tbuckley/cabot-search huggingface dataset:
[18F]-FDG-PET in germ cell tumors following chemotherapy: Results of the German multicenter trial
Authors: M. De Wit, M. Hartmann, W. Brenner, L. Weiβbach, H. Amthauer, C. Franzius, S. Kliesch, S. Krege, R. Heicappell, R. Bares, C. Bokemeyer
Journal: Journal of Clinical Oncology (2006)

4521 Background: The aim of this study was to evaluate the viability of residual masses following chemotherapy in patients (pts) with germ cell cancer (GCT) using FDG-PET. Methods: Pts with diagnosis of GCT at primary diagnosis or at relapse were included if residual masses (&gt; 1 cm) were present following chemotherapy. 140 pts, 27 with primary extragonadal GCT, aged 15.7–59.2 (mean age: 32.7 years) treated in 18 centers were examined with concurrent FDG-PET and CT. FDG-PET was performed in fasting state. Images were reconstructed by filtered back projection. All PET-scanners were calibrated using the same phantom. The presented data are based on visual scan analysis. All pts underwent surgery for residual masses. Thus, all results were validated by histology. Results: Histology of the primary tumor included 20 seminoma and 109 NSGCT, while 11 pts had no primary histology. 88 pts (63%) had no persistent GCT. 120 pts (86%) demonstrated residual masses in retroperitoneal lymph nodes; in 56 pts (40%) residual masses were localized in the thorax and in 8 pts elsewhere (multiples possible). 40 pts (29%) presented active residual carcinoma and 54 (39%) presented residual teratoma (combination possible) following chemotherapy. Correct classification of the residual mass by FDG-PET was achieved in 79 of 140 (56%), while CT scans were correct in 58 of 140 pts (42%). 46 of 89 patients with a positive FDG-PET turned out to have viable tumor while in 36 out of 52 patients with a negative scan no lymph node metastases were found. FDG-PET turned out to show a sensitivity of 73% and specificity of 44%. Positive and negative predictive value (PPV, NPV) were 48% and 69% and accuracy 56%, respectively. In NSGCT 58 pts had no active tumor and 28 were true negative with FDG-PET resulting in a specificity of 47% and a NPV of 67%. 36 patients were true positive with a PPV of 54% and a sensitivity of 72%. Conclusion: FDG-PET for GCT following chemotherapy has a higher accuracy than CT, but sensitiviy is still too low to avoid subsequent resections in patients with NSGCT. [Table: see text] No significant financial relationships to disclose.
Myocardial Function in Patients With Radiation-Associated Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement
Authors: Christophe Martinez, Marianna Cicenia, Muriel Sprynger, Adriana Postolache, Federica Ilardi, Raluca Dulgheru, Marc Radermecker, Giovanni Esposito, Patrick Marechal, Victoria Marechal, Nathalie Donis, Julien Tridetti, Mai-Linh Nguyen Trung, Tadafumi Sugimoto, Toshimitsu Tsugu, Yun Yun Go, Augustin Coisne, David Montaigne, Khalil Fattouch, Alain Nchimi, Cécile Oury, Patrizio Lancellotti
Journal: JACC. Cardiovascular imaging (2020)
KRAS mutation in lung cancer patients: A poor prognostic factor but not a predictive factor of EGFR-TKI and chemotherapy?
Authors: Jilin Guan, Wenzhao Zhong, Shejuan An, Jian Su, Zhihong Chen, Ying Huang, Zhimin Huang, Xuchao Zhang, Jinji Yang, Yi Long Wu
Journal: Journal of Clinical Oncology (2012)

e18090 Background: At present, prognostic and predictive value for KRAS mutation in lung cancer patients remains to be controversial. Biases in disease stage, treatment regimens and small scale patient population led to inconsistent results in previous studies. Methods: we collected 91 consecutive lung cancer patients with KRAS mutation detected in Guangdong Lung Cancer Institute from January 2007 to may 2010. And each patient with mutant KRAS was paired randomly to a patient with KRAS/EGFR wild-type and a patient with mutant EGFR according to the identical TNM stage. All patients were followed up for treatment regimes, tumor response, progression-free survival (PFS) and overall survival (OS). Results: The patients with KRAS mutation were associated with a significantly shorter overall survival compared with patient without KRAS mutation (P=0.0005), and the same trend of disease free survival was also found in R0 resected lung cancer patients (P=0.039). Multivariate analyses proved the status of KRAS mutation was an independent prognostic factor (HR=2.69, 95%CI: 1.91-3.80, P=0.0005). No difference was found in PFS and tumor response between the first or second line EGFR-TKI treated patients harboring KRAS mutation and KRAS/EGFR wild-type (The first line: P=0.23, 0.82; The second line: P=1.00, 0.48). In the first and second line chemotherapy, there was no significant difference for PFS among the three groups (P=0.15, 0.52). Conclusions: KRAS mutation was a poor prognosis factor, but not an independent predictive factor for EGFR-TKI and chemotherapy in lung cancer patients. EGFR wild-type is major reason for resistant to EGFR-TKI in patients with KRAS mutation.
Expression of folate pathway regulators and pemetrexed (pem) activity in patients (pts) with advanced non-small cell lung cancer (NSCLC).
Authors: Letizia Gianoncelli, Luca Toschi, Barbara Canal, Chiara Lo Russo, Luca Rubino, Giovanna Finocchiaro, Laura Giordano, Annarita Destro, Isabella M.G. Garassino, Raffaele Cavina, Licia Siracusano, Massimo Roncalli, Antonino Carbone, Armando Santoro
Journal: Journal of Clinical Oncology (2012)

7585 Background: Thymidylate synthase (TS) expression has been reported to predict pem activity in pts with advanced NSCLC. Besides TS, pem inhibits multiple enzymes of the folate pathway including dihydrofolate reductase (DHFR), glycinamide ribonucleotide formyltransferase (GART) and aminoimidazole carboxamide ribonucleotide formyltransferase (AICAR). Aim of present study was to investigate whether these or other biomarkers influence pem activity in NSCLC pts. Methods: Advanced pretreated NSCLC pts who received at least two cycles of single agent pem were considered eligible if they had available tumor tissue to assess at least one of the proposed biomarkers. TS, DHFR, GART and AICAR protein expression was assessed by immunohistochemistry (IHC) in FFPE tumor samples. Pts were grouped as IHC+ and IHC– according to staining intensity. Additionally, presence of EGFR and KRAS mutations was investigated. Results: Ninety-six pts were included in the study. The majority of subjects was male (72%), smokers (93%), with adenocarcinoma (72%). Response rate (RR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were 12%, 47%, 2.3 and 9.5 months, respectively. Most pts resulted TS-(72%), AICAR-(82%), DHFR+ (68%), GART- (61%). EGFR and KRAS mutations were identified in 15% and 25% of assessable cases. None of the biomarkers was significantly associated with pts characteristics (gender, histology, smoking status), nor with RR or DCR. GART- pts experienced longer PFS when compared with the GART+ group (HR 0.56, p=.052), while no difference was observed according to TS, DHFR and AICAR status. A significantly longer OS was observed for TS- (HR 0.52, p=.012), GART- (HR 0.50, p=.037) and AICAR- (HR 0.40, p=.028) pts. No significant difference in the distribution of EGFR mutant pts receiving EGFR TKIs after pem failure was observed between IHC+ and IHC- groups. Conclusions: Low TS, GART and AICAR protein expression predicts significantly prolonged survival in single agent pem-treated pts with advanced NSCLC. The lack of PFS difference according to TS and AICAR status suggests prognostic rather than predictive relevance for these biomarkers.
EVALUATION OF THE ACADEMIC RESEARCH CONSORTIUM HIGH BLEEDING RISK DEFINITION IN PATIENTS TREATED WITH DRUG-COATED STENTS AND BARE-METAL STENTS FROM THE LEADERS FREE I &amp; II TRIALS
Authors: Guillaume Marquis-Gravel, Philip M. Urban, Samuel Copt, Sara Sadozai Slama, Hans-Peter Stoll, Roxana Mehran, Davide Capodanno, Martin Leon, Sunil Rao, Stuart Pocock, Marie Morice, Mitchell Krucoff
Journal: Journal of the American College of Cardiology (2020)
IMPACT OF CORONARY LESION STABILITY ON THE BENEFIT OF EMERGENT PERCUTANEOUS CORONARY INTERVENTION AFTER SUDDEN CARDIAC ARREST
Authors: Nicole Karam, Louis Pechmajou, Eloi Marijon, Olivier Varenne, Florence Dumas, Frankie Beganton, Daniel Jost, Lionel Lamhaut, Eric Lecarpentier, Thomas Loeb, Frederic Adnet, Marc Agostinucci, Wulfran Bougouin, Christian Spaulding, Alain Cariou, Xavier Jouven
Journal: Journal of the American College of Cardiology (2020)
Abstract #3740: A clinical trial of the Bruton\#8217;s tyrosine kinase (Btk) inhibitor PCI-32765 in naturally occurring canine lymphoma
Authors: Lee Honigberg, Ashley Smith, David Loury, Joseph Buggy, Douglas Thamm
Journal: Cancer Research (2009)

Bruton\#8217;s tyrosine kinase is a Tec family kinase that functions downstream of the B cell antigen receptor (BCR) in both developing and mature B cells. BCR expression is frequently maintained in non-Hodgkin\#8217;s lymphoma (NHL), suggesting that tonic or antigen-driven activation of the BCR pathway may contribute to tumor cell survival. PCI-32765 is an orally bioavailable selective inhibitor of Btk that covalently binds to Cys-481 in the active site (ChemMedChem 15:58, 2007). We have shown previously that PCI-32765 inhibits BCR signaling, induces apoptosis in a subset of human lymphoma cell lines, and suppresses tumor growth in B cell lymphoma xenograft models in the mouse (Blood 110:475A, 2007). In preparation for clinical trials in human lymphoma, we have initiated a trial of PCI-32765 in naturally occurring B cell NHL in companion dogs. Canine NHL shares many characteristics with human NHL, including diagnostic classifications and response to CHOP chemotherapies. In the current study, both treatment naive and relapsed dogs are being enrolled and PCI-32765 is dosed once per day in capsule form. In order to monitor inhibition of Btk in vivo we have developed a novel pharmacodynamic assay using a fluorescent probe derived from PCI-32765. The probe can be added to protein lysates ex vivo and probe-labeled Btk can be visualized by fluorescent gel scanning. Because the probe binds at the same site as PCI-32765, inhibition of Btk by PCI-32765 prevents subsequent probe labeling. Using this assay we found that in all dogs, a single dose of PCI-32765 (20 mg/kg) is sufficient to fully occupy Btk in peripheral blood and tumor tissue for 24 hours. To date, four dogs have been treated and we have observed a partial response (RECIST) in one dog, in which total tumor burden was reduced 79% after 4 weeks of dosing. In conclusion, PCI-32765 is capable of completely inhibiting tumor-associated Btk in canine lymphoma and may be an effective therapy in human lymphoma. In addition, clinical evaluation in spontaneous cancer in dogs is a valuable approach to explore safety, efficacy and dose scheduling prior to human clinical trials.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3740.
Recurrence after imatinib treatment for gastrointestinal stromal tumor: Japanese experience in a single institute
Authors: A. Sawaki, N. Mizuno, K. Takahashi, T. Nakamura, M. Tajika, H. Kawai, H. Inoue, A. Masatoshi, Z. Ahmed, K. Yamao
Journal: Journal of Clinical Oncology (2006)

19504 Background: Although imatinib is the most effective agent for metastatic gastrointestinal stromal tumors (GISTs), resistance to imatinib develops in most patients. While the effectiveness of an oral multitageted tyrosine kinase inhibitor for intolerant GIST is already reported, many of imatinib resistant patients are not available. We report clinical results of first imatinib and post imatinib treatment in a patient with metastatic or unresectable GIST. Methods: A retrospective review was undertaken in patients with metastatic or unresectable GIST treated with imatinib at Aichi Cancer Center Hospital between June 2001 and December 2005. Treatment schedule was four or six 100-mg capsules of imatinib orally once daily. Patients were evaluated for treatment, recurrence, and survival. Results: Forty-five patients (26 males and 43 metastatic patients) were treated with imatinib at first. The median age was 58 years (range 25–79). Primary tumor sites were as follow; stomach was 13, duodenum 9, small intestine except for duodenum 18, and colorectum 5. Metastatic sites were liver (21 patients), peritoneum (11 patients), both of them (10 patients), and the other (1 patient). The response rate (by RECIST) and PFS was 71.1% (32/45) and 24 months, respectively. Imatinib was well tolerated; only two patients stopped treatment due to nausea and vomiting. Twenty-six patients with disease progression were treated by the combination of many methods, and the following methods underwent as the second therapy; 9 patients underwent surgical resection, 7 patients underwent transarterial chemoembolization (TACE) for liver metastases, 9 patients enrolled in a clinical trial, and 9 patients continued imatininb because of clinical benefit and no other therapeutic options. PFS of surgery and TACE were 6 and 7 months, respectively. Out of 16 patients treated with surgery or TACE, 2 patients were well controlled by TACE more than 1 year. One patient, however, was suffering from intractable liver abscess after TACE. Conclusions: The efficacy and safety of imatinib for GIST is almost the same as in U.S. reports. TACE may be an effective treatment for liver metastases if new agents are not available. No significant financial relationships to disclose.
Carboplatin and etoposide followed by once-daily thoracic radiotherapy in limited-disease small-cell lung cancer.
Authors: Ufuk Yılmaz, Ceyda Anar, Esra Korkmaz, Sena Yapicioglu, Ilker Karadogan, Serdar Ozkok
Journal: Journal of Clinical Oncology (2013)

e18540 Background: There has been a trend to replace cisplatin with carboplatin in the treatment of small-cell lung carcinoma. The goal of the present study was to determine the efficacy of carboplatin and etoposide followed by thoracic radiotherapy in patients with previously untreated limited disease small-cell lung carcinoma. Methods: From February 2001 to March 2007, 47 patients with limited disease small-cell lung cancer were enrolled in the study. Etoposide, 100 mg/m 2 , was administrated intravenously on days 1-3 in combination with carboplatin, AUC 6, on day 1 every 21 days for 6 cycles. In cases considered to have non-progressive disease following induction chemotherapy, thoracic radiotherapy was given with in a once daily fraction of 2.0 Gy, 5/wk, up to 50-60 Gy. Results: Forty-one patients were evaluated. Median age was 62 (range, 40-78), 88% of patients were male. ECOG PS was 0-1 in 38 patients. Seven of the 41 patients (17.5%) had pleural effusion (one malignant) and 7 patients (17.5%) had involved supraclavicular lymph nodes. Ninety percent of patients had elevated serum lactate dehydrogenase levels. Median follow-up was 13.5 mo. A total of 209 cycles of chemotherapy was administered (median, 6; range, 1-6). Thoracic irradiation was given to 33 patients. The overall response rate to combined modality on an intention-to-treat basis was 73%. Median survival time was 13.7 months (95% CI, 10.3-17.1), and median progression-free survival was 9.5 months (95% CI, 8.6-10.4). Two- and four-year overall survival was 23% and 7%, respectively. Grade 3-4 neutropenia and leukopenia were the most common adverse events and occurred in 46.0% and 24.0% of the patients, respectively. Six (14%) patients experienced febrile neutropenia. Three patients (7%) died of sepsis and neutropenic fever. Non-hematological toxicities were mild. Conclusions: Carboplatin and etoposide chemotherapy followed by thoracic radiotherapy in LD-SCLC appears to be unsatisfactory.
Relative importance of oncologist access and patient pre-selection in limiting the uptake of companion diagnostic tests for solid cancers in the United States.
Authors: Jackie Ilacqua, Pieter De Richter
Journal: Journal of Clinical Oncology (2013)

e22157 Background: The speed of uptake of Companion Diagnostics (CDx) tests in the oncologist community is a product of (1) the number of physicians adopting the test in the months following launch, and (2) the % of patients under those physicians’ care who are being tested. Here, we investigate which one of the two factors was the most significant in terms of limiting the speed of uptake within the initial 3 months after launch of two recently approved CDx tests in the U.S. Methods: A panel of oncologists in the US (N=130) were asked to report on their stated tested levels of EML4-ALK testing for their current stage IIIB and IV NSCLC patients, and BRAF mutation testing for their current stage IV melanoma patients. This data was collected through an online survey between August and November 2012. Results: Of the 130 physicians surveyed, only 5 (4%) did not use EML4-ALK testing for their patients at all, and just under 33% used EML4-ALK testing for all their stage IIIB/IV NSCLC patients. The majority (64%) used EML4-ALK testing for a subset of their stage IIIB/IV NSCLC patients only, indicating they preselected their patients for testing. This compares to as many as 55% of surveyed physicians using BRAF for 100% of their stage IV melanoma patients, with a further 29% using it for a subset of their stage IV melanoma patients and 7% not using the test at all. Conclusions: As the vast majority (96% and 93% respectively) of surveyed physicians used EML4-ALK and BRAF testing for at least a subset of their patients within the first 6 months after launch, a lack of access to the tests did not appear to be a major barrier to uptake. Instead, the % of an individual oncologist’s patients being tested through pre-selection for testing was the primary factor determining the volume of testing. Pre-selection was more common for EML4-ALK testing than for BRAF testing, possibly due to the higher incidence of BRAF mutations than EML4-ALK translocations.
Enhancing the expression and function of an EBV-TCR on engineered T cells by combining Sc-TCR design with CRISPR editing to prevent mispairing
Authors: Shao-An Xue, Yuan Chen, Ralf-Holger Voss, Virad Kisan, Bo Wang, Ke-Ke Chen, Feng-Qin He, Xiao-Xia Cheng, Laura Scolamiero, Angelika Holler, Liquan Gao, Emma Morris, Hans J. Stauss
Journal: Cellular and Molecular Immunology (2020)
INTER-ARM SYSTOLIC BLOOD PRESSURE DIFFERENCES AND INCIDENT CARDIOVASCULAR DISEASE AND TOTAL MORTALITY IN A MULTI-ETHNIC POPULATION WITHOUT OVERT CARDIOVASCULAR DISEASE: THE MESA STUDY
Authors: Daniel A. Duprez, David R. Jacobs, Julie O. Denenberg, Robyn McClelland, Leah Andrews, Isac Thomas, Matthew Allison
Journal: Journal of the American College of Cardiology (2020)
Investigation of human mammary stem and progenitor subpopulations from BRCA1 mutation carriers and noncarriers
Authors: E. Lim, F. Vaillant, D. Wu, N. Forrest, B. Pal, D. Gyorki, G. K. Smyth, J. Visvader, G. Lindeman
Journal: Journal of Clinical Oncology (2009)

504 Background: We have previously isolated discrete populations of mouse mammary epithelial cells (MECs) and defined a population that expresses ‘basal’ markers and is highly enriched for mammary stem cells. This subset was ‘triple negative’ for ER, PR and ErbB2 expression and is reminiscent of the basal subtype of breast cancer, suggesting that the mammary stem cell may be the ‘cell of origin’ for this poor prognosis group. Since tumors arising in BRCA1 mutation carriers often exhibit a ‘basal’ phenotype, we hypothesized that the mammary stem cell pool is aberrant in these women. Our objective was to define the human MEC hierarchy and evaluate the functional characteristics of MECs from BRCA1± and normal breast tissue. Methods: Single cell suspensions prepared from fresh human BRCA1± and normal breast tissue were sorted by flow cytometry. Hematopoietic (CD45+, CD235a+) and endothelial (CD31+) cells were removed, and the remaining viable ‘lineage minus’ (Lin-) MECs fractionated based on cell surface markers. These subpopulations were evaluated by immunostaining, RNA profiling, in vitro culture in Matrigel and in vivo xenotransplantation into ‘humanised’ mammary fat pads of immunocompromised mice. Results: Lin- cells fractionated with α6-integrin (CD49f) and epithelial cell adhesion molecule (EpCAM) revealed three discrete MEC subpopulations. A stem/progenitor population that preferentially yields breast outgrowths in vivo has been identified. These subpopulations gave rise in vitro to colonies that were either large and heterogenous or small and homogenous. Only the latter differentiated into milk-producing cells when exposed to lactogenic stimuli. Immunostaining confirmed their origins from myoepithelial and luminal progenitor cells respectively. Intriguingly, BRCA1± MECs exhibited perturbed in vitro growth properties when compared to normal controls. Conclusions: Our studies provide evidence for a human MEC hierarchy, a model to interrogate the perturbation noted in pre-neoplastic tissue derived from BRCA1 mutation carriers and the identification of the cell of transformation in BRCA1 associated breast cancer. These findings may have implications on developing prevention strategies for hereditary breast cancer. No significant financial relationships to disclose.
HALF OF VETERANS OVER 80 YEARS OF AGE WITH IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS WHO ARE FRAIL OR COGNITIVELY IMPAIRED DO NOT HAVE AN ADVANCE DIRECTIVE FOR LIFE SUSTAINING TREATMENT
Authors: Warren Backman, Michael V. Dicaro, Jane A. Driver, Adelqui Peralta, Ariela R. Orkaby
Journal: Journal of the American College of Cardiology (2020)
Prevalence of cardiovascular disease (CVD) risk factors and preventive care among U.S. cancer survivors.
Authors: Kevin A. Pearlstein, Laura H. Hendrix, Ronald C. Chen
Journal: Journal of Clinical Oncology (2013)

9592 Background: CVD is a major cause of mortality in cancer survivors. Prior claims-based studies suggested underutilization of preventive care in cancer survivors, but most CVD preventive care items are not available in claims data. We directly examined the prevalence of CVD risk factors and receipt of care in survivors compared to the non-cancer general population (control) using the National Health Interview Survey. Methods: 32,934 cancer survivors interviewed between 1999 and 2011 were matched to 65819 controls based on age, race, and history of CVD events (angina, myocardial infarction, stroke). Statistical analysis accounted for population sampling weight. Results: CVD risk factors were prevalent among cancer survivors (Table), and 33% continued to smoke. Primary care visits were reported more often among survivors compared to controls (83% vs 74%, p&lt;0.001). A high proportion of survivors and controls received monitoring for diagnosed CVD risk factors, while rates of interventions to modify the risk factors were more modest. On multivariable logistic regression models, having a general doctor visit was associated with increased monitoring for all CVD risk factors examined (hypertension, hyperlipidemia, diabetes, obesity, smoking), but there was no significant difference between cancer vs control. Conclusions: Cancer survivors in the US receive comparable monitoring and interventions for CVD risk factors compared to non-cancer individuals. Survivorship care involving a general doctor was associated with improved monitoring of CVD risk factors. [Table: see text]
Genome editing of mutant KRAS through supramolecular polymer-mediated delivery of Cas9 ribonucleoprotein for colorectal cancer therapy
Authors: Tao Wan, Yuxuan Chen, Qi Pan, Xiaojie Xu, Yu Kang, Xue Gao, Feihe Huang, Chuanbin Wu, Yuan Ping
Journal: Journal of Controlled Release (2020)
Evaluation of the Effectiveness of Surveillance and Containment Measures for the First 100 Patients with COVID-19 in Singapore — January 2–February 29, 2020
Authors: Yixiang Ng, Zongbin Li, Yi Xian Chua, Wei Liang Chaw, Zheng Zhao, Benjamin Er, Rachael Pung, Calvin J. Chiew, David C. Lye, Derrick Heng, Vernon J. Lee
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

First detected in China in late 2019, coronavirus disease 2019 (COVID-19) transmission has spread globally. Singapore implemented a multipronged surveillance and containment strategy that contributed to enhanced case ascertainment and slowing of the outbreak.