tbuckley/cabot-search huggingface dataset:
Results of a randomized phase II trial of amrubicin (AMR) versus topotecan (Topo) in patients with extensive-disease small cell lung cancer (ED-SCLC) sensitive to first-line platinum-based chemotherapy
Authors: R. Jotte, P. Conkling, C. Reynolds, L. Klein, J. F. Fitzgibbons, R. McNally, M. Renschler, J. W. Oliver
Journal: Journal of Clinical Oncology (2009)

8028 Background: SCLC presents as ED-SCLC in 60%-70% of patients (pts). AMR, a synthetic anthracycline, is approved for these pts in Japan. We compare the efficacy and safety of single-agent AMR vs topotecan in non-Japanese pts with 2 nd -line ED-SCLC sensitive to 1 st -line platinum-based chemotherapy. Methods: This phase II, open-label, multicenter study enrolled pts with ED-SCLC sensitive to 1 st -line platinum-based chemotherapy (recurrence or progression ≥90 days from 1 st -line treatment). Pts aged ≥18 years with ECOG performance status (PS) ≤2 and only 1 prior therapy were eligible. Pts were randomized (2:1) to receive IV AMR 40 mg/m 2 /d (d, 1–3) or IV topotecan 1.5 mg/m 2 /d (d 1–5) and treated every 21 days until progression, unacceptable toxicity, or withdrawal. The primary endpoint, overall response rate (ORR, complete + partial response), used RECIST criteria. Secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. Results: In all, 76 pts were randomized to AMR (n=50) or topotecan (n=26) with AMR given for a median of 6 cycles (range 1–16) and topotecan 3 cycles (1–16). AMR significantly improved ORR rates vs topotecan (p&lt;0.012; Table ). Median PFS/OS was 4.3 months (95% CI 2.0, 6.1)/9.3 months (95% CI 5.7, 12.0) with AMR vs 3.5 months (95% CI 2.1, 6.3)/8.9 months (95% CI 4.8, 13.8) with topotecan. There was a higher proportion of ECOG PS 2 pts in the AMR group (n=6) vs the topotecan group (n=2). A trend towards improved OS was observed in the ECOG 0–1 subgroup of 68 pts: median OS was 10.5 months with AMR vs 9.7 months with topotecan. The most common grade ≥3 adverse events with AMR vs topotecan were neutropenia (53% vs 74%), thrombocytopenia (31% vs 52%) and leukopenia (27% vs 30%). Three AMR pts (6%) and 1 topotecan pt (4%) died of neutropenic infection. Conclusions: AMR significantly improves ORR and has acceptable tolerability as 2 nd -line treatment in pts with sensitive ED-SCLC. [Table: see text] [Table: see text]
Phase I study of safety and immunogenicity of ADU-623, a live-attenuated <i>Listeria monocytogenes </i>vaccine (Δ<i>actA</i>/Δ<i>inlB</i>) expressing EGFRvIII and NY-ESO-1, in patients with WHO grade III/IV astrocytomas.
Authors: Marka Crittenden, Keith S. Bahjat, Rui Li, Pankaj A. Gore, Chris Fountain, Bill Hanson, Justin Skoble, Peter Lauer, Aimee Murphy, Thomas Walter Dubensky, Dirk G. Brockstedt, Walter John Urba
Journal: Journal of Clinical Oncology (2015)

TPS3106 Background: The neo-antigen EGFRvIII is expressed in multiple tumor types, including high-grade astrocytomas. It is associated with a poor prognosis and resistance to conventional therapies such as chemotherapy and radiation that are part of the standard treatment. We propose that immunization with a live-attenuated Listeria-based vaccine, ADU-623, expressing EGFRvIII and NY-ESO-1 will elicit robust tumor-specific immune responses capable of killing EGFRvIII and/or NY-ESO-1-expressing tumor cells and improve survival of the patients. In addition, ADU-623 induces a potent innate immune response that can kill transformed cells even in the absence of neo-antigens. We designed a translational vaccine study to evaluate the safety and immunogenicity of this vaccine in patients with high-grade astrocytomas after standard of care therapy or at progression. Methods: Patients with a pathologic diagnosis of WHO Grade III/IV astrocytic tumors that have completed standard of care external beam radiation therapy and concurrent temozolomide followed by adjuvant temozolamide or with radiographic evidence of progression following standard of care radiation and chemotherapy treatment, including those who have gone on to a second surgical resection are eligible. Patients are enrolled and assigned consecutively to one of the following ADU-623 dose level cohorts: Cohort 1 3x107 cfu, Cohort 2 3x108 cfu, or Cohort 3 1x109 cfu, each administered IV on Days 0, 21, 42 and 63. Adverse events are monitored throughout the treatment and patients are followed for up to 24 months. Patients are currently accruing to Cohort 3. The primary objective is to determine the maximum tolerated dose and characterize the safety profile of ADU-623 in patients with treated and recurrent WHO Grade III/IV astrocytomas. Secondary objectives include progression free survival, time to progression and overall survival rates in patients vaccinated with ADU-623. Exploratory studies of EGFRvIII-, NY-ESO-1-, vector-specific and innate immune responses will be performed. Clinical trial information: NCT01967758.
THE IMPACT OF TRANSAORTIC GRADIENT AND TRANSAORTIC FLOW ON THE DISCREPANCY BETWEEN ECHOCARDIOGRAPHIC AND CARDIAC CATHETERIZATION EVALUATION OF SEVERE AORTIC STENOSIS WITH PRESERVED EJECTION FRACTION
Authors: Zaher Fanari, Prasad Gunasekaran, Jhapat Thapa, Arslan Shaukat, Kamleish Persad, Sumaya Hammami, Mark Wiley, Buddhadeb Dawn, Joseph West, William Weintraub, Andrew Doorey, Peter Tadros
Journal: Journal of the American College of Cardiology (2017)
REFERRAL FOR PHARMACOLOGIC TESTING, A MARKER OF POOR EXERCISE CAPACITY, CONFERS A HIGHER RISK OF SHORT AND LONG TERM MORTALITY THAN MOST TRADITIONAL CARDIAC RISK FACTORS EXCEPT AGE
Authors: Serge C. Harb, Yuping Wu, Leslie Cho, Carol Rouphael, Paul Cremer, Venu Menon, Wael Jaber
Journal: Journal of the American College of Cardiology (2017)
Gene expression profile changes following erlotinib treatment in patients with metastatic breast cancer
Authors: X. Yang, A. R. Tan, D. Nguyen, S. Lipkowitz, S. M. Swain
Journal: Journal of Clinical Oncology (2004)

577 Background: We previously described changes in EGFR kinase activity and downstream signaling pathways using IHC in tumor biopsies in 15 patients with metastatic breast cancer pre and post treatment with erlotinib (150 mg daily for 1 month). There were no clinical responses and no changes in Ki67 in tumors after erlotinib. One tumor expressed significant levels of EGFR which decreased after treatment. Aims of this study are to delineate erlotinib induced changes in gene expression profiles in EGFR positive (+) and negative (-) tumors. Methods: RNA was isolated from frozen tumor cores and gene expression profiles in 9 paired pre-post treatment tumors were measured with Affymetrix U133A GeneChip containing 22283 human genes. Results were analyzed using Affymetrix MS5.0 comparison analysis algorithm and principle components analysis. EGFR expression was validated by IHC. Results: Only 1/9 tumor expressed EGFR by IHC. cDNA array data were 100% concordant with IHC for EGFR expression. In EGFR + tumor, EGFR RNA did not change with erlotinib treatment. About 300 genes were significantly changed in distinct paired tumors, independent of EGFR expression. These included genes encoding extracellular matrix components, matrix metalloproteinases, drug metabolism, protein translation, and transcription factors. EGFR interacting genes, tissue inhibitor of metalloproteinases-1 and -3 were up-regulated > 2 fold in the EGFR+ tumor, down-regulated > 2 fold in 6 EGFR- tumors, unchanged in 2 EGFR- tumors. Examples of other altered genes are: Rab GTPases - members of ras oncogene family; heterogeneous nuclear ribonucleoprotein C (C1/C2); insulin-like growth factor binding protein 3, 4, 5, 7; serine proteinase inhibitor, clade A; heat shock 70kDa protein 1B; cytochrome P450 family members. Conclusions: Erlotinib is associated with changes in gene expression in EGFR+ and –tumors. This suggests that the drug has additional targets. The decrease in EGFR protein induced by erlotinib in the EGFR+ tumor was not due to transcriptional effects and may be due to the accelerated ubiquitylation and degradation of the receptor. Validation by IHC and real-time RT-PCR is in progress. No significant financial relationships to disclose.
INCREASED ERYTHROCYTE AGGREGATION AND DECREASED ERYTHROCYTE DEFORMABILITY IN PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION
Authors: Yalin Yaylali, Emine Kilic-Toprak, Yusuf Ekbic, Yasin Ozdemir, Vural Kucukatay, Hande Senol, Nese Dursunoglu, Melek Bor-Kucukatay
Journal: Journal of the American College of Cardiology (2017)
Axillary recurrences in early breast cancer patients treated with sentinel node biopsy. Experience at the Instituto Nacional de Enfermedades Neoplasicas.
Authors: Jorge Antonio Dunstan, Carlos Castaneda Altamirano, Julio E. Abugattas Saba, Jose M. Cotrina, Franco F. Doimi, Jaime Montes Gil, Valeria Villegas Bernaola, Miluska Castillo Garcia, Carolina Belmar Lopez, Ketty Dolores Cerna, Henry Leonidas Gomez
Journal: Journal of Clinical Oncology (2015)

e12068 Background: Sentinel node biopsy (SNB) is the standard of care for clinically node-negative breast cancer patients and has been introduced to the Institute from 1996 Methods: We have selected all early cases who went to SNB and breast tumor resection as first treatment, and excluded bilateral breast cancer, non-invasive breast cancer, past history of other malignancy. We evaluated 1272 cases. Adjuvant therapy and breast irradiation were decided by physician’s discretion and patient’s preference. To evaluate the risk of recurrences, clinicopathological factors were analyzed using the Cox regression model. Results: Median Age was 52;Clinical T1(40%),T2(53%) and T3(5.5%).Ductal(90%),lobular(4.5%).Luminal A(32%),B(34.7%),TN(18.8%) and HER2(6.4%). Median extracted SNB was 2 and was positive in 33.7%.Axillar dissection(AD) was performed in 43%.After a median follow-up of 61 months, there were 7.63% recurrences and 2.36% deaths.Recurrence at bed scare(28.4%),axillary lymph nodes(18.56%),supraclavicular lymph nodes(12.37%),bones(20.62%),lung(22.68%) and liver(12.37%). Axillar recurrences were a more frequent location in SNB-negative(26%)than in SNB positive(12%)(p = 0.042). Cases with T1,HG-1,ER+ and luminal A phenotype had better DFS and OS in SNB- negative and positive.Two and 3 positive nodes in SNB evaluation was associated to higher number of positive nodes in AD evaluation than cases with only 1 positive node in SNB (p0.01).Two and 3 positive nodes in SNB had similar DFS(p = 0.68) and OS(p = 0.76) than 1 positive node of SNB evaluation Conclusions: Axillary recurrence was higher event afterSNB than AD. Survival is similar among 1 or 2-3 positive-SNB.
Correlation of educational status and clinicopathological characteristics of breast cancer: A single center experience.
Authors: Omer Diker, Taner Babacan, Hakan Buyukhatipoglu, Neyran Kertmen, Ozan Balakan, Ali Rıza Sever, Ozan Unlu, Ozturk Ates, Saim Furkan Sarici, Serkan Akin, Veli Sunar, Yusuf Karakas, Sahin Lacin, Kadri Altundag
Journal: Journal of Clinical Oncology (2015)

e11549 Background: Educational status may be an important parameter in assessing breast cancer risk and prognosis. The aim of this study was to investigate the correlation between the level of education and clinicopathological characteristics of breast cancer, including tumor grade, HER-2 and estrogen receptor status, tumor size, axillary lymph node involvement and metastasis. Methods: The study included 1800 women who were diagnosed with invasive breast cancer during 2005-2013 at Hacettepe University Cancer Institute. Patients were divided into three groups according to their educational status at the time of diagnosis. This was classified as low (illiterate and elementary school, 5 years or less of education), medium (secondary school and upper secondary school, 6–12 years of education) and high (university level, more than 12 years of education). The associations between educational status and clinicopathologic features of breast cancer at the time of diagnosis were evaluated. Results: In all patient, a significant relationship was found between educational status and T stages (p < 0.0001). Patients with higher educational levels were reported to have smaller tumor size regardless to their age. Patients with high educational level were less likely to have axillary lymph node involvement (p = 0.001) or metastasis (p = 0.001). A significant correlation was found between educational status and estrogen receptor levels in patients over 50 years of age (p = 0,03). When the whole population was evaluated, no statistically significant correlation was shown (p = 0.27). A significant relationship was found between educational status and HER-2 status (p = 0.003), regardless of patients’ age. HER-2 positivity increased in patients with low educational status, however the significant increase was lost in patients over the age of 50 (p = 0.1). Conclusions: The relationship between educational status and biological factors in breast cancer are not conclusive as of yet, but this particular retrospective study revealed that, educational status played a major influence in each of the five breast cancer prognostic factors: hormone receptor status, HER-2 status, tumor size, lymph node status and metastasis.
ASSOCIATION OF CORONARY EPICARDIAL ENDOTHELIAL DYSFUNCTION WITH LOW ENDOTHELIAL SHEAR STRESS IN PATIENTS WITH MILD CORONARY ATHEROSCLEROSIS WHO PRESENTED WITH CHEST PAIN
Authors: Gerasimos Siasos, Jaskanwal Sara, Marina Zaromytidou, Kyoung H. Park, Shi-Wei Yang, Ahmet Coskun, Lilach Lerman, Dimitris Fotiadis, Lampros Michalis, Michail Papafaklis, Kostas Stefanou, Michelle Lucier, Charles Feldman, Amir Lerman, Peter Stone
Journal: Journal of the American College of Cardiology (2017)
Particularités cliniques et endoscopiques des hémorragies digestives sous anticoagulants oraux directs: à propos d'une série multicentrique française
Authors: D Deutsch, P Romegoux, C Boustiere, JM Sabate, R Benamouzig, P Albaladejo
Journal: Endoscopy (2017)

Les anticoagulants oraux directs (AODs), anti-IIa pour le Dabigatran et anti-Xa pour le Rivaroxaban et l'Apixaban, représentaient 30% des prescriptions d'anticoagulants oraux en 2014. Leur prescription dans la prise en charge de la fibrillation atriale non valvulaire et dans la maladie thromboembolique veineuse semble associée à un moindre risque hémorragique global (notamment cérébral) mais au prix d'une possible augmentation du risque d'hémorragie digestive (RR 1,25). A notre connaissance, il n'existe pas à ce jour de série décrivant les hémorragies digestives sous AODs. Le but de ce travail était de décrire les particularités cliniques et endoscopiques des patients présentant une hémorragie digestive sous AODs.
RIGHT-SIDED VENTRICULO-ARTERIAL COUPLING INDICES ARE ASSOCIATED WITH CLINICAL OUTCOMES AMONG PATIENTS RECEIVING BIVENTRICULAR IMPELLA (BIPELLA) SUPPORT FOR CARDIOGENIC SHOCK
Authors: Sudeep Kuchibhotla, Michele Esposito, Michael Kiernan, Mark Grise, Dennis Morris, Duc Thinh Pham, Navin Kapur
Journal: Journal of the American College of Cardiology (2017)
Final updated results of the NRG Oncology/NSABP Protocol P-2: Study of Tamoxifen and Raloxifene (STAR) in preventing breast cancer.
Authors: Donald Lawrence Wickerham, Reena S. Cecchini, Victor G. Vogel, Joseph P. Costantino, Walter M. Cronin, Therese Bartholomew Bevers, Louis Fehrenbacher, Eduardo R. Pajon, James Lloyd Wade, Andre Robidoux, Richard G. Margolese, Joan M. James, Carolyn D. Runowicz, Patricia A. Ganz, Steven E. Reis, Worta J. McCaskill-Stevens, Leslie G. Ford, V. Craig Jordan, Norman Wolmark
Journal: Journal of Clinical Oncology (2015)

1500 Background: NSABP P-2 (STAR) was a randomized, double-blinded trial of tamoxifen vs raloxifene for the reduction of breast cancer incidence. The initial report from 2006 found raloxifene to be as effective as tamoxifen in preventing invasive breast cancer, but with fewer associated toxicities. In 2010 updated results indicated that raloxifene retained 76% of the effectiveness of tamoxifen in preventing invasive breast cancer and remained less toxic. Methods: May 31, 2012, STAR was permanently closed to followup. This current and final update is based on data through the end of followup for invasive and noninvasive breast cancer, other cancers, vascular events, and deaths. The final analysis comprises the same 19,490 women (9736 in the tamoxifen group and 9754 in the raloxifene group) as the 2010 update report. The median time of followup as of May 31, 2012, was 9.7 yrs. Results: Similar to the previous update, raloxifene remains less effective in preventing invasive breast cancer than tamoxifen (RR = 1.19, 95% CI = 1.04–1.37). For noninvasive breast cancer, the borderline statistically significant difference between treatment groups seen in the original findings continues to decrease (RR = 1.09, 95% CI = 0.88–1.36). Raloxifene also continues to have a better profile than tamoxifen re thromboembolic events (RR = 0.80, 95% CI = 0.66–0.96) and uterine cancer (RR = 0.56, 95% CI = 0.40–0.79). There were no statistically significant differences between treatment groups for any other site of cancer. There was, however, a borderline statistically significant all-cause mortality difference between the treatment groups. The death rates per 1000 in the raloxifene and tamoxifen groups were 4.10 and 4.73, respectively (RR = 0.87, 95% CI = 0.75–1.00). Conclusions: Raloxifene has retained approximately 81% of the effectiveness of tamoxifen in preventing invasive breast cancer and continued to grow closer to tamoxifen in preventing noninvasive breast cancer. Raloxifene has also maintained a better profile with respect to uterine disease, thromboembolic events, and death. Support: U10CA37377, -69974; -180868 -180822; -189867; -44066; Elli Lilly and Company; AstraZeneca Clinical trial information: NCT00003906.
A RARE CAUSE OF MYOCARDIAL INJURY IN A PATIENT WITH SYSTEMIC LUPUS ERYTHEMATOSUS: HYDROXYCHLOROQUINE INDUCED CARDIOMYOPATHY
Authors: Shakil Shaikh, Vikram Grewal, Ahmad Turk, Jaime Hernandez Montfort, Mara Slawsky, Josephine Chou Catanzaro
Journal: Journal of the American College of Cardiology (2017)
Differences in biomarker expression in HNSCC according to p53 status.
Authors: Rebecca Anne Feldman-Moreno, Ariane C. Kemkes, Joanne Xiu, Richard Blevins, Paula Esmay, Leslie Battaglia, Katrina Radebach, Inga Rose, Curtis Johnston, Zoran Gatalica
Journal: Journal of Clinical Oncology (2012)

5523 Background: Patients with p53 wildtype head and neck squamous cell carcinoma (HNSCC) tend to be HPV-positive, which associates with better prognosis. The purpose of this study was to explore biomarker expression profiles for insight into molecular differences in HNSCC patients based on p53 status. Methods: TP53 gene sequencing using the AmpliChip p53 microarray (Roche Molecular Systems, Inc.) was attempted on 61 HNSCC patients previously tested with Caris Target Now tumor profiling service. DNA was extracted from a FFPE sample, amplified and processed on the AmpliChip p53 microarray to detect single base pair substitution and deletion mutations in exons 2 - 11 and their flanking splice sites in the TP53 gene (GenBank X54156). EGFR FISH , HER2 IHC and 22 other predictive biomarkers, e.g. TS, TOPO2A, MGMT, etc., were assayed and retrospectively analyzed. All tests were performed in a CLIA-certified lab and interpreted by board-certified pathologists or cytogeneticists. Statistical analysis was performed using SPSS (PASW statistics17) for parametric and non-parametric tests of independence. Results: 52 cases provided sufficient quality DNA for p53 analysis and results revealed a mutation rate of 25% in HNSCC patients. Interestingly, only EGFR FISH and HER2 IHC (p=.002 and p=.004, respectively) were differentially expressed in wildtype vs. mutated p53. Matched-pair analysis in the p53 mutated subgroup (n=13) showed no significant trend regarding EGFR status (p=.763) but a slight trend towards HER-2 negativity (p=.020). In the p53 wildtype subgroup (n=39), a strong association with EGFR FISH non-amplification (n=28, 71.8%, p&lt;.001) as well as HER-2 negativity (n=38, 97.4%, p&lt;.001) was shown. Conclusions: To our knowledge, this is the first analysis of differential biomarker expression profiles in HNSCC based on p53 status. We hypothesize that the absence of EGFR amplification in the p53 wildtype cancers may be a contributing factor to the improved prognosis observed in HPV-positive HNSCC. Additionally, the strong association between p53 wildtype HNSCC patients and EGFR non-amplification suggests EGFR-targeted therapies like cetuximab would likely fail in p53 wildtype patients.
Heterogeneous prevalence of somatic mutations in <i>KRAS</i>, <i>BRAF</i>, and <i>PIK3CA</i> genes among patients with colorectal carcinoma: Clues from Sardinia.
Authors: Grazia Palomba, Maria Colombino, Antonio Silverio Contu, Bruno Massidda, Giovanni Baldino, Antonio Pazzola, Maria Teresa Ionta, Francesca Capelli, Vittorio Trova, Tito Sedda, Francesco Tanda, Giuseppe Palmieri, Antonio Cossu
Journal: Journal of Clinical Oncology (2012)

e14094 Background: Role of KRAS, BRAF and PIK3CA mutations in pathogenesis of colorectal cancer (CRC) has been mostly clarified. In this population-based study, we investigated the incidence rates and roles for such somatic mutations in genetically isolated population of Sardinia. Methods: From April 2009 to July 2011, formalin-fixed paraffin-embedded tissues (n=478) were prospectively collected from Sardinian CRC patients at clinics across the entire island. Genomic DNA was isolated from tissue sections and screened for mutations in KRAS, BRAF, and PIK3CA genes by automated DNA sequencing. Results: Overall, KRAS tumor mutation rate was 30% (145/478 positive cases). Distribution of mutation carriers was however different within the island: 87/204 (43%) in North Sardinia vs. 58/274 (21%) in Middle-South Sardinia (p=0.023). Among 384 CRC cases whose DNA was available, only one (0.3%) mutation in BRAF gene was observed; conversely, PIK3CA was found mutated in 158/384 (41%) patients. An inverse distribution of PIK3CA mutation rates was observed within Sardinian population: 60/181 (33%) cases from northern vs. 98/203 (48%) cases from central-southern island. This heterogeneity in frequencies of KRAS/PIK3CA somatic mutations is consistent with already-reported discrepancies in distribution of germline mutations for other malignancies within Sardinian population. Preliminary clinical evaluation of 118 KRAS wild-type patients undergoing anti-EGFR-based treatment indicated lack of role for PIK3CA in predicting response to therapy in our series. Conclusions: Our findings further support the hypothesis that patients’ origin and genetic background may contribute to even determine the incidence rate of somatic mutations in candidate cancer genes.
포스터전시 : 원발성 간암의 폐 및 뼈전이를 평가하는데 있어서 PET-CT의 유용성; 폐컴퓨터 단층촬영 및 뼈스캔과의 비교 (초)
Authors: 김상균, 김영석, 정승원, 장재영, 이세환, 박종규, 문종호, 김홍수, 이문성, 김부성
Journal: Clinical and Molecular Hepatology (2010)