Comparing Different Planning Strategies for Pencil Beam Scanning Carbon Ion Radiotherapy for Stage I Peripheral Non-Small Lung Cancer: Toward Optimized Clinical Decision-Making.

Abstract

To identify the optimal planning strategy for pencil beam scanning carbon-ion radiotherapy (CIRT) in stage I peripheral non-small cell lung cancer (NSCLC), including ground-glass opacity (GGO) and solid lesions. Thirty patients (15 GGO, 15 solid) receiving 8 Gy (RBE) × 9 fractions were analyzed. The clinical target volume (CTV) was defined as a 7 mm isotropic expansion of the internal gross tumor volume. Eight plans per patient were generated by combining three strategies: margin expansion (ME, CTV+7 mm), density override (DO), and robust optimization (RO). The accumulated deformed dose was calculated from two 4-dimensional quality assurance CTs (QACTs, pre- and mid-CIRT, weighted 5:4). Target coverage was assessed by the percentage volume of CTV receiving ≥ 95% prescription dose (CTV V95%); ipsilateral lung (excluding internal gross tumor volume) dose by mean lung dose (MLD) and the percentage of the lung volume receiving ≥ x Gy (RBE) (Vx, V5-V70). Range and setup uncertainties were assessed by applying ±3.5% stopping power variations and 3-mm translational shifts in six cardinal directions, respectively, with accumulated doses generated using the same workflow. All single strategies improved CTV V95% but increased lung dose. DO increased CTV V95% by 3.3-4.1% with minimal MLD increase of 0.15-0.92 Gy (RBE). RO increased CTV V95% by 4.8-5.1% with a moderate MLD increase of 1.77-1.79 Gy (RBE). ME yielded similar CTV gains but the highest MLD increase of 3.78-4.86 Gy (RBE). For GGOs, CTV+RO provided adequate coverage with the lowest lung dose. For solid tumors, CTV+RO+DO achieved near-complete coverage with improved consistency (range: 92.8-100% vs 85.2-100%) and a minimal additional MLD of ∼0.15 Gy (RBE). With range and setup uncertainties, results remained consistent with nominal conditions when RO was applied. In the absence of RO, the addition of DO to CTV+ME reduced the risk of target underdosage for both GGO and solid tumors at a cost of increased MLD of (-0.08)-0.53 Gy (RBE). This study provides quantitative data for evidence-based planning strategy selection in stage I peripheral NSCLC receiving CIRT. Without RO, larger margin (CTV+ME) is recommended; DO is advised for solid tumors and may also benefit GGOs under uncertainty. With RO, a smaller margin (CTV) is sufficient, and DO remains valuable for solid tumors.