Long-term Results of a Dose Searching Trial in Chordomas and Chondrosarcomas of the Skull Base and Cervical Spine

Article Outline

• Purpose/Objective(s)
• Materials/Methods
• Results
• Conclusions
• Copyright

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Purpose/Objective(s) 

To report a prospective randomized Phase I/II dose searching trial in adult patients with chordomas and chondrosarcomas of the skull base and cervical spine treated with high dose, 3D-conformal fractionated proton-photon therapy.

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Materials/Methods 

A prospective randomized Phase I/II dose searching trial in adult patients with chordomas (CH) and chondrosarcomas (CSA) of the skull base (SB) and cervical spine (CS) enrolled 105 patients between February 1987 and April 1993. Median patient age was 41 y (18-79 y). There were 55 males and 50 females. 56 patients had CH, and 49 had CSA. 93 patients had SB tumors (89%) and 12 (11%) had CS tumors. Median follow-up was 16.7 y (range 4.5 - 20.3 y). Proton treatment was given at the Harvard Cyclotron Laboratory in Cambridge, MA. ≤30% of the dose was given with photons at MGH. Daily dose was 1.92 CGE (CGE = proton Gy x RBE 1.1), and 1.8 Gy for protons and photons, respectively. Patients were randomized to either a lower dose (70.2 CGE, LD) or a higher dose (76 CGE, HD) in 37 or 40 fractions, respectively. The defined tumor volume received a non-homogeneous dose in all patients, since dose constraints for adjacent critical structures were lower then the prescribed tumor dose. End points were patient survival and tumor progression by imaging studies or histology.

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Results 

Fifty patients died, with median overall survival being 15.1 y. Overall survival for all patients at 5, 10, and 15 y was 81%, 61%, and 57% for the LD group, and 81%, 55%, and 45% for the HD group, respectively (p = 0.465). There were 23 deaths in the LD group, occurring between 7 m and 15.1 y. Median survival was not reached in the LD group. The 27 deaths in the HD group occurred at a median time of 10.5 y (5 m - 13.6 y). Treatment failure was documented in 55 patients, 25 in the LD and 30 in the HD groups. Median time to failure was 11.9 y (5 m - 15.1 y) in all patients, and was 16.8 y in the LD and 9.0 y in the HD group. Except for improved failure-free survival (FFS) in LD CSA SB patients relative to HD CSA SB patients (FFS at 5, 10, and 15 y was 94%, 89%, and 89% vs. 85%, 67%, and 58%, respectively, p = 0.045), there were no significant differences in outcome between the LD and the HD groups, when analyzed by histology and gender.

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Conclusions 

This trial did not demonstrate superiority of either dose level studied for the treatment of SB CH. FFS was better in SB CSA patients receiving the lower dose. Because of low patient numbers, no conclusion were possible regarding either dose level for patients with CS tumors of either histology. The protocol was modified in April 1993, and an analysis of patients randomized since then is underway.