman
Journal: Journal of Clinical Oncology (2018)

10087 Background: Cancer survivors have higher risks of dying from suicide compared with noncancer patients as well as the general United States population. This risk may differ based on gender and may be increasing due to the concomitant increase in the number of cancer survivors in the United States. This study aimed at describing the differences and identifying suicide risk trends based on gender. Methods: We queried the Surveillance, Epidemiology and End Results 18 database from 2000-2014 for all cancer deaths confirmed as suicide. Mortality rates from suicide was estimated for the 20 most common cancers in the United States, including lung, pancreatic, and head and neck cancers, three sites with leading suicide rates. Multivariate Poisson regression estimated mortality rate ratios (RRs) and 95% confidence intervals (CIs), stratified by sex (when applicable), and adjusting for site, race, marital status, age, year and stage of diagnosis. Results: There were 4,769 suicides observed among 4,427,272 cancer survivors from 2000-2014, yielding an incidence rate of 23.6 suicides per 100,000 person-years. Of these, 84.1% were suicides among male cancer survivors. Males cancer survivors were almost six times more likely to die from suicide compared with females (aRR = 5.62, 95% CI:5.17, 6.11). For males, increasing age (ref: 20-39 years) was associated with increasing risk of suicide: 40-59 years (aRR = 1.50, 95% CI: 1.22, 1.84), 60-69 years (aRR = 1.85, 95% CI: 1.50, 2.28), 70+ years (aRR = 2.52, 95% CI: 2.04, 3.11). It was the reverse in female survivors, where 60-69 (aRR = 0.71, 95% CI 0.61, 0.82) and 70+ year olds (aRR = 0.49, 95% CI 0.42, 0.57) were less likely than 20-39 years to commit suicide. Finally, compared with 2000-2004, female survivors diagnosed in 2010-2014 were 32% (aRR = 1.32, 95% CI: 1.19, 1.47) more likely to commit suicide, whereas male survivors were only 12% (aRR = 1.12, 95% CI 1.02, 1.23) more likely to commit suicide in the same period. Conclusions: There are significant male vs. female differences in suicide risks among cancer survivors, and there may have been an increased risk of suicide among women of reproductive age, and in the last decade. Survivors of cancer need surveillance to optimize survivorship and decrease suicide risks.
Meta-analysis to identify emerging biomarkers of pancreatic adenocarcinoma pathogenesis.
Authors: Kamal Khorfan, Jihad Aljabban, Laraib Safeer, Hisham Aljabban, Maryam Panahiazar, Anne M. Noonan, Dexter Hadley
Journal: Journal of Clinical Oncology (2018)

e16239 Background: Pancreatic adenocarcinoma (PAC) is the fourth leading cause of cancer-related deaths in the US and is particularly known for its aggressiveness and lack of effective therapeutic options. Most PAC cases are linked with old age and lifestyle, while inheritance is linked to a minority of cases. As more is being discovered of the genetic progression of PAC, research is focused on finding genetic determinants of PAC pathogenesis and new candidates for targeted therapy. Methods: We employed our Search Tag Analyze Resource (STARGEO) platform to conduct meta-analysis using the National Center for Biotechnology’s (NCBI) Gene Expression Omnibus (GEO) to define PAC pathogenesis. We tagged 228 pancreatic samples from PAC patients and used an equal number of healthy pancreatic samples as a control. We then analyzed the signature in Ingenuity Pathway Analysis, restricting genes that showed statistical significance (p < 0.05) and an absolute experimental log ratio greater than 0.15 between disease and control. Results: The meta-analysis identified GP6 signaling, stellate cell activation, integrin signaling, and NRF2-mediated signaling as top canonical pathways. Also, the LXR/RXR signaling canonical pathway was strongly inhibited. ERBB2, TGFB1, and lipopolysaccharide were activated, top upstream regulators. Our analysis revealed strong upregulation of tumor promoting proteins including S100P (calcium sensor), PPP5D1 (MAPK signaling), and carcinoembryonic antigen CEACAM5 (regulates differentiation, apoptosis, and cell polarity). We also found downregulation of metabolic and cell integrity proteins such as pancreatic lipase, carboxyl ester lipase, and PLA2G1B. Conclusions: PAC pathogenesis likely reflects a multi-factorial disease process driven by several pathways. Our analysis lends credence to emerging markers of PRC progression such as GP6 and integrin signaling, ERBB2, LXR/RXR signaling, among others. We also identified potential therapeutic and prognostic candidates.
Survival outcomes in patients with chronic phase chronic myeloid leukemia (CP-CML) receiving third- or subsequent line (3L) treatment prior to the availability of ponatinib.
Authors: Daniel R Stellato, Lisa McGarry, Hui Huang, Shaina Hastings, Thomas E. Delea
Journal: Journal of Clinical Oncology (2017)

e18553 Background: PACE was a phase 2 single-arm trial of ponatinib, a 3rd-generation tyrosine kinase inhibitor (TKI), in 449 highly-refractory patients with CML or Philadelphia-chromosome positive (Ph+) acute lymphocytic leukemia (ALL) or who had the BCR-ABL T315I mutation. Overall survival (OS) for 3L CP-CML patients in PACE at 1, 2, 3 and 4 years was estimated to be 91%, 83%, 80%, and 79%, respectively. Expected survival for 3L CP-CML patients prior to the availability of ponatinib has not been documented. Methods: A systematic literature review was conducted to estimate OS in patients with CP-CML receiving 3L treatment prior to ponatinib. Studies were identified from a review by Lipton et al. (2015), updated with studies identified from searches of electronic databases (MEDLINE, EMBASE, Cochrane Libraries) and abstract databases of key conferences. Landmark and median survival were extracted from study reports. Pseudo-individual patient data (IPD) for survival outcomes were derived from digitized Kaplan-Meier (KM) survival curves then pooled and analyzed using KM methods. Results: Fifteen studies (717 patients) were identified that reported median, landmark, or KM curves for survival outcomes for CP-CML patients receiving 3L treatment without ponatinib. KM curves for OS were obtained for 6 arms (3 nilotinib and/or dasatinib; 3 other TKIs). OS at 1, 2 and 3 years based on the pooled IPD is reported in the Table. To avoid confounding of OS from post-progression treatment with ponatinib, 1 study was excluded that included follow-up after the date of ponatinib’s approval. Conclusions: EstimatedOS in patients with CP-CML receiving 3L treatment prior to ponatinib appears to be shorter than that observed among ponatinib-treated patients in PACE: 4-year survival probability in PACE is higher than estimated 2-year survival probability prior to ponatinib. Further analyses are needed to identify and adjust for potentially confounding factors. [Table: see text]
Time to treatment and survival in veterans with stage I-IIIA lung cancer eligible for curative intent therapy.
Authors: Duc Ha, Andrew L Ries, Mark M Fuster
Journal: Journal of Clinical Oncology (2018)

e20519 Background: The Institute of Medicine emphasizes care timeliness as an important quality metric. We assessed treatment timeliness in stage I-IIIA lung cancer patients deemed eligible for curative intent treatment and analyzed the relationship between time to treatment (TTT) and timely treatment (TT) with survival. Methods: We retrospectively reviewed consecutive lung cancer cases diagnosed/managed at the VA San Diego Healthcare System between 10/2010-4/2017. We included stage I-IIIA patients deemed eligible for curative intent treatment and collected information on variables known to be associated with TTT and/or survival in lung cancer: age, sex, race, tobacco exposure, performance status, comorbidities, tumor size, clinical stage, histology, and treatment type. We used the simplified comorbidity score (SCS) to incorporate the effects of comorbidities and their respective weights on survival, defined TTT as days from chest tumor board to treatment initiation and TT using guideline recommendations, and used the Kaplan-Meier method and univariable (UVA) and multivariable (MVA) Cox proportional hazards regressions. Results: In 177 veterans, the median TTT was 35 days (TT occurred in 33-77% of cases) and median overall survival (OS) time 42 months. Patient characteristics associated with longer TTT included other cancer history, high SCS, smaller tumor size, stage I disease, and definitive radiation treatment. In UVA, tobacco exposure, SCS, diffusion capacity of the lung for carbon monoxide (DLCO, % predicted), stage, and treatment category were associated with OS. In MVA, DLCO (HR 0.86 for each 10% predicted, p = 0.02) and treatment category (surgical resection/chemoradiation HR 0.31, p = 0.003; definitive radiation/chemoradiation HR 0.38, p = 0.006) were associated with OS. TTT/TT were not associated with better OS in UVA or MVA. In 122 stage I patients, 35 (29%) had disease recurrence/progression; TTT/TT were not associated with disease-free survival (DFS) in UVA or MVA. Conclusions: Treatment was not timely in 27-66% of veterans with stage I-IIIA lung cancer deemed eligible for curative intent therapy. TTT and TT were not associated with better OS, or DFS in stage I patients.
Presence of human papillomavirus in breast cancer and its association with clinical features.
Authors: Marco Galvez, Carolina Belmar-Lopez, Gabriela Calderon, Joselyn Sanchez, Miluska Castillo Garcia, Carlos Chavez, Carlos Castaneda Altamirano, Jose M. Cotrina, Henry Leonidas Gomez
Journal: Journal of Clinical Oncology (2018)

e13566 Background: Breast cancer (BC) is the most common cancer and leading cause of cancer-related deaths. Recent evidence indicates that a substantial proportion of BC may be caused by viral infections. The presence of high-risk genotypes of human papillomavirus (HPV) has been demostrated in BC and associated with hispotathological features. The aims of this study were to evaluate the prevalence rate of high-risk HPV DNA in BC and clinical features associated to it. Methods: A total of 200 BC samples were prospectively collected from patients who underwent surgical resection between 2016 and 2017 at INEN, Perú. All tumor samples were assessed for the presence of high-risk human papillomavirus by quantitative PCR. p16 expression status was evaluated by immunohistochemistry in HPV positive samples and in a HPV negative control group with same number of samples. HPV status was analyzed against clinicopathologic parameters and a p≤0.05 was considered statistically significant. Results: Median age was 53 years, 76.1% was invasive ductal carcinoma, 66.7% was high histological grade, 73.3% was positive HR status and only 32% was positive HER2Neu status; the most frequent phenotype frequent was Luminal B with 54% followed to triple negative with 15%, clinical positive nodes were found in 54.5% and clinical stage II was 46.9%. High-risk HPV DNA was detected in 5.5% (HPV16: 9/200; HPV18: 2/200) of the population. HPV positive cases was associated to high histological grade (p = 0.009). No differences were found by age (p = 0.49), histology (p = 0.17), HR status (p = 1.00), phenotype (p = 0.88) or clinical stage (p = 0.71). p16 expression status was found in 63.6% (7/11) of HPV positive cases and in 45.4% (5/11) of patients without evidence of HPV. No correlation between HPV DNA and p16 expression was found (p = 0.23). Conclusions: Presence of high-risk HPV DNA was associated with high histological grade, the most frequent genotype was HPV16, and no found correlation with p16 expression, these findings provide evidence of presence of high-risk HPV DNA in Peruvian patients with BC and suggest that high-risk HPV infections could be a risk factor associated with BC development. This study was supported by the CIENCIACTIVA-CONCYTEC-204-2015-FONDECYT.
TCT-349 The acute and early outcome of magnesium bioresorbable scaffold implantation in acute coronary syndrome - initial report from ACS-Magmaris Registry
Authors: Magdalena Lanocha, Adrian Wlodarczak, Artur Jastrzebski, MAciej Pecherzewski, Marek Szudrowicz, Waldemar Jastrzebski, Joanna Nawrot, Pawel Kozak, Maciej Lesiak
Journal: Journal of the American College of Cardiology (2018)