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Annals of Oncology plotted and examined for phosphorylation expression of 183 proteins serving as nodes in 120 signaling pathways registered in the NCI-Nature curated pathway (NCI-Nature_Curated.bp2.owl 2011.12.19). The sensitivity (IC50 value) of the 23 HCC cell lines to sofafenib was quantified using the CellTiter-Glo Luminescent Cell Viability Assay kit. Results: Use of fluorescence dye significantly expanded the sensitivity and dynamic range of the RPPAs. We found that the relative level of phosphorylation of ribosomal protein S6 (p-rpS6) at the Ser235/236 residues showed the highest correlation with sensitivity to sorafenib among the 183 signaling nodes (P = 0.0044, Spearman correlation analysis), followed by phosphorylation of the same protein at the Ser240/ 244 residues (P = 0.0070). Immunoblot analysis confirmed that the sorafenib-resistant cell lines had the highest level of rpS6 phosphorylation. We found that in some HCC cell lines the mitogen-activated protein kinase (MAPK) pathway was activated downstream of RAF kinase and showed sensitivity to MEK (CI-1040) and RSK (SL0101) inhibitors. Conclusions: To achieve personalization of molecular therapies, precise mapping of activated signaling pathways in individual patients is essential. RPPA requires only a small amount of protein and is ideal for application to clinical settings. We are collecting tumor biopsy samples from HCC patients to verify the present findings, and plan to present the data at the meeting. Disclosure: All authors have declared no conflicts of interest. 1675P PRECLINICAL AND PRELIMINARY CLINICAL ACTIVITY OF NVP-BKM120, AN ORAL PAN-CLASS I PI3K INHIBITOR, IN THE BRAIN M. Maira 1 , C. Schnell 1 , P. Lollini 2 , C. Chouaid 3 , P. Schmid 4 , P. Nanni 5 , D. Lam 6 , E. Di Tomaso 7 , C. Massacesi 8 , J. Rodon 9 1 Oncology, Novatis Institute for Biomedical Research, Basel, SWITZERLAND, 2 Department of Hematology and Oncological Sciences, University of Bologna, Bologna, ITALY, 3 Pulmonology, Hopital Saint-Antoine, Paris, FRANCE, 4 Clinical Investigation and Research Unit, Brighton and Sussex Medical School, Brighton, UNITED KINGDOM, 5 Department of Experimental Pathology, University of Bologna, Bologna, ITALY, 6 Oncology, Novartis, Florham Park, NJ, UNITED STATES OF AMERICA, 7 Institutes for Biomedical Research, Novartis, Cambridge, MA, UNITED STATES OF AMERICA, 8 Oncology, Novartis, Paris, FRANCE, 9 Medical Oncology, Vall d’Hebron University Hospital, Barcelona, SPAIN Background: New therapies that penetrate the blood–brain barrier (BBB) are needed to combat brain metastases (BM). Activity of BKM120, an oral pan-class I PI3K inhibitor, in the brain was assessed in vivo, with additional evidence collected from Ph I/II clinical trials. Methods: The ability of BKM120 to penetrate the BBB and inhibit PI3K signaling was determined by: (1) comparison of IHC staining of insulin-induced S473P-AKT levels in the brains of untreated/BKM120-treated (5 mg/kg, po, once) rats; and (2) regular monitoring of drug concentrations and S473P-AKT levels over 24 hrs upon BKM120 (50 mg/kg, po, once) or pan-PI3K inhibitor GDC0941 (150 mg/kg, po, once) treatment in plasma, tumor and brain tissue of Rat1-myr-p110 tumor-bearing (subcutaneous) mice. Activity of BKM120 against BM was also assessed in 1 preclinical model of HER2+ breast cancer (BC) BM and in 2 clinical trials of pts with advanced solid tumors (CBKM120X2101) and metastatic NSCLC (CBKM120D2201). Results: BKM120 strongly reduced insulin-induced S473P-AKT in the brain vs. untreated controls, with the most notable effects observed in the cerebellum. Uptake of BKM120 in Rat1-myr-p110 tumor-bearing mice over 24 hrs was similar across plasma, tumor and brain tissues, with the highest concentration of BKM120 at 1 hr post-administration. At this time point, BKM120 completely reduced S473P-AKT in both tumor and brain samples. In contrast, uptake of GDC0941 was undetectable in the brain and had no effect on S473P-AKT levels in this tissue. Uptake of GDC0941 and inhibition of S473P-AKT was similar to BKM120 in plasma and tumor. In addition, BKM120 strongly inhibited growth of BM by human HER2+ BC cells MDA-MB-453 in immunodeficient Rag2 −/- / Il2rg −/- mice. In 2 clinical trials, 4 pts with BM have been treated with single-agent BKM120 to date: 1 pt with metastatic BC had a 29% reduction in a brain lesion, while disappearance of a non-target brain lesion was seen in 1 pt with squamous NSCLC. Conclusions: Preclinical data suggest that BKM120 penetrates the BBB and inhibits PI3K signaling in the brain. This unique property of BKM120 is not a class effect. Preliminary clinical evidence supports these findings. Clinical trials of BKM120 in pts with BM are planned. Disclosure: M. Maira: Stock ownership and employee of Novartis. C. Schnell: Stockholder and employee of Novartis. C. Chouaid: Member of the advisory boards for Lilly, Amgen, Roche and has undertaken research sponsored by Lilly, Amgen, Roche, Novartis and AstraZeneca. D. Lam: Employee of Novartis. E. Di Tomaso: Employee of Novartis. C. Massacesi: Employee of Novartis. All other authors have declared no conflicts of interest. 1676P GEMCITABINE, PI3KINASE-AKT PATHWAY INHIBITION AND RADIATION IN HUMAN GLIOMA CELL LINES M.S. Elnaggar 1 , P. Sminia 2 , S. Shehata 3 , C. Fedrigo 4 , G. Peters 1 1 Medical Oncology Department, VUMC, Amsterdam, NETHERLANDS, 2 Radiation Oncology, VUMC, Amsterdam, NETHERLANDS, 3 Clinical Oncology Department, Assiut University Hospital, Assiut, EGYPT, 4 Medicina e Ciências da Saúde, 2Pontifícia Universidade Católica do Rio Grande do Sul, Rio Grande do Sul, BRAZIL Introduction: Glioblastoma multiforme (GBM) is the most common primary brain tumor. Standard treatment is surgery and Radiotherapy (RT) with temozolomide. The median survival is ranging from 12-14 months. However, patients with an unmethylated MGMT gene promoter do not show a survival advantage for temozolomide, and might be eligible for alternative treatment. Gemcitabine is an excellent radiosensitizer and is investigated as an alternative for temozolomide in GBM patients. Activation of the PI3Kinase-Akt pathway may preclude effective RT; therefore we investigated the radiosensitizing effect of gemcitabine in combination with the Akt inhibitor MK-2206. Materials and methods: Three malignant glioma cell lines (U87, U251, and D384) were tested on cell proliferation (SRB assay) cell survival (clonogenic assay) and spheroid growth following treatment by the allosteric Akt-inhibitor MK-2206 (1 uM, 10 uM), gemcitabine and γ-irradiation (4 Gy single dose or 5 fractions of 2 Gy). Expression of Akt and pAkt was assessed by Western blot. Results: The U87 cell line was most sensitive and D384 was the most resistant one. MK-2206 decreased the IC50 of gemcitabine in all cell lines from 86, 237, 903 nM for gemcitabine alone to 57, 93, 860 nM, respectively. MK-2206 down regulated pAkt expression in a concentration and time dependent manner; at 0.1 µM pAkt was partly inhibited at 30 min and completely at 1, 2, 4 and 24 h, but started to recover at 48 h. At 1 µM pAkt inhibition was immediate and lasted longer. Since 25 nM gemcitabine and 4 GY RT alone stimulated pAKT expression, cells were preincubated with MK-2206 (1 µM for 1h). MK-2206 was additive to Gemcitabine and RT in reducing clonogenic cell survival, but MK-2206 was synergistic with gemcitabine alone and with RT in inhibition of spheroid growth The effect was more pronounced with RT. Conclusion: Addition of MK-2206 to gemcitabine significantly enhanced inhibition of cell proliferation and spheroid growth and inhibited the gemcitabine and RT mediated pAkt stimulation. The use of gemcitabine in combination with PI3kinase-Akt pathway inhibitors is a promising tool in GBM therapy and might be an alternative for patients resistant to temozolomide. Disclosure: All authors have declared no conflicts of interest. 1677P COMBINING EXTERNAL BEAM RADIOTHERAPY WITH MEASLES-VIRUS ONCOLYTIC THERAPY AND SAR-020106, A NOVEL RADIOSENSITIZER, IN HEAD AND NECK CANCER MODELS Y. Touchefeu 1 , A. Khan 2 , V. Roulstone 2 , K.J. Harrington 2 1 Institut des Maladies de ’Appareil Digestif, University Hospital, Nantes, FRANCE, 2 Targeted Therapy Laboratory, Institute of Cancer Reserach, London, UNITED KINGDOM We have previously demonstrated the antitumour activity of a treatment combining a replication-defective adenovirus encoding the sodium iodide symporter (NIS), external beam radiotherapy (EBRT) and DNA repair inhibitors. Engineered Measles viruses (MeV) expressing NIS are replication-competent, oncolytic viruses, currently being tested in phase 1 trials. The aim of this study was to evaluate the therapeutic efficacy of a combination of MeV-NIS, EBRT, and a novel checkpoint-1 inhibitor, SAR-020106. This approach was investigated in HN-3, HN-5 and PJ-41 head and neck cancer models. In vitro toxicity was assessed by MTS and clonogenic assays. CD46 (cell receptor for MeV) expression on head and neck cell lines was evaluated by flow cytometry. NIS viral transgene expression was assessed by 125I uptake assays. Apoptosis was evaluated by Caspase Glo® and western blot assays. In vivo therapy experiments were performed in CD1 nude mice with subcutaneous tumour xenografts. In this study, we have demonstrated that EBRT and MeV-NIS had in vitro synergistic antitumour effects in head and neck cancer cell lines. EBRT did increase neither CD46 expression nor viral replication, but significantly increased viral gene expression in infected cells. In vitro, SAR-020106 had synergistic antitumour effect with EBRT. This effect was related to increased apoptosis. In vitro, the combination of MeV-NIS and SAR-020106 was associated with a significantly increased antitumour effect, as compared with control, MeV-NIS alone or SAR-020106 alone (P < 0.05). In the HN5 in vivo model, we observed significant differences in overall survival. In the control and EBRT groups, we observed a median survival of 32.5 and 35 days, respectively. In the MeV-NIS, MeV-NIS with EBRT and the MeV-NIS combined with EBRT and SAR-020106 groups we observed significantly improved overall survival (Log-rank (Mantel-Cox) Χ2 = 12.8; df = 5; p = 0.025) with fewer than 50% of animals in each group achieving humane end point. Our study strongly supports further translational and clinical research on MeV in combination with radiation therapy and radiosensitising agents in head and neck cancers. Disclosure: All authors have declared no conflicts of interest. Volume 23 | Supplement 9 | September 2012 doi:10.1093/annonc/mds417 | ix537
1678P PREDICTIVE VALUE OF TWO PHENOTYPING PROBES FOR THE PHARMACOKINETICS OF SUNITINIB IN CANCER PATIENTS J.S.L. Kloth 1 , H.J. Klumpen 2 , C.F. Samer 3 , K. Eechoute 1 , N.A.G. Lankheet 4 , B.L. Kam 5 , M. Wong 6 , J.H.M. Schellens 7 , R.H.J. Mathijssen 8 , H. Gurney 9 1 Medical Oncology, Erasmus Medical Center, Rotterdam, NETHERLANDS, 2 Medical Oncology, Academic Medical Center (AMC), Amsterdam, NETHERLANDS, 3 Swiss Center for Applied Human Toxicities (SCAHT), Geneva University, Geneve, SWITZERLAND, 4 Department of Pharmacy and Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Amsterdam, NETHERLANDS, 5 Department of Nuclear Medicine, Erasmus Medical Center, Rotterdam, NETHERLANDS, 6 Department of Nuclear Medicine, Westmead institute for Cancer Research, Sydney, NSW, AUSTRALIA, 7 Department of Clinical Pharmacology, The Netherlands Cancer Institute, Amsterdam, NETHERLANDS, 8 Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, NETHERLANDS, 9 Medical Oncology, Westmead Hospital, Sydney, NSW, AUSTRALIA Background: Cancer patients treated with sunitinib show a wide inter-patient variability in drug exposure. This may at least partly explain the variation in toxicity and efficacy related to sunitinib treatment. The primary aim of this study was to investigate whether the clearance of 2 phenotyping probes are related to the pharmacokinetics (PK) of sunitinib. Patients and methods: A prospective multi-center study was performed in cancer patients treated with single agent sunitinib. PK of sunitinib and its active metabolite N-desethyl-sunitinib were measured at start of sunitinib intake and within 4 weeks of continuous daily dosing. A correlation analysis was performed between these PK data and midazolam clearance (as a CYP3A phenotyping probe) and hepatic 99m Tc-MIBI scans (as a probe for ABCB1 [P-glycoprotein] activity). Results: A total of 52 GIST and renal cell cancer patients were included in this study, of whom 46 were evaluable for analysis of sunitinib PK. Mean trough level of sunitinib, adjusted for dose, at day 1 of a new course was 14.7 ng/mL (range 7.2-28.9 ng/mL), and 56.2 ng/mL (range 19.1-151.1 ng/mL) in the 4 th week of a treatment cycle. A significant correlation between N-desethyl-sunitinib trough levels and plasma clearance of midazolam (r = 0.58, P = 0.006) within 24 hours after the first intake of sunitinib was found. In addition, a trend was seen for the correlation between midazolam clearance and sunitinib trough levels at steady state (r = 0.26, P = 0.09). No correlation between sunitinib trough levels and hepatic 99m Tc-MIBI clearance was seen in an interim analysis after 27 patients. Conclusions: These observations show a correlation between the midazolam clearance test that serves as a probe for CYP3A and the exposure to sunitinib. Meanwhile, a lack of correlation was seen between sunitinib PK and the studied ABCB1 probe. These data could ultimately lead to a further personalization of sunitinib dosing. Additional investigations are in progress, including population PK modeling of sunitinib, and incorporation of pharmacogenetic parameters to further unravel the mechanisms behind these findings. Disclosure: All authors have declared no conflicts of interest. 1679P HEAT SHOCK PROTEIN 90 INHIBITION DOWNREGULATES C-KIT EXPRESSION IN GIST CELLS THROUGH DIMINISHING TRANSCRIPTION AND ENHANCING PROTEIN DEGRADATION VIA BOTH AUTOPHAGY AND PROTEASOME PATHWAYS Y. Hsueh 1 ,C.Yen 2 , N. Shih 1 , N. Chiang 1 ,C.Li 3 , L. Chen 1 1 National Institute of Cancer Research, National Health Research Institutes, Tainan, TAIWAN, 2 Hematology/Oncology, Taipei Veteran General Hospital, Taipei, TAIWAN, 3 Department of Pathology, Chi-Mei Foundation Medical Center, Tainan, TAIWAN Background: Gastrointestinal stromal tumor (GIST) is a mutant oncoprotein c-Kit droved cancer. Patients suffered drug resistance after prolonged standard treatment of tyrosine kinase inhibitor (TKI), imatinib mesylate (IM). Inhibition of heat-shock protein 90 (Hsp90), a chaperone responsible for protein maturation and stability, causing its client proteins degradation, as c-Kit, is a developing therapy for cancer. However, the mechanisms of Hsp90 inhibition-induced c-Kit downregulation in post-translational and transcriptional levels have rarely been investigated. Methods and results: Our data showed that NVP-AUY922 (AUY922), a new class of Hsp90 inhibitor, inhibited the growth of GIST882 and GIST48 cells with mutant c-Kit protein expression that was accompanied with reduction of both total and phosphor-c-Kit protein and induction of apoptosis. Pharmacological inhibition on either autophagy or proteasome degradation pathway could partially reverse endogenous c-Kit turnover and AUY922-induced c-Kit reduction. These findings were further confirmed by the co-localization of c-Kit with either LC-3B or acridine orange-labeled autophagosome in confocal microscopy, and delay of c-Kit degradation by silencing autophagosome essential Beclin-1 protein. In addition, AUY922 could also reduce c-Kit mRNA without affecting its degradation. Our preliminary data showed that activities and nuclear levels of several transcription factors in GIST cells were diminished after AUY922 treatment. DNA affinity precipitation assay and chromatin immunoprecipitation (ChIP) will be performed to validate the binding of the candidate transcript factors on the c-Kit promoter. Annals of Oncology Conclusions: This is the first report showing the involvement of autophagy in endogenous as well as Hsp90 inhibitor-induced c-Kit degradation. Moreover, AUY922 treatment resulted in downregulation of c-Kit through protein degradation and transcriptional mRNA regulation in GIST cells. These findings address the mechanisms of AUY922 on c-Kit protein downregulation and highlight the potential use of AUY922 in TKI-refractory, c-Kit-expressing GIST. Disclosure: All authors have declared no conflicts of interest. 1680P MOLECULAR PROFILING OF HIGH-RISK LOCALIZED PROSTATE CANCER (HRLPC) TREATED WITH DOCETAXEL (D) AND COMPLETE ANDROGEN BLOCKADE (CAB) PRIOR TO RADICAL PROSTATECTOMY M. Marín-Aguilera 1 , A. Font 2 , E. Gallardo 3 , A. Alcaraz 4 , V. Pereira 5 , M.J. Ribal 4 , J. Areal 6 , N. Hannaoui 7 , P. Gascon 8 , B. Mellado 5 1 Translational Oncology Laboratory, Fundacio Clínic per a la Recerca Biomèdica, Barcelona, SPAIN, 2 Medical Oncology, Institut Català d’Oncologia-Badalona, Badalona, SPAIN, 3 Oncologia Medica, Hospital de Sabadell Corporacis Parc Tauli, Sabadell, SPAIN, 4 Urology, Hospital Clínic, Barcelona, SPAIN, 5 Medica Oncology, Hospital Clínic, Barcelona, SPAIN, 6 Urology, Hospital Germans Trias i Pujol, Badalona, SPAIN, 7 Urology, Hospital Parc Tauli, Sabadell, SPAIN, 8 Medical Oncology, Hospital Clinic y Provincial de Barcelona, Barcelona, SPAIN Background: HRLPC has an increased risk of positive margins and recurrence after local treatment. Neoadjuvant docetaxel has not shown to increase the percentage of pathological complete responses (pRCs) respect to hormone-therapy alone. In a previous phase II trial of neoadjuvant D plus CAB in patients with HRLPC we reported a 6% pRCs. (Mellado B, Br J Cancer 2009). We proposed that the molecular analysis of residual tumor cells after D + CAB may help to identify molecular mechanisms of treatment resistance. Methods: 93 genes potentially involved in D resistance were selected from a previous molecular study of our group (Marin-Aguilera M, Mol Cancer Ther 2012). Gene transcriptional levels were analyzed by using Taqman low density arrays in 28 formalin-fixed paraffin-embedded (FFPE) tumors from HRLPC patients treated with D + CAG prior radical prostatectomy, and in 36 HRLPC patients who underwent radical prostatectomy without neoadjuvant therapy. GUSB housekeeping gene was the reference for normalization. Gene expression determination was performed with RQ Manager Software for manual data analysis. Results: Differential gene expression of 67.7% (63 of 93 analyzed genes) was found in neoadjuvant treated tumors versus samples without neoadjuvant treatment (P < 0.05). Among them, there were found differences in the expression of genes related with androgen receptor signalling, NFkB transcription factor and epithelial-mesenquimal transition processes. Data on gene expression and its correlation with clinical outcome will be presented at the meeting. Conclusions: Residual tumor cells in prostatectomy specimens after neoadjuvant hormone- and chemotherapy treatment already exhibits a gene expression profile that may be involved in hormone/chemo resistant phenotype. Disclosure: All authors have declared no conflicts of interest. 1681P THE ROLE OF MACROPHAGES POLARIZATION IN PREDICTING PROGNOSIS IN RADICALLY RESECTED GASTRIC CANCER F. Pantano 1 , P. Berti 1 , F.M. Guida 1 , S. Intagliata 1 , F. Graziano 2 , G. Perrone 3 , A. Onetti Muda 3 , B. Vincenzi 1 , G. Tonini 1 , D. Santini 1 1 Medical Oncology, University Campus Bio-Medico, Rome, ITALY, 2 Medical Oncology, Ospedale di Urbino, Urbino, ITALY, 3 Department of Pathology, University Campus Bio-Medico, Rome, ITALY Introduction: Macrophages are one of the major populations of tumor-infiltrating immune cells. Tumor associated Macrophages (TAM) present two different phenotypes or polarizations: classical (M1) characterized by immunostimulation activity and tumor suppression; alternative (M2) characterized by angiogenesis, tumor promotion, and immune suppression. Despite these opposite properties, most of the previous studies focused merely on evaluating absolute TAM count. In this work, for the first time in literature, we evaluated the correlation between the two forms of TAM with survival time in patients affected by gastric cancer after radical surgery. Methods: 52 chemo- and radio-naïve gastric cancer patients undergone to resection for curative intent were included in this retrospective study. Two slides were prepared for each patients and double-stained for CD68/NOS2 (M1) or CD68/CD163 (M2) and five representative high-power fields (×400 magnification) per slide were evaluated for TAM count. The median value of the two macrophage populations density (M1 = 7.0; M2 = 6.4) and the median value of M1/M2 ratio (1.16) was used as cut-off. Results: 27 patients with M1 density above the median had a significantly higher survival compared to those below the median (median OS of 25.6 months, CI95%:22.33-44.85 vs 17.1 months, CI95%:13.66-27.98; P = 0.041). 26 patients with M1/M2 ratio above the median showed median OS of 27.2 months (CI95%:25.45-47.51) compared to 15.5 months (CI95%:11.36-25.50) of the patients below the median (P = 0.001). No statistically significant difference in terms of M1/ M2 ratio was observed between intestinal vs diffuse histological type. No association ix538 | Abstracts Volume 23 | Supplement 9 | September 2012
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Annals of Oncology www.annonc.oxfor
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subscriptions A subscription to Ann
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Annals of Oncology Official Journal
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The European Society for Medical On
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Audit Committee Chair: Fortunato Ci
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Familial cancer Judith Balmaña, Ba
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ESMO 2012 Congress Travel Grants 47
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Exhibitors The following companies
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ESMO Fellowships, 1989-2011 The Eur
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Ondrej Gojis, Czech Republic 2008-2
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abstracts hpv biology and implicati
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abstracts the characterization of l
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abstracts description of intra-tumo
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prevent cell death. It is anticipat
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22IN TARGETING THE HOST IN TNBC G.
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abstracts a paradigm shift in early
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abstracts how can medical oncologis
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feasibility), but by how high the c
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abstracts re-inventing the medical
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abstracts emerging diagnostic and t
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abstracts biologically based treatm
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abstracts molecular targets in mali
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abstracts melanoma therapy: from fr
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diagnosis and can also be used for
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analysis at 11 months median follow
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mouse model of Kras mutant NSCLC. I
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abstracts subtyping soft tissue sar
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abstracts key topics in supportive
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ESMO-CSCO Joint Symposium: Building
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ESMO-EANM-ESR Joint Symposium: Imag
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ESMO-ESTRO Joint Symposium: Innovat
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ESMO-MASCC Joint Symposium: Integra
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ESO Society Symposium: Celebrating
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Results: TIMP-1 expression was incr
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will benefit from this targeted the
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cytomegalovirus (CMV). Analysis of
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functional consequences of Endoglin
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elationship between the ROR score,
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183P EPIDERMAL GROWTH FACTOR RECEPT
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Plasma adiponectin level on the pre
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Table: 198P PFS OS Median, mo HR Me
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204P EVALUATION OF PTEN AND PIK3CA
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Material and methods: We searched P
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Results: The median concentration o
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Table: 226P Methods: Pts were rando
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However, additional analysis sugges
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number of biomarkers have been trie
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Table: 248O 249PD PROTEOMIC PREDICT
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Conclusions: BW and serum Ctrough o
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261P BREAST CANCER SUBTYPES AND OUT
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90 mg/m2-cyclophophamide 600 mg/m2
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to 9 weeks after dosing. Trastuzuma
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Patients and methods: We reviewed d
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sector patients. The aim of this st
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Linear Logistic Model with Relaxed
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Results: The median CTC fold change
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312: Table: Chemotherapy uptake wit
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abstracts breast cancer, locally ad
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Results: 8 trials (2092 pts) with 1
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absolute difference of median value
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Novartis, Genentech, and sanofi-ave
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Results: Three RCTs with 1023 patie
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collected from all patients for det
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355P FIRST REPORT OF LONG-TERM RESP
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361P A RETROSPECTIVE ANALYSIS OF PL
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publications and aggregated in a me
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Thus the primary aim to target BCSC
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383 WHY DO WOMEN WITH BREAST CANCER
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Results: We evaluated 76 pts with M
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more than 6 cycles of capecitabine.
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406TiP PHASE II TRIAL OF PRIMARY SY
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abstracts CNS tumors 410O CONDITION
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Conclusions: Our data suggested tha
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Conclusions: As in other cancer typ
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432 GAMMA KNIFE RADIOSURGERY AS A M
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abstracts developmental therapeutic
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1PR), but no responses were seen in
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RO and Cd, as well as PD data for c
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and vulvar Ca), and 11 SDs were obs
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knowing HLA-A status double-blindly
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Acquired-resistance to EGFR inhibit
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474P PHASE 1 STUDY OF THE SELECTIVE
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TST is active in breast and gastric
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Treatment-induced shedding of circu
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Methods: Either co-cultures of peri
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501 PRECLINICAL DATA INVESTIGATING
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509TiP LUX-LUNG 8: A RANDOMIZED, OP
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(P = 0.64). Synchronous BBC was sig
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abstracts gastrointestinal tumors,
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Disclosure: M. Lee: I am an employe
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plus intravenous Bev(7.5mg/kg q 21d
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anti-EGFR treatment. The present st
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patients harboring a T/T genotype t
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551P ADJUVANT CHEMOTHERAPY (AC) USE
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experienced significantly more ≥
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functioning scales. Exploratory ana
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oxaliplatin (100 mg/m 2 )/raltitrex
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572P PANERB STUDY: WHICH CATEGORY O
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Results: 92/114 patients were preop
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585P CHANGES IN THE INTESTINAL ENVI
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592P PHASE II TRIAL OF COMBINED CHE
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minutes. In a previous study, 30-mi
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Patients and methods: Chemotherapy-
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612P ARE PATIENTS WITH RESECTABLE R
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Conclusions: AMPK and ACC activatio
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of surgical monotherapy in patients
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Table: 632 633 AFLIBERCEPT/FOLFIRI
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factors play the determining role i
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Abstract withdrawn in exceptional c
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were respectively 10.6 vs 8.5 vs 3.
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Results: 20 gastrointestinal cancer
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abstracts gastrointestinal tumors,
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Day 8. A second identical course wa
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proven in stage I GC. The aim of th
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Conclusions: Longer OS to FOLFOX wa
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692P PRELIMINARY SAFETY DATA FROM A
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subgroup. Taking into consideration
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Results: Three years of adjuvant im
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considered sufficient to give an 80
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721P FIRST-LINE TREATMENT WITH FOLF
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after Gem-based therapy. The additi
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735P RADIOGRAPHIC PARAMETERS IN PRE
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validate the revised AJCC 7th stagi
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Results: Among 862 MM we identified
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Results: Frequently reported advers
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gastric cancer patients with CNS me
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discriminate the prognosis of HCC p
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prospective, non-interventional stu
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abstracts genitourinary tumors, non
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787O EXTERNAL VALIDATION OF THE ASS
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patient preference for P over S, an
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798PD OPEN-LABEL PHASE II TRIAL OF
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Hb, PS and LM. Median PFS for patie
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may have led to reduced dose and sh
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Results: 1,622 patients were identi
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RCC) was designed to address an unm
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Patients and methods: This is a sin
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treatment at week 4, and week 12 by
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effective in second or further line
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Conclusions: In pts with RCC treate
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using Drug inCode ® pharmacogeneti
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Table: 857P standard, but is not av
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efused HDCT. Of 23 patients, 20 com
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we identified 49 and 220 patients w
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879 TREATMENT OF PATIENTS WITH META
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Median overall survival (OS) was 26
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abstracts Genitourinary tumors, pro
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and week 13 BPI-SF Q3 scores), 28%
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Working Group (PCWG)-2 guidelines r
Page 301 and 302:
atio HR 0.39; CI 0.18, 0.83, p = 0.
Page 303 and 304:
We observed tumor responses and pro
Page 305 and 306:
Here we report emerging data from t
Page 307 and 308:
928P LHRH AGONIST-INDUCED SUPPRESSI
Page 309 and 310:
Disclosure: S. Oudard: Has acted as
Page 311 and 312:
939P NEOADJUVANT SIPULEUCEL-T IN LO
Page 313 and 314:
945 BONE TURNOVER MARKERS AND POTEN
Page 315 and 316:
952 SEQUENTIAL ANDROGEN DEPRIVATION
Page 317 and 318:
managed in a multidisciplinary (MD)
Page 319 and 320:
or hypercalcemia at screening; prio
Page 321 and 322:
meeting. The prevalence of LGSC is
Page 323 and 324:
Table: 975PD Continued AMG 386 + pa
Page 325 and 326:
physicians in the U.S. and Europe.
Page 327 and 328:
989P PHASE II STUDY OF COMBINATION
Page 329 and 330:
elated with stage, nodal involvemen
Page 331 and 332:
1004P CASE CONTROL STUDY ON TWO DIF
Page 333 and 334:
eight patients who had infertility
Page 335 and 336:
abstracts head and neck cancer 1016
Page 337 and 338:
same CT/RT; Arm B2: 3 cycles of ind
Page 339 and 340:
induction chemotherapy in the treat
Page 341 and 342:
patients. We have developed a rando
Page 343 and 344:
evaluated by the screening instrume
Page 345 and 346:
morbidities that radiation would le
Page 347 and 348:
Conclusions: Through adequate selec
Page 349 and 350:
abstracts hematological malignancie
Page 351 and 352:
anthracyclines in vitro. A favorabl
Page 353 and 354:
1076P RITUXIMAB PLUS SUBCUTANEOUS C
Page 355 and 356:
than the standard target of ≥2.5
Page 357 and 358:
Patients: From November 2002 to May
Page 359 and 360:
lymphadenopathy and multiple cutane
Page 361 and 362:
prospective non-interventional stud
Page 363 and 364:
Funding: GSK Biologicals Disclosure
Page 365 and 366:
survival rates of 13-25% (Prieto et
Page 367 and 368:
high response rates and prolonged p
Page 369 and 370:
GlaxoSmithKline, Merck Sharp & Dohm
Page 371 and 372:
advisor for Merck Sharp & Dohme, an
Page 373 and 374:
or cutaneous melanoma. A survival u
Page 375 and 376:
systemic therapy or were intolerant
Page 377 and 378:
abstracts neuroendocrine tumors and
Page 379 and 380:
morbidity, with G3 tumors behaving
Page 381 and 382:
pts. Poorly differentiated endocrin
Page 383 and 384:
Adenocarcinoma was present in 25 pa
Page 385 and 386:
Method: Endobronchial ultrasound gu
Page 387 and 388:
widely used by single agent or plat
Page 389 and 390:
disease after surgery were treated
Page 391 and 392:
stage IIIA NSCLC, EML4-ALK fusion-p
Page 393 and 394:
1200P CONCOMITANT CHEMORADIATION GI
Page 395 and 396:
Patients and methods: The study was
Page 397 and 398:
months (95% CI:13-25). The PFS and
Page 399 and 400:
maintenance therapy had favourable
Page 401 and 402:
abstracts non-small cell lung cance
Page 403 and 404:
Ingelheim, GSK Biologicals (compens
Page 405 and 406:
1234PD RANDOMIZED PHASE III TRIAL O
Page 407 and 408:
GlaxoSmithKline (myself, compensate
Page 409 and 410:
1243P IDENTIFICATION OF MICRORNA (M
Page 411 and 412:
N-arm n=34 P-arm n=32 All n=66 Male
Page 413 and 414:
1255P POPULATION BASED EVALUATION O
Page 415 and 416:
1262P DISTINCT SPREAD OF EGFR MUTAT
Page 417 and 418:
1268P VISUAL DISTURBANCES IN PATIEN
Page 419 and 420:
MERCK SERONO: Advisor, speaker in s
Page 421 and 422:
Conclusions: These data from SAiL a
Page 423 and 424:
NSCLC diagnosis and time of BM diag
Page 425 and 426:
1291P PHASE I/II DOSE-FINDING STUDY
Page 427 and 428:
Network utilization of WBCGF in the
Page 429 and 430:
1303P COST EFFECTIVENESS OF PEMETRE
Page 431 and 432:
Results: The patients’ characteri
Page 433 and 434:
EGFR mut at exons 18, 19, 21, and K
Page 435 and 436:
Methods: EML4-ALK fusion was screen
Page 437 and 438:
Results: The median survival time (
Page 439 and 440:
enefit from sustained EGFR blockade
Page 441 and 442:
epresented by 19 pts (32%) female,
Page 443 and 444:
and at least one prior course of ch
Page 445 and 446:
Methods: NSCLC patients with radiog
Page 447 and 448:
1367TiP LONG-TERM ERLOTINIB THERAPY
Page 449 and 450:
Austria, Czech Republic, Finland, G
Page 451 and 452:
were every 6 weeks (wk) (S1), every
Page 453 and 454:
Advantage enrollees (83% vs. 25%) [
Page 455 and 456:
Results: Based on 10,000 simulation
Page 457 and 458:
cancer tumors 12%, Germ cell tumor
Page 459 and 460:
Material and methods: 50 lung cance
Page 461 and 462:
1414TiP IMPLEMENTATION OF CANCER RE
Page 463 and 464:
abstracts palliative care 1422O EFF
Page 465 and 466:
Method and results: A total of 317
Page 467 and 468:
1436P SURVEY ON MODELS OF INTEGRATI
Page 469 and 470:
care unit (PCU) at the National Can
Page 471 and 472:
Characteristic No. % Total 63 1 st
Page 473 and 474:
hysterectomised-9.10% and cervix ca
Page 475 and 476:
abstracts psycho-oncology 1462PD IN
Page 477 and 478:
events, tumour response, and surviv
Page 479 and 480:
abstracts sarcoma 1477O ADHESION TO
Page 481 and 482:
1481PD A PHASE II STUDY OF DOVITINI
Page 483 and 484:
1488P ORGANISATION OF SARCOMA PATIE
Page 485 and 486:
Patients and methods: From August 2
Page 487 and 488: chemotherapy respectively. At a med
Page 489 and 490: of this group Those with relapsed d
Page 491 and 492: 1515 PREDICTORS OF SURVIVAL IN ADOL
Page 493 and 494: abstracts small cell lung cancer an
Page 495 and 496: emaining receiving either CAV or to
Page 497 and 498: 1533P EXPRESSION OF WILM⍰TUMOUR G
Page 499 and 500: more than 3 months after first line
Page 501 and 502: lower recurrence rate of NE. Pegfil
Page 503 and 504: egimens (HR = 2.5, p < 0.001). Phys
Page 505 and 506: 1561P PREDICTIVE DIAGNOSTICS FOR RE
Page 507 and 508: Methods: A prospective multicentre
Page 509 and 510: Table: 1574P Pharmacokinetic parame
Page 511 and 512: Novartis and unrestricted research
Page 513 and 514: studies have shown that chemotherap
Page 515 and 516: (Grade 1) and moderate to severe (G
Page 517 and 518: declined to relatively lower level
Page 519 and 520: 1609P PHYSICAL ACTIVITY (PA) AND PH
Page 521 and 522: patients were admitted to the oncol
Page 523 and 524: Dicarbamin 100 mg/day on day 5 befo
Page 525 and 526: Results: Anemia was detected in 83.
Page 527 and 528: important to carry out randomized s
Page 529 and 530: abstracts translational research 16
Page 531 and 532: expression. Then, we analyzed PB sa
Page 533 and 534: Table: 1657P TH BV + TH HR (95% CI)
Page 535 and 536: BRAF mutations. Circulating free DN
Page 537: 1671P PHASE I CLINICAL TRIAL OF CAN
Page 541 and 542: theorized that the PI3K/AKT pathway
Page 543 and 544: Material and methods: 101 patients
Page 545 and 546: overexpressing and 232 had triple n
Page 547 and 548: author index author index A Aamdal
Page 549 and 550: author index Badran A. ix288 (874)
Page 551 and 552: author index Bösmüller H. ix209 (
Page 553 and 554: author index Chen A. ix319 (966O) C
Page 555 and 556: author index De Droogh E. ix452 (13
Page 557 and 558: author index Esposito G. ix209 (618
Page 559 and 560: author index Geiges G. ix306 (930P)
Page 561 and 562: author index Hartono S. ix70 (155P)
Page 563 and 564: author index Iwasaki H. ix542 (1694
Page 565 and 566: author index Kodaira M. ix90 (228P)
Page 567 and 568: author index Lichtensztejn D. ix350
Page 569 and 570: author index Martinez A. ix496 (153
Page 571 and 572: author index Morishita N. ix432 (13
Page 573 and 574: author index Okamoto N. ix432 (1320
Page 575 and 576: author index Piau S. ix456 (1401P)
Page 577 and 578: author index Rodríguez Rodríguez
Page 579 and 580: author index Scoggins C.R. ix371 (1
Page 581 and 582: author index Stern L. ix272 (823P)
Page 583 and 584: author index Trypaki M. ix429 (1308
Page 585 and 586: author index Whitmore J.B. ix310 (9
Page 587 and 588: subject index subject index A AAV-H
Page 589 and 590:
subject index ix115 (316TiP), ix116
Page 591 and 592:
subject index diffuse large B-cell
Page 593 and 594:
subject index (1033P), ix340 (1036P
Page 595 and 596:
subject index medical information,
Page 597 and 598:
subject index (612P), ix214 (633),
Page 599 and 600:
subject index RCC, ix274 (830P) re-
Page 601 and 602:
subject index TR-FRET, ix84 (206P)
Page 603 and 604:
drug index drug index 1248P, 1250P,
Page 605 and 606:
translational research index transl
Page 607 and 608:
Page 609:
show all

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