R0/R1 Surgical Management of Primary Skull Base Osteosarcomas: Impact of Margin Status and Patterns of Relapse

Background: Primary skull base osteosarcomas are aggressive neoplasms characterized by extensive bony invasion and extracompartmental soft tissue extension that can pose as obstacles to achieving an oncologic resection. Overall management is further complicated by the relative paucity of data pertaining to the efficacy of surgery within the context of multimodality therapy.

Objective: The goal of this study was to identify the impact of margin status on tumor control rates and disease specific surgical in surgically treated primary osteosarcoma of the skull base.

Methods: A retrospective review was performed of 38 patients with high grade osteosarcoma who underwent a RO/R1 surgical resection (R0—gross-total resection with negative margins, R1—gross-total resection with positive margins). Data pertaining to patient demographics, diagnosis, previous treatments, treatments at our institution, patterns of relapse and survival were collected. Univariate log-rank and Cox regression analysis was performed to determine the impact of margin status on the progression free survival (primary outcome) and disease specific survival (secondary outcome).

Results: Previous treatments prior to presentation at our institution included: surgery (42%), chemotherapy (23.7%), radiation therapy (28.9%). R0 resection was achieved in 68% and R1 in 32% of the cohort. Over the study period, the following patterns of relapse were noted: local (9, 23.4%), distant (7 patients, 18.4%). When the entire cohort was assessed regardless of previous treatments, negative surgical margins had a near significant impact on progression free survival (PFS) (156.1 vs. 14.2 months, p = 0.07) and a significant impact on disease-specific survival (DSS) (157.8 vs. 31.2 months, p = 0.001). In controlling for previous treatments, in patients not previously treated with an osteosarcoma specific chemotherapy protocol, negative surgical margins had significant impact on PFS (173.7 vs. 13.7 months, p = 0.038) and DSS (163.1 vs. 26.8 months, p = 0.014). For radiation-naive patients, significant improvements in PFS (181.6 vs. 13.0 months, p = 0.05) and DSS (176.1 vs. 23.7 months, p = 0.014) were noted with negative margins.

Conclusion: Osteosarcoma of the skull base presents significant management challenges where both local and systemic disease progression is the cause of mortality. The ability to achieve a gross-total resection with negative margins significantly improves tumor control rates and survival in treatment naïve patients when performed within the context of multimodality therapy. A potential role for salvage surgery may exist in patients previously treated with radiation but not when previous osteosarcoma specific chemotherapy has failed. Further work is needed to determine optimal chemo- and radiation treatment strategies—especially in “high risk” patients with positive margins. This data represents the largest such series reported to date.