Pathological fractures in predicting clinical outcomes for patients with osteosarcoma

The present study examined the prognostic importance of pathologic fractures for osteosarcoma patients. The patients of both groups were comparable in age, tumor stage and size, local recurrence, and necrosis rate. Our results revealed no significant difference in the OS, PFS, 5-year, and 10-year survival between the two groups. The findings are similar to previous studies indicating that pathological fractures in osteosarcoma do not adversely affect survival [9, 13], unless the presence of lung metastasis. Furthermore, our study also supports the contention that proper evaluation of preoperative imaging, following by appropriate chemotherapy regimens, and surgical approaches can result in no difference in tumor necrosis rates or the risk of local recurrence between patients with fractures and without fracture, suggesting that an effective multidisciplinary team can provide consistent outcomes in spite of the management of fractured patients is more difficult.

In this study, lung metastasis was a significant predictor for fracture and one of significant risk factors for death for the entire study population. Comparing to the incidence rates of lung metastasis in osteosarcoma patients with fractures in previous studies, 19.3% [17] or 23% [11], this study clearly demonstrated a much higher proportion of patients with fractures had lung metastases, with 50% in patients with fractures and 32% in those without fracture. Although a pathological fracture per se was not a significant predictor for survival, lung metastases and fractures could promote the progression of osteosarcoma and led to an inferior survival in fractured patients. Metastasis at diagnosis is the only widely accepted prognostic factor [2]. The contemporary treatment regimens can result in up to 70% survival for patients with localized osteosarcoma of the extremity. But the survival estimates for patients with metastatic disease were much worse, ranging from 8.3% for 5-year [25], 23% for 5-year [26], 30% for 4-year [27], 53.3% for 5-year [28], to 55% for 2-year [29]. However, these studies varied widely in many variables, making comparisons impossible. The long-term survival data were neither reported.

Local recurrence can be a result of poor response to chemotherapy or inadequate surgical margins [30, 31]. The rates of local recurrence following osteosarcoma surgery generally ranged 4–10% [32–34]. In our study, the rates were relatively higher (21.8% and 23.5%), but lower than a more recent study reporting the rates in patients with adequate (30.5%) and inadequate (38%) surgical margins, and in which, 15% patients had pathological fractures [35]. Consistent with previous observations [32, 35, 36], local recurrence was correlated with poor prognosis in terms of survival in the present study. To determine the impact of surgical margin on the development of local recurrence, further investigation remains necessary.

Tumor size has been considered as an important risk factor for osteosarcoma patients [15] and a potential confounding factor associated with poor prognosis for those with fractures [13, 37]. Increased tumor volume might result in poor response to chemotherapy [38]; however, other studies did not find an influence of tumor size [11]. In our series, tumor size was not significantly correlated with OS for all patients, patients with or without fractures (data not shown). Moreover, we found that fractured female patients had a better survival than male counterparts in exploratory subgroup analyses, which has never been reported. We also analyzed the 10-year survival rates that were generally lack in most studies. Although the data of this study was relevant to both pediatric and adult patients, the sample size remained small so that the exploratory analyses for subgroups were limited.