Long-term clinical safety of high-dose proton radiotherapy delivered with pencil beam scanning technique for extracranial chordomas and chondrosarcomas in adult patients: Clinical evidence of spinal cord tolerance

Publication date: Available online 4 September 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Sonja Stieb, James W. Snider, Lorenzo Placidi, Ulrike Kliebsch, Anthony J. Lomax, Ralf A. Schneider, Damien C. Weber
Purpose/ObjectivesTo assess the radiation dose tolerance of the spinal cord, we reviewed our institutional experience regarding the incidence of radiation-induced spinal cord toxicity following high dose, pencil beam scanning proton therapy (PBSPT).Materials/MethodsSeventy-six patients (median age, 53 years; range: 23–79), treated for spinal chordoma (n=55) or chondrosarcoma (n=21) met the following criteria and were retrospectively analyzed: PBSPT only, no re-irradiation or concomitant chemotherapy, maximum dose (Dmax) to the spinal cord of ≥45 Gy(RBE), ≥18 years of age, and follow-up of ≥12 months. The delivered dose was 59.4–75.2 Gy(RBE) (median, 73.9) delivered with conventional fractionation between 2000–2014. The Dmax, D2%, V40–V60 of the surface (sSC) and center (cSC) of the spinal cord were recorded. Toxicity was scored according to the Common Toxicity Criteria of Adverse Events (CTCAE v4.03).ResultsMedian follow-up was 65.5 months (range, 13–173). Patients received a mean Dmax and D2% to the sSC of 59.0 (median 58.7, range: 48.3 – 75.9), and 55.3 Gy(RBE) (median, 52.7, range: 43.1 – 73.8), respectively. The corresponding values for the cSC were 52.3 (median, 52.7, range: 32.3 – 73.3) and 51.1 Gy(RBE) (median, 52.0, range: 25.3 – 73.1), respectively. Four patients (5%) developed acute radiation-induced neurotoxicity (G1, n=1; G2, n=3). Twelve patients (16%) experienced late neurologic toxicities (G1, n=7; G2, n=4; G4, n=1). One patient with a history of pre-PBSPT symptomatic spinal cord compression redeveloped tetraplegia (G4) after receiving a Dmax of 57.8 Gy(RBE) to the sSC and 54.1 Gy(RBE) to the cSC. No significant correlation was found between sSC Dmax and D2%, cSC Dmax and D2%, or the length of CTV and toxicity.ConclusionsHigh-dose conformal PBSPT may be delivered safely in close proximity to the spinal cord with minimal neurotoxicity. Dose constraints of 64 Gy(RBE) as D2% for the sSC and 54 Gy(RBE) for the cSC appear appropriate for clinical use.

Teaser

Limited clinical data to define the radiotherapy tolerance of the spinal cord are available to clinicians. To add further clarity, we retrospectively evaluated our patients treated with proton therapy only for spinal chordomas and chondrosarcomas, who received a spinal cord dose in excess of 45 Gy(RBE) with special regard to neurotoxicity. Radiation doses reaching 64 Gy(RBE) to the surface of the spinal cord were associated with limited toxicity, defining this cut-off dose level as a safe threshold for appropriate clinical use.


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