Patient selection, inter-fraction plan robustness and reduction of toxicity risk with deep inspiration breath hold in intensity-modulated radiotherapy of locally advanced non-small cell lung cancer

Kristine Fjellanger; Linda Rossi; Ben J M Heijmen; Helge Egil Seime Pettersen; Inger Marie Sandvik; Sebastiaan Breedveld; Turid Husevåg Sulen; Liv Bolstad Hysing

doi:10.3389/fonc.2022.966134

Patient selection, inter-fraction plan robustness and reduction of toxicity risk with deep inspiration breath hold in intensity-modulated radiotherapy of locally advanced non-small cell lung cancer

Front Oncol. 2022 Aug 30:12:966134. doi: 10.3389/fonc.2022.966134. eCollection 2022.

Authors

Kristine Fjellanger^{1

2}, Linda Rossi³, Ben J M Heijmen³, Helge Egil Seime Pettersen¹, Inger Marie Sandvik¹, Sebastiaan Breedveld³, Turid Husevåg Sulen¹, Liv Bolstad Hysing^{1

2}

Affiliations

¹ Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway.
² Institute of Physics and Technology, University of Bergen, Bergen, Norway.
³ Department of Radiotherapy, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, Netherlands.

Abstract

Background: State-of-the-art radiotherapy of locally advanced non-small cell lung cancer (LA-NSCLC) is performed with intensity-modulation during free breathing (FB). Previous studies have found encouraging geometric reproducibility and patient compliance of deep inspiration breath hold (DIBH) radiotherapy for LA-NSCLC patients. However, dosimetric comparisons of DIBH with FB are sparse, and DIBH is not routinely used for this patient group. The objective of this simulation study was therefore to compare DIBH and FB in a prospective cohort of LA-NSCLC patients treated with intensity-modulated radiotherapy (IMRT).

Methods: For 38 LA-NSCLC patients, 4DCTs and DIBH CTs were acquired for treatment planning and during the first and third week of radiotherapy treatment. Using automated planning, one FB and one DIBH IMRT plan were generated for each patient. FB and DIBH was compared in terms of dosimetric parameters and NTCP. The treatment plans were recalculated on the repeat CTs to evaluate robustness. Correlations between ΔNTCPs and patient characteristics that could potentially predict the benefit of DIBH were explored.

Results: DIBH reduced the median D_mean to the lungs and heart by 1.4 Gy and 1.1 Gy, respectively. This translated into reductions in NTCP for radiation pneumonitis grade ≥2 from 20.3% to 18.3%, and for 2-year mortality from 51.4% to 50.3%. The organ at risk sparing with DIBH remained significant in week 1 and week 3 of treatment, and the robustness of the target coverage was similar for FB and DIBH. While the risk of radiation pneumonitis was consistently reduced with DIBH regardless of patient characteristics, the ability to reduce the risk of 2-year mortality was evident among patients with upper and left lower lobe tumors but not right lower lobe tumors.

Conclusion: Compared to FB, DIBH allowed for smaller target volumes and similar target coverage. DIBH reduced the lung and heart dose, as well as the risk of radiation pneumonitis and 2-year mortality, for 92% and 74% of LA-NSCLC patients, respectively. However, the advantages varied considerably between patients, and the ability to reduce the risk of 2-year mortality was dependent on tumor location. Evaluation of repeat CTs showed similar robustness of the dose distributions with each technique.

Keywords: Deep inspiration breath hold (DIBH); autoplanning; gating; iCE; lung cancer radiotherapy; normal tissue complication probability (NTCP); radiation toxicity; radiotherapy robustness.