Wilfried Ernst Erich Eberhardt1, Christoph Pöttgen2, Thomas Christoph Gauler2, Godehard Friedel2, Stefanie Veit2, Vanessa Heinrich2, Stefan Welter2, Wilfried Budach2, Werner Spengler2, Martin Kimmich2, Berthold Fischer2, Heinz Schmidberger2, Dirk De Ruysscher2, Claus Belka2, Sebastian Cordes2, Rodrigo Hepp2, Diana Lütke-Brintrup2, Nils Lehmann2, Martin Schuler2, Karl-Heinz Jöckel2, Georgios Stamatis2, Martin Stuschke2. 1. Wilfried Ernst Erich Eberhardt, Christoph Pöttgen, Thomas Christoph Gauler, Sebastian Cordes, Rodrigo Hepp, Diana Lütke-Brintrup, Nils Lehmann, Martin Schuler, Karl-Heinz Jöckel, and Martin Stuschke, West German Cancer Center, University Hospital Essen, Essen; Stefan Welter and Georgios Stamatis, Ruhrlandklinik, Essen-Heidhausen; Godehard Friedel, Stefanie Veit, and Martin Kimmich, Robert-Bosch-Krankenhaus Klinik Schillerhöhe, Gerlingen; Vanessa Heinrich, Wilfried Budach, and Werner Spengler, Universitätsklinikum Tübingen, Tübingen; Berthold Fischer and Heinz Schmidberger, Universitätsmedizin der Johannes-Gutenberg-Universität Mainz, Mainz; Claus Belka, Klinikum der Universität München, München, Germany; and Dirk De Ruysscher, Maastro Clinic, Maastricht, the Netherlands. wilfried.eberhardt@uni-duisburg-essen.de. 2. Wilfried Ernst Erich Eberhardt, Christoph Pöttgen, Thomas Christoph Gauler, Sebastian Cordes, Rodrigo Hepp, Diana Lütke-Brintrup, Nils Lehmann, Martin Schuler, Karl-Heinz Jöckel, and Martin Stuschke, West German Cancer Center, University Hospital Essen, Essen; Stefan Welter and Georgios Stamatis, Ruhrlandklinik, Essen-Heidhausen; Godehard Friedel, Stefanie Veit, and Martin Kimmich, Robert-Bosch-Krankenhaus Klinik Schillerhöhe, Gerlingen; Vanessa Heinrich, Wilfried Budach, and Werner Spengler, Universitätsklinikum Tübingen, Tübingen; Berthold Fischer and Heinz Schmidberger, Universitätsmedizin der Johannes-Gutenberg-Universität Mainz, Mainz; Claus Belka, Klinikum der Universität München, München, Germany; and Dirk De Ruysscher, Maastro Clinic, Maastricht, the Netherlands.
Abstract
PURPOSE:Concurrent chemoradiotherapy with or without surgery are options for stage IIIA(N2) non-small-cell lung cancer. Our previous phase II study had shown the efficacy of induction chemotherapy followed by chemoradiotherapy and surgery in patients with IIIA(N2) disease and with selected IIIB disease. Here, we compared surgery with definitive chemoradiotherapy in resectable stage III disease after induction. PATIENTS AND METHODS: Patients with pathologically proven IIIA(N2) and selected patients with IIIB disease that had medical/functional operability receivedinduction chemotherapy, which consisted of three cycles of cisplatin 50 mg/m(2) on days 1 and 8 and paclitaxel 175 mg/m(2) on day 1 every 21 days, as well as concurrent chemoradiotherapy to 45 Gy given as 1.5 Gy twice daily, concurrent cisplatin 50 mg/m(2) on days 2 and 9, and concurrent vinorelbine 20 mg/m(2) on days 2 and 9. Those patients whose tumors were reevaluated and deemed resectable in the last week ofradiotherapy were randomly assigned to receive a chemoradiotherapy boost that was risk adapted to between 65 and 71 Gy in arm A or to undergo surgery (arm B). The primary end point was overall survival (OS). RESULTS:After 246 of 500 planned patients were enrolled, the trial was closed after the second scheduled interim analysis because of slow accrual and the end of funding, which left the study underpowered relative to its primary study end point. Seventy-five patients had stage IIIA disease and 171 had stage IIIB disease according to the Union for International Cancer Control TNM classification, sixth edition. The median age was 59 years (range, 33 to 74 years). After induction, 161 (65.4%) of 246 patients with resectable tumors were randomly assigned; strata were tumor-node group, prophylactic cranial irradiation policy, and region. Patient characteristics were balanced between arms, in which 81 were assigned to surgery and 80 were assigned to a chemoradiotherapy boost. In arm B, 81% underwent R0 resection. With a median follow-up after random assignment of 78 months, 5-year OS and progression-free survival (PFS) did not differ between arms. Results were OS rates of 44% for arm B and 40% for arm A (log-rank P = .34) and PFS rates of 32% for arm B and 35% for arm A (log-rank P = .75). OS at 5 years was 34.1% (95% CI, 27.6% to 40.8%) in all 246 patients, and 216 patients (87.8%) receiveddefinitive local treatment. CONCLUSION: The 5-year OS and PFS rates in randomly assigned patients with resectable stage III non-small-cell lung cancer were excellent with both treatments. Both are acceptable strategies for this good-prognosis group.
RCT Entities:
PURPOSE: Concurrent chemoradiotherapy with or without surgery are options for stage IIIA(N2) non-small-cell lung cancer. Our previous phase II study had shown the efficacy of induction chemotherapy followed by chemoradiotherapy and surgery in patients with IIIA(N2) disease and with selected IIIB disease. Here, we compared surgery with definitive chemoradiotherapy in resectable stage III disease after induction. PATIENTS AND METHODS: Patients with pathologically proven IIIA(N2) and selected patients with IIIB disease that had medical/functional operability received induction chemotherapy, which consisted of three cycles of cisplatin 50 mg/m(2) on days 1 and 8 and paclitaxel 175 mg/m(2) on day 1 every 21 days, as well as concurrent chemoradiotherapy to 45 Gy given as 1.5 Gy twice daily, concurrent cisplatin 50 mg/m(2) on days 2 and 9, and concurrent vinorelbine 20 mg/m(2) on days 2 and 9. Those patients whose tumors were reevaluated and deemed resectable in the last week of radiotherapy were randomly assigned to receive a chemoradiotherapy boost that was risk adapted to between 65 and 71 Gy in arm A or to undergo surgery (arm B). The primary end point was overall survival (OS). RESULTS: After 246 of 500 planned patients were enrolled, the trial was closed after the second scheduled interim analysis because of slow accrual and the end of funding, which left the study underpowered relative to its primary study end point. Seventy-five patients had stage IIIA disease and 171 had stage IIIB disease according to the Union for International Cancer Control TNM classification, sixth edition. The median age was 59 years (range, 33 to 74 years). After induction, 161 (65.4%) of 246 patients with resectable tumors were randomly assigned; strata were tumor-node group, prophylactic cranial irradiation policy, and region. Patient characteristics were balanced between arms, in which 81 were assigned to surgery and 80 were assigned to a chemoradiotherapy boost. In arm B, 81% underwent R0 resection. With a median follow-up after random assignment of 78 months, 5-year OS and progression-free survival (PFS) did not differ between arms. Results were OS rates of 44% for arm B and 40% for arm A (log-rank P = .34) and PFS rates of 32% for arm B and 35% for arm A (log-rank P = .75). OS at 5 years was 34.1% (95% CI, 27.6% to 40.8%) in all 246 patients, and 216 patients (87.8%) received definitive local treatment. CONCLUSION: The 5-year OS and PFS rates in randomly assigned patients with resectable stage III non-small-cell lung cancer were excellent with both treatments. Both are acceptable strategies for this good-prognosis group.
Authors: A Swaminath; E T Vella; K Ramchandar; A Robinson; C Simone; A Sun; Y C Ung; K Yasufuku; P M Ellis Journal: Curr Oncol Date: 2019-06-01 Impact factor: 3.677
Authors: Maja Guberina; Wilfried Eberhardt; Martin Stuschke; Thomas Gauler; Clemens Aigner; Martin Schuler; Georgios Stamatis; Dirk Theegarten; Walter Jentzen; Ken Herrmann; Christoph Pöttgen Journal: Eur J Nucl Med Mol Imaging Date: 2019-02-01 Impact factor: 9.236
Authors: Sarah A Wieczorek; Frank Breitenbuecher; Aashish Soni; Katja Paul-Konietzko; Sophie Ziegler; Ali Sak; George Iliakis; Martin Schuler Journal: J Cancer Res Clin Oncol Date: 2017-04-21 Impact factor: 4.553