Dose-averaged linear energy transfer within the gross tumor volume of non-small-cell lung cancer affects the local control in carbon-ion radiotherapy

Abstract

Background and purpose

High linear energy transfer (LET) radiation exhibits stronger tumor-killing effect. However, the correlation between LET and the therapeutic efficacy in Carbon-ion radiotherapy (CIRT) for locally advanced non-small-cell lung cancer (LA-NSCLC) is currently not clear. This study aimed to investigate the relationship between the dose-averaged LET (${\mathrm{LET}}_d$) distribution within tumor and local recurrence for LA-NSCLC treated with CIRT.

Methods and materials

An analysis of 62 consecutive patients with LA-NSCLC who underwent CIRT from 2018 to 2022 was conducted. The ${\mathrm{LET}}_d$ distribution was calculated based on their treated plans, and the correlation between local recurrence and ${\mathrm{LET}}_d$, relative biological effectiveness (RBE)-weighted doses ($D_{\mathrm{RBE}}$) and clinical factors was investigated. Receiver operating characteristic (ROC) curve, log-rank test, and Cox regression analysis were performed based on that.

Results

16 patients were defined as local recurrence. Overall survival (OS) and local control (LC) at 24 months were 76.9 % and 73.2 %, respectively. The mean ${\mathrm{LET}}_d$ in internal gross tumor volume (iGTV) in the local recurrence group was 48.7 keV/µm, significantly lower than the mean ${\mathrm{LET}}_d$ of 53.2 keV/µm in the local control group (p = 0.016). No significant difference was observed in $D_{\mathrm{RBE}}$ between the local recurrence and local control groups. ROC curve analysis indicated that a percentage of 88 % of volume in iGTV receiving at least 40 keV/µm ($V_{40keV/\mu m}$) is the optimal threshold for predicting local recurrence (Area under curve (AUC) = 0.7636). The log-rank test and Cox regression analysis revealed that the ${\mathrm{LET}}_d$ value covering 98 % volume of iGTV (${\mathrm{LET}}_{d}98\%$) was a significant risk factor for LC (p = 0.020).

Conclusions

Our study revealed an association between ${\mathrm{LET}}_d$ distribution and local recurrence in patients with LA-NSCLC. These findings suggest that lower ${\mathrm{LET}}_d$ may increase the probability of local recurrence. We suggest that ${\mathrm{LET}}_d$ distribution within iGTV should be routinely assessed in CIRT for lung cancer.