Purpose The effect of a close surgical margin (CSM) due to the preservation of vital structures in limb salvage surgery (LSS) for high-grade osteosarcoma (OS) is still controversial. This article aimed to study the prognosis of LSS with a close peri-neurovascular margin (PNM). Methods We retrospectively reviewed 196 cases that underwent LSS from January 2010 to December 2015 at our institution, of which 88 involved high-grade extremity osteosarcoma with a potential risk of an “inadequate” wide margin (15 mm) according to the Enneking classification system. Data on surgical and tumor-related factors were collected together with the width of the PNM. Survival analysis and machine learning (ML) algorithms with cross-validation were used to construct the prognostic model for oncological outcomes after LSS. Results PNM was associated with a higher local recurrence (LR) rate, while greater tumor size was a risk factor for metastasis and overall survival in the multivariate Cox regression model. Using ML algorithms, a decision tree (DT) model was constructed, indicating that a closer PNM was significantly correlated with higher LR-free survival only when the tumor size was less, but not greater, than 31.6% of the limb (with a significant interaction effect). Interestingly, a conventional survival analysis and receiver operating characteristic plot confirmed the robust interaction effect of PNM and tumor size on not only LR, but also metastasis and overall survival, with an even larger effect size than that of each factor alone. Conclusion The prognostic effect of CSM in high-grade osteosarcoma is dependent on the tumor size. We found that a close PNM ( 2.4 mm) in LSS due to the preservation of critical structures is a risk factor for LR and survival in patients with small-sized osteosarcomas. For a large-sized tumor, the prognosis is unsatisfactory regardless of the state of the CSM. Further studies are needed to explore the mechanisms underlying such heterogeneity in LSS.
Shi et al. (Fri,) studied this question.