D P Modest1, T Denecke2, J Pratschke3, I Ricard4, H Lang5, M Bemelmans6, T Becker7, M Rentsch8, D Seehofer9, C J Bruns10, B Gebauer2, H I Modest11, S Held12, G Folprecht13, V Heinemann14, U P Neumann15. 1. Department of Medicine III, Hospital of the University of Munich (LMU), Munich, Germany; German Cancer Consortium (DKTK), German Cancer Research Centre (DKFZ), Heidelberg, Germany. Electronic address: dominik.modest@med.uni-muenchen.de. 2. Institute of Radiology, Charité, Berlin, Germany. 3. General, Visceral, and Transplantation Surgery, Charité - Universitätsmedizin Berlin, Berlin, Germany. 4. Institute of Medical Informatics, Biometry and Epidemiology, University of Munich (LMU), Munich, Germany. 5. Department of General, Abdominal and Transplantation Surgery, University Medical Center, Mainz, Germany. 6. Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands. 7. Department of General and Thoracic Surgery, University Hospital Schleswig-Holstein, Kiel, Germany. 8. Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the University of Munich, Munich, Germany. 9. Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital Leipzig, Leipzig, Germany. 10. Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany. 11. German Aerospace Centre, Oberpfaffenhofen, Germany. 12. ClinAssess GmbH, Leverkusen, Germany. 13. University Cancer Center/Medical Department I, University Hospital Carl Gustav Carus, Dresden, Germany. 14. Department of Medicine III, Hospital of the University of Munich (LMU), Munich, Germany; German Cancer Consortium (DKTK), German Cancer Research Centre (DKFZ), Heidelberg, Germany. 15. Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands; Department of General, Visceral and Transplantation Surgery, University Hospital Aachen, Aachen, Germany.
Abstract
BACKGROUND: The FIRE-3 trial investigated combination chemotherapy plus either cetuximab or bevacizumab in patients with untreated metastatic colorectal cancer (mCRC) not scheduled for upfront surgery. We aimed to determine the number of patients who present with potentially resectable disease during systemic first-line therapy and to compare the findings with study reports concerning resections and outcome. PATIENTS AND METHODS: This evaluation of 448 patients was performed as central review blinded for treatment, other reviewers' evaluations and conducted interventions. Resectability was defined if at least 50% of the reviewers recommended surgical-based intervention. Overall survival was assessed by Kaplan-Meier method. RESULTS:Resectability increased from 22% (97/448) at baseline before treatment to 53% (238/448) at best response (P < 0.001), compared with an actual secondary resection rate for metastases of 16% (72/448). At baseline (23% versus 20%) and best response (53% versus 53%), potential resectability of metastases in this molecular unselected population was similar in cetuximab-treated patients versus bevacizumab-treated patients and not limited to patients with one-organ disease. The actual resection rate of metastases was significantly associated with treatment setting (P = 0.02; university hospital versus hospital/practice). Overall survival was 51.3 months (95% confidence interval [CI] 35.9-66.7) in patients with resectable disease who received surgery, 30.8 months (95% CI 26.6-34.9) in patients with resectable disease without surgery and 18.6 months (95% CI 15.8-21.3) in patients with unresectable disease (P < 0.001). CONCLUSIONS: Our findings illustrate the potential for conversion to resectability in mCRC, certain reluctance towards metastatic resections in clinical practice and the need for pre-planned and continuous evaluation for metastatic resection in high-volume centres. CLINICALTRIALS. GOV-IDENTIFIER: NCT00433927.
RCT Entities:
BACKGROUND: The FIRE-3 trial investigated combination chemotherapy plus either cetuximab or bevacizumab in patients with untreated metastatic colorectal cancer (mCRC) not scheduled for upfront surgery. We aimed to determine the number of patients who present with potentially resectable disease during systemic first-line therapy and to compare the findings with study reports concerning resections and outcome. PATIENTS AND METHODS: This evaluation of 448 patients was performed as central review blinded for treatment, other reviewers' evaluations and conducted interventions. Resectability was defined if at least 50% of the reviewers recommended surgical-based intervention. Overall survival was assessed by Kaplan-Meier method. RESULTS: Resectability increased from 22% (97/448) at baseline before treatment to 53% (238/448) at best response (P < 0.001), compared with an actual secondary resection rate for metastases of 16% (72/448). At baseline (23% versus 20%) and best response (53% versus 53%), potential resectability of metastases in this molecular unselected population was similar in cetuximab-treated patients versus bevacizumab-treated patients and not limited to patients with one-organ disease. The actual resection rate of metastases was significantly associated with treatment setting (P = 0.02; university hospital versus hospital/practice). Overall survival was 51.3 months (95% confidence interval [CI] 35.9-66.7) in patients with resectable disease who received surgery, 30.8 months (95% CI 26.6-34.9) in patients with resectable disease without surgery and 18.6 months (95% CI 15.8-21.3) in patients with unresectable disease (P < 0.001). CONCLUSIONS: Our findings illustrate the potential for conversion to resectability in mCRC, certain reluctance towards metastatic resections in clinical practice and the need for pre-planned and continuous evaluation for metastatic resection in high-volume centres. CLINICALTRIALS. GOV-IDENTIFIER: NCT00433927.
Authors: Marlen Haderlein; Sebastian Lettmaier; Melanie Langheinrich; Axel Schmid; Sabine Semrau; Markus Hecht; Michael Beck; Daniela Schmidt; Robert Grützmann; Rainer Fietkau; Axel Denz Journal: Int J Colorectal Dis Date: 2018-07-02 Impact factor: 2.571
Authors: Dominik Paul Modest; Volker Heinemann; Gunnar Folprecht; Timm Denecke; Johann Pratschke; Hauke Lang; Marc Bemelmans; Thomas Becker; Markus Rentsch; Daniel Seehofer; Christiane J Bruns; Bernhard Gebauer; Swantje Held; Arndt Stahler; Kathrin Heinrich; Jobst C von Einem; Sebastian Stintzing; Ulf P Neumann; Ingrid Ricard Journal: Ann Surg Oncol Date: 2020-03-14 Impact factor: 5.344