Expanded HILUS Trial: A Pooled Analysis of Risk Factors for Toxicity From Stereotactic Body Radiation Therapy of Central and Ultracentral Lung Tumors

Research output: Contribution to journalJournal articleResearchpeer-review

  • Sara Lindberg
  • Vitali Grozman
  • Kristin Karlsson
  • Eva Onjukka
  • Elias Lindbäck
  • Karam Al Jirf
  • Ingmar Lax
  • Peter Wersäll
  • Azza Ahmed Khalil
  • Ditte Sloth Møller
  • Lone Hoffmann
  • Marianne Marquard Knap
  • Jan Nyman
  • Ninni Drugge
  • Per Bergström
  • Jörgen Olofsson
  • Lotte Victoria Rogg
  • Rebecca Knoph Hagen
  • Anne Sofie Frøland
  • Christina Ramberg
  • Charlotte Kristiansen
  • Stefan Starup Jeppesen
  • Tine Bjørn Nielsen
  • Britta Lödén
  • Hans Olov Rosenbrand
  • Silke Engelholm
  • André Haraldsson
  • Charlotte Billiet
  • Rolf Lewensohn
  • Karin Lindberg

Purpose: Stereotactic body radiation therapy for tumors near the central airways implies high-grade toxic effects, as concluded from the HILUS trial. However, the small sample size and relatively few events limited the statistical power of the study. We therefore pooled data from the prospective HILUS trial with retrospective data from patients in the Nordic countries treated outside the prospective study to evaluate toxicity and risk factors for high-grade toxic effects. Methods and Materials: All patients were treated with 56 Gy in 8 fractions. Tumors within 2 cm of the trachea, the mainstem bronchi, the intermediate bronchus, or the lobar bronchi were included. The primary endpoint was toxicity, and the secondary endpoints were local control and overall survival. Clinical and dosimetric risk factors were analyzed for treatment-related fatal toxicity in univariable and multivariable Cox regression analyses. Results: Of 230 patients evaluated, grade 5 toxicity developed in 30 patients (13%), of whom 20 patients had fatal bronchopulmonary bleeding. The multivariable analysis revealed tumor compression of the tracheobronchial tree and maximum dose to the mainstem or intermediate bronchus as significant risk factors for grade 5 bleeding and grade 5 toxicity. The 3-year local control and overall survival rates were 84% (95% CI, 80%-90%) and 40% (95% CI, 34%-47%), respectively. Conclusions: Tumor compression of the tracheobronchial tree and high maximum dose to the mainstem or intermediate bronchus increase the risk of fatal toxicity after stereotactic body radiation therapy in 8 fractions for central lung tumors. Similar dose constraints should be applied to the intermediate bronchus as to the mainstem bronchi.

Original languageEnglish
JournalInternational Journal of Radiation Oncology Biology Physics
Issue number5
Pages (from-to)1222-1231
Number of pages10
Publication statusPublished - 2023

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