TY - JOUR
T1 - Overall Severe Morbidity After Chemo-Radiation Therapy and Magnetic Resonance Imaging-Guided Adaptive Brachytherapy in Locally Advanced Cervical Cancer
T2 - Results From the EMBRACE–I Study
AU - Vittrup, Anders Schwartz
AU - Kirchheiner, Kathrin
AU - Pötter, Richard
AU - Fokdal, Lars Ulrik
AU - Jensen, Nina Boje Kibsgaard
AU - Spampinato, Sofia
AU - Haie-Meder, Christine
AU - Schmid, Maximilian Paul
AU - Sturdza, Alina Emiliana
AU - Mahantshetty, Umesh
AU - Hoskin, Peter
AU - Segedin, Barbara
AU - Bruheim, Kjersti
AU - Rai, Bhavana
AU - Wiebe, Ericka
AU - van der Steen-Banasik, Elzbieta
AU - Cooper, Rachel
AU - van Limbergen, Erik
AU - Sundset, Marit
AU - Pieters, Bradley Rumwell
AU - Kirisits, Christian
AU - Lindegaard, Jacob Christian
AU - Jürgenliemk-Schulz, Ina M.
AU - EMBRACE Collaborative Group
AU - Nout, Remi
AU - Tanderup, Kari
N1 - Funding Information: The EMBRACE study was supported by Elekta AB and Varian Medical System through unrestricted research grants and study sponsoring through Medical University of Vienna. The work of this manuscript was supported via a research grant from the Danish Cancer Society (grant number R146-A9459-16-S2). Funding Information: Disclosures: A.V., K.T. and S.S. report grants from Danish Cancer Society, during the conduct of the study. C.K., K.K. and A.S. report grants from Elekta AB and Varian Medical Systems, during the conduct of the study. K.T., R.N and R.P. report grants from Varian Medical Systems and Elekta AB, outside the submitted work. K.T. reports a leadership role in the European Society for Radiation therapy and Oncology. M.Sc. report grants from Elekta AB during the conduct of the study and personal fees for workshops and lectures from Elekta AB; and a 2017 United States Patent and Trademark Office Pre-Granted publication (patent number US20170120072). R.N. reports grants from Accuray, Dutch Cancer Society, and Dutch Research Council, outside the submitted work. A.S. reports grants from Stiftung Philanthropie Österreich during the conduct of the study, and personal fees from Elekta and support for attending meetings or travel from the University of Vienna, outside the submitted work. P.H. reports grants from Cancer Research UK, Prostate Cancer UK, outside the submitted work, and is a member of Data Monitoring and Ethics Committees and a Chair of the NICE committee on Problem Gambling. All other authors have no disclosures to declare. Publisher Copyright: © 2023 The Authors
PY - 2023/7/15
Y1 - 2023/7/15
N2 - Purpose: To evaluate overall severe late morbidity (grade ≥3) in patients with locally advanced cervical cancer treated with chemo-radiation therapy and magnetic resonance image guided adaptive brachytherapy within the prospective EMBRACE-I study, and to compare the results with published literature after standard radiograph based brachytherapy (BT). Methods and Materials: From 2008 to 2015 the EMBRACE-I study enrolled 1416 patients. Morbidity was assessed (Common Terminology Criteria for Adverse Events version 3.0) every 3 months the 1st year, every 6 months the second and third year, and yearly thereafter and 1251 patients had available follow-up on late morbidity. Morbidity events (grade 3-5) were summarized as the maximum grade during follow-up (crude incidence rates) and actuarial estimates at 3 and 5 years. To compare with the published literature on standard radiograph based BT, Common Terminology Criteria for Adverse Events scores from the EMBRACE-I study were retrospectively converted into a corresponding score in the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer system. Results: In total, 534 severe events occurred in 270 patients; 429 events were grade 3 and 105 were grade 4 events. Actuarial estimates for grade ≥3 gastrointestinal (GI), genitourinary (GU), vaginal and fistula events at 5 years were 8.5% (95% confidence interval [CI], 6.9%-10.6%), 6.8% (95% CI, 5.4%-8.6%), 5.7% (95% CI, 4.3%-7.6%), and 3.2% (95% CI, 2.2%-4.5%), respectively. The 5-year actuarial estimate for organ-related events (GI, GU, vaginal, or fistula) was 18.4% (95% CI, 16.0%-21.2%). The 5-year actuarial estimate when aggregating all G≥3 endpoints (GI, GU, vaginal, fistulas, and non-GI/GU/vaginal) was 26.6% (95% CI, 23.8%-29.6%). Thirteen patients had a treatment-related death, 8 of which were associated with GI morbidity. Conclusions: This report assesses severe morbidity from the largest prospective study on chemo-radiation therapy and image guided adaptive brachytherapy for locally advanced cervical cancer to date. Severe late morbidity was limited per endpoint and organ category, but considerable when aggregated across organs and all endpoints. The late morbidity results in the EMBRACE-I study compare favorably with published literature on standard radiograph based BT for GI morbidity, vaginal morbidity, and fistulas.
AB - Purpose: To evaluate overall severe late morbidity (grade ≥3) in patients with locally advanced cervical cancer treated with chemo-radiation therapy and magnetic resonance image guided adaptive brachytherapy within the prospective EMBRACE-I study, and to compare the results with published literature after standard radiograph based brachytherapy (BT). Methods and Materials: From 2008 to 2015 the EMBRACE-I study enrolled 1416 patients. Morbidity was assessed (Common Terminology Criteria for Adverse Events version 3.0) every 3 months the 1st year, every 6 months the second and third year, and yearly thereafter and 1251 patients had available follow-up on late morbidity. Morbidity events (grade 3-5) were summarized as the maximum grade during follow-up (crude incidence rates) and actuarial estimates at 3 and 5 years. To compare with the published literature on standard radiograph based BT, Common Terminology Criteria for Adverse Events scores from the EMBRACE-I study were retrospectively converted into a corresponding score in the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer system. Results: In total, 534 severe events occurred in 270 patients; 429 events were grade 3 and 105 were grade 4 events. Actuarial estimates for grade ≥3 gastrointestinal (GI), genitourinary (GU), vaginal and fistula events at 5 years were 8.5% (95% confidence interval [CI], 6.9%-10.6%), 6.8% (95% CI, 5.4%-8.6%), 5.7% (95% CI, 4.3%-7.6%), and 3.2% (95% CI, 2.2%-4.5%), respectively. The 5-year actuarial estimate for organ-related events (GI, GU, vaginal, or fistula) was 18.4% (95% CI, 16.0%-21.2%). The 5-year actuarial estimate when aggregating all G≥3 endpoints (GI, GU, vaginal, fistulas, and non-GI/GU/vaginal) was 26.6% (95% CI, 23.8%-29.6%). Thirteen patients had a treatment-related death, 8 of which were associated with GI morbidity. Conclusions: This report assesses severe morbidity from the largest prospective study on chemo-radiation therapy and image guided adaptive brachytherapy for locally advanced cervical cancer to date. Severe late morbidity was limited per endpoint and organ category, but considerable when aggregated across organs and all endpoints. The late morbidity results in the EMBRACE-I study compare favorably with published literature on standard radiograph based BT for GI morbidity, vaginal morbidity, and fistulas.
UR - http://www.scopus.com/inward/record.url?scp=85147860641&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ijrobp.2023.01.002
DO - https://doi.org/10.1016/j.ijrobp.2023.01.002
M3 - Article
C2 - 36641039
SN - 0360-3016
VL - 116
SP - 807
EP - 824
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 4
ER -