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1. Supplementary Figure 2 from Complex Tumor Genomes Inferred from Single Circulating Tumor Cells by Array-CGH and Next-Generation Sequencing

Author: Michael R. Speicher, Jochen B. Geigl, Thomas Bauernhofer, Sabine Riethdorf, Klaus Pantel, Hellmut Samonigg, Heinz Sill, Florian Eisner, Gerald Höfler, Carolin Lackner, Oliver Mauermann, Julie Waldispuehl-Geigl, Sigurd Lax, Eva Maria Hoffmann, Peter Ulz, Martin Pichler, Christin Gasch, Martina Auer, and Ellen Heitzer
Abstract: PDF file - 940K, Evaluation of available material from patient #6. (a-b) Array CGH profiles of the primary tumor (a) and metastasis (b). The multicolor bar codes at the top or bottom of the ratio profiles illustrate the results obtained during the iterative calculations with various window sizes, the single green and red bars summarize the regions which were gained or lost based on all calculations (Supplementary Methods). Black parts in the profile represent balanced regions, lost regions appear in red and gained regions in green.
Published: 2023
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2. Supplementary Figure 8 from Complex Tumor Genomes Inferred from Single Circulating Tumor Cells by Array-CGH and Next-Generation Sequencing

Author: Michael R. Speicher, Jochen B. Geigl, Thomas Bauernhofer, Sabine Riethdorf, Klaus Pantel, Hellmut Samonigg, Heinz Sill, Florian Eisner, Gerald Höfler, Carolin Lackner, Oliver Mauermann, Julie Waldispuehl-Geigl, Sigurd Lax, Eva Maria Hoffmann, Peter Ulz, Martin Pichler, Christin Gasch, Martina Auer, and Ellen Heitzer
Abstract: PDF file - 3383K, Calculation of different integer copy number profiles for CTC03 from patient #6 assuming diploidy (a), triploidy (b), or tetraploidy (c) and the respective array CGH profile (d).
Published: 2023
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3. Supplementary Figure 7 from Complex Tumor Genomes Inferred from Single Circulating Tumor Cells by Array-CGH and Next-Generation Sequencing

Author: Michael R. Speicher, Jochen B. Geigl, Thomas Bauernhofer, Sabine Riethdorf, Klaus Pantel, Hellmut Samonigg, Heinz Sill, Florian Eisner, Gerald Höfler, Carolin Lackner, Oliver Mauermann, Julie Waldispuehl-Geigl, Sigurd Lax, Eva Maria Hoffmann, Peter Ulz, Martin Pichler, Christin Gasch, Martina Auer, and Ellen Heitzer
Abstract: PDF file - 868K, Ratio bin distributions for CTC12 (a) and CTC03 (b) from patient #6. The large bin 13 peak indicates the frequency of oligonucleotides with balanced ratio values. The bins to the right of 13 represent the bins for oligonucleotides with deleted, the bins to the left oligonucleotides with increased values. (a) In CTC12 only one of the bins for deleted values was increased (i.e. bin 15), suggesting that this cell is diploid. In a diploid cell the log2 ratio for balanced values ranges from 0.295 to -0.293 and therefore extends to bins adjacent to 13, which is reflected by the small increases in the bins 12 and 14. The peaks at bins 11 and 12 reflect trisomies (i.e. a 3:2 ratio or an integer copy number of 3), the peak at 9 indicates tetrasomies (i.e. 4:2) or 4 copies). (b) CTC03 had clearly more discrete deleted copy number states visible at bins 15 to 18, suggesting that this cell is tetraploid. In a tetraploid cell the log2 ratio range for balanced values is narrower (i.e. 0.161 to -0.208) as in a diploid cell, which is reflected in the almost empty bins 12 and 14. Bin 15 represents oligonucleotides with ratio values translating to 3 copies, bins 16 and 17 to two copies and bin 18 to one copy. Bin 10 represents 5 copies, bins 8 and 9 six copies, bin 7 seven copies, and bin 4 eight copies.
Published: 2023
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4. Supplementary Table 2 from Complex Tumor Genomes Inferred from Single Circulating Tumor Cells by Array-CGH and Next-Generation Sequencing

Author: Michael R. Speicher, Jochen B. Geigl, Thomas Bauernhofer, Sabine Riethdorf, Klaus Pantel, Hellmut Samonigg, Heinz Sill, Florian Eisner, Gerald Höfler, Carolin Lackner, Oliver Mauermann, Julie Waldispuehl-Geigl, Sigurd Lax, Eva Maria Hoffmann, Peter Ulz, Martin Pichler, Christin Gasch, Martina Auer, and Ellen Heitzer
Abstract: PDF file - 95K, List of 68 genes, which, according to the COSMIC database, are frequently mutated in colorectal carcinoma (CRC) and analyzed in our study.
Published: 2023
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5. Supplementary Figure 3 from Complex Tumor Genomes Inferred from Single Circulating Tumor Cells by Array-CGH and Next-Generation Sequencing

Author: Michael R. Speicher, Jochen B. Geigl, Thomas Bauernhofer, Sabine Riethdorf, Klaus Pantel, Hellmut Samonigg, Heinz Sill, Florian Eisner, Gerald Höfler, Carolin Lackner, Oliver Mauermann, Julie Waldispuehl-Geigl, Sigurd Lax, Eva Maria Hoffmann, Peter Ulz, Martin Pichler, Christin Gasch, Martina Auer, and Ellen Heitzer
Abstract: PDF file - 1303K, Evaluation of available material from patient #9. (a-b) Array CGH profiles of the primary tumor (a) and metastasis (peritoneal carcinomatosis) (b). Regarding the color bar codes please see legend to Supp. Fig. 2.
Published: 2023
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6. Supplementary Figure 6 from Complex Tumor Genomes Inferred from Single Circulating Tumor Cells by Array-CGH and Next-Generation Sequencing

Author: Michael R. Speicher, Jochen B. Geigl, Thomas Bauernhofer, Sabine Riethdorf, Klaus Pantel, Hellmut Samonigg, Heinz Sill, Florian Eisner, Gerald Höfler, Carolin Lackner, Oliver Mauermann, Julie Waldispuehl-Geigl, Sigurd Lax, Eva Maria Hoffmann, Peter Ulz, Martin Pichler, Christin Gasch, Martina Auer, and Ellen Heitzer
Abstract: PDF file - 188K, Sequencing of UCR41 and flanking regions: UCR41 is a 217-bp-long ultra-conserved region depicted in dark green. The gray bar indicates the extremely conserved sequence. The region is flanked by two SNPs that are frequent in the European population (blue arrows). The black curve indicates the mutability, which is higher in non-conserved regions compared with conserved segments. The black bars illustrate the 5 overlapping amplicons used for amplification. Mutations identified in our samples are indicated with red arrows. The genomic coordinates refer to the hg18 assembly of the human genome. (The graph is reproduced with permission from De Grassi et al.)
Published: 2023
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7. Supplementary Figure 5 from Complex Tumor Genomes Inferred from Single Circulating Tumor Cells by Array-CGH and Next-Generation Sequencing

Author: Michael R. Speicher, Jochen B. Geigl, Thomas Bauernhofer, Sabine Riethdorf, Klaus Pantel, Hellmut Samonigg, Heinz Sill, Florian Eisner, Gerald Höfler, Carolin Lackner, Oliver Mauermann, Julie Waldispuehl-Geigl, Sigurd Lax, Eva Maria Hoffmann, Peter Ulz, Martin Pichler, Christin Gasch, Martina Auer, and Ellen Heitzer
Abstract: PDF file - 346K, Analysis of CTC03 of patient #22: The array-CGH ratio profile demonstrates losses on chromosomes 3, 4, 5, 8p, and 18 and gains on chromosomes 7p, 17q, and 20.
Published: 2023
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8. Supplementary Table 3 from Complex Tumor Genomes Inferred from Single Circulating Tumor Cells by Array-CGH and Next-Generation Sequencing

Author: Michael R. Speicher, Jochen B. Geigl, Thomas Bauernhofer, Sabine Riethdorf, Klaus Pantel, Hellmut Samonigg, Heinz Sill, Florian Eisner, Gerald Höfler, Carolin Lackner, Oliver Mauermann, Julie Waldispuehl-Geigl, Sigurd Lax, Eva Maria Hoffmann, Peter Ulz, Martin Pichler, Christin Gasch, Martina Auer, and Ellen Heitzer
Abstract: PDF file - 92K, Identification of mutations in cancer candidate (CAN) genes in patient samples using next-generation sequencing. Mutations that are shared between primary tumor and/or metastasis and/or CTCs are highlighted in bold.
Published: 2023
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9. TP53 Mutational Status and Prediction of Benefit from Adjuvant 5-Fluorouracil in Stage III Colon Cancer Patients

Author: Daniela Kandioler, Martina Mittlböck, Sonja Kappel, Harald Puhalla, Friedrich Herbst, Cord Langner, Brigitte Wolf, Jörg Tschmelitsch, Walter Schippinger, Günther Steger, Friedrich Hofbauer, Hellmut Samonigg, Michael Gnant, Bela Teleky, and Irene Kührer
Subjects: TP53, Predictive biomarker, Stage III colon cancer, Adjuvant 5-fluorouracil, Varying treatment efficacy, Medicine, Medicine (General), R5-920
Abstract: We investigated the hypothesis that the varying treatment efficacy of adjuvant 5-fluorouracil (5FU) in stage III colon cancer is linked to the TP53 mutational status. ABCSG-90 was a prospective randomized trial in which effect of adjuvant 5FU was studied in stage III colon cancer patients. Tumor material of 70% of these patients (389/572) was available for analysis of the biomarker TP53 using a TP53-gene-specific Sanger sequencing protocol. Median follow-up was 88 months. TP53 mutation frequency was 33%. A significant interaction between TP53 status, outcomes and nodal category was found (P = 0.0095). In the N1 category, TP53 wildtype patients had significantly better overall survival than TP53 mutated (81.0% vs. 62.0% overall survival at 5 years; HR = 2.131; 95% CI: 1.344–3.378; P = 0.0010). In the N2 category, the TP53 status did not affect survival (P = 0.4992). In TP53 wildtype patients, the prognostic significance of N category was significantly enhanced (P = 0.0002). In TP53 mutated patients, survival curves of N1 and N2 patients overlapped and nodal category was no longer prognostic. The biomarker TP53 independently predicted effect of adjuvant 5FU in N1 colon cancer patients. TP53 was not predictive in N2 patients, in whom 5FU is known to have no effect.
Published: 2015
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10. Risk stratification for venous thromboembolism in patients with testicular germ cell tumors.

Author: Angelika Bezan, Florian Posch, Ferdinand Ploner, Thomas Bauernhofer, Martin Pichler, Joanna Szkandera, Georg C Hutterer, Karl Pummer, Thomas Gary, Hellmut Samonigg, Joerg Beyer, Thomas Winder, Thomas Hermanns, Christian D Fankhauser, Armin Gerger, and Michael Stotz
Subjects: Medicine, Science
Abstract: BACKGROUND:Patients with testicular germ cell tumors (TGCT) have an increased risk for venous thromboembolism (VTE). We identified risk factors for VTE in this patient cohort and developed a clinical risk model. METHODS:In this retrospective cohort study at the Medical University of Graz we included 657 consecutive TGCT patients across all clinical stages. A predictive model for VTE was developed and externally validated in 349 TGCT patients treated at the University Hospital Zurich. RESULTS:Venous thromboembolic events occurred in 34 (5.2%) patients in the Graz cohort. In univariable competing risk analysis, higher clinical stage (cS) and a retroperitoneal lymphadenopathy (RPLN) were the strongest predictors of VTE (p
Published: 2017
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11. Desmoid Tumor Treated with Polychemotherapy Followed by Imatinib: A Case Report and Review of the Literature

Author: Gudrun Knechtel, Herbert Stoeger, Joanna Szkandera, Katrin Dorr, Alfred Beham, and Hellmut Samonigg
Subjects: Desmoid tumor, Aggressive fibromatosis, Chemotherapy, Imatinib, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Desmoid tumors, also known as aggressive fibromatosis, are tumors of intermediate dignity, which grow slowly but are locally aggressive. These tumors do not metastasize but can be potentially life threatening when infiltrating vital structures. The therapy strategy consists of surgery, radiation and systemic therapy with non-steroidal anti-inflammatory drugs, antiestrogen compounds and cytotoxic chemotherapy. We report on a 40-year-old male patient with advanced fibromatosis of the neck who has been treated with 7 cycles of polychemotherapy (adriablastin, ifosfamide and dacarbazine) followed by targeted therapy with imatinib. Tumor response was evaluated clinically and by magnetic resonance imaging. The tumor decreased significantly after the first cycle of chemotherapy and tumor-related symptoms declined. The response continued after switching to targeted therapy with imatinib, which is currently ongoing. The best treatment for this rare tumor remains under discussion. Doxorubicin and dacarbazine are frequently used agents. We included ifosfamide in our therapy, which is standard in the treatment of soft tissue tumors. The tyrosine kinase inhibitor imatinib seems to offer new possibilities and is currently investigated in randomized trials. We conclude that combination chemotherapy including doxorubicin, ifosfamide and dacarbazine in the treatment of aggressive fibromatosis should be considered for patients suffering from unresectable, advanced disease and clinical symptoms which require a rapid response to therapy.
Published: 2010
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12. Prevalence of comorbidity in cancer patients scheduled for systemic anticancer treatment in Austria

Author: Michael Fiegl, Wolfgang Hilbe, Hellmut Samonigg, David Fuchs, H. Stöger, Maria Johanna Schandl, Josef Thaler, Heinz Ludwig, Marija Balic, Peter Krippl, Andreas L. Petzer, Beate Mayrbäurl, Reinhard Stauder, Richard Greil, Sylvia Gusel, Brigitte Mlineritsch, Florian Eisner, Wolfgang Stangl, Ansgar Weltermann, and Karin Hegenbarth
Subjects: medicine.medical_specialty, education.field_of_study, Performance status, business.industry, Population, Cancer, Hematology, Disease, medicine.disease, Comorbidity, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Oncology, 030220 oncology & carcinogenesis, Internal medicine, medicine, Gastrointestinal cancer, business, Lung cancer, education, 030215 immunology
Abstract: Summary The purpose of this observational study was to determine the prevalence of comorbid conditions in cancer patients with solid tumours selected for specific treatment at 12 divisions of medical oncology in Austria. Data from 1137 patients were collected using a standardized questionnaire; of these, 1036 datasets were evaluable for further analysis. Data were prospectively collected from patients during an in- or outpatient hospital visit over a 4-month period in 2011. Of these patients 42% had gastrointestinal cancer, 31% had breast cancer, 9% lung cancer and the remaining had urogenital cancer, sarcoma or other types of rare cancers. Around two-thirds of patients had metastatic disease (59%), confined to a single organ site in 55% of patients. A high proportion of patients had a good performance status (Eastern Cooperative Oncology Group [ECOG] 0, 1: 82%). Comorbid conditions were classified according to the Charlson scheme score and were present in 86% of patients with a median age of 64 years. The predominant conditions were cardiovascular diseases (57%), metabolic diseases (44%), endocrinological diseases (30%), gastrointestinal diseases (26%), neurological (23%) and respiratory diseases (23%). As has been reported by others we found a clear association between number of comorbid conditions and age. While 60% of the whole population had at least 2 comorbidities, most patients of the elderly population (89%) had more than three comorbidities. The high proportion of patients with comorbidities and accompanying medication represents a substantial challenge for medical oncologists in selecting the optimal cancer-specific treatment especially in the era of novel targeted and immunotherapies. Comorbid conditions and accompanying comedications require special precautions concerning potential interactions and unexpected adverse reactions from prescribed tumour-specific treatment.
Published: 2019
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13. Evaluation of uric acid as a prognostic blood-based marker in a large cohort of pancreatic cancer patients.

Author: Michael Stotz, Joanna Szkandera, Julia Seidel, Tatjana Stojakovic, Hellmut Samonigg, Daniel Reitz, Thomas Gary, Peter Kornprat, Renate Schaberl-Moser, Gerald Hoefler, Armin Gerger, and Martin Pichler
Subjects: Medicine, Science
Abstract: BackgroundRecently, chemical blood parameters gain more attraction as potential prognostic parameters in pancreatic cancer (PC). In the present study we investigated the prognostic relevance of the uric acid (UA) level in blood plasma at the time of diagnosis for overall survival (OS) in a large cohort of patients with PC.Patients and methodsData from 466 consecutive patients with ductal adenocarcinoma of the pancreas were evaluated retrospectively. Overall survival (OS) was analysed using the Kaplan-Meier method. To further evaluate the prognostic significance of the UA level, univariate and multivariate Cox regression models were calculated.ResultsNone of the clinicopathological parameters (tumour grade, clinical stage, age, CA19-9 level, Karnofski Index (KI) or surgical resection) except gender was associated with UA level. In univariate analysis we observed the elevated UA level (ConclusionIn conclusion, we identified the UA level at time of diagnosis as an independent prognostic factor in PC patients. Our results indicate that the UA level might represent a novel and useful marker for patient stratification in PC management.
Published: 2014
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14. Pre-treatment anemia is a poor prognostic factor in soft tissue sarcoma patients.

Author: Joanna Szkandera, Armin Gerger, Bernadette Liegl-Atzwanger, Michael Stotz, Hellmut Samonigg, Ferdinand Ploner, Tatjana Stojakovic, Andreas Leithner, and Martin Pichler
Subjects: Medicine, Science
Abstract: Anemia refers to low hemoglobin (Hb) levels, represents a common symptom and complication in cancer patients and was reported to negatively influence survival in patients with various malignancies. In the present study, we aimed to explore the prognostic impact of pre-operative Hb levels on clinical outcome in a large cohort of soft tissue sarcoma (STS) patients after curative surgery.Retrospective data from 367 STS patients, which were operated between 1998 and 2013, were included in the study. Cut-off levels for anemia were defined as Hb
Published: 2014
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15. Herausforderungen an eine Universität

Author: Hellmut Samonigg
Published: 2021
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16. External validation of the derived neutrophil to lymphocyte ratio as a prognostic marker on a large cohort of pancreatic cancer patients.

Author: Joanna Szkandera, Michael Stotz, Florian Eisner, Gudrun Absenger, Tatjana Stojakovic, Hellmut Samonigg, Peter Kornprat, Renate Schaberl-Moser, Wael Alzoughbi, Anna Lena Ress, Friederike Sophia Seggewies, Armin Gerger, Gerald Hoefler, and Martin Pichler
Subjects: Medicine, Science
Abstract: BackgroundWith growing evidence on the role of inflammation in cancer biology, the presence of a systemic inflammatory response has been postulated as having prognostic significance in a wide range of cancer types. The derived neutrophil to lymphocyte ratio (dNLR), which represents an easily determinable potential prognostic marker in daily practise and clinical trials, has never been externally validated in pancreatic cancer (PC) patients.MethodsData from 474 consecutive PC patients, treated between 2004 and 2012 at a single centre, were evaluated retrospectively. Cancer-specific survival (CSS) was assessed using the Kaplan-Meier method. To evaluate the prognostic relevance of dNLR, univariate and multivariate Cox regression models were applied.ResultsWe calculated by ROC analysis a cut-off value of 2.3 for the dNLR to be ideal to discriminate between patients' survival in the whole cohort. Kaplan-Meier curve reveals a dNLR≥2.3 as a factor for decreased CSS in PC patients (pConclusionIn the present study we confirmed elevated pre-treatment dNLR as an independent prognostic factor for clinical outcome in PC patients. Our data encourage independent replication in other series and settings of this easily available parameter as well as stratified analysis according to tumor resectability.
Published: 2013
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17. Optimization of Diagnostic Elisa - Based Tests for the Detection of Auto-Antibodies Against Tumor Antigens in Human Serum

Author: Daria Štefatić, Monika Riederer, Marija Balić, Nadia Dandachi, Stefanie Stanzer, Birgit Janesch, Margit Resel, Darko Ler, Hellmut Samonigg, and Thomas Bauernhofer
Subjects: Auto-antibody, tumor marker, ELISA, colorectal cancer, Biology (General), QH301-705.5
Abstract: Colorectal cancer is one of the most common cancer types worldwide and it continues to be a serious public health problem. Early detection and diagnosis are of great importance in cancer management. At present, diagnostic blood tests are based on the detection of tumor-associated markers such as carcinoembryonic antigen (CEA), the cancer antigen CA19-9 for gastrointestinal cancer, CA15-3 for breast cancer or CA125 for ovarian cancer. The lack of sensitivity and specificity of these markers prevents their general use in cancer screening of an average risk population. Therefore, new cancer biomarkers or better screening methods are necessary to improve the diagnostics of the disease. This study was directed to the optimization of a diagnostic, enzyme linked immunosorbent assay (ELISA) based test to identify and validate new serum markers, such as extracellular Protein Kinase A (ecPKA) and Nicotinamide A-Meth- yltransferase (NNMT). In this type of assay, the cancer antigens are quantified indirectly - by detecting the presence of auto-antibodies against tumor proteins in human serum. The result of the optimization and validation process was in the case of ecPKA a reproducible and stable assay. In case of NNMT the assay was probably not sensitive enough.
Published: 2008
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18. Neoadjuvant Chemotherapy with Capecitabine, Oxaliplatin and Bevacizumab Followed by Concomitant Chemoradiation and Surgical Resection in Locally Advanced Rectal Cancer with High Risk of Recurrence – A Phase II Study

Author: Michael Gnant, Hellmut Samonigg, Alexander de Vries, Gudrun Piringer, Richard Greil, Dietmar Öfner, Austrian Breast, Josef Thaler, J. Tschmelitsch, Wolfgang Eisterer, and Lidija Sölkner
Subjects: Adult, Male, Risk, 0301 basic medicine, Cancer Research, medicine.medical_specialty, Organoplatinum Compounds, Bevacizumab, Colorectal cancer, Antineoplastic Agents, Capecitabine, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Mucositis, Humans, Aged, Performance status, Rectal Neoplasms, business.industry, Chemoradiotherapy, General Medicine, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Total mesorectal excision, Neoadjuvant Therapy, Oxaliplatin, Surgery, Treatment Outcome, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Concomitant, Female, Neoplasm Recurrence, Local, business, medicine.drug
Abstract: Aim To evaluate feasibility and safety of neoadjuvant chemotherapy with capecitabine, oxaliplatin and bevacizumab followed by concomitant standard chemoradiation and surgical resection in patients with high-risk locally advanced rectal cancer. Patients and methods Magnetic resonance imaging (MRI)-defined high-risk cT3/4 rectal cancer patients were treated with 3 cycles of neoadjuvant chemotherapy with capecitabine (1,000 mg/m2 twice daily days 1-14, 22-35, 43-56), oxaliplatin (130 mg/sqm on days 1, 22, 43) and bevacizumab (7.5 mg/kg on days 1, 22, 43) followed by capecitabine (825 mg/m2 twice daily on radiotherapy days week 1-4) concomitantly with radiotherapy (1.8 Gy daily up to 45 Gy in 5 weeks) and surgical resection by total mesorectal excision. Feasibility, safety, response rate and postoperative morbidity were evaluated. Results Twenty-five patients were recruited. Median age was 62 years (range=24-78 years) and all patients had Eastern Cooperation Oncology Group (ECOG) performance status 0. From all patients, 79.2% finished neoadjuvant chemotherapy. Twenty patients underwent surgery. Pathologic complete remission rate, R0 resection and T-downstaging were achieved in 25%, 95% and 54.2% of the "intention to treat" (ITT) patients. The most common grade 3 adverse events (AEs) during neoadjuvant chemotherapy were diarrhea (16.6%) and mucositis (12.5%). In one patient, a grade 4 acute renal failure occurred (4.2%). During chemoradiation, skin reactions (5.3%) were the most common grade 3 AEs. Two major perioperative complications required re-intervention. Conclusion Neoadjuvant chemotherapy with bevacizumab, capecitabine and oxaliplatin followed by concomitant standard chemoradiation is feasible in patients with high-risk locally advanced rectal cancer (LARC) and resulted in complete pathologic remission (pCR) rate of 25% and neoadjuvant chemotherapy completion rate of 80%.
Published: 2017
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19. A Pilot Randomized Trial Assessing the Effect of a Psychoeducational Intervention on Psychoneuroimmunological Parameters Among Patients With Nonmetastatic Breast Cancer

Author: Thomas Bauernhofer, Clemens Farkas, Stefanie Stanzer, Verena Ladinek, Thomas Augustin, Barbara Obermayer-Pietsch, Hellmut Samonigg, Elisabeth Andritsch, and S. Zloklikovits
Subjects: medicine.medical_specialty, Psychoeducational intervention, Breast Neoplasms, Pilot Projects, Anxiety, T-Lymphocytes, Regulatory, law.invention, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Randomized controlled trial, Patient Education as Topic, Interquartile range, law, Internal medicine, Outcome Assessment, Health Care, medicine, Humans, In patient, Applied Psychology, Aged, business.industry, Cancer, Psychoneuroimmunology, Middle Aged, medicine.disease, 030227 psychiatry, Psychotherapy, Psychiatry and Mental health, T cell subset, Female, business, 030217 neurology & neurosurgery, State-Trait Anxiety Inventory, Follow-Up Studies
Abstract: OBJECTIVE The aim of this study was to determine a potential benefit of the specific psychoeducational intervention "Learning to Live with Cancer" (LTLWC) for patients with operated nonmetastatic breast cancer, with respect to psychological variables and endocrine and immune parameters. METHODS Fifty-two postmenopausal women with operated stage I to III breast cancer were randomized to either a breast cancer intervention group (BCIG, n = 30) who immediately began participating in the LTLWC intervention program or to a breast cancer control group (BCCG, n = 22). Matched healthy women were asked to participate as a noncancer comparison group (n = 26). All participants were evaluated at three different time points (t1-t3) using a set of standardized questionnaires and blood samples were taken to analyze immune cell subsets and stress hormone levels. RESULTS A significant reduction in trait anxiety/State Trait Anxiety Inventory score was observed in the BCIG (t1: median = 35.0 [interquartile range = 28.0-38.0] versus t3: median = 26.0 [interquartile range = 18.5-37.0], p = .0001) compared with the BCCG (t1: median = 41.0 [interquartile range =32.75-49.0]; t3: median = 38.5 [interquartile range = 30.75-46.5], p = .01524; p interaction = .001). In parallel, a significant rise of serotonin levels (t1: median = 66.5 ng/ml [interquartile range = 11.50-106.00] versus t3: median = 80.5 ng/ml [interquartile range =59.00-118.00], p = .00008) as well as a significant reduction of the elevated number of Treg cells at baseline (t1: median = 4.45% [interquartile range = 4.00-5.33] versus t3: median = 2.80% [interquartile range = 2.68-3.13], p < .00001) were observed in the BCIG versus no change in the BCCG. A significant statistical association between reduced trait anxiety and decreased Treg cell number could be demonstrated in the BCIG (r = .62, p < .01). CONCLUSIONS The observed results of this study provide preliminary support for the efficacy of the LTLWC program in significantly improving psychoneuroimmunological parameters in patients with nonmetastatic breast cancer.
Published: 2018

20. TP53 Mutational Status and Prediction of Benefit from Adjuvant 5-Fluorouracil in Stage III Colon Cancer Patients

Author: Jörg Tschmelitsch, Friedrich Hofbauer, Hellmut Samonigg, Sonja Kappel, Harald Puhalla, Cord Langner, Daniela Kandioler, Michael Gnant, Walter Schippinger, Bela Teleky, Irene Kührer, Friedrich Herbst, Günther G. Steger, Brigitte Wolf, and Martina Mittlböck
Subjects: Male, Oncology, medicine.medical_specialty, endocrine system diseases, Colorectal cancer, medicine.medical_treatment, lcsh:Medicine, Varying treatment efficacy, General Biochemistry, Genetics and Molecular Biology, stomatognathic system, Internal medicine, Biomarkers, Tumor, medicine, Humans, TP53, Prospective cohort study, Survival rate, neoplasms, Survival analysis, lcsh:R5-920, LEV, levamisole, INF, interferon, business.industry, Hazard ratio, lcsh:R, HR, hazard ratios, General Medicine, medicine.disease, Adjuvant 5-fluorouracil, Surgery, FFPE, formalin-fixed paraffin-embedded, 5FU, 5-fluorouracil, Predictive biomarker, CI, confidence intervals, Fluorouracil, ABCSG, Austrian Breast and Colorectal Cancer Study Group, Colonic Neoplasms, Mutation, Biomarker (medicine), Original Article, Female, Stage III colon cancer, Tumor Suppressor Protein p53, business, lcsh:Medicine (General), Adjuvant, medicine.drug
Abstract: We investigated the hypothesis that the varying treatment efficacy of adjuvant 5-fluorouracil (5FU) in stage III colon cancer is linked to the TP53 mutational status. ABCSG-90 was a prospective randomized trial in which effect of adjuvant 5FU was studied in stage III colon cancer patients. Tumor material of 70% of these patients (389/572) was available for analysis of the biomarker TP53 using a TP53-gene-specific Sanger sequencing protocol. Median follow-up was 88 months. TP53 mutation frequency was 33%. A significant interaction between TP53 status, outcomes and nodal category was found (P = 0.0095). In the N1 category, TP53 wildtype patients had significantly better overall survival than TP53 mutated (81.0% vs. 62.0% overall survival at 5 years; HR = 2.131; 95% CI: 1.344–3.378; P = 0.0010). In the N2 category, the TP53 status did not affect survival (P = 0.4992). In TP53 wildtype patients, the prognostic significance of N category was significantly enhanced (P = 0.0002). In TP53 mutated patients, survival curves of N1 and N2 patients overlapped and nodal category was no longer prognostic. The biomarker TP53 independently predicted effect of adjuvant 5FU in N1 colon cancer patients. TP53 was not predictive in N2 patients, in whom 5FU is known to have no effect., Highlights • The TP53 status was found to be an independent predictive marker for the effect of adjuvant 5FU in stage III colon cancer. • In the N1 category, patients with wildtype TP53 experienced a significant survival benefit from adjuvant 5FU. • In TP53 mutant patients survival curves of N1 and N2 patients overlapped and nodal category was no longer prognostic. Postoperative chemotherapy is recommended for all patients with lymph node positive colon cancer. In colon cancer, mutations in the TP53 gene are present in more than 30% of tumors. We found that the most commonly used postoperative chemotherapy resulted in a marked survival benefit for patients with normal TP53 status while it was associated with significant survival disadvantage in TP53 mutant patients. Overall the survival disadvantage of the mutated patients almost balanced the survival benefit of the TP53 normal patients. This might be an explanation why chemotherapy resulted in less progress in survival of colon cancer than we would have expected.
Published: 2015

21. The derived neutrophil/lymphocyte ratio predicts poor clinical outcome in soft tissue sarcoma patients

Author: Tatjana Stojakovic, Andreas Leithner, Joerg Friesenbichler, Hellmut Samonigg, Michael Stotz, Joanna Szkandera, Bernadette Liegl-Atzwanger, Armin Gerger, and Martin Pichler
Subjects: Male, Oncology, medicine.medical_specialty, Multivariate analysis, Neutrophils, Soft Tissue Neoplasms, Disease-Free Survival, Leukocyte Count, Predictive Value of Tests, Internal medicine, medicine, Humans, Lymphocytes, Aged, Retrospective Studies, Receiver operating characteristic, Surrogate endpoint, business.industry, Soft tissue sarcoma, Hazard ratio, Cancer, Sarcoma, General Medicine, Middle Aged, medicine.disease, Confidence interval, Surgery, Treatment Outcome, Cohort, Female, business
Abstract: Background Inflammation plays an important role in tumor proliferation and survival in cancer patients. The aim of this study was to investigate the prognostic impact of the pre-operative–derived neutrophil/lymphocyte ratio (dNLR) in a large cohort of soft tissue sarcoma (STS) patients after curative surgical resection. Methods The impact of preoperative dNLR on disease-free survival (DFS) and overall survival (OS) in retrospectively evaluated 340 STS patients was assessed using Kaplan–Meier curves and Cox proportional models. Results Applying receiver operating curve analysis, we determined a cut-off value of 2.39 for the dNLR to be optimal for discrimination of patients' survival in the whole cohort. Kaplan–Meier curves revealed a dNLR greater than or equal to 2.39 as a marker for decreased DFS ( P = .031) and OS ( P = .007, log-rank test) in STS patients. In multivariate analysis, increased dNLR was significantly associated with poor OS (hazard ratio 1.60, 95% confidence interval 1.07 to 2.40, P = .022). Conclusions This study demonstrates that preoperative dNLR might represent a well-correlated surrogate marker for the widely validated NLR. The dNLR is easily obtainable and can provide important information for individual risk assessment in clinical trials.
Published: 2015
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22. Prognostic value of KRAS mutations in stage III colon cancer: post hoc analysis of the PETACC8 phase III trial dataset

Author: Josef Thaler, Richard Greil, Johannes Gaenzer, Wolfgang Eisterer, Joerg Tschmelitsch, Hellmut Samonigg, August Zabernigg, Franz Schmid, Günther Steger, Robert Steinacher, Johannes Andel, Alois Lang, Reinhold Függer, Friedrich Hofbauer, Ewald Woell, Dietmar Geissler, Alfred Lenauer, Manfred Prager, Jean-Luc Van Laethem, Eric Van Cutsem, Geert D'Haens, Gauthier Demolin, Joseph Kerger, Guido Deboever, Gilbert Ghillebert, Marc Polus, Hassan RezaieKalantari, Thierry Delaunoit, Jean Charles Goeminne, Marc Peeters, Philippe Vergauwe, Ghislain Houbiers, Yves Humblet, Jos Janssens, Dirk Schrijvers, Erik Vanderstraeten, Jan Vermorken, Daniel Van Daele, Michel Ferrante, Frederic Forget, Alain Hendlisz, Mette Yilmaz, Svend Erik Nielsen, Lene Vestermark, Jim Larsen, Marc Ychou, Ayman Zawadi, Mohamed-Ayman Zawadi, Olivier Bouche, Laurent Mineur, Jaafar Bennouna-Louridi, Louis Marie Dourthe, Eveline Boucher, Julien Taieb, Denis Pezet, Francoise Desseigne, Michel Ducreux, Patrick Texereau, Laurent Miglianico, Philippe Rougier, Serge Fratte, Charles-Briac Levache, Yacine Merrouche, Stephen Ellis, Christophe Locher, Jean-Francois Ramee, Claire Garnier, Frederic Viret, Bruno Chauffert, Isabelle Cojean-Zelek, Pierre Michel, Cedric Lecaille, Christian Borel, Jean-Francois Seitz, Denis Smith, Catherine Lombard-Bohas, Thierry Andre, Jean-Marc Gornet, Francine Fein, Marie-Aude Coulon-Sfairi, Marie-Christine Kaminsky, Jean-Paul Lagasse, Dominique Luet, Pierre-Luc Etienne, Mohamed Gasmi, Andre Vanoli, Suzanne Nguyen, Thomas Aparicio, Hervé Perrier, Noel Stremsdoerfer, Philippe Laplaige, Dominique Arsene, Dominique Auby, Laurent Bedenne, Romain Coriat, Bernard Denis, Patrick Geoffroy, Gilles Piot, Yves Becouarn, Gilbert Bordes, Gael Deplanque, Olivier Dupuis, Frederic Fruge, Rosine Guimbaud, Thierry Lecomte, Gérard Lledo, Iradej Sobhani, Amani Asnacios, Ahmed Azzedine, Christophe Desauw, Marie-Pierre Galais, Dany Gargot, You-Heng Lam, Abakar Abakar-Mahamat, Jean-Francois Berdah, Sylviane Catteau, Marie-Christine Clavero-Fabri, Jean-Francois Codoul, Jean-Louis Legoux, Denis Goldfain, Pierre Guichard, Denis Pere Verge, Jocelyne Provencal, Bruno Vedrenne, Catherine Brezault-Bonnet, Denis Cleau, Jean-Paul Desir, David Fallik, Bruno Garcia, Marie-Hélène Gaspard, Dominique Genet, Johannes Hartwig, Yves Krummel, Tamara MatysiakBudnik, Vanessa Palascak-Juif, Harizo Randrianarivelo, Yves Rinaldi, Albert Aleba, Ariane Darut-Jouve, Aimery de Gramont, Herve Hamon, Frederic Wendehenne, Axel Matzdorff, Michael Konrad Stahl, Wolfgang Schepp, Martin Burk, Lothar Mueller, Gunnar Folprecht, Michael Geissler, Luisa Mantovani-Loeffler, Thomas Hoehler, Walter Asperger, Hendrik Kroening, Ludwig Fischer von Weikersthal, Stefan Fuxius, Matthias Groschek, Johannes Meiler, Tanja Trarbach, Jacqueline Rauh, Nicolas Ziegenhagen, Albrecht Kretzschmar, Ullrich Graeven, Arnd Nusch, Goetz von Wichert, Ralf-Dieter Hofheinz, Gerhard Kleber, Karl-Heinz Schmidt, Ursula Vehling-Kaiser, Claudia Baum, Jochen Schuette, Georg Martin Haag, Wilhelm Holtkamp, Jochen Potenberg, Tobias Reiber, Georg Schliesser, Hans-Joachim Schmoll, Wolfgang Schneider-Kappus, Wolfgang Abenhardt, Claudio Denzlinger, Jan Henning, Bartscht Marxsen, Hans GuenterDerigs, Helmut Lambertz, Ingulf Becker-Boost, Karel Caca, Christian Constantin, Thomas Decker, Henning Eschenburg, Sigrun Gabius, Holger Hebart, Albrecht Hoffmeister, Heinz-August Horst, Stephan Kremers, Malte Leithaeuser, Sebastian Mueller, Siegfried Wagner, Severin Daum, Frank Schlegel, Martina Stauch, Volker Heinemann, Roberto Labianca, Giuseppe Colucci, Dino Amadori, Enrico Mini, Alfredo Falcone, Corrado Boni, Evaristo Maiello, Luciano Latini, Alberto Zaniboni, Giuseppe Aprile, Sandro Barni, Rodolfo Mattioli, Andrea Martoni, Rodolfo Passalacqua, Mario Nicolini, Enzo Pasquini, Carla Rabbi, Enrico Aitini, Alberto Ravaioli, Carlo Barone, Guido Biasco, Stefano Tamberi, Angelo Gambi, Claudio Verusio, Marina Marzola, Giorgio Lelli, Stefano Cascinu, Paolo Bidoli, Massimo Vaghi, Giorgio Cruciani, Francesco Di Costanzo, Alberto Sobrero, Roberto Petrioli, Massimo Aglietta, Oscar Alabiso, Federico Capuzzo, Domenico Cristi Corsi, Stefania Salvagni, Silvana Chiara, Francesco Ferraù, Francesco Giuliani, Sara Lonardi, Nicola Gebbia, Giovanni Mantovani, Evaristo Sanches, Juan Carlos Mellidez, Pedro Santos, Joao Freire, Cristina Sarmento, Luis Costa, Antonio Moreira Pinto, Sergio Barroso, Jorge Espirito Santo, Fátima Guedes, Amélia Monteiro, Anabela Sa, Irene Furtado, Josep Tabernero, Ramon Salazar, Enrique Aranda Aguilar, Fernando Rivera Herrero, Javier Sastre Valera, Manuel ValladaresAyerbes, Jaime FeliuBatlle, Silvia Gil, Carlos Garcia-Giron, Guillermo Lopez Vivanco, Antonia Salud Salvia, Vicente Alonso Orduña, Ruth Vera Garcia, Javier Gallego, Bartomeu Massuti Sureda, Jordi Remon, Maria Jose Safont Aguilera, Luis CireraNogueras, BernadoQueralt Merino, Cristina Gravalos Castro, Purificacion Martinez de Prado, Carlos PijaumePericay, Manuel ConstenlaFigueiras, InmaculadaGuasch Jordan, Maria Jose GomeReina, Amelia Lopez-Ladron Garcia, Antonio Arrivi Garcia-Ramos, Andres Cervantes, Carlos Fernandez Martos, Eugenio MarcuelloGaspar, Ines Cabezas Montero, Pilar Escudero Emperador, Ana Leon Carbonero, Manuel Gallen Castillo, Teresa Garcia Garcia, Jose Garcia Lopez, Encarnacion Gonzalez Flores, Monica GuillotMorales, Marta LlanosMuñoz, Ana López Martín, Joan Maurel, Juan Carlos Camara, Rosario Dueñas Garcia, Mercedes Salgado, Isabel HernandezBusquier, Teresa Checa Ruiz, Adelaida LacastaMuñoa, MiquelNogue Aliguer, Amalia Velasco Ortiz de Taranco, Miguel Mendez Ureña, Ferran Losa Gaspa, Jose Juan Ponce, Carlos Bosch Roig, Pedro Valero Jimenez, Antonio GalanBrotons, Santiago AlbiolRodriguez, Jose Ales Martinez, Liliana Canosa Ruiz, Margarita CentellesRuiz, John Bridgewater, Rob Glynne-Jones, Saad Tahir, Tamas Hickish, Jim Cassidy, and Leslie Samuel
Subjects: Oncology, Hematology
Published: 2015
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23. Prospective validation of a lymphocyte infiltration prognostic test in stage III colon cancer patients treated with adjuvant FOLFOX

Author: Jean-François Emile, Catherine Julié, Karine Le Malicot, Come Lepage, Josep Tabernero, Enrico Mini, Gunnar Folprecht, Jean-Luc Van Laethem, Stéphanie Dimet, Camille Boulagnon-Rombi, Marc-Antoine Allard, Frédérique Penault-Llorca, Jaafar Bennouna, Pierre Laurent-Puig, Julien Taieb, Josef Thaler, Richard Greil, Johannes Gaenzer, Wolfgang Eisterer, Joerg Tschmelitsch, Felix Keil, Hellmut Samonigg, August Zabernigg, Franz Schmid, Günther Steger, Robert Steinacher, Johannes Andel, Björn Jagdt, Alois Lang, Michael Fridrik, Reinhold Függer, Friedrich Hofbauer, Ewald Woell, Dietmar Geissler, Alfred Lenauer, Manfred Prager, Geert D'Haens, Gauthier Demolin, Joseph Kerger, Guido Deboever, Gilbert Ghillebert, Marc Polus, Eric Van Cutsem, Hassan Rezaie Kalantari, Thierry Delaunoit, Jean Charles Goeminne, Marc Peeters, Philippe Vergauwe, Ghislain Houbiers, Yves Humblet, Jos Janssens, Dirk Schrijvers, Erik Vanderstraeten, Jan Vermorken, Daniel Van Daele, Michel Ferrante, Frederic Forget, Alain Hendlisz, Mette Yilmaz, Svend Erik Nielsen, Lene Vestermark, Jim Larsen, Mohamed-Ayman Zawadi, Olivier Bouche, Laurent Mineur, Jaafar Bennouna-Louridi, Louis Marie Dourthe, Marc Ychou, Eveline Boucher, Denis Pezet, Francoise Desseigne, Michel Ducreux, Patrick Texereau, Laurent Miglianico, Philippe Rougier, Serge Fratte, Charles-Briac Levache, Yacine Merrouche, Stephen Ellis, Christophe Locher, Jean-Francois Ramee, Claire Garnier, Frederic Viret, Bruno Chauffert, Isabelle Cojean-Zelek, Pierre Michel, Cedric Lecaille, Christian Borel, Jean-Francois Seitz, Denis Smith, Catherine Lombard-Bohas, Thierry Andre, Jean-Marc Gornet, Francine Fein, Marie-Aude Coulon-Sfairi, Marie-Christine Kaminsky, Jean-Paul Lagasse, Dominique Luet, Pierre-Luc Etienne, Mohamed Gasmi, Andre Vanoli, Suzanne Nguyen, Thomas Aparicio, Hervé Perrier, Noel Stremsdoerfer, Philippe Laplaige, Dominique Arsene, Dominique Auby, Laurent Bedenne, Romain Coriat, Bernard Denis, Patrick Geoffroy, Gilles Piot, Yves Becouarn, Gilbert Bordes, Gael Deplanque, Olivier Dupuis, Frederic Fruge, Rosine Guimbaud, Thierry Lecomte, Gérard Lledo, Iradej Sobhani, Amani Asnacios, Ahmed Azzedine, Christophe Desauw, Marie-Pierre Galais, Dany Gargot, You-Heng Lam, Abakar Abakar-Mahamat, Jean-Francois Berdah, Sylviane Catteau, Marie-Christine Clavero-Fabri, Jean-Francois Codoul, Jean-Louis Legoux, Denis Goldfain, Pierre Guichard, Denis Pere Verge, Jocelyne Provencal, Bruno Vedrenne, Catherine Brezault-Bonnet, Denis Cleau, Jean-Paul Desir, David Fallik, Bruno Garcia, Marie-Hélène Gaspard, Dominique Genet, Johannes Hartwig, Yves Krummel, Tamara Matysiak Budnik, Vanessa Palascak-Juif, Harizo Randrianarivelo, Yves Rinaldi, Albert Aleba, Ariane Darut-Jouve, Aimery de Gramont, Herve Hamon, Frederic Wendehenne, Axel Matzdorff, Michael Konrad Stahl, Wolfgang Schepp, Martin Burk, Lothar Mueller, Michael Geissler, Luisa Mantovani-Loeffler, Thomas Hoehler, Walter Asperger, Hendrik Kroening, Ludwig Fischer von Weikersthal, Stefan Fuxius, Matthias Groschek, Johannes Meiler, Tanja Trarbach, Jacqueline Rauh, Nicolas Ziegenhagen, Albrecht Kretzschmar, Ullrich Graeven, Arnd Nusch, Goetz von Wichert, Ralf-Dieter Hofheinz, Gerhard Kleber, Karl-Heinz Schmidt, Ursula Vehling-Kaiser, Claudia Baum, Jochen Schuette, Georg Martin Haag, Wilhelm Holtkamp, Jochen Potenberg, Tobias Reiber, Georg Schliesser, Hans-Joachim Schmoll, Wolfgang Schneider-Kappus, Wolfgang Abenhardt, Claudio Denzlinger, Jan Henning, Bartscht Marxsen, Hans Guenter Derigs, Helmut Lambertz, Ingulf Becker-Boost, Karel Caca, Christian Constantin, Thomas Decker, Henning Eschenburg, Sigrun Gabius, Holger Hebart, Albrecht Hoffmeister, Heinz-August Horst, Stephan Kremers, Malte Leithaeuser, Sebastian Mueller, Siegfried Wagner, Severin Daum, Frank Schlegel, Martina Stauch, Volker Heinemann, Evaristo Maiello, Luciano Latini, Alberto Zaniboni, Dino Amadori, Giuseppe Aprile, Sandro Barni, Rodolfo Mattioli, Andrea Martoni, Rodolfo Passalacqua, Mario Nicolini, Enzo Pasquini, Carla Rabbi, Enrico Aitini, Alberto Ravaioli, Carlo Barone, Guido Biasco, Stefano Tamberi, Angelo Gambi, Claudio Verusio, Marina Marzola, Giorgio Lelli, Corrado Boni, Stefano Cascinu, Paolo Bidoli, Massimo Vaghi, Giorgio Cruciani, Francesco Di Costanzo, Alberto Sobrero, Roberto Petrioli, Massimo Aglietta, Oscar Alabiso, Federico Capuzzo, Alfredo Falcone, Domenico Cristi Corsi, Roberto Labianca, Stefania Salvagni, Silvana Chiara, Libero Ciuffreda, Francesco Ferraù, Francesco Giuliani, Sara Lonardi, Nicola Gebbia, Giovanni Mantovani, Evaristo Sanches, Juan Carlos Mellidez, Pedro Santos, Joao Freire, Cristina Sarmento, Luis Costa, Antonio Moreira Pinto, Sergio Barroso, Jorge Espirito Santo, Fátima Guedes, Amélia Monteiro, Anabela Sa, Irene Furtado, Ramon Salazar, Enrique Aranda Aguilar, Fernando Rivera Herrero, Javier Sastre Valera, Manuel Valladares Ayerbes, Jaime Feliu Batlle, Silvia Gil, Albert Abad Esteve, Carlos Garcia-Giron, Guillermo Lopez Vivanco, Antonia Salud Salvia, Vicente Alonso Orduña, Ruth Vera Garcia, Javier Gallego, Bartomeu Massuti Sureda, Jordi Remon, Maria Jose Safont Aguilera, Luis Cirera Nogueras, Bernado Queralt Merino, Cristina Gravalos Castro, Purificacion Martinez de Prado, Carlos Pijaume Pericay, Manuel Constenla Figueiras, Inmaculada Guasch Jordan, Maria Jose Gome Reina, Amelia Lopez-Ladron Garcia, Antonio Arrivi Garcia-Ramos, Andres Cervantes, Carlos Fernandez Martos, Eugenio Marcuello Gaspar, Ines Cabezas Montero, Pilar Escudero Emperador, Ana Leon Carbonero, Manuel Gallen Castillo, Teresa Garcia Garcia, Jose Garcia Lopez, Encarnacion Gonzalez Flores, Monica Guillot Morales, Marta Llanos Muñoz, Ana López Martín, Joan Maurel, Juan Carlos Camara, Rosario Dueñas Garcia, Mercedes Salgado, Isabel Hernandez Busquier, Teresa Checa Ruiz, Adelaida Lacasta Muñoa, Miquel Nogue Aliguer, Amalia Velasco Ortiz de Taranco, Miguel Mendez Ureña, Ferran Losa Gaspa, Jose Juan Ponce, Carlos Bosch Roig, Pedro Valero Jimenez, Antonio Galan Brotons, Santiago Albiol Rodriguez, Jose Ales Martinez, Liliana Canosa Ruiz, Margarita Centelles Ruiz, John Bridgewater, Rob Glynne-Jones, Saad Tahir, Tamas Hickish, Jim Cassidy, Leslie Samuel, UE 1373 Fourrages Environnement Ruminants Lusignan, Institut National de la Recherche Agronomique ( INRA ) -Physiologie Animale et Systèmes d'Elevage ( PHASE ) -Environnement et Agronomie ( E.A. ) -Biologie et Amélioration des Plantes ( BAP ) -Fourrages Environnement Ruminants Lusignan ( FERLUS ), Service de pathologie [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, Service de Biostatistique, Fédération Francophone de la Cancérologie Digestive, FFCD, Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Vall d'Hebron University Hospital [Barcelona], Dpt of Internal Medicine, Section of Immunoallergology and Respiratory [Florence] Diseases, University of Florence, Carl Gustav Carus University Hospital, Erasme Hospital, Brussels, Centre Hepato-Biliaire, AP-HP Hôpital Paul Brousse, Modèles de Cellules Souches Malignes et Thérapeutiques, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne ( IMoST ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Clermont Auvergne ( UCA ), Institut de cancérologie de l'Ouest - Nantes ( ICO Nantes ), CRLCC Paul Papin-CRLCC René Gauducheau, Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers ( CRCINA ), Université d'Angers ( UA ) -Université de Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche en Santé de l'Université de Nantes ( IRS-UN ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ), Université de Nantes ( UN ), Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique ( MEPPOT - U1147 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Klinikum Wels Grieskirchen, Oncology department [Salzburg], Salzburger Landesklinikum - Uniklinikum Salzburg ( SALK ), Institute of Chemical Reaction Engineering, Hamburg University of Technology, Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung ( AWI ), Department of Medical Oncology, Medical University Vienna, Department of Internal Medicine, Hospital of Steyr, Department Internal Medicine 3, Centre for Hematology and Medical Oncology, General Hospital Linz, Department Medicine LKH, Institut für Festköperfirschung, Institut des Sciences Moléculaires de Marseille ( ISM2 ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Centrale de Marseille ( ECM ) -Aix Marseille Université ( AMU ), University Hospitals Leuven [Leuven], Katholieke Universiteit Leuven ( KU Leuven ), Pharmacology and Toxicology, Ahvaz Jundishapur University of Medical Sciences, Institut de Biologie Computationnelle ( IBC ), Centre de Coopération Internationale en Recherche Agronomique pour le Développement ( CIRAD ) -Institut National de la Recherche Agronomique ( INRA ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut des Sciences Moléculaires ( ISM ), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique ( CNRS ), Faculty of Veterinary Medicine, Ghent University [Belgium] ( UGENT ), Medical Oncology, Antwerp University Hospital [Edegem], Recombinaison et Expression Génétique, Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier de L'Ardenne (Libramont), Department of Cardiology [Sivas, Turkey], Cumhuriyet University [Sivas, Turkey], Department of Earth Sciences, Durham University, Department of Oncology, Rigshospitalet [Copenhagen], Odense Hospital, CP Kelco ApS, Centre Hospitalier Universitaire de Reims ( CHU Reims ), Institut de Recherche en Cancérologie de Montpellier ( IRCM - U1194 Inserm - UM ), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Université du Québec à Montréal ( UQAM ), Université Panthéon-Sorbonne ( UP1 ), École nationale supérieure d'architecture de Nantes ( ENSA Nantes ), Department of Hepatogastroenterology and Oncology, Hopital Ambroise Pare, 9, Avenue Charles de Gaulle, 92104, Boulogne Cedex, France., Hôpital Ambroise Paré, CH Belfort-Montbéliard, Polyclinique Francheville, Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne ( CHU de Saint-Etienne ), Centre Hospitalier de Meaux, Service d'hématologie, Clinique Catherine de Sienne, Unité de recherche sur les Biopolymères, Interactions Assemblages ( BIA ), Institut National de la Recherche Agronomique ( INRA ), Université de la Méditerranée - Aix-Marseille 2, Centre hospitalier universitaire d'Amiens ( CHU Amiens-Picardie ), CHU Amiens-Picardie, Pôle oncologie médicale, Hôpital des Diaconesses, Génétique du cancer et des maladies neuropsychiatriques ( GMFC ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Bretagne Occidentale - École de sages-femmes ( UBO UFR MSS ESF ), Université de Brest ( UBO ) -Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Service d'Oncologie Médicale [Centre hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Service d'Oncologie Médicale [CHU Saint -Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), Service Gastro-Entérologie, CHU Besançon, Université de Franche-Comté ( UFC ) -Université de Franche-Comté ( UFC ), Centre Alexis Vautrin ( CAV ), Ecophysiologie Végétale, Agronomie et Nutritions ( EVA ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Recherche Agronomique ( INRA ), Image et ville ( IV ), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique ( CNRS ), Département informatique ( INFO ), Université européenne de Bretagne ( UEB ) -Télécom Bretagne-Institut Mines-Télécom [Paris], Service de Gastro-entérologie [Avicenne], Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Agence de l'Environnement et de la Maîtrise de l'Energie - ADEME, Service d'hépato-gastroentérologie, CHU Caen-Hôpital côte de nacre, Département de Médecine, Centre hospitalier de Libourne, Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Fondation FondaMental, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor, Variabilité de réponse aux psychotropes ( VariaPsy - U1144 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Diderot - Paris 7 ( UPD7 ), Département d'oncologie digestive, Institut Bergonié - CRLCC Bordeaux, Hôpital St Joseph, Service de Gynécologie et d'Obstétrique ( CHU Lyon ), Hospices Civils de Lyon ( HCL ), Gastro - Entérologie et Nutrition, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Génétique, Immunothérapie, Chimie et Cancer ( GICC ), Université de Tours-Centre National de la Recherche Scientifique ( CNRS ), Université Montpellier 1 ( UM1 ), Service de gastro-entérologie - Hôpital Henri Mondor, Laboratoire Matière et Systèmes Complexes ( Laboratoire MSC ), Université Paris Diderot - Paris 7 ( UPD7 ) -UFR de Physique, France, Amériques, Espagne – Sociétés, pouvoirs, acteurs ( FRAMESPA ), Université Toulouse - Jean Jaurès ( UT2J ) -Centre National de la Recherche Scientifique ( CNRS ), Regional Hospital of Orleans, Histoire, Archéologie et littératures des Mondes chrétiens et musulmans médiévaux ( CIHAM ), École normale supérieure - Lyon ( ENS Lyon ) -Université Lumière - Lyon 2 ( UL2 ) -École des hautes études en sciences sociales ( EHESS ) -Université Jean Moulin - Lyon III ( UJML ) -Université d'Avignon et des Pays de Vaucluse ( UAPV ) -Centre National de la Recherche Scientifique ( CNRS ), Neurobiologie des signaux intercellulaires ( NSI ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Dept Med Genet, Hôpital Erasme (Bruxelles), Polyclinique de Limoges - site François Chénieux [Limoges], Clinique Médicale B, CHU Strasbourg, Service de gastro-entérologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Hôpital Européen [Fondation Ambroise Paré - Marseille], Asklepios Klinikum Uckermark GmbH, DESY, Notkestr 85, D-22607 Hamburg, Germany, NASA Ames Research Center ( ARC ), Department of Chemistry, Center for Structural Biology, Vanderbilt University [Nashville], Biostatistique et Processus Spatiaux ( BIOSP ), Institute of Ecology [Jena], Friedrich-Schiller-Universität Jena, University of Rostock [Germany], Universität Stuttgart [Stuttgart], Oneonta, Zentrum für Innere Medizin, Klinikum Schwäbisch Gmünd/Stauferklinik, Physiopathologie du stress pancréatique, Institut Armand Frappier ( INRS-IAF ), Institut National de la Recherche Scientifique [Québec] ( INRS ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut Armand Frappier, Institut de Mathématiques de Marseille ( I2M ), Aix Marseille Université ( AMU ) -Ecole Centrale de Marseille ( ECM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Department of Computer Science [Freiburg], University of Freiburg [Freiburg], Institut für Mathematik [Berlin], Technische Universität Berlin ( TUB ), Department of Information Engineering, Computer Science and Mathematics, Università degli Studi dell'Aquila [L'Aquila] ( UNIVAQ.IT ), Department of Animal Sciences, North Carolina Agricultural and Technical State University, FEEM, Romagna Cancer Registry, IRST, Luigi Pierantoni Hospital, Observatoire sociologique du changement ( OSC ), Sciences Po-Centre National de la Recherche Scientifique ( CNRS ), Dipartimento di Chimica, Fisica e Ambiente, Università degli Studi di Udine - University of Udine [Italie], Department of Nuclear Medicine, PET/CT Centre, Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Clinica di Oncologia Medica, AO Ospedali Riuniti, Università Politecnica delle Marche [Ancona] ( UNIVPM ), Universidade Nova de Lisboa ( UNINOVA ), Ottawa Hospital Research Institute [Ottawa] ( OHRI ), Oncologia Medica, Ospedali Riuniti, Ospedale 'San Vincenzo', NIPE, CIPES, European Synchrotron Radiation Facility ( ESRF ), Departamento de Engenharia Informática, Faculdade de Engenharia [Porto] ( FEUP ), Universidade do Porto [Porto]-Universidade do Porto [Porto], 3Decide, Unité de recherche Amélioration, Génétique et Physiologie Forestières ( UAGPF ), Universidade Federal de Campina Grande [Campina Grande] ( UFCG ), Instituto de Engenharia de Sistemas e Computadores ( INESC ), Departamento de Ciências Biológicas, Universidade Regional do Cariri ( URCA Brasil ), Department of Biochemistry and Molecular Biology [Barcelona, Spain], Universitat de Barcelona ( UB ), Associated Unit to Consejo Superior de Investigaciones Científicas - CSIC [Barcelona, Spain], University of Barcelona-Institute of Biomedicine - IBUB [Barcelona, Spain], IRCELYON-Caractérisation et remédiation des polluants dans l'air et l'eau ( CARE ), Institut de recherches sur la catalyse et l'environnement de Lyon ( IRCELYON ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'analyse et d'architecture des systèmes [Toulouse] ( LAAS ), Centre National de la Recherche Scientifique ( CNRS ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse ( INSA Toulouse ), Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Institut National Polytechnique [Toulouse] ( INP ), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier ( ICGM ICMMM ), Université Montpellier 1 ( UM1 ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Ecole Nationale Supérieure de Chimie de Montpellier ( ENSCM ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Instituto de Ciencia de Materiales de Madrid [Madrid] ( ICMM ), Interactions, Corpus, Apprentissages, Représentations ( ICAR ), École normale supérieure - Lyon ( ENS Lyon ) -Université Lumière - Lyon 2 ( UL2 ) -INRP-Ecole Normale Supérieure Lettres et Sciences Humaines-Centre National de la Recherche Scientifique ( CNRS ), Institut d'Investigacions Biomèdiques August Pi i Sunyer ( IDIBAPS ), North Region Cancer Registry of Portugal, UMR 5805 Environnements et Paléoenvironnements Océaniques et Continentaux ( EPOC ), Observatoire aquitain des sciences de l'univers ( OASU ), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -École pratique des hautes études ( EPHE ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Paediatrics and Intensive Care, Hospital Universitari Sant Joan de Deu, Laboratoire de Psychologie Sociale ( LPS ), Aix Marseille Université ( AMU ), Universitat de València ( UV ), Instituto de Cienca de Materiales de Madrid [Madrid] ( ICMM ), Biology, New Mexico State University, New Mexico State University, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ), Centre de recherche sur les Ions, les MAtériaux et la Photonique ( CIMAP - UMR 6252 ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Supérieure d'Ingénieurs de Caen ( ENSICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ), Institut d'Electronique et de Télécommunications de Rennes ( IETR ), Université de Nantes ( UN ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National des Sciences Appliquées - Rennes ( INSA Rennes ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ), Computer Science Department - Carnegie Mellon University, University of Pittsburgh, Laboratoire de Sciences Actuarielle et Financière ( SAF ), Université de Lyon-Université de Lyon, Instituto de Oncologia Corachan ( IDOC ), Laboratoire d'informatique de l'école normale supérieure ( LIENS ), École normale supérieure - Paris ( ENS Paris ) -Centre National de la Recherche Scientifique ( CNRS ), Experimental Quantum Optics and Photonics Group, University of Strathclyde, Institut de recherches Asiatiques ( IrAsia ), Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Européen de Réalité Virtuelle ( CERV ), École Nationale d'Ingénieurs de Brest ( ENIB ), Sol Agro et hydrosystème Spatialisation ( SAS ), Institut National de la Recherche Agronomique ( INRA ) -AGROCAMPUS OUEST, Grenoble Institut des Neurosciences ( GIN ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Grenoble-Université Joseph Fourier - Grenoble 1 ( UJF ), Centre de recherche cerveau et cognition ( CERCO ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Laboratoire Géomatériaux et Environnement ( LGE ), Université Paris-Est Marne-la-Vallée ( UPEM ), Hôpital Ambroise Paré [AP-HP], Université Paris-Saclay, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Centre hépato-biliaire (CHB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Université de Nantes (UN), Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Salzburger Landesklinikum - Uniklinikum Salzburg (SALK), Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung (AWI), Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Institut de Biologie Computationnelle (IBC), Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Moléculaires (ISM), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Universiteit Gent = Ghent University [Belgium] (UGENT), Antwerp University Hospital [Edegem] (UZA), Hillerød Hospital, Copenhagen University Hospital-Copenhagen University Hospital, Centre Hospitalier Universitaire de Reims (CHU Reims), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université du Québec à Montréal = University of Québec in Montréal (UQAM), Université Paris 1 Panthéon-Sorbonne (UP1), École nationale supérieure d'architecture de Nantes (ENSA Nantes), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bretagne Occidentale - École de sages-femmes (UBO UFR MSS ESF), Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Alexis Vautrin (CAV), Ecophysiologie Végétale, Agronomie et Nutritions (EVA), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Recherche Agronomique (INRA), Image et ville (IV), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Département informatique (INFO), Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Agence de l'Environnement et de la Maîtrise de l'Energie (ADEME), Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Libourne, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation FondaMental [Créteil], Variabilité de réponse aux Psychotropes (VariaPsy - U1144), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Service de Gynécologie et d'Obstétrique (CHU Lyon), Hospices Civils de Lyon (HCL), Génétique, immunothérapie, chimie et cancer (GICC), UMR 7292 CNRS [2012-2017] (GICC UMR 7292 CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1), Service de gastro-entérologie [Henri Mondor AP-HP, Créteil], Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Hôpital privé Toulon Hyères : Sainte Marguerite, Clinique des Quatre Pavillons, Lormont, France, Neurobiologie des signaux intercellulaires (NSI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), NASA Ames Research Center (ARC), Biostatistique et Processus Spatiaux (BioSP), Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], University of Rostock, State University of New York at Oneonta (SUNY Oneonta), State University of New York (SUNY), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Armand Frappier (INRS-IAF), Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS), Institut de Mathématiques de Marseille (I2M), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Klinikum Deggendorf, Technische Universität Berlin (TU), Università degli Studi dell'Aquila (UNIVAQ), North Carolina A&T State University, University of North Carolina System (UNC)-University of North Carolina System (UNC), Observatoire sociologique du changement (OSC), Sciences Po (Sciences Po)-Centre National de la Recherche Scientifique (CNRS), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Università Politecnica delle Marche [Ancona] (UNIVPM), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Ottawa Hospital Research Institute [Ottawa] (OHRI), European Synchrotron Radiation Facility (ESRF), Departamento de Engenharia Informática [Porto], Faculdade de Engenharia da Universidade do Porto (FEUP), Universidade do Porto-Universidade do Porto, Universidade Federal de Campina Grande [Campina Grande] (UFCG), Instituto de Engenharia de Sistemas e Computadores (INESC), Universidade Regional do Cariri (URCA Brasil), Universitat de Barcelona (UB), IRCELYON-Catalytic and Atmospheric Reactivity for the Environment (CARE), Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Laboratoire d'analyse et d'architecture des systèmes (LAAS), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC), Instituto de Ciencia de Materiales de Madrid (ICMM), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Interactions, Corpus, Apprentissages, Représentations (ICAR), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-INRP-Ecole Normale Supérieure Lettres et Sciences Humaines (ENS LSH)-Centre National de la Recherche Scientifique (CNRS), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), UMR 5805 Environnements et Paléoenvironnements Océaniques et Continentaux (EPOC), Observatoire aquitain des sciences de l'univers (OASU), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Hospital Universitario de Valme, Anenida de Bellavista s/n, Sevilla 41014, Spain, Hospital Son Llatzer, Universitat de València (UV), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hospital Universitari Son Espases, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Instituto de Oncologia Corachan (IDOC), Laboratoire d'informatique de l'école normale supérieure (LIENS), École normale supérieure - Paris (ENS Paris), Institut de recherches Asiatiques (IrAsia), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre Européen de Réalité Virtuelle (CERV), École Nationale d'Ingénieurs de Brest (ENIB), Sol Agro et hydrosystème Spatialisation (SAS), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Géomatériaux et Environnement (LGE), Université Paris-Est Marne-la-Vallée (UPEM), Fédération Francophone de Cancérologie Digestive (FFCD), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service d'Oncologie Médicale [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Recherche Agronomique (INRA)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Department of Information Engineering, Computer Science and Mathematics = Dipartimento di Ingegneria e Scienze dell'Informazione e Matematica [L'Aquila] (DISIM), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Département d'informatique - ENS Paris (DI-ENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU), Institute of Biomedicine - IBUB [Barcelona, Spain]-University of Barcelona, Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Université Sciences et Technologies - Bordeaux 1-Université Montesquieu - Bordeaux 4-Institut de Chimie du CNRS (INC), AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Physiologie Animale et Systèmes d'Elevage (PHASE), Institut National de la Recherche Agronomique (INRA)-Environnement et Agronomie (E.A.)-Biologie et Amélioration des Plantes (BAP)-Fourrages Environnement Ruminants Lusignan (FERLUS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Ambroise Paré, University of Florence (UNIFI), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Institut de cancérologie de l'Ouest - Nantes (ICO Nantes), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique (CNRS), Ghent University [Belgium] (UGENT), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université du Québec à Montréal (UQAM), Université Panthéon-Sorbonne (UP1), Centre hospitalier universitaire d'Amiens (CHU Amiens-Picardie), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Franche-Comté (UFC)-Université de Franche-Comté (UFC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Avicenne, Optimisation Thérapeutique en Neuropsychopharmacologie (VariaPsy - U1144), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Biostatistique et Processus Spatiaux (BIOSP), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Technische Universität Berlin (TUB), Università degli Studi dell'Aquila [L'Aquila] (UNIVAQ.IT), Universidade Nova de Lisboa (NOVA), Faculdade de Engenharia [Porto] (FEUP), Unité de recherche Amélioration, Génétique et Physiologie Forestières (UAGPF), IRCELYON-Caractérisation et remédiation des polluants dans l'air et l'eau (CARE), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Consejo Superior de Investigaciones Científicas [Spain] (CSIC), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-INRP-Ecole Normale Supérieure Lettres et Sciences Humaines-Centre National de la Recherche Scientifique (CNRS), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM), Emile, J, Julie, C, Le Malicot, K, Lepage, C, Tabernero, J, Mini, E, Folprecht, G, Van Laethem, J, Dimet, S, Boulagnon-Rombi, C, Allard, M, Penault-Llorca, F, Bennouna, J, Laurent-Puig, P, Taieb, J, Bidoli, P, Emile, J. -F., Julie, C., Le Malicot, K., Lepage, C., Tabernero, J., Mini, E., Folprecht, G., Van Laethem, J. -L., Dimet, S., Boulagnon-Rombi, C., Allard, M. -A., Penault-Llorca, F., Bennouna, J., Laurent-Puig, P., Taieb, J., Thaler, J., Greil, R., Gaenzer, J., Eisterer, W., Tschmelitsch, J., Keil, F., Samonigg, H., Zabernigg, A., Schmid, F., Steger, G., Steinacher, R., Andel, J., Jagdt, B., Lang, A., Fridrik, M., Fugger, R., Hofbauer, F., Woell, E., Geissler, D., Lenauer, A., Prager, M., D'Haens, G., Demolin, G., Kerger, J., Deboever, G., Ghillebert, G., Polus, M., Van Cutsem, E., Kalantari, H. R., Delaunoit, T., Goeminne, J. C., Peeters, M., Vergauwe, P., Houbiers, G., Humblet, Y., Janssens, J., Schrijvers, D., Vanderstraeten, E., Vermorken, J., Van Daele, D., Ferrante, M., Forget, F., Hendlisz, A., Yilmaz, M., Nielsen, S. E., Vestermark, L., Larsen, J., Zawadi, M. -A., Bouche, O., Mineur, L., Bennouna-Louridi, J., Dourthe, L. M., Ychou, M., Boucher, E., Pezet, D., Desseigne, F., Ducreux, M., Texereau, P., Miglianico, L., Rougier, P., Fratte, S., Levache, C. -B., Merrouche, Y., Ellis, S., Locher, C., Ramee, J. -F., Garnier, C., Viret, F., Chauffert, B., Cojean-Zelek, I., Michel, P., Lecaille, C., Borel, C., Seitz, J. -F., Smith, D., Lombard-Bohas, C., Andre, T., Gornet, J. -M., Fein, F., Coulon-Sfairi, M. -A., Kaminsky, M. -C., Lagasse, J. -P., Luet, D., Etienne, P. -L., Gasmi, M., Vanoli, A., Nguyen, S., Aparicio, T., Perrier, H., Stremsdoerfer, N., Laplaige, P., Arsene, D., Auby, D., Bedenne, L., Coriat, R., Denis, B., Geoffroy, P., Piot, G., Becouarn, Y., Bordes, G., Deplanque, G., Dupuis, O., Fruge, F., Guimbaud, R., Lecomte, T., Lledo, G., Sobhani, I., Asnacios, A., Azzedine, A., Desauw, C., Galais, M. -P., Gargot, D., Lam, Y. -H., Abakar-Mahamat, A., Berdah, J. -F., Catteau, S., Clavero-Fabri, M. -C., Codoul, J. -F., Legoux, J. -L., Goldfain, D., Guichard, P., Verge, D. P., Provencal, J., Vedrenne, B., Brezault-Bonnet, C., Cleau, D., Desir, J. -P., Fallik, D., Garcia, B., Gaspard, M. -H., Genet, D., Hartwig, J., Krummel, Y., Budnik, T. M., Palascak-Juif, V., Randrianarivelo, H., Rinaldi, Y., Aleba, A., Darut-Jouve, A., de Gramont, A., Hamon, H., Wendehenne, F., Matzdorff, A., Stahl, M. K., Schepp, W., Burk, M., Mueller, L., Geissler, M., Mantovani-Loeffler, L., Hoehler, T., Asperger, W., Kroening, H., von Weikersthal, L. F., Fuxius, S., Groschek, M., Meiler, J., Trarbach, T., Rauh, J., Ziegenhagen, N., Kretzschmar, A., Graeven, U., Nusch, A., von Wichert, G., Hofheinz, R. -D., Kleber, G., Schmidt, K. -H., Vehling-Kaiser, U., Baum, C., Schuette, J., Haag, G. M., Holtkamp, W., Potenberg, J., Reiber, T., Schliesser, G., Schmoll, H. -J., Schneider-Kappus, W., Abenhardt, W., Denzlinger, C., Henning, J., Marxsen, B., Derigs, H. G., Lambertz, H., Becker-Boost, I., Caca, K., Constantin, C., Decker, T., Eschenburg, H., Gabius, S., Hebart, H., Hoffmeister, A., Horst, H. -A., Kremers, S., Leithaeuser, M., Mueller, S., Wagner, S., Daum, S., Schlegel, F., Stauch, M., Heinemann, V., Maiello, E., Latini, L., Zaniboni, A., Amadori, D., Aprile, G., Barni, S., Mattioli, R., Martoni, A., Passalacqua, R., Nicolini, M., Pasquini, E., Rabbi, C., Aitini, E., Ravaioli, A., Barone, C., Biasco, G., Tamberi, S., Gambi, A., Verusio, C., Marzola, M., Lelli, G., Boni, C., Cascinu, S., Bidoli, P., Vaghi, M., Cruciani, G., Di Costanzo, F., Sobrero, A., Petrioli, R., Aglietta, M., Alabiso, O., Capuzzo, F., Falcone, A., Corsi, D. C., Labianca, R., Salvagni, S., Chiara, S., Ciuffreda, L., Ferrau, F., Giuliani, F., Lonardi, S., Gebbia, N., Mantovani, G., Sanches, E., Mellidez, J. C., Santos, P., Freire, J., Sarmento, C., Costa, L., Pinto, A. M., Barroso, S., Santo, J. E., Guedes, F., Monteiro, A., Sa, A., Furtado, I., Salazar, R., Aguilar, E. A., Herrero, F. R., Valera, J. S., Ayerbes, M. V., Batlle, J. F., Gil, S., Esteve, A. A., Garcia-Giron, C., Vivanco, G. L., Salvia, A. S., Orduna, V. A., Garcia, R. V., Gallego, J., Sureda, B. M., Remon, J., Safont Aguilera, M. J., Nogueras, L. C., Merino, B. Q., Castro, C. G., de Prado, P. M., Pericay, C. P., Figueiras, M. C., Jordan, I. G., Gome Reina, M. J., Garcia, A. L. -L., Garcia-Ramos, A. A., Cervantes, A., Martos, C. F., Gaspar, E. M., Montero, I. C., Emperador, P. E., Carbonero, A. L., Castillo, M. G., Garcia, T. G., Lopez, J. G., Flores, E. G., Morales, M. G., Munoz, M. L., Martin, A. L., Maurel, J., Camara, J. C., Garcia, R. D., Salgado, M., Busquier, I. H., Ruiz, T. C., Munoa, A. L., Aliguer, M. N., de Taranco, A. V. O., Urena, M. M., Gaspa, F. L., Ponce, J. J., Roig, C. B., Jimenez, P. V., Brotons, A. G., Rodriguez, S. A., Martinez, J. A., Ruiz, L. C., Ruiz, M. C., Bridgewater, J., Glynne-Jones, R., Tahir, S., Hickish, T., Cassidy, J., and Samuel, L.
Subjects: 0301 basic medicine, Oncology, Male, Cancer Research, Organoplatinum Compounds, Colorectal cancer, medicine.medical_treatment, Medizin, Leucovorin, Prospective cohort study, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, FOLFOX, Organoplatinum Compounds/therapeutic use, Antineoplastic Combined Chemotherapy Protocols, tudy, Lymphocytes, Prospective Studies, Leucovorin/therapeutic use, Middle Aged, Prognosis, 3. Good health, Colorectal carcinoma, Fluorouracil, 030220 oncology & carcinogenesis, Predictive value of tests, Colonic Neoplasms, Biomarker (medicine), Lymphocytes/pathology, Female, Adjuvant, medicine.drug, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Fluorouracil/therapeutic use, Biomarkers, Tumor/analysis, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, Predictive Value of Tests, Biomarker, Immune response, Internal medicine, medicine, Biomarkers, Tumor, Humans, Survival analysis, Aged, business.industry, medicine.disease, Survival Analysis, Surgery, 030104 developmental biology, Prospective cohort&nbsp, Multivariate Analysis, Colonic Neoplasms/diagnosis, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, business
Abstract: IF 6.029; International audience; BackgroundThe prognostic value of lymphocyte infiltration (LI) of colorectal carcinoma (CC) has been demonstrated by several groups. However, no validated test is currently available for clinical practice. We previously described an automated and reproducible method for testing LI and aimed to validate it for clinical use.Patients and methodsAccording to National Institutes of Health criteria, we designed a prospective validation of this biomarker in patients included in the PETACC8 phase III study. Primary objective was to compare percentage of patients alive and without recurrence at 2 years in patients with high versus low LI (#NCT02364024). Associations of LI with patient recurrence and survival were analysed, and multivariable models were adjusted for treatment and relevant factors. Automated testing of LI was performed on virtual slides without access to clinical data.ResultsAmong the 1220 CC patients enrolled, LI was high, low and not evaluable in 241 (19.8%), 790 (64.8%) and 189 (15.5%), respectively. Primary objective was met with a 2-year recurrence rate of 14.4% versus 21.1% in patients with high and low LI, respectively (p = 0.02). Patients with high LI also had better disease free survival (DFS) and overall survival (OS). Tumour stage, grade, RAS status and BRAF status were with LI the only prognostic markers in multivariable analysis for OS. Subgroup analyses revealed that high LI had better DFS and OS in mismatch repair (MMR) proficient patients, and in patients without RAS mutation, but not in MMR deficient and RAS mutated patients.ConclusionAlthough this is the first validation with high level of evidence (IIB) of the prognostic value of a LI test in colon cancers, it still needs to be confirmed in independent series of colon cancer patients.
Published: 2017
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24. MiR-96-5p influences cellular growth and is associated with poor survival in colorectal cancer patients

Author: Elke Winter, Thomas Bauernhofer, Hellmut Samonigg, Gerald Hoefler, Alexander Deutsch, Verena Stiegelbauer, Sigurd Lax, Stefan Jahn, Armin Gerger, Daniela Schwarzenbacher, Hui Ling, Tobias Kiesslich, Anna Lena Ress, and Martin Pichler
Subjects: Cancer Research, Oncogene, Proportional hazards model, Colorectal cancer, Cancer, Biology, medicine.disease, Bioinformatics, medicine.disease_cause, Cyclin D1, microRNA, Gene expression, medicine, Cancer research, KRAS, Molecular Biology
Abstract: Expression of miR-96-5p is frequently altered in various types of cancer and the KRAS oncogene has been identified as one of its potential targets. However, the biological role of miR-96-5p expression in colorectal cancer (CRC) and its ability to predict the clinical course of patients have not been investigated yet. In this study, we explored miR-96-5p expression in 80 CRC patients and evaluated the impact on clinical outcome by Kaplan-Meier curves and multivariate Cox proportional models. In vitro miR-96-5p inhibition and overexpression were performed in CRC cells and the effects on cellular growth, anchorage-independent growth, apoptosis, and epithelial-mesenchymal transition (EMT)-related gene expression were explored. Low miR-96-5p expression levels in tumor tissue were associated with distant metastasis (P = 0.025) and multivariate Cox regression analysis identified low levels of miR-96-5p as an independent prognostic factor with respect to cancer-specific survival (hazard ratio = 1.78, 95%CI = 1.03-3.03, P
Published: 2014
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25. The elevated preoperative platelet to lymphocyte ratio predicts decreased time to recurrence in colon cancer patients

Author: Joanna Szkandera, Alexander Avian, Franziska Arminger, Renate Schaberl-Moser, Hellmut Samonigg, Melanie Weissmueller, Michael Stotz, Gudrun Absenger, Martin Pichler, Tatjana Stojakovic, Armin Gerger, and Peter Kornprat
Subjects: Adult, Male, medicine.medical_specialty, Time Factors, Multivariate analysis, Colorectal cancer, Lymphocyte, Gastroenterology, Internal medicine, medicine, Humans, Lymphocyte Count, Aged, Retrospective Studies, Aged, 80 and over, Univariate analysis, Platelet Count, business.industry, Hazard ratio, Retrospective cohort study, General Medicine, Middle Aged, Prognosis, medicine.disease, Confidence interval, Surgery, medicine.anatomical_structure, Tumor progression, Colonic Neoplasms, Multivariate Analysis, Preoperative Period, Female, Neoplasm Recurrence, Local, business
Abstract: Background Recent evidence indicates that tumor progression involves factors of systemic inflammation, such as platelets and lymphocytes. In this study, we investigated the prognostic relevance of the preoperative platelet to lymphocyte (P/L) ratio on time to recurrence (TTR) and overall survival (OS) in patients with stage II and III colon cancer (CC) who underwent curative resection. Methods In this retrospective study, 372 CC patients were included. Kaplan–Meier curves and multivariate Cox proportional models were calculated for TTR and OS. Results In univariate analysis, the elevated P/L ratio was significantly associated with decreased TTR (HR = 1.60, 95% CI=1.02 to 2.51, P = .040) and remained significant in multivariate analysis (HR = 1.65, 95% CI=1.05 to 2.58, P = .030), where HR and CI represent Hazard ratio and confidence interval, respectively. Patients with elevated P/L ratio showed a median TTR of 116 months. In contrast, patients with low P/L ratio had a median TTR of 132 months. In OS analysis, the elevated P/L ratio showed a trend toward decreased OS in univariate analysis (HR = 1.54, 95% CI=.95 to 2.48, P = .079). Conclusion In this study, we identified the preoperative P/L ratio as a prognostic marker for TTR in stage II and III CC patients.
Published: 2014
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26. Differential survival trends of stage II colorectal cancer patients relate to promoter methylation status of PCDH10, SPARC, and UCHL1

Author: Friedrich Hofbauer, Margit Resel, Nadia Dandachi, Fritz Wrba, Marija Balic, Renate Schaberl-Moser, Sigurd Lax, Martin Filipits, Hellmut Samonigg, Michael Gnant, Gerhard Böhm, Otto Dietze, Bettina Weißenbacher, Ellen Heitzer, Monika Artl, Ricarda Graf, Gerald Höfler, and Richard Greil
Subjects: Adult, Male, Oncology, medicine.medical_specialty, Pathology, Colorectal cancer, medicine.medical_treatment, Leucovorin, Kaplan-Meier Estimate, Polymerase Chain Reaction, Disease-Free Survival, Pathology and Forensic Medicine, law.invention, Randomized controlled trial, law, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Osteonectin, Clinical significance, Promoter Regions, Genetic, Watchful Waiting, Aged, Neoplasm Staging, Proportional Hazards Models, Chemotherapy, business.industry, Proportional hazards model, Methylation, DNA Methylation, Middle Aged, Cadherins, Prognosis, medicine.disease, Primary tumor, Protocadherins, Clinical trial, Chemotherapy, Adjuvant, Female, Fluorouracil, Colorectal Neoplasms, business, Ubiquitin Thiolesterase
Abstract: Surgical excision of colorectal cancer at early clinical stages is highly effective, but 20-30% of patients relapse. Therefore, it is of clinical relevance to identify patients at high risk for recurrence, who would benefit from adjuvant chemotherapy. The objective of this study was to identify prognostic and/or predictive methylation markers in stage II colorectal cancer patients. Therefore, we selected six gene promoters (FZD9, PCDH10 (protocadherin 10), SFRP2, SPARC (secreted protein acidic and rich in cysteine), UCHL1 (ubiquitin carboxyl-terminal hydrolase 1), and WIF1) for methylation analysis in formalin-fixed, paraffin-embedded primary tumor samples of colorectal cancer patients (n=143) who were enrolled in a prospective randomized phase III trial of the Austrian Breast and Colorectal cancer Study Group. Patients were randomized to adjuvant chemotherapy with 5-fluorouracil and leucovorin or surveillance only. Survival analyses revealed that combined evaluation of three promoters (PCDH10, SPARC, and UCHL1) showed differential effects with regard to disease-free survival and overall survival in the two treatment groups (significance level 0.007). In the chemotherapy arm, a statistically insignificant trend for patients without methylation toward longer survival was observed (P=0.069 for disease-free survival and P=0.139 for overall survival). Contrary, patients in the surveillance arm without methylation in their gene promoters had shorter disease-free survival and overall survival (P=0.031 for disease-free survival and P=0.003 for overall survival), indicating a prognostic effect of methylation in this group (test for interaction, P=0.006 for disease-free survival and P=0.018 for overall survival). These results indicate that promoter methylation status of PCDH10, SPARC, and UCHL1 may be used both as prognostic and predictive molecular marker for colorectal cancer patients and, therefore, may facilitate treatment decisions for stage II colorectal cancer.
Published: 2014
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27. An internally and externally validated prognostic score for metastatic breast cancer: analysis of 2269 patients

Author: M. P. Ufen, Jan Eucker, I. Novopashenny, R. Wolters, Andrea Weigel, Kurt Possinger, Manfred Wischnewsky, Anne C. Regierer, Hellmut Samonigg, and C. H. Köhne
Subjects: Adult, Oncology, medicine.medical_specialty, Multivariate analysis, Breast Neoplasms, Disease, Disease-Free Survival, Prognostic score, Young Adult, Breast cancer, Internal medicine, Outcome Assessment, Health Care, medicine, Humans, Neoplasm Metastasis, Young adult, skin and connective tissue diseases, Aged, Retrospective Studies, Aged, 80 and over, Neoplasm Grading, business.industry, Retrospective cohort study, Original Articles, Hematology, Middle Aged, medicine.disease, Metastatic breast cancer, Treatment Outcome, Multivariate Analysis, Regression Analysis, Female, Neoplasm Recurrence, Local, business
Abstract: The prognosis of metastatic breast cancer (MBC) is extremely heterogeneous. Although patients with MBC will uniformly die to their disease, survival may range from a few months to several years. This underscores the importance of defining prognostic factors to develop risk-adopted treatment strategies. Our aim has been to use simple measures to judge a patient's prognosis when metastatic disease is diagnosed.We retrospectively analyzed 2269 patients from four clinical cancer registries. The prognostic score was calculated from the regression coefficients found in the Cox regression analysis. Based on the score, patients were classified into high-, intermediate-, and low-risk groups. Bootstrapping and time-dependent receiver operating characteristic curves were used for internal validation. Two independent datasets were used for external validation.Metastatic-free interval, localization of metastases, and hormone receptor status were identified as significant prognostic factors in the multivariate analysis. The three prognostic groups showed highly significant differences regarding overall survival from the time of metastasis [intermediate compared with low risk: hazard ratio (HR) 1.76, 95% confidence interval (CI) 1.36-2.27, P0.001; high compared with low risk: HR 3.54, 95% CI 2.81-4.45, P0.001). The median overall survival in these three groups were 61, 38, and 22 months, respectively. The external validation showed congruent results.We developed a prognostic score, based on routine parameters easily accessible in daily clinical care. Although major progress has been made, the optimal therapeutic management of the individual patient is still unknown. Besides elaborative molecular classification of tumors, simple clinical measures such as our model may be helpful to further individualize optimal breast cancer care.
Published: 2014
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28. Validation of C-reactive protein levels as a prognostic indicator for survival in a large cohort of pancreatic cancer patients

Author: Anna Lena Ress, Wael Al-Zoughbi, Martin Pichler, Peter Kornprat, Armin Gerger, Renate Schaberl-Moser, Tatjana Stojakovic, Joanna Szkandera, C. Lackner, F S Seggewies, Gerald Hoefler, Michael Stotz, Gudrun Absenger, and Hellmut Samonigg
Subjects: Male, Cancer Research, Pathology, medicine.medical_specialty, pancreatic cancer, Kaplan-Meier Estimate, Gastroenterology, C-reactive protein, Cohort Studies, Internal medicine, Pancreatic cancer, medicine, Humans, ddc:610, prognostic factor, Molecular Diagnostics, Aged, Proportional Hazards Models, Retrospective Studies, Univariate analysis, biology, business.industry, Hazard ratio, Reproducibility of Results, Cancer, Middle Aged, Prognosis, medicine.disease, Confidence interval, Pancreatic Neoplasms, Oncology, Quartile, biology.protein, Adenocarcinoma, Female, business, Carcinoma, Pancreatic Ductal
Abstract: Background: Recent evidence indicates that the host inflammatory response has an important role in the tumour progression. Elevated C-reactive protein (CRP) levels have been previously associated with poor prognosis in several cancer types including small-scale studies in pancreatic cancer (PC) patients. The purpose of the present study was to validate the prognostic impact of plasma CRP levels at date of diagnosis on cancer-specific survival (CSS) in a large cohort of PC patients. Methods: Data from 474 consecutive patients with adenocarcinoma of the pancreas, treated between 2004 and 2012 at a single centre, were evaluated retrospectively. CSS was analysed using the Kaplan–Meier method. To evaluate the prognostic significance of plasma CRP levels, univariate and multivariate Cox analyses were applied. Results: High plasma CRP levels at diagnosis were significantly associated with well-established prognostic factors, including high tumour stage and tumour grade and the administration of chemotherapy (P
Published: 2013
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29. The elevated pre-operative plasma fibrinogen level is an independent negative prognostic factor for cancer-specific, disease-free and overall survival in soft-tissue sarcoma patients

Author: Katharina Eberhard, Bernadette Liegl-Atzwanger, Hellmut Samonigg, Ferdinand Ploner, Michael Stotz, Armin Gerger, Andreas Leithner, Joanna Szkandera, Gudrun Absenger, Martin Pichler, and Tatjana Stojakovic
Subjects: Oncology, medicine.medical_specialty, Prognostic factor, Multivariate analysis, business.industry, Proportional hazards model, Soft tissue sarcoma, Cancer, General Medicine, Nomogram, medicine.disease, Fibrinogen, Surgery, Fibrinogen levels, Internal medicine, medicine, business, medicine.drug
Abstract: Background and Objectives Accumulating evidence indicates an important pathophysiological role of fibrinogen on tumor cell progression and metastases in different types of cancer. The aim of the present study was to evaluate the prognostic relevance of pre-operative fibrinogen levels on clinical outcome in a large cohort of STS patients. Methods Two hundred ninety-four consecutive STS patients were retrospectively evaluated. Cancer-specific survival (CSS), disease-free survival (DFS), and overall survival (OS) were assessed using the Kaplan–Meier curves and Cox regression models. Finally, we supplemented the well-established Kattan nomogram by the fibrinogen level and evaluated the gain of predictive accuracy of this novel nomogram by Harrell's concordance index (c-index). Results An elevated plasma fibrinogen level was significantly associated with established prognostic factors, including age, tumor grade, size, and depth (P
Published: 2013
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30. Validation of the prognostic relevance of plasma C-reactive protein levels in soft-tissue sarcoma patients

Author: Hellmut Samonigg, Werner Maurer-Ertl, Gudrun Absenger, Andreas Leithner, Joanna Szkandera, Tatjana Stojakovic, Martin Pichler, Armin Gerger, Michael Stotz, Ferdinand Ploner, and Bernadette Liegl-Atzwanger
Subjects: Male, Cancer Research, Pathology, medicine.medical_specialty, Inflammation, Disease-Free Survival, C-reactive protein, Biomarkers, Tumor, Humans, Medicine, ddc:610, Survival rate, Aged, Retrospective Studies, biology, business.industry, Soft tissue sarcoma, Disease progression, Reproducibility of Results, Sarcoma, soft-tissue sarcoma, Middle Aged, Nomogram, Prognosis, medicine.disease, Plasma C-reactive protein, Survival Rate, Nomograms, Oncology, Clinical Study, Disease Progression, biology.protein, Female, medicine.symptom, business
Abstract: Background: The concept of the involvement of systemic inflammation in cancer progression and metastases has gained attraction within the past decade. C-reactive protein (CRP), a non-specific blood-based marker of the systemic inflammatory response, has been associated with decreased survival in several cancer types. The aim of the present study was to validate the prognostic value of pre-operative plasma CRP levels on clinical outcome in a large cohort of soft-tissue sarcoma (STS) patients. Methods: Three hundred and four STS patients, operated between 1998 and 2010, were retrospectively evaluated. CRP levels and the impact on cancer-specific survival (CSS), disease-free survival (DFS) and overall survival (OS) were assessed using Kaplan–Meier curves and univariate as well as multivariate Cox proportional models. Additionally, we developed a nomogram by supplementing the plasma CRP level to the well-established Kattan nomogram and evaluated the improvement of predictive accuracy of this novel nomogram by applying calibration and Harrell’s concordance index (c-index). Results: An elevated plasma CRP level was significantly associated with established prognostic factors, including age, tumour grade, size and depth (P
Published: 2013
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31. The predictive impact of body mass index on the efficacy of extended adjuvant endocrine treatment with anastrozole in postmenopausal patients with breast cancer: an analysis of the randomised ABCSG-6a trial

Author: B. Mlineritsch, Michael Gnant, Michael Stierer, Michael Seifert, Marija Balic, Georg Pfeiler, Christian Fesl, Raimund Jakesz, Werner Kwasny, Florian Fitzal, Hellmut Samonigg, Herbert Stöger, Günther G. Steger, Richard Greil, and Peter Dubsky
Subjects: Adult, Oncology, obesity, Cancer Research, medicine.medical_specialty, Neoplasms, Hormone-Dependent, Adolescent, Antineoplastic Agents, Hormonal, medicine.medical_treatment, Anastrozole, extended therapy, Breast Neoplasms, Overweight, Drug Administration Schedule, Body Mass Index, law.invention, BMI, Young Adult, breast cancer, Breast cancer, Randomized controlled trial, law, Internal medicine, Nitriles, medicine, Humans, Endocrine system, Retrospective Studies, endocrine therapy, Aromatase Inhibitors, business.industry, Retrospective cohort study, Middle Aged, Triazoles, medicine.disease, Surgery, Postmenopause, Chemotherapy, Adjuvant, aromatase inhibitor, Clinical Study, Female, medicine.symptom, business, Body mass index, Adjuvant, medicine.drug
Abstract: Background: We investigated whether body mass index (BMI) can be used as a predictive parameter indicating patients who benefit from extended aromatase inhibitor (AI) treatment. Methods: The ABCSG-6a trial re-randomised event-free postmenopausal hormone receptor-positive patients from the ABCSG-6 trial to receive either 3 additional years of endocrine therapy using anastrozole vs nil. In this retrospective analysis, we investigated the prognostic and predictive impact of BMI on disease outcome and safety. Results: In all, 634 patients (177 normal weight, 307 overweight, and 150 obese) patients were included in this analysis. Normal weight patients with additional 3 years of anastrozole halved their risk of disease recurrence (disease-free survival (DFS) HR 0.48; P=0.02) and death (HR 0.45; P=0.06) and had only a fifth of the risk of distant metastases (HR 0.22; P=0.05) compared with normal weight patients without any further treatment. In contrast, overweight+obese patients derived no benefit from additional 3 years of anastrozole (DFS HR 0.93; P=0.68; distant recurrence-free survival HR 0.91; P=0.78; and OS HR 0.9; P=0.68). The possible predictive impact of BMI on extended endocrine treatment could be strengthened by a Cox regression interaction model between BMI and treatment (P=0.07). Conclusion: Body mass index may be used to predict outcome benefit of extended AI treatment in patients with receptor-positive breast cancer.
Published: 2013
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32. Association of common gene variants in vitamin D modulating genes and colon cancer recurrence

Author: Tanja Langsenlehner, Wilfried Renner, Martin Pichler, Gudrun Absenger, Armin Gerger, Michael Stotz, Hellmut Samonigg, and Joanna Szkandera
Subjects: Adult, Male, Oxidoreductases Acting on CH-CH Group Donors, Cancer Research, medicine.medical_specialty, Time Factors, Colorectal cancer, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Gastroenterology, Viral Envelope Proteins, Polymorphism (computer science), Internal medicine, Biomarkers, Tumor, medicine, Vitamin D and neurology, Humans, Vitamin D, Cytochrome P450 Family 2, Lymph node, Aged, Neoplasm Staging, Retrospective Studies, Aged, 80 and over, Univariate analysis, Hematology, business.industry, Cancer, Retrospective cohort study, DNA, Neoplasm, General Medicine, Middle Aged, Prognosis, medicine.disease, medicine.anatomical_structure, Endocrinology, Oncology, Colonic Neoplasms, Cholestanetriol 26-Monooxygenase, Female, Neoplasm Grading, Neoplasm Recurrence, Local, business, Follow-Up Studies
Abstract: Low concentrations of 25-hydroxyvitamin D3 (25(OH)D) have been associated with increased risk and poor prognosis of various cancer types, including colon cancer. Common genetic variants in genes that influence circulating 25(OH)D levels may affect vitamin D concentrations and risk of vitamin D insufficiency. In the present study, we investigated the association of three functional gene variants in GC (rs2282679 T>G), DHCR7 (rs12785878 G>T) and CYP2R1 (rs10741657 A>G) with time to recurrence (TTR) in patients with stages II and III colon cancer. Two hundred and sixty-four patients were included in this retrospective study. Genomic DNA was genotyped for GC rs2282679 T>G, DHCR7 rs12785878 G>T and CYP2R1 rs10741657 A>G by 5′-exonuclease (TaqMan™) technology. In the univariate analysis, GC rs2282679 GG was significantly associated with decreased TTR (HR = 3.30, 95 % CI 1.09–9.97, p = 0.034) in patients with surgery alone and remained significantly associated in multivariate analysis including lymph node involvement and clinical stage (HR = 3.64, 95 % CI 1.16–11.46, p = 0.027). In patients with adjuvant chemotherapy, GC rs2282679 T>G was not significantly associated with TTR (HR = 1.02, 95 % CI 0.44–2.37, p = 0.964). Furthermore, we observed a trend toward decreased TTR in patients harboring the CYP2R1 rs10741657 A>G gene variant including all patients (HR = 1.50, 95 % CI 0.98–2.28, p = 0.060). No association was found between DHCR7 rs12785878 G>T and TTR in our study cohort. In conclusion, our results may indicate a prognostic effect of GC rs2282679 in stages II and III colon cancer patients with surgery alone. Larger studies have to be performed to validate our findings.
Published: 2013
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33. Clinico-pathological characteristics and clinical outcome of different histological types of pancreatic cancer in a large Middle European series

Author: Armin Gerger, Martin Pichler, Joanna Szkandera, Peter Kornprat, Carolin Lackner, Michael Stotz, Florian Eisner, Hellmut Samonigg, and Gudrun Absenger
Subjects: Male, Pathology, medicine.medical_specialty, CA-19-9 Antigen, Disease, Neuroendocrine differentiation, Pathology and Forensic Medicine, Surgical pathology, Carcinoembryonic antigen, Pancreatic cancer, Biomarkers, Tumor, Humans, Medicine, Aged, Neoplasm Staging, Retrospective Studies, biology, Carcinoma, Acinar Cell, business.industry, General Medicine, Middle Aged, Prognosis, medicine.disease, Adenocarcinoma, Mucinous, Pancreatic Neoplasms, Survival Rate, Treatment Outcome, Austria, Cohort, biology.protein, Adenocarcinoma, Female, Clinico pathological, Neoplasm Grading, business, Carcinoma, Pancreatic Ductal
Abstract: Pancreatic cancer (PC) is a heterogeneous disease in terms of histological and molecular subtypes. The aim of this study was to evaluate the prognostic impact of different histological subtypes on cancer-specific survival (CSS) in a large single-centre Middle European cohort.We retrospectively studied the records of 400 consecutive PC patients who were treated from 2004 to 2010 at a single tertiary academic centre. The association of histological subtypes and parameters such as tumour stage, tumour grade, levels of tumour markers carcinoembryonic antigen and CA19-9 at diagnosis, was studied. CSS was calculated using the Kaplan-Meier method, and the influence of each parameter on CSS was assessed with univariate and multivariable Cox proportional models.The survival time was significantly shorter in the ductal adenocarcinoma and acinar histological subtypes compared to neuroendocrine differentiation (p0.001). No survival difference was observed between ductal adenocarcinomas and patients with a histological variant of ductal adenocarcinoma, namely, mucinous non-cystic adenocarcinoma (p=0.7). In multivariable analysis, ductal adenocarcinoma (HR=3.1, CI 1.6 to 6.1, p=0.001) and acinar carcinoma (HR=3.2, CI 1.3 to 8.5, p=0.016) were identified as independent predictors for CSS.Our findings suggest that the main histological subtype is an independent predictor of CSS in patients with PC. Thus, our data underline the importance of routine assessment of histological type in PC for individual risk assessment. However, no clinical rationale for the subdivision of ductal adenocarcinoma and mucinous non-cystic adenocarcinoma can be supported by our study.
Published: 2013
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34. A common and functional gene variant in the vascular endothelial growth factor a predicts clinical outcome in early-stage breast cancer

Author: Michael Stotz, Tanja Langsenlehner, Thomas Winder, Martin Pichler, Wilfried Renner, Joanna Szkandera, Gudrun Absenger, Armin Gerger, Uwe Langsenlehner, and Hellmut Samonigg
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Univariate analysis, Angiogenesis, Biology, medicine.disease, Minor allele frequency, Vascular endothelial growth factor, Vascular endothelial growth factor A, chemistry.chemical_compound, Cyclin D1, Breast cancer, chemistry, Internal medicine, Genotype, Immunology, medicine, Molecular Biology
Abstract: Angiogenesis and cell cycle control play critical roles in breast cancer susceptibility and clinical outcome and are mainly controlled by vascular endothelial growth factor (VEGF) and cyclin-dependent kinases, respectively. Functional germline polymorphisms in these genes alter the function, thereby causing inter-individual differences in breast cancer risk and clinical outcome. In this study, we investigated the influence of the functional polymorphisms VEGF-A rs3025039 C > T and CCND1 rs9344 G > A on risk and clinical outcome in early-stage breast cancer. DNA of 539 female patients with histologically confirmed early-stage breast cancer and 804 control subjects was genotyped for these polymorphisms. Genotypes were tested for associations with breast cancer risk and clinical outcome. There was no significant association between the polymorphisms and breast cancer risk. However, the minor allele of VEGF-A rs3025039 C > T was significantly associated with decreased recurrence-free survival (HR 1.845; 95% confidence interval [CI] 1.035-3.290; P = 0.038) and remained significant in multivariate analysis (HR 1.880; 95% CI 1.020-3.465; P = 0.043). Patients carrying at least one A-allele in CCND1 rs9344 G > A showed a trend towards decreased recurrence-free survival in univariate analysis (HR 2.379; 95% CI 0.841-6.728; P = 0.068). This study provides evidence that the functional VEGF-A rs3025039 C > T polymorphism influences recurrence-free survival in early-stage breast cancer.
Published: 2013
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35. A common gene variant in PLS3 predicts colon cancer recurrence in women

Author: Hellmut Samonigg, Wilfried Renner, Tanja Langsenlehner, Thomas Winder, Gudrun Absenger, Melanie Weissmueller, Armin Gerger, Martin Pichler, Michael Stotz, and Joanna Szkandera
Subjects: Adult, Male, medicine.medical_specialty, Pathology, Genotype, Colorectal cancer, Biology, Polymorphism, Single Nucleotide, Gastroenterology, Germline, Metastasis, Sex Factors, Internal medicine, medicine, Humans, X chromosome, Aged, Retrospective Studies, Aged, 80 and over, Univariate analysis, Membrane Glycoproteins, Microfilament Proteins, Hazard ratio, General Medicine, Middle Aged, Prognosis, medicine.disease, Minor allele frequency, Female, Neoplasm Recurrence, Local, Colorectal Neoplasms
Abstract: Recent evidence suggests that PLS3 (T-Plastin), an important member of the actin filamentous network, significantly influences cell invasion and metastasis. Germline polymorphisms within the PLS3 gene may impact the gene’s function, resulting in inter-individual differences in tumor recurrence capacity. In the present study, we investigated the association of germline polymorphisms in PLS3 to predict time to recurrence (TTR) in patients with stage II and III colon cancer. A total of 264 patients with histologically confirmed colon cancer were included in this retrospective study. Germline DNA was genotyped for rs871773 C>T, rs757124 C>G, rs1557770 G>T, rs6643869 G>A, and rs2522188 C>T in the PLS3 gene by 5′-exonuclease (TaqMan™) technology. As the PLS3 gene is located on the X chromosome, a gender-specific statistical analysis was performed. In univariate analysis, the minor allele of PLS3 rs871773 C>T was significantly associated with decreased TTR in women (hazard ratio (HR) = 5.02; 95 % confidence interval (CI) = 1.251–20.114; p = 0.023) and remained significantly associated in multivariate analysis (HR = 6.165; 95 % CI = 1.538–24.716; p = 0.010). Female patients carrying the C/T genotype in PLS3 rs871773 showed a median TTR of 69 months. In contrast, female patients with homozygous C/C had a median TTR of 112 months. There were no significant associations between PLS3 rs871773 C>T and TTR in male and between the other polymorphisms and TTR in male or female colon cancer patients. In conclusion, we identified a common gene variant in PLS3 as an independent prognostic marker in female patients with stage II and III colon cancer. Larger prospective trials are warranted to confirm these findings.
Published: 2013
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36. Elevated preoperative neutrophil/lymphocyte ratio is associated with poor prognosis in soft-tissue sarcoma patients

Author: Joanna Szkandera, Martin Pichler, Hellmut Samonigg, Bernadette Liegl-Atzwanger, M. Zacherl, Tatjana Stojakovic, Gudrun Absenger, Armin Gerger, Mathias Glehr, Andreas Leithner, and Michael Stotz
Subjects: Cancer Research, Poor prognosis, Pathology, medicine.medical_specialty, Tumor microenvironment, business.industry, Lymphocyte, Soft tissue sarcoma, soft-tissue sarcoma, medicine.disease, Preoperative care, medicine.anatomical_structure, Text mining, Oncology, neutrophil/lymphocyte ratio, Medicine, Sarcoma, Young adult, prognostic biomarker, tumour microenvironment, business, Molecular Diagnostics
Abstract: Background: Recent data indicate that tumour microenvironment, which is influenced by inflammatory cells, has a crucial role in cancer progression and clinical outcome of patients. In the present study, we investigated the prognostic relevance of preoperative neutrophil/lymphocyte (N/L) ratio on time to tumour recurrence (TTR) and overall survival (OS) in soft-tissue sarcoma (STS) patients who underwent curative surgical resection. Methods: In all, 260 STS patients were included in this retrospective study. Kaplan–Meier curves and multivariate Cox proportional models were calculated for TTR and OS. Results: In univariate analysis, elevated N/L ratio was significantly associated with decreased TTR (hazard ratio (HR), 2.32; 95% confidence interval (CI), 1.30–4.14; P=0.005) and remained significant in the multivariate analysis (HR, 1.98; 95%CI, 1.05–3.71; P=0.035). Patients with elevated N/L ratio showed a median TTR of 77.9 months. In contrast, patients with low N/L ratio had a median TTR of 99.1 months. Regarding OS, elevated N/L ratio was also significantly associated with decreased survival in univariate analysis (HR, 2.90; 95%CI, 1.82–4.61; P=0.001) and remained significant in multivariate analysis (HR, 1.88; 95%CI, 1.14–3.12; P=0.014). Conclusion: In conclusion, our findings suggest that an elevated preoperative N/L ratio predicts poor clinical outcome in STS patients and may serve as a cost-effective and broadly available independent prognostic biomarker.
Published: 2013
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37. Efficacy of tamoxifen±aminoglutethimide in normal weight and overweight postmenopausal patients with hormone receptor-positive breast cancer: an analysis of 1509 patients of the ABCSG-06 trial

Author: B. Mlineritsch, Michael Gnant, Werner Kwasny, Ferdinand Ploner, Christian F. Singer, Martin Moik, Michael Seifert, Georg Pfeiler, P. Sandbichler, Richard Greil, Peter Dubsky, Friedrich Hofbauer, U Selim, Hellmut Samonigg, Florian Fitzal, Marija Balic, Christian Fesl, Raimund Jakesz, Herbert Stöger, Günther G. Steger, and K Renner
Subjects: Oncology, obesity, Cancer Research, medicine.medical_specialty, Antineoplastic Agents, Hormonal, Breast Neoplasms, Receptors, Cell Surface, Overweight, Body Mass Index, law.invention, BMI, breast cancer, Breast cancer, Randomized controlled trial, law, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Prospective Studies, skin and connective tissue diseases, Prospective cohort study, Aged, Aged, 80 and over, Gynecology, tamoxifen, Aromatase Inhibitors, business.industry, Middle Aged, medicine.disease, Aminoglutethimide, Postmenopause, Treatment Outcome, Hormone receptor, aromatase inhibitor, Clinical Study, Female, medicine.symptom, business, Tamoxifen, medicine.drug, Hormone
Abstract: Background: There exists evidence that body mass index (BMI) impacts on the efficacy of aromatase inhibitors in patients with breast cancer. The relationship between BMI and the efficacy of tamoxifen is conflicting. We investigated the impact of BMI on the efficacy of single tamoxifen and tamoxifen plus an aromatase inhibitor in the well-defined prospective study population of the ABCSG-06 trial. Methods: ABCSG-06 investigated the efficacy of tamoxifen vs tamoxifen plus aminoglutethimide in postmenopausal women with hormone receptor-positive breast cancer. Taking BMI at baseline, patients were classified as normal weight (BMI=18.5–24.9 kg m−2), overweight (BMI=25–29.9 kg m−2), and obese (30 kg m−2) according to WHO criteria. Results: Overweight+obese patients had an increased risk for distant recurrences (hazard ratio (HR): 1.51; Cox P=0·018) and a worse overall survival (OS; HR: 1·49; Cox P=0·052) compared with normal weight patients. Analysing patients treated with single tamoxifen only, no difference between overweight+obese patients and normal weight patients regarding distant recurrence-free survival (HR: 1.35; Cox P=0·24) and OS (HR: 0.99; Cox P=0·97) could be observed. In contrast, in the group of patients treated with the combination of tamoxifen plus aminoglutethimide, overweight+obese patients had an increased risk for distant recurrences (1.67; Cox P=0·03) and a worse OS (1.47; Cox P=0·11) compared with normal weight patients. Conclusion: BMI impacts on the efficacy of aromatase inhibitor-based treatment but not single tamoxifen.
Published: 2013
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38. The ethics of space, design and color in an oncology ward

Author: A. K. Kasparek, Hellmut Samonigg, Elisabeth Andritsch, Hans Andritsch, H. Stöger, R. Schaberl-Moser, Thomas Bauernhofer, and Ferdinand Ploner
Subjects: Oncology, medicine.medical_specialty, Organizational innovation, Color, Space (commercial competition), Patient care, Nursing, Oncology Service, Hospital, Internal medicine, Patients' Rooms, Health care, medicine, Humans, Family, General Nursing, business.industry, General Medicine, Professional responsibility, Organizational Innovation, Europe, Psychiatry and Mental health, Clinical Psychology, Family member, Patient room, Patient perceptions, Psychology, business, Interior Design and Furnishings
Abstract: Change affects all areas of healthcare organizations and none more so than each aspect of the oncology ward, beginning with the patient's room. It is there that the issues faced by the major players in healing environments – administrator, caregiver, family member, and, most importantly, the patient – come sharply into focus. Hospitals are building new facilities or renovating old ones in order to adapt to new environmental demands of patient care and security. Driven by ethical and professional responsibility, the oncological team headed by Professor Hellmut Samonigg of Graz Medical University Graz pursued a vision of designing a model oncology ward unique in Europe. Friedensreich Hundertwasser, the world-famous artist, was the creative force behind the design. The oncology ward became a place of healing, permeated with a colorful sense of life and harmonious holistic care. The successful outcome was confirmed by the extraordinarily positive feedback by patients, families, and healthcare staff.
Published: 2012
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39. Tamoxifen and Anastrozole As a Sequencing Strategy: A Randomized Controlled Trial in Postmenopausal Patients With Endocrine-Responsive Early Breast Cancer From the Austrian Breast and Colorectal Cancer Study Group

Author: Richard Greil, Hellmut Samonigg, Susanne Taucher, Lidija Filipcic, Günther G. Steger, Florian Fitzal, Sabine Pöstlberger, Paul Sevelda, Brigitte Mlineritsch, Christoph Tausch, G. Luschin-Ebengreuth, Michael Stierer, Herbert Stöger, Karin Haider, Raimund Jakesz, Christian F. Singer, Rupert Bartsch, Margaretha Rudas, Werner Kwasny, Michael Gnant, and Peter Dubsky
Subjects: Oncology, Gynecology, Cancer Research, medicine.medical_specialty, education.field_of_study, Colorectal cancer, business.industry, Population, Hazard ratio, Anastrozole, medicine.disease, Breast cancer, Internal medicine, medicine, skin and connective tissue diseases, Prospective cohort study, education, business, Survival rate, Tamoxifen, medicine.drug
Abstract: Purpose Anastrozole (ANA) alone delivers significant disease-free survival benefits over tamoxifen (TAM) monotherapy in postmenopausal women with early estrogen receptor–positive breast cancer. The ABCSG-8 (Austrian Breast and Colorectal Cancer Study Group 8) study is a large phase III clinical trial addressing the sequence strategy containing ANA in comparison with 5 years of TAM in a low- to intermediate-risk group of postmenopausal patients. Patients and Methods Endocrine receptor–positive patients with G1 or G2 tumors were eligible. After surgery, patients were randomly assigned to 5 years of TAM or 2 years of TAM followed by 3 years of ANA. Adjuvant chemotherapy and G3 and T4 tumors were exclusion criteria. Intention-to-treat and censored analyses of on-treatment recurrence-free survival (RFS) were performed, and exploratory survival end points and toxicity were investigated. Results Information from 3,714 patients, including 17,563 woman-years, with a median of 60 months of follow-up was available for this analysis. Median age was 63.8 years, 75% were node negative, and 75% had T1 tumors. Sequencing of ANA after identical 2-year treatment with TAM in both arms did not result in a statistically significant improvement of RFS (hazard ratio [HR], 0.80; 95% CI, 0.63 to 1.01; P = .06). Exploratory analyses of distant relapse-free survival indicated a 22% improvement (HR, 0.78; 95% CI, 0.60 to 1.00). On-treatment adverse events and serious adverse events were consistent with known toxicity profiles of ANA and TAM treatment. Conclusion Despite a low overall rate of recurrence in a population with breast cancer at limited risk of relapse, the a priori sequence strategy of 2 years of TAM followed by 3 years of ANA led to small outcome and toxicity benefits.
Published: 2012
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40. Analysis of common germline polymorphisms as prognostic factors in patients with lymph node-positive breast cancer

Author: Hellmut Samonigg, Joanna Szkandera, Tanja Langsenlehner, Gudrun Knechtel, Uwe Langsenlehner, Armin Gerger, Gerald L. Wolf, Wilfried Renner, Giinter Hofmann, and Peter Krippl
Subjects: Adult, Oncology, Cancer Research, medicine.medical_specialty, Pathology, Genotype, Breast Neoplasms, Polymorphism, Single Nucleotide, Disease-Free Survival, Germline, Metastasis, Breast cancer, Germline mutation, Gene Frequency, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, fas Receptor, Germ-Line Mutation, Aged, Neoplasm Staging, Aged, 80 and over, business.industry, Cancer, General Medicine, Middle Aged, Prognosis, medicine.disease, Interleukin-10, Lymphatic Metastasis, Multivariate Analysis, Disease Progression, Female, Lymph Nodes, Lymph, Breast disease, business
Abstract: Women with breast cancer that initially involves local lymph nodes have a higher risk for local recurrence or developing metastases. Recent data suggest that germline polymorphism is a significant, previously unrecognized factor in breast cancer progression and metastasis. We assessed the influence of 16 selected common germline polymorphisms in disease-free survival and overall survival among 216 women diagnosed with lymph node-positive breast cancer.The rare allele of FAS 1377GA was significantly associated with prolonged disease-free survival (P = 0.012, risk ratio of recurrence (RR) = 0.557, 95% confidence interval (CI) = 0.353-0.878) in univariate analysis. After adjusting for known breast cancer prognostic factors the association remained significant (P = 0.050, RR = 0.500, CI = 0.309-0.809). In overall survival analysis we found a significant association of the FAS 1377GA (P = 0.040, RR = 0.451, CI = 0.496-1.188) and IL10 592CA polymorphisms (P = 0.020, RR = 1.707, CI = 1.087-2.680) in the univariate Cox regression. The effect remained statistically significant in the multivariate analysis for the IL10 592CA polymorphism (P = 0.013, RR 1.841, CI 1.140-2.973). No association was found for MTHFR 677CT, VEGF 936CT, CCND1 870GA, TGFB1 29TC, FASLG 844CT, FAS 670AG, GPB3 825CT, ITGA2 807CT, ITGA2 1648GA, ITGB3 176TC, MMP1 -1607 1G/2G, MMP3 5A/6A, PTGS2 8473TC, IL10 592CA and SULT1A1 638GA polymorphisms and disease-free survival or overall survival.Our data suggest that the FAS 1377GA and IL10 592CA polymorphisms could modify disease-free and overall survival in women with lymph node-positive breast cancer.
Published: 2010
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41. The role of activation-induced cell death in the higher onset of spontaneous apoptosis of NK cell subsets in patients with metastatic epithelial cancer

Author: Margit Resel, Stefanie Stanzer, Hellmut Samonigg, Thomas Bauernhofer, Birgit Janesch, and Thomas Augustin
Subjects: Adult, Male, Programmed cell death, NK Cell Lectin-Like Receptor Subfamily K, Immunology, Apoptosis, chemical and pharmacologic phenomena, MHC class I, medicine, Humans, Apoptosis Marker, Neoplasms, Glandular and Epithelial, fas Receptor, Neoplasm Metastasis, Aged, Cell Death, biology, Histocompatibility Antigens Class I, Cancer, Middle Aged, medicine.disease, NKG2D, Fas receptor, Killer Cells, Natural, biology.protein, Female
Abstract: To address the question whether the higher onset of apoptosis of circulating NK cell subsets might be activation induced in cancer patients, surface expression of NKG2D and serum (s) levels of MHC class I chain-related (MIC) proteins in relation to apoptosis marker and CD95 expression on NK cells were evaluated. Patients showed a significantly higher onset of spontaneous apoptosis of CD56dim NK cells. No difference in the CD95 expression could be detected between patients and normal controls (NCs). Patients' CD56bright NK cells demonstrated a higher expression of NKG2D compared to CD56dim NK cells. The sMICB levels showed a higher level in patients versus NCs. No correlation between sMIC protein levels with both NKG2D expression and onset of spontaneous apoptosis of NK cell subsets was found. Our data suggest that the higher onset of apoptosis of circulating NK cell subsets of patients is not triggered by activation-induced cell death.
Published: 2010
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42. Evaluation of High-Resolution Melting Analysis as a Diagnostic Tool to Detect the BRAF V600E Mutation in Colorectal Tumors

Author: Nadia Dandachi, Christoph Ausch, Christian Guelly, Thomas Bauernhofer, Hellmut Samonigg, Marija Balic, Martina Wild, Gerald Hoefler, Martin Pichler, and Elke Stadelmeyer
Subjects: Adult, Proto-Oncogene Proteins B-raf, Tissue Fixation, Colorectal cancer, DNA Mutational Analysis, Mutant, Biology, medicine.disease_cause, Sensitivity and Specificity, DNA sequencing, High Resolution Melt, Pathology and Forensic Medicine, Denaturing high performance liquid chromatography, chemistry.chemical_compound, Cell Line, Tumor, Formaldehyde, medicine, Humans, Transition Temperature, Aged, Aged, 80 and over, Mutation, Reproducibility of Results, Middle Aged, medicine.disease, Molecular biology, Molecular Diagnostic Techniques, chemistry, Molecular Medicine, Colorectal Neoplasms, DNA, Regular Articles
Abstract: BRAF V600E is the predominantly occurring mutation of the cytoplasmic kinase BRAF, and, in colorectal cancer, its determination provides a diagnostic exclusion criterion for hereditary nonpolyposis colorectal cancer. The aim of our study was to develop a sensitive BRAF V600E high resolution melting (HRM) assay. We first established and optimized the BRAF HRM assay using a cell line dilution model, enabling us to detect 1% mutant DNA in a background of wild-type DNA. In a comparison, DNA sequencing and real-time allele-specific PCR in the cell line dilution model HRM assay proved to be more sensitive than DNA sequencing and denaturing high performance liquid chromatography, retaining the same sensitivity as real-time allele-specific PCR. In a learning set of 13 patients with known BRAF V600 status, the mutation was detected with high concordance by all four methods. Finally, we validated the HRM assay on 60 formalin-fixed, paraffin-embedded colorectal cancer samples. Although all mutated samples were correctly identified by HRM, the detection limit of the HRM assay decreased when using low-quality DNA derived from formalin-fixed, paraffin-embedded samples. In conclusion, HRM analysis is a powerful diagnostic tool for detection of BRAF V600E mutation with a high sensitivity and high-throughput capability. Despite the expected decrease in sensitivity, HRM can reliably be applied in archival formalin-fixed, paraffin-embedded samples tissues.
Published: 2009
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43. A common hereditary single-nucleotide polymorphism in the gene of FAS and colorectal cancer survival

Author: Peter Krippl, Florentine Fuerst, Tanja Langsenlehner, B. Yazdani-Biuki, Hellmut Samonigg, Heimo Clar, Uwe Langsenlehner, Wilfried Renner, Armin Gerger, and Guenter Hofmann
Subjects: Risk, Oncology, Heterozygote, medicine.medical_specialty, Genotype, Colorectal cancer, colorectal cancer, Single-nucleotide polymorphism, Biology, survival, Polymorphism, Single Nucleotide, polymorphism, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, fas Receptor, Survival rate, Proportional Hazards Models, Retrospective Studies, Polymorphism, Genetic, Cell Death, Proportional hazards model, Homozygote, apoptosis, Cell Biology, FAS, medicine.disease, Genotype frequency, Gene Expression Regulation, Neoplastic, Fluorouracil, Apoptosis, Immunology, Regression Analysis, Molecular Medicine, Colorectal Neoplasms, medicine.drug
Abstract: Apoptosis plays an important role in embryogenesis, autoimmunity and tumourigenesis. Cell surface death receptors such as TNFRSF6 (FAS) confer a major apoptotic effect. A single-nucleotide polymorphism in the FAS promoter gene, -670A/G, modulates apoptotic signalling and has been related to susceptibility and progression of a variety of cancers. The present study aimed to evaluate the role of this polymorphism for survival of patients with colorectal cancer. We performed a retrospective analysis including 433 patients with histologically confirmed colorectal cancer. A Cox regression model including FAS -670 genotypes, age at diagnosis, tumour grading, primary tumour size, number of lymph nodes examined, number of metastatic lymph nodes, tumour stage and application of fluorouracil-based adjuvant chemotherapy was used to estimate the effect of the FAS genotype on survival. FAS -670A/G genotype frequencies were 24.2% (AA), 46.3% (AG) and 29.5% (GG). Forty-nine patients were excluded from the Cox regression analysis because of missing values. Out of the remaining 384 patients, 69 (18%) died during a follow-up of maximum 10 years. Mean follow-up time was 58 +/- 34 months (median 55 months). Carriers of the homozygous FAS -670GG genotype had a significantly lower survival rate compared with AA/AG genotype carriers (relative risk 1.76, 95% confidence interval 1.08-2.87; P= 0.023). The FAS -670A/G polymorphism may be associated with overall survival time of patients with colorectal cancer.
Published: 2009
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44. Einsatz von Erythropoese-stimulierenden Proteinen bei anämischen Patienten mit malignen Erkrankungen

Author: Ulrich Jäger, Christoph C. Zielinski, Robert Pirker, Felix Stockenhuber, Gabriela Kornek, Georg Hopfinger, Heinz Ludwig, Felix Keil, Alexander Reinthaller, Michael Studnicka, Günter Weiss, Werner Linkesch, Elisabeth Pittermann, Thomas Auberger, Günther G. Steger, Hellmut Samonigg, Michael Gnant, Edgar Petru, and Otto Ch. Burghuber
Subjects: Gynecology, medicine.medical_specialty, business.industry, medicine, General Medicine, business
Published: 2008
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45. Anemia Is a Significant Prognostic Factor in Local Relapse-Free Survival of Premenopausal Primary Breast Cancer Patients Receiving Adjuvant Cyclophosphamide/Methotrexate/5-Fluorouracil Chemotherapy

Author: Peter, Dubsky, Paul, Sevelda, Raimund, Jakesz, Hubert, Hausmaninger, Hellmut, Samonigg, Michael, Seifert, Ursula, Denison, Brigitte, Mlineritsch, Günther, Steger, Werner, Kwasny, Herbert, Stöger, Rupert, Bartsch, Michael, Stierer, Susanne, Taucher, Michael, Fridrik, Walter, Schippinger, Richard, Greil, Richard, Pötter, Michael, Gnant, and W, Neunteufel
Subjects: Adult, Oncology, Cancer Research, medicine.medical_specialty, Colorectal cancer, Anemia, medicine.medical_treatment, Breast Neoplasms, Kaplan-Meier Estimate, Disease-Free Survival, Breast cancer, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Breast-conserving surgery, Humans, Cyclophosphamide, Radiotherapy, business.industry, CMF Regimen, Cancer, Prognosis, medicine.disease, Combined Modality Therapy, Surgery, Methotrexate, Premenopause, Chemotherapy, Adjuvant, Female, Fluorouracil, Breast disease, business, Mastectomy
Abstract: Purpose: To determine the effects of anemia on local relapse-free, relapse-free, and overall survival (LRFS, RFS, and OS, respectively) in premenopausal, primary breast cancer patients receiving adjuvant polychemotherapy, and to determine which conventional prognostic factors affected these outcomes. Experimental Design: Four hundred twenty-four premenopausal patients with early-stage primary breast cancer and hormone receptor–expressing tumors were treated with i.v. cyclophosphamide/methotrexate/5-fluorouracil (CMF) polychemotherapy as part of an adjuvant phase III trial (Austrian Breast and Colorectal Cancer Study Group Trial 5). The influence of anemia (hemoglobin Results: Of 424 patients, 77 (18.2%) developed anemia on CMF chemotherapy. After a median follow-up time of 5 years, 8.9% of nonanemic patients had local relapse compared with 19.6% of anemic patients (P = 0.0006). Although mastectomy was associated with anemia (26% versus 13.7% in breast conserving surgery; P = 0.002), multivariate analysis did not show mastectomy per se to be a significant risk factor for LRFS. Age, lymph node status, and hemoglobin had an independent significant influence on LRFS (P < 0.005). Anemic patients had a relative risk of 2.96 (95% confidence interval, 1.41-6.23) for developing local relapse in comparison with nonanemic patients. Conclusion: Premenopausal breast cancer patients who developed anemia during the CMF regimen had significantly worse LRFS. In Austrian Breast and Colorectal Cancer Study Group Trial 5, anemia may have contributed to an almost doubled incidence of local recurrence in the chemotherapy arm. Molecular targets associated with tumor hypoxia and distinct from erythropoiesis should receive further attention in experimental and clinical settings.
Published: 2008
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46. In vivo confocal laser scanning microscopy of melanocytic skin tumours: diagnostic applicability using unselected tumour images

Author: Josef Smolle, Hellmut Samonigg, Uwe Langsenlehner, Verena Ahlgrimm-Siess, Wolfgang Weger, Michael Horn, Erika Richtig, Rainer Hofmann-Wellenhof, Armin Gerger, and Silvia Koller
Subjects: medicine.medical_specialty, Pathology, business.industry, Confocal, Melanoma, Cancer, Anatomical pathology, Dermatology, medicine.disease, law.invention, Skin tumours, In vivo, Confocal microscopy, law, medicine, Skin cancer, business, Nuclear medicine
Abstract: Summary Background In vivo confocal laser scanning microscopy (CLSM) represents a novel imaging tool that allows the noninvasive examination of skin cancer morphology in real time at a ‘quasi-histopathological’ resolution viewing microanatomical structures and individual cells. Objectives To validate diagnostic confocal examination of melanocytic skin tumours using unselected tumour images. Methods In the present study, we used a total of 3709 unselected CLSM tumour images obtained from 20 malignant melanomas and 50 benign naevi. The entire set of images derived from each tumour was evaluated by independent observers. Classification tree analysis based on a subsample of 857 tumour images was performed to develop a diagnostic algorithm. Results Overall, sensitivity and specificity of 97·5% and 99% could be achieved by the independent observers (positive predictive value 97·5%, negative predictive value 99%). Classification tree analysis yielded a three-step algorithm based on only three morphological CLSM features, facilitating a correct classification in 92·4% of the benign naevus images and 97·6% of melanoma images. Conclusions In vivo CLSM augurs a sea change in the way we will view skin tumour processes clinically at the bedside and merits application for use as a screening tool in skin oncology.
Published: 2008
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47. Resistance to Apoptosis and Expansion of Regulatory T Cells in Relation to the Detection of Circulating Tumor Cells in Patients with Metastatic Epithelial Cancer

Author: Nadia Dandachi, Marija Balic, Margit Resel, Stefanie Stanzer, Hellmut Samonigg, and Thomas Bauernhofer
Subjects: CD4-Positive T-Lymphocytes, Male, T cell, Immunology, Apoptosis, Biology, T-Lymphocytes, Regulatory, TCIRG1, Interleukin 21, Immune system, Antigens, CD, T-Lymphocyte Subsets, Cancer stem cell, medicine, Humans, Immunology and Allergy, Cytotoxic T cell, CTLA-4 Antigen, Lymphocyte Count, fas Receptor, IL-2 receptor, Annexin A5, Neoplasm Metastasis, Antigen-presenting cell, Aged, Carcinoma, Interleukin-2 Receptor alpha Subunit, Middle Aged, medicine.anatomical_structure, Female
Abstract: Regulatory T cells may be crucial in the development of T cell tolerance to malignancies and contribute to immune dysfunctions. We investigated the percentage, activity, and onset of apoptosis of T cell subpopulations by multicolor flow cytometry in metastatic epithelial cancer patients compared to normal controls. Furthermore, a possible relationship between the presence of circulating tumor cells detected by immunocytochemistry and immune cell abnormalities was evaluated. Our study demonstrated a significantly elevated proportion of regulatory T cells in cancer patients (p < 0.001). In contrast to all other T cell subpopulations, regulatory T cells showed comparable Annexin V-binding characteristics in patients and normal controls. No relationship between the detection of circulating tumor cells and immune dysfunction was observed. These results indicate that cancer patients have a higher number of regulatory T cells with resistance to apoptotic stimuli partly responsible for immune dysfunctions as often observed in cancer patients.
Published: 2007
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48. Common single nucleotide polymorphisms in the vascular endothelial growth factor gene and colorectal cancer risk

Author: Peter Krippl, Tanja Langsenlehner, Heimo Clar, Guenter Hofmann, B. Yazdani-Biuki, Wilfried Renner, U. Langsenlehner, Martin Wehrschuetz, Hellmut Samonigg, and Armin Gerger
Subjects: Adult, Male, Vascular Endothelial Growth Factor A, Oncology, Cancer Research, medicine.medical_specialty, Angiogenesis, Colorectal cancer, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, chemistry.chemical_compound, Risk Factors, Internal medicine, Genotype, Biomarkers, Tumor, medicine, Humans, Genetic Predisposition to Disease, Aged, Aged, 80 and over, Neovascularization, Pathologic, business.industry, Cancer, General Medicine, Middle Aged, medicine.disease, Genotype frequency, Vascular endothelial growth factor, HIF1A, chemistry, Case-Control Studies, Immunology, Female, Colorectal Neoplasms, business
Abstract: Tumor growth requires the formation of new blood vessels, a phenomenon known as angiogenesis. The most important regulator of angiogenesis is vascular endothelial growth factor (VEGF). Several common polymorphisms in the VEGF-gene have been associated with different VEGF expression, production and plasma levels according to allele status, and influence the risk of developing different types of cancer. Therefore, these variants might be risk factors for colorectal cancer (CRC).In the present case-control study, VEGF genotypes of the +936 CT, -2578 CA and -634 GC polymorphisms were determined in 427 patients with histologically verified CRC and 427 age and sex-matched healthy control subjects. Genotypes were analyzed by a fluorogenic exonuclease assay (TaqMan). P-value for age at diagnosis was analyzed by student's t test, P-values for tumor characteristics were determined by Pearson's Chi-square test. Threshold for significance was P0.05.At the time of diagnoses, patients were between 29 and 83 years of age, with a mean age of 61+/-10.9 years. VEGF -2578 CA and VEGF -634 GC genotype frequencies were similar among patients and controls. Carriers of the 936T-allele were found slightly more frequent among controls (27.2%) than among patients (22.5%), but this difference did not reach statistical significance (P=0.07). Furthermore, no correlation was found between all these variants and tumor characteristics like size, histological grading, positive regional lymph node metastases or tumor stage.We conclude that the investigated polymorphisms are not associated with individual susceptibility to colorectal cancer.
Published: 2007
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49. The Predictive Value of EGFR and HER-2/neu in Tumor Tissue and Serum for Response to Anthracycline-Based Neoadjuvant Chemotherapy of Breast Cancer

Author: Hellmut Samonigg, Walter Schippinger, Nadia Dandachi, Peter Regitnig, Thomas Bauernhofer, Günter Hofmann, Rainer Neumann, and Marija Balic
Subjects: Adult, Oncology, medicine.medical_specialty, Pathology, Anthracycline, Receptor, ErbB-2, medicine.medical_treatment, Breast Neoplasms, Breast cancer, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, medicine, Humans, Anthracyclines, Epidermal growth factor receptor, Neoadjuvant therapy, Aged, Chemotherapy, biology, business.industry, Anatomical pathology, General Medicine, Middle Aged, medicine.disease, Chemotherapy regimen, Neoadjuvant Therapy, Confidence interval, ErbB Receptors, Treatment Outcome, ROC Curve, biology.protein, Female, business
Abstract: We investigated the predictive value of HER-2/neu and epidermal growth factor receptor (EGFR) in tumor tissue and prechemotherapy serum for histopathologic response in 108 patients with breast cancer undergoing neoadjuvant anthracycline-based chemotherapy. Response to chemotherapy, assessed by histopathologic classification of regression (grade 0 [no therapy effect] to 4 [no residual tumor]), correlated significantly with prechemotherapy serum HER-2/neu levels. Median prechemotherapy serum HER-2/neu levels were significantly higher in patients with regression grades 1 through 4 compared with those in patients with regression grade 0 (9.6 vs 8.55 ng/mL; P = .011; 95% confidence interval [CI], .009-.014). Median pretreatment serum HER-2/neu levels of patients with complete pathologic response (pCR) were significantly higher than in patients with moderate or no treatment response (10.95 vs 9.1 ng/mL; P = .041; 95% CI, .036-.046). Receiver operating characteristic curve analysis revealed a serum HER-2/neu value of more than 10.3 ng/mL to predict a pCR with 80% sensitivity and 69.4% specificity. There was no significant correlation of response with HER-2/neu and EGFR scores in tumor tissue or with serum EGFR levels. Results demonstrate prechemotherapy serum HER-2/neu to be a significant predictor of response to neoadjuvant anthracycline-based chemotherapy for breast cancer.
Published: 2007
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50. A prospective randomised phase III trial of adjuvant chemotherapy with 5-fluorouracil and leucovorin in patients with stage II colon cancer

Author: R Thödtmann, Josef Thaler, Peter Wohlmuth, Renate Schaberl-Moser, M Jagoditsch, Günther G. Steger, Raimund Jakesz, Hans Rabl, Friedrich Hofbauer, Richard Greil, Michael Gnant, F. Herbst, Hellmut Samonigg, Joerg Tschmelitsch, and Walter Schippinger
Subjects: stage II, Adult, Male, Cancer Research, medicine.medical_specialty, medicine.drug_class, Colorectal cancer, medicine.medical_treatment, Leucovorin, Kaplan-Meier Estimate, Adenocarcinoma, Lower risk, Antimetabolite, Gastroenterology, Disease-Free Survival, Internal medicine, Clinical Studies, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Aged, Neoplasm Staging, Chemotherapy, business.industry, Hazard ratio, Cancer, Middle Aged, medicine.disease, Surgery, adjuvant chemotherapy, Clinical trial, colon cancer, Oncology, Chemotherapy, Adjuvant, Fluorouracil, Colonic Neoplasms, Female, Neoplasm Recurrence, Local, business, medicine.drug
Abstract: The purpose of this trial was to investigate the efficacy of adjuvant chemotherapy with 5-fluorouracil (5-FU) and leucovorin (LV) in stage II colon cancer. Patients with stage II colon cancer were randomised to either adjuvant chemotherapy with 5-FU/LV (100 mg m(-2) LV+450 mg m(-2) 5-FU weekly, weeks 1-6, in 8 weeks cycles x 7) or surveillance only. Five hundred patients were evaluable for analyses. After a median follow-up of 95.6 months, 55 of 252 patients (21.8%) have died in the 5-FU/LV arm and 58 of 248 patients (23.4%) in the surveillance arm. There was no statistically significant difference in overall survival (OS) between the two treatment arms (hazard ratios, HR 0.88, 95% CI 0.61-1.27, P=0.49). The relative risk for tumour relapse was higher for patients on the surveillance arm than for those on the 5-FU/LV arm; however, this difference was not statistically significant (HR 0.69, 95% CI 0.45-1.06, P=0.09). Consequently, disease-free survival (DFS) was not significantly different between the two trial arms. In conclusion, results of this trial demonstrate a trend to a lower risk for relapse in patients treated with adjuvant 5-FU/LV for stage II colon cancer. However, in this study with limited power to detect small differences between the study arms, adjuvant chemotherapy failed to significantly improve DFS and OS.
Published: 2007
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