tbuckley/cabot-search huggingface dataset:
Multiple independent methods fail to confirm MET amplification rate reported in literature for metastatic colorectal cancer (mCRC).
Authors: Kanwal Pratap Singh Raghav, Chad Tang, M. Pia Morelli, Hesham M. Amin, Ken Chen, Ganiraju C. Manyam, Bradley McIntosh Broom, AmirAli Talasaz, Michael J. Overman, Kenna Rael Shaw, Funda Meric-Bernstam, Dipen M. Maru, Cathy Eng, David S. Hong, Scott Kopetz
Journal: Journal of Clinical Oncology (2015)

572 Background: MET inhibition is emerging as a potent therapeutic strategy and MET gene amplification has shown predictive significance. MET amplification rate in mCRC, as previously reported in literature, varies from 9% in primary to 18% in metastases but intermixes increased copy number from chromosomal level aberrations with focal gene amplification. Validation of MET amplification rate in mCRC is needed. Methods: We performed analyses of MET amplification in mCRC patients (pts) (n = 636) across multiple cohorts. Cohort 1 (n = 103) included tissue microarray from liver metastases analysed using fluorescence in situ hybridization (FISH) [cMET and CEP7 probes, MET/CEP7 ratio &gt; 2]. Cohort 2 (n = 205) included pts referred for phase I trials who had MET amplification testing using FISH. Cohort 3 (n = 279) included cases sequenced with HiSeq (Illumina) with full exome coverage for 202 genes including MET (average depth 800) with focal gene amplification (≥ 4 copies) identified by an in-house algorithm. Cohort 4 (n = 49) included pts refractory to EGFR monoclonal antibodies enrolled in the ATTACC (a prospective molecular screening) program for mCRC, in whom plasma circulating-free DNA (cfDNA) was analyzed by Guardant sequencing technology. Results: In tissue based analyses, focal MET amplification rate was 1.7% and was higher in primary tumors compared to metastases [3.1% (9/291) vs. 0.4% (1/288), p = 0.02] [Table]. In cohorts 2 &amp; 3 MET amplification was found in 4 [MET/CEP7: 2.1 – 7.7; primary (4/130), metastases (0/75)] and 6 [copy number: 4.0 – 6.7; primary (5/161), metastases (1/110)] cases, respectively. MET amplification rate in pts who had progressed on anti-EGFR therapy was 14.3% (Table). Conclusions: Contrary to prior reports, in this large cohort, MET amplification was a rare event in mCRC pts and the rate was not higher in metastatic sites. However, MET amplification occurred in a sizable subset of pts refractory to anti-EGFR therapy as identified by cfDNA analysis. MET amplification appears to play a minor role in de novo colorectal carcinogenesis but may play an important role in acquired resistance to anti-EGFR therapy. [Table: see text]
An open, multicenter clinical study on cetuximab combined with intensity modulated radiotherapy (IMRT) plus concurrent chemotherapy in nasopharyngeal carcinoma (NPC): Preliminary report.
Authors: T. Lu, C. Zhao, C. Chen, L. Gao, J. Lang, J. Pan, C. Hu, F. Jin, R. Wang, C. Xie
Journal: Journal of Clinical Oncology (2010)

5577 Background: To evaluate the safety and efficacy of cetuximab combined with IMRT + concurrent cisplatin chemotherapy in patients with loco-regionally advanced NPC in a Chinese multicenter clinical study. Methods: Patients with primary stage III – IVb non- keratinizing NPC were enrolled. The planned dose of IMRT to gross tumor volume (GTV) was 66 - 75.9 Gy in 30-33 fractions. Cisplatin (80mg/m2,q3week [w]) and cetuximab (400mg/m2 one w before radiation, and then 250mg/m2/w) were given concurrently for 6 - 7 weeks. The response rate was evaluated according to RECIST, and adverse events (AEs) were graded according to CTCAE v3.0. Results: From July 2008 to April 2009, 100 patients were enrolled with 74 male and 26 female. Median age was 43 years old. The proportion of patients with stage III, IVa and IVb disease was 71%, 22% and 7%, respectively. Actual median dose to GTV was 69.96 Gy. Median dose of cisplatin was 133.17 mg, median first-dose of cetuximab was 690 mg, and median weekly dose was 410 mg. 99% of all included patients finished the planned treatment. AEs were well tolerated and manageable, mainly consisting of acneiform skin eruptions, dermatitis, mucositis, xerostomia and slight ALT elevations (grade 1 - 2). Only one patient had a mild allergic reaction, happening in the first w of cetuximab therapy. 64% of patients had ≥ grade 2 acneiform eruptions, mainly starting at the third week of cetuximab treatment. From the third week of radiotherapy, 58% and 90% of the patients began to suffer from grade 1 dermatitis and ≥ grade 2 mucositis, respectively, while grade 4 mucositis (spontaneous bleeding) was observed in 2% of the patients. 40% of patients experienced ≥ grade 2 xerostomia. Besides mucositis, no other grade 4 AEs were observed. Bone marrow suppression was mild, and only 8%, 4% and 5% patients had ≥ grade 2 decreased ANC, Plt and Hb, respectively. At the third month after treatment, 1 patient died of dysphagia. Clinical remission rate (CR + PR) was 100%. Conclusions: The combined treatment modality of IMRT + concurrent chemotherapy + cetuximab in loco- regionally advanced NPC was well tolerated, with a very encouraging clinical response rate. No significant financial relationships to disclose.
Sensitivity of 6-[F-18]fluoro-L-dihydroxyphenylalanine positron emission tomography for localizing tumors causing catecholamine excess
Authors: H. Fiebrich, A H Brouwers, M. N. Kerstens, M. E. Pijl, I. P. Kema, J. R. de Jong, J. E. van der Wal, W. J. Sluiter, E. G. de Vries, T. P. Links
Journal: Journal of Clinical Oncology (2009)

11064 Background: Positron emission tomography (PET) using the catecholamine precursor 6-[F-18]fluoro-L-dihydroxyphenylalanine ((18)F-DOPA) has emerged as promising technique to localize tumors with catecholamine excess. This study investigated the sensitivity of (18)F-DOPA PET, compared to (123)I-metaiodobenzylguanidine ((123)I-MIBG) scintigraphy and computer tomography (CT)/ magnetic resonance imaging (MRI) in patients with catecholamine excess. METHODS: In a single center prospective study (18)F-DOPA PET was compared to (123)I-MIBG and CT/MRI in patients with catecholamine excess. The performance of each imaging modality was analyzed for individual patients and individual lesions. (18)F-DOPA PET, (123)I-MIBG, and CT/MRI were compared using a composite reference standard derived from all available imaging, clinical and histological information. Sensitivities were calculated and discordance between imaging techniques was compared. (18)F-DOPA PET uptake was measured to determine whole body metabolic burden. Correlations between (18)F-DOPA PET imaging and biochemical data were evaluated. RESULTS: 48 patients were included. The tumor localization was found in 45 patients, 43 with (18)F-DOPA PET, 31 with (123)I-MIBG and 32 with CT/MRI, resulting with surgery in final diagnosis of pheochromocytoma in 40, adrenal hyperplasia in 2, paraganglioma in 2, ganglioneuroma in 1 and 3 unknown (as yet no lesion detected). Per patient based analysis showed sensitivities for (18)F-DOPA PET, (123)I-MIBG and CT/MRI of 90, 65 and 67% (P<.01 (18)F-DOPA PET vs (123)I-MIBG, P<.01 (18)F-DOPA PET vs CT/MRI, P=1.0 (123)I-MIBG vs CT/MRI). Corresponding sensitivities in the lesion based analysis were 73, 48 and 44%, respectively (P<.001 for both (18)F-DOPA PET vs (123)I-MIBG and vs CT/MRI, P=.51 (123)I-MIBG vs CT/MRI). The (8)F-DOPA PET+CT/MRI combination was superior to (123)I-MIBG+CT/MRI (93 vs 76%, P<.001) Whole body metabolic burden measured with (18)F-DOPA PET correlated with plasma free normetanephrine (r=.82) and 24h urinary total normetanephrine (r=.84) and metanephrine (r=.57). CONCLUSIONS: The sensitivity of (18)F-DOPA PET to localize tumors with catecholamine excess is superior to either (123)I-MIBG scintigraphy or CT/MRI. No significant financial relationships to disclose.
Sunitinib in papillary renal cell carcinoma (pRCC): Results from a single-arm phase II study.
Authors: E. R. Plimack, E. Jonasch, B. N. Bekele, W. Qiao, C. S. Ng, N. M. Tannir
Journal: Journal of Clinical Oncology (2010)

4604 Background: Frontline sunitinib has been shown to produce a high response rate (RR), and improved progression-free survival (PFS) and overall survival (OS) in patients (pts) with clear cell RCC (ccRCC). Retrospective data suggest sunitinib may be effective in papillary and chromophobe RCC. We initiated a phase II trial of sunitinib in non-clear cell RCC (nccRCC), and report here on the pRCC subset. Methods: A two stage design was used to evaluate sunitinib (50 mg daily, 4 weeks on 2 weeks off) in nccRCC. Eligibility criteria included PS 0-2, measurable disease, and a maximum of 2 prior regimens. Pts with brain metastases were not excluded. Response assessment was performed at 6 wks, 12 wks and at 12 wk intervals thereafter. Primary endpoints were RR and PFS. Secondary endpoints were safety and OS. Results: Between 3/2007 and 5/2009, 23 pts with pRCC were enrolled (total nccRCC accrual 48). Median age was 64 (44-80). Fifteen pts (65%) had prior nephrectomy. Three pts (13%) had poor risk and 14 (61%) had intermediate risk disease by MSKCC criteria. Two pts had type I, 8 had type II, and 13 had pRCC type not specified. Three pts discontinued protocol treatment due to toxicity prior to completion of cycle 1 (one pt had MI 12 days after start of therapy), leaving 20 pts evaluable for response and PFS. All 23 pts were evaluable for toxicity and OS. There were no major responses. Eight pts had stable disease as best response. The radiologically assessed 6-mon PFS rate was 0.34 (95% CI, 0.18- 0.63). Median PFS was 1.6 months (95% CI, 1.3-12). Fifteen pts have died resulting in a median OS of 10.8 months (95% CI, 6.2-NE). Fewer disease sites, better performance status, prior nephrectomy, and normal baseline albumin and LDH levels correlated with longer OS. Common (> 1 pt) treatment related grade 3/4 toxicities included fatigue (6 pts), hypertension (3 pts), mucositis (3 pts), neutropenia (3 pts) and thrombocytopenia (2 pts). Dose reduction or interruption was required in 9 pts (39%). There were no treatment related deaths. Conclusions: In this phase II trial, sunitinib yielded no major responses and short PFS and OS underscoring the need to develop more effective therapies for pRCC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer
DNA aneuploidy and cell proliferation in relation to histology and prognosis in patients with Hodgkin's disease
Authors: F.L. Erdkamp, W.P. Breed, H.C. Schouten, W.C. Janssen, J.J. Hoffmann, J.Th. Wijnen, G.H. Blijham
Journal: Annals of Oncology (1993)
Omalizumab facilitates rapid oral desensitization for peanut allergy
Authors: Andrew J. MacGinnitie, Rima Rachid, Hana Gragg, Sara V. Little, Paul Lakin, Antonella Cianferoni, Jennifer Heimall, Melanie Makhija, Rachel Robison, R. Sharon Chinthrajah, John Lee, Jennifer Lebovidge, Tina Dominguez, Courtney Rooney, Megan Ott Lewis, Jennifer Koss, Elizabeth Burke-Roberts, Kimberly Chin, Tanya Logvinenko, Jacqueline A. Pongracic, Dale T. Umetsu, Jonathan Spergel, Kari C. Nadeau, Lynda C. Schneider
Journal: Journal of Allergy and Clinical Immunology (2016)
Exosomal microRNA as prognostic biomarkers in metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Manish Kohli, Xiaoyi Huang, Tiezheng Yuan, Zhifu Sun, Brian Addis Costello, Fernando Quevedo, Winston Tan, Debashis Nandy, Sherri Longenbach, Liang Wang
Journal: Journal of Clinical Oncology (2014)

260 Background: The purpose of this study was to evaluate cell free nucleic acid based biomarkers for prognosis in mCRPC stage. Methods: Uniformly collected blood from mCRPC patients was processed for plasma which was used for exosomal RNA extraction. RNA sequencing was applied to examine microRNA (miRNA) profiles initially in a discovery cohort of 23 mCRPC patients. The sequences from fastq files were mapped to human miRBase (release 19) for known miRNA read counts. A software package (miRDeep2) was used for novel miRNA prediction. Cox regression was used for association of candidate miRNAs with overall survival (OS), defined as time from development of mCRPC to death or last follow up after adjusting for Gleason Score (GS) and time on androgen deprivation (AD) for hormone sensitive disease. miRNAs significantly associated with OS (FDR&lt;0.05) were then validated in an independent cohort of 100 mCRPC subjects using univariate Cox regression. Results: RNA sequencing generated &gt;10 million mappable reads per specimen in the discovery cohort. Among these reads ~50% were known miRNAs which included 1237 unique RNA sequences. Due to low abundance of most RNA transcripts, only miRNAs (n=250) with &gt;/= 32 reads (on average) were analyzed. Four mRNAs (miR-1290, -1246, -375 and a predicted miRNA on chr. 12) were associated with OS(FDR&lt;0.05). These were evaluated as prognotic markers in the independent cohort (N=100) using real time RT-PCR. Median time on AD for this cohort prior to progression to mCRPC was 35.7 (range: 3.5-136) months; median GS was 7; median follow up after mCRPC development was 12.5 (1-41) months at which time 28 patients had died. Elevated expression for miR-1290 and -375 were associated with shorter OS after adjusting for GS and AD time with a Hazard Ratio (HR) for miR-375 of 1.19 (CI: 1.006-1.18); (p=0.04) and a HR for miR1290 of 1.58 (CI:1.01-2.4); (p=0.04). A stronger association with shorter OS was observed for elevated expression of both miRs-HR of 2.02 (CI: 1.1-3.6) (p=0.01). Conclusions: Blood-based nucleic acid assays are easily accessible for biomarker development in mCRPC. Results from this study suggest specific exosomal miRs are of prognostic value in mCRPC and should be validated in larger cohorts.
Abstract 10610: Severity of Hypertrophy and Increased QTc Interval Predict Appropriate ICD Therapies in Hypertrophic Cardiomyopathy
Authors: Belinda Gray, Caroline Medi, Jodie Ingles, Christopher Semsarian
Journal: Circulation (2012)

Background: Hypertrophic cardiomyopathy (HCM) is the leading cause of sudden cardiac death (SCD) in those aged <35 years. Implantation of a cardioverter defibrillator (ICD) is offered to select pat...
Changes in cancer tissue induced by treatment with bevacizumab in metastatic breast cancer.
Authors: G. Kesisis, P. Touplikioti, E. Yiannaki, F. Paulidou, F. Ziouti, M. Koumpanaki, I. Boukovinas, L. Kontovinis, A. H. Kortsaris, K. Papazisis
Journal: Journal of Clinical Oncology (2010)

1134 Background: Bevacizumab in combination with several cytotoxic chemotherapy option has recently emerged as a standard treatment of HER2-negative metastatic breast cancer. This study tries to identify molecular changes induced by treatment with bevacizumab. Methods: 19 patients with metastatic breast cancer were biopsied (only skin, lymph node, breast tumor biopsies were allowed) on day 0 and 15 days after a single administration of bevacizumab (10mg/kg intravenously infused over 90 minutes). RNA was extracted from the tissue and the expression of genes involved in notch signaling were examined with the use of superarray technology (commercially available through Bioscience Corporation). At the same time points blood samples were drawn from the patients and were tested for the presence of CEC (circulating endothelial cells) with FACS and angiogenic factors with ELISA. Patients enrolled had a PS of 0-1, adequate liver and kidney function and no contraindications for the use of bevacizumab. Results: Although expression of Notch receptors was not altered with a single dose of bevacizumab, increased expression of Notch target genes such as Hey1 and Hey2 was observed. Expression of Jag-2, ADAM-10, ADAM-17, and HOXB4 was also increased. The levels of VEGF increased but CEC and PDGF levels showed mixed responses. Analysis of the results is ongoing. Conclusions: Increased expression of Notch target genes may indicate activation of the Notch pathway in patients treated with bevacizumab. No significant financial relationships to disclose.
Prospective phase II trial of sorafenib combined with doxorubicin eluting bead-transarterial chemoembolization for patients with unresectable hepatocellular carcinoma: Efficacy analysis.
Authors: Jean-Francois Geschwind, Allen Feng, Diane K. Reyes, Ihab R. Kamel, Vivek Gowdra Halappa, Celia Pamela Corona-Villalobos, David Cosgrove, Timothy M. Pawlik
Journal: Journal of Clinical Oncology (2013)

4124 Background: This study reports the final analysis (n=50) of a prospective phase II study evaluating the efficacy of the combination of sorafenib and doxorubicin eluting bead transarterial chemoembolization (DEB-TACE) in patients with unresectable hepatocellular carcinoma (HCC). Methods: Protocol consisted of 6-week cycles with sorafenib at 800 mg/day beginning 1 week prior to DEB-TACE; up to 4 DEB-TACE treatments within 6 months. Tumor response was assessed by RECIST and EASL criteria using MRI at baseline and at 1 month follow-up. Time to untreatable progression (TTUP) was defined as the interval from initiation of sorafenib therapy until inability of patient to further receive intra-arterial therapy. Overall survival (OS) and TTUP were calculated with the Kaplan-Meier method; outcomes were stratified by BCLC A/B and C and compared with the log-rank test. Results: DEB-TACE + sorafenib successfully performed in 50 patients: mean 62yrs (range, 31-88 yrs), Child-Pugh A/B (92%/8%), BCLC A/B/C (10%/28%/62%), ECOG 0/1 (52%/48%), HCV/HBV (44%/8%), mean tumor burden 20%, mean tumor size 7.2cm (range, 1–17.6), and mean tumor enhancement 78%. Patients were enrolled for a median of 3 (range, 1-22) cycles including a median of 1 (range, 0-6) DEB-TACE procedure. Median dose regimen was 400mgQD and the median dose taken while on study was 318 mg/day (range, 100-800). 1 month follow-up showed a mean tumor enhancement reduction of 48.2% (n=46, p&lt;0.001) and an average reduction in lesion diameter of 8.5%(n=48, p=0.02). The Disease Control Rate was 98% using the EASL amendment and RECIST. Median TTUP was 11.9 mths (95% CI, 1.8-22 mths) with a significant difference between BCLC A/B (median 22.9 mths) and BCLC C (median 6.2mths) patients (log-rank, p=0.01). Median OS was 24.5 mths (95% CI, 14.3-35 mths) with a significant difference between BCLC C (median 17.1 mths) and BCLC A/B (median 33.7 mths) patients (log-rank, p=0.001). Conclusions: The results of this phase II study suggest a potential benefit to the combination of sorafenib and DEB-TACE. Single arm and non-randomization are limitations of the study. Clinical trial information: NCT00844883.
Systemic chemotherapy (sCT) plus surgery alone in management of resectable colorectal liver metastasis (RCLM): Systematic review of literature and meta-analisys of randomized clincal trials (RCTs).
Authors: E. Tamburini, D. Tassinari, C. Pittureri, M. Papi, G. Oliverio, F. Desiderio, E. Amaducci, T. Parma, E. Pasquini, A. Ravaioli
Journal: Journal of Clinical Oncology (2010)

e14118 Background: Surgery is considered the only potentially curative approach for patients with RCLM. The role of sCT remains controversial. Methods: A systematic review of MEDLINE, EMBASE and Cochrane Systematic reviews databases from January 1966 to December 2009 was performed independently by two Authors. All randomized phase III trials comparing preoperative, postoperative or perioperative chemotherapy with surgery alone in RCLM were considered eligible and included into the analysis. Primary end point was the progression-free survival (PFS). Heterogeneity between the trials was assessed using the Mantel-Haenszel test, and the pooled odds ratios (ORs) were calculated using a fixed effects model. An alpha error < 5% was assumed as index of statistical significance. All selected trials were analyzed and pondered using the Nicolucci and Jadad score. Results: Electronic searches retrieved 865 citations (390 reviews, 463 clinical trials and 12 systematic revisions with meta-analysis). 642 patients of three trials were included into the analysis. No statistically significant heterogeneity between studies was observed. The study showed a not significant trend favouring adding of sCT to surgery alone: HR PFS = 0.76 (95% CI; 0.55-1.06: p = 0.11). Conclusions: Our data suggest that addition of sCT to surgery alone in RCLM not improve PFS. However the trend observed in favour of chemotherapy group and the lack of properly designed trials do not allow us to find any unanimous conclusions in merit of the role of sCT in RCLM. Further trials are urgently needed to solve these questions both for the great progress of hepatic surgery in metastatic colorectal cancer and for the increasing number of patients radically resected for liver metastases from colorectal cancer. No significant financial relationships to disclose.
Differential impact of additional chromosomal abnormalities in myeloid vs lymphoid blast phase of chronic myelogenous leukemia in the era of tyrosine kinase inhibitor therapy
Authors: Z Chen, J E Cortes, J L Jorgensen, W Wang, C C Yin, M J You, E Jabbour, H M Kantarjian, L J Medeiros, S Hu
Journal: Leukemia (2016)
Abstract 14739: Malnutrition Assessed by Geriatric Nutritional Index Predicts Mode of Death in Patients Admitted With Acute Decompensated Heart Failure
Authors: Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Yusuke Iwasaki, Masato Kawasaki, Kentaro Ozu, Takumi Kondo, Kaoruko Sengoku, Hironori Yamomoto, Tsutomu Kawai, Satoshi Takahashi, Masashi Ishimi, Hideyuki Hakui, Masatake Fukunami
Journal: Circulation (2013)

Backgrounds: Malnutrition is associated with increased mortality risk in patients with heart failure. Prediction of mode of death (sudden cardiac death (SCD) and pump failure death (PFD)) in patien...
Variation in practice, comorbidity, and treatment in newly diagnosed lung cancer patients.
Authors: D. B. Grose, G. Devereux, R. D. Jones, D. Sharma, C. Selby, K. Docherty, D. McIntosh, P. Downer, M. Nicolson, R. Milroy
Journal: Journal of Clinical Oncology (2010)

e12056 Background: Treatment and survival rates within Scotland for patients with lung cancer appear lower than in many other European countries with the 5-year survival being quoted as 5-6% compared with 8%-15% in other European countries and the United States no study of lung cancer has attempted to specifically investigate the association between variation in investigation, comorbidity and treatment and outcome between different centres. Methods: Patient demographics (gender, age, postcode, smoking history), WHO/ECOG performance status (at presentation and estimated 6 months prior) and primary treatment modality were recorded. If a histological diagnosis was not achieved, this, along with the reason(s) why not, was recorded (age, poor performance status, comorbidity, nondiagnostic investigations, patient choice) along with the investigations attempted, clinical/radiologic stage and primary treatment plan. In addition to recording the comorbidities present in each patient, the severity of each comorbidity graded on a four point scale (0-3) using validated severity scales. Data was collected as the patient was investigated and entered in an anonnoymised format into an access database designed for the study. Results: Data was prospectively collected from 882 patients diagnosed with lung cancer in four Scottish centres. A number of statistically significant differences were identified between centres. These included investigation, treatment between centres (i.e., surgical rates), age, tumour histology, smoking history, socioeconomic profile, ventilatory function and performance status. Predictors of declining performance status included increasing severity of a number of comorbidities, age, lower socioeconomic status and specific centres. Conclusions: This study has identified many significant intercentre differences within Scotland. We believe this to be the first study to identify non-tumour factors independent of performance status that together limit the ability to deliver aggressive, possibly radical, therapy to our lung cancer population. It is only by identifying such factors that we can hope to improve upon the relatively poor outlook for the majority of Scottish lung cancer patients. No significant financial relationships to disclose.