Hypoxia-targeted RBE and OER weighted dose optimization for carbon ion therapy in lung cancer

Background Hypoxia, prevalent in solid tumors including lung cancer, is linked to treatment resistance and poor outcomes. This study evaluates the RBE- and OER-weighted dose (ROWD) optimization framework for carbon ion radiotherapy, comparing its performance with conventional intensity-modulated carbon ion radiotherapy (IMCT) plans. Methods ¹⁸F-FMISO PET/CT images from 13 lung cancer patients were retrospectively analyzed to design hypoxia-guided ROWD plans. Feasibility was assessed by comparing dose-volume histogram (DVH) metrics, physical dose distributions, dose-averaged linear energy transfer (LET_d), tumor control probability (TCP) and normal tissue complication probability (NTCP) between ROWD optimization and IMCT plans. All statistical analyses employed the Wilcoxon signed-rank test for paired comparisons. Results The ROWD optimization achieved over 95% prescription dose coverage in the planning gross tumor volume (PGTV) while constraining doses to organs-at-risk (OARs) below tolerance limits, even in hypoxic regions. Compared with IMCT, ROWD improved physical dose distribution in hypoxic tumor volumes (HTV), with minimal alteration in LET_d. For the conventional IMCT plans, hypoxia reduced the average TCP in HTV from 76.15% (normoxic baseline) to 72.50%. In contrast, the ROWD optimization plans restored the TCP under hypoxic conditions to 76.20%, matching normoxic benchmark levels. Moreover, the ROWD optimization plans maintained similar NTCP values for OARs while decreasing the NTCP for pulmonary complications from 2.01% to 1.34%. Conclusions Thus, our study demonstrates the significant potential of the ROWD optimization technique as an improved approach to enhance the efficacy of carbon ion radiotherapy for lung cancer with hypoxic regions.