Management of Chordoma and Chondrosarcoma with Fractionated Stereotactic Radiotherapy

Abstract

Objective: To evaluate the efficacy and toxicity of fractionated stereotactic radiotherapy (FSRT) for chordoma and chondrosarcoma.

Methods: Twenty consecutive patients with a histopathologic diagnosis of chordoma (n = 16) or chondrosarcoma (n = 4) treated between 2010 and 2016 were retrospectively identified. All patients underwent FSRT in five fractions to a median dose of 37.5 Gy (range: 25-40 Gy) and followed with serial magnetic resonance imaging. Overall survival (OS), local recurrence-free survival (LRFS), and event-free survival (EFS) were estimated using the Kaplan-Meier method.

Results: With a median follow-up of 28 months after FSRT and 40 months after initial surgery, crude OS and LRFS were 90%. Nine patients (45%) reported grade 1-3 acute toxicity, and two patients (10%) experienced grade 4, 5 late toxicity. One patient previously treated with proton therapy died from radiation vasculopathy 9 months after FSRT. The use of FSRT for recurrent disease or in patients with prior radiation therapy was associated with significantly decreased EFS.

Conclusion: FSRT for chordoma and chondrosarcoma is associated with high rates of OS and local control. Although many patients experience acute toxicity, there is a low incidence of late toxicity or irreversible treatment related morbidity despite the frequency of prior radiotherapy in this population. FSRT is an effective adjuvant or salvage treatment for chordoma and chondrosarcoma.

Keywords: CyberKnife; chondrosarcoma; chordoma; fractionated stereotactic radiotherapy; stereotactic body radiotherapy.

Figures

Figure 1

Overall survival (OS) and local recurrence free survival in all patients. OS across all 20 patients shown relative to (A) time of fractionated stereotactic radiotherapy (FSRT) and (B) time of initial surgery or biopsy. Two deaths were reported during follow-up, the first 9 months after FSRT (11 months after surgery) for recurrent clival chordoma and the second 25 months after FSRT (59 months after surgery) in a patient with recurrent sacral chordoma. Local recurrence-free survival across all 20 patients shown relative to (C) time of FSRT and (D) time of initial surgery or biopsy revealed two local recurrences in the follow-up period. Median follow-up from time of FSRT was 28 months, and median follow-up from time of initial surgery/biopsy was 40 months.

Figure 2

Event-free survival in selected patient subgroups relative to time of fractionated stereotactic radiotherapy (FSRT). (A) When separating FSRT in the upfront (solid line) versus recurrent (dashed line) setting, a minority of patients (n = 5) received FSRT for recurrent disease, and this group encompassed all patients with significant events (3/5). (B) Considering prior history of radiation therapy (protons or EBRT) (n = 6), all patients with reported events (3/6) received radiation therapy before undergoing FSRT. (C) With respect to definitive (solid line) versus preoperative (dashed line) versus postoperative FSRT (dotted line), the majority of patients (n = 14) received FSRT in the postoperative setting, including all patients with significant events (4/14). (D) Based on anatomic site of the tumor, one local recurrence was in a sacral tumor (dashed line), and the second recurrence was in a tumor in the cervical spine (dotted line). For skull base tumors (black), one death but no local recurrences were observed. (E) With regard to histological subtype, the majority of patients were diagnosed with chordoma (n = 16, black line) compared to chondrosarcoma (n = 4, dashed), and all three events occurred in chordoma patients. Significant events were defined as tumor recurrence (local, regional, or distant) or death, and reported p-values are from the log-rank (Mantel–Cox) test.