Dosimetric analysis of local failures in skull-base chordoma and chondrosarcoma following pencil beam scanning proton therapy

BACKGROUND: Despite combined modality treatment involving surgery and radiotherapy, a relevant proportion of skull-base chordoma and chondrosarcoma patients develop a local recurrence (LR). This study aims to analyze patterns of recurrence and correlate LR with a detailed dosimetric analysis. METHODS: 222 patients were treated with proton radiotherapy for chordoma (n = 151) and chondrosarcoma (n = 71) at the PSI between 1998 and 2012. All patients underwent surgery, followed by pencil-beam scanning proton therapy to a mean dose of 72.5 ± 2.2Gy(RBE). A retrospective patterns of recurrence analysis was performed: LR were contoured on follow-up MRI, registered with planning-imaging and the overlap with initial target structures (GTV, PTV(high-dose), PTV(low-dose)) was calculated. DVH parameters of planning structures and recurrences were calculated and correlated with LR using univariate and multivariate cox regression. RESULTS: After a median follow-up of 50 months, 35 (16%) LR were observed. Follow-up MRI imaging was available for 27 (77%) of these recurring patients. Only one (3.7%) recurrence was located completely outside the initial PTV (surgical pathway recurrence). The mean proportions of LR covered by the initial target structures were 48% (range 0–86%) for the GTV, 70% (range 0–100%) for PTV(high) and 83% (range 0–100%) for PTV(low). In the univariate analysis, the following DVH parameters were significantly associated with LR: GTV(V < 66Gy(RBE), p = 0.01), GTV(volume, p = 0.02), PTV(high)(max, p = 0.02), PTV(high)(V < 66Gy(RBE), p = 0.03), PTV(high)(V < 59Gy(RBE), p = 0.02), PTV(high)(volume, p = 0.01) and GTV(D95, p = 0.05). In the multivariate analysis, only histology (chordoma vs. chondrosarcoma, p = 0.01), PTV(high)(volume, p = 0.05) and GTV(V < 66Gy(RBE), p = 0.02) were independent prognostic factors for LR. CONCLUSION: This study identified DVH parameters, which are associated with the risk of local recurrence after proton therapy using pencil-beam scanning for patients with skull-base chordoma and chondrosarcoma.