tbuckley/cabot-search huggingface dataset:
Molecular classification of gastric cancers by parallel examination of multiple gene amplifications.
Authors: Petra Minarikova, Lucie Benesova, Barbora Belsanova, Inna Tuckova, Frantisek Belina, Ladislav Dusek, Miroslav Zavoral, Marek Minarik
Journal: Journal of Clinical Oncology (2014)

74 Background: Gastric cancer is characterized by heterogeneity in morphology as well as on the molecular level resulting in diverse response to anticancer therapy. The subtypes are currently recognized based on histology (Lauren classification). The aim of this work was to investigate an alternative approach for description of inherent molecular mechanisms resulting in its biological behavior. Methods: Genomic DNA was extracted from formalin-fixed paraffin-embedded (FFPE) sections from 80 patients with histologically confirmed gastric cancer. A set of 70 genes was simultaneously examined by Multiplex Ligation-dependent Probe Amplification (MLPA) technique. The obtained gene amplification patterns were processed by hierarchical data clustering and evaluated in combination with clinical patientd data by multifactorial analysis. Results: The overall success rate of DNA extraction from the gastric FFPE samples was at a level of 85%. As expected HER2, MYC, p16 and b-catenin genes were among the most frequently amplified. Both statistical approaches delivered similarities in data clustering. The resulting dendrograms revealed comparably constituted subclusters of samples. Conclusions: Presence of specific gene amplification resulting from aberrant activation of various signaling pathways indicate distinct tumor characteristics that may lead to specific tumor behavior. A correlation to monitoring parameters such as progression-free survival or overall survival is ongoing. Supported by the Czech Ministry of Health grant no. NT13640.
With quality and safety for all: Risking optimal care with VIP patients.
Authors: Sandra Blackburn
Journal: Journal of Clinical Oncology (2016)

142 Background: The person deemed a VIP is generally considered differentiated from the average person by virtue of fame, notoriety (positive or negative), or success through talent, tenacity or simple luck. Because society often views VIPs as special, this can generate strong feelings ranging from excitement and awe to resentment in those who encounter a VIP. VIPs and/or their entourage may request or demand special attention. The unique factors associated with caring for a VIP can jeopardize patient safety and optimal care of the VIP patient. Methods: Typology associated with the labeling of VIP patients will be used as a framework. For example, an objective VIP patient is someone who is indisputably famous or notorious. These individuals are typically in the public eye such as a famous actress, professional athlete, elected official or rock star. Persons who are subjectively designated as a VIP are usually labeled by a person of power or authority such as a hospital administrator or the Development office and they are largely unknown until they are so designed as a VIP in a specific facility. They may be the brother-in-law of the hospital CEO or a major benefactor who has a low or unknown public profile. Both objective and subjective VIPs pose problems because of the expectations placed on staff whether implied or explicit. Results: This presentation will review typical operational problems and named syndromes that are associated with the medical care of the VIP patient. These syndromes typically outline how the whirlwind of activity and expectations surrounding a VIP patient can cause a flummoxed staff to make decisions that can lead to worse care for the patient. Conclusions: For example, ‘Chief Syndrome’ is a demand, request, or intentional substitution for the “top person” in a department to provide care to the VIP patient. Problems can result if the top person, or chief, has been behind an administrative desk for the past five years and they are not as practiced as a usual provider who sees patients daily. Other cautionary notes and preventable actions that can lead to sub-optimal care of the VIP patient will be presented.
mTOR/P70S6K signaling pathway as a potential target for advanced gallbladder cancer therapy.
Authors: Juan Carlos Roa, Pamela Leal, Helga Weber, Patricia Garcia, Alejandra Sandoval, Kurt Buchegger, Oscar Tapia, Bruno Nervi, Manuel Grez
Journal: Journal of Clinical Oncology (2014)

242 Background: Gallbladder cancer (GBC) is a highly malignant tumor usually diagnosed at advanced stages and characterized by a poor prognosis. Effective therapeutic strategies are urgently needed to improve the prognosis of GBC patients. Our objective was to analyze the expression of mTOR/p70S6K pathway in primary tumors and GBC cell lines, and to evaluate the effect of mTOR inhibitors in in vitro and in vivo models of GBC. Methods: The expression of mTOR/p70S6K signaling pathway components was examined by immunohistochemistry in primary tumors and chronic cholecystitis (CC), and by Western blot in eight GBC cell lines. The in vitro effect of mTOR inhibitors (LY294002, Rapamycin, Everolimus and AZD8055) on cell viability and migration was assessed by MTS and Transwell chamber assays. The therapeutic effect of Rapamycin was evaluated in subcutaneous tumor models (NOD/SCID mice). Treatment started when tumor volumes had reached 100mm 3 . Animals (G-415 and TGBC-2TKB xenografts) were randomly divided (n=5 per group) and treated with Polietilenglicol solution as vehicle and 10mg/kg of Rapamycin, daily IP injection (5 days/week for 3 weeks). Mice were sacrificed 30 days after treatment and tumors were dissected and measured. Tumor volume was calculated as π/6 × (large diameter) × (small diameter) 2 . Results: Our findings indicate that mTOR/p70S6K pathway is frequently activated in GBC (&gt;60% of tumors showed high expression of phospho-mTOR and phospho-p70S6K, compared to CC). GBC patients whose tumors overexpressed phospho-mTOR had a poorer prognosis (p=0.02). G-415 and TGBC-2TKB cells showed a constitutive activation of this pathway and the treatment with different mTOR inhibitors significantly reduced their viability and migration capacity (p&lt;0.001). In subcutaneous tumor models, treatment with Rapamycin significantly reduced the weight and tumor volume compared with the control group (p&lt;0.001). Conclusions: mTOR/p70S6K signaling pathway is frequently activated in gallbladder cancer tissues and cells lines, which suggest that this pathway is a potential therapeutic target for the treatment of advanced GBC, using Rapamycin or other specific inhibitors. Supported by FONDECYT 1090171 and DIUFRO DI11-0039.
Laparoscopic hysterectomy versus abdominal hysterectomy in early-stage endometrial cancer.
Authors: M. J. Mourits, C. J. Bijen, K. M. Vermeulen, A. G. Zee, G. de Bock
Journal: Journal of Clinical Oncology (2010)

5054 Background: To investigate the cost-effectiveness in early stage endometrial cancer patients treated by total laparoscopic hysterectomy (TLH) versus total abdominal hysterectomy (TAH). Methods: A multicentre RCT, including 21 hospitals in the Netherlands. Only skilled laparoscopic surgeons, proven by an assessment, participated. Patients with clinical stage I endometrioid adenocarcinoma or complex atypical hyperplasia were randomized (2:1) for TLH or TAH. In total 275 patients were required to detect a significant difference of 15% in major complication rate between TLH and TAH (80% power; α-0.05). Effectiveness was expressed as major complication rate, as assessed by an independent complication review board. Costs were evaluated from a societal perspective including operative procedure costs, hospital stay and costs incurred during the postoperative period over a three months time horizon. Analysis was by intention-to-treat. Results: In total, 283 patients were randomized (TLH n = 187; TAH n = 96). The major complication rate was 14.6% in the TLH group versus 14.9% in the TAH group (p = 0.95). The intra operative major complication rate during TLH (2.7%) was lower than during TAH (4.3%) (NS). Conversion occurred in 10.8% of the laparoscopic procedures. Total costs for a TLH were €3,453 and €3,577 for a TAH. An amount of €3,700 will be saved per additional major complication-free patients in case of performing TLH instead of TAH. Conclusions: TLH is as safe and as cost effective as TAH on the condition of ‘skilled surgeons in early-stage endometrial cancer patients. No significant financial relationships to disclose.
Stereotactic body radiotherapy (SBRT) for effective palliation of lung tumors.
Authors: A. P. Sandhu, B. S. Gill, D. Kim, L. Bazhenova, W. L. Read, P. D. Nobiensky
Journal: Journal of Clinical Oncology (2011)

e19632 Background: Numerous studies have reported excellent local control using SBRT for treatment of early-stage non-small cell lung cancer. We report our single institution experience in using protracted course of SBRT (compared to standard 3-5 fractions used for curative intent) as a palliative treatment for lung tumors. Methods: Patients with symptomatic lung lesions treated with palliative intent SBRT were retrospectively reviewed. These patients were not amenable to curative treatment due to previous irradiation, large sized lesions, or advanced disease. Patients received 50-52 Gy in 10-12 fractions daily for 2 weeks. Results: Ten patients, 5 males and 5 females, were treated over a three-year period. Seven primary, 2 metastatic, and 1 recurrent primary lesions were treated. Ages ranged from 41-84 with a mean age of 72 years. With a median follow-up of 11.5 months, the median overall survival was 18 months. Of 14 symptoms that were treated, 9 (64%) had complete resolution (Table). Two symptoms treated (14%) partially improved and two symptoms (14%) did not respond. One symptom (7%) worsened following treatment. The median time to response was 27 days. Symptoms relapsed in three patients with median time of 3.7 months. A majority of patients (70%) remained symptom free until last follow-up. None of the patients experienced grade 3 or higher toxicity. Conclusions: SBRT is a safe, effective, and durable treatment modality for palliating lung tumors that are not suitable for curative treatment. Symptom characteristics and response rates. Number treated Initial response Relapse Complete improvement Partial improvement Stable Worsening Pain 3 2 (67%) 1 (33%) 0 (0%) 0 (0%) 1 (33%) Cough 4 2 (50%) 0 (0%) 1 (25%) 1 (25%) 2 (50%) Dyspnea 5 3 (60%) 1 (20%) 1 (20%) 0 (0%) 1 (20%) Hemoptysis 2 2 (100%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 14 9 (65%) 2 (14%) 2 (14%) 1 (7%) 3 (21%)
A comparison of surgical resection for distal esophageal, gastroesophageal junction, and proximal gastric cancers in the Memphis metropolitan area (MMA).
Authors: M. C. Evangelist, W. S. Orr, M. Ul-Haq, A. Farooq, A. Khattak, J. Denbo, A. Mahmoud, R. A. Dilawari, J. C. Sachdev, R. U. Osarogiagbon
Journal: Journal of Clinical Oncology (2011)

147 Background: The incidence of distal esophageal (DE) and gastroesophageal junction (GEJ) tumors has increased rapidly in recent decades. They are often included in gastric cancer trials. The 7th AJCC staging has reclassified tumors of the DE, GEJ, and proximal stomach (PS) as esophageal cancers. We compared the historical management of these tumors in our community. Methods: Review of all curative-intent DE, GEJ, and PS cancer resections at two healthcare institutions in the MMA from 1999-2008. Results: Seventy patients were identified (Table). Males predominated. The histology was adenocarcinoma in 48% of DE, 91% of GEJ, and 100% of PS cancers. Preoperative endoscopic ultrasound (EUS) was performed in 10% of DE, 6% of GEJ, and 7% of PS patients. Neoadjuvant therapy was given to 29% of DE, 35% of GEJ and 0% of PS patients. R0 resection rates were similiar. Fewer DE and GEJ patients had up to 15 lymph nodes removed, yet lymph node metastasis was identified in 52% and 35% respectively, compared to 20% of PS patients (Table). Five-year survival rates were numerically higher in the DE and GEJ patients. Conclusions: We identified differences in DE, GEJ, and PS tumors in a community setting with respect to preoperative management and lymph node sampling. Reclassification of DE, GEJ, and PS tumors by the AJCC suggests these groups now be treated uniformly as esophageal cancers, a shift from previous management as gastric cancers. Further, prospective evaluation is needed to assess the patterns of management and outcomes in tumors of the DE, GEJ and PS. [Table: see text] No significant financial relationships to disclose.
Clinical Impact of Complex Karyotype, Monosomal Karyotype and Acquisition of Chromosomal Abnormalities in Patients with Myelodysplastic Syndromes
Authors: June Takeda, Hiroshi Kawabata, Kazunari Aoki, Shuichi Shiga, Masahiro Kawahara, Toshio Kitawaki, Masakatsu Hishizawa, Tadakazu Kondo, Toshiyuki Kitano, Noboru Yonetani, Sumie Tabata, Nobuhiro Hiramoto, Akiko Matsushita, Hisako Hashimoto, Takayuki Ishikawa, Norimitsu Kadowaki, Akifumi Takaori
Journal: Blood (2014)
Survival outcomes of patients with multiple myeloma (MM) achieving stringent complete response (sCR) following upfront autologous stem cell transplantation (SCT).
Authors: P. Kapoor, S. Kumar, A. Dispenzieri, M. Lacy, D. Dingli, S. R. Hayman, F. Buadi, P. R. Greipp, R. A. Kyle, S. V. Rajkumar, M. A. Gertz
Journal: Journal of Clinical Oncology (2011)

8069 Background: sCR, a category introduced in the uniform response criteria for MM is becoming an attainable therapeutic goal with strategies combining novel agents and SCT. In addition to the criteria for CR, sCR requires normalization of serum free light chain (FLC) ratio and absence of clonal cells as determined by the marrow immunofluorescence or immunohistochemistry (IHC). Our previous report comparing this response category with CR had demonstrated an improvement in the time to progression but not overall survival (OS). Herein we report the results of a study evaluating the prognostic value of varying degrees of CR [nCR (near CR or immunofixation-positive CR), CR and sCR] in a cohort of patients with extended follow-up who underwent SCT within 12 months of their diagnosis of MM. Methods: The medical records of prospectively followed 659 consecutive MM patients who underwent SCT from 09/14/2002 through 6/30/2009 were reviewed. To determine the best response achieved after 60 days of SCT, we utilized the traditional serum and urine monoclonal protein studies in addition to the FLC assay and IHC. OS was estimated by the Kaplan Meier method and the curves were compared by Log-Rank test. Results: One hundred and eighty-nine patients undergoing SCT within 12 months of their diagnosis had attained varying degrees of CR (24% nCR, 15% CR and 61% sCR) as their best response. The median estimated follow up of the cohort was 58 months from diagnosis and 53 months from SCT. The median OS from diagnosis was 53 months for patients achieving nCR (n=46), 59 months for patients achieving CR (n=28), but not reached for those achieving sCR (n=115) as their best response (p=0.0004). The 4-year OS from SCT was 86% and 60% for those achieving sCR and CR, respectively (p=0.007). The OS from SCT was not significantly different between those achieving nCR and CR. Conclusions: Compared to CR and nCR, the attainment of sCR post-SCT represents a greater depth of response with an improvement in OS of myeloma patients. Clinical trials reporting on the response rates should identify patients achieving sCR and CR separately due to markedly disparate outcomes of the two response categories.
Value of FGFR2 expression for advanced gastric cancer patients receiving pazopanib plus CapeOX (capecitabine and oxaliplatin).
Authors: Seung Kim, Young-Woong Won, Jung Hoon Kim, Joon Ho Park
Journal: Journal of Clinical Oncology (2016)

65 Background: The aim of this study was to use immunohistochemistry (IHC) to determine the effect of FGFR2 and VEGFR2 expression on treatment outcomes for patients with metastatic or recurrent advanced gastric cancer (AGC) receiving a combination of pazopanib with CapeOx (capecitabine and oxaliplatin). Methods: We conducted a single-arm, open-label phase II study to determine the efficacy and toxicity of the combination of pazopanib with CapeOx in 66 patients with metastatic or recurrent AGC (ClinicalTrials.gov NCT01130805). IHC analysis of FGFR2 and VEGFR2 was possible in 54 patients (81.8%). Results: Among 54 patients, the median age was 51.5 years (range, 23–72 years). Most patients were men (59.3%). Seven patients (13.5%) had tumor tissues that expressed FGFR2 by IHC. No patients had tumors that expressed VEGFR2. Among 7 patients with tumors with FGFR2 expression, 6 achieved partial response (PR) with a 85.7% response rate and one patient with stable disease. Among 47 patients with tumors without FGFR2 expression, one had complete response and 27 had PR (59.5%). A significant difference in PFS was seen between patients who were positive and negative for FGFR2 using IHC (8.5 vs. 5.6 months, p = 0.050). By prognostic analysis for PFS, only FGFR2 status by IHC (positive vs. negative) had significant prognostic value for predicting PFS. Conclusions: FGFR2 expression by IHC might be a useful biomarker for predicting treatment outcomes of patients with metastatic or recurrent AGC treated with a combination of pazopanib and CapeOx.
Selecting colorectal cancer (CRC) patients for therapy based on mutational analysis by next generation sequencing: Are we analyzing the appropriate tumor?
Authors: J. S. Vermaat, I. J. Nijman, F. L. Gerritse, M. Mokry, W. M. Roessingh, M. Koopman, P. J. van Diest, E. Cuppen, E. E. Voest
Journal: Journal of Clinical Oncology (2010)

3578 Background: Mutational profiles are increasingly used to select cancer patients for appropriate targeted therapies. The primary tumor, excised at an early disease stage, is often used for mutational analysis. However metastases occurring later in the disease may be genetically altered due to tumor progression. To test this hypothesis we studied the mutational profile of a cancer genome of 1,265 genes, including the kinome and pathways concerning epigenetic, cell cycle, apoptotic and angiogenesis genes. Next-generation sequencing was used to analyze genetic tumor changes over time within the same CRC patients. Methods: Formalin-fixed paraffin-embedded primary tumor and corresponding metastasis were collected from 4 CRC patients. We used laser microdissection to obtain > 80% tumor samples. Isolated DNA was enriched for the ‘cancer genome’ using custom DNA capture arrays (Agilent) and sequenced on an AB/SOLiD platform. Sequence data were mapped against the reference genome (GRCh37) and genetic variations (SNPs and indels) were retrieved using custom bioinformatic scripts. Results: All tumor samples were successfully sequenced (mean coverage 111x, range:82-148x). In total 9,675 novel genetic variations were found in the 8 samples. 731 variations were located in coding regions, on which further analysis was focused. On average 126 novel (range:107-148) genetic alterations were observed per primary tumor. More modifications were demonstrated in the corresponding metastases (mean 142, range:123-179). Interestingly, all primary tumors shared 4 novel genetic alterations in CASP9, DFFB, INPP1 and NLRP4. All metastases had 38 similar novel variations, of which DFFB, DPP6, DYSF, KDM4B, KIF1A, NCAPG2, PCBD2, TOP1MT and TRIO were identified more than once. All novel identified alterations potentially affect relevant pathways, e.g., histone modulation, apoptosis or cell cycle. Conclusions: Although primary tumors and metastases share many genetic alterations, there are significant differences that may indicate that therapeutic decisions should be based on real-time information from the metastases to ensure optimal efficacy of targeted therapy. No significant financial relationships to disclose.
Clinicopathologic features of patients with malignant mesothelioma in a multicenter, retrospective study.
Authors: Manlio Mencoboni, Paolo A. Zucali, Giulia Pasello, Adolfo G. Favaretto, Giovanni Luca Ceresoli, maria Grazia Sauta, Matteo Perrino, Fabio De Vincenzo, Valentina Polo, Loredana Urso, Andrea Bruzzone, Lisette DelCorso, Rosangela Filiberti, Gianni Tunesi, Claudio Simonassi, Maria Grazia Covesnon, Antonella La Camera
Journal: Journal of Clinical Oncology (2014)

e18544 Background: Malignant mesothelioma (MM) is an aggressive tumor of mesothelial surfaces. The major risk factor involved in the etiology is environmental and occupational exposure to asbestos. The optimal modality of therapy is controversial. The present study evaluated retrospectively the characteristics and survival of patients (pts) who were examined and treated in 4 different medical oncology centers in Italy. Methods: 185 pts have been included. Results: 78.4% of pts were male, 22,6% female. The median age was 69.6 years (range: 35.7-84.7). PS was 0-1 in 96.2% of pts, 2 or more in 1.6%. 81% of patients had a history of exposure to asbestos. Epithelioid (83.1%) was the most common histology. Sarcomatoid histology was 3,4%, mixed was 4%, unspecified 9,6%. Surgery was used in 15.7 % of pts. Radiotherapy was performed to 22% in a palliative setting. 58% of all pts received only chemotherapy and 15% received chemoradiotherapy after surgery. 37% received BSC.Carbo-Pem was administered to 60% of pts, Carbo-Pem + experimental drug to 9,2% of pts, Cis-Pem to 4,3% of pts. 27,5 % of pts receveid other chemotherapies. At diagnosis, Hb was < 14 gr/dl in 57% of pts, WBC was > 8,300 in 42 %, lactic dehydrogenasis was > 500 in 7% ,platelets were > 400,000 in 16%. These data have been recorded because some reports correlate them with prognosis. Conclusions: this data base is enrolling new pts. Univariate and multivariate analysis between these clinic-pathological data and OS, PFS will be performed in next future.
Age-dependent regulation of remodeling factors during allergic airway inflammation
Authors: K. Dietz, M. De Los Reyes Jimenez, E. Gollwitzer, A. Chaker, U. Zissler, N. Harris, M. Konigshoff, C. Schmidt-Weber, B. Marsland, J. Esser-Von Bieren
Journal: Allergy (2016)

Reference EPFL-CONF-225230View record in Web of Science Record created on 2017-01-24, modified on 2017-05-12