Nathalie Arians1, Meinhard Kieser2, Laura Benner2, Nathalie Rochet3, Sonja Katayama3, Florian Sterzing3, Klaus Herfarth3, Kai Schubert3, Lars Schröder4, Christina Leitzen5, Andreas Schneeweiss6, Christof Sohn6, Jürgen Debus3, Katja Lindel3. 1. National Center for Radiation Oncology, Heidelberg Institute for Radiation Oncology, Heidelberg, Germany; Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany. Electronic address: nathalie.arians@med.uni-heidelberg.de. 2. Institute for Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany. 3. National Center for Radiation Oncology, Heidelberg Institute for Radiation Oncology, Heidelberg, Germany; Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany. 4. Department of Gynecology and Obstetrics, Center for Integrated Oncology (CIO) Köln/Bonn, Bonn, Germany. 5. Department of Radiation Oncology, University Hospital Bonn, Bonn, Germany. 6. Department of Gynecology and Obstetrics, University Hospital Heidelberg, Heidelberg, Germany.
Abstract
PURPOSE: To assess treatment tolerance and toxicity rates of consolidative whole-abdominal radiation therapy (WART) following cytoreductive surgery and carboplatin/paclitaxel chemotherapy in high-risk patients with advanced ovarian cancer (International Federation of Gynecology and Obstetrics stage III) using intensity modulated radiation therapy. METHODS AND MATERIALS: The OVAR-IMRT-02 study is a multicenter, single-arm, phase 2 trial. Twenty patients with optimally debulked ovarian cancer (International Federation of Gynecology and Obstetrics stage III) with complete remission after chemotherapy were treated with intensity modulated WART as a consolidation therapy. A total dose of 30 Gy in 20 fractions of 1.5 Gy was applied to the entire peritoneal cavity. The primary endpoint was treatment tolerability, defined as lack of any Common Terminology Criteria for Adverse Events grade 4 toxicity within 10 weeks after start of treatment; secondary objectives were acute and chronic toxicity, quality of life, rates of therapy disruption and abortion, and progression-free and overall survival. RESULTS: Intensity modulated WART resulted in excellent coverage of the whole peritoneal cavity, with effective sparing of all organs at risk. The primary analysis included all 20 enrolled patients, of whom 19 did not experience Common Terminology Criteria for Adverse Events grade 4 toxicity. Only 1 patient experienced acute grade 4 hematologic toxicity. Thus, the tolerability rate of intensity modulated WART was significantly higher than 70%. No gastrointestinal acute toxicities higher than grade 2 have been observed. During WART, mean global health status decreased by 18.1 points (95% confidence interval 7.1, 29.0). Six weeks after WART, global health status had already increased, with a mean score difference of 4.6 (95% confidence interval -11.1, 20.4) compared with baseline. Similar characteristics were observed for all function scale scores. CONCLUSION: Intensity modulated WART after aggressive surgery and carboplatin/paclitaxel chemotherapy is associated with an acceptable risk of acute toxicity and a treatment tolerability rate significantly higher than 70%. Together with our knowledge about clinical feasibility, meaning excellent coverage of the planning target volume and effective sparing of organs at risk, intensity modulated WART could offer a new therapeutic option for consolidation treatment of patients with advanced ovarian cancer.
PURPOSE: To assess treatment tolerance and toxicity rates of consolidative whole-abdominal radiation therapy (WART) following cytoreductive surgery and carboplatin/paclitaxel chemotherapy in high-risk patients with advanced ovarian cancer (International Federation of Gynecology and Obstetrics stage III) using intensity modulated radiation therapy. METHODS AND MATERIALS: The OVAR-IMRT-02 study is a multicenter, single-arm, phase 2 trial. Twenty patients with optimally debulked ovarian cancer (International Federation of Gynecology and Obstetrics stage III) with complete remission after chemotherapy were treated with intensity modulated WART as a consolidation therapy. A total dose of 30 Gy in 20 fractions of 1.5 Gy was applied to the entire peritoneal cavity. The primary endpoint was treatment tolerability, defined as lack of any Common Terminology Criteria for Adverse Events grade 4 toxicity within 10 weeks after start of treatment; secondary objectives were acute and chronic toxicity, quality of life, rates of therapy disruption and abortion, and progression-free and overall survival. RESULTS: Intensity modulated WART resulted in excellent coverage of the whole peritoneal cavity, with effective sparing of all organs at risk. The primary analysis included all 20 enrolled patients, of whom 19 did not experience Common Terminology Criteria for Adverse Events grade 4 toxicity. Only 1 patient experienced acute grade 4 hematologic toxicity. Thus, the tolerability rate of intensity modulated WART was significantly higher than 70%. No gastrointestinal acute toxicities higher than grade 2 have been observed. During WART, mean global health status decreased by 18.1 points (95% confidence interval 7.1, 29.0). Six weeks after WART, global health status had already increased, with a mean score difference of 4.6 (95% confidence interval -11.1, 20.4) compared with baseline. Similar characteristics were observed for all function scale scores. CONCLUSION: Intensity modulated WART after aggressive surgery and carboplatin/paclitaxel chemotherapy is associated with an acceptable risk of acute toxicity and a treatment tolerability rate significantly higher than 70%. Together with our knowledge about clinical feasibility, meaning excellent coverage of the planning target volume and effective sparing of organs at risk, intensity modulated WART could offer a new therapeutic option for consolidation treatment of patients with advanced ovarian cancer.