tbuckley/cabot-search huggingface dataset:
Glioblastoma in the Canton of Zurich, Switzerland, revisited (2005-2009).
Authors: Dorothee Gramatzki, Silvia Dehler, Elisabeth Jane Rushing, Kathrin Zaugg, Silvia Hofer, Yasuhiro Yonekawa, Helmut Bertalanffy, Anton Valavanis, Sabine Rohrmann, Joachim Oberle, Patrick Roth, Hiroko Ohgaki, Michael Weller
Journal: Journal of Clinical Oncology (2015)

e13025 Background: In 2005 a randomized phase III study of the European Organization for Research and Treatment of Cancer and National Cancer Institute of Canada Clinical Trials Group reported an improved median survival of 14.6 months for glioblastoma patients treated with radiotherapy plus temozolomide (TMZ/RT→TMZ), compared with 12.1 months for treatment with RT alone. Subsequently TMZ/RT→TMZ has become the standard of care. A population-based analysis of patterns of care and outcome in glioma patients diagnosed 1980-1994 in the Canton of Zurich, Switzerland, has provided a powerful database, confirming the overall poor prognosis of glioblastoma (H. Ohgaki et al. Cancer Res. 64:6892-9, 2004). To explore changes in outcome over the last decades, the registry data were re-evaluated for patients diagnosed in the time frame 2005-2009. Methods: Patients diagnosed for glioblastoma in the Canton of Zurich from 2005-2009 were identified by the Cancer Registry Zurich. Clinical and epidemiological data were included in a filemaker database, and analyzed using the Kaplan-Meier method and the Cox proportional hazards model. Results: In the current database, there were 264 patients with glioblastoma, including 197 with primary glioblastomas with an annual incidence of 3.98 compared to 3.55 in the former patient group. Median age at diagnosis was 60.5 years recently as opposed to 62.2 years previously. Median overall survival (OS) was 11.1 months for the period ending 2009 versus 4.9 for the patient population of 1980 to 1994. In the present study, median OS was 2.1 months for patients treated with surgery alone, 4.9 months with combined surgery and radiotherapy, and 16.6 months for patients who received surgery followed by TMZ/RT→TMZ. OS was 45% at 1 year, 21.4% at 2 years and 14% at 3 years in the present study while previously the OS was significantly lower, namely 17.7% at 1 year, 3.3% at 2 years and 1.2% at 3 years, respectively. Age and extent of resection were strongly associated with survival in the present patient cohort. Conclusions: The OS of patients in the Canton of Zurich with newly diagnosed glioblastoma has markedly improved from the period of 1980-1994 to 2005-2009. Age, extent of resection, and treatment regimens remain strong indicators of outcome.
A randomized, double-blinded, phase II study of paclitaxel/carboplatin (PC) plus CT-322 versus PC plus bevacizumab (Bev) as first-line treatment for advanced nonsquamous non-small cell lung cancer (NSCLC).
Authors: Eugene Henry Paschold, Julien Mazieres, Hervé Lena, Giorgio Cruciani, Glen Laird, Ian B. Walters, Allen C. Chen, Ovidiu C. Trifan
Journal: Journal of Clinical Oncology (2012)

7584 Background: CT- 322 is a pegylated protein engineered from the tenth type III human fibronectin domain thatspecifically blocks VEGFR-2 signaling by all known ligands. This international randomized study assessed the efficacy and safety of PC + CT-322 compared to PC + Bev as first-line treatment for advanced non-squamous NSCLC. Methods: In addition to paclitaxel 200 mg/m 2 and carboplatin AUC 6 given on day 1 of a 21 day cycle(maximum 6 cycles), subjects, stratified by ECOG performance status, disease stage, and site, were randomized 1:1 to receive either CT-322 2 mg/kg on days 1, 8, and 15 (arm A) or Bev 15 mg/kg on day 1 and placebo on days 8 and 15 (arm B). CT -322 and Bev/placebo were continued as maintenance until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), response rate, and safety. Results: 255 subjects were randomized to arm A (n=127) or arm B (n=128). Baseline characteristics were wellbalanced. After a median follow- up of 13.8 months, 9 subjects on arm A and 24 on arm B remained on study treatment. The median treatment duration was 19 weeks in arm A and 26.3 weeks on arm B. The median PFS in arm A was 5.6 months compared to 6.8 months in arm B (HR 1.51, 1 -sided p=0.997). In all prespecified subgroups, PFS was favored in arm B. The response rate was 25.2% in arm A compared to 32.8% in arm B. Median OS was 12.5 months in arm A compared to 15.2 months in arm B. The most common grade ≥ 3 adverse events (Arm A vs B) were neutropenia (47.2% vs 49.2%), thrombocytopenia (11.8% vs 6.3%), and fatigue (10.2% in both arms). Grade ≥ 3 hypertension was more frequently reported in arm A (8.7% vs 3.1%). Grade ≥ 3 venous thrombosis (5.5% vs 6.3%), proteinuria (1.6% vs 2.3%), and bleeding events (0.8% vs 1.6%) were similar. Conclusions: PC + CT-322 failed to improve PFS, OS, or response rate compared to PC + Bev. However, thesafety profile in the PC + CT-322 arm was consistent with the anti-angiogenic mechanism of action, suggesting that CT-322 has biological activity as an inhibitor of VEGFR-2.
Preoperative chemoradiation versus preoperative chemotherapy alone for esophageal cancer: Higher response rates but equivalent survival.
Authors: Brendon Matthew Stiles, Abu Nasar, Subroto Paul, Paul Chinfai Lee, Jeffrey L. Port, Manish A. Shah, Nasser K. Altorki
Journal: Journal of Clinical Oncology (2014)

4071 Background: Controversy exists over the optimal neoadjuvant therapy in patients with locally advanced esophageal cancer (EC). While most groups favor neoadjuvant chemoradiation (nCRT), some advocate preoperative chemotherapy (nCT) without radiation. The objective of this study was to compare outcomes in EC patients undergoing either regimen, followed by surgery. Methods: We reviewed a prospectively collected database of EC patients undergoing esophagectomy following nCT or nCRT (1989-2013). Choice of therapy was at the discretion of the multidisciplinary team. Demographic data, clinical and pathologic staging, and survival (KM) were compared. Results: From 600 patients, 261 patients were identified with EC treated with nCRT (n=63) or nCT (n=199) followed by surgery. Patients were well matched for age, gender, PS, histology, and clinical stage. Following therapy, more nCRT patients had a complete clinical response (36% vs. 14%, p<0.001) by post-induction endoscopy and CT/PET. At surgery, 88% and 92% of CRT and CT patients underwent transthoracic esophagectomy. nCRT, in comparison to nCT, was associated with similar rates of cardiovascular (23% vs. 28%, p=0.43), pulmonary (24% vs. 25%, p=0.95), and infectious (13% vs. 9%, p=0.38) postoperative complications, and higher anastomotic leaks (23% vs. 14%, p=0.09). Perioperative (6% vs. 2%, p=0.06) and 90-day (11% vs. 4%, p=0.03) mortality was higher in nCRT than nCT patients. Following nCRT, 30% of patients had complete pathologic response vs. 6% of nCT patients (p<0.01). nCRT patients were more often node negative on final pathology (62% vs. 33%, p<0.001). Despite improved pathologic downstaging, nCRT patients had no improvement in 3-year disease-free (33% vs. 39%, p=0.84) or overall (54% vs. 52%, p=0.36) survival. No benefit of nCRT vs. nCT was apparent in 3-year overall survival in either adenocarcinoma (52% vs. 47%, p=0.25) or squamous cell carcinoma (44% vs. 61%, p=0.51). Conclusions: For patients undergoing surgery for EC, nCRT leads to increased local tumor response compared to nCT alone. However, nCRT is associated with increased early mortality and did not translate to improved long-term survival.
TGF-α and amphiregulin levels in non-small cell lung cancer (NSCLC) patients (pts) treated with erlotinib/placebo in the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) BR.21
Authors: G. D. Goss, C. Addison, F. Shepherd, L. Seymour, A. LeMaitre, K. Ding
Journal: Journal of Clinical Oncology (2009)

11023 Background: In BR.21, erlotinib prolonged survival of previously treated NSCLC pts. We examined the predictive/ prognostic effects of the EGFR ligands, TGFa and amphiregulin(Am). Methods: Plasma was collected prior to treatment in consenting pts. TGFa and Am were analyzed by ELISA (R&amp;D Systems). Samples were blinded, measured in duplicate and ligand concentrations determined following interpolation of a standard curve generated from known quantities of recombinant proteins. Sensitivity was ∼3pg/ml. Cutoff points for TGFa were &lt;10 (low) and ≥10 (high); for Am &lt;1.5 (low) vs 1.5–10 (intermediate) vs &gt;10 (high). Standard statistical methods were used to correlate biomarker data with baseline characteristics and outcomes. Results: In 731 randomized pts, 539 were evaluable for both markers; there was a significant interaction (p=0.03) between the evaluable and inevaluable cohorts (erlotinib benefit favoring the evaluable cohort); evaluable pts were more likely to be male, &gt; 60 and to have EGFR amplification. Baseline high TGFa was associated with poorer ECOG PS (p=0.03) while high Am was associated with worse PS (p&lt;0.0001), anemia (p&lt;0.0001), non response to prior therapies (p=0.01) and no-prior platinum therapy (p=0.02). Although TGFa was not prognostic for OS (HR=1.0, p=0.99), high Am was (HR: Middle vs low: 0.94, 95% C.I 0.49 -1.81; high vs.low: 2.04, 95% C.I 1.43 - 2.91; p=0.0002). High TGFa was a poor prognostic factor for PFS (HR 1.4, p=0.07) as was elevated Am (HR: Middle vs low: 1.02, 95% C.I 0.56 -1.85; high vs. low: 1.67, 95% C.I 1.19 - 2.35, p=0.01). In multivariate analyses including both ligands, high Am remained prognostic, but neither ligand was predictive. Conclusions: High levels of baseline Am appears to be a poor prognostic factor, while low levels of TGFa showed a trend to predict benefit from erlotinib in univariate analyses. [Table: see text] [Table: see text]
Contents, Vol. 42, 1984
Authors: Herbert Weiner, Adolf-Ernst Meyer, W. Senf, H. Kordy, M. von Rad, W. Bräutigam, Peter E. Sifneos, Cairns Aitken, Chase Patterson Kimball, Alec Ramsay, Michael von Rad, Johannes Siegrist, Adolf-Ernst Meyer, Herbert Weiner, Adolf-Ernst Meyer, Hubert Speidel, W. Bräutigam, M. von Rad, Adolf-Ernst Meyer, Antje Haag, Christian Müller, Volker Tschuschke, Walter Volk, Reinhard Költzow, Fritz A. Muthny, Adam J. Krakowski, A. Heerlein, G. de la Parra, S. Aronsohn, F. Lolas, W. Ehlers, D. Czogalik, E. Gaus, M. Klingenburg, K. Köhle, Hertha Appelt, Bernhard Strauss, K.W. Bash, Hans-Werner Künsebeck, Wolfgang Lempa, Hellmuth Freyberger, Eike G. Fischer, Nora E. Falke, Antje Haag, Adam J. Krakowski, M.A. Rea, D.H. Hellhammer
Journal: Psychotherapy and Psychosomatics (1984)
A 19-gene prognostic GEP signature (DecisionDx-Thymoma) to determine metastatic risk associated with thymomas.
Authors: Yesim Gokmen-Polar, Chirayu Pankaj Goswami, Robert W. Cook, Kristen M. Oelschlager, Derek Maetzold, Ioan Tudor Vladislav, Kristen L Shirar, Kenneth Kesler, Patrick J. Loehrer, Sunil S. Badve
Journal: Journal of Clinical Oncology (2012)

7106 Background: The treatment of thymomas is predominantly based on the stage of disease. Histologic classification is of limited value as all types of thymomas can give rise to metastases. In order to better predict the metastatic behavior of these tumors, we performed genome-wide gene expression analysis and identified a set of genes associated with presence or absence of metastases. In the current study, we sought to further develop and validate the gene signature using quantitative RT-PCR analysis. Methods: Thymomas with archived blocks and long-term follow-up data were reviewed. This training set study consisted of 50 cases, including 34 cases on which the discovery microarray analysis had been performed. RNA was extracted from 5 x 10-micron thick sections in a CAP-accredited CLIA certified laboratory and analyzed by RT-PCR using custom TLDA cards on an ABI7900HT instrument. Expression data and biostatistical analysis were performed using GeNorm and JMP Genomics (SAS). Predictive modeling using Partition Tree Analysis (PTA) and Logistic Regression Analysis (LRA) was performed. Metastasis-free survival (MFS) was assessed using Kaplan-Meier analysis. Results: A 19-gene expression profile (GEP) signature was developed using a cohort of 50 thymomas for predicting metastasis. PTA yielded ROC of 0.97 (met. accuracy = 96%, non-met. accuracy = 81%), while LRA yielded ROC of 0.895 (met. accuracy = 87%, non-met. accuracy = 85%). PTA classification showed 5-year MFS rates of 100% and 31% for predicted low risk (Class 1) and high risk (Class 2) of metastasis (median MFS = NR and 4.1 yrs, resp., P&lt;0.0001 Log-Rank), respectively. LRA showed 5-year MFS rates of 100% and 17% for predicted Class 1 and high risk Class 2 of metastasis (median MFS = NR and 2.9 yrs, resp., P&lt;0.0001 Log-Rank), respectively. Analysis of additional cohorts is ongoing. Conclusions: We have successfully completed development of a 19-gene signature (DecisionDx-Thymoma) that appears to predict metastatic behavior of thymomas more accurately than traditional staging. If validated in larger cohort, this signature will provide insight for the future management of patients with this rare malignancy.
Elevated Levels of Circulating Nucleosomes Are Not Associated with Venous Thrombosis or Neutrophil Activation in Patients with Multiple Myeloma
Authors: Mandy N. Lauw, Frank W.G. Leebeek, Moniek P.M. de Maat, Gerard J. van Mierlo, Saskia Middeldorp, Sacha S. Zeerleder
Journal: Blood (2016)
Clinical implications of a prostate cancer risk SNP profile in two treatment cohorts.
Authors: Chee Leng Goh, Ed Saunders, Daniel Leongamornlert, Tokhir Dadaev, Malgorzata Tymrakiewicz, Karen Thomas, Elizabeth Selvadurai, Ruth Woode-Amissah, Nadiya Mahmud, Elena Castro, David Olmos, Michelle Guy, Koveela Govindasami, Rosemary Wilkinson, Emma Sawyer, Ali Amin Al Olama, Douglas Easton, Zsofia Kote-Jarai, Chris Parker, Ros A. Eeles
Journal: Journal of Clinical Oncology (2013)

e16000 Background: Prostate cancer (PCa) has a heritable risk and genome-wide association studies (GWAS) have so far identified 76 single nucleotide polymorphisms (SNPs) associated with PCa risk. Currently these SNPs have only been evaluated against overall PCa risk and several disease parameters. Their clinical utility remains undefined. We explore the potential prognostic role of the risk SNP profile in 2 PCa cohorts; Active Surveillance (AS) and androgen deprivation therapy (ADT). Methods: PCa patients at the Royal Marsden Hospital who consented for DNA analyses were eligible. 2 separate cohorts were identified; those undergoing AS and those receiving ADT. The risk SNPs were genotyped using Sequenom or Fluidigm platforms. The cumulative SNP risk scores for each patient were calculated by summing risk alleles for each loci using the weighted effect as estimated in previous studies (log-additive model). For the AS group, the risk scores were analysed against defined adverse outcomes in AS, including adverse histology on repeat biopsy and time to treatment, to determine their prognostic value. For the ADT group, the risk scores were assessed against time to relapse, defined by either biochemical relapse or evidence of progression on imaging. Results: In the AS group, 391 patients’ DNA were studied. 31% of those have since undergone treatment and 30% have histological upgrade on repeat biopsies. On univariate analysis, there was no significant relationship between the risk scores and biopsy upgrade or time to treatment (p&gt;0.05). When analysing differences in outcomes between the higher and lower risk groups (top 25% and lowest 25% of the genetic risk distribution), there was again no relationship (p&gt;0.05). In the ADT group, 567 patients’ DNA were studied. The mean duration of response was 30 months. No significant associations were found when risk scores were analysed as a continuous variable against time to relapse on ADT, or when analysing difference between the top and bottom 25% of the risk distribution (p&gt;0.05). Conclusions: PCa SNP risk scores have not been shown to be prognostic factors in either AS or ADT. This is the first study analysing the potential prognostic role of the latest GWAS risk SNPs in PCa treatment cohorts.
A randomized, open-label phase II study of AZD4547 (AZD) versus Paclitaxel (P) in previously treated patients with advanced gastric cancer (AGC) with Fibroblast Growth Factor Receptor 2 (FGFR2) polysomy or gene amplification (amp): SHINE study.
Authors: Yung-Jue Bang, Eric Van Cutsem, Wasat Mansoor, Russell D. Petty, Yee Chao, David Cunningham, David Ferry, Donal Landers, Paul Stockman, Neil R. Smith, Catherine Geh, Elaine Kilgour
Journal: Journal of Clinical Oncology (2015)

4014 Background: The prognosis for AGC patients failing 1st line treatment is poor. FGFR2 amplification occurs in ~5-10% and polysomy in > 20% of gastric cancers (GCs). AZD is a selective FGFR1-3 inhibitor with activity in FGFR2 amplified models. SHINE assessed the efficacy and safety of AZD in AGC patients with FGFR2amplification or polysomy. Methods: Patients with disease progression after 1 prior line of therapy were assigned to FGFR2 amplified or polysomy arms and randomised to oral AZD (80mg bd, 2weeks on/1week off) or P. The primary endpoint was progression-free survival (PFS). Secondary endpoints included safety. FGFR2 status confirmed by FISH testing. Exploratory biomarker analysis assessed FGFR2 gene expression by nanostring and intra-tumoral heterogeneity of FGFR2amplification by image analysis of FISH stained sections. Results: Of 960 pts enrolled, 71 patients were randomised (41 AZD arm, 30 P arm). AGC FGFR2 amp prevalence was 9%. The overall median PFS on the AZD arm was 1.8 mths vs 3.5 mths for P and for the FGFR2 amplified arm was 1.5 mths for AZD vs 2.3 months for P. Pts on AZD mostly experienced G1/G2 AEs. Most common AEs causally related to AZD were stomatitis (8 pts/20%), dry mouth (7 pts/17.5%) and RPED (6/15% pts) and fully resolved off treatment. Elevations in plasma phosphate were observed on the AZD arm during the 2 week dosing period and resolved during the 1 week off. Only 21% of FGFR2amplified tumors had elevated FGFR2 expression and Image analysis showed four out of seven tumor samples, highly amplified by FISH, were amplified in < 20% of the tumor section. Conclusions: AZD was well-tolerated. The analysis of PFS did not show any statistically significant difference in favour of the AZD arm, compared with the P arm in FGFR2 amplified or polysomy patients selected by FISH. Exploratory biomarker analysis revealed marked intra-tumor heterogeneity of FGFR2 amplification and low concordance with elevated FGFR2 expression. The observed increase in plasma phosphate provides evidence that AZD at this dose and schedule causes pharmacologic target inhibition. Clinical trial information: NCT01457846.
Updated results of a prospective noninterventional study of everolimus after use of 1 VEGFR-TKI.
Authors: Lothar Bergmann, Peter J. Goebell, Ulrich Kube, Manfred Kindler, Edwin Herrmann, Jan Janssen, Joerg Schmitz, Steffen Weikert, Susanne Kloss, Gabriel Steiner, Andreas Jakob, Michael D. Staehler, Thomas Steiner, Friedrich Overkamp, Gernot Guderian, Christian Doehn
Journal: Journal of Clinical Oncology (2012)

e15044 Background: Everolimus (EVE, Afinitor) is approved for the treatment of metastatic renal cell cancer (mRCC) after failure of VEGF-targeted therapy. The option to treat mRCC with six approved targeted agents has sparked debate on proper sequencing of these agents. However, data beyond clinical trials is limited. Here, we report prospective non-interventional data on EVE in routine use after failure of the 1 st VEGFR-TKI. Methods: A prospective, single arm non-interventional study for patients with mRCC enrolled 383 patients in Germany between 08/2009 and 01/2012 to determine effectiveness defined as time between first EVE intake until disease progression due to any cause (TTP) and treatment duration. A first interim analysis was previously conducted and presented (Bergmann et al., J Clin Oncol 29: 2011 [suppl; abstr 4552]). Here we present a second interim analysis which was carried out 10 months after the first to corroborate the previous results. Results: 196 pts were included at 79 sites between 08/2009 and 07/2011 and had been followed for a median of 4.5 months at the time of analysis. The safety population (pts with information on EVE treatment) and efficacy population (pts who fulfilled all criteria per observational plan) consisted of 195 pts and 165 pts, respectively. At the cut-off date for the interim analysis, 136 pts (69%) had discontinued the study. Median treatment duration was 7.3 months (95% CI: 4.7 mo; 10.9 mo) and median time to progression (TTP) was 7.0 months (95% CI: 5.1 mo; 9.0 mo) for the efficacy population. A total of 600 AEs were reported in 70% of pts of the safety population including 148 SAEs in 67 pts (34%). Subgroup analysis according to duration of prior VEGF-targeted treatment &lt;6 months and ≥6 months revealed median TTPs of 6.8 months (95% CI: 4.4 mo; 13.4 mo) and 7.4 months (95% CI: 4.6 mo; 10.1 mo), respectively. Conclusions: This 2 nd interim analysis of a non-interventional study on EVE in treatment of mRCC after prior failure of the 1 st VEGFR-TKI confirms the longer TTP reported in the 1 st interim analysis compared to the pivotal trial. The results also provide evidence that TTP under EVE does not necessarily correlate with time on prior treatment.
Comparing the ability of clinicians and a nomogram model at predicting future <sup>99m</sup>Tc-bone scan (BS) positivity in patients (pts) with rising prostate-specific antigen (PSA) following radical prostatectomy (RP) for prostate cancer (PCa).
Authors: Michael W. Kattan, Changhong Yu, Andrew J. Stephenson, A. Oliver Sartor, Bertrand Tombal
Journal: Journal of Clinical Oncology (2012)

4652 Background: Nomograms that assist clinicians in predicting which PCa pts have a high risk of developing M1 disease have been developed, but clinicians still tend to use their own judgment of risk when managing individual pts. This is the first study to compare the ability of clinicians vs a nomogram at predicting future BS positivity in pts with PCa. Only androgen deprivation therapy- (ADT-) naive post-RP pts were considered, as there are currently no nomograms for predicting M1 disease in pts receiving ADT. The Slovin nomogram (Slovin et al. Clin Cancer Res 2005; 11: 8669-8673) was chosen based on considerations of the numbers of pts analyzed and the follow-up intervals used in its development. Methods: During an advisory board in June 2011, 24 PCa experts were given details of 25 ADT-naive post-RP PCa pts with biochemical recurrence who were randomly selected from the Cleveland Clinic Database of 759 pts. The predicted 1-yr from today probability of freedom from metastasis was generated using the Slovin nomogram and estimated by the clinicians. The predictive accuracy was quantified using the concordance index (C-index). Results: All pts were Caucasian and median age was 62 yrs. Median PSA level at biochemical recurrence was 1.2 ng/mL and PSADT varied between 1.3 and 11.7 months. The data used for each of the pts was acquired between 4 and 133 months after the RP procedure. Eight pts had a positive BS within 1 yr. Considerable variation between the clinicians’ predictions for each pt was observed. The nomogram gave a higher C-index compared to the clinicians (0.812 and 0.628, respectively; p=0.003). The clinicians typically overestimated the risk of developing M1 disease. The nomogram outperformed all of the clinicians (C-index range: 0.47 to 0.75). Urologists predictions were superior to those of oncologists (p=0.048). Conclusions: The Slovin nomogram was more accurate than expert clinicians in predicting 1-yr BS positivity. We suggest nomograms should become an integral part of the clinical decision process in the PCa setting.