Tumor enlargement after chemotherapy is considered one of the high-risk factors for local recurrence and survival in osteosarcoma. We hypothesized patients with this risk factor will have similar survival regardless of the development of local recurrence.
We asked (1) the prognostic factors for survival in our cohort, (2) how much effect local recurrence has on survival among patients with similar preoperative risk factors, and (3) what prognostic factors are important for survival in these selected patients.
We analyzed the prognostic factors for survival in 449 patients with extremity osteosarcoma without metastatic disease at initial diagnosis and treatment (38 with local recurrence, 411 without local recurrence). We compared the survival difference between patients with local recurrence (n = 38) and without local recurrence (control, n = 76) matched for age, location, initial tumor volume, and tumor volume change after chemotherapy, and assessed prognostic factors in this subgroup.
In a cohort study, multivariate analysis revealed initial tumor volume, tumor enlargement, inadequate margin, and local recurrence predicted poor survival. In the case-control study, the 10-year metastasis-free survival rates of two groups were 13.1 ± 10.7% and 19.3 ± 9%, respectively. In the case-controlled groups, tumor enlargement and initial tumor volume showed multivariate significance.
Local recurrence has a small impact on survival in patients with high-risk osteosarcoma.
Level of Evidence
Level III, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.
This is a preview of subscription content, log in to check access.
Andreou D, Bielack SS, Carrle D, Kevric M, Kotz R, Winkelmann W, Jundt G, Werner M, Fehlberg S, Kager L, Kuhne T, Lang S, Dominkus M, Exner GU, Hardes J, Hillmann A, Ewerbeck V, Heise U, Reichardt P, Tunn PU. The influence of tumor- and treatment-related factors on the development of local recurrence in osteosarcoma after adequate surgery: an analysis of 1355 patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. Ann Oncol. 2011;22:1228–1235.
Bacci G, Ferrari S, Lari S, Mercuri M, Donati D, Longhi A, Forni C, Bertoni F, Versari M, Pignotti E. Osteosarcoma of the limb: amputation or limb salvage in patients treated by neoadjuvant chemotherapy. J Bone Joint Surg Br. 2002;84:88–92.
Bacci G, Ferrari S, Longhi A, Perin S, Forni C, Fabbri N, Salduca N, Versari M, Smith KV. Pattern of relapse in patients with osteosarcoma of the extremities treated with neoadjuvant chemotherapy. Eur J Cancer. 2001;37:32–38.
Bacci G, Forni C, Longhi A, Ferrari S, Mercuri M, Bertoni F, Serra M, Briccoli A, Balladelli A, Picci P. Local recurrence and local control of non-metastatic osteosarcoma of the extremities: a 27-year experience in a single institution. J Surg Oncol. 2007;96:118–123.
Bacci G, Longhi A, Cesari M, Versari M, Bertoni F. Influence of local recurrence on survival in patients with extremity osteosarcoma treated with neoadjuvant chemotherapy: the experience of a single institution with 44 patients. Cancer. 2006;106:2701–2706.
Chi SN, Conklin LS, Qin J, Meyers PA, Huvos AG, Healey JH, Gorlick R. The patterns of relapse in osteosarcoma: the Memorial Sloan-Kettering experience. Pediatr Blood Cancer. 2004;42:46–51.
Enneking WF, Spanier SS, Goodman MA. A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop Relat Res. 1980;153:106–120.
Gobel V, Jurgens H, Etspuler G, Kemperdick H, Jungblut RM, Stienen U, Gobel U. Prognostic significance of tumor volume in localized Ewing’s sarcoma of bone in children and adolescents. J Cancer Res Clin Oncol. 1987;113:187–191.
Grimer RJ, Sommerville S, Warnock D, Carter S, Tillman R, Abudu A, Spooner D. Management and outcome after local recurrence of osteosarcoma. Eur J Cancer. 2005;41:578–583.
Grimer RJ, Taminiau AM, Cannon SR; Surgical Subcommittee of the European Osteosarcoma Intergroup. Surgical outcomes in osteosarcoma. J Bone Joint Surg Br. 2002;84:395–400.
Holscher HC, Bloem JL, Vanel D, Hermans J, Nooy MA, Taminiau AH, Henry-Amar M. Osteosarcoma: chemotherapy-induced changes at MR imaging. Radiology. 1992;182:839–844.
Kempf-Bielack B, Bielack SS, Jurgens H, Branscheid D, Berdel WE, Exner GU, Gobel U, Helmke K, Jundt G, Kabisch H, Kevric M, Klingebiel T, Kotz R, Maas R, Schwarz R, Semik M, Treuner J, Zoubek A, Winkler K. Osteosarcoma relapse after combined modality therapy: an analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS). J Clin Oncol. 2005;23:559–568.
Kim MS, Cho WH, Song WS, Lee SY, Jeon DG. Time dependency of prognostic factors in patients with stage II osteosarcomas. Clin Orthop Relat Res. 2007;463:157–165.
Kim MS, Lee SY, Cho WH, Song WS, Koh JS, Lee JA, Yoo JY, Jeon DG. Tumor necrosis rate adjusted by tumor volume change is a better predictor of survival of localized osteosarcoma patients. Ann Surg Oncol. 2008;15:906–914.
Kim MS, Lee SY, Cho WH, Song WS, Koh JS, Lee JA, Yoo JY, Jung ST, Jeon DG. Effect of increases in tumor volume after neoadjuvant chemotherapy on the outcome of stage II osteosarcoma regardless of histological response. J Orthop Sci. 2009;14:292–297.
Nathan SS, Gorlick R, Bukata S, Chou A, Morris CD, Boland PJ, Huvos AG, Meyers PA, Healey JH. Treatment algorithm for locally recurrent osteosarcoma based on local disease-free interval and the presence of lung metastasis. Cancer. 2006;107:1607–1616.
Picci P, Sangiorgi L, Bahamonde L, Aluigi P, Bibiloni J, Zavatta M, Mercuri M, Briccoli A, Campanacci M. Risk factors for local recurrences after limb-salvage surgery for high-grade osteosarcoma of the extremities. Ann Oncol. 1997;8:899–903.
Picci P, Sangiorgi L, Rougraff BT, Neff JR, Casadei R, Campanacci M. Relationship of chemotherapy-induced necrosis and surgical margins to local recurrence in osteosarcoma. J Clin Oncol. 1994;12:2699–2705.
Rodriguez-Galindo C, Shah N, McCarville MB, Billups CA, Neel MN, Rao BN, Daw NC. Outcome after local recurrence of osteosarcoma: the St. Jude Children’s Research Hospital experience (1970–2000). Cancer. 2004;100:1928–1935.
Rosen G, Marcove RC, Huvos AG, Caparros BI, Lane JM, Nirenberg A, Cacavio A, Groshen S. Primary osteogenic sarcoma: eight-year experience with adjuvant chemotherapy. J Cancer Res Clin Oncol. 1983;106(suppl):55–67.
Rougraff BT, Simon MA, Kneisl JS, Greenberg DB, Mankin HJ. Limb salvage compared with amputation for osteosarcoma of the distal end of the femur: a long-term oncological, functional, and quality-of-life study. J Bone Joint Surg Am. 1994;76:649–656.
Shin KH, Moon SH, Suh JS, Yang WI. Tumor volume change as a predictor of chemotherapeutic response in osteosarcoma. Clin Orthop Relat Res. 2000;376:200–208.
Simon MA, Aschliman MA, Thomas N, Mankin HJ. Limb-salvage treatment versus amputation for osteosarcoma of the distal end of the femur. J Bone Joint Surg Am. 1986;68:1331–1337.
Song WS, Jeon DG, Kong CB, Cho WH, Koh JS, Lee JA, Yoo JY, Jung ST, Shin DS, Lee SY. Tumor volume increase during preoperative chemotherapy as a novel predictor of local recurrence in extremity osteosarcoma. Ann Surg Oncol. 2011;18:1710–1716.
Weeden S, Grimer RJ, Cannon SR, Taminiau AH, Uscinska BM; European Osteosarcoma Intergroup. The effect of local recurrence on survival in resected osteosarcoma. Eur J Cancer. 2001;37:39–46.
We thank to Minkyo Song, MD, at Seoul National University for technical assistance of statistical analysis.
The authors certify that they have no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might constitute a conflict of interest in connection with the submitted article.
All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research editors and board members are on file with the publication and can be viewed on request.
The authors certify that their institution approved the human protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.
This work was performed at Korea Cancer Center Hospital.
About this article
Cite this article
Kong, C., Song, W.S., Cho, W.H. et al. Local Recurrence has only a Small Effect on Survival in High-risk Extremity Osteosarcoma. Clin Orthop Relat Res 470, 1482–1490 (2012) doi:10.1007/s11999-011-2137-y
- Local Recurrence
- Tumor Volume
- Surgical Margin
- Preoperative Chemotherapy
- Limb Salvage