TY - JOUR
T1 - Long-Term Toxicity and Health-Related Quality of Life After Adjuvant Chemoradiation Therapy or Radiation Therapy Alone for High-Risk Endometrial Cancer in the Randomized PORTEC-3 Trial
AU - Post, Cathalijne C B
AU - de Boer, Stephanie M
AU - Powell, Melanie E
AU - Mileshkin, Linda
AU - Katsaros, Dionyssios
AU - Bessette, Paul
AU - Haie-Meder, Christine
AU - Ottevanger, Nelleke P B
AU - Ledermann, Jonathan A
AU - Khaw, Pearly
AU - D'Amico, Romerai
AU - Fyles, Anthony
AU - Baron, Marie Hélène
AU - Kitchener, Henry C
AU - Nijman, Hans W
AU - Lutgens, Ludy C H W
AU - Brooks, Susan
AU - Jürgenliemk-Schulz, Ina M
AU - Feeney, Amanda
AU - Goss, Geraldine
AU - Fossati, Roldano
AU - Ghatage, Prafull
AU - Leary, Alexandra
AU - Do, Viet
AU - Lissoni, Andrea A
AU - McCormack, Mary
AU - Nout, Remi A
AU - Verhoeven-Adema, Karen W
AU - Smit, Vincent T H B M
AU - Putter, Hein
AU - Creutzberg, Carien L
N1 - Funding Information:
The PORTEC-3 study was supported by a grant from the Dutch Cancer Society (grant number UL2006-4168/CKTO 2006-04 ), the Netherlands. PORTEC 3 was supported in the United Kingdom by Cancer Research UK (grant number C7925/A8659 ). Participation in the PORTEC-3 trial by the Australia and New Zealand Gynaecologic Oncology Group (ANZGOG) and the Trans-Tasman Radiation Oncology Group (TROG) was supported by the NHMRC Project (grant number 570894, 2008 ) and by a Cancer Australia Grant (awarded through the 2011 round of the priority-driven Collaborative Cancer Research Scheme and funded by Cancer Australia). Participation by the Italian MaNGO group was partly supported by a grant from the Italian Medicines Agency AIFA (grant number FARM84BCX2 ). Canadian participation in the PORTEC-3 trial was supported by the Canadian Cancer Society Research Institute (grant numbers 015469 , 021039 ).
Funding Information:
Disclosures: C.L.C. reports grants from Dutch Cancer Society, during the conduct of the study. H.W.N. reports grants from Dutch Cancer Society, grants and other from Aduro, nonfinancial support from Merck, grants and other from DCPrime, and nonfinancial support from Bionovion, outside the submitted work. P.B. reports grants and personal fees from Canadian Cancer Trials Group (CCTG), during the conduct of the study and outside the submitted work. R.N. reports grants from Elekta, Varian, and Accuray, outside the submitted work. All other authors declare no competing interests in relation to this study.
Funding Information:
We thank all the participating groups: DGOG (the Netherlands), NCRI (United Kingdom), ANZGOG (Australia and New Zealand), MaNGO (Italy), Fedegyn (France), and the Canadian Cancer Trials Group (Canada) and their coordinating teams, principal investigators, staff, and clinical research teams at the groups’ participating centers for all their work and effort. We especially thank all women who greatly contributed by repeatedly filling in the questionnaires throughout the study years. The PORTEC-3 trial involved a strong international collaboration within the Gynaecological Oncology InterGroup (GCIG), and the support of the GCIG officers and member groups is gratefully acknowledged. We also thank the members of the data safety monitoring board for their invaluable work and guidance throughout the duration of the trial.
Publisher Copyright:
© 2020 The Author(s)
PY - 2021/3/15
Y1 - 2021/3/15
N2 - 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.
AB - 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.
U2 - 10.1016/j.ijrobp.2020.10.030
DO - 10.1016/j.ijrobp.2020.10.030
M3 - Article
C2 - 33129910
SN - 0360-3016
VL - 109
SP - 975
EP - 986
JO - International Journal of Radiation Oncology, Biology, Physics
JF - International Journal of Radiation Oncology, Biology, Physics
IS - 4
ER -