tbuckley/cabot-search huggingface dataset:
Does chemotherapy work in reversal of malignant obstruction due to gastric cancer?
Authors: Vanessa Montes Santos, Renata Gondim Meira Velame Azevedo, Rossana Veronica Mendoza Lopez, Paulo Marcelo Hoff, Jorge Sabbaga, Joao Glasberg
Journal: Journal of Clinical Oncology (2017)

e21676 Background: Malignant obstruction (MO) is a common complication in patients with gastric cancer. Although palliative chemotherapy has already shown beneficial for overall survival in advanced cases, its value for MO reversal is still unknown. Methods: Inthis retrospective study we analyzed all consecutive patients with metastatic gastric cancer admitted with MO at the Instituto do Câncer do Estado de São Paulo (ICESP) from 2008 to 2016. The primary and secondary endpoints were overall survival and obstruction reversal rate respectively. Clinical measures other than chemotherapy and alimentary pause included the use of octreotide 0.1 mg, 3 times a day, steroids, antiemetics and anticholinergic drugs. Survival curves were calculated by Kaplan-Meier and log-rank test was used to compare them. The Cox regression model was used to evaluate risk factors for overall survival and the hazard ratio (HR) was calculated with its respective 95% confidence intervals. The analysis was performed in SPSS v.18 for Windows statistical software, and the significance level was 5%. Results: One hundred and eighteen(118)patients were included. Median overall survival was 11.2 months and survival time after the MO was 3.6 months for the whole group. Median time of use of octreotide was 3 days. Reversal of obstruction was seen in 16 of 36 patients (38.4%) in which chemotherapy was used and only in 22 of the 92 patients (24%) treated with exclusive clinical measures. In spite of these figures a significant better overall survival (p 0.002) was achieved in the group of patients that reached obstruction reversal without chemotherapy (13.6 months vs. 11.6 months for the clinical treatment group). Conclusions: This study suggests that chemotherapy even when reversing MO, has no impact in patients overall survival. These finding is particularly relevant for cost contingency in settings with limited resources. .
Risk stratification of lung cancer patients at initial presentation: A retrospective cohort study.
Authors: Jean-Michel Lavoie, Cheryl Ho, Sophie Sun
Journal: Journal of Clinical Oncology (2017)

e20062 Background: Early detection and treatment of non-small cell lung cancer (NSCLC) has been shown to improve survival. Current screening guidelines focus on at-risk populations, overlooking a significant proportion of patients (pts) who will develop NSCLC. There is a need for further risk stratification in this group. Methods: A retrospective cohort analysis was conducted on pts referred to the BC Cancer Agency – Vancouver Centre for NSCLC. Records were reviewed for the date of first abnormal imaging and 6 clinical factors (CF) noted by the referring clinician at initial presentation. CFs were: ECOG PS &gt; 2, new-onset dyspnea &gt; MRC 3, chest pain, hemoptysis, weight loss &gt; 10% and systemic symptoms (seizure, bone pain, or paraneoplastic syndrome). Individuals meeting current low-dose CT screening criteria (age 55-74, 30 pack-year smoking history within the last 15 years) were also identified. Results: 435 cases were identified from Jan 1 to Dec 31, 2013; 308 had sufficient information to be included for analysis. Median age: 69; smoking history: 69%; stage: I = 5%, II = 9%, III = 26%, IV = 60%. Multivariate analysis identified 4 of 6 CF were associated with worse overall survival (OS, p &lt; 0.05); hemoptysis and weight loss were not significant predictors and were not retained for analysis. Cases were stratified based by the number of CFs. Pts with no CF had significantly improved OS (median 30.5 mo) compared to those with 1 (12.1 mo), 2 (8.1 mo) or 3-4 (2.5 mo; p &lt; 0.001 for all comparisons) CF. Screening criteria were met for 94 pts (31%). For the other 214 pts (69%), number of CF was 0 = 29%, 1 = 29%, 2 = 33%, 3-4 = 9%. OS was similar whether or not pts were eligible for screening. In the subset of ineligible pts, CFs retained their predictive value (p &lt; 0.05). Conclusions: Four clinical factors predict poor outcomes in pts presenting with abnormal imaging suspicious for NSCLC. In this population, 31% of patients would have been eligible for low-dose CT screening. An additional 49% of patients with abnormal imaging had at least one CF identifiable upon initial contact with a healthcare provider. Determination of key clinical factors may assist in risk stratification of pts ineligible for screening who warrant further investigation for lung cancer.
Serial genome-wide sequencing of cell-free DNA (cfDNA) by assays used in non-invasive prenatal testing (NIPT) to identify copy number alterations (CNAs) associated with immunotherapy response.
Authors: Aaron Goodman, Taylor Jensen, Shumei Kato, Christopher Ellison, Lisa Tran, Amin Mazloom, Daniel S. Grosu, Mathias Ehrich, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2017)

e14533 Background: cfDNA derived from tumor cells can be detected in the plasma of many cancer patients. Noninvasive methods to detect CNAs have been developed to detect chromosomal abnormalities in the setting of prenatal screening. We hypothesized that similar methods can be used to enable quantitative detection of CNAs in cfDNA, as represented by a genome instability number (GIN), in patients with cancer and used to monitor response to immunotherapy. Methods: Peripheral blood for CNA analysis was collected from patients with diverse cancers for whom immunotherapy was planned. Plasma was separated from peripheral blood using centrifugation. cfDNA was collected and subjected to low-coverage, genome-wide sequencing. CNAs were detected using methods developed for noninvasive prenatal testing. GIN was calculated as the cumulative sum of the deviation from baseline for all detected autosomal CNAs. The current analysis focused on patients with a complete or partial response (CR/PR) or progressive disease (PD). Results: Of 48 patients, 11 (23%) attained CR/PR; 17 (35%), PD; 20, stable disease. Twelve of the 28 patients (43%) with CR/PR (5 (42%)) or PD (7 (58%)) had a GIN value consistent with the presence of CNAs at treatment initiation and ≥ 1 additional sample for comparison. Four of the 5 patients with CR/PR had a decrease in their GIN from their baseline while all 7 patients with PD had a sustained increase in their GIN. The mean (standard error of the mean (SEM)) change in GIN from maximum to minimum for responders was –2753.8 (+/-1643); mean (SEM) change in GIN from minimum to maximum for progressors was 1373.76 (+/-576) (p = 0.0221). Interestingly, 3 of the 5 responders had an initial increase in their GIN after 2-3 weeks of treatment followed by a decline, while all 7 progressors had a continuous increase in their GIN. Conclusions: GIN can be used to monitor response to immune checkpoint inhibitors in cancer patients. Serial evaluation shows an initial GIN increase followed by decline in patients who eventually attain CR/PR, but a sustained increase in patients with progression.
Effect of genetic and environmental factors on the tumor microenvironment of tongue and buccal cancers.
Authors: Amitabha Chaudhuri
Journal: Journal of Clinical Oncology (2016)

e17500 Background: A critical phase in the development of cancer is the conversion of growth-suppressive normal tissue microenvironment into a growth-promoting tumor microenvironment. This transformation shapes the fate of the growing tumor by providing tumor-promoting signals, protecting tumor cells from immune onslaught and supplying nutrients and oxygen through neo-angiogenesis. These functions are performed by the complex mix of tissue fibroblasts, endothelial cells and immune cells that comprises the tumor stroma. Investigating mechanisms that regulate conversion of of growth-suppressive tissue stroma into a tumor-promoting malignant stroma can lead to better insights into the mechanism of tumor growth. The expectation is that by blocking this conversion tumors can be held in a chronic benign state preventing them from becoming malignant. Methods: We have used our proprietary and optimized RNA-seq data analysis platform for all steps leading to the identification of differentially expressed genes. The platform combines proprietary and open source algorithms for analyzing NGS data. Results: We have applied next generation sequencing to interrogate the tumor epithelial and the stromal compartments in a cohort of tongue and buccal cancers. These cancers are highly prevalent in regions where use of tobacco and alcohol is common. We wanted to investigate the influence of tobacco and alcohol in shaping the tumor microenvironment. Using DNA and RNA-seq data we estimated the relative abundance of epithelial, stromal and immune cells and correlated these with the mutational burden of individual tumors. We show that the presence of driver mutations block immune cell infiltration in both buccal and tongue cancers. By contrast, smoking and use of alcohol sharply increased immune infiltration in buccal, but not in tongue cancers, suggesting that carcinogenic impact differentially affect the composition of the tumor stroma in these cancers. Conclusions: Gene expression analysis is a powerful tool to investigate alterations in the tumor microenvironment contributed by genetic and environmental factors.
Investigation of metformin (MET) in patients with castration resistant prostate cancer (CRPC) in combination with enzalutamide (ENZ) vs. ENZ alone: A randomized, open label, phase 2 trial. SAKK 08/14—IMPROVE.
Authors: Christian Alexander Rothermundt, Richard Cathomas, Alexandros Xyrafas, Martina Schneider, Christine Biaggi Rudolf, Enrico Roggero, Natalie Fischer, Sacha Rothschild, Anna Patrikidou, Walter B. Mingrone, Thomas Hermanns, Tobias Wehrhahn, Andreas Erdmann, Beat Mueller, Pierre Oliver Bohanes, Karin Ribi, Silke Gillessen
Journal: Journal of Clinical Oncology (2018)

TPS5086 Background: The current first-line treatment for patients with CRPC and disease progression is either treatment with abiraterone acetate/prednisone, ENZ, or treatment with docetaxel in more symptomatic patients. There is preclinical data on synergism of ENZ and the biguanide MET: studies on mice orthotopically implanted with ENZ-resistant cells demonstrated that the combination of ENZ and clomipramine or MET significantly reduced tumor growth compared to control groups. Rothermundt et al. previously reported favorable effects of single agent MET in a phase 2 trial: objective PSA responses, disease stabilization and improvement of metabolic endpoints in patients with CRPC. Therefore addition of MET to ENZ might have positive impact on tumor progression, on body composition and insulin sensitivity. Methods: This is a prospective 1:1 randomized multicenter phase 2 trial. Primary endpoint is disease control (DC) at 15 months. Progression is defined as having 2 of the following events: radiographic progression, symptomatic/clinical progression, or PSA progression. Secondary endpoints include overall response according to modified RECIST v1.1 and PCWG2 recommendations, event-free survival, adverse events, quality of life, pain and overall survival. Translation research comprises liquid biopsy, metabolomics, hyperglycemia, and pyruvate dehydrogenase substudies. Assuming a 20% difference in the DC rate at 15 months (50% vs. 70% in the combination arm) with alpha 0.10 and power 80%, 168 patients are required in total. Eligibility criteria are as follows: asymptomatic or minimally symptomatic mCPRC (adenocarcinoma) documented by imaging, ongoing androgen deprivation therapy (ADT) with GnRH agonists or antagonists or bilateral orchiectomy, total testosterone levels ≤ 1.7 nmol/L, tumor progression at the time of registration, no prior treatment for mCRPC other than ADT, no history of diabetes and metformin use, and adequate organ function. Patients receive either ENZ 160mg qd in combination with MET 850mg bd or ENZ 160mg qd alone. 62 patients have been enrolled since accrual began in March, 2016. Clinical trial information: NCT02640534.
Association between certain NSCLC driver mutations and sensitivity markers for chemotherapy or PD-(L)1 inhibition: A large-sample analysis.
Authors: Wenhua Liang, Yi Zhao, Hengrui Liang, Haiying Yang, Zhen Wang, Wenting Chen, Chuhong Xu, Xinyun Yang, Jianxing He
Journal: Journal of Clinical Oncology (2018)

8542 Background: Driver gene alterations play a pivotal role in NSCLC and are predictive markers for specific targeted therapy. However, few evidence has correlated certain mutation types with the sensitivity markers for different chemo-agents or immune-checkpoint inhibitors which are inevitable during the whole course of treatment. Methods: Specimens and clinical data were obtained from a consecutive cohort of resectable NSCLC patients from 2016-03 to 2017-11. Hybridization-capture sequencing (Ion Proton) of 8 important NSCLC-related drivers was conducted. The slides were tested for PD-L1 (SP142), ERCC1, RRM1, TS and β-tubulin3 by immunohistochemical staining. Results: Among a total of 785 patients, 498 (63.4%) patients had at least 1 driver alterations. The prevalence of each driver agreed with previous reports and their association with sensitivity markers were summarized as The overall percentage was used as a cut-off for each marker. *, representing good sensitivity to corresponding drugs. According to the results, preferable regimens might be indicated; the sensitivity indication was consistent with previous observations. For Kras+ patients, PD-(L)1 inhibition is an optimal option and platinum should be included when using chemo; for BRAF mutation where limited data presented, anti PD-(L)1 is optionable and taxanes might be the most sensitive chemo-agents. Conclusions: These results may aid in selecting optimal salvage regimen after targeted therapy failure, or adjuvant chemo-regimen where targeted therapy has not been a routine option. Further validation using true response data was warranted. Type Prevalence % ERCC1 low % RRM1 low % TS low % β-tubulin3 low % PD-L1(+) % Overall 100 11.70 66.30 72.00 57.00 27.60 Wide Type 36.56 14.9 * 50.00 54.60 61.8 * 36.4 * EGFR 19DEL 21.40 2.90 76.8 * 87.6 * 58.90 16.10 EGFR L859R 23.18 7.20 81.2 * 82.7 * 60.3 * 18.90 EGFR rare 2.42 16.7 * 91.7 * 100 * 85.7 * 20.00 ALK 3.18 22.7 * 69.6 * 95.7 * 39.10 25.00 HER2 0.25 0.00 100 * 100 * 0.00 - RAS 9.81 28.6 * 58.90 58.90 39.00 44.9 * RET 1.15 14.3 * 50.00 57.10 28.60 0.00 ROS1 1.02 0.00 66.7 * 66.70 14.30 60 * BRAF 0.64 0.00 20.00 40.00 60 * 60 * MET (mut) 0.38 33.3 * 66.7 * 33.30 33.30 66.7 *
Ultrastructural study of tumor-infiltrating СD4+ Т-lymphocytes in colon cancer.
Authors: Anastasia Grankina, Elena Yurievna Zlatnik, Inna Arnoldovna Novikova, Svetlana Yu. Filippova, Aleksandr K. Logvinov, Vladimir Kolesnikov
Journal: Journal of Clinical Oncology (2017)

e23074 Background: The purpose of the study was to assess stress-induced metabolic changes in СD4+ T-lymphocytes among tumor-infiltrating lymphocytes (TILs) according to ultrastructural morphometric parameters. Methods: Samples (n = 12) of colon adenocarcinoma, corresponding resection line tissues and blood of patients and healthy donors were studied. After grinding the samples and PBMC isolation using the density gradient, CD4+ T-lymphocytes separation with magnetic columns was performed using CD4 MicroBeads, human (MACS Miltenyi Biotech). The pellet obtained after centrifugation was embedded in agarose and prepared for transmission electron microscopy. Mitochondria images on ultrathin sections of Т-lymphocytes were randomly selected for the analysis. The total number of mitochondria studied were 71 (tumor), 78 (normal tissue), 78 (blood of patients), 80 (blood of healthy donors). For each image the unchanged cristae area was determined as a percentage of the total area of mitochondria cross section. Results: We found no differences in the structures of mitochondria of blood lymphocytes in patients and in healthy donors. Comparison of parameters of CD4+ Т-lymphocyte mitochondria in the colon unchanged tissues and in the blood of patients did not show significant differences indicating minimal damage during TILs` isolation from the tissues. Electron microscopy of TILs derived from tumor tissue showed more frequent apoptotic and necrotic death of lymphocytes, as well as some mitochondrial swelling with changes in the shape and the number of cristae compared to the norm. Statistical analysis revealed significant decrease in the relative area of unchanged cristae: 57% in tumor against 73% in the normal tissue (p &lt; 0.0001, χ2Test). Conclusions: The results suggest that stress-induced changes are developed in tumor-infiltrating CD4+ T-lymphocytes, and these changes apparently enhance their death as demonstrated by ultrastructural characteristics of mitochondria.
Mixed and Matched Metallo‐Nanotexaphyrin for Customizable Biomedical Imaging
Authors: Joseph M. Keca, Michael S. Valic, Miffy H. Y. Cheng, Wenlei Jiang, Marta Overchuk, Juan Chen, Gang Zheng
Journal: Advanced Healthcare Materials (2018)

Abstract The discovery and synthesis of multifunctional organic building blocks for nanoparticles have remained challenging. Texaphyrin macrocycles are multifunctional, all‐organic compounds that possess versatile metal‐chelation capabilities and unique theranostics properties for biomedical applications. Unfortunately, there are significant difficulties associated with the synthesis of texaphyrin‐based subunits capable of forming nanoparticles. Herein, the detailed synthesis of a texaphyrin‐phospholipid building block is reported via a key 1,2‐dinitrophenyl‐phospholipid intermediate, along with stable chelation of two clinically relevant metal ions into texaphyrin‐lipid without compromising their self‐assembly into texaphyrin nanoparticles or nanotexaphyrin. A postinsertion methodology to quantitatively insert a variety of metal‐ions into preformed nanotexaphyrins is developed and employed to synthesize a structurally stable, mixed 111 indium‐manganese‐nanotexaphyrin for dual modal single‐photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). In vivo dual SPECT/MRI imaging of 111 In‐Mn‐nanotexaphyrins in an orthotopic prostatic PC3 mouse model demonstrates complementary signal enhancement in the tumor with both modalities at 22 h post intravenous administration. This result highlights the utility of hybrid metallo‐nanotexaphyrins to achieve sensitive and accurate detection of tumors by accommodating multiple imaging modalities. The power of this mixed and matched metallo‐nanotexaphyrin strategy can be unleashed to allow a diverse range of multifunctional biomedical imaging.
Chemotherapy: Multicombination Approach Suppresses <i>Listeria monocytogenes</i>‐Induced Septicemia‐Associated Acute Hepatic Failure: The Role of iRhom2 Signaling (Adv. Healthcare Mater. 17/2018)
Authors: Min‐Xuan Xu, Chen‐Xu Ge, Yu‐Ting Qin, Ting‐Ting Gu, De‐Shuai Lou, Qiang Li, Lin‐Feng Hu, Jun Tan
Journal: Advanced Healthcare Materials (2018)

Biomaterials functionalized with nano-scale drug carriers exhibit excellent biological properties. In article 1800427, a novel design by Min-Xuan Xu, Jun Tan, and co-workers, highlights the latest advanced approach regarding the multicombination drug delivery for the chemoprevention of septicemia-associated acute hepatic failure. The multifunctional nanoparticles can effectively suppress septicemia, systemic inflammatory response syndrome, and corresponding fatal hepatic injury by inhibition of oxidative stress and inflammation.
Cold Agglutinins in Mycoplasma Infection
Authors: Brett G. Fischer, Amiran Baduashvili, Arthur T. Evans
Journal: JAMA (2018)

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Use of alternative or supportive care products among hematology patients in a pediatric hematology outpatient clinic.
Authors: Sule Unal, Turan Bayhan, Fatma Gumruk, Mualla Cetin
Journal: Journal of Clinical Oncology (2016)

e21585 Background: Alternative or supportive care products (ASCP) are sometimes preferred for use in addition to standard medical care by some of the patients with chronic disorders. In the current study, we aimed to question the rate and types of the use of these ASCP. Methods: A total of 115 patients with chronic hematological disorders were questioned for the use of ASCP with a query given to caregivers. Results: Of these patients 53% had an underlying diagnosis of ALL, 2.6% AML, 1.7% CML and rest were those with benign hematological disorders. Of the study group, 57 (49.6%) were found to use ASCP and 22 were found to use more than one ASCP. Of the ASCP, carob was the most common (n = 27), followed by royal jelly (n = 12), pollen (n = 6), grape molasses (n = 6), dead nettle (n = 5), grape seeds syrup (n = 5), grape seeds extract (n = 4), fish-oil (n = 2), parsley extract (n = 2), camomile tea (n = 2). Additionaly one patient was given shark meat and anothe was given turtle blood. Of the patients who used these ASCP; 43.9% used without information of the following physician. Of those who used ASCP, 36% claimed that they had beneficial effects of these products. Only the patient who used shark meat developed hypertransaminasemia, as an adverse event detected. Of the patients with acute leukemia, 62.5% were understood to be under ASCP. Conclusions: The use of CP among patients with hematologica/oncological disorders is high and more common among patients with oncological disorders. Since almost half of these patients use these products without informing their physicians, the families should be instructed for the importance of these products and potential risks.
TCT-510 Dutch multicenter experience using the STENTYS Xposition S self-expanding stent in complex coronary lesions
Authors: Selina Vlieger, Cihan Simsek, Samer Somi, Gillian Jessurun, Giovanni Amoroso, Floris Kauer, Anais Balland, David Bouchez, Alexander Ijsselmuiden
Journal: Journal of the American College of Cardiology (2018)