Cathalijne C B Post1, Stephanie M de Boer2, Melanie E Powell3, Linda Mileshkin4, Dionyssios Katsaros5, Paul Bessette6, Christine Haie-Meder7, Nelleke P B Ottevanger8, Jonathan A Ledermann9, Pearly Khaw10, Romerai D'Amico11, Anthony Fyles12, Marie Hélène Baron13, Henry C Kitchener14, Hans W Nijman15, Ludy C H W Lutgens16, Susan Brooks17, Ina M Jürgenliemk-Schulz18, Amanda Feeney9, Geraldine Goss19, Roldano Fossati20, Prafull Ghatage21, Alexandra Leary22, Viet Do23, Andrea A Lissoni24, Mary McCormack25, Remi A Nout2, Karen W Verhoeven-Adema26, Vincent T H B M Smit27, Hein Putter28, Carien L Creutzberg2. 1. Radiation Oncology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: c.c.b.post@lumc.nl. 2. Radiation Oncology, Leiden University Medical Center, Leiden, The Netherlands. 3. Clinical Oncology, Barts Health NHS Trust, London, United Kingdom. 4. Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia. 5. Surgical Sciences and Gynecology, Città della Salute and S Anna Hospital, Torino, Italy. 6. Gynaecologic Oncology, University of Sherbrooke, Sherbrooke, Quebec, Canada. 7. Radiotherapy, Institus Gustave Roussy, Villejuif, France. 8. Medical Oncology, Radboudumc, Nijmegen, The Netherlands. 9. Cancer Research UK and UCL Cancer Trials Centre, UCL Cancer Institute, London, United Kingdom. 10. Radiation Oncology, Peter MacCallum Cancer Center, Melbourne, Australia. 11. Radiotherapy, Azienda Socio Sanitaria Territoriale, Lecco, Italy. 12. Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Canada. 13. Radiotherapy, Centre Hospitalier Régional Universitaire de Besançon, Besançon, France. 14. Institute of Cancer Sciences, University of Manchester, Manchester, United Kingdom. 15. Gynecologic Oncology, University Medical Center Groningen, Groningen, The Netherlands. 16. Radiation Oncology, MAASTRO, Maastricht, The Netherlands. 17. Radiation Oncology, Auckland City Hospital, Auckland, New Zealand. 18. Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands. 19. Medical Oncology, Box Hill Hospital, Melbourne, Australia. 20. Medical Oncology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. 21. Gynecologic Oncology, Calgary-Tom Baker Cancer Centre, Calgary, Alberta, Canada. 22. Cancer Medicine and Gynecological Tumor Translational Research Lab, Gustave Roussy Cancer Center, INSERM U981, Université Paris Saclay, Villejuif, France. 23. Radiation Oncology, Liverpool & Macarthur Cancer Therapy Centre, NSW, Australia. 24. Obstetrics and Gynecology, San Gerardo Hospital, Monza, Italy. 25. Clinical Oncology, University College London Hospitals NHS Foundation Trust, London, United Kingdom. 26. Central Data Management and Trial Coordination, Comprehensive Cancer Center Netherlands, Rotterdam, The Netherlands. 27. Pathology, Leiden University Medical Center, Leiden, The Netherlands. 28. Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands.
Abstract
PURPOSE: The survival results of the PORTEC-3 trial showed a significant improvement in both overall and failure-free survival with chemoradiation therapy versus pelvic radiation therapy alone. The present analysis was performed to compare long-term adverse events (AE) and health-related quality of life (HRQOL). METHODS AND MATERIALS: In the study, 660 women with high-risk endometrial cancer were randomly assigned to receive chemoradiation therapy (2 concurrent cycles of cisplatin followed by 4 cycles of carboplatin/paclitaxel) or radiation therapy alone. Toxicity was graded using Common Terminology Criteria for Adverse Events, version 3.0. HRQOL was measured using EORTC QLQ-C30 and CX24/OV28 subscales and compared with normative data. An as-treated analysis was performed. RESULTS: Median follow-up was 74.6 months; 574 (87%) patients were evaluable for HRQOL. At 5 years, grade ≥2 AE were scored for 78 (38%) patients who had received chemoradiation therapy versus 46 (24%) who had received radiation therapy alone (P = .008). Grade 3 AE did not differ significantly between the groups (8% vs 5%, P = .18) at 5 years, and only one new late grade 4 toxicity had been reported. At 3 and 5 years, sensory neuropathy toxicity grade ≥2 persisted after chemoradiation therapy in 6% (vs 0% after radiation therapy, P < .001) and more patients reported significant tingling or numbness at HRQOL (27% vs 8%, P < .001 at 3 years; 24% vs 9%, P = .002 at 5 years). Up to 3 years, more patients who had chemoradiation therapy reported limb weakness (21% vs 5%, P < .001) and lower physical (79 vs 87, P < .001) and role functioning (78 vs 88, P < .001) scores. Both treatment groups reported similar long-term global health/quality of life scores, which were better than those of the normative population. CONCLUSIONS: This study shows a long-lasting, clinically relevant, negative impact of chemoradiation therapy on toxicity and HRQOL, most importantly persistent peripheral sensory neuropathy. Physical and role functioning impairments were seen until 3 years. These long-term data are essential for patient information and shared decision-making regarding adjuvant chemotherapy for high-risk endometrial cancer.
RCT Entities:
PURPOSE: The survival results of the PORTEC-3 trial showed a significant improvement in both overall and failure-free survival with chemoradiation therapy versus pelvic radiation therapy alone. The present analysis was performed to compare long-term adverse events (AE) and health-related quality of life (HRQOL). METHODS AND MATERIALS: In the study, 660 women with high-risk endometrial cancer were randomly assigned to receive chemoradiation therapy (2 concurrent cycles of cisplatin followed by 4 cycles of carboplatin/paclitaxel) or radiation therapy alone. Toxicity was graded using Common Terminology Criteria for Adverse Events, version 3.0. HRQOL was measured using EORTC QLQ-C30 and CX24/OV28 subscales and compared with normative data. An as-treated analysis was performed. RESULTS: Median follow-up was 74.6 months; 574 (87%) patients were evaluable for HRQOL. At 5 years, grade ≥2 AE were scored for 78 (38%) patients who had received chemoradiation therapy versus 46 (24%) who had received radiation therapy alone (P = .008). Grade 3 AE did not differ significantly between the groups (8% vs 5%, P = .18) at 5 years, and only one new late grade 4 toxicity had been reported. At 3 and 5 years, sensory neuropathy toxicity grade ≥2 persisted after chemoradiation therapy in 6% (vs 0% after radiation therapy, P < .001) and more patients reported significant tingling or numbness at HRQOL (27% vs 8%, P < .001 at 3 years; 24% vs 9%, P = .002 at 5 years). Up to 3 years, more patients who had chemoradiation therapy reported limb weakness (21% vs 5%, P < .001) and lower physical (79 vs 87, P < .001) and role functioning (78 vs 88, P < .001) scores. Both treatment groups reported similar long-term global health/quality of life scores, which were better than those of the normative population. CONCLUSIONS: This study shows a long-lasting, clinically relevant, negative impact of chemoradiation therapy on toxicity and HRQOL, most importantly persistent peripheral sensory neuropathy. Physical and role functioning impairments were seen until 3 years. These long-term data are essential for patient information and shared decision-making regarding adjuvant chemotherapy for high-risk endometrial cancer.