tbuckley/cabot-search huggingface dataset:
tPA as marker of thrombosis development after surgical treatment for pancreatic cancer.
Authors: Umar Muhmadovich Gaziev, Oleg Ivanovich Kit, Elena Mikhaylovna Frantsiyants, Larisa Kozlova, Stanislav Stanislavovich Mezentsev
Journal: Journal of Clinical Oncology (2016)

e15679 Background: Blood rheology maintenance is associated with activity of blood coagulation system and content of prothrombokinase (tPA-Ag) and active thrombokinase (tPA-act) in particular. The purpose of the study was to detect individual predisposition of patients to postoperative thromboses (T) in pancreatic cancer (PC). Methods: tPA in blood plasma (BP) of 62 patients with PC (T3 N0 M0 ) was determined by ELISA before the surgery, on days 1-2 and 7 and at discharge, tPA-Ag/tPA-act ratio was calculated and the results were compared to the values in 39 donors (N). Results: 33 patients underwent pancreatoduodenal resection (PDR) and 29 patients - palliative surgical bypass. 7 patients (11.3%) developed T after discharge, including 4 patients with PDR and 3 with bypass surgery. tPA-Ag in BP of patients with T was 25.0% higher than N and in patients without T – 3.7 times lower than N; tPA-act in all patients was 8.8-11.2 times higher than N without significant differences between the two groups. Day 1-2, patients with T: tPA-Ag was 1.5-2.4 times higher than N, tPA-act was 26.3-43.4 times higher than N and tPA-Ag/tPA-act was 13.2-25.9 times lower than N. The results were similar with the values on day 7 and at discharge. Day 1-2, 54 patients without T: tPA-Ag was 2.1 lower than N, tPA-act was 4.3 times higher than N and tPA-Ag/tPA-act was 3.8 times higher than in patients with T. The results were similar with the values on day 7 and at discharge. Conclusions: tPA-Ag/tPA-act values in 55 patients without T were over 50 on days 1-2 after the surgery, while in 7 patients with T tPA-Ag/tPA-act was under 50. The data can be used for individual thrombosis predisposition prognosis, reproducibility 87.1%. Individual predisposition to thromboses is not associated with the type of surgery.
Decreasing telomerase activity of adenocarcinoma cancer cell line (AGS) is associated with different concentrations of sodium selenite and cadmium chloride and selenium l methionine
Authors: S.S. Hosseini-Asl, A. Fazabakhsh, M. Sagha
Journal: Annals of Oncology (2018)

Background: Selenium (Se) has been recognized as an essential element for animals and humans. In the late 1960s, it was first suggested that selenium might have anti-cancer properties. Selenium controls apoptosis in cell cycle. Cadmium (Cd) is a widely used heavy metal that affects human health through occupational and environmental exposure and has been reported as a cause of cancers such as lung, prostate and kidney. The previous studies on Ovarian and breast cancer have shown that cadmium increases telomerase activity and expression level of hTERT. In the present study, we find out the effect of sodium selenite and selenium l methionine and cadmium chloride on telomerase activity in adenocarcinoma cancer cell line (AGS). Methods: The adenoma carcinoma gastric cancer cells (AGS) were cultured in RPMI1640 supplemented with 10 % fetal bovine serum (FBS) and 1% pen/strep. Concentrations of cadmium chloride, selenium l methionine and sodium selenite were added the adenocarcinoma gastric cancer cells (AGS). Finally, the telomerase activity was measured by telomeric repeat amplification protocol (TRAP) and qRT-TRAP assays. Results: Average telomerase activity (as threshold cycle (CT)) has been detected for three concentrations (5μM and 10μM and 20 μM) of the noted compounds. The results were 24.82±0.51, 25.31±1 and 25.63±1.32 for Sodium selenite, 24.56±0.25, 25.29±0.98 and 25.60±1.21 for Cadmium chloride and 24.49±0.18, 25.30±0.99 and 25.73±1.32 for Seleniul l methionine, respectively. Representing the signification decreasing telomerase activity at treated samples compared with the controls (p ≤ 0.05). Conclusions: Decreasing in the telomerase activity which was caused by treating with Cadmium chloride, Selenium l methionine and Sodium selenite is in conflict with some previous findings indicating the increasing in the telomerase activity by treating Cadmium. Legal entity responsible for the study: Ardabil University of Medical Sciences. Funding: Ardabil University of Medical Sciences. Disclosure: All authors have declared no conflicts of interest.
Comparative analysis of outcomes in African American (AA) and white (W) patients (pts) with multiple myeloma (MM) treated with lenalidomide (LEN) or pomalidomide (POM).
Authors: Sikander Ailawadhi, Philip L. McCarthy, Sarah A. Holstein, Gail Larkins, Weiyuan Chung, Shankar Srinivasan, Amit Agarwal, Sagar Lonial
Journal: Journal of Clinical Oncology (2018)

8050 Background: AA are ≈2-fold more likely to develop MM, and racial and ethnic minorities may not have similar access to novel MM treatment (Tx). Outcomes are often worse in AA vs W pts with cancer, but data are mixed in MM. Thus, we compared outcomes in AA and W pts treated with LEN or POM. Methods: We performed a subgroup analysis with data from 4 clinical trials. E4A03 (Rajkumar et al. Lancet Oncol 2010) used LEN + high- or low-dose dexamethasone (LEN-D or LEN-d) as a first-line MM Tx. CALGB 100104 (McCarthy et al. NEJM 2012) studied LEN or placebo (PBO) maintenance after transplant. MM-009 (Weber et al. NEJM 2007) and MM-002 (Richardson et al. Blood 2014) used LEN-D or PBO-D and POM or POM-d, respectively, for relapsed/refractory MM. We compared baseline characteristics and Tx outcomes in AA vs W pts from the LEN-d arm of E4A03, all arms of CALGB and MM-009, and the combined POM and POM-d arms of MM-002. Results: Detailed results are in the Table. Baseline characteristics were generally similar in each trial. PFS/OS was similar in AA and W pts treated with LEN or POM except in the MM-002 trial, where PFS was longer in AA pts. Neutropenia was the most common hematologic Tx-emergent adverse event across the studies. Conclusions: Tx with LEN or POM resulted in similar or better outcomes in AA vs W pts in multiple Tx settings, emphasizing the importance of equitable access to Tx. E4A03 CALGB 100104 MM-009 MM-002 AA W AA W AA W AA W Tx, n LEN-d 24 LEN-d 194 LEN 40 PBO 44 LEN 175 PBO 171 LEN-D 25 PBO-D 17 LEN-D 141 PBO-D 148 POM ± d 33 POM ± d 178 Median age, yrs 66.3 65.3 55.0 56.5 59.0 58.0 63.0 59.0 64.0 62.0 60.0 64.0 Male, % 54 55 43 52 55 58 40 12 63 64 52 54 Median PFS, mos 18.7 21.6 72.0 37.0 56.9 28.8 9.2 3.7 13.1 4.6 5.6 2.8 HRa (95% CI) P 0.98 (0.47- 2.05) .96 1.07 (0.66-1.73) .78 1.30 (0.75-2.25) .36 0.56 (0.35-0.89) .01 Median OS, mos 40.4 39.2 NR 81.6 NR 72.9 44.0 41.3 36.5 29.4 17.4 14.2 HRa (95% CI) P 1.72 (0.68-4.36) .25 1.33 (0.68-2.60) .41 1.15 (0.64-2.07) .63 0.69 (0.44-1.08) .11 ORR, % 63 67 88 89 90 84 72 6 57 20 30 26 Neutropenia, % 4 3 85 50 74 51 52 12 46 7 36 48 Anemia, % 4 2 28 11 21 14 48 18 33 19 15 35 Thrombocytopenia, % 0 1 58 36 72 55 28 18 25 8 15 25 Leukopenia, % 0 1 28 14 22 16 8 6 8 1 3 17 aHR: AA vs W in LEN/POM arms. NR, not reached.
Prognostic significance of neutrophil-to-lymphocyte ratio and lymphocyte-to-monocyte ratio in myelodysplastic syndromes.
Authors: Muhammad Umair Mushtaq, Abdullah Ali, Kiyomi Morita, Ronald Pinheiro, Azra Raza
Journal: Journal of Clinical Oncology (2016)

7062 Background: Inflammatory and immune response in tumor microenvironment plays a critical role in cancer progression. Neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR) and platelet-to-lymphocyte ratio (PLR) have been reported as prognostic factors in solid and lymphoid malignancies. We explored predictors of overall survival (OS) in Myelodysplastic Syndromes(MDS) patients. Methods: A retrospective review of 282 MDS patients, from Columbia University Medical Center Tissue Repository, was conducted. Karyotype and clinical factors were ascertained at the time of referral. Univariate and multivariate cox regression analyses were conducted to correlate factors with OS. Hazard ratios (HR) with 95% confidence intervals (CI) were obtained. Kaplan-Meier and receiver operating characteristic analyses were also conducted. Results: Median age was 73 years. Bone marrow was hypercellular in 90% patients with 2% median myeloblasts. Karyotype was good (65%), intermediate (20%) and poor (15%).Median values for clinical factors were: hemoglobin 9.6 g/dL, platelets 109,000 cells/uL, neutrophils 1895 cells/uL, lymphocytes 1197 cells/uL, monocytes 359 cells/uL, erythropoietin 72 mU/mL, ferritin 610 ng/mL, LDH 199 U/L, NLR 1.6, LMR 3.4 and PLR 100.Median IPSS and revised IPSS (IPSS-R) scores were 0.5 (scale 0-3) and 3 (scale 0-9.5) respectively.Median OS was 105 months (95% CI 90.5-119.5). In age-adjusted multivariate model, high myeloblasts (HR 1.10, 95% CI 1.05-1.14, P < 0.001), poor karyotype (HR 2.52, 95% CI 1.56-4.07, P < 0.001), high NLR (HR 1.07, 95% CI 1.01-1.15, P = 0.031) and high LMR (HR 1.02, 95% CI 1.01-1.04, P = 0.002) independently predicted OS. When adjusted for IPSS and IPSS-R scores, NLR (HR 1.07, 95% CI 1.01-1.14, P = 0.040), LMR (HR 1.02, 95% CI 1.01-1.04, P = 0.010) and IPSS-R score (HR 1.48, 95% CI 1.08-2.03, P = 0.014) were independent predictors of OS. Median OS in patients with LMR of 5 or more was 67 months (95% CI 40-94) versus 126 months (95% CI 105.5-146.5) in those with LMR < 5 (P < 0.001). No NLR cut-off reached statistical significance to predict OS. Conclusions: High IPSS-R score, high NLR and high LMR were independent predictors of poor OS in MDS patients.
Algorithmic matching of genomic profiles to precision cancer medicine clinical trials at DFCI.
Authors: James Lindsay, Catherine Del Vecchio Fitz, Zachary Zwiesler, Priti Kumari, Khanh Tu Do, Geoffrey Shapiro, Ethan Cerami
Journal: Journal of Clinical Oncology (2017)

6620 Background: Genomic profiling and access to precision medicine clinical trials are now standard at leading cancer institutes and many community practices. Interpreting patient-specific genomic information and tracking the complex criteria for precision medicine trials requires specialized computational tools, especially for multi-institutional basket studies such as NCI-MATCH and TAPUR. Methods: To address this challenge we have developed an open source computational platform for patient-specific clinical trial matching at Dana-Farber Cancer Institute (DFCI) called MatchMiner, which aides in both patient recruitment to precision medicine trials, as well as decision support for oncologists. Trial matches are computed based on genomic criteria, including mutations, CNAs, and SVs, as well as clinical and demographic information, including cancer type, age, and gender. A formal standard called clinical trial markup language (CTML) to encode complex clinical trial eligibility criteria has also been created. Results: MatchMiner is now available at DFCI. Currently 123 precision medicine clinical trials have been transformed into CTML and 13,000 patient records are available, with over 88% of current patients having at least 1 match (average 2.6). A total of 103 genes are specified as criteria for at least 1 trial. KRAS, TP53, PTEN, PIK3CA and BRAF are the genes driving the most number of matches. General usage statistics and trial enrollment rates are currently being monitored to determine the system effectiveness. As this is an open source initiative, the software is also now publically available at https://github.com/dfci/matchminer. Conclusions: We have developed an open source computational platform that enables patient-specific matching and recruitment to precision medicine clinical trials at DFCI. We are actively seeking collaborators and plan to make CTML a multi-institution standard for encoding complex clinical trial eligibility in a computable form.
Phase II prospective trial of cetuximab and radiotherapy for locally advanced, squamous cell carcinomas of the head and neck in patients &gt;70 years old or with comorbidities not-eligible for platinum-based chemotherapy.
Authors: Paul Swiecicki, Matthew J Schipper, Kelly M Malloy, Chaz Stucken, Andrew G Shuman, Matthew E Spector, Douglas Brian Chepeha, Keith Casper, Scott A McLean, Jeffrey Moyer, Gregory T. Wolf, Mark E Prince, Carol Rossier Bradford, Thomas E. Carey, Avraham Eisbruch, Shruti Jolly, Francis P. Worden
Journal: Journal of Clinical Oncology (2016)

6071 Background: We designed a single arm phase II trial to determine the efficacy and toxicity of concurrent cetuximab (C) radiotherapy (RT) in patients non-eligible for standard chemotherapy. Non-eligibility was defined as age > 70 years (yrs), co-morbidities that preclude platinum-based chemotherapy, or creatinine clearance (CrCl) < 30 mL/min. Primary endpoint was progression free survival. Methods: 22 stage III/IVA patients (pts) were enrolled. The median age was 70 years (range: 40-85), 50% had eGFR with < 90 mL/min, 64% were males, 36% were females; 64% Caucasian, 36 % had an ECOG performance status (PS) of 0, 64% ECOG PS of 1. All pts received C 400 mg/m2 day (d) 0, then 250 mg/m2 d 7 and weekly during RT. Pts were treated with a planned 70 Gray (Gy) in 35 fractions over 7 weeks to the gross tumor and 50-60 Gy to subclinical target volumes.Results: As of January 2016 with a median follow up of 22.8 months and 22 evaluable pts, the median PFS was 30.07 months (95% CI: 2.93, > 50). The overall survival was 33.8 months (95% CI: 9.2, > 50). 6 pts (27%) have recurred, all of whom have died. Treatment related grade 3 toxicities were seen in 7 pts (32%), no grade 4 toxicities were seen. The most common grade 3 toxicities were mucositis (5 pts), dysphagia (4 pts), and dermatitis (3 pts). Conclusions: The results of this phase II prospective study suggest that in patients > 70 yrs old or with comorbidities, precluding platinum-based chemotherapy, tolerate treatment with C+RT well, though survival rates are lesser when compared with historical controls. Clinical trial information: NCT00904345.
Molecular alterations to predict survival and response to chemotherapy of pediatric low-grade glioma.
Authors: Michal Zapotocky, Scott Ryall, Anthony Arnoldo, Matthew Mistry, Alvaro Lassaletta, Ana Sofia Guerreiro Stucklin, Rahul Krishnatry, Vijay Ramaswamy, Suzanne Laughlin, Peter Dirks, Annie Huang, Ute Katharina Bartels, Eric Bouffet, Uri Tabori, Cynthia Hawkins
Journal: Journal of Clinical Oncology (2017)

10503 Background: RAS/MAPK pathway mutations have been identified as the major drivers of pediatric low-grade glioma (pLGG). The impact of these alterations on outcome and response to therapy is still unknown. Methods: We performed a large population based study of all pLGG diagnosed from 1985-2015. Detailed treatment and very long term outcome data was collected on all patients. Known pLGG-related alterations were detected using NanoString and QX200™Droplet Digital™PCR. Molecular data was correlated with outcome and response to chemotherapy. Results: In our cohort of 614 patients, BRAF was found to be altered in 57% and wild-type (WT) in 43% of patients without neurofibromatosis 1 (NF1). Among BRAF-WT we identified H3.3K27M, FGFR1-TACC1, MYBL1 and other alterations. Molecular alterations stratified pLGG into several risk groups. Ten-year progression free survival (PFS) was 72.3% for NF1, 69.5% for KIAA1549-BRAF, 53.5% for BRAF-WT, 30.3% for BRAF-V600E and 0% for H3.3K27M mutations (p &lt; 0.0001). Similarly, overall survival (OS) at 10 years delineated difference between excellent survival of KIAA1549-BRAF and NF1 compared to BRAF-V600E and BRAF-WT (p = 0.0005). Interestingly, all patients with FGFR1-TACC1 and MYBL1 were alive despite observed progressions. Strikingly, response to chemotherapy determined by changes in tumor size at 6 months of therapy correlated with pLGG alteration. Objective response to first line chemotherapy was observed in 46% of patients with KIAA1549-BRAF and 35% of NF1. In contrast, only 15% BRAF-V600E and 18% BRAF-WT responded and 41% tumors grew after six months of chemotherapy. Moreover, 5-year PFS after chemotherapy was strikingly low for BRAF-V600E and BRAF-WT (25% and 31.9% respectively) compared to KIAA1549-BRAF (50%) and NF1 (76.7%) (p = 0.001). This translated to decreased OS for BRAFV600E and BRAF-WT patients (p = 0.042). Conclusions: Our study provides evidence that molecular alterations dictate the outcome of pLGG. KIAA1549-BRAF harbors excellent prognosis and choice of therapy should be made in favor of less toxic agents to minimize deleterious late effects. In contrast, poor prognosis is associated with lack of response to chemotherapy in BRAF-V600E and BRAF-WT tumors.
Serum thioredoxin reductase 1 as a diagnostic marker for non-small cell lung cancer.
Authors: Xiaozheng Kang, Chaoran Dong, Bocun Shen, Hanwei Yin, Guobing Xu, Ke-Neng Chen, Huihui Zeng
Journal: Journal of Clinical Oncology (2017)

e23069 Background: Non-invasive diagnostic markers for patients with suspicious non-small cell lung cancer (NSCLC) may provide needed guidance on invasive diagnostic and therapeutic decisions. Thioredoxin reductase 1 (TrxR1) is a pivotal intracellular redox sensor and antioxidant enzyme, and plays an important part in tumor growth, progression, metastasis, and chemotherapy resistance. The goal of this study is to test the feasibility of developing plasma TrxR1 as a novel diagnostic marker for NSCLC. Methods: The plasma TrxR1 activity was determined spectrophotometrically by monitoring the NADPH-dependent production of 2-nitro-5-thiobenzoate at 412nm and at 37℃. All detection kits and automatic analyzer possess independent intellectual property rights, and have been widely used in breast cancer screening. Results: In this study, the plasma levels of TrxR1 were measured in 109 treatment-naïve resectable NSCLC patients and 15 individuals with benign tumor-like pulmonary diseases. Taking plasma TrxR1 activity of 5.0 as reference, the overall concordance rate was 58.1%, while those of CEA, CA199, CA125, NSE, CYFRA21-1 and SCC were 19.2%, 8.2%, 2.1%, 45.9%, 25.3% and 9.5%, respectively. Furthermore, using TNM staging (AJCC 7th ed.) as classifier, the concordance rates of TrxR1 in benign tumor-like pulmonary diseases, local and regional stage NSCLC subgroups were 53.3% (8/15), 57.5% (46/80) and 63.0% (17/27), respectively. A multipoint linear fitting correlation model was created, and the equation was TrxR1 = 5.716 + 0.4898*Stage. Conclusions: Our data suggest that plasma TrxR1 activity is a useful non-invasive diagnostic marker for NSCLC, and there may be a linear correlation between TrxR1 activity and pathological stage.
Dynamics of soluble programmed death-ligand 1 (soluble PDL1) during chemotherapy and its prognostic implication in cancer patients.
Authors: Hyerim Ha, Ju-Hee Bang, Ah-Rong Nam, Ji Eun Park, Mei Hua Kim, Yung-Jue Bang, Do-Youn Oh
Journal: Journal of Clinical Oncology (2017)

11542 Background: The soluble form Programmed Death-Ligand 1(sPDL1) is suggested to have immunosuppressive activity and under investigation as candidate biomarker for immuno-oncology drug development. In this study, we measured the serum sPDL1 at pre-and post-chemotherapy and evaluated its prognostic implication and dynamics during chemotherapy in biliary tract cancer (BTC) patients. Methods: From 90 advanced BTC patients (training cohort 42 patients, validation cohort 48 patients) who were candidates for palliative 1 st -line chemotherapy, blood was collected at pre-and post-chemotherapy. sPDL1 was measured using an enzyme-linked immunosorbent assay. Response to chemotherapy, overall survival (OS) and other prognostic factors including neutrophil-lymphocyte ratio (NLR) were also obtained. Results: OS of all patients was 11.5 months (95% CI; 9.7-16.2). The best response was CR in 7 patients (7.8%), PR 20 patients (22.2%), SD 52 patients (57.8%) and PD 11 patients (12.2%). Median sPDL1 at pre-chemotherapy was 0.97 ng/mL (range 0.6-1.9). Patients with high pre-chemo sPDL1 (≥ 1.30 ng/mL) showed worse OS than patients with low pre-chemo sPDL1 (9.1 vs. 12.5 months, p =0.003). In multivariate analysis, high pre-chemo sPDL1 (HR 1.96, 95% CI; 1.2-3.9, p = 0.011) and pre-chemo NLR (HR 1.82, 95% CI; 1.1-3.0, p = 0.020) were independent poor prognostic factors for OS. Post-chemotherapy sPDL1 and its changes compared with pre-chemotherapy were not significantly different across tumor response groups. However, at the time of disease progression, sPDL1 was increased significantly compared with pre-chemo sPDL1 (1.59 ng/mL vs 0.72 ng/mL, p = 0.003). In PR group, sPDL1 at pre-chemo, post-chemo, and PD was 1.19, 0.98, and 2.77 ng/mL, respectively. In SD group, sPDL1 at pre-chemo, post-chemo, and PD was 1.16, 1.19, and 1.83 ng/mL, respectively. In PD group, sPDL1 at pre-chemo and PD was 0.62, and 1.04 ng/mL. Conclusions: sPDL1 at pre-chemotherapy confers the prognostic value for OS in BTC patients under palliative chemotherapy. The dynamics of sPDL1 during chemotherapy correlates with disease progression.
Home hospice care and its genesis in Nepal.
Authors: Rashmey Pun, Sandhya Chapagain Acharya
Journal: Journal of Clinical Oncology (2018)

e22164 Background: Home hospice is relatively a new concept in Nepal. Up to 90% of approximately 30,000 cancer patients diagnosed in Nepal every year die within a year. We share our initial experience with home hospice program in Nepal. Methods: The home hospice (HH) program was established in January 2016. This program serves the patients in Kathmandu Valley in, Nepal. This is a joint collaborative program of Cancer Care Nepal (CCN) with technical support from National Hospital and Cancer Research Center, Jawalakhel. The HH services are provided free of cost to the patients at their homes. We evaluated the 126 enrolled patients from January 2016 to October 2017. Results: Among 126 patients, 78 were women and 56 men. Median age was 61 Years (27-85 years). Majority of the patients had lung cancer 28(22%) followed by gastrointestinal 24(19%), cervix 16(13%), hepatobiliary 16(13%), Breast 10(8%), haematological malignancy 7(9%), colo-rectal 7(6%) and 16(13%) were miscellaneous cancers. Commonest symptoms included nausea (85.71%), pain (76.19%), cough (66.69%) and constipation (57.14 %). Patients were treated with morphine and tramadol for pain management. 19 patients with moderate to severe pain responded well rendering pain score to mild. Average dose of morphine prescribed was 40 mg (range: 20 – 60 mg). 64 patients died at home and 6 in hospital and 56 are still under home hospice care. The average length of stay in hospice care from admission until death was one month. Conclusions: The home hospice program though in very early stage has helped many patients with terminal cancer, and their families. The essence of home hospice is to provide care that embraces not only physical needs but also emotional, social and spiritual support. Home hospice care is able to value the strong cultural bond that many patients during their end of life want to be at home surrounded with family members and die peacefully. We believe that HH is able to preserve this core cultural value of our society. Due to our socio- cultural and economic environment, free services like our program, may encourage the enrollment of many more patients to avail the service and help them have quality life and die with dignity.