tbuckley/cabot-search huggingface dataset:
Associations between baseline serum biomarker levels and cachexia/precachexia in pretreated non-small cell lung cancer (NSCLC) patients.
Authors: Gabriela C. Lobato, Mary J. Fidler, Jared D. Fialkoff, Maneet Multani, Ibtihaj Fughhi, Connor Wakefield, Sanjib Basu, Marta Batus, Philip D. Bonomi, Jeffrey Allen Borgia
Journal: Journal of Clinical Oncology (2019)

3054 Background: We previously reported associations of pretreatment serum biomarkers with clinical outcomes in a cohort of advanced NSCLC patients that progressed on front-line therapy. This study aims to elucidate mechanisms underlying cancer cachexia/ pre-cachexia by evaluating relationships between baseline serum biomarker values and sequential changes in body weight, body mass index (BMI), and neutrophil/lymphocyte ratio (NLR) in NSCLC patients. Methods: We used Luminex immunobead assays to survey 101 protein biomarkers in sera from advanced NSCLC (n = 138) collected prior to their salvage regimen. Serial parameters associated with cancer cachexia included body weight, BMI, and NLR. Outcome variables (progression-free survival (PFS) and overall survival (OS)) were extracted with full IRB-approval. Biomarkers were evaluated as continuous variables with the cachexia surrogates using Pearson correlations, whereas associations of PFS and OS were accomplished with the Cox PH test. Results: High baseline values of BMI and low baseline NLR were associated with both OS and PFS (each p &lt; 0.05), though weight failed to reach significance. PFS and OS were similarly associated with percent changes (relative to baseline) in weight (p &lt; 0.01), BMI (p &lt; 0.01), and NLR (p &lt; 0.001). Thirteen biomarkers were found to be associated (p &lt; 0.05) with baseline BMI values, including positive correlations with leptin, sol.VEGFR2, and c-peptide and inverse correlations with adiponectin, ferritin, ghrelin, IGFBP-1 and IL-8; fifteen biomarkers were associated with baseline NLR (all p &lt; 0.05), including positive correlations with visfatin, insulin, and serum amyloid A and inverse correlations with IGF-II. Fifteen biomarkers were found to be associated (p &lt; 0.05) in common with percent weight and BMI changes, including positive correlations with IGFBP-3 and inverse correlations with insulin, FGF-2, TNF-alpha, and resistin. Only prolactin and placental growth factor were found to be associated (p &lt; 0.05) with percent change in NLR. Conclusions: A series of circulating protein biomarkers primarily connected with metabolic regulation and systemic inflammation/ acute phase response were found to be associated with cachexia/ pre-cachexia in NSCLC patients. Additional cohorts are currently being tested to verify these findings.
Efficacy of different TCM treatment techniques combined with standardized step therapy for cancer pain: A network.
Authors: Peng Lv, Ya Li, Zhenzhu Zhang, Fengqin Shi, Li Hou
Journal: Journal of Clinical Oncology (2019)

e23131 Background: Comparative study results between the efficacies of traditional Chinese medicine (TCM) therapy with Western medicine therapy in the treatment of cancer pain remain controversial. We use the standardized step treatment as a common control to compare the effectiveness of different Chinese medical methods combined with standardized step therapy for cancer pain using a network meta-analysis. Methods: Randomized controlled trials of the effectiveness of various Chinese medical methods and standardized ladder treatments in PubMed, The Cochrane Library, EmBase, Web of Science, CNKI, VIP, and Wan-Fang databases were searched. Stata14.0 and WinBUGS1.4.3 software were used for statistical analysis. Risk ratio(RR) with their 95% confidence interval were estimated as effect size between treatments. Results: Seventy RCTs were included, a total of 6,936 patients with cancer pain, involving five treatments.The results of network meta-analysis showed that there were significant statistical differences between the four Chinese medical methods combined with standardized step treatment and simple standardized step treatment: Chinese medicine orally combined with standardized step treatment vs simple standardized step treatment: RR = 2.60, 95% CI (2.09, 3.30); Chinese medicine external application combined with standardized ladder treatment vs simple standardized ladder treatment: RR = 2.83, 95% CI (2.31, 3.50); acupuncture physiotherapy combined with standardized ladder treatment vs simple standardized ladder treatment: RR = 3.56, 95% CI (1.92, 7.26); Chinese medicine injection combined with standardized ladder treatment vs simple standardized ladder treatment: RR = 2.22, 95% CI (1.63, 3.05). Conclusions: There are significant statistical differences between different Chinese medical methods combined with standardized step treatment and simple standardized step treatment. For patients with cancer pain, standardized step therapy combined with acupuncture physiotherapy or external application of traditional Chinese medicine can be preferred. Due to the lack of existing research, the conclusions of the study need to be confirmed by high quality RCT.
Insurance disparity in the United States cancer survivors’ smoking rates: A trend study from NHIS 2008-2017.
Authors: Yannan Zhao, Binbin Zheng-Lin, Biyun Wang, Xi-Chun Hu, Changchuan Jiang
Journal: Journal of Clinical Oncology (2019)

1553 Background: Smoking rates have been decreasing in the U.S over the last decade. Smoking cessation is a critical part of cancer treatment and survivorship care. However, little is known about the trend of smoking rates in U.S. cancer survivors and how it varied by individuals’ insurance coverages. Methods: We conducted a retrospective study to evaluate the temporal trend of smoking rates using the National Health Interview Survey from 2008 through 2017. Adult cancer survivors (n = 20122) were included in the analysis. The outcomes were self-reported current smoking behavior. Insurance coverage was categorized into any private (age ≤65), other coverage (age ≤65), uninsured (age ≤65), Medicare + any private (age &gt; 65), and other coverage (age &gt; 65). We combined every two years data to improve statistical power in the subgroup analysis. Weighted analyses were performed with SAS 9.4 to account for the complex design. Results: The smoking rates in cancer survivors decreased from 18.4% in 2008 to 12.5% in 2017. However, the smoking rates varied remarkably by insurance status (p &lt; 0.001). There was a decreasing trend of smoking rates in participants with any private (age ≤65) (17.3% in 2008/2009 to 12.0% in 2016/2017), Medicare + any private (age &gt; 65) (7.5% in 2008/2009 to 5.9% in 2016/2017), and other coverage (age &gt; 65) (13.2% in 2008/2009 to 9.2% in 2016/2017) whereas the current smoking rates remains high in cancer survivors with other coverage (age ≤65) (40.1% in 2008/2009 to 34.4% in 2016/2017) and uninsured (age ≤65) (43.4% in 2008/2009 to 43,1% in 2016/2017). Conclusions: Cancer survivors report less smoking behaviors over the last decade which is similar to the general population. However, the smoking rate remains dangerously high in non-elderly cancer survivors without any private insurance.
A phase II trial of preoperative chemoradiotherapy and pembrolizumab for locally advanced esophageal squamous cell carcinoma (ESCC).
Authors: Min Hee Hong, HyeRyun Kim, Seong Yong Park, Dae Joon Kim, Chang Geol Lee, Jaeho Cho, Jong Hoon Kim, Hyeong Ryul Kim, Yong-Hee Kim, Sook Ryun Park, Byoung Chul Cho
Journal: Journal of Clinical Oncology (2019)

4027 Background: Even though preoperative chemoradiotherapy (CRT) showed survival improvement in patients with resectable ESCC in a randomized trial over upfront surgery, ESCC still has a dismal prognosis. With the potential benefit of combining PD-1 blockade to CRT, we conducted a phase II trial which assessed the efficacy, feasibility, and safety of the combination of preoperative CRT and pembrolizumab (PEM) in ESCC. Methods: Patients (pts) with histologically confirmed ESCC (clinical stage Ib to III according to the American Joint Committee on Cancer 7 th staging system) were enrolled. Pts received concurrent neoadjuvant chemotherapy (weekly paclitaxel and carboplatin), radiotherapy (44.1 Gy in 21 fractions), and PEM (every 3 week, 200 mg) during 5 weeks followed by surgery. After surgery, pts were treated with PEM during 2 years or until progression, unacceptable toxicity, death, or pts’ refusal, which came first. The primary endpoint was pathologic complete response (pCR) rate in the primary tumor and secondary endpoints were overall survival (OS), disease-free survival (DFS), the incidence of adverse events, and etc. Results: In a total of 28 enrolled pts (median age 60), 26 pts received esophagectomy. Two pts did not undergo surgery due to death (hematemesis) and consent withdrawal. There were two in-hospital mortality cases after surgery, which were resulted from acute lung injury. The pCR in primary tumor was achieved in 46.1% of pts who underwent resection (95% CI: 28.8 – 64.6). With a median follow-up of 11.7 months, median OS was not reached. Six-month and 12-month OS rates were 89.3% and 82.1%, respectively. There was a trend toward better DFS in the pCR group (n = 12) compared with the non-pCR group (n = 14) (HR = 0.33, p = 0.1). Most common treatment-related adverse events were neutropenia (50.0%) and liver enzyme elevation (30.8%) in the neoadjuvant and adjuvant period, respectively. Conclusions: The addition of PEM to preoperative CRT in ESCC demonstrated promising efficacy with acceptable toxicity. Based on the results, further investigation is warranted in a phase III clinical trial. The exploratory endpoints including biomarkers analyses are ongoing. Clinical trial information: NCT02844075.
Management of high, moderate, and low penetrance ovarian cancer susceptibility gene mutations: An assessment of current practice patterns.
Authors: Catherine H. Watson, Brittany Anne Davidson, Laura Jean Havrilesky, Paula S. Lee, Leah McNally, Haley Moss, Rebecca A. Previs, Allison Puechl, Angeles Alvarez Secord, Andrew Berchuck, Noah D. Kauff
Journal: Journal of Clinical Oncology (2019)

1536 Background: Limited information exists regarding appropriate risk-reduction strategies for women with moderate and low penetrance ovarian cancer (OVCA) susceptibility mutations. We sought to assess current practice patterns for women with these genetic changes through a survey of members of the Society of Gynecologic Oncology (SGO). Methods: All full SGO members were e-mailed a survey consisting of two vignettes: 1) a 35-year-old premenopausal woman who desires pregnancy; 2) a 55-year-old postmenopausal woman with multiple comorbidities. Each vignette contained sub-scenarios in which the patient had either a BRCA1 (RR = 30-60), RAD51C (RR = 5.0) or ATM (RR 1.5-2.0) OVCA susceptibility mutation. Respondents were queried about their preferred management approach. Chi-square test was used for statistical analysis. Results: 193 (15%) of 1284 SGO members responded. 58% were in academic practice. For the premenopausal woman, 52%, 13% and 6% would perform an RRSO prior to age 40 in the setting of a BRCA1, RAD51C and ATM mutation respectively. 47%, 68% and 9% would perform RRSO at 40-50; and 0%, 9% and 23% would perform RRSO at menopause, depending on the gene mutated. For the postmenopausal woman with comorbidities, 98%, 85% and 42% would proceed with RRSO in the setting of a BRCA1, RAD51C and ATM mutation respectively; 2%, 8% and 39% would observe (with/without screening); and 0%, 7% and 19% would do further research prior to proceeding. Distribution of responses for carriers of RAD51C and ATM mutations were different from BRCA1 in both vignettes [p &lt; 0.001]. Conclusions: Respondents were more likely to perform RRSO earlier and more frequently in the setting of a BRCA1 mutation compared to either a RAD51C or ATM mutation. However, there was lack of consensus in management of the moderate and low penetrance OVCA susceptibility mutations. These patterns likely reflect the limited information available regarding the timing and magnitude of risk associated with these genes. Given the immediate and long-term morbidity of oophorectomy, more data regarding age-specific risks and appropriate risk-reduction strategies for moderate and low penetrance OVCA susceptibility mutations is needed.
Intestinal Adaptation
Authors: Robin C. N. Williamson
Journal: New England Journal of Medicine (1978)

THE mucosal lining of the intestinal tract is in a constant state of renewal. Enteric* epithelium has the fastest rate of turnover† for any tissue in the body, exceeded only by a few rapidly growing malignant tumors.1 Nonetheless, proliferation of epithelial cells may be further accelerated by a number of stimuli, notably partial intestinal resection. Survival of animals and man is possible after the loss of most of the small bowel, and postoperative diarrhea and malabsorption tend to improve with time. Clearly, the gut, like the liver and kidney, has both a functional reserve and a . . .
Reply to Rodolfo Montironi, Liang Cheng, Marina Scarpelli, Alessia Cimadamore, Francesco Montorsi, and Antonio Lopez-Beltran's Letter to the Editor re: Gillian Vandekerkhove, Werner J. Struss, Matti Annala, et al. Circulating Tumor DNA Abundance and Potential Utility in De Novo Metastatic Prostate Cancer. Eur Urol 2019;75:667–75: How Does Circulating DNA Reach the Blood Stream?
Authors: Alexander W. Wyatt, Kim N. Chi, Martin E. Gleave
Journal: European Urology (2019)
Carboplatin-based chemotherapy (C) versus immunotherapy (IO) in metastatic urothelial carcinoma (mUC).
Authors: Emily Feld, Joanna Harton, Neal J. Meropol, Blythe J.S. Adamson, Ravi Bharat Parikh, Matt D. Galsky, Aaron B. Cohen, Vivek Narayan, John Paul Christodouleas, David J. Vaughn, Rebecca A. Hubbard, Ronac Mamtani
Journal: Journal of Clinical Oncology (2019)

e16003 Background: There are limited data comparing first-line (1L) C versus IO in cisplatin-ineligible mUC patients. The primary evidence guiding treatment decisions was a May 2018 Food and Drug Administration (FDA) safety alert based on early review of two ongoing phase III trials, reporting shorter survival in PD-L1 negative patients receiving IO relative to chemotherapy. Final results from these trials are unknown and may not be applicable to a real-world cohort. Methods: We conducted a retrospective cohort study of mUC patients receiving 1L C or IO from January 1, 2011 to May 18, 2018 using the Flatiron Health electronic health record-derived database. The primary outcome was overall survival (OS) from start of 1L treatment to date of death. We compared 12- and 36-month OS, and hazard ratios before and after 12 months. Propensity score-based inverse probability of treatment weighting (IPTW) was used to address confounding in Kaplan-Meier (KM) and Cox multivariable regression model estimates of comparative-effectiveness. Results: Of 2,243 patients, 562 received IO and 1,681 received C. Baseline characteristics were balanced between groups, with few exceptions (Table). In the first 12 months, IO was associated with an increased hazard of death compared to C (HR 1.38, 95% CI 1.16-1.66). Among patients who survived one year, survival was improved with IO compared to C (HR 0.50, 95% CI 0.27-0.92). Conclusions: In routine clinical practice, 1L IO was associated with inferior 12-month OS relative to C, but superior OS beyond 12 months. Clinicians and patients should carefully consider how to balance the early benefit of C against the late benefit of IO. Currently pending trial results will contribute additional evidence to inform treatment decision making. [Table: see text]
miR-301a promotes lung tumorigenesis by suppressing Runx3
Authors: Xun Li, Mingtian Zhong, Jiexuan Wang, Lei Wang, Zhanwen Lin, Zhi Cao, Zhujuan Huang, Fengxue Zhang, Yong Li, Ming Liu, Xiaodong Ma
Journal: Molecular Cancer (2019)

Our previous report demonstrated that genetic ablation of miR-301a reduces Kras-driven lung tumorigenesis in mice. However, the impact of miR-301a on host anti-tumor immunity remains unexplored. Here we assessed the underlying molecular mechanisms of miR-301a in the tumor microenvironment. The differentially expressed genes were identified by using deep sequencing. The immune cell counts, and cytokines expression were analyzed by realtime PCR, immunohistochemistry and flow cytometry. The role of miR-301a/Runx3 in lung tumor was evaluated on cell growth, migration and invasion. The function of miR-301a/Runx3 in regulating tumor microenvironment and tumor metastasis were evaluated in Kras transgenic mice and B16/LLC1 syngeneic xenografts tumor models. In this work, we identified 1166 up-regulated and 475 down-regulated differentially expressed genes in lung tumor tissues between KrasLA2 and miR-301a−/−; KrasLA2 mice. Immune response and cell cycle were major pathways involved in the protective role of miR-301a deletion in lung tumorigenesis. Overexpression of the miR-301a target, Runx3, was an early event identified in miR-301a−/−; KrasLA2 mice compared to WT-KrasLA2 mice. We found that miR-301a deletion enhanced CD8+ T cell accumulation and IFN-γ production in the tumor microenvironment and mediated antitumor immunity. Further studies revealed that miR-301a deficiency in the tumor microenvironment effectively reduced tumor metastasis by elevating Runx3 and recruiting CD8+ T cells, whereas miR-301a knockdown in tumor cells themselves restrained cell migration by elevating Runx3 expression. Our findings further underscore that miR-301a facilitates tumor microenvironment antitumor immunity by Runx3 suppression in lung tumorigenesis.
Cardiac fibrosis – A short review of causes and therapeutic strategies
Authors: Svenja Hinderer, Katja Schenke-Layland
Journal: Advanced Drug Delivery Reviews (2019)

Fibrotic diseases cause annually more than 800,000 deaths worldwide, whereof the majority accounts for lung and cardiac fibrosis. A pathological remodeling of the extracellular matrix either due to ageing or as a result of an injury or disease leads to fibrotic scars. In the heart, these scars cause several cardiac dysfunctions either by reducing the ejection fraction due to a stiffened myocardial matrix, or by impairing electric conductance, or they can even lead to death. Today it is known that there are several different types of cardiac scars depending on the underlying cause of fibrosis. In this review, we present an overview of what is known about cardiac fibrosis including the role of cardiac cells and extracellular matrix in this disease. We will further summarize current diagnostic tools and highlight pre-clinical or clinical therapeutic strategies to address cardiac fibrosis.
Analysis of healthy breast tissue from Komen Tissue Bank shows distinct histology, decreased proliferation, and lower periductal collagen deposition in women with prolonged history of breastfeeding.
Authors: Mustafa Basree, Neelam Shinde, Zaibo Li, Sarmila Majumder, Bhuvaneswari Ramaswamy
Journal: Journal of Clinical Oncology (2019)

1538 Background: Epidemiological studies have shown that prolonged breastfeeding is associated with a reduced risk of developing triple negative/basal-like breast cancer (TN/BLBC). We have modeled abrupt involution (AI) following short breastfeeding and gradual involution (GI) of the mammary gland that occurs over time upon prolonged breastfeeding in wild-type FVB/N mice and discovered prominent histological and molecular changes in the AI glands over time. Further, we demonstrated that breast tissue from healthy women who breastfed &lt;6 months showed enrichment in stem-cell and cell renewal pathways. Here, we corroborate those studies using normal human breast tissue obtained from Susan G. Komen for the Cure Tissue Bank (KTB). Methods: FFPE breast tissue sections obtained from KTB (Protocol #2017CO184). Donors were parous women, aged 18 to 45, without history of breast cancer and for whom breastfeeding history was available. H&amp;E sections and TDLU, the primary anatomical source of most breast cancers, of women who breastfed for ≥6 months (GI, n=49) vs. those who breastfed for ≤3 months (AI, n=20) were evaluated by a blinded pathologist. Masson Trichrome stain was used to measure collagen deposition. Ki67 immunohistochemistry was utilized to determine proliferation. Statistical significance was measured using Fisher’s exact t-test and two-sample t-test with a p-value of &lt;0.05. Results: H&amp;E analysis revealed that breast tissue obtained from women in the AI cohort exhibited histological features of inflammation (p-value= 0.025). Using Ki67 IHC (AI, n=15; GI, n=32) and Masson Trichome stain (AI, n=3; GI, n=4), sections in the AI cohort showed 2-fold increase in proliferation of lobular epithelium (p-value= 0.048) and 1.4-fold increase in periductal collagen deposition (p-value= 0.027) when compared to GI cohort. Age, race, and BMI were not statistically different between AI and GI cohorts. Conclusions: Breast tissue from parous women who breastfed ≤3 months is histologically different than tissue of women with ≥6 months history of breastfeeding. We are currently staining more breast tissue samples obtained from KTB. Experiments are underway to assess the long-term effect of breastfeeding on breast epithelial cell hierarchy and biomarkers of inflammation. Understanding this mechanistic link will help in developing prevention strategies, particularly for African-American women who have lower prevalence of breastfeeding and higher incidence of TN/BLBC.
Association between heart dosimetric parameters, cardiac events and overall survival for patients with stage III esophageal cancer treated with definitive radiotherapy.
Authors: Guoxin Cai, Jinming Yu, Xue Meng
Journal: Journal of Clinical Oncology (2019)

e15561 Background: Heart exposure to irradiation can cause cardiac events (CEs). The impact of radiation heart dosimetric parameters (RHDPs) on overall survival (OS) in esophageal cancer is not known. The aim of this study was to determine the association between heart dosimetric parameters and CEs and OS in patients with stage III esophageal cancer. Methods: 346 patients with esophageal cancer treated with definitive radiotherapy (RT) from 2011 to 2013 were enrolled retrospectively. We mainly observed three types of CEs: ischemic diseases (myocardial infarction and unstable angina), pericardial diseases (symptomatic effusion and pericarditis), and arrhythmia. We performed logistic regression or Cox proportional hazards models to evaluate the relationship between RHDPs, CEs and OS. Results: Median follow-up was 28 months and median prescribed doses was 60 Gy. Three and five-year OS was 43.9% and 16.8%, respectively. The number of patients who had ischemic diseases, pericardial diseases and arrhythmia in five years since they received treatment was 19, 12 and 26, respectively. Ischemic diseases was associated with pre-existing heart disease (P = .0016) and percentage of heart volume receiving ≥5 Gy (heart V5) (P = .0037), arrhythmia was associated with pre-existing heart disease (P = .0020), heart V5 (P = .0003) and mean heart dose (MHD) (P = .0021), but pericardial diseases was not correlated with RHDPs. In univariate analysis, smoking status, performance status, tumor location, lung V5, mean lung dose (MLD), heart V30, MHD and gross tumor volume (GTV) were significantly associated with three-year OS, and performance status, tumor location, concurrent or sequential chemotherapy, lung V5, heart V5, heart V30, MHD and GTV were correlated with five-year OS. In multivariate analysis, only poor performance status (hazard ratio (HR) 1.56; 95% confidence interval (CI), 1.16-2.10; P = .003 and HR 1.80; 95% CI, 1.15-2.82; P = .010) and larger GTV (HR 1.53; 95% CI, 1.14-2.05; P = .004 and HR 1.64; 95% CI, 1.07-2.49; P = 0.023) independently indicate worse three and five-year OS, and smoking status (HR 1.37; 95% CI, 1.03-1.82; P = 0.032) predict three-year OS only. Conclusions: Heart dose is associated with the occurrence of CEs, but it could not independently predict OS for patients with stage III esophageal cancer treated with definitive radiotherapy.