Balancing benefits and limitations of linear energy transfer optimization in carbon ion radiotherapy for large sacral chordomas

Background and Purpose: A low linear energy transfer (LET) in the target can reduce the effectiveness of carbon ion radiotherapy (CIRT). This study aimed at exploring benefits and limitations of LET optimization for large sacral chordomas (SC) undergoing CIRT. Materials and Methods: Seventeen cases were used to tune LET-based optimization, and seven to independently test interfraction plan robustness. For each patient, a reference plan was optimized on biologically-weighted dose cost functions. For the first group, 7 LET-optimized plans were obtained by increasing the gross tumor volume (GTV) minimum LETd (minLETd) in the range 37-55 keV/mu m, in steps of 3 keV/mu m. The optimal LET-optimized plan (LETOPT) was the one maximizing LETd, while adhering to clinical acceptability criteria. Reference and LETOPT plans were compared through dose and LETd metrics (Dx, Lx to x% volume) for the GTV, clinical target volume (CTV), and organs at risk (OARs). The 7 held-out cases were optimized setting minLETd to the average GTV L98% of the investigation cohort. Both reference and LETOPT plans were recalculated on re-evaluation CTs and compared. Results: GTV L98% increased from (31.8 +/- 2.5)keV/mu m to (47.6 +/- 3.1)keV/mu m on the LETOPT plans, while the fraction of GTV receiving over 50 keV/mu m increased on average by 36% (p < 0.001), without affecting target coverage goals, or impacting LETd and dose to OARs. The interfraction analysis showed no significant worsening with minLETd set to 48 keV/m. Conclusion: LETd optimization for large SC could boost the LETd in the GTV without significantly compromising plan quality, potentially improving the therapeutic effects of CIRT for large radioresistant tumors.