TY - JOUR
T1 - Distant Metastasis After Chemoradiation and Image Guided Adaptive Brachytherapy in Locally Advanced Cervical Cancer
AU - Knoth, Johannes
AU - Nout, Remi A.
AU - Pötter, Richard
AU - Mahantshetty, Umesh
AU - Jürgenliemk-Schulz, Ina
AU - Haie-Meder, Christine
AU - Fortin, Israel
AU - Fokdal, Lars U.
AU - Sturdza, Alina
AU - Hoskin, Peter
AU - Segedin, Barbara
AU - Bruheim, Kjersti
AU - Huang, Fleur
AU - Rai, Bhavana
AU - Cooper, Rachel
AU - Haverkort, Marie A.D.
AU - van Limbergen, Erik
AU - Pieters, Bradley R.
AU - Tan, Li Tee
AU - Boryshchuk, Daniela
AU - Ristl, Robin
AU - Hawaldar, Rohini
AU - Kannan, Sadhana
AU - de Leeuw, Astrid A.C.
AU - Eder-Nesvacil, Nicole
AU - Tanderup, Kari
AU - Kirisits, Christian
AU - Lindegaard, Jacob C.
AU - Schmid, Maximilian P.
N1 - Publisher Copyright:
© 2025 The Authors
PY - 2025/10/10
Y1 - 2025/10/10
N2 - Purpose: This study aimed to assess patterns and risks of distant metastasis (DM) in patients with cervical cancer treated with chemoradiation therapy and MR-image guided adaptive brachytherapy (IGABT) and to explore a potential dose-effect relationship of concomitant cisplatin. Methods and Materials: Data were derived from EMBRACE I, an international, prospective, and multicenter cohort study conducted at 24 centers across Europe, Asia, and North America from July 30, 2008, to December 29, 2015. The study included 1416 patients with biopsy-confirmed cervical cancer (International Federation of Gynecology and Obstetrics [FIGO2009] stage IB-IVA or stage IVB limited to paraaortic lymph nodes below the L1/L2 interspace). Treatment involved external beam radiation therapy (45-50.4 Gy), weekly cisplatin (40 mg/m², 30 mg/m², or paused), and IGABT. DM was defined as extra-pelvic recurrence excluding paraaortic nodes. Results: The analysis included 1318 patients with a median age of 49 years and a median follow-up of 52 months. The 5-year cumulative incidence of DM was 14%, with the lungs (26%), mediastinal lymph nodes (15%), and bones (10%) identified as the most common metastatic sites. Key risk factors for DM included nonsquamous histology (HR, 1.89; 95% CI, 1.30-2.75), nodal involvement at diagnosis (pelvic-only nodes: HR, 1.56; 95% CI, 1.07-2.26; paraaortic nodes: HR, 3.15; 95% CI, 1.93-5.16), and large target volume at brachytherapy (HR, 1.93; 95% CI, 1.21-3.08). Patients receiving fewer than 4 cycles of chemotherapy demonstrated a significantly higher risk of DM (HR, 1.52; 95% CI, 1.08-2.13). Conclusion: DM is a substantial burden in patients with locally advanced cervical cancer, with the lungs, distant lymph nodes, and bones being the most frequent sites. Risk factors such as nonsquamous histology, nodal involvement, and large target volumes at brachytherapy are critical considerations for identifying high-risk patients in future studies. These findings highlight the need for tailored strategies to mitigate DM in this patient population.
AB - Purpose: This study aimed to assess patterns and risks of distant metastasis (DM) in patients with cervical cancer treated with chemoradiation therapy and MR-image guided adaptive brachytherapy (IGABT) and to explore a potential dose-effect relationship of concomitant cisplatin. Methods and Materials: Data were derived from EMBRACE I, an international, prospective, and multicenter cohort study conducted at 24 centers across Europe, Asia, and North America from July 30, 2008, to December 29, 2015. The study included 1416 patients with biopsy-confirmed cervical cancer (International Federation of Gynecology and Obstetrics [FIGO2009] stage IB-IVA or stage IVB limited to paraaortic lymph nodes below the L1/L2 interspace). Treatment involved external beam radiation therapy (45-50.4 Gy), weekly cisplatin (40 mg/m², 30 mg/m², or paused), and IGABT. DM was defined as extra-pelvic recurrence excluding paraaortic nodes. Results: The analysis included 1318 patients with a median age of 49 years and a median follow-up of 52 months. The 5-year cumulative incidence of DM was 14%, with the lungs (26%), mediastinal lymph nodes (15%), and bones (10%) identified as the most common metastatic sites. Key risk factors for DM included nonsquamous histology (HR, 1.89; 95% CI, 1.30-2.75), nodal involvement at diagnosis (pelvic-only nodes: HR, 1.56; 95% CI, 1.07-2.26; paraaortic nodes: HR, 3.15; 95% CI, 1.93-5.16), and large target volume at brachytherapy (HR, 1.93; 95% CI, 1.21-3.08). Patients receiving fewer than 4 cycles of chemotherapy demonstrated a significantly higher risk of DM (HR, 1.52; 95% CI, 1.08-2.13). Conclusion: DM is a substantial burden in patients with locally advanced cervical cancer, with the lungs, distant lymph nodes, and bones being the most frequent sites. Risk factors such as nonsquamous histology, nodal involvement, and large target volumes at brachytherapy are critical considerations for identifying high-risk patients in future studies. These findings highlight the need for tailored strategies to mitigate DM in this patient population.
UR - https://www.scopus.com/pages/publications/105006944364
U2 - 10.1016/j.ijrobp.2025.04.037
DO - 10.1016/j.ijrobp.2025.04.037
M3 - Article
C2 - 40354949
AN - SCOPUS:105006944364
SN - 0360-3016
VL - 123
SP - 503
EP - 512
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 2
ER -
