tbuckley/cabot-search huggingface dataset:
HER2/neu status in primary breast cancer and in metastatic site as detected using FNA.
Authors: Francesco Giotta, Maria Consilia Asselti, Stella Petroni, Onsina Popescu, Vincenza Rubini, Agnese Latorre, Vito Lorusso, Cosimo Gadaleta, Giovanni Simone
Journal: Journal of Clinical Oncology (2013)

e11502 Background: As for hormonal receptor (ER, PgR), also human epidermal growth factor receptor-2 (HER-2) expression in breast cancer primitive tumor (PT) could be different from that of metastatic site (MS). These differences arise some questions about clinically useful information given and accuracy of methods to detect biological features. Fine Needle Aspiration (FNA) of metastatic sites could be an available tool to characterize biologic pattern of lesions, using immunocytochemical and/or molecular assay. The aim of the study is to compare prognostic and predictive factors obtained from PT and corresponding MS. Methods: Thirty-eight consecutive metastatic breast cancer patients underwent FNA on metastatic sites in order to re-evaluate receptor status, proliferative activity and HER-2/Neu amplification. In MS the material was achieved using FNA with a 21-23 G needle and obtaining monolayer and the corresponding cito-inclusion. MS were localized in liver (21), lung (8) and distant lymph-nodes (9). ERs, PgRs and Ki-67 were detected in both PT and MS, in 38 cases by immunochemistry, whereas HER-2/Neu amplification was detected on citoinclusion in 35 evaluable cases by FISH. Results: ERs, PgRs and Ki-67 were detected in both PT and in MS, in 36, 34, 25 out of 38 cases respectively, showing a significant loss of hormonal receptors and a decreased proliferative activity in MS versus PT (t-test p: 0.0195, &lt;0.0001 and 0.0120 respectively). Regarding to HER-2/Neu amplification, 28 out of 35 evaluable cases were not amplified while 6 were amplified both in PT and in MS (Pearson Test: r=0.9 p: &lt;0.0001). Another case, HER/Neu amplified in TP, after therapy with trastuzumab resulted not amplified in MS. Conclusions: According to other authors, our data demonstrated that the lost of HER/Neu amplification in MS is a possible event and that FNA samples of MS are available for HER/Neu detection.
GEM2005MAS65試験に参加の高齢多発性骨髄腫患者におけるボルテゾミブ+サリドマイドまたはボルテゾミブ+プレドニゾンによる維持療法
Authors: Mateos Maria-Victoria, Oriol Albert, Martinez-Lopez Joaquin, Gutierrez Norma, Teruel Ana-Isabel, DE La Guia Ana Lopez, Lopez Javier, Bengoechea Enrique, Perez Montserrat, Polo Marta, Palomera Luis, DE Arriba Felipe, Gonzalez Yolanda, Hernandez Jose-Mariano, Granell Miquel, Bello Jose-Luis, Bargay Joan, Penalver Francisco-Javier, Ribera Jose-Maria, Martin-Mateos Maria-Luisa, Garcia-Sanz Ramon, Lahuerta Juan-Jose, Blade Joan, F San-Miguel Jesus
Journal: Blood (2012)
Improving cancer treatment handoffs: Wilmot Cancer Institute’s (WCI) ASCO Quality Training Program experience.
Authors: David W. Dougherty, Elizabeth Scarsella, Tammy Clarke, Elizabeth Alvino, Lynn Rich, Sean Goonan, Karen Mietus, Nathaniel Wade, Alex Alongi, Melanie Bobry, Elizabeth A. Guancial, Margaret Blaney, Stephanie Buia Amport, Chintan Pandya
Journal: Journal of Clinical Oncology (2017)

139 Background: Ineffective handoffs contribute to gaps in patient care and medication errors, jeopardizing patient safety and leading to poor quality of care. Ineffective handoffs accounted for 59% of reported medication events at WCI Infusion Center. The completion rate of WCI’s existing electronic medical record (EMR) based free text handoff note for patients treated with anti-cancer therapy on the same day as a clinic visit was 32%. The project aim is to create an effective EMR integrated treatment handoff tool and establish standard workflow processes to ensure optimal communication among WCI providers for improved patient safety and quality of care. Methods: We convened a multidisciplinary team to develop an efficient and safe treatment handoff tool. WCI nurses were surveyed to evaluate the baseline state of the handoff process. Tool development was performed over a series of phases, including creation of a project charter and aim statement, outlining current workflow process, identifying gaps and limitations in the process, identifying potential causes of ineffective hand-off and using a Pareto chart to prioritize them. Utilizing the Situation-Background-Assessment-Recommendation framework, an EMR-integrated handoff tool with standardized workflow process was developed, along with an educational plan for the tool. Results: 52% (N = 22/42) of nurses found the current handoff note to be ineffective at preventing errors and 48% (N = 20/42) identified incomplete or missing information as a significant factor for ineffective communication. Other barriers identified included poor note design, lack of standardization in workflow and variation in note use. During the 1 week implementation of the new handoff tool, the utilization rate was 100% (N = 32) with completion rate of 41% (13 of 32). Further data collection is ongoing and nursing perception of the new tool will be evaluated at 3 months. Conclusions: Multidisciplinary stakeholders’ guided development and implementation of an EMR-integrated treatment handoff tool to optimize the communication between cancer care providers during patient transition is associated with improvement in handoff tool utilization and communication.
Phase I/II trial evaluating the anti-VEGF MAb bevacizumab in combination with erlotinib, a HER1/EGFR-TK inhibitor, for patients with recurrent non-small cell lung cancer
Authors: A. B. Sandler, G. R. Blumenschein, T. Henderson, J. Lee, M. Truong, E. Kim, B. Mass, B. Garcia, D. H. Johnson, R. S. Herbst
Journal: Journal of Clinical Oncology (2004)

2000 Background VEGF and HER1/EGFR play a pivotal role in many types of cancer. Bevacizumab (Avastin) is a recombinant, humanized anti-VEGF MAb, and erlotinib HCl (Tarceva) is a potent, reversible, and highly selective HER1/EGFR tyrosine-kinase inhibitor. Both have demonstrated antitumor activity in patients with previously treated non-small cell lung cancer (NSCLC). In addition, xenograft experiments performed in various tumor types suggest that growth inhibition using bevacizumab plus erlotinib (AT) is greater than with either agent alone. Therefore, there is compelling rationale for using AT as a therapy for NSCLC. Methods A multicenter, Phase I/II study examined AT in patients with either Stage IIIB/IV or recurrent NSCLC treated with at =1 prior chemotherapy regimen. In Phase I, erlotinib 150mg/day p.o. plus bevacizumab 15mg/kg i.v. every 21 days was established as the Phase II dose, although no true dose-limiting toxicities were observed. Phase II examined the efficacy and tolerability of the combination. Pharmacokinetic and pharmacodynamic parameters were monitored. Results Forty patients have been enrolled and treated, including 34 patients at the Phase II dose level. Patient characteristics (n=40) were: median age 59 (range 36–72), 21 female/19 male, 30 with adenocarcinoma histology, and 24 received =2 prior regimens and 3 =3. The most commonly reported adverse events were rash, diarrhea, and proteinuria, which were never more than mild to moderate. Preliminary data indicate no pharmacokinetic interaction between these two agents. Seven patients (17.5%) had partial responses, two (5%) had minor responses, and 14 (35%) had stable disease. The median overall survival and time to progression for patients on the Phase II dose level (n=31) was 9.3 and 4.6 months, respectively. Conclusions The encouraging antitumor activity and favorable safety profile of AT support further development of this combination for advanced NSCLC. A randomized Phase II trial is planned comparing AT with docetaxel plus bevacizumab and docetaxel plus placebo in advanced NSCLC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Inc. Genentech; OSI Genentech, Inc. Aventis; Genentech
Updated safety and efficacy results from a phase I/II study of the oral BRAF inhibitor dabrafenib (GSK2118436) combined with the oral MEK 1/2 inhibitor trametinib (GSK1120212) in patients with BRAFi-naive metastatic melanoma.
Authors: Jeffrey S. Weber, Keith T. Flaherty, Jeffrey R. Infante, Gerald Steven Falchook, Richard Kefford, Adil Daud, Omid Hamid, Rene Gonzalez, Ragini Reiney Kudchadkar, Donald P. Lawrence, Howard A. Burris, Georgina V. Long, Alain Patrick Algazi, Karl D Lewis, Kevin B. Kim, Igor Puzanov, Peng Sun, Shonda M Little, Kiran Patel, Jeffrey Alan Sosman
Journal: Journal of Clinical Oncology (2012)

8510 Background: In preclinical models, the BRAFi/MEKi combination has demonstrated enhanced activity against BRAF-mutant cancer cells compared with either drug alone, delayed emergence of BRAFi resistance, and prevented BRAFi-related proliferative skin lesions. A 3-part study investigating the dabrafenib/trametinib combination was conducted in patients (pts) with V600 BRAF mutant solid tumors. Interim data from the study were previously reported (Infante, ASCO 2011); updated safety and efficacy data are presented. Methods: In Part 2, 125 pts with V600 BRAF mutant solid tumors enrolled, including 77 melanoma pts with no prior BRAFi, and measurable disease according to RECIST 1.1. Pts were treated on 4 escalating dose levels of dabrafenib/trametinib (mg BID/mg QD): 75/1, 150/1, 150/1.5, 150/2. Demographic and efficacy data for the 77 melanoma pts with no prior BRAFi and safety data for all 125 Part 2 pts are reported. Results: Among 77 melanoma pts, median age was 52 years, 61% male, 57% ECOG PS of 0, 91% V600E, 65% M1c stage, 26% prior brain metastases, and 52% LDH &gt; ULN. Confirmed ORR was 56% (95% CI: 44.1%-67.2%) with 4 CR, 39 PR, 29 SD and, 3 PD. Confirmed response rate for each dose level, respectively, was 67% (n=6), 64% (n=22), 48% (n=25), and 54% (n=24). Median PFS (months) for each dose level, respectively, was: 8.7, 8.3, 5.5; PFS is not mature for 150/2. Overall PFS was 7.4 (95% CI: 5.5-9.2). Among the 125 pts, there were 2 grade (G) 5 adverse events (AEs), pneumonia and hyponatraemia. The most common G3/4 AEs were pyrexia (n=6, 5%), fatigue (n=6, 5%) and dehydration (n=6, 5%). Skin toxicity ≥ G2 occurred in 17 (14%) pts. Cutaneous squamous cell carcinoma occurred in 3 (2%) pts and actinic keratoses in 2 (2%). Conclusions: The combination of dabrafenib/trametinib has an acceptable safety profile, with a lower incidence of MEKi-related rash and BRAFi-induced hyperproliferative skin lesions compared with the single agents. The clinical activity of dabrafenib/trametinib observed in pts with V600 BRAF mutant metastatic melanoma is encouraging and will be investigated further in a phase III trial.
Transcatheter and Surgical Aortic Valve Replacement in Patients With End-Stage Renal Disease
Authors: Viraj Bhise, Pushkar Kanade, Ghanshyam P.S. Shantha, Prakash Balan, Tom C. Nguyen, Pranav Loyalka, Biswajit Kar, Anthony Estrera, Richard W. Smalling, Abhijeet Dhoble
Journal: Journal of the American College of Cardiology (2017)
Empowering patients to self-identify financial assistance programs using an online application.
Authors: Jonathan Nicolla, Fred Friedman, Ian Manners, Yousuf Zafar
Journal: Journal of Clinical Oncology (2017)

4 Background: Available financial resources are relatively unknown to many patients with cancer facing high treatment-related costs. PAPNavigator is a web-based app designed to reduce out-of-pocket treatment costs by connecting patients to financial assistance programs specific to them. Traditionally used by financial counselors, PAPNavigator was modified to be patient-facing for this study, testing preliminary usability and effectiveness. Methods: Eligible patients with cancer were receiving anti-cancer treatment and reported out-of-pocket treatment costs. Patients interacted with PAPNavigator, inputted personal and financial data, and reviewed personalized financial resource results. Usability was assessed via the validated System Usability Scale (SUS). Effectiveness was assessed by two measures: “PAPNavigator improved my knowledge about financial aspects of cancer care and what can be done about it” and “Using this website was helpful with my financial concerns.” For all items, patients responded using a 5-point Likert scale. Results: 19 of 20 patients completed pilot testing (95%, 1 withdrew due to illness). 53% of patients were male, 26% were non-white, 79% had greater than a high school education, and 21% were employed full- or part-time. Median annual household income was $77,500. The median SUS score was 75 out of 100 (with &gt;68 considered above average.) In response to statements, “I think that I would need assistance to be able to use this website,” and “I felt very confident using this website,” the median scores were 2 and 5 respectively. Additionally, in response to the statements, “PAPNavigator improved my knowledge about financial aspects of cancer care and what can be done about it,” and “Using this website was helpful with my financial concerns,” the median score for each was 4. Conclusions: The modified version of PAPNavigator demonstrated high usability and preliminary effectiveness in improving knowledge about financial aspects of cancer care and potential interventions to reduce cost. Further testing in larger samples is necessary.
Predictive value of Serum S-100B protein in predicting relapse in patients with melanoma
Authors: R. Lastra, R. Andres, J. I. Mayordomo, E. Ortega, J. Lambea, R. Lara, E. Polo, A. Saenz, J. Godino, A. Tres
Journal: Journal of Clinical Oncology (2004)

7532 Background: S-100B protein is correlated with clinical stage in patients (p.) with melanoma. A few studies have been reported a significant correlation with progression of disease in p. receiving antitumoral treatment. We investigated the value of S-100B a predictor of relapse and survival in p. during follow-up. Methods: From January.02 to October.03 273 peripheral blood samples were obtained from 110 p. diagnosed with melanoma. Serum concentrations of S-100B protein were measured by ELISA. Normal range of S-100B was 0 to 0,150 micrograms/L. Median age was 49.5 years (range 4 - 81), with 55 males and 55 females. 39 (35.5 %) p. were stage I, 21 p. (19.1 %) stage II, 31 p. (28.2 %) stage III and 19 p. (17.3 %) stage IV. Results: Median number of determinations of S-100B was: 2.48 (range:1–5). Median follow-up was 555 days. The frequency of relapse in p with S-100 <0.150 micrograms/L was 8.33 % versus 25.93 % in p with S-100>0.150 in a single determination, and 52.17 % in p with S-100>0.150 in two or more determinations. Stage was an independent factor of progression (p<0.05) but S100B protein was not borderline statistically significant (p= 0.0557)in a multivariate analysis (Cox regression). Conclusions: Level of serum S100B protein is a predictor factor of progression or relapse in melanoma, although should be confirm with more studies. No significant financial relationships to disclose.
AG879, a c-erbB2 tyrosine kinase inhibitor, causes G1 arrest in pancreas cancer cells through p27Kipl independent transcriptional repression of cyclin Dl
Authors: A. N. Salesiotis, R. N. Samara, J. Kauh, L. M. Laguinge, S. Lin, J. L. Marshall, J. M. Jessup
Journal: Journal of Clinical Oncology (2004)

4095 Background: Pancreatic cancer has a poor prognosis because of high cell proliferation and low apoptosis. Cyclin D1 controls cell proliferation and survival and is stimulated by the c-erbB2/HER-2/neu growth factor which is activated in 80% of pancreatic cancer. We postulated that inhibition of c-erbB-2 tyrosine kinase activity by tyrphostin AG879 would block cyclin D1 function through a different mechanism than loss of c-erbB-2 protein expression by siRNA. Methods: COLO-357, L3.6pL and L3.5sL human pancreas adenocarcinoma cell lines were studied. Cell proliferation and apoptosis were measured by MTT assay and flow cytometry. Western blots monitored the expression of cyclin-dependent kinase inhibitors (CDKIs) pl6, ARF, p21, and p27 and cyclin D1, Rb phosphorylation, c-erbB-2, EGFR, and cdk-2/4/6. Cyclin D1 transcription was measured by luciferase-Cyclin D1 promoter construct transfection. Proteosomal function was assessed with Lactacystin. Results: Treatment with either AG879 or c-erbB-2 siRNA induced a G1 cell cycle arrest in 50–80% of cells with apoptosis. Inhibition of c-erbB-2 expression by siRNA increased p27Kipl expression with inhibition of STAT3 activation. However, AG879 treatment did not effect CDKI expression but repressed transcription of cyclin D1 message as well as decreased expression of cyclin D2, CDK 2 and 4 with altered phosphorylation of RB. AG879 did not stimulate proteasome-mediated ubiquitination and degradation of cyclin D1. Conclusions: Tyrosine kinase inhibition of c-erbB-2/HER-2/neu induces cell cycle arrest and apoptosis through a different mechanism from that mediated by decreased expression of growth factor achieved by siRNA. Inhibition of both c-erbB-2 kinase activity and protein expression may be necessary to target c-erbB-2 effectively. No significant financial relationships to disclose.
A French multicentric and prospective validation study for ALK translocation diagnosis in lung adenocarcinomas.
Authors: Sylvie Lantuejoul, Isabelle Rouquette, Hugues Begueret, Helene Blons, Frederique Penault-Llorca, Marie-Christine Copin, Martine Antoine, Paul Hofman, Jean-Philippe Merlio, Anne McLeer Florin, Francoise Galateau-Salle, Jean-Michel Vignaud, Stéphane Garcia, Francoise Thivolet, Mojgan Shisheboran-Devouassoux, Marie Brevet, Veronique Hofman, Audrey Mansuet-Lupo, Claire Danel
Journal: Journal of Clinical Oncology (2013)

8100 Background: ALK rearrangements occur in nearly 5% of NSCLC and lead to a permanent ALK protein activation, targeted by a small molecule, the crizotinib. To date, FISH (Fluorescent In situ Hybridization) is considered as the gold standard to identify ALK abnormalities, but dual testing and pre-screening by immunohistochemistry have been proposed. Methods: The purpose of the study was to compare immunohistochemistry (IHC) using 5A4 and D5F3 Abs, with FISH and quantitative RT-PCR in a series of 500 surgical specimens, collected within one year from 15 French Thoracic Pathology Departments and INCa genetic platforms. Our study was deliberately enriched in ALK positive cases and clinicopathological data were recorded. Results: Among the 459 cases included to date, 340 were both FISH and IHC ALK negative, and 85 were ALK FISH and IHC positive. Fifteen cases were FISH neg/IHC pos, but with low staining scores; 12 cases were FISH pos/IHC neg, most provided by two centers. Seven cases were non interpretable by FISH, but 5 were ALK IHC positive. Regarding RTqPCR, nearly 50% of ALK positive cases presented a variant 1, 30% a variant 3a/b, and less than 5%, variants 2 or 7; 20%were negative or non interpretable. Discordant cases will be further discussed according to the crizotinib response. ALK positive patients were more frequently women (65 vs 42%) and younger than ALK negative patients (mean age 59 vs 64yrs); 72% were non or light smokers, whereas 75% of ALK negative patients were smokers (mean of 41PY). Histologically, most ALK positive and negative tumors presented a solid or acinar predominant architecture and were P63 negative. However, ALK positive tumors were more frequently TTF1 positive (91 vs 76%). Conclusions: 5A4 or D5F3 immunohistochemistry is a reliable and easy technique for routine diagnosis of ALK abnormalities, while FISH and RT-qPCR still dependent on pre-analytic conditions and technical expertise. However, in case of a suggestive clinical presentation, double testing with FISH remains the safer testing option as false negative IHC cases exist.
Cancer-derived Circulating MicroRNAs Promote Tumor Angiogenesis by Entering Dendritic Cells to Degrade Highly Complementary MicroRNAs
Authors: Jiaqi Wang, Huamao Ye, Dandan Zhang, Kai Cheng, Yijun Hu, Xiya Yu, Lei Lu, Jingjing Hu, Changjing Zuo, Baohua Qian, Yongwei Yu, Shupeng Liu, Geng Liu, Chuanbin Mao, Shanrong Liu
Journal: Theranostics (2017)

Understanding the interaction between cancer cells and immunocytes will inspire new cancer therapy strategies. However, how cancer-derived circulating miRNAs modulate such interaction remains unclear. Here we discovered that circulating miR-410-5p, secreted by prostate cancer cells, entered dendritic cells (DCs), with the aid of argonaute-2 protein. The cancer cell antigens stimulated the DCs to produce miR-410-3p, a highly complementary counterpart of miR-410-5p derived from pre-miR-410. The DC-internalized miR-410-5p degraded the miR-410-3p by base pairing and thus inhibited its function in suppressing tumor angiogenesis, promoting tumor growth. Furthermore, blockade of the miR-410-5p upregulated the miR-410-3p to inhibit tumor growth. Our work suggests a new miRNA-mediated role of immunocytes in cancer progression and a new strategy of cancer therapy through suppressing circulating miRNAs.
Possible aids to remove the burdens during informed consent process in clinical trials: A case of National Surgical Adjuvant Study of Breast Cancer 02 (N-SAS BC 02)
Authors: M. Yamauchi, Y. Ohashi, S. Morita, T. Watanabe
Journal: Journal of Clinical Oncology (2004)

6114 Background: To clarify the difficulty in the process of informed consent (IC) in a specific Japanese cancer clinical trial (CT), we surveyed investigators who were taking part in a randomized CT, the N-SAS BC02 which started in December 2001. Methods: During June-July 2003, to 298 doctors, we dispatched a questionnaire which asked the burdens of patients' enrollment to the trial, possible aids which may support both health professionals and patients during the IC process, the time spent for the IC and the number of patients who were explained about the trial and enrolled. Finally we examined the relationship between the patients' accrual rate and each factor mentioned above. Results:119 of 298 (40%) questionnaires were returned. The major obstacles to patient enrollment perceived by doctors are: 1) patient chooses one treatment arm (19.3%), 2) patient does not want to have chemotherapy itself (11.3%), 3) patient refuses one treatment arm (11.3%) and 4) patient's family members are against participating in the CT (4.4%). Aids identified as helpful are: 1) easily-understandable IC form (94.7%), 2) brief leaflet of CT (95.7%) and 3) panel which explains the CT (87.1%). Clinical Research Coordinators (CRCs) are needed, however, their support is rarely provided to this kind of investigator initiated trial in Japan by administrative reason and the limitation of human resource. There is no significant relationship between the accrual rate and possible burdens. Conclusions: The key aspects for high-rate patients' accrual in the investigator initiated CTs are: (1) to consider the family members during the IC process because they seem to have a great impact on patient's decision making and (2) to create the environment where the CRCs can provide constant support to patients. No significant financial relationships to disclose.