TY - JOUR
T1 - Nomogram Predicting Overall Survival in Patients With Locally Advanced Cervical Cancer Treated With Radiochemotherapy Including Image-Guided Brachytherapy
T2 - A Retro-EMBRACE Study
AU - Sturdza, Alina Emiliana
AU - Pötter, Richard
AU - Kossmeier, Michael
AU - Kirchheiner, Kathrin
AU - Mahantshetty, Umesh
AU - Haie-Meder, Christine
AU - Lindegaard, Jacob Christian
AU - Jurgenliemk-Schulz, Ina
AU - Tan, Li Tee
AU - Hoskin, Peter
AU - van Limbergen, Erik
AU - Gillham, Charles
AU - Segedin, Barbara
AU - Tharavichitkul, Ekkasit
AU - Iturre, Elena Villafranca
AU - Fokdal, Lars Ulrik
AU - Polterauer, Stephan
AU - Kirisits, Christian
AU - Tanderup, Kari
N1 - Funding Information:
The RetroEMBRACE study was supported by Elekta AB and Varian Medical System through unrestricted research grants and study sponsoring through the Medical University of Vienna. The work of this manuscript was supported via grants from Dr Oliver Jungnickel through Stiftung Philanthropie Österreich. Disclosures: A.S., C.K., K.T., K.K., and R.P. report grants from Elekta AB and Varian Medical System during the conduct of the study. A.S. reports grants from Stiftung Philanthropie Österreich through Dr. Oliver Jungnickel. K.T. report grants from the Danish Cancer Society during the conduct of the study. J.C.L. reports grants from Varian Medical System outside the submitted work. C.K. and A.S. report grants from Elekta AB outside the submitted work.
Funding Information:
The RetroEMBRACE study was supported by Elekta AB and Varian Medical System through unrestricted research grants and study sponsoring through the Medical University of Vienna. The work of this manuscript was supported via grants from Dr Oliver Jungnickel through Stiftung Philanthropie Österreich.
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/9/1
Y1 - 2021/9/1
N2 - Purpose: To present a nomogram for prediction of overall survival (OS) in patients with locally advanced cervical cancer (LACC) undergoing definitive radiochemotherapy including image-guided adaptive brachytherapy (IGABT). Methods and Materials: Seven hundred twenty patients with LACC treated with radiochemotherapy including IGABT in 12 institutions (median follow-up 56 months) were analyzed; 248 deaths occurred. Thirteen candidate predictors for OS were a priori chosen on the basis of the literature and expert knowledge. Missing data (7.2%) were imputed using multiple imputation and predictive mean matching. Univariate analysis with a multivariable Cox regression model for OS stratified by center was performed. Stepwise selection of predictive factors with the Akaike Information Criterion was used to obtain a predictive model and construct a nomogram for OS predictions 60 months from diagnosis; this was internally validated by concordance probability as a measure of discrimination and a calibration plot. Results: Thirteen potential predictive factors were evaluated; 10 factors reached statistical significance in univariate analysis (age, Hemoglobin, FIGO Stage2009, tumor width, corpus involvement, lymph node involvement, concurrent chemotherapy, dose to 90% of the high-risk clinical target volume, volume of CTV at the first brachytherapy [CTVHRVolumeBT], overall treatment time [OTT]). Four factors were confirmed significant within the multivariable Cox regression model (FIGO Stage2009, lymph node involvement, concurrent chemotherapy, CTVHRVolumeBT). The predictive model and corresponding nomogram were based on 7 Akaike Information Criterion–selected factors (age, corpus involvement, FIGO Stage2009, lymph node involvement, concurrent chemotherapy, CTVHRVolumeBT, OTT) and showed promising calibration and discrimination (cross-validated concordance probability c = 0.73). Conclusions: This is the first nomogram to predict OS in patients with LACC treated with IGABT. In addition to previously reported factors (age, FIGO2009 stage, corpus involvement, chemotherapy delivery, OTT, lymph node involvement), status of primary tumor at the time of brachytherapy seems to be an essential outcome predictor. These results can facilitate individualized tailoring of treatment and patient counseling during the treatment.
AB - Purpose: To present a nomogram for prediction of overall survival (OS) in patients with locally advanced cervical cancer (LACC) undergoing definitive radiochemotherapy including image-guided adaptive brachytherapy (IGABT). Methods and Materials: Seven hundred twenty patients with LACC treated with radiochemotherapy including IGABT in 12 institutions (median follow-up 56 months) were analyzed; 248 deaths occurred. Thirteen candidate predictors for OS were a priori chosen on the basis of the literature and expert knowledge. Missing data (7.2%) were imputed using multiple imputation and predictive mean matching. Univariate analysis with a multivariable Cox regression model for OS stratified by center was performed. Stepwise selection of predictive factors with the Akaike Information Criterion was used to obtain a predictive model and construct a nomogram for OS predictions 60 months from diagnosis; this was internally validated by concordance probability as a measure of discrimination and a calibration plot. Results: Thirteen potential predictive factors were evaluated; 10 factors reached statistical significance in univariate analysis (age, Hemoglobin, FIGO Stage2009, tumor width, corpus involvement, lymph node involvement, concurrent chemotherapy, dose to 90% of the high-risk clinical target volume, volume of CTV at the first brachytherapy [CTVHRVolumeBT], overall treatment time [OTT]). Four factors were confirmed significant within the multivariable Cox regression model (FIGO Stage2009, lymph node involvement, concurrent chemotherapy, CTVHRVolumeBT). The predictive model and corresponding nomogram were based on 7 Akaike Information Criterion–selected factors (age, corpus involvement, FIGO Stage2009, lymph node involvement, concurrent chemotherapy, CTVHRVolumeBT, OTT) and showed promising calibration and discrimination (cross-validated concordance probability c = 0.73). Conclusions: This is the first nomogram to predict OS in patients with LACC treated with IGABT. In addition to previously reported factors (age, FIGO2009 stage, corpus involvement, chemotherapy delivery, OTT, lymph node involvement), status of primary tumor at the time of brachytherapy seems to be an essential outcome predictor. These results can facilitate individualized tailoring of treatment and patient counseling during the treatment.
KW - Adult
KW - Aged
KW - Brachytherapy/methods
KW - Chemoradiotherapy/methods
KW - Female
KW - Humans
KW - Middle Aged
KW - Neoplasm Staging
KW - Nomograms
KW - Proportional Hazards Models
KW - Radiotherapy, Image-Guided/methods
KW - Uterine Cervical Neoplasms/mortality
UR - http://www.scopus.com/inward/record.url?scp=85108546664&partnerID=8YFLogxK
U2 - 10.1016/j.ijrobp.2021.04.022
DO - 10.1016/j.ijrobp.2021.04.022
M3 - Article
C2 - 33932530
AN - SCOPUS:85108546664
SN - 0360-3016
VL - 111
SP - 168
EP - 177
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 1
ER -