Osteosarcoma is an aggressive bone

Osteosarcoma is an aggressive bone neoplasm arising from primitive transformed dihydrofolate reductase of mesenchymal origin. It was such a fatal disease that “months to metastasis” rather than actual survival time, was used to measure the outcomes of treatment in studies of early stage. In the 1950s, there was no optional therapy that could significantly increase the survival rate, with a 5-year survival rate of 22% [1]. However, with the aid of effective chemotherapeutic drugs the survival rate of osteosarcoma has been significantly improved since the late 1970s [2,3]. Recently, the gold standard of osteosarcoma chemotherapy have been based on around 5 drugs; high-dose methotrexate (HDMTX) with leucovorin rescue, doxorubicin (adriamycin), cisplatin, ifosfamide, and etoposide [4]. Combinations of these drugs, mostly in the form of neoadjuvant as well as adjuvant MAP, are the current management for osteosarcoma [5], and various chemotherapy protocols are still under investigation. The experience with radiotherapy is limited, as osteosarcoma is long considered resistant to applicable doses of radiation. However, recent data suggest that the combined approach of irradiation with chemotherapy may be useful in patients who have microscopic residual tumor foci following intralesional resection [6]. With the advent of effective neoadjuvant chemotherapy in the 1970s, limb salvage surgery (LSS) has been taken as a potential treatment for osteosarcoma [7,8]. Usually, LSS has functional and physiological advantages over traditional amputative procedures when combined with neoadjuvant or adjuvant chemotherapy [9]. It is now generally accepted that LSS is indicative for localized osteosarcoma, while surgical amputation is adopted for high malignancy osteosarcoma. However, there are still some surgeons holding the view that immediate and aggressive removal of the tumor will prevent the progression of fracture-induced disease, and consequently amputation is considered to be a better option for osteosarcoma patients with pathologic fracture [10–13]. Conflicting findings have been reported on the survival and function recovery between treatments of LSS and amputation in patients with osteosarcoma. Toward this end, a meta-analysis of published clinical trials was performed to compare the clinical efficacy of LSS and amputation treatments in terms of local recurrence, 5-year overall survival rate, and metastatic occurrence. Several studies have attempted similar meta-analysis [14]; however, the included studies were much smaller, and their scopes were restricted to specific therapies compared with this meta-analysis. Through more extensive osteosarcoma literature, this meta-analysis tries to give a comprehensive conclusion on the outcomes in osteosarcoma patients receiving LSS and amputation. Such information will help us determine the most appropriate osteosarcoma-treating method.
Material and methods
Results
Discussion With the improved efficacy of chemotherapy, the number of patients with osteosarcoma who received LSS instead of amputation has significantly increased recent years [33–37]. Moreover, LSS benefits not only malignant primary osteosarcoma patients, but also high-grade, localized osteosarcoma patients. However, there are substantial studies showing that the survival rate and local recurrence between LSS and amputation for osteosarcoma have been conflicting [25,38]. In this study, it was concluded that patients treated with LSS had a similar local recurrence and a lower metastasis occurrence compared with those treated with amputation, which was identical with that of Yin [14] but with more expansive literature included in our study. In addition, we found that 5-year overall survival rate of patients treated with LSS was higher than those treated with amputation. Therefore, our results provide more comprehensive evidence to support LSS for the treatment of osteosarcoma patients. In the meta-analysis of local recurrence of LSS vs. amputation for the treatment of osteosarcoma, there was no significant difference in the two surgery methods (OR: 1.03 with 95% CI ranging from 0.65 to 3.30; Z=0.14, P=0.89) (Table 3; Fig. 3). In five of 17 articles, the local recurrence rate in patients undergoing LSS was dramatically higher than those receiving amputation [15,19,23,25,29]. The sample sizes of these five studies were relatively small. Differently from these studies, other included studies revealed similar local recurrence rates between the two surgery methods. Moreover, in a study of Bacci et al. [17] with more than 500 samples investigated, local recurrence rates were found to be similar between LSS and amputation, which offered solid evidence to evaluate the local recurrence of LSS for the treatment of osteosarcoma. In this meta-analysis, the overall survival at 5 years was slightly better in those treated by LSS than those who had amputation(OR: 1.47 with 95% CI ranging from 1.10 to 1.97; Z=2.61, P<0.05)for treating osteosarcoma patients. Among the included studies, only two studies of Xu et al., Hegyi et al. [21,29] found that the amputation resulted in better 5-year survival. Abudu et al. [15] found that amputation didn’t come with a prolonged overall survival, though it provide better eradication of local tumor than LSS. However, in another article which was not included in the meta-analysis [39], it was indicated that LSS did not affect the survival rate. Even through our analysis results were somewhat inconsistent with previous research, we still concluded that LSS had a similar 5-year overall survival rate to that of amputation.