J Orthop Sci (2015) 20:174–179 DOI 10.1007/s00776-014-0665-5
ORIGINAL ARTICLE
Spontaneous necrosis and additional tumor necrosis induced by preoperative chemotherapy for osteosarcoma: a case–control study Won Seok Song · Dae‑Geun Jeon · Wan Hyeong Cho · Chang‑Bae Kong · Sang Hyun Cho · Seung Yong Lee · Soo‑Yong Lee
Received: 4 August 2014 / Accepted: 15 October 2014 / Published online: 30 October 2014 © The Japanese Orthopaedic Association 2014
Abstract 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
W. S. Song · D.‑G. Jeon (*) · W. H. Cho · C.‑B. Kong · S. H. Cho · S. Y. Lee · S.‑Y. Lee Department of Orthopedic Surgery, Korea Cancer Center Hospital, 215‑4 Gongneung‑dong, Nowon‑gu, Seoul 139‑706, Korea e-mail: [email protected]
13
higher in cases of large tumors (p = 0.02). In patients with upfront surgery followed by chemotherapy, 5-year eventfree survival rate of patients with >20 and 20 % spontaneous necrosis show poorer survival than 20 % (%)
P value
9 (40.9) 13 (59.1)
0.17
10 (45.5) 12 (54.5)
0.42
11 (50.0) 11 (50.0)
0.15
18 (77.3) 4 (18.2)
0.12
14 (63.6) 5 (22.7) 2 (9.1) 0 (0) 1 (4.6)
0.61
6 (27.3) 9 (40.9) 7 (31.8)
0.86
17 (77.3) 3 (13.6) 2 (9.1) 0 (0)
0.66
22 (100) 0 (0)
0.49
(cutoff; 150 cc; p = 0.01) and non-osteoblastic subtype tumors (p = 0.02) (Table 2). Of the 39 patients with Stage IIB at presentation, 6 (15.4 %) developed metastasis and 1 had local recurrence. Twenty-one patients showed 20 % necrosis. The 5-year continuous disease free survival rates for 39 stage IIB patients was 80.5 ± 12.8 % and the 5-year continuous disease free survival rates for patients with >20 and 150 cc 7 (25.9) Enneking stage IIB 25 (85.2) III 2 (7.4) Location Femur 14 (51.9) Tibia 8 (29.6) Humerus 4 (14.8) Fibula 1 (3.7) Pelvis 0 (0) Pattern on plain radiograph Lytic 7 (25.9) Mixed 11 (40.7) Blastic 9 (33.4) Pathologic subtype Osteoblastic 22 (81.5) Chondroblastic 1 (3.7) Fibroblastic 3 (11.1) Small cell 1 (3.7) Final outcome Alive 26 (96.3) Dead 1 (3.7) Total
22 (100 %)
15 and ≤40 >40 Gender Male Female Tumor volume ≤150 >150 Location Distal femur Proximal tibia Proximal humerus Proximal femur Distal tibia Fibula Pathologic subtype Osteoblastic Chondroblastic Fibroblastic Others Histologic response
ORIGINAL ARTICLE
Spontaneous necrosis and additional tumor necrosis induced by preoperative chemotherapy for osteosarcoma: a case–control study Won Seok Song · Dae‑Geun Jeon · Wan Hyeong Cho · Chang‑Bae Kong · Sang Hyun Cho · Seung Yong Lee · Soo‑Yong Lee
Received: 4 August 2014 / Accepted: 15 October 2014 / Published online: 30 October 2014 © The Japanese Orthopaedic Association 2014
Abstract 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
W. S. Song · D.‑G. Jeon (*) · W. H. Cho · C.‑B. Kong · S. H. Cho · S. Y. Lee · S.‑Y. Lee Department of Orthopedic Surgery, Korea Cancer Center Hospital, 215‑4 Gongneung‑dong, Nowon‑gu, Seoul 139‑706, Korea e-mail: [email protected]
13
higher in cases of large tumors (p = 0.02). In patients with upfront surgery followed by chemotherapy, 5-year eventfree survival rate of patients with >20 and 20 % spontaneous necrosis show poorer survival than 20 % (%)
P value
9 (40.9) 13 (59.1)
0.17
10 (45.5) 12 (54.5)
0.42
11 (50.0) 11 (50.0)
0.15
18 (77.3) 4 (18.2)
0.12
14 (63.6) 5 (22.7) 2 (9.1) 0 (0) 1 (4.6)
0.61
6 (27.3) 9 (40.9) 7 (31.8)
0.86
17 (77.3) 3 (13.6) 2 (9.1) 0 (0)
0.66
22 (100) 0 (0)
0.49
(cutoff; 150 cc; p = 0.01) and non-osteoblastic subtype tumors (p = 0.02) (Table 2). Of the 39 patients with Stage IIB at presentation, 6 (15.4 %) developed metastasis and 1 had local recurrence. Twenty-one patients showed 20 % necrosis. The 5-year continuous disease free survival rates for 39 stage IIB patients was 80.5 ± 12.8 % and the 5-year continuous disease free survival rates for patients with >20 and 150 cc 7 (25.9) Enneking stage IIB 25 (85.2) III 2 (7.4) Location Femur 14 (51.9) Tibia 8 (29.6) Humerus 4 (14.8) Fibula 1 (3.7) Pelvis 0 (0) Pattern on plain radiograph Lytic 7 (25.9) Mixed 11 (40.7) Blastic 9 (33.4) Pathologic subtype Osteoblastic 22 (81.5) Chondroblastic 1 (3.7) Fibroblastic 3 (11.1) Small cell 1 (3.7) Final outcome Alive 26 (96.3) Dead 1 (3.7) Total
22 (100 %)
15 and ≤40 >40 Gender Male Female Tumor volume ≤150 >150 Location Distal femur Proximal tibia Proximal humerus Proximal femur Distal tibia Fibula Pathologic subtype Osteoblastic Chondroblastic Fibroblastic Others Histologic response
