TY - JOUR
T1 - Prognostic Implications of Uterine Cervical Cancer Regression During Chemoradiation Evaluated by the T-Score in the Multicenter EMBRACE I Study
AU - Lindegaard, Jacob Christian
AU - Petric, Primoz
AU - Schmid, Maximilian Paul
AU - Nesvacil, Nicole
AU - Haie-Meder, Christine
AU - Fokdal, Lars Ulrik
AU - Sturdza, Alina Emiliana
AU - Hoskin, Peter
AU - Mahantshetty, Umesh
AU - Segedin, Barbara
AU - Bruheim, Kjersti
AU - Huang, Fleur
AU - Rai, Bhavana
AU - Cooper, Rachel
AU - van der Steen-Banasik, Elzbieta
AU - Van Limbergen, Erik
AU - Pieters, Bradley Rumwell
AU - Tan, Li Tee
AU - Nout, Remi A.
AU - De Leeuw, Astrid Agatha Catharina
AU - Kirchheiner, Kathrin
AU - Spampinato, Sofia
AU - Jürgenliemk-Schulz, Ina
AU - Tanderup, Kari
AU - Kirisits, Christian
AU - Pötter, Richard
N1 - Funding Information:
Funding was obtained from Aarhus University Hospital , Medical University of Vienna , Danish Cancer Society , Health Research Foundation of Central Denmark Region , Varian Medical Systems , Elekta AB , and Austrian Science Fund ( KLI695-B33 ).
Funding Information:
Funding was obtained from Aarhus University Hospital, Medical University of Vienna, Danish Cancer Society, Health Research Foundation of Central Denmark Region, Varian Medical Systems, Elekta AB, and Austrian Science Fund (KLI695-B33). Disclosures: J.L. reports support from the Health Research Foundation of Central Denmark Region. M.S. reports support from Elekta AB and Varian Medical Systems for the EMBRACE study through unrestricted research grants and study sponsoring through the Medical University of Vienna; personal fees for workshops and lectures from Elekta AB; methods and systems for brachytherapy planning based on imaging data (Nucletron Operations B.V.); and a 2017 United States Patent and Trademark Office Pre-Granted publication (patent number US20170120072) and related patents in other countries. N.N. reports support from the Austrian Science Fund, project KLI695-B33. A.S. reports support from Elekta AB in the form of payment to institution, and personal fees for teaching, as well as grants from Oliver Jungnickel through Stiftung Philanthropie Österreich. U.M. reports honoraria for lectures from Brachyacademy; membership in the radiation therapy steering committee of the CALLA study sponsored by AstraZeneca; and a secretary position in the Indian Brachytherapy Society. B.R.P. reports a research grant to institution from Elekta AB. R.N. reports grants from the Dutch Cancer Society, Dutch Research Council, Elekta AB, Varian Medical Systems, and Accuray; consulting fees to institution from Merck for advisory board activities; and an unpaid leadership role in the Dutch Gynaecological Oncology Group and Dutch Platform for Radiotherapy Gynecological Tumors. K.K. reports support from Elekta AB and Varian Medical Systems for the EMBRACE study through unrestricted research grants and study sponsoring through the Medical University of Vienna. S.S. reports grants from the Danish Cancer Society. K.T. reports a leadership role in the European Society for Radiotherapy and Oncology, and unrestricted research grants paid to institution from Varian Medical Systems, Elekta AB, and the Danish Cancer Society. C.K. reports support from Elekta AB and Varian Medical Systems for the EMBRACE study through unrestricted research grants and study sponsoring through the Medical University of Vienna; travel expense and honoraria for educational events from Elekta AB; support for attending meetings from the European Society for Radiotherapy and Oncology; methods and systems for brachytherapy planning based on imaging data (Nucletron Operations B.V.); a 2017 United States Patent and Trademark Office Pre-Granted publication (patent number US20170120072) and related patents in other countries; and a leadership role in the GEC-ESTRO Brachytherapy Committee. R.P. reports support from Elekta AB and Varian Medical Systems for the EMBRACE study through unrestricted research grants and study sponsoring through the Medical University of Vienna. All other authors have no disclosures to declare.
Publisher Copyright:
© 2022 Elsevier Inc.
Copyright © 2022 Elsevier Inc. All rights reserved.
PY - 2022/6/1
Y1 - 2022/6/1
N2 - Purpose: A simple scoring system (T-score, TS) for integrating findings from clinical examination and magnetic resonance imaging (MRI) of the primary tumor at diagnosis has shown strong prognostic capability for predicting local control and survival in locally advanced cervical cancer treated with chemoradiation and MRI-guided brachytherapy (BT). The aim was to validate the performance of TS using the multicenter EMBRACE I study and to evaluate the prognostic implications of TS regression obtained during initial chemoradiation. Methods and Materials: EMBRACE I recruited 1416 patients, of whom 1318 were available for TS. Patients were treated with chemoradiation followed by MRI-guided BT. A ranked ordinal scale of 0 to 3 points was used to assess 8 anatomic locations typical for local invasion of cervical cancer. TS was calculated separately at diagnosis (TSD) and at BT (TSBT) by the sum of points obtained from the 8 locations at the 2 occasions. Results: Median TSD and TSBT was 5 and 4, respectively. TS regression was observed in 71% and was an explanatory variable for BT technique (intracavitary vs intracavitary/interstitial) and major dose-volume histogram parameters for BT, such as high-risk clinical target (CTVHR), CTVHR D90 (minimal dose to 90% of the target volume), D2cm3 bladder (minimal dose to the most exposed 2 cm3 of the bladder), and D2cm3 rectum. TS regression (TSBT≤5) was associated with improved local control and survival and with less morbidity compared with patients with TSBT remaining high (>5) despite initial chemoradiation. TS regression was significant in multivariate analysis for both local control and survival when analyzed in consort with already established prognostic parameters related to the patient, disease, and treatment. Conclusions: TS was validated in a multicenter setting and proven to be a strong multidisciplinary platform for integration of clinical findings and imaging with the ability to quantitate local tumor regression and its prognostic implications regarding BT technique, dose-volume histogram parameters, local control, survival, and morbidity.
AB - Purpose: A simple scoring system (T-score, TS) for integrating findings from clinical examination and magnetic resonance imaging (MRI) of the primary tumor at diagnosis has shown strong prognostic capability for predicting local control and survival in locally advanced cervical cancer treated with chemoradiation and MRI-guided brachytherapy (BT). The aim was to validate the performance of TS using the multicenter EMBRACE I study and to evaluate the prognostic implications of TS regression obtained during initial chemoradiation. Methods and Materials: EMBRACE I recruited 1416 patients, of whom 1318 were available for TS. Patients were treated with chemoradiation followed by MRI-guided BT. A ranked ordinal scale of 0 to 3 points was used to assess 8 anatomic locations typical for local invasion of cervical cancer. TS was calculated separately at diagnosis (TSD) and at BT (TSBT) by the sum of points obtained from the 8 locations at the 2 occasions. Results: Median TSD and TSBT was 5 and 4, respectively. TS regression was observed in 71% and was an explanatory variable for BT technique (intracavitary vs intracavitary/interstitial) and major dose-volume histogram parameters for BT, such as high-risk clinical target (CTVHR), CTVHR D90 (minimal dose to 90% of the target volume), D2cm3 bladder (minimal dose to the most exposed 2 cm3 of the bladder), and D2cm3 rectum. TS regression (TSBT≤5) was associated with improved local control and survival and with less morbidity compared with patients with TSBT remaining high (>5) despite initial chemoradiation. TS regression was significant in multivariate analysis for both local control and survival when analyzed in consort with already established prognostic parameters related to the patient, disease, and treatment. Conclusions: TS was validated in a multicenter setting and proven to be a strong multidisciplinary platform for integration of clinical findings and imaging with the ability to quantitate local tumor regression and its prognostic implications regarding BT technique, dose-volume histogram parameters, local control, survival, and morbidity.
KW - Brachytherapy/methods
KW - Chemoradiotherapy/methods
KW - Female
KW - Humans
KW - Magnetic Resonance Imaging/methods
KW - Prognosis
KW - Radiotherapy Dosage
KW - Uterine Cervical Neoplasms/diagnostic imaging
UR - http://www.scopus.com/inward/record.url?scp=85129712124&partnerID=8YFLogxK
U2 - 10.1016/j.ijrobp.2022.02.005
DO - 10.1016/j.ijrobp.2022.02.005
M3 - Article
C2 - 35157992
AN - SCOPUS:85129712124
SN - 0360-3016
VL - 113
SP - 379
EP - 389
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 2
ER -