Planning Strategy to Optimize the Dose-Averaged LET Distribution in Large Pelvic Sarcomas/Chordomas Treated with Carbon-Ion Radiotherapy

SIMPLE SUMMARY: Carbon-ion radiotherapy (CIRT) is a potentially curative treatment for unresectable pelvic sarcomas/chordomas. Tumor control remains suboptimal in large pelvic sarcomas/chordomas compared with the control of small tumors. We hypothesized that lower dose-averaged LET (LETd) distribution in the majority of large tumors could be one of the contributing factors for local relapse. The high-LETd region lies at the end of the beam range. As the tumor size increases, the volume of tumor covered by high LETd decreases. A statistically significant difference was observed in LETd distribution between small and large pelvic sarcomas/chordomas. To improve the high-LETd component in large tumors, LETd optimization using ‘distal patching’ was explored in a planning setting (not implemented clinically). Distal patching significantly increased (a) median LETd in the targets, (b) LETdmin in low-LETd regions of the targets, (c) the GTV fraction receiving LETd of ≥50 keV/µm, and (d) the high-LETd component in the central region of the GTV, without significant compromise in relative biological effectiveness (RBE)-weighted absorbed-dose (D(RBE)) distribution. ABSTRACT: To improve outcomes in large sarcomas/chordomas treated with CIRT, there has been recent interest in LET optimization. We evaluated 22 pelvic sarcoma/chordoma patients treated with CIRT [large: HD-CTV ≥ 250 cm(3) (n = 9), small: HD-CTV < 250 cm(3) (n = 13)], D(RBE|LEM-I) = 73.6 (70.4–73.6) Gy (RBE)/16 fractions, using the local effect model-I (LEM-I) optimization and modified-microdosimetric kinetic model (mMKM) recomputation. We observed that to improve high-LETd distribution in large tumors, at least 27 cm(3) (low-LETd region) of HD-CTV should receive LETd of ≥33 keV/µm (p < 0.05). Hence, LETd optimization using ‘distal patching’ was explored in a treatment planning setting (not implemented clinically yet). Distal-patching structures were created to stop beams 1–2 cm beyond the HD-PTV-midplane. These plans were reoptimized and D(RBE|LEM-I), D(RBE|mMKM), and LETd were recomputed. Distal patching increased (a) LETd50% in HD-CTV (from 38 ± 3.4 keV/µm to 47 ± 8.1 keV/µm), (b) LETdmin in low-LETd regions of the HD-CTV (from 32 ± 2.3 keV/µm to 36.2 ± 3.6 keV/µm), (c) the GTV fraction receiving LETd of ≥50 keV/µm, (from <10% to >50%) and (d) the high-LETd component in the central region of the GTV, without significant compromise in D(RBE) distribution. However, distal patching is sensitive to setup/range uncertainties, and efforts to ascertain robustness are underway, before routine clinical implementation.