tbuckley/cabot-search huggingface dataset:
Prevalence and quantity of circulating tumor cells (CTCs) after adjuvant chemotherapy in patients with HER2-negative early breast cancer (EBC).
Authors: Fabienne Schochter, Ulrich Andergassen, Julia Katharina Neugebauer, Thomas W. P. Friedl, Aurelia Pestka, Julia Kathrin Jueckstock, Bernadette Jaeger, Jessica Christine Salmen, Philip Gm Hepp, Georg Heinrich, Oumar Camara, Thomas Decker, Angelika Ober, Tanja N. Fehm, Klaus Pantel, Peter A. Fasching, Andreas Schneeweiss, Matthias W. Beckmann, Wolfgang Janni, Brigitte Kathrin Rack
Journal: Journal of Clinical Oncology (2013)

e22075 Background: Prevalence of CTCs after adjuvant chemotherapy in patients with EBC might indicate both treatment response and prognosis. Here we present data on CTC prevalence and quantity assessed after chemotherapy in correlation with tumor characteristics and chemotherapeutic treatment in patients with Her2-negative EBC from the German SUCCESS C study. Methods: The SUCCESS C trial is a randomized, open-label, Phase III study comparing disease free survival (DFS) in patients with HER2-negative EBC treated with either 3 cycles of Epirubicin-Fluorouracil-Cyclophosphamide(FEC) followed by 3 cycles of Docetaxel(DOC), or 6 cycles of a anthracycline-free regimen with Docetaxel-Cyclophosphamide(DOC-C). The CTC status at chemotherapy cycle 6 was prospectively evaluated using the FDA-approved CellSearch System (Veridex, USA). Results: Valid data on CTC status after chemotherapy were available for 2,336 patients (78% estrogen receptor positive, 6% pT3 or pT4, 12% pN2 or pN3). CTCs were found in 278 (11.9%) patients (median 1, range 1 – 69 CTCs). One CTC was detected in 164 (59%), two CTCs in 57 (21%), three to five CTCs in 45 (16%), and more than five CTCs in 12 (4%) of these patients. CTC prevalence was not significantly associated with tumor size (pT1, pT2, pT3, pT4), nodal stage (pN0, pN+), grading (G1, G2, G3), histological type (invasive ductal, invasive lobular, other), estrogen receptor status, progesterone receptor status, or treatment arm (FEC-DOC, DOC-C), as revealed by both univariate analyses (Chi-square tests, all p &gt; 0.1) and a logistic regression with CTC prevalence as dependent variable. Conclusions: In about 12% of patients with Her2-negative EBC, CTCs in the peripheral blood were detected at the end of adjuvant chemotherapy treatment. However, neither CTC prevalence nor quantity of CTCs were related to tumor characteristics or type of chemotherapeutic regimen. The low rate of CTC-positive patients might be attributed to the negative HER2 status and reflects therefore the relatively low risk of these patients to develop metastatic relaps. Clinical trial information: NCT00847444.
Preoperative vascular grading in patients undergoing surgery for pancreatic cancer: Does radiologic arterial or venous involvement predict margin status?
Authors: Sanjay S. Reddy, Andreas Karachristos, Karen Ruth, John Parker Hoffman
Journal: Journal of Clinical Oncology (2017)

319 Background: The use of neoadjuvant therapy has been widely used for borderline resectable pancreatic cancer (BLRPC). Controversy exists on the definition of BLRPC, and because of this, we examined the association of vascular involvement and margin status in patients who had initial resection. Methods: Records of 137 patients who had surgery for resectable or BLRPC were collected. Included were radiologist grading of venous/arterial involvement based on preoperative imaging. For patients with both staging recorded, we categorized vascular involvement as none, arterial only, venous only, or both. We examined the association of vascular involvement and margin status using Chi-square tests, and logistic regression. Results: Of 137 patients, all underwent surgery first. 85% had a Whipple without vascular resection, and 13% with. Of 134 patients with Ishikawa staging, there were 63% stage I, 17% stage II, 11% stage III, and 9% stage IV. Of 96 patients with arterial staging, there were 74% stage i, 16% stage ii, and 10% stage iii. Of 93 patients with both Ishikawa and arterial staging recorded, 61% had no vascular involvement, 7% arterial, 14% venous, and 17% had both. Ishikawa stage I-IV was associated with a positive SMA margin, and was seen in 14%, 44%, 53%, and 58%, respectively (p &lt; 0.001). However, for arterial staging the association was weaker, and for arterial stages i-iii, a positive SMA margin was seen in 20%, 40%, and 40%, respectively (p = 0.06). Therefore, Ishikawa staging was more predicative of arterial involvement. Higher Ishikawa staging was associated with increased positive SMV margins; 5%, 26%, 33%, respectively (p &lt; 0.001), while preoperative arterial staging was not predictive (p = 0.63). In logistic regression for any positive margin, only venous staging was significant in predicting a positive margin. Conclusions: The use of imaging in predicting positive margins is more accurate when using a venous grading system as opposed to an arterial one. With a more standard approach of designating degree of vein involvement, and better preoperative imaging, further studies will be needed to substantiate these findings.
Final analysis of phase II study of EZN-2208 (PEG-SN38) in metastatic breast cancer (MBC).
Authors: Cynthia R. C. Osborne, Joyce O'Shaughnessy, Frankie Ann Holmes, Hyun Sue Kim, Darren M. Kocs, Michael S. Steinberg, Paul D. Richards, Svetislava J. Vukelja, Noah C. Berkowitz, Aby Buchbinder
Journal: Journal of Clinical Oncology (2012)

1017 Background: EZN-2208 is a water-soluble PEGylated conjugate of SN38. EZN-2208 results in prolonged exposure of tumors to SN38 via preferential accumulation of EZN-2208 in the tumor and prolonged release of SN38. These data represent the final analysis of our study evaluating EZN-2208 in MBC. Methods: EZN-2208 9 mg/m 2 (SN38 equivalents) was delivered as a 60-minute IV infusion, weekly for 3 wks in 4‑wk cycles. The primary objective was to determine the overall response rate (RR) in female patients with metastatic breast cancer (MBC) who had received prior adjuvant or metastatic therapy with either 1) anthracycline and taxane (AT) or 2) anthracycline, taxane, and capecitabine (ATX). Secondary objectives included evaluation of RR based on tumor receptor status, duration of response, progression-free survival (PFS), overall survival (OS), and safety. Results: Patients with MBC (n=164) were treated with a median (range) of 3.3 (0.3-22) cycles of EZN-2208. The objective response rate (RR) was 20% for AT and 9% for ATX. The clinical benefit rate (CBR=%CR + %PR + %SD ≥6 months) was 41% and 27% in patients in the AT and ATX cohorts, respectively. The RR and CBR among ER+ patients were 11% (10/91 pts) and 41.8% (38/91 pts). In patients who progressed during or within 30 days of prior platinum-containing regimens (Platinum Progressors), the CBR was 20% (8/40 pts). Among triple negative breast cancer (TNBC) patients, the RR and CBR were 22.5% (11/49 pts) and 36.7% (18/49 pts). For TNBC, Platinum Progressors, the CBR was 26.1% (6/23 pts). Overall, most common reported drug-related adverse events were diarrhea, nausea and neutropenia. Conclusions: EZN-2208 has notable activity in patients with previously treated MBC and appears to be an active agent for treatment of TNBC. Patients with TNBC, who had been previously treated with a platinum-based regimen, also derive clinical benefit from EZN-2208. The safety profile of EZN-2208 is acceptable with good tolerability in most patients. Further evaluation of EZN-2208 in MBC in general and TNBC in particular is warranted.
Folate Receptor-Positive Circulating tumor cell detected by LT-PCR based method as a diagnostic biomarker for non-small cell lung cancer.
Authors: Xiaoxia Chen, Fei Zhou, Xuefei Li, Guohua Yang, Ling Zhang, Shengxiang Ren, Chao Zhao, Qin-fang Deng, Wei Li, Guanghui Gao, Aiwu Li, Caicun Zhou
Journal: Journal of Clinical Oncology (2015)

11032 Background: To investigate the diagnostic performance of folate receptor (FR) positive circulating tumor cells (CTCs) in distinguishing non-small cell lung cancer (NSCLC) from lung benign disease by using a novel ligand-targeted polymerase chain reaction (LT-PCR) detection technique. Methods: CTCs were enriched from 3ml peripheral blood by immune-magnetic depletion of leukocytes and then labeled with a conjugate of a tumor-specific ligand folic acid and a synthesized oligonucleotide. After washing off free conjugates, the stripped bound conjugates were analyzed by quantitative PCR. Results: 756 participants (473 patients with NSCLC, 227 patients with lung benign disease, and 56 healthy donors) were randomly assigned to a training set and a test set. The CTC levels in patients with NSCLC were significant higher than those with lung benign disease (P < 0.001) and healthy donors (P < 0.001). Compared with CEA, NSE, and Cyfra21-1, CTCs displayed the highest area under curve (AUC) (training set: 0.815; validation set: 0.813) in the diagnosis of NSCLC, with a markedly sensitivity (training set: 72.46%; validation set: 76.37%) and specificity (training set: 88.65%; validation set: 82.39%). The model combining CTCs with CEA, NSE, and Cyfra21-1 was more effective for the diagnosis of NSCLC than tumor makers alone (sensitivity and specificity in the training set: 84.21%, 83.91%; validation set: 88.78%, 87.36%). In addition, the CTC levels were higher in patients with stage III/IV NSCLC compared with those with stage I/II disease. Conclusions: LT-PCR technique was feasible and reliable for detecting FR-positive CTCs in NSCLC patients and CTC levels could be used as a useful biomarker for the diagnosis of NSCLC.
Clinical characteristics and whole exome/transcriptome sequencing of coexisting chronic myeloid leukemia and myelofibrosis
Authors: Malathi Kandarpa, Yi‐Mi Wu, Dan Robinson, Patrick William Burke, Arul M. Chinnaiyan, Moshe Talpaz
Journal: American Journal of Hematology (2017)

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell (HSC) disorders that can be classified on the basis of genetic, clinical, phenotypic features. Genetic lesions such as JAK2 mutations and BCR-ABL translocation are often mutually exclusive in MPN patients and lead to essential thrombocythemia, polycythemia vera, or myelofibrosis or chronic myeloid leukemia, respectively. Nevertheless, coexistence of these genetic aberrations in the same patient has been reported. Whether these aberrations occur in the same stem cell or a different cell is unclear, but an unstable genome in the HSCs seems to be the common antecedent. In an effort to characterize the underlying genetic events that might contribute to the appearance of more than one MPN in a patient, we studied neoplastic cells from patients with dual MPNs by next-generation sequencing. We observed that most patients with two MPNs harbored mutations in genes known to contribute to clonal hematopoiesis through altered epigenetic regulation such as TET2, ASXL1/2, SRSF2, and IDH2 at varying frequencies (1%-47%). In addition, we found that some patients also harbored oncogenic mutations in N/KRAS, TP53, BRAF, EZH2, and GNAS at low frequencies, which probably represent clonal evolution. These findings support the hypothesis that hematopoietic cells from MPN patients harbor multiple genetic aberrations, some of which can contribute to clonal dominance. Acquiring mutations in JAK2/CALR/MPL or the BCR-ABL translocation probably drive the oncogenic phenotype towards a specific MPN. Further, we propose that the acquisition of BCR-ABL in these patients is frequently a secondary event resulting from an unstable genome.
Pharmacogenetics as predictor of sunitinib and mTOR inhibitors toxicity in patients with metastatic renal cell carcinoma (mRCC).
Authors: Yuksel Urun, Kathryn P. Gray, Sabina Signoretti, David F. McDermott, Michael B. Atkins, Megan E. Lampron, Matthew Freedman, Toni K. Choueiri, Mark M Pomerantz
Journal: Journal of Clinical Oncology (2013)

4570 Background: Single nucleotide polymorphisms (SNPs) in major pharmacokinetics (PK) and pharmacodynamics (PD) pathways of targeted agents may affect the incidence of drug toxicities. Methods: Germline DNA was extracted fromwhole blood or normal kidney parenchyma frommRCC pts of European ancestry in two cohorts: those treated with VEGF-targeted therapy (sunitinib) (n=159) or with an mTOR inhibitor (everolimus or temsirolimus) (n=62). Ten SNPs in 6 candidate genes: CYP3A4 (rs2242480, rs4646437, rs2246709), CYP3A5 (rs15524), ABCB1 (rs2032582, rs1045642), VEGFR2 (rs2305948), NR1I3 (rs2307424, rs2307418), FLT3 (rs1933437) were genotyped using Sequenom iPlex Gold platform. Logistic regression model tested the association of genotype variants with adverse events of 1) grade 3/4 (G3/4) toxicity and G3/4 hypertension (for sunitinib cohort) and 2) grade 3/4 toxicity and all grade pneumonitis (for mTOR inhibitors cohort), adjusted for clinical factors associated with toxicity outcomes. Results: In the sunitinib cohort, median treatment duration was 7.7 months (IQR=3-15.5), 83 (52%) pts had grade 3/4 toxicities and 22 (14%) had grade 3/4 hypertension. Rare variant (AG) of CYP3A4 rs464637 was associated with the reduced risk of grade 3/4 toxicities (4 events/17 cases) vs. wild-type (GG, 73 events/134 cases), (Odds Ratio (OR) = 0.27, 95%CI: 0.08-0.88, p=0.03). No association between SNPs and hypertension was observed. In the mTOR inhibitor cohort, median treatment duration was 3.4 months (IQR=1.4-6), 21(34%) pts had G3/4 toxicities and 27 (43%) had all grade pneumonitis. No association between SNPs and G3/4 toxicities was observed. Rare homozygote (GG) of FLT3 SNP rs1933437 was associated with increased risk of all grade pneumonitis (7 events/ 9 cases) vs. wild-type (AA, 4 events/12 cases), however, given the very small variant group size, further investigation is required to verify the association. Conclusions: The minor allele of SNP rs464637 in the gene CYP3A4 may influence sunitinib toxicity. Further validation is needed to determine if the marker could be used for in targeted therapy dosing strategies and direct patient care. (IQR=Interquartile Range).
The psychological features of patellofemoral pain: a systematic review
Authors: Liam R. Maclachlan, Natalie J. Collins, Mark L.G. Matthews, Paul W. Hodges, Bill Vicenzino
Journal: British Journal of Sports Medicine (2017)

Background Patellofemoral pain (PFP) is prevalent in adolescence and adulthood and often persists. In contrast to other persistent musculoskeletal conditions, for which non-physical, psychological features are implicated, PFP remains largely conceptualised in mechanical terms. Aims To (1) identify whether the psychological characteristics of individuals with PFP differs from asymptomatic controls and (2) evaluate the correlations between psychological characteristics and PFP severity. Study design Systematic review Methods A systematic review of the literature was conducted according to PRISMA guidelines. The Epidemiological Appraisal Instrument was used to evaluate quality. Studies measuring psychological constructs with patient-reported measures were included. Standardised mean differences were calculated and supported by narrative synthesis. Results Twenty-five studies were eligible. Quality results ranged from 28.3% to 61.7%. Psychological constructs were reported under four groupings: mental health, cognitive factors, behavioural factors and other factors. There is limited evidence of mental health and cognitive differences in some individuals with PFP. Features demonstrating linear correlations with pain and physical function included anxiety/depression, catastrophising, praying and hoping and pain-related fear. Conclusions Anxiety, depression, catastrophising and fear of movement may be elevated in individuals with PFP and correlate with pain and reduced physical function. These results derive from a limited number of studies. Future research should aim to evaluate if and how psychological factors contribute to PFP. Clinical relevance Patients are likely to benefit from clinician vigilance to the presence of psychological factors.
Interest of the XN-10® Analyzer to Screen for Myelodysplastic Syndromes on Complete Blood Count (CBC) Especially with Hemoglobin Levels and Neut-WX
Authors: Robin Boutault, Sebastien Tremblais, Mathilde De Oliveira Lopes, Pierre Peterlin, Yannick Le Bris, Catherine Godon, Olivier Theisen, Marie C Bene, Marion Eveillard
Journal: Blood (2016)
Subject Index Vol. 71, 2002
Authors: Tom Sensky, Luigi Grassi, Theo K. Bouman, Manfred M. Fichter, Stefan Büchi, Claus Buddeberg, Richard Klaghofer, Erich W. Russi, Otto Brändli, Corinne Schlösser, Thomas Stoll, Peter M. Villiger, Vladan Starcevic, Ad J.J.M. Vingerhoets, Maaike van Huijgevoort, Guus L. van Heck, Wolfgang Hiller, Rolf Leibbrand, Winfried Rief, James Satriano, Alessia Serra, Bruno Biancosino, Spyridon Zotos, Laura Sighinolfi, Florio Ghinelli, Francesco Fallo, Luisa Barzon, Franco Rabbia, Cecilia Navarrini, Andrea Conterno, Franco Veglio, Manuela Cazzaro, Giovanni A. Fava, Nicoletta Sonino, Paolo Scocco, Ellen Frank
Journal: Psychotherapy and Psychosomatics (2002)

disorders 263 Apolipoprotein A1 117 Arousal 47 Arthritis 112 Assessment 158, 333 Atypical antipsychotic drug-induced diabetes, management 244 --drug-related diabetes, mechanism 244 --drugs 244 Avoidance 47 Axis II comorbidity 269 Behaviour therapy 255 Benzodiazepines 263 Bipolar disorder 2, 39, 180 Body dissatisfaction 54 Breast cancer 162
A phase II study of RO4929097 (RO), a gamma-secretase inhibitor, in advanced platinum (Pt)-resistant (R) ovarian cancer (OC): A study of the PMH, Chicago, and California phase II consortia.
Authors: Ivan Diaz-Padilla, Blaise A Clarke, Hal W. Hirte, Stephen Welch, Helen Mackay, James Joseph Biagi, Michael Reedijk, Johanne Ingrid Weberpals, Gini F. Fleming, Lisa Wang, Jennifer Li, Elizabeth Laureen Strevel, Anne Eisenhauer, S. Percy Ivy, Amit M. Oza
Journal: Journal of Clinical Oncology (2012)

5019 Background: Notch signalling pathway plays a critical role in regulating cellular differentiation, proliferation, and apoptosis in preclinical cancer models. The Notch receptor, its ligands, and down-stream effectors are over-expressed in OC. Inhibition of γ-secretase-mediated Notch cleavage is a primary focus for the development of targeted therapeutics. Methods: Women (pts) with progressive, measurable (RECIST), Pt-R OC treated with ≤ 2 chemotherapy regimens for recurrent disease were treated with oral RO at 20mg od, 3 days on/4 days off every week, q3w. The primary objective was to determine the antitumor efficacy of RO in Pt-R OC by the progression-free survival (PFS) rate at the end of 4 cycles. Secondary objectives were to assess the safety of RO and to explore molecular correlates of outcome in archival tumor tissue. A Simon two-stage design was used. The study would open to second stage accrual if &gt; 4 pts of the first 17 accrued remain progression-free at the end of 4 cycles. Results: 39 pts have been enrolled after first-stage criteria were met. Median age was 59 (range 26-81). Median number of cycles was 2 (range 1-18). 30 (83%) pts had high-grade serous OC. 34 pts were evaluable for response. 8 pts (20%) were progression-free after 4 cycles.12 pts (35%) had stable disease, with a median duration of 3.9 months (range 2.5-12.2). Median PFS was 1.3 months (1.2-2.3). The most common drug-related adverse events (AEs) of any grade (% pts) were: nausea (36), fatigue (28), anorexia (15), hypophosphatemia (15), anemia (13), and increased alanine aminotransferase [ALT] (13). There were 5 G3-4 AEs at least possibly related with RO: increased liver transaminases (2), diarrhea (1), headache (1), and hypophosphatemia (1). Intracellular Notch (NIC) and JAG1 protein expression on high-grade serous OC were correlated with response in 17 pts. Median PFS for pts with high NIC (n=6) was 3.3 months (1.0-not reached), compared to 1.3 months (1.1-2.6) for pts with low NIC (n=11), p=0.09. Conclusions: RO has limited clinical activity in unselected Pt-R OC as a single agent. Future studies need to assess potential for cohort enrichment using NIC expression.
Application of the French prognostic score (FPS) to assess overall survival (OS) in a U.S.-based cohort of patients (pts) treated with azacitidine (Aza).
Authors: Amer Zeidan, Zhuoxin Sun, Thomas Prebet, Peter Greenberg, Mark Juckett, Mitchell Reed Smith, Elisabeth Paietta, Janice Lynn Gabrilove, Harry P. Erba, Steven Gore, Martin S. Tallman
Journal: Journal of Clinical Oncology (2013)

7126 Background: In pts with IPSS high-risk myelodysplastic syndrome (HR-MDS), Aza prolonged OS. The FPS was developed for Aza-treated HR-MDS pts based on 4 baseline clinical criteria: Performance status, karyotype, presence of circulating blasts, and RBC transfusion dependency (TD) (Itzykson et al, Blood 2011). The FPS discriminated 3 risk groups [low-risk [LR), intermediate-risk (IR), and high-risk (HR), with significantly different median OS at 32, 15, and 6 months (M), respectively. We sought to validate the FPS in a U.S.-based cohort. Methods: The North American Leukemia Intergroup Trial E1905 randomized 150 pts with MDS, CMML, and AML with dysplastic changes to Aza 50 mg/m 2 /day (d) for 10 d +/- entinostat (Ent) 4 mg/m 2 /d on d3 and d10. OS was defined as time from registration to death from any cause, with follow-up censored at last contact. Kaplan-Meier estimates were used for survival distribution. Results: The FPS could be determined for 115 pts. Median follow-up was 48.5 M. The median OS was significantly different between the HR, IR, and LR FPS groups in the 115 pts (9.7, 14.7, 25.3 M, respectively, log Rank test P=0.017), and for pts in Aza arm (n=55) (7.8, 19.3, 26.4 M, respectively, P=0.008), but not for patients in the Aza+Ent arm (n=60) (12.5, 12.4, 24.1 M, respectively, P=0.21). Using multivariate Cox model with WBC count, hemoglobin, disease type, and platelet TD, the prognostic effect of HR vs. LR FPS groups remained significant for the entire cohort (P=0.046) and for the Aza arm (P=0.037). No significant differences in response rates were observed. Conclusions: The FPS warrants further evaluation as a baseline prognostic tool that can define a subgroup of pts with lower probabilities of achieving survival benefit from Aza therapy. Such pts might be considered from alternative therapeutic interventions.