TY - JOUR
T1 - Dose-Volume Predictors of Fatal Bronchopulmonary Bleeding After Stereotactic Body Radiation Therapy of Centrally Located Lung Tumors
T2 - An Analysis of the Expanded HILUS Cohort
AU - Karlsson, Kristin
AU - Rancati, Tiziana
AU - Lindbäck, Elias
AU - Lindberg, Sara
AU - Grozman, Vitali
AU - Al-Jirf, Karam
AU - Lax, Ingmar
AU - Hoffmann, Lone
AU - Møller, Ditte Sloth
AU - Khalil, Azza
AU - Knap, Marianne Marquard
AU - Nielsen, Tine Bjørn
AU - Land, Lotte Holm
AU - Kristiansen, Charlotte
AU - Ramberg, Christina
AU - Rogg, Lotte Victoria
AU - Hagen, Rebekka Knoph
AU - Frøland, Anne-Sofie
AU - Drugge, Ninni
AU - Nyman, Jan
AU - Josipovic, Mirjana
AU - Persson, Gitte Fredberg
AU - Olofsson, Jörgen
AU - Bergström, Per
AU - Rosenbrand, Hans-Olov
AU - Lödén, Britta
AU - Haraldsson, André
AU - Engelholm, Silke
AU - Billiet, Charlotte
AU - Onjukka, Eva
AU - Lindberg, Karin
N1 - Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.
PY - 2026/1/13
Y1 - 2026/1/13
N2 - PURPOSE: The expanded HILUS study showed that bronchial dose and bronchial tumor compression are risk factors for bronchopulmonary bleedings after stereotactic body radiation therapy of centrally located lung tumors. In the current analysis of the same cohort, the aim was to identify the dose-volume histogram (DVH) parameter that best predicts fatal bronchopulmonary bleeding and to develop a predictive model for this endpoint.METHODS AND MATERIALS: The HILUS cohort included 230 patients with 238 central targets treated with stereotactic body radiation therapy of 7 Gy × 8 to the periphery of the planning target volume, where 21 patients developed grade-5 bronchopulmonary bleeding. Cox regression-based normal-tissue complication probability models were developed, accounting for the dose to the main and intermediate bronchi and bronchial tumor compression. Three alternative DVH parameters were explored: the dose to a certain volume (Dv), the volume receiving a certain dose (Vd), and the equivalent uniform dose. Internal validation was performed with the bootstrap method.RESULTS: The best fits of the bivariable normal-tissue complication probability models included bronchial tumor compression in combination with the DVH parameters of D0.31 cm3, V82Gy,EQD2 (equivalent dose in 2-Gy fractions), and equivalent uniform dose with n = 0.024, respectively. This indicates that a high dose to a small volume may lead to grade-5 bronchopulmonary bleeding. The probability of fatal bleeding at 2 years without bronchial tumor compression was 10% for a D0.31 cm3 of 107 Gy3 EQD2, and 20% at 165 Gy3 EQD2, whereas the probability with bronchial tumor compression was 10% at 0 Gy3 and 20% at 58 Gy3 EQD2. The model showed good discrimination and calibration.CONCLUSIONS: Bronchial tumor compression is a strong predictor for grade-5 bleeding, and the most relevant dose parameter appears to be the dose to a small volume of the main and intermediate bronchi.
AB - PURPOSE: The expanded HILUS study showed that bronchial dose and bronchial tumor compression are risk factors for bronchopulmonary bleedings after stereotactic body radiation therapy of centrally located lung tumors. In the current analysis of the same cohort, the aim was to identify the dose-volume histogram (DVH) parameter that best predicts fatal bronchopulmonary bleeding and to develop a predictive model for this endpoint.METHODS AND MATERIALS: The HILUS cohort included 230 patients with 238 central targets treated with stereotactic body radiation therapy of 7 Gy × 8 to the periphery of the planning target volume, where 21 patients developed grade-5 bronchopulmonary bleeding. Cox regression-based normal-tissue complication probability models were developed, accounting for the dose to the main and intermediate bronchi and bronchial tumor compression. Three alternative DVH parameters were explored: the dose to a certain volume (Dv), the volume receiving a certain dose (Vd), and the equivalent uniform dose. Internal validation was performed with the bootstrap method.RESULTS: The best fits of the bivariable normal-tissue complication probability models included bronchial tumor compression in combination with the DVH parameters of D0.31 cm3, V82Gy,EQD2 (equivalent dose in 2-Gy fractions), and equivalent uniform dose with n = 0.024, respectively. This indicates that a high dose to a small volume may lead to grade-5 bronchopulmonary bleeding. The probability of fatal bleeding at 2 years without bronchial tumor compression was 10% for a D0.31 cm3 of 107 Gy3 EQD2, and 20% at 165 Gy3 EQD2, whereas the probability with bronchial tumor compression was 10% at 0 Gy3 and 20% at 58 Gy3 EQD2. The model showed good discrimination and calibration.CONCLUSIONS: Bronchial tumor compression is a strong predictor for grade-5 bleeding, and the most relevant dose parameter appears to be the dose to a small volume of the main and intermediate bronchi.
U2 - 10.1016/j.ijrobp.2025.12.007
DO - 10.1016/j.ijrobp.2025.12.007
M3 - Journal article
C2 - 41532892
SN - 0360-3016
JO - International journal of radiation oncology, biology, physics
JF - International journal of radiation oncology, biology, physics
ER -