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preliminary chordoma carbon-ion LET

Multi-RBE LET optimization increased target LET by 29% in sacral chordoma

Multi-RBE carbon-ion optimization increased near-minimum GTV LET by 29.2% while maintaining conventional dose coverage and interfraction robustness.

RadOncToday · ·1 min read

KEY POINTS

  • The study reports the first 10 consecutive sacral chordoma patients treated at CNAO with a carbon-ion planning strategy combining two RBE models and explicit LET optimization. Nine patients were treatment-naïve and one had recurrent disease; none had received prior radiotherapy. Median GTV volume was a substantial 171.1 cm³, ranging up to 636.7 cm³.
  • Treatment used pencil-beam scanning and a 16-fraction sequential-boost strategy. The conventional benchmark plan was optimized with the Local Effect Model to 73.6 Gy(RBE), while the new workflow began with Microdosimetric Kinetic Model optimization to 67.2 Gy(RBE), iteratively ensured acceptability under both models, and then escalated minimum LET within the GTV.
  • The median LET optimization objective was 44 keV/μm. Near-minimum GTV LET, measured as L98%, increased by 29.2%, from 32.9 to 42.5 keV/μm. Median GTV LET also shifted upward, with L50% increasing from 39.4 to 46.4 keV/μm.
  • The benefit extended beyond LET. When conventional LEM-optimized plans were recalculated with MKM, 7 of 10 patients failed the D95% acceptance criterion for the low-risk target, while MKM D2% exceeded the clinical limit in all patients for both sequential treatment components. The multi-model plans met the predefined criteria under both RBE systems.
  • Importantly, LET escalation did not create a major robustness penalty. On re-evaluation CTs, target-coverage deviations remained <1.5%, and overall dose and LET deviations were below approximately 2% relative to the nominal plans.
  • Early clinical imaging showed tumor-volume reduction in 8 of 10 patients, classified as partial responses, while two had stable disease. These response data are extremely immature and cannot establish improved local control from LET escalation.
  • Toxicity was mostly grade 1–2 after accounting for baseline symptoms. One patient, who had the largest GTV at approximately 637 cm³, developed grade 3 motor-sensory neuropathy and urinary dysfunction. Longer follow-up is required particularly for sacral insufficiency fractures and late lumbosacral neuropathy.

CLINICAL TAKEAWAY

This is a genuine clinical implementation of something usually confined to planning studies: carbon-ion optimization that tries to remain acceptable under two biological-effect models while deliberately moving high LET into the tumor. It appears feasible and robust, but with only 10 patients and very early follow-up there is no evidence yet that the 29% LET increase translates into better local control.

SOURCE

International Journal of Radiation Oncology, Biology, Physics