Impact of adjuvant radiation therapy on outcomes in grade 2 conventional chondrosarcoma

OBJECTIVE: While histological subtype and grade are important for guiding treatment of skull base chondrosarcomas, the role of adjuvant radiation therapy (RT) and the optimal radiation modality for grade 2 conventional chondrosarcoma (cCS) are not well defined. The aim of this study was to further elucidate optimal treatment strategies for grade 2 cCS. METHODS: Multi-institutional data from the Skull Base Chondrosarcoma Consortium, including patient demographics, radiological features, and outcomes, were analyzed retrospectively. Clinical and radiological follow-up data were used to assess disease stability or progression after different treatments. The impact of RT on progression-free survival (PFS) was evaluated with an interaction model and a pairwise comparison. RESULTS: A total of 79 patients (44 female, mean age 47 years) with grade 2 cCS were identified, with a mean follow-up duration of 74.6 ± 67 months. The 10-year overall survival rate was 68%. Forty-four patients (56%) were treated with surgery followed by postoperative surveillance and 35 patients (44%) were treated with surgery and adjuvant RT. Gross-total resection (GTR) was achieved in 29 patients (36.7%), and adjuvant RT was most frequently used after subtotal resection (STR) (61%, 28/46). The prevailing RT technique used was proton beam RT (PBRT) (71%, n = 25). In terms of PFS, adjuvant RT significantly decreased the likelihood of disease progression (HR 0.26, 95% CI 0.10-0.65; p = 0.004). Adjuvant RT had significantly greater benefit after incomplete resection, with significant PFS improvement after incomplete resection (HR 3.73, 95% CI 1.24-11.1; p = 0.02) but only a nonsignificant positive trend toward benefit after GTR (HR 0.15, 95% CI 0.001-1.36; p = 0.105). While the interaction term (HR 1.36, 95% CI 0.12-191.05; p = 0.838) was not significant, the pairwise comparison between STR alone and STR+RT was significant (p = 0.008), demonstrating a clear impact of adjuvant RT in this subgroup. CONCLUSIONS: These findings suggest that in the setting of an incomplete resection, adjuvant RT is indicated to achieve optimal long-term tumor control rates. Surgery with subsequent close follow-up after complete resection in grade 2 cCS appears to be an acceptable decision, but more evidence is needed. The capacity of PBRT to concentrate higher radiation doses at the tumor site appears to be an important factor in local control.