Spontaneous necrosis and additional tumor necrosis induced by preoperative chemotherapy for osteosarcoma: a case-control study.

Background: Extent of spontaneous necrosis in untreated osteosarcoma may imply tumor aggressiveness. Reports regarding this issue are scarce and there are several points to be clarified; (1) the correlation between tumor size and extent of spontaneous necrosis displayed was conflicting, (2) whether there is difference in necrosis rate between intra- and extra-medullary portion of tumor is not described, if it does, its relation with other clinico-pathologic variables, (3) in patients with surgical treatment only, >20 % spontaneous necrosis was a poor prognostic factor, however, whether that cutoff is still valid in chemotherapy cohort remains to be determined, (4) expected additional tumor necrosis by chemotherapy was made by simply comparing the necrosis rates of untreated and treated osteosarcoma cohort.

Methods: We evaluated spontaneous necrosis in 43 osteosarcoma patients (39 Stage IIB, 4 Stage III). We evaluated overall necrosis rate and separately evaluated the necrosis rate of intra- and extra-medullary portion of tumor. These results were compared with other clinico-pathologic variables. To evaluate additional tumor necrosis induced by neoadjuvant chemotherapy, case (38 without preoperative chemotherapy)-control (76 with preoperative chemotherapy) study was performed.

Results: The mean spontaneous necrosis rate was 23 %. Overall spontaneous necrosis was not associated with tumor volume. Necrosis rate of extramedullary tumors was higher in cases of large tumors (p = 0.02). In patients with upfront surgery followed by chemotherapy, 5-year event-free survival rate of patients with >20 and <20 % spontaneous necrosis were 82 ± 17 and 79 ± 18.5 %, respectively (p = 0.75). After chemotherapy, regardless of tumor volume and location, control group tumors showed an increase in the tumor necrosis of approximately 50 %.

Conclusion: In chemotherapy era, the extent of spontaneous necrosis has no relation with survival. The expected additional tumor-killing effect of preoperative chemotherapy is around 50 % of initial tumor volume.