Radiation-Induced Lung Density Changes on CT Scan for NSCLC: No Impact of Dose-Escalation Level or Volume

Abstract

Dose-escalation for patients with non-small cell lung cancer (NSCLC) in the positron emission tomography (PET)-boost trial (NCT01024829) exposes portions of normal lung tissue to high radiation doses. The relationship between lung parenchyma dose and density changes on computed tomography (CT) was analyzed. The CT scans of 59 patients with stage IB to III NSCLC, randomized between a boost to the whole primary tumor and an integrated boost to its 50% SUVmax (maximum standardized uptake value) volume. Patients were treated with concurrent or sequential chemoradiation or radiation only. Deformable registration mapped the 3-month follow-up CT to the planning CT. Hounsfield unit differences (ΔHU) were extracted to assess lung parenchyma density changes. Equivalent dose in 2 Gy fractions (EQD2)-ΔHU response was described sigmoidally, and regional response variation was studied by polar analysis. Prognostic factors of ΔHU were obtained through generalized linear modeling. Saturation of ΔHU was observed above 60Gy. No interaction was found between boost dose distribution (D1cc and V70Gy) and ΔHU at lower doses. ΔHU was lowest peripherally from the tumor and peaked posteriorly at 3cm from the tumor border (3.1 HU/Gy). Right lung location was an independent risk factor for ΔHU (P=.02). No apparent increase of lung density changes at 3-month follow-up was observed above 60Gy EQD2 for patients with NSCLC treated with (concurrent or sequential chemo) radiation. The mild response observed peripherally in the lung parenchyma might be exploited in plan optimization routines minimizing lung damage.