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

Abstract

Background: Local recurrence (LR) in osteosarcoma is associated with very poor prognosis. We sought to evaluate which factors correlate with LR in patients who achieved complete surgical remission with adequate margins. Patients and methods:We analyzed 1355 patients with previously untreated high-grade central osteosarcoma of the extremities, the shoulder and the pelvis registered in neoadjuvant Cooperative Osteosarcoma Study Group trials between 1986 and 2005. Seventy-six patients developed LR.Results: Median follow-up was 5.56 years. No participation in a study, pelvic tumor site, limb-sparing surgery, soft tissue infiltration beyond the periosteum, poor response to neoadjuvant chemotherapy, failure to complete the planned chemotherapy protocol and biopsy at a center other than the one performing the tumor resection were significantly associated with a higher LR rate. No differences were found for varying surgical margin widths. Surgical treatment at centers with small patient volume and additional surgery in the primary tumor area, other than biopsy and tumor resection, were significantly associated with a higher rate of ablative surgery.Conclusions: Patient enrollment in clinical trials and performing the biopsy at experienced institutions capable of undertaking the tumor resection without compromising the oncological and functional outcome should be pursued in the future.

Survival, Recurrence, and Function After Epiphyseal Preservation and Allograft Reconstruction in Osteosarcoma of the Knee

“…Canadell et al [5] performed transepiphyseal resection in 12 high-grade osteosarcomas and had one local recurrence in their series. Our incidence of local recurrences is similar to that observed in other patients with osteosarcomas treated with limb-sparing surgery with other techniques [2,5,8,12,14]. Ferrari et al [8] reported 18 local recurrences (8%) in 230 patients who had conservative surgery.…”

“…However, although we selected these patients with clinical and imaging parameters, six were not good responders, but the margins obtained were free of tumor and no other surgical approach was performed. Andreou et al [2] reported that patients participating in a study fared significantly better (p \ 0.0001) than those who were only registered and followed prospectively. This could be the cause of the higher patient survival in our series because although six patients were histologically poor responders, they could have other favorable characteristics such as small tumor size, adequate biopsy, or absence of soft tissue infiltration.…”

“…Although there is no consensus regarding what constitutes an appropriate margin for resection of an osteosarcoma with a good response to chemotherapy, in our series, leaving a margin of at least 1 cm, we observed no local recurrences in the remaining bony epiphysis. Andreou et al [2] reported that limb-sparing procedures were associated with a higher local recurrence rate (7.5%), with no difference in diseasespecific survival (p = 0.118). They also found that surgical margin width in bone did not correlate with the local recurrence rate, either in the group as a whole (p = 0.126) or in subgroup analyses of limb-sparing procedures only (p = 0.692), margin width of 10 mm or less only (p = 0.223), 20 mm or less only (p = 0.379), or when comparing a width of 10 mm or less with a width of 11 to 20 mm.…”

CORR Insights®: Survival, Recurrence, and Function After Epiphyseal Preservation and Allograft Reconstruction in Osteosarcoma of the Knee

“…The relatively small patient population, limited analysis of margins and the retrospective nature of the study prevent from further inference and speculation; all of these represent potential areas of opportunity for future research. However, even much larger, cooperative retrospective studies are unlikely to provide homogeneous data and definitive answers to the problem [1]. Prospective cooperative collection of homogeneous data related to the known risk factors, and including disease course after relapse and updated followup, should be pursued.…”

“…Local recurrence is the first sign of recurrent disease in approximately half of the cases, whereas it follows or presents synchronously with distant metastases in the remaining patients [1,3]. While isolated local recurrence after inadequate surgery presumably ''permits'' metastatic relapse, at least in some of the patients, its occurrence after a negative margin and in association with or shortly after distant metastasis suggests they both are signs of biologic aggressiveness.…”