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

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.

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 LET_d (minLET_d) in the range 37-55 keV/μm, in steps of 3 keV/μm. The optimal LET-optimized plan (LET_OPT) was the one maximizing LET_d, while adhering to clinical acceptability criteria. Reference and LET_OPT plans were compared through dose and LETd metrics (D , L to x% volume) for the GTV, clinical target volume (CTV), and organs at risk (OARs). The 7 held-out cases were optimized setting minLET_d to the average GTV L_98% of the investigation cohort. Both reference and LET_OPT plans were recalculated on re-evaluation CTs and compared.

GTV L_98% increased from (31.8 ± 2.5)keV/μm to (47.6 ± 3.1)keV/μm on the LET_OPT plans, while the fraction of GTV receiving over 50 keV/μm increased on average by 36% (p < 0.001), without affecting target coverage goals, or impacting LET_d and dose to OARs. The interfraction analysis showed no significant worsening with minLET_d set to 48 keV/μm.

LET_d optimization for large SC could boost the LET_d in the GTV without significantly compromising plan quality, potentially improving the therapeutic effects of CIRT for large radioresistant tumors.