Comparison of Intensity Modulated Radiation Therapy, Adaptive Radiation Therapy, Proton Radiation Therapy, and Adaptive Proton Radiation Therapy for Small Cell Lung Cancer

Abstract

Proton radiation therapy for non-small cell lung cancer (NSCLC) can minimize radiation dose to adjacent organs at risk (OARs), which can potentially reduce patient (pt) morbidity. Although early data suggests promising outcomes with protons in NSCLC, no data exists for SCLC, perhaps due to concerns that rapid tumor volume changes during proton therapy could lead to loss of plan validity and overdosing of OARs. This study compares non-adaptive intensity-modulated radiation therapy (IMRT), adaptive IMRT (AIMRT), non-adaptive proton therapy (PBT) and adaptive proton therapy (APBT) for SCLC. Seven consecutive pts with limited-stage SCLC enrolled on IRB-approved adaptive imaging protocols from January 2010-September 2012 treated with twice daily photon radiation therapy to 45 Gy in 30 fractions over 3 weeks were analyzed. Pts underwent repeat CT imaging after their first (10 fractions) and second (20 fractions) weeks of treatment. Dosimetric differences between IMRT, AIMRT, PBT and APBT were quantified (n = 28 plans). Adaptive plans treated based on the initial simulation CT scan to 15 Gy, first re-imaging CT to 30 Gy and second re-imaging CT to 45 Gy. All 3 CT data sets were contoured for each pt. Friedman test was used for non-parametric dependent multi-group analysis of a small-sized population. Wilcoxon signed rank sum testing was used subsequently for non-parametric dependent pairwise comparisons. All plans provided comparable target volume coverage. Numerically lower esophageal mean (17.1 Gy, 15.7 Gy, and 14.4 Gy) and V30 (30.6%, 29.0%, and 26.5%) doses for AIMRT, PBT and APBT were not significantly different from each other but were improved over IMRT (18.2 Gy, 33.2%). Compared with IMRT, AIMRT also lowered the ipsilateral brachial plexus maximum dose (Dmax) (p = 0.02). Compared to IMRT and AIMRT, PBT significantly lowered lung mean (p = 0.03 and 0.04, respectively) and V5 (both p = 0.02), heart mean (p = 0.03, p = 0.02) and doses received by 1/3 and 2/3 of the heart (all p ≤ 0.02). PBT also trended to lower the ipsilateral brachial plexus Dmax (p = 0.06) compared with IMRT. In addition to lower lung and heart doses, APBT lowered the ipsilateral (IMRT p = 0.02, AIMRT p = 0.05) and contralateral (AIMPT p = 0.02) brachial plexus Dmax. APBT only improved cord Dmax (29.3 Gy vs 26.7 Gy, p = 0.02) over PBT. Lung V20 was similar across all plans. Proton therapy maintained optimal tumor coverage while significantly reducing dose to OARs compared with photon plans and should be considered for SCLC. Adaptive planning provided more limited dosimetric benefit. Based on this study, we will begin a prospective clinical trial treating limit-staged SCLC pts with proton therapy using adaptive planning as necessary based on weekly verification scans.