The HILUS-Trial—a Prospective Nordic Multicenter Phase 2 Study of Ultracentral Lung Tumors Treated With Stereotactic Body Radiotherapy

Karin Lindberg*, Vitali Grozman, Kristin Karlsson, Sara Lindberg, Ingmar Lax, Peter Wersäll, Gitte Fredberg Persson, Mirjana Josipovic, Azza Ahmed Khalil, Ditte Sloth Moeller, Jan Nyman, Ninni Drugge, Per Bergström, Jörgen Olofsson, Lotte Victoria Rogg, Christina Ramberg, Charlotte Kristiansen, Stefan Starup Jeppesen, Tine Bjørn Nielsen, Britta LödénHans Olov Rosenbrand, Silke Engelholm, André Haraldsson, Charlotte Billiet, Rolf Lewensohn

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

2 Citations (Scopus)
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Introduction: Stereotactic body radiation therapy of thoracic tumors close to the central airways implies risk of severe toxicity. We report a prospective multicenter phase 2 trial for tumors located less than or equal to 1 cm from the proximal bronchial tree with primary end point of local control and secondary end point of toxicity. Methods: Stereotactic body radiation therapy with 7 Gy × 8 was prescribed to the 67% isodose encompassing the planning target volume. The patients were stratified to group A (tumors ≤ 1 cm from the main bronchi and trachea) or group B (all other tumors). Risk factors for treatment-related death were tested in univariate analysis, and a logistic regression model was developed for fatal bronchopulmonary bleeding versus dose to the main bronchi and trachea. Results: A total of 65 patients (group A/group B, n = 39/26) were evaluated. The median distance between the tumor and the proximal bronchial tree was 0 mm (0–10 mm). The 2-year local control was 83%. Grade 3 to 5 toxicity was noted in 22 patients, including 10 cases of treatment-related death (bronchopulmonary hemorrhage, n = 8; pneumonitis, n = 1; fistula, n = 1). Dose to the combined structure main bronchi and trachea and tumor distance to the main bronchi were important risk factors. Dose modeling revealed minimum dose to the “hottest” 0.2 cc to the structure main bronchi and trachea as the strongest predictor for lethal bronchopulmonary hemorrhage. Conclusions: On the basis of the presented data, 7 Gy × 8, prescribed to the planning target volume-encompassing isodose, should not be used for tumors located within 1 cm from the main bronchi and trachea. Group B-type tumors may be considered for the treatment on the basis of an individual risk-benefit assessment and a maximum dose to the main bronchi and trachea in the order of 70 to 80 Gy (equivalent dose in 2 Gy fractions).

Original languageEnglish
JournalJournal of Thoracic Oncology
Pages (from-to)1200-1210
Number of pages11
Publication statusPublished - Jul 2021


  • Central
  • Lung tumors
  • SBRT
  • Stereotactic
  • Ultracentral
  • RISK
  • 60 GY


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