182 results on '"O. Gautschi"'
Search Results
2. 138P Cost-effectiveness of nivolumab and ipilimumab versus chemotherapy (with and without bevacizumab) in patients with unresectable malignant pleural mesothelioma in Switzerland
- Author
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M.C. Barbier, A. Fengler, and O. Gautschi
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Pulmonary and Respiratory Medicine ,Oncology - Published
- 2023
3. 365P Patterns of progression on first-line osimertinib in patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC): A Swiss cohort study
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A. Schuler, J. Huser, S. Schaer, S. Schmid, A. Scherz, O. Gautschi, L.A. Mauti, T. Von Briel, C. Waibel, L. Wannesson De Nicola, J. Pankovics, M.T. Mark, S.I. Rothschild, A. Addeo, W-D. Janthur, M. Siano, C. Britschgi, and M. Frueh
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Oncology ,Hematology - Published
- 2022
4. [Oncological emergencies with special consideration of the side effects of checkpoint inhibitors]
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P, Niederberger, M, Christ, and O, Gautschi
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Drug-Related Side Effects and Adverse Reactions ,Paraneoplastic Syndromes ,Neoplasms ,Hypercalcemia ,Humans ,Emergencies - Abstract
Oncological patients are already exceedingly burdened due to their underlying disease, so that another complication can quickly cause significant deterioration of the state of health. Febrile neutropenia should be rapidly treated with anti-infective agents and malignant hypercalcemia requires a rapid diagnosis. In the case of suspected checkpoint inhibitor-associated toxicity, an interdisciplinary consultation is often necessary.Onkologische Patienten sind durch ihre Grundkrankheit bereits außerordentlich belastet, sodass eine weitere Komplikation eine rasche Verschlechterung des Gesundheitszustandes bewirken kann. Eine febrile Neutropenie soll rasch antiinfektiös behandelt werden; eine maligne Hyperkalzämie braucht eine rasche Diagnose. Im Fall einer vermuteten Checkpoint-Inhibitor-assoziierten Toxizität ist oft eine interdisziplinäre Abstimmung nötig.
- Published
- 2022
5. Onkologische Notfälle mit besonderer Berücksichtigung der Nebenwirkungen von Checkpoint-Inhibitoren
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M. Christ, O. Gautschi, and P. Niederberger
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Gynecology ,03 medical and health sciences ,medicine.medical_specialty ,0302 clinical medicine ,business.industry ,Internal Medicine ,Emergency Medicine ,medicine ,030208 emergency & critical care medicine ,Emergency Nursing ,030204 cardiovascular system & hematology ,Critical Care and Intensive Care Medicine ,business - Abstract
Onkologische Patienten sind durch ihre Grundkrankheit bereits auserordentlich belastet, sodass eine weitere Komplikation eine rasche Verschlechterung des Gesundheitszustandes bewirken kann. Eine febrile Neutropenie soll rasch antiinfektios behandelt werden; eine maligne Hyperkalzamie braucht eine rasche Diagnose. Im Fall einer vermuteten Checkpoint-Inhibitor-assoziierten Toxizitat ist oft eine interdisziplinare Abstimmung notig.
- Published
- 2021
6. Chemotherapy negatively impacts the tumor immune microenvironment in NSCLC: an analysis of pre- and post-treatment biopsies in the multi-center SAKK19/09 study
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M L Amrein, S Savic-Prince, Adrian F. Ochsenbein, Michael A. Amrein, Elias D. Bührer, Rolf Jaggi, Sacha I. Rothschild, Lukas Bubendorf, Qiyu Li, Carsten Riether, and O. Gautschi
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Male ,Cancer Research ,Lung Neoplasms ,LAG3 ,Biopsy ,medicine.medical_treatment ,Immunology ,Gene Expression ,chemical and pharmacologic phenomena ,610 Medicine & health ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Carcinoma, Non-Small-Cell Lung ,Tumor Microenvironment ,Humans ,Chemotherapy ,Immunology and Allergy ,Medicine ,030212 general & internal medicine ,Lung cancer ,TNFRSF18 ,business.industry ,FOXP3 ,Cancer ,medicine.disease ,Immune checkpoint ,Immune microenvironment ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Female ,Original Article ,business ,Non-small-cell lung cancer - Abstract
Background Over the past few years, immune checkpoint inhibitors have changed the therapeutic landscape of non-small-cell lung cancer (NSCLC). Response to immune checkpoint inhibitors correlates with a pre-existing anti-tumoral immune response. Checkpoint inhibitors have been introduced as second-line therapy and are only very recently used as monotherapy or in combination with chemotherapy as first-line treatment of NSCLC. However, the effect of conventional first-line platinum-based chemotherapy on the immune infiltrate in the tumor is largely unknown. Methods We measured the gene expression of a custom set of 201 cancer- and immune-related genes in 100 NSCLC tumor biopsies collected before chemotherapy and 33 re-biopsies after platinum-based chemotherapy at the time point of progression. For 29 patients matched pre- and post-chemotherapy samples could be evaluated. Results We identified a cluster of 47 co-expressed immune genes, including PDCD1 (PD1) and CD274 (PD-L1), along with three other co-expression clusters. Chemotherapy decreased the average gene expression of the immune cluster while no effect was observed on the other three cluster. Within this immune cluster, CTLA4, LAG3, TNFRSF18, CD80 and FOXP3 were found to be significantly decreased in patient-matched samples after chemotherapy. Conclusion Our results suggest that conventional platinum-based chemotherapy negatively impacts the immune microenvironment at the time point of secondary progression.
- Published
- 2020
7. Efficacité et sécurité du selpercatinib (LOXO-292) par dernier traitement systémique reçu chez les patients (pts) atteints de cancer bronchique non à petites cellules (CBNPC) ayant une fusion du gène RET (RET+)
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O. Gautschi, A. Drilon, D. Shao Wen Tan, G.R. Oxnard, C. Mccoach, K. Goto, K. Park, G. Alonso Casal, F. De Braud, P. French, V. Soldatenkova, and B. Besse
- Subjects
Pulmonary and Respiratory Medicine - Published
- 2022
8. Mise à jour de l’efficacité/sécurité globales du selpercatinib chez les patients (pts) atteints de cancer bronchique non à petites cellules (CBNPC) ayant une fusion du gène RET (RET+)
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B. Besse, A.E. Drillon, B.J. Solomon, V. Subbiah, D. Shao-Weng Tan, K. Park, F.G. De Braud, G. Alonso, J. Wolf, V. Soldatenkova, A.K. Lin, P. Plernjit French, K. goto, and O. Gautschi
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Pulmonary and Respiratory Medicine - Published
- 2022
9. 46P Prognostic impact of immune checkpoint inhibition in patients with metastatic non-small cell lung cancer (NSCLC): Real-world study in central Switzerland
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V. Allmann, O. Gautschi, D. Lehnick, D. Dyntar, C. Schwegler, M. Dressler, J. Godau, P. Niederberger, K. Zeidler, and J. Diebold
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Oncology ,Hematology - Published
- 2022
10. 27P Durability of efficacy and safety with selpercatinib in patients (pts) with RET fusion+ non-small cell lung cancer (NSCLC)
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A. Drilon, V. Subbiah, O. Gautschi, P. Tomasini, F.G.M. De Braud, B. Solomon, D. Shao-Weng Tan, G. Alonso, J. Wolf, K. Park, K. Goto, V. Soldatenkova, S. Szymczak, S. Barker, T. Puri, A.B. Lin, H.H.F. Loong, and B. Besse
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Oncology ,Hematology - Published
- 2022
11. Strategien zur Überwindung der erworbenen EGFR-TKI-Resistenz durch T790M spezifische Substanzen am Beispiel von Osimertinib
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M. Kimmich, R. Pirker, Frank Griesinger, O. Gautschi, Martin Sebastian, Juergen Wolf, A. Lüers, C. Schulz, W. Brugger, Rainer Wiewrodt, Martin Früh, S. Radke, and B. Deschler-Baier
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0301 basic medicine ,Pulmonary and Respiratory Medicine ,Gynecology ,03 medical and health sciences ,medicine.medical_specialty ,030104 developmental biology ,0302 clinical medicine ,business.industry ,030220 oncology & carcinogenesis ,Medicine ,business - Abstract
Zusammenfassung Die Resistenzbildung gegenüber der 1. und 2. Generation von Tyrosinkinase-Inhibitoren (TKIs) des epidermalen Wachstumsfaktors (EGFR) stellt bei der Behandlung von Patienten mit nicht kleinzelligem Lungenkarzinom, die eine aktivierende Mutation im EGFR aufweisen, ein großes Problem dar. Drittgenerations-EGFR-TKIs richten sich sowohl gegen aktivierende als auch gegen die Resistenz-vermittelnde T790M-Mutation. EGFR-TKIs der 3. Generation zeigen in klinischen Studien bei T790M-positiven Patienten relevante Wirksamkeit bei meist milden bis moderaten klassenspezifischen Nebenwirkungen. Molekularpathologischen Analysen kommt bei der Entscheidung zur Therapie mit Drittgenerations-EGFR-TKIs eine bedeutsame Rolle zu. In dieser Übersichtsarbeit wird der aktuelle Entwicklungsstand von Drittgenerations-EGFR-TKIs dargestellt mit einem Schwerpunkt auf Osimertinib, dem ersten und bislang einzigen in Deutschland zugelassenen Wirkstoff dieser Klasse. Zudem wird die Relevanz einer molekularen Diagnostik an Tumorgewebe bzw. an zirkulierender Tumor-DNA diskutiert.
- Published
- 2018
12. 1279P Impact of KRAS mutations and subtypes on efficacy of immune-checkpoint inhibitors (ICI) in non-small cell lung cancer (NSCLC)
- Author
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S. Couraud, Alexis B. Cortot, Joel W. Neal, Amélie Lusque, O. Gautschi, Fabrice Barlesi, J. Mazieres, Remi Veillon, Mohamed Boucekine, Sanjay Popat, J. Milia Baron, A. Drilon, Laurent Mhanna, Terry L. Ng, Pascale Tomasini, Valérie Gounant, L. Greillier, and A. Thai
- Subjects
Oncology ,business.industry ,Immune checkpoint inhibitors ,medicine ,Cancer research ,non-small cell lung cancer (NSCLC) ,Hematology ,KRAS ,medicine.disease_cause ,business ,medicine.disease - Published
- 2020
13. Patterns of progression on osimertinib in EGFR T790M positive NSCLC: A Swiss cohort study
- Author
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S. Aeppli, Luciano Wannesson, Dirk Klingbiel, Miklos Pless, Martin Früh, O. Gautschi, D. Foerbs, Izadora Demmer, Sacha I. Rothschild, W.-D. Janthur, Wolfram Jochum, Christian Britschgi, Stephan Schmid, University of Zurich, and Schmid, S
- Subjects
Adult ,Male ,0301 basic medicine ,Pulmonary and Respiratory Medicine ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Treatment duration ,EGFR T790M ,610 Medicine & health ,Gastroenterology ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Medicine ,In patient ,Osimertinib ,1306 Cancer Research ,Aged ,Retrospective Studies ,Aged, 80 and over ,Antitumor activity ,Acrylamides ,Aniline Compounds ,business.industry ,Middle Aged ,Survival Analysis ,ErbB Receptors ,030104 developmental biology ,Oncology ,Drug Resistance, Neoplasm ,2740 Pulmonary and Respiratory Medicine ,030220 oncology & carcinogenesis ,Mutation ,10032 Clinic for Oncology and Hematology ,Disease Progression ,Female ,2730 Oncology ,Non small cell ,business ,Switzerland ,Egfr tyrosine kinase ,Follow-Up Studies ,Cohort study - Abstract
Introduction Osimertinib is an EGFR tyrosine kinase inhibitor (TKI) with antitumor activity in non-small cell lung cancer (NSCLC) with EGFR T790 M mutations. The incidence of oligo-progression (PD) on osimertinib is unknown. Methods We retrospectively analyzed 50 pre-treated EGFR T790M-positive NSCLC patients treated with osimertinib at seven Swiss centers. Oligo-PD was defined as PD in ≤ 5 lesions. Mutational profiling of pre- and post-osimertinib tumor samples was performed. Results Median age was 62 years (37–89), 64% were females, 86% had a PS ≤ 1, 54%/13% were never/current smokers. Median follow-up was 15.3 (IQR: 8.6–21.6) months. Overall response rate was 80%, median progression-free survival 12.1 months (95% CI 8.3–18.3), median overall survival 28 months (95% CI 20.2-not reached [NR]) and median treatment duration 18.8 months (95%CI 16-8-NR). PD occurred in 36 patients (72%). 73% had oligo-PD. Median osimertinib treatment duration in patients with oligo-PD was 19.6 vs. 7 months if systemic PD (p = 0.007). The number of progressive lesions in patients with oligo-PD was 1 (27%), 2 (35%) and 3–5 (39%). Sites of PD included lungs (56%), bones (44%), and brain (17%). Sixteen patients with oligo-PD continued treatment with osimertinib for a median of 6.7 months beyond PD. Thirteen received local ablative treatment (LAT). In pre- and post-PD tumor tissue multiple molecular alterations were detected. Conclusion In patients with acquired resistance to osimertinib, we observed a high rate (73%) of oligo-PD. Outcomes of patients receiving LAT were favorable, supporting the concept of osimertinib treatment beyond progression in combination with LAT of progressing lesions.
- Published
- 2019
14. [Strategies to Overcome Acquired Resistance to EGFR-TKI Therapy Based on T790M Specific Substances using Osimertinib as an Example]
- Author
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F, Griesinger, S, Radke, A, Lüers, B, Deschler-Baier, M, Kimmich, M, Sebastian, C, Schulz, W, Brugger, R, Wiewrodt, R, Pirker, M, Früh, O, Gautschi, and J, Wolf
- Subjects
ErbB Receptors ,Acrylamides ,Aniline Compounds ,Lung Neoplasms ,Drug Resistance, Neoplasm ,Carcinoma, Non-Small-Cell Lung ,Germany ,Mutation ,Humans ,Antineoplastic Agents ,Molecular Targeted Therapy ,Protein Kinase Inhibitors ,Piperazines - Abstract
Tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) are widely used in non-small cell lung cancer patients harboring activating EGFR mutations. However, resistance mechanisms, particularly the T790 M mutation, hamper longer-term therapeutic success of first and second generation EGFR-TKIs. To address this unmet medical need, EGFR-TKIs of the third generation are under clinical development. Relevant clinical efficacy with mainly mild to moderate class-specific side effects has been shown for third-generation EGFR-TKIs. Molecular testing is of major importance in deciding for treatment with third generation EGFR-TKIs. This article elucidates the developmental state of third generation EGFR-TKIs with its focus on Osimertinib, the first and currently the only compound in this class which is approved in Germany. Additionally, the medical importance of molecular diagnosis using tumor tissue and circulating tumor DNA is discussed.Die Resistenzbildung gegenüber der 1. und 2. Generation von Tyrosinkinase-Inhibitoren (TKIs) des epidermalen Wachstumsfaktors (EGFR) stellt bei der Behandlung von Patienten mit nicht kleinzelligem Lungenkarzinom, die eine aktivierende Mutation im EGFR aufweisen, ein großes Problem dar. Drittgenerations-EGFR-TKIs richten sich sowohl gegen aktivierende als auch gegen die Resistenz-vermittelnde T790M-Mutation. EGFR-TKIs der 3. Generation zeigen in klinischen Studien bei T790M-positiven Patienten relevante Wirksamkeit bei meist milden bis moderaten klassenspezifischen Nebenwirkungen. Molekularpathologischen Analysen kommt bei der Entscheidung zur Therapie mit Drittgenerations-EGFR-TKIs eine bedeutsame Rolle zu. In dieser Übersichtsarbeit wird der aktuelle Entwicklungsstand von Drittgenerations-EGFR-TKIs dargestellt mit einem Schwerpunkt auf Osimertinib, dem ersten und bislang einzigen in Deutschland zugelassenen Wirkstoff dieser Klasse. Zudem wird die Relevanz einer molekularen Diagnostik an Tumorgewebe bzw. an zirkulierender Tumor-DNA diskutiert.
- Published
- 2018
15. Neoadjuvant chemotherapy and extrapleural pneumonectomy of malignant pleural mesothelioma with or without hemithoracic radiotherapy (SAKK 17/04): a randomised, international, multicentre phase 2 trial
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K. Eckhardt, Clemens B. Caspar, Kristiaan Nackaerts, Michael Beyeler, A. Xyrafas, Martin Früh, llja F Ciernik, Isabelle Opitz, Walter Weder, Wolfgang Nagel, Oliver Riesterer, O. Gautschi, Christoph Mamot, Carlo Mordasini, Daniel M. Aebersold, Karin Ribi, Adrian F. Ochsenbein, Richard Cathomas, Solange Peters, Rolf A. Stahel, Jerome Krayenbuehl, Ralph A. Schmid, Alfred Zippelius, Michael Töpfer, University of Zurich, and Stahel, Rolf A
- Subjects
Extrapleural Pneumonectomy ,medicine.medical_specialty ,Performance status ,business.industry ,medicine.medical_treatment ,610 Medicine & health ,medicine.disease ,10044 Clinic for Radiation Oncology ,3. Good health ,Surgery ,Pneumonectomy ,Pemetrexed ,Oncology ,10032 Clinic for Oncology and Hematology ,medicine ,2730 Oncology ,Thoracotomy ,Mesothelioma ,Pleural Neoplasm ,business ,Neoadjuvant therapy ,medicine.drug - Abstract
Summary Background Postoperative hemithoracic radiotherapy has been used to treat malignant pleural mesothelioma, but it has not been assessed in a randomised trial. We assessed high-dose hemithoracic radiotherapy after neoadjuvant chemotherapy and extrapleural pneumonectomy in patients with malignant pleural mesothelioma. Methods We did this phase 2 trial in two parts at 14 hospitals in Switzerland, Belgium, and Germany. We enrolled patients with pathologically confirmed malignant pleural mesothelioma; resectable TNM stages T1–3 N0–2, M0; WHO performance status 0–1; age 18–70 years. In part 1, patients were given three cycles of neoadjuvant chemotherapy (cisplatin 75 mg/m 2 and pemetrexed 500 mg/m 2 on day 1 given every 3 weeks) and extrapleural pneumonectomy; the primary endpoint was complete macroscopic resection (R0–1). In part 2, participants with complete macroscopic resection were randomly assigned (1:1) to receive high-dose radiotherapy or not. The target volume for radiotherapy encompassed the entire hemithorax, the thoracotomy channel, and mediastinal nodal stations if affected by the disease or violated surgically. A boost was given to areas at high risk for locoregional relapse. The allocation was stratified by centre, histology (sarcomatoid vs epithelioid or mixed), mediastinal lymph node involvement (N0–1 vs N2), and T stage (T1–2 vs T3). The primary endpoint of part 1 was the proportion of patients achieving complete macroscopic resection (R0 and R1). The primary endpoint in part 2 was locoregional relapse-free survival, analysed by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00334594. Findings We enrolled patients between Dec 7, 2005, and Oct 17, 2012. Overall, we analysed 151 patients receiving neoadjuvant chemotherapy, of whom 113 (75%) had extrapleural pneumonectomy. Median follow-up was 54·2 months (IQR 32–66). 52 (34%) of 151 patients achieved an objective response. The most common grade 3 or 4 toxic effects were neutropenia (21 [14%] of 151 patients), anaemia (11 [7%]), and nausea or vomiting (eight [5%]). 113 patients had extrapleural pneumonectomy, with complete macroscopic resection achieved in 96 (64%) of 151 patients. We enrolled 54 patients in part 2; 27 in each group. The main reasons for exclusion were patient refusal (n=20) and ineligibility (n=10). 25 of 27 patients completed radiotherapy. Median total radiotherapy dose was 55·9 Gy (IQR 46·8–56·0). Median locoregional relapse-free survival from surgery, was 7·6 months (95% CI 4·5–10·7) in the no radiotherapy group and 9·4 months (6·5–11·9) in the radiotherapy group. The most common grade 3 or higher toxic effects related to radiotherapy were nausea or vomiting (three [11%] of 27 patients), oesophagitis (two [7%]), and pneumonitis (two [7%]). One patient died of pneumonitis. We recorded no toxic effects data for the control group. Interpretation Our findings do not support the routine use of hemithoracic radiotherapy for malignant pleural mesothelioma after neoadjuvant chemotherapy and extrapleural pneumonectomy. Funding Swiss Group for Clinical Cancer Research, Swiss State Secretariat for Education, Research and Innovation, Eli Lilly.
- Published
- 2015
16. 557P Binimetinib, pemetrexed (Pem) and cisplatin (Cis), followed by maintenance of Binimetinib and Pem in patients with advanced non-small cell lung cancer (NSCLC) and KRAS mutations: The phase Ib SAKK 19/16 trial
- Author
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Cristiana Sessa, Sabine Schmid, C. Rusterholz, H.E. Thut, I. Colombo, G. Godar, Patrizia Froesch, Michael Mark, M. Früh, O. Gautschi, Sacha I. Rothschild, Qiyu Li, and Y. Metaxas
- Subjects
Cisplatin ,business.industry ,non-small cell lung cancer (NSCLC) ,Binimetinib ,Hematology ,medicine.disease_cause ,medicine.disease ,chemistry.chemical_compound ,Pemetrexed ,Oncology ,chemistry ,medicine ,Cancer research ,In patient ,KRAS ,business ,medicine.drug - Published
- 2020
17. Preoperative chemoradiotherapy with cisplatin and docetaxel for stage IIIB non-small-cell lung cancer: 10-year follow-up of the SAKK 16/01 trial
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S. Peters, René-Olivier Mirimanoff, M. Früh, A. Xyrafas, O. Gautschi, Hans-Beat Ris, Miklos Pless, and Roger Stupp
- Subjects
0301 basic medicine ,Oncology ,Cisplatin ,Stage IIIB non-small cell lung cancer ,medicine.medical_specialty ,Preoperative chemoradiotherapy ,business.industry ,10 year follow up ,Hematology ,Preoperative care ,Clinical trial ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Docetaxel ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,business ,Chemoradiotherapy ,medicine.drug - Abstract
To the best of our knowledge, this is one of very few reports on long-term survival after trimodality therapy for locally advanced stage IIIB NSCLC. It demonstrates that selected patients can be cured by such an intensive treatment. Extended follow-up beyond 5 years, including chest imaging and optimal control of cardiovascular risk factors should be integrated in future clinical trials.
- Published
- 2016
18. A multicentre randomized phase III trial comparing pembrolizumab (P) vs single agent chemotherapy (CT) for advanced pre-treated malignant pleural mesothelioma (MPM): Results from the European Thoracic Oncology Platform (ETOP 9-15) PROMISE-meso trial
- Author
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S. Rusakiewicz, R. Shah, Ernest Nadal, David Gilligan, Sanjay Popat, Solange Peters, Patricia Fisher, A. Pope, Alessandra Curioni-Fontecedro, V. Polydoropoulou, R. López Castro, Mary O'Brien, O. Gautschi, Rolf A. Stahel, James Spicer, H. Roschitzki-Voser, Arup Roy, R. García Campelo, W.-D. Janthur, and Barbara Ruepp
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Poor prognosis ,business.industry ,Pleural mesothelioma ,Immune checkpoint inhibitors ,Hematology ,Never smokers ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,Family medicine ,Overall survival ,Single agent chemotherapy ,Medicine ,Single agent ,business ,Objective response - Abstract
Background MPM is an aggressive malignancy of increasing prevalence and poor prognosis. At relapse after platinum-based (pb) CT, single agent CT is commonly used and single arm trials of immune checkpoint inhibitors have demonstrated encouraging activity. Methods PROMISE-meso is an open-label 1:1 randomized phase III trial investigating the efficacy of P (200 mg/Q3W) vs institutional choice single agent CT (gemcitabine or vinorelbine) in relapsed MPM patients (pts) failing one previous line of pb CT. Pts were of PS 0-1 and unselected for PD-L1 status. P beyond progression (PD) for clinical benefit and crossover to P at PD on CT were allowed. Primary endpoint was progression-free survival (PFS, RECIST 1.1) by independent radiological review (IR). The trial was designed to detect an increase in median PFS from 3.5 months (ms) to 6ms with P (HR = 0.58, 80% power, 1-sided α = 0.025). 142 pts were needed to observe the required 110 events. Secondary endpoints were overall survival (OS), investigator assessed (IA) PFS, objective response rate (ORR), adverse events (AE), while efficacy by PD-L1 status was exploratory. Results Between 09/17 and 08/18, 144 pts were randomized, 73 to P and 71 to CT. At 20/02/19 data lock, 70 pts were on follow-up (median 12ms). Pts were of median age 70 years, 82% males, 77% poor EORTC prognostic score, 50% never smokers, 89% epithelioid histology and 65% (of 102 available) TPS≥1%. ORRs were 22% in P, 6% in CT (p = 0.004). 62 IR PFS events were observed in P vs 56 in CT, median PFS 2.5ms (95%CI 2.1-4.2) vs 3.4ms (2.2-4.3), HR = 1.06 (0.73–1.53), p = 0.76. Median OS was 10.7ms for P vs 11.7ms for CT, HR = 1.05 (0.66-1.67), p = 0.85. 45 CT pts crossed over to P. Accounting for crossover yielded similar OS results. Treatment-related AEs grade ≥3 were experienced by 19% P vs 24% CT pts, one fatal per arm. Most common AEs were fatigue (19%) in P vs nausea (27%) and fatigue (31%) in CT. Conclusions This is the first randomized trial evaluating the efficacy of P vs single agent CT in MPM pts progressing after or on previous pb CT. In unselected pts, whilst associated with an improved ORR, P does not improve PFS or OS over single agent CT. Clinical trial identification NCT02991482. Legal entity responsible for the study European Thoracic Oncology Platform (ETOP). Funding MSD Merck Sharp & Dohme AG. Disclosure S. Popat: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Boehringer Ingelheim; Research grant / Funding (institution): Epizyme; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Research grant / Funding (institution): Clovis Oncology; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Research grant / Funding (institution): Lilly; Honoraria (self), Research grant / Funding (institution): Takeda; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self): Chugai Pharma; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Sharp & Dohme; Advisory / Consultancy: Guardant Health; Advisory / Consultancy: AbbVie. A. Curioni-Fontecedro: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Merck Sharp and Dohme; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Takeda. R. Shah: Advisory / Consultancy: Merck Sharp & Dohme; Advisory / Consultancy: Lilly. M. O’Brien: Advisory / Consultancy: Merck Sharp & Dohme; Advisory / Consultancy: BMS; Advisory / Consultancy: AbbVie; Advisory / Consultancy: Pierre fabre; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy, Teaching role for Roche: Roche. P. Fisher: Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Sharp & Dohme. D. Gilligan: Honoraria (self): Merck Sharp & Dohme. E. Nadal: Advisory / Consultancy: Merck Sharp & Dohme. R. Lopez Castro: Honoraria (self), Travel / Accommodation / Expenses: Takeda; Honoraria (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Boehringer Ingelheim; Honoraria (self), Research grant / Funding (self), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Honoraria (self), Travel / Accommodation / Expenses: Merck Serono; Honoraria (self), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy: Aristo. R. Garcia Campelo: Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Sharp & Dohme. S. Peters: Honoraria (self): AbbVie; Honoraria (self): Amgen; Honoraria (self): AstraZeneca; Honoraria (self): Bayer; Honoraria (self): Biocartis; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Clovis; Honoraria (self): Daiichi Sankyo; Honoraria (self): Debiopharm; Honoraria (self): Lilly; Honoraria (self): Roche; Honoraria (self): Foundation Medicine; Honoraria (self): Illumina; Honoraria (self): Janssen; Honoraria (self): Merck Sharp and Dohme; Honoraria (self): Merck Serono; Honoraria (self): Merrimack; Honoraria (self): Novartis; Honoraria (self): Pharma Mar; Honoraria (self): Pfizer; Honoraria (self): Regeneron; Honoraria (self): Sanofi; Honoraria (self): Seattle Genetics ; Honoraria (self): Takeda. R.A. Stahel: Honoraria (self): AbbVie; Honoraria (self), Research grant / Funding (self): AstraZeneca; Honoraria (self), Research grant / Funding (self): Boehringer Ingelheim; Honoraria (self), Research grant / Funding (self): Merck Sharp & Dohme; Honoraria (self), Research grant / Funding (self): Pfizer; Honoraria (self), Research grant / Funding (self): Roche; Honoraria (self): Takeda; Research grant / Funding (self): BMS; Research grant / Funding (self): Genentech. All other authors have declared no conflicts of interest.
- Published
- 2019
19. Circulating microRNA profiling in patients with advanced non-squamous NSCLC receiving bevacizumab/erlotinib followed by platinum-based chemotherapy at progression (SAKK 19/05)
- Author
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C. Droege, O. Gautschi, Peter Brauchli, Florent Baty, Sacha I. Rothschild, Daniel Betticher, Miklos Pless, Dirk Klingbiel, Rolf A. Stahel, Adrian F. Ochsenbein, M. Früh, Markus Joerger, Francesco Zappa, R. von Moos, Martin Brutsche, University of Zurich, and Joerger, M
- Subjects
Male ,Oncology ,Cancer Research ,Lung Neoplasms ,medicine.medical_treatment ,Gene Expression ,Bioinformatics ,0302 clinical medicine ,Risk Factors ,Carcinoma, Non-Small-Cell Lung ,Antineoplastic Combined Chemotherapy Protocols ,1306 Cancer Research ,Prospective Studies ,Aged, 80 and over ,0303 health sciences ,Middle Aged ,Prognosis ,Combined Modality Therapy ,3. Good health ,Bevacizumab ,030220 oncology & carcinogenesis ,Disease Progression ,2730 Oncology ,Female ,Erlotinib ,medicine.drug ,Adult ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,610 Medicine & health ,Antibodies, Monoclonal, Humanized ,Erlotinib Hydrochloride ,03 medical and health sciences ,Internal medicine ,microRNA ,medicine ,Humans ,In patient ,Lung cancer ,Aged ,Neoplasm Staging ,Platinum ,030304 developmental biology ,Chemotherapy ,business.industry ,Gene Expression Profiling ,Reproducibility of Results ,medicine.disease ,MicroRNAs ,Circulating MicroRNA ,2740 Pulmonary and Respiratory Medicine ,Non squamous ,10032 Clinic for Oncology and Hematology ,Quinazolines ,business - Abstract
Objectives Molecular subclassification of non small-cell lung cancer (NSCLC) is essential to improve clinical outcome. This study assessed the prognostic and predictive value of circulating micro-RNA (miRNA) in patients with non-squamous NSCLC enrolled in the phase II SAKK (Swiss Group for Clinical Cancer Research) trial 19/05, receiving uniform treatment with first-line bevacizumab and erlotinib followed by platinum-based chemotherapy at progression. Materials and methods Fifty patients with baseline and 24h blood samples were included from SAKK 19/05. The primary study endpoint was to identify prognostic (overall survival, OS) miRNA's. Patient samples were analyzed with Agilent human miRNA 8x60K microarrays, each glass slide formatted with eight high-definition 60K arrays. Each array contained 40 probes targeting each of the 1347 miRNA. Data preprocessing included quantile normalization using robust multi-array average (RMA) algorithm. Prognostic and predictive miRNA expression profiles were identified by Spearman's rank correlation test (percentage tumor shrinkage) or log-rank testing (for time-to-event endpoints). Results Data preprocessing kept 49 patients and 424 miRNA for further analysis. Ten miRNA's were significantly associated with OS, with hsa-miR-29a being the strongest prognostic marker (HR=6.44, 95%-CI 2.39–17.33). Patients with high has-miR-29a expression had a significantly lower survival at 10 months compared to patients with a low expression (54% versus 83%). Six out of the 10 miRNA's (hsa-miRN-29a, hsa-miR-542-5p, hsa-miR-502-3p, hsa-miR-376a, hsa-miR-500a, hsa-miR-424) were insensitive to perturbations according to jackknife cross-validation on their HR for OS. The respective principal component analysis (PCA) defined a meta-miRNA signature including the same 6 miRNA's, resulting in a HR of 0.66 (95%-CI 0.53–0.82). Conclusion Cell-free circulating miRNA-profiling successfully identified a highly prognostic 6-gene signature in patients with advanced non-squamous NSCLC. Circulating miRNA profiling should further be validated in external cohorts for the selection and monitoring of systemic treatment in patients with advanced NSCLC.
- Published
- 2014
20. MA 15.11 CCNE1, PTGS2, TGFA and WISP2 Predict Benefit from Bevacizumab and Chemotherapy in Patients with Advanced Non-Small Cell Lung Cancer (SAKK19/09)
- Author
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Rolf A. Stahel, Daniel C. Betticher, Martina Schneider, Miklos Pless, Thilo Zander, Carsten Riether, Martin Früh, Richard Cathomas, N Schuster, Spasenija Savic, Rolf Jaggi, Sacha I. Rothschild, Michael A. Amrein, Christine Biaggi, Qiyu Li, Alfred Zippelius, Martin Brutsche, Daniel Rauch, O. Gautschi, Adrian F. Ochsenbein, and Lukas Bubendorf
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,Chemotherapy ,TGF alpha ,Bevacizumab ,business.industry ,medicine.medical_treatment ,medicine.disease ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,In patient ,Non small cell ,business ,Lung cancer ,medicine.drug - Published
- 2017
21. Evolution and clinical impact of EGFR mutations in circulating free DNA in the BELIEF trial
- Author
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Miguel Angel Molina, H. Roschitzki-Voser, A. Curioni, Enriqueta Felip, Sinead Cuffe, Solange Peters, Sanjay Popat, Rolf A. Stahel, M. Kassapian, Urania Dafni, Santiago Ponce, B. Massuti, Enric Carcereny, Miklos Pless, Roswitha Kammler, O. Gautschi, Rafael Rosell, Niki Karachaliou, Ramon Palmero, and M. Früh
- Subjects
Oncology ,Circulating free DNA ,business.industry ,Egfr mutation ,Cancer research ,Medicine ,Hematology ,business - Published
- 2018
22. Patterns of recurrence to Osimertinib in T790m positive NSCLC: A Swiss cohort study
- Author
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Christian Britschgi, Stefanie Aeppli, Sabine Schmid, W.-D. Janthur, L. Wannesson De Nicola, Dirk Klingbiel, I. Demmer, D. Foerbs, Wolfram Jochum, Miklos Pless, M. Früh, O. Gautschi, and Sacha I. Rothschild
- Subjects
Oncology ,T790M ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,Osimertinib ,Hematology ,business ,Cohort study - Published
- 2018
23. Neoadjuvant chemoradiotherapy with or without panitumumab in patients with wild-type KRAS, locally advanced rectal cancer (LARC): a randomized, multicenter, phase II trial SAKK 41/07
- Author
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Lucas Widmer, Elisabeth Oppliger Leibundgut, Daniela Baertschi, D. Helbling, Axel Madlung, H. Sun, F. Bosman, Markus Borner, R. Burkhard, Daniel Rauch, Ralph Winterhalder, Dieter Koeberle, György Bodoky, Beat Gloor, Piercarlo Saletti, O. Gautschi, Pu Yan, S. Bougel, and Jean Benhattar
- Subjects
Adult ,Diarrhea ,Male ,Oncology ,medicine.medical_specialty ,Colorectal cancer ,medicine.medical_treatment ,DNA Mutational Analysis ,Phases of clinical research ,610 Medicine & health ,Adenocarcinoma ,medicine.disease_cause ,Deoxycytidine ,Gastroenterology ,Proto-Oncogene Proteins p21(ras) ,Capecitabine ,Proto-Oncogene Proteins ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Panitumumab ,Neoadjuvant therapy ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Rectal Neoplasms ,business.industry ,Surrogate endpoint ,Antibodies, Monoclonal ,Chemoradiotherapy ,Hematology ,Middle Aged ,medicine.disease ,Neoadjuvant Therapy ,Treatment Outcome ,ras Proteins ,Female ,Fluorouracil ,KRAS ,business ,medicine.drug - Abstract
BACKGROUND We conducted a randomized, phase II, multicenter study to evaluate the anti-epidermal growth factor receptor (EGFR) mAb panitumumab (P) in combination with chemoradiotherapy (CRT) with standard-dose capecitabine as neoadjuvant treatment for wild-type KRAS locally advanced rectal cancer (LARC). PATIENTS AND METHODS Patients with wild-type KRAS, T3-4 and/or N+ LARC were randomly assigned to receive CRT with or without P (6 mg/kg). The primary end-point was pathological near-complete or complete tumor response (pNC/CR), defined as grade 3 (pNCR) or 4 (pCR) histological regression by Dworak classification (DC). RESULTS Forty of 68 patients were randomly assigned to P + CRT and 28 to CRT. pNC/CR was achieved in 21 patients (53%) treated with P + CRT [95% confidence interval (CI) 36%-69%] versus 9 patients (32%) treated with CRT alone (95% CI: 16%-52%). pCR was achieved in 4 (10%) and 5 (18%) patients, and pNCR in 17 (43%) and 4 (14%) patients. In immunohistochemical analysis, most DC 3 cells were not apoptotic. The most common grade ≥3 toxic effects in the P + CRT/CRT arm were diarrhea (10%/6%) and anastomotic leakage (15%/4%). CONCLUSIONS The addition of panitumumab to neoadjuvant CRT in patients with KRAS wild-type LARC resulted in a high pNC/CR rate, mostly grade 3 DC. The results of both treatment arms exceeded prespecified thresholds. The addition of panitumumab increased toxicity.
- Published
- 2013
24. Immune response and adverse events to influenza vaccine in cancer patients undergoing PD-1 blockade
- Author
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H. Laeubli, Michal A. Stanczak, Mohammedyaseen Syedbasha, O. Gautschi, Lukas Kaufmann, Adrian Egli, Sacha I. Rothschild, Deborah R. Vogt, Alfred Zippelius, and Cathrin Balmelli
- Subjects
Oncology ,medicine.medical_specialty ,Influenza vaccine ,business.industry ,Internal medicine ,medicine ,Cancer ,Pd 1 blockade ,Hematology ,Adverse effect ,medicine.disease ,business - Published
- 2017
25. Src Inhibitors in Lung Cancer: Current Status and Future Directions
- Author
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O. Gautschi, Faye M. Johnson, Sacha I. Rothschild, and Eric B. Haura
- Subjects
Pulmonary and Respiratory Medicine ,Clinical Trials as Topic ,Cancer Research ,Lung Neoplasms ,business.industry ,Angiogenesis ,medicine.medical_treatment ,Cancer ,Pharmacology ,medicine.disease ,Targeted therapy ,Radiation therapy ,Dasatinib ,src-Family Kinases ,Oncology ,medicine ,Cancer research ,Humans ,Lung cancer ,business ,Protein Kinase Inhibitors ,Bosutinib ,medicine.drug ,Proto-oncogene tyrosine-protein kinase Src - Abstract
Src tyrosine kinases regulate multiple genetic and signaling pathways involved in the proliferation, survival, angiogenesis, invasion, and migration of various types of cancer cells They are frequently expressed and activated in many cancer types, including lung cancer. Several Src inhibitors, including dasatinib, saracatinib, bosutinib, and KX2-391, are currently being investigated in clinical trials. Preliminary results of the use of single-agent Src inhibitors in unselected patients with lung cancer show that these inhibitors have a favorable safety profile and anticancer activity. Their combination with cytotoxic chemotherapy, other targeted therapy, and radiation therapy is currently being explored. In this review, we summarize the rationale for and the current status of Src inhibitor development and discuss future directions based on emerging preclinical data.
- Published
- 2010
26. Pembrolizumab (pembro) for relapsed malignant pleural mesothelioma (MPM): Outcomes in real-life setting in Australia (AUS) and Switzerland (CH)
- Author
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T. Bartnick, Laetitia A. Mauti, Miklos Pless, Prudence A. Russell, Sabine Schmid, Anna K. Nowak, Kenneth J. O'Byrne, Brett G.M. Hughes, H. Bouchaab, Dirk Klingbiel, Thomas John, R. von Moos, Nick Pavlakis, O. Gautschi, Sacha I. Rothschild, S. Savic Prince, Gareth Rivalland, Y. Metaxas, S. Kao, and Bibhusal Thapa
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Hematology ,Pembrolizumab ,03 medical and health sciences ,Relapsed Malignant Pleural Mesothelioma ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,In real life ,business - Published
- 2017
27. Molekulare Therapie beim Lungenkarzinom
- Author
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O Gautschi and D C Betticher
- Subjects
Antisense therapy ,Chemotherapy ,Kinase ,business.industry ,Matrix metalloproteinase inhibitor ,government.form_of_government ,medicine.medical_treatment ,Genetic enhancement ,General Medicine ,medicine.disease ,Neovascularization ,government ,Cancer research ,Medicine ,medicine.symptom ,business ,Receptor ,Lung cancer - Abstract
Every year more than 370,000 new cases of lung cancer occur in Europe. About 70% of the patients are not curable because of local or distant spread of tumor cells. Despite the use of chemotherapy, median survival of these patients is less than one year In the last two decades, important advances in cancer research have been achieved. This led to the development of a new class of potential anti-cancer agents, selectively targeting molecules which are important for the growth and the spread of tumor cells. Focussing on lung cancer, this review presents compounds that are furthest in clinical development, covering epidermal growth factor receptor inhibitors, receptor tyrosin kinase inhibitors, anti-angiogenic agents, matrix metalloproteinase inhibitors, gene therapy and antisense therapy.
- Published
- 2004
28. Pembrolizumab as second or further line treatment in relapsed malignant pleural mesothelioma: A Swiss registry
- Author
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S. Pratsch Peter, Laetitia A. Mauti, Sacha I. Rothschild, W. Mingrone, S. Wolleb Schild, Miklos Pless, Patrizia Froesch, R. von Moos, M. Loeffler, Ulf Petrausch, Y. Metaxas, H. Bouchaab, Sabine Schmid, S. Savic Prince, O. Gautschi, Dirk Klingbiel, and T. Bartnick
- Subjects
Oncology ,medicine.medical_specialty ,Relapsed Malignant Pleural Mesothelioma ,business.industry ,Internal medicine ,medicine ,Hematology ,Pembrolizumab ,Line (text file) ,business - Published
- 2017
29. Early detection of lung cancer: a statement from an expert panel of the Swiss university hospitals on lung cancer screening
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T, Frauenfelder, M A, Puhan, R, Lazor, C, von Garnier, J, Bremerich, T, Niemann, A, Christe, X, Montet, O, Gautschi, W, Weder, M, Kohler, P, Gasche, and University of Zurich
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Lung Neoplasms ,10255 Clinic for Thoracic Surgery ,Population ,Alternative medicine ,610 Medicine & health ,Risk Assessment ,Early Detection of Cancer/standards ,Hospitals, University ,Epidemiology ,medicine ,Humans ,Mass Screening ,ddc:612 ,Lung cancer ,Intensive care medicine ,education ,Early Detection of Cancer ,Lung Neoplasms/radiography ,education.field_of_study ,10042 Clinic for Diagnostic and Interventional Radiology ,business.industry ,10060 Epidemiology, Biostatistics and Prevention Institute (EBPI) ,medicine.disease ,Surgery ,2740 Pulmonary and Respiratory Medicine ,Practice Guidelines as Topic ,Position paper ,National Lung Screening Trial ,Observational study ,10178 Clinic for Pneumology ,business ,Tomography, X-Ray Computed ,Lung cancer screening ,Switzerland - Abstract
The discussion about setting up a program for lung cancer screening was launched with the publication of the results of the National Lung Screening Trial, which suggested reduced mortality in high-risk subjects undergoing CT screening. However, important questions about the benefit-harm balance and the details of a screening program and its cost-effectiveness remain unanswered. A panel of specialists in chest radiology, respiratory medicine, epidemiology, and thoracic surgery representing all Swiss university hospitals prepared this joint statement following several meetings. The panel argues that premature and uncontrolled introduction of a lung cancer screening program may cause substantial harm that may remain undetected without rigorous quality control. This position paper focuses on the requirements of running such a program with the objective of harmonizing efforts across the involved specialties and institutions and defining quality standards. The underlying statement includes information on current evidence for a reduction in mortality with lung cancer screening and the potential epidemiologic implications of such a program in Switzerland. Furthermore, requirements for lung cancer screening centers are defined, and recommendations for both the CT technique and the algorithm for lung nodule assessment are provided. In addition, related issues such as patient management, registry, and funding are addressed. Based on the current state of the knowledge, the panel concludes that lung cancer screening in Switzerland should be undertaken exclusively within a national observational study in order to provide answers to several critical questions before considering broad population-based screening for lung cancer.
- Published
- 2013
30. [Lung cancer - on the way to a molecular classification]
- Author
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S, Savic and O, Gautschi
- Subjects
Lung Neoplasms ,Humans - Abstract
Treatment options for patients with advanced lung cancer have greatly improved in recent years. New molecular-targeted drugs are avaliable based on predictive biomarkers. Molecular diagnostics are key to successful therapy. Guidelines and recommendations for lung cancer testing and treatment are evolving, and it is increasingly challenging to stay up-to-date. In view of the rapid development in the lung cancer field, the current article discusses the current evidence for lung cancer classification and testing, and illustrates new perspectives in modern oncology.
- Published
- 2012
31. Successful treatment of chemotherapy-refractory Sézary syndrome with alemtuzumab (Campath-1H)
- Author
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T. Hunziker, M. Streit, O. Gautschi, N. Blumenthal, R. Zenhäusern, and M. Solenthaler
- Subjects
medicine.medical_specialty ,CD52 ,business.industry ,Cutaneous T-cell lymphoma ,Erythroderma ,Hematology ,General Medicine ,CHOP ,medicine.disease ,Gastroenterology ,Lymphoma ,Leukemia ,Internal medicine ,Immunology ,medicine ,Alemtuzumab ,business ,Sezary Cell ,medicine.drug - Abstract
Introduction: Sezary syndrome (SS) is a cutaneous T-cell lymphoma characterized by erythroderma, lymphadenopathy and circulating atypical T cells. Median survival after diagnosis is 10 yr, with chemotherapy resistance being a major problem in advanced disease. Alemtuzumab (Campath-1H) is a monoclonal antibody directed against the lymphocytic antigen CD52, expressed on B- and T-cells. Alemtuzumab is approved for relapsing chronic B-cell leukemia and seems to be active also in T-cell lymphomas such as T-cell prolymphocytic lymphoma, SS and mycosis fungiodes. Case history: A 32-yr-old male patient presented with advanced stage, extensively pretreated SS with heavily itching erythroderma, peripheral lymphadenopathy, circulating Sezary cells and bone marrow infiltration. The disease had not responded to PUVA/interferon-α and progressed on chemotherapy with CHOP, 2-CDA, vinorelbine, etoposide and liposomal doxorubicin. Following treatment with alemtuzumab (30 mg i.v. three times per week for 10 wk), itching resolved rapidly and an almost complete remission was achieved within 3 months after starting this treatment. At 12-month follow up, no disease progression was present. Conclusion: In accordance with previous data, this single case underlines the potent activity of alemtuzumab in advanced, chemotherapy-refractory SS.
- Published
- 2003
32. [Chemotherapy for malignant tumors of lung and pleura]
- Author
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S, Rothschild and O, Gautschi
- Subjects
Male ,Lung Neoplasms ,Carcinoma, Non-Small-Cell Lung ,Pleural Neoplasms ,Humans ,Antineoplastic Agents ,Female - Abstract
Lung Cancer is the leading cause of cancer-related mortality worldwide, with nearly 1.4 million deaths each year. There has been an overall decrease in the incidence of lung cancer in men, although in women this trend has only been noted very recently in the United States and in many countries in Western Europe. In contrast, in many parts of the world the number of cases and deaths related to lung cancer is on the rise. These increased death rates are in close correlation to smoking habits in the different countries. It is also increasingly becoming a disease of the elderly, with a median age at diagnosis of 70 years. In Switzerland about 2'500 men and 1'200 women are yearly diagnosed with lung cancer. Lung cancer is diagnosed at an advanced stage in a majority of patients, which explains the high mortality rate associated with this disease. In the current review we give on overview on the current treatment practice for small cell lung cancer (SCLC) as well as on non-small cell lung cancer (NSCLC). The main focus is on the novel treatment options for advanced, metastatic NSCLC and the current use of predictive biomarkers in order to personalize therapy. Malignant pleural mesothelioma is a rare cancer occurring mainly in older men who have been exposed to asbestos, although it occurs decades after exposure (20 - 40 years later). The disease is difficult to treat and median overall survival is only about one year.
- Published
- 2012
33. Der ALK/MET-Inhibitor Crizotinib hemmt die Expression von ID1 (inhibitor of differentiation 1) und die Migration von Lungenkrebszellen
- Author
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SI Rothschild, MP Tschan, E Stutz, Matthias Gugger, O Gautschi, and MF Fey
- Subjects
Pulmonary and Respiratory Medicine - Published
- 2012
34. Neuer Synergismus zwischen Azacitidin und Dasatinib in der Behandlung von Lungenkarzinomzellen
- Author
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SI Rothschild, O Gautschi, Matthias Gugger, and MP Tschan
- Subjects
Pulmonary and Respiratory Medicine - Published
- 2012
35. Neue Therapiekonzepte beim Bronchuskarzinom
- Author
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O. Gautschi, M. Pless, C Betticher, Spasenija Savic, MT Henzi, A Zippelius, J. Diebold, Martin Brutsche, A Solermann, L Bubendorf, S Rothschild, I Letovanec, and Mathias Gugger
- Subjects
business.industry ,Medicine ,business - Published
- 2011
36. Targeted Therapy for Braf-Mutant Lung Cancer: Results from the European Euraf Cohort Study
- Author
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Egbert F. Smit, Martin Schuler, Julie Milia, Juergen Wolf, Solange Peters, J. Mazieres, G. Zalcman, Martin Früh, M.V. Bluthgen, and O. Gautschi
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,Mutant ,medicine ,Cancer ,Hematology ,Lung cancer ,medicine.disease ,business ,Cohort study - Published
- 2015
37. Successful treatment of chemotherapy-refractory Sézary syndrome with alemtuzumab (Campath-1H)
- Author
-
O, Gautschi, N, Blumenthal, M, Streit, M, Solenthaler, T, Hunziker, and R, Zenhäusern
- Subjects
Adult ,Male ,Skin Neoplasms ,Antibodies, Neoplasm ,Drug Resistance ,Antibodies, Monoclonal ,Antineoplastic Agents ,Neoplasms, Second Primary ,Antibodies, Monoclonal, Humanized ,Hodgkin Disease ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Sezary Syndrome ,Alemtuzumab - Abstract
Sézary syndrome (SS) is a cutaneous T-cell lymphoma characterized by erythroderma, lymphadenopathy and circulating atypical T cells. Median survival after diagnosis is 10 yr, with chemotherapy resistance being a major problem in advanced disease. Alemtuzumab (Campath-1H) is a monoclonal antibody directed against the lymphocytic antigen CD52, expressed on B- and T-cells. Alemtuzumab is approved for relapsing chronic B-cell leukemia and seems to be active also in T-cell lymphomas such as T-cell prolymphocytic lymphoma, SS and mycosis fungiodes.A 32-yr-old male patient presented with advanced stage, extensively pretreated SS with heavily itching erythroderma, peripheral lymphadenopathy, circulating Sézary cells and bone marrow infiltration. The disease had not responded to PUVA/interferon-alpha and progressed on chemotherapy with CHOP, 2-CDA, vinorelbine, etoposide and liposomal doxorubicin. Following treatment with alemtuzumab (30 mg i.v. three times per week for 10 wk), itching resolved rapidly and an almost complete remission was achieved within 3 months after starting this treatment. At 12-month follow up, no disease progression was present.In accordance with previous data, this single case underlines the potent activity of alemtuzumab in advanced, chemotherapy-refractory SS.
- Published
- 2004
38. Cardiac memory mimicking myocardial ischaemia
- Author
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O Gautschi and B Naegeli
- Subjects
Myocardial ischaemia ,medicine.medical_specialty ,Myocardial ischemia ,Cardiac pacing ,Myocardial Ischemia ,Case Reports ,Sick sinus syndrome ,Diagnosis, Differential ,03 medical and health sciences ,Electrocardiography ,0302 clinical medicine ,Heart Conduction System ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,skin and connective tissue diseases ,Aged ,Aged, 80 and over ,Sick Sinus Syndrome ,medicine.diagnostic_test ,business.industry ,Memoria ,Cardiac Pacing, Artificial ,General Medicine ,Ventricular pacing ,medicine.disease ,030227 psychiatry ,cardiovascular system ,Cardiology ,Female ,sense organs ,Electrical conduction system of the heart ,business - Abstract
Cardiac memory describes the phenomenon whereby the T-wave abnormalities that result from a change in the direction of cardiac activation, as during ventricular pacing, persist for a while after the end of pacing.
- Published
- 2003
39. Acute respiratory failure and cerebral hemorrhage due to primary Epstein-Barr virus infection
- Author
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O. Gautschi, J. Gubler, I. Laube, and C. Berger
- Subjects
Pulmonary and Respiratory Medicine ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Mononucleosis ,Adolescent ,viruses ,Pneumonia, Viral ,medicine.disease_cause ,Virus ,Herpesviridae ,hemic and lymphatic diseases ,medicine ,Gammaherpesvirinae ,Humans ,Epstein–Barr virus infection ,Cerebral Hemorrhage ,biology ,business.industry ,Brain ,medicine.disease ,biology.organism_classification ,Epstein–Barr virus ,Virology ,Respiratory failure ,Immunology ,Acute Disease ,DNA, Viral ,Female ,Radiography, Thoracic ,Viral disease ,business ,Respiratory Insufficiency ,Tomography, X-Ray Computed - Abstract
Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus with worldwide distribution. Primary infection with EBV occurs early in life and typically presents as infectious mononucleosis. The usual course of the disease is benign and most patients recover uneventfully. Severe infections are reported particularly in immunocompromised patients. Mild, asymptomatic pneumonitis is reported in about 5–10% of cases of infectious mononucleosis, but severe pneumonitis with hypoxemia is very rare in immunocompetent individuals. We report a young female adolescent in whom an acute EBV infection led to severe bilateral pneumonitis, a systemic inflammatory response and intracerebral bleeding. The clinical course and results of quantitative viral DNA determinations in plasma are presented.
- Published
- 2002
40. Prospective Evaluation of Circulating Vegf in Patients with Advanced Non-Small Cell Lung Cancer Treated with Bevacizumab, Pemetrexed and Cisplatin in the Trial Sakk19/09
- Author
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E. Oppliger Leibundgut, Solange Peters, M. Frueh, Alfred Zippelius, Sacha I. Rothschild, N. Mach, B. Huegli, L. Stalder, O. Gautschi, Richard Cathomas, Qiyu Li, and Adrian F. Ochsenbein
- Subjects
Oncology ,medicine.medical_specialty ,Bevacizumab ,business.industry ,Phases of clinical research ,Hematology ,medicine.disease ,Chemotherapy regimen ,Carboplatin ,Surgery ,Vascular endothelial growth factor ,chemistry.chemical_compound ,Pemetrexed ,chemistry ,Maintenance therapy ,Internal medicine ,medicine ,Lung cancer ,business ,medicine.drug - Abstract
Aim: Bevacizumab is a monoclonal antibody directed against the vascular endothelial growth factor (VEGF). The previous phase II trial ABIGAIL (Reck, 2010) suggested circulating VEGF as a prognostic, but not predictive, biomarker for patients (pts) with non-small cell lung cancer (NSCLC) treated with bevacizumab. We prospectively measured VEGF in the multicenter phase II trial SAKK19/09 (NCT01116219). Methods: SAKK19/09 enrolled 77 evaluable patients (pts) with previously untreated, advanced nonsquamous NSCLC and EGFR wild type. Pts received 4 cycles of cisplatin 75mg/m2 (or carboplatin AUC5), pemetrexed 500mg/m2 and bevacizumab 7.5mg/kg, followed by maintenance therapy with pemetrexed and bevacizumab until progression by RECIST1.1. Follow-up CT scans were performed every 6 weeks until week 54 and every 12 weeks thereafter. Baseline EDTA blood samples were sent by same-day courier to the central laboratory for centrifugation, aliquoting, and freezing. Upon completion of enrollment, aliquots were thawed, and VEGF quantification was performed centrally using Luminex® Performance Assay Human Base Kit A (RD 95%CI: 1.43- 4.57; p = 0.0015) and OS (8.7 vs 17.5 months, HR = 2.67; 95%CI: 1.37-5.20; p = 0.0041), but not with best response rate (p = 0.2256). Conclusions: Consistent with the ABIGAIL trial, circulating VEGF was prognostic, but not predictive for response, in the current trial. Further work is ongoing to identify potentially predictive biomarkers for bevacizumab, using comprehensive proteomic analyses. Disclosure: S.I. Rothschild: I received honoraria for the participation in advisory boards from Eli Lilly and Roche and for presentations at scientific symposiums sponsored by Roche; O. Gautschi: Honoraria for advisory boards of Eli Lilly and Roche; R. Cathomas: Advisory board member: Eli Lilly. All other authors have declared no conflicts of interest.
- Published
- 2014
41. Final Results of the Sakk 16/00 Trial: a Randomized Phase III Trial Comparing Neoadjuvant Chemoradiation to Chemotherapy Alone in Stage Iiia/N2 Non-Small Cell Lung Cancer (Nsclc)
- Author
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Dieter Rauch, A. Xyrafas, Alfred Zippelius, Sandra Thierstein, Rolf A. Stahel, Solange Peters, O. Gautschi, M. Gerard, Martin Früh, Christoph Mamot, Miklos Pless, Richard Cathomas, Daniel C. Betticher, Urs R. Meier, A. Roth, Roger Stupp, Walter Weder, Hans-Beat Ris, Adrian F. Ochsenbein, and R.O. Mirimanoff
- Subjects
medicine.medical_specialty ,Performance status ,business.industry ,medicine.medical_treatment ,non-small cell lung cancer (NSCLC) ,Hematology ,medicine.disease ,Chemotherapy regimen ,Surgery ,Regimen ,Oncology ,Docetaxel ,Medicine ,business ,Survival rate ,Febrile neutropenia ,Neoadjuvant therapy ,medicine.drug - Abstract
Aim: One standard option in the treatment of stage IIIA/N2 NSCLC is neoadjuvant chemotherapy followed by surgery. We investigated in a randomized trial whether the addition of neoadjuvant radiotherapy would improve the outcome. Here we present the final results of this study. Methods: Patients (pts.) with pathologically proven, resectable stage IIIA/N2 NSCLC, performance status 0-1, and adequate organ function were randomized 1:1 to chemoradiation (CRT) with 3 cycles of neoadjuvant chemotherapy (cisplatin 100 mg/m2 and docetaxel 85 mg/m2 d1, q3weeks) followed by accelerated concomitant boost radiotherapy (RT) with 44 Gy in 22 fractions in 3 weeks, or neoadjuvant chemotherapy alone (CT), with subsequent surgery for all pts. The primary endpoint was event-free survival (EFS). Results: 232 pts. were randomized in 23 centers, the median follow-up was 53 months. Two thirds were men, median age was 60 years (range 37-76). Histology was squamous cell in 33%, adenocarcinoma in 43%. Response rate to CRT was 61% vs. 44% with CT. 85% of all pts. underwent surgery, 30-day postoperative mortality was 1%. The rate of complete resection was 91% (CRT) vs. 81% (CT) and the pathological complete remission (pCR) rate was 16% vs. 12%. The median EFS was 13.1 months (95% CI 9.9 - 23.5) for the CRT group vs. 11.8 months (95% CI 8.4 – 15.2) in the CT arm (p 0.665). The median overall survival (OS) with CRT was 37.1 months (95% CI 22.6 -50), with CT 26.1 months ( 95% CI 26.1 – 52.1, p 0.938). The local failure rate was 23% in both arms. In the CT arm 12 pts. were given postoperative radiotherapy (PORT) for R1 resection, 6 pts. received PORT in violation of the protocol. Pts. with a pCR, mediastinal downstaging to ypN0/1 and complete resection had a better outcome. Toxicity of chemotherapy was substantial, especially febrile neutropenia was common, whereas RT was well tolerated. Conclusions: This is the first completed phase III trial to evaluate the role of induction chemoradiotherapy and surgery, in comparison to neoadjuvant CT alone followed by surgery. RT was active, it increased response, complete resection and pCR rates. However, this failed to translate into an improvement of local control, EFS or OS. Notably, surgery after induction treatment was safe, including pneumonectomy. The overall survival rates of our neoadjuvant regimen are very encouraging, especially for a multicenter setting. Disclosure: M. Pless: Advisory Board for Sanofi; R. Cathomas: Advisory Board Sanofi D.C. Betticher: Advisory Board Sanofi. All other authors have declared no conflicts of interest.
- Published
- 2014
42. Neoadjuvant Chemotherapy and Extrapleural Pneumonectomy (Epp) of Malignant Pleural Mesothelioma (Mpm) with or Without Hemithoracic Radiotherapy: Final Results of the Randomized Multicenter Phase Ii Trial Sakk17/04
- Author
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Christoph Mamot, C Mordasini, Walter Weder, X Alexandros, Ralph A. Schmid, K Clemens, W Nagel, O. Gautschi, Richard Cathomas, Martin Früh, Daniel M. Aebersold, Adrian F. Ochsenbein, K. Eckhardt, Alfred Zippelius, Solange Peters, Kristiaan Nackaerts, Michael Beyeler, Isabelle Opitz, Rolf A. Stahel, and Oliver Riesterer
- Subjects
medicine.medical_specialty ,Surrogate endpoint ,business.industry ,medicine.medical_treatment ,Phases of clinical research ,Hematology ,Chemotherapy regimen ,Surgery ,Radiation therapy ,Pemetrexed ,Oncology ,Tolerability ,Multicenter trial ,medicine ,Clinical endpoint ,business ,medicine.drug - Abstract
Aim: We have previously documented the feasibility of neoadjuvant chemotherapy and EPP in a multicenter trial of MPM (Weder, Ann Oncol 18: 1196, 2007). The objectives of the trimodality trial SAKK17/04 (NCT00334594) were to evaluate the time to loco-regional relapse with or without high dose hemithoracic radiotherapy in a prospective multicenter randomized phase II trial in patients with R0 and R1 resection after neoadjuvant chemotherapy and EPP. Methods: Eligible patients had pathologically confirmed MPM, surgically resectable TNM stage (T1-3 N0-2 M0), PS0-1, ages 18-70 years. Part 1 had a phase II design, and included neoadjuvant chemotherapy with 3 cycles of cisplatin and pemetrexed, followed by restaging and EPP. The primary endpoint of part 1 was complete macroscopic resection (R0-1). Part 2 randomized consenting patients with R0-1 resection into two parallel phase II arms (control arm A and radiotherapy arm B). The primary endpoint for part 2 was loco-regional relapse-free survival (RFS). To detect a 1 year increase with 80% power and 10% alpha, 37 patients were needed for arm B. Secondary endpoints included operability, tolerability of chemotherapy and radiotherapy, survival, and translational research Results: Because accrual of part 2 was slower than planned, the trial was stopped in 2013. Overall, 153 patients entered the trial, of whom 125 underwent surgery and 99 had a complete macroscopic resection (primary endpoint part 1). Of the later patients, 54 could be randomized 1:1 into each arm. Reasons for non-randomization included patient refusal in 24 and ineligibility or protocol deviations in 21. Of the 27 patients randomized to hemithoracic radiotherapy, 25 completed the treatment as planned. For part 1 the median RFS was 8.8 (95%CI: 7.3–10.7) and median OS was 15.0 (95% CI: 12.1–19.3) months. For part 2 the median local RFS for group A was 7.6 (95%CI: 5.5–10.7) and for group B 9.4 (95%CI: 6.5-11.9) months (primary endpoint part 2), while the overall RFS and OS for group A were 5.7 (95%CI: 3.5-8.8) and 16.9 (95%CI: 10.7-23.6) months and for group B 7.6 (95% CI:5.2-10.6) and 14.9 (95%CI: 7.0–17.6) months. Conclusions: This study did not reach the primary endpoint which was defined as one-year increase in loco-regional relapse-free survival and thus does not support the routine use of hemithoracic RT after neoadjuvant chemotherapy and EPP. Disclosure: All authors have declared no conflicts of interest.
- Published
- 2014
43. Persistent polyclonal B-cell lymphocytosis is an expansion of functional IgD(+)CD27(+) memory B cells
- Author
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A, Himmelmann, O, Gautschi, M, Nawrath, U, Bolliger, J, Fehr, and R A, Stahel
- Subjects
Adult ,Chromosomes, Human, Pair 14 ,Male ,B-Lymphocytes ,Staphylococcus aureus ,Immunoblotting ,bcl-X Protein ,Apoptosis ,Immunoglobulin D ,Lymphocytosis ,Middle Aged ,Polymerase Chain Reaction ,Translocation, Genetic ,Clone Cells ,Tumor Necrosis Factor Receptor Superfamily, Member 7 ,Immunoglobulin M ,Proto-Oncogene Proteins c-bcl-2 ,Case-Control Studies ,Proto-Oncogene Proteins ,Humans ,Interleukin-2 ,Female ,Chromosomes, Human, Pair 18 ,Immunologic Memory ,bcl-2-Associated X Protein - Abstract
Persistent polyclonal B-cell lymphocytosis (PPBL) is a rare disorder of unknown aetiology affecting predominantly young to middle-aged women. It is characterized by a polyclonal expansion of B cells, including typical binucleated lymphocytes, and is associated with the presence of the translocation t(14;18), involving the bcl-2 oncogene. The stage of differentiation of the B cells expanded in PPBL is not known. We analysed the immunophenotype of the expanded B-cell subset in five new patients with PPBL and found a large uniform expansion of a recently defined human memory B-cell population, IgD(+)CD27(+) memory B cells. After in vitro stimulation with interleukin 2 (IL-2) and Staphylococcus aureus Cowan strain I, B cells from PPBL patients produced high levels of IgM immunoglobulins, which is a characteristic feature of IgD(+)CD27(+) memory B cells. Using a quantitative real-time polymerase chain reaction method, we found a high frequency of the translocation t(14;18) in the range of 1000-3000 per 106 B cells in PPBL patients. In contrast, a much smaller number of cells with a t(14;18) was found in B cells from healthy individuals. Our finding that PPBL is an accumulation of memory B cells further suggests that chronic antigeneic stimulation plays an important part in the pathogenesis of this disorder. This IgD(+)CD27(+) memory B-cell population might harbour a certain number of 'physiological' t(14;18) translocations that increases as this population expands in PPBL patients and constitutes the majority of peripheral blood lymphocytes.
- Published
- 2001
44. Bcl-xl antisense treatment induces apoptosis in breast carcinoma cells
- Author
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A P, Simões-Wüst, R A, Olie, O, Gautschi, S H, Leech, R, Häner, J, Hall, D, Fabbro, R A, Stahel, and U, Zangemeister-Wittke
- Subjects
Neoplasms, Hormone-Dependent ,Cell Death ,Cell Survival ,bcl-X Protein ,Down-Regulation ,Apoptosis ,Breast Neoplasms ,Estrogens ,Oligonucleotides, Antisense ,Proto-Oncogene Proteins c-bcl-2 ,Tumor Cells, Cultured ,Humans ,RNA, Messenger ,Cell Division ,Signal Transduction - Abstract
Upregulated expression of bcl-xL is involved in the initiation and progression of breast cancer by inhibiting tumor cell apoptosis. Here we describe the use of the 2;-O-methoxy-ethoxy antisense oligonucleotide 4259 targeting nucleotides 687-706 of the bcl-xL mRNA, a sequence that does not occur in the pro-apoptotic bcl-xS transcript, to restore apoptosis in estrogen-dependent and independent breast carcinoma cells. The antisense effect of oligonucleotide 4259 was examined on the mRNA and protein level using real-time PCR and Western blot analysis, respectively, and the induction of cell death was investigated in viability and apoptosis assays. Treatment of MCF7 cells with oligonucleotide 4259 at a concentration of 600 nM for 20 hr decreased bcl-xL mRNA and protein levels by more than 80% and 50%, respectively. This resulted in the induction of apoptosis characterized by mitochondrial cytochrome c release, decrease of mitochondrial transmembrane potential, and the appearance of condensed nuclei in approximately 40% of cells. Moreover, oligonucleotide 4259 efficiently downregulated bcl-xL expression and decreased cell growth in the breast carcinoma cell lines T-47D, ZR-75-1, and MDA-MB-231. Our data emphasize the importance of bcl-xL as a survival factor for breast carcinoma cells and suggest that oligonucleotide 4259 deserves further investigations for use in breast cancer therapy.
- Published
- 2000
45. A novel bispecific antisense oligonucleotide inhibiting both bcl-2 and bcl-xL expression efficiently induces apoptosis in tumor cells
- Author
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U, Zangemeister-Wittke, S H, Leech, R A, Olie, A P, Simões-Wüst, O, Gautschi, G H, Luedke, F, Natt, R, Häner, P, Martin, J, Hall, C M, Nalin, and R A, Stahel
- Subjects
Cell Nucleus ,Lung Neoplasms ,Time Factors ,Dose-Response Relationship, Drug ,Caspase 3 ,Blotting, Western ,bcl-X Protein ,Down-Regulation ,Apoptosis ,DNA Fragmentation ,Oligonucleotides, Antisense ,Polymerase Chain Reaction ,Genes, bcl-2 ,Proto-Oncogene Proteins c-bcl-2 ,Carcinoma, Non-Small-Cell Lung ,Caspases ,Tumor Cells, Cultured ,Humans ,RNA, Messenger ,Carcinoma, Small Cell ,Propidium - Abstract
Bcl-2 and Bcl-xL are inhibitors of apoptosis frequently overexpressed in solid tumors. The bcl-2 and bcl-xL mRNAs share a region of homology comprising nucleotides 605-624 and 687-706, respectively, which differs by only three nucleotides. This sequence does not occur in the proapoptotic splice variant bcl-xS. To test the possibility that oligonucleotides targeting this region have the potential to down-regulate bcl-2 and bcl-xL expression simultaneously, three 2'-O-methoxy-ethoxy-modified phosphorothioate oligonucleotides were designed. These oligonucleotides differed in the number of mismatches to bcl-2 and bcl-xL and in the number of nucleotides to which the modifications were made. The effects of these oligonucleotides on bcl-2 and bcl-xL expression, as well as their abilities to induce apoptosis, were assessed in small cell and non-small cell lung cancer cell lines expressing different basal levels of bcl-2 and bcl-xL. Although all oligonucleotides down-regulated bcl-2 and bcl-xL expression, oligonucleotide 4625, which has no mismatching nucleotides to bcl-2 but three to bcl-xL, two of which were modified by 2'-O-methoxy-ethoxy residues, showed the strongest bispecific activity on the transcript and protein level. In all cell lines this bispecific activity induced apoptotic cell death, as demonstrated by increased uptake of propidium iodide, a 10-100-fold increase in caspase-3-like protease activity, and nuclear condensation and fragmentation. This is the first report of a bcl-2/bcl-xL bispecific antisense oligonucleotide that deserves attention as a therapeutic compound in lung cancer and other malignancies in which bcl-2 and/or bcl-xL are overexpressed.
- Published
- 2000
46. Induction of apoptosis in lung-cancer cells following bcl-xL anti-sense treatment
- Author
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S H, Leech, R A, Olie, O, Gautschi, A P, Simões-Wüst, S, Tschopp, R, Häner, J, Hall, R A, Stahel, and U, Zangemeister-Wittke
- Subjects
Lung Neoplasms ,Proto-Oncogene Proteins c-bcl-2 ,Caspase 3 ,Caspases ,Tumor Cells, Cultured ,bcl-X Protein ,Humans ,Apoptosis ,Carcinoma, Small Cell ,Oligonucleotides, Antisense - Abstract
Over-expression of the anti-apoptotic protein bcl-xL is frequently found in lung cancer where it potentially contributes to tumor development, progression and drug resistance. To override the apoptotic block in lung-adenocarcinoma and small-cell-lung-cancer (SCLC) cells caused by over-expression of bcl-xL, an anti-sense oligodeoxynucleotide was designed targeting a sequence unique to the bcl-xL coding region and not shared by the pro-apoptotic splice variant bcl-xS. Moreover, to improve the biophysical properties of the anti-sense compound, 2;-methoxy-ethoxy modifications were made to selected deoxy-ribose residues. The resulting gapmer oligonucleotide 4259 was tested on lung-adenocarcinoma and SCLC cell lines in vitro. Treatment of the adenocarcinoma cell lines A549 and NCI-H125 and the SCLC cell lines SW2 and NCI-H69 with 600 nM 4259 reduced bcl-xL levels by 70 to 90%. In the lung-adenocarcinoma cell lines, apoptosis was induced, as indicated by caspase-3-like protease activation and nuclear condensation and fragmentation. In contrast, in the SCLC cell lines, no induction of apoptosis could be demonstrated. These findings imply that bcl-xL is a more critical survival factor for lung adenocarcinomas than for SCLC, and suggest the use of oligonucleotide 4259 for therapy of this major sub-type of lung cancer.
- Published
- 2000
47. P-484 CCND1/Cyclin D1 A870G gene polymorphism is associated with non-small cell lung cancer (NSCLC) risk, and affects prognosis and response to chemotherapy
- Author
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J. Heighway, Naomi L. Bowers, Daniel Ratschiller, Annemarie Ziegler, O. Gautschi, Colette Bigosch, B. Huegli, Rolf A. Stahel, and Daniel C. Betticher
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Chemotherapy ,business.industry ,medicine.medical_treatment ,non-small cell lung cancer (NSCLC) ,medicine.disease ,Cyclin D1 ,Internal medicine ,Cancer research ,Medicine ,Gene polymorphism ,business - Published
- 2005
48. 25PD CIRCULATING MICRO-RNA PROFILING IN PATIENTS WITH ADVANCED NON-SQUAMOUS NON SMALL-CELL LUNG CANCER RECEIVING BEVACIZUMAB/ERLOTINIB FIRST-LINE TREATMENT FOLLOWED BY PLATINUM-BASED CHEMOTHERAPY AT DISEASE PROGRESSION (SAKK 19/05)
- Author
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Peter Brauchli, O. Gautschi, Daniel C. Betticher, M. Pless, Florent Baty, R. von Moos, Rolf A. Stahel, Markus Joerger, Martin Brutsche, and Francesco Zappa
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Chemotherapy ,business.industry ,medicine.medical_treatment ,Disease progression ,medicine.disease ,First line treatment ,Non squamous ,Internal medicine ,Bevacizumab/Erlotinib ,microRNA ,medicine ,In patient ,business ,Lung cancer - Published
- 2013
49. Is there a Role for Targeted Agents or Biologicals in Stage I–III NSCLC?
- Author
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O. Gautschi
- Subjects
Oncology ,medicine.medical_specialty ,Cetuximab ,business.industry ,Afatinib ,Hematology ,medicine.disease_cause ,respiratory tract diseases ,Clinical trial ,Gefitinib ,Internal medicine ,medicine ,KRAS ,Erlotinib ,Progression-free survival ,business ,neoplasms ,medicine.drug ,EGFR inhibitors - Abstract
More than half of the patients with non-small cell lung cancer (NSCLC), including different tumor stages and histology subtypes, have actionable driver mutations. In patients with advanced NSCLC and activating EGFR mutations, randomized phase III trials with EGFR inhibitors (gefitinib, erlotinib and afatinib) demonstrated superior response rates and progression free survival compared with chemotherapy. Phase II trials showed high response rates for crizotinib in advanced NSCLC with ALK-translocation and the results of two randomized phase III trials are awaited. Preliminary data from phase I-II trials and retrospective series suggest further targets for tumor-specific therapies, including MET, ROS1, HER2, BRAF, KRAS, PI3K and others. Moreover, bevacizumab and cetuximab have shown clinical activity in phase III trials in combination with chemotherapy in patients with advanced NSCLC selected by histology and EGFR expression, respectively. Rapid molecular testing is now available at many institutions, and the translation of these novel therapies from stage IV to earlier stages has begun. Caution is warranted, because cure – not tumor response – is the ultimate goal of therapy, and the use of new drugs outside of a clinical trial in patients with stage I-III NSCLC may be risky. Of note, S0023 and BR.19 showed no benefit with the addition of gefitinib to a radical treatment in patients with localized NSCLC, irrespective of EGFR mutation status. Furthermore, phase III trials suggested a possible antagonism when EGFR-TKIs were combined with chemotherapy in patients with stage IV NSCLC. More recent studies indicate that such negative interaction may be avoided by pharmacodynamic separation (or "intercalation"), and that EGFR-TKIs as single agents could be used safely and effectively as induction therapy before surgery in carefully selected patients with stage I-III NSCLC. At the meeting, these data will be reviewed, and ongoing trials in this field will be discussed, including RADIANT (erlotinib), ADJUVANT (gefitinib), and ECOG 1505 (bevacizumab). Clinical cases will be presented to highlight problems and pitfalls of treating patients outside of controlled trials, and new avenues for clinical and translational research will be elucidated. Disclosure The author has declared no conflicts of interest.
- Published
- 2012
50. Neoadjuvant chemoradiation (CRT) with or without panitumumab (Pan) in patients with K-ras-unmutated, locally advanced rectal cancer (LARC): A randomized multicenter phase II trial (SAKK 41/07)
- Author
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György Bodoky, Dieter Rauch, Pu Yan, Piercarlo Saletti, Axel Madlung, D. Koeberle, R. Burkhard, Markus Borner, O. Gautschi, Beat Gloor, Daniela Baertschi, F. Bosman, H. Sun, Ralph Winterhalder, D. Helbling, and Lucas Widmer
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Cetuximab ,biology ,Colorectal cancer ,business.industry ,medicine.disease ,Surgery ,Capecitabine ,Tumor Status ,Internal medicine ,medicine ,Clinical endpoint ,biology.protein ,Panitumumab ,Epidermal growth factor receptor ,business ,Grading (tumors) ,medicine.drug - Abstract
3546 Background: Disappointingly low rates of pathologic complete remission (pCR) have been noted in several phase II studies in patients (pts) with LARC and unselected K-ras tumor status when combining CRT with the epidermal growth factor receptor (EGFR) inhibitor cetuximab. Pan is a fully human monoclonal antibody binding to the EGFR. Methods: Patients with centrally tested K-ras unmutated, mrT3-4 and/or mrN+ disease, without distant metastases were recruited in 19 centers. Treatment consisted of CRT (1.8 Gy for 25 days) with capecitabine (825mg/m2 bid day1-35) in the standard arm (arm B). Pan (6mg/m2) was added on days -7, 7, 21, 35, 49 in arm A. Surgical resection was performed on day 77 (+/- 7 days). All pts received preemptive treatment including doxycyline and skin care. Primary endpoint was pathological complete tumour response (pCR) prospectively defined as grade 3 (near complete regression) or 4 (complete regression) in the histological grading of regression according to Dworak classification (D...
- Published
- 2011
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