Pattern of disease recurrence and prognostic factors in patients with osteosarcoma treated with contemporary chemotherapy

Abstract

BACKGROUNDThe goal of the current study was to define the clinical features and outcome of recurrent osteosarcoma (OS) in children and young adults initially treated with contemporary chemotherapy.METHODSThe authors reviewed the clinical features, therapy, and outcome for 59 patients from the Mayo Clinic (Rochester, MN) and Children's Hospital and Regional Medical Center (Seattle, WA). They were diagnosed initially with OS between January 1990 and December 2000, received multiagent chemotherapy (most frequently cisplatin, doxorubicin, high‐dose methotrexate, and ifosfamide), and developed disease recurrence after achieving an initial complete response (CR).RESULTSThe most common site of initial disease recurrence was the lung only (n = 36 patients), followed by distant bone (n =8 patients), combined lung and other sites (n =7 patients), and other sites (n =8 patients). The median time to first disease recurrence was 15 months (range, 2–92 months) from the initial diagnosis. Thirty patients with isolated pulmonary recurrence achieved a second CR, either with surgery alone (n =15 patients) or surgery and salvage chemotherapy (n =15 patients). For this group, the 4‐year disease‐free survival (DFS) and overall survival rates were 7% (95% confidence interval [95% CI], 0–16%) and 28% (95% CI, 11–45%), respectively. For all 59 patients with recurrent OS, the 4‐year DFS and overall survival rates were 6% (95% CI, 0–12%) and 23% (95% CI, 10–36%), respectively. The only factors associated with improved DFS and overall survival rates were unilateral pulmonary recurrence, solitary pulmonary nodule at recurrence, more than 24 months between the initial diagnosis and first disease recurrence, and achievement of a second CR.CONCLUSIONSThe DFS and overall survival rates for recurrent OS after contemporary therapy remained poor even for patients with isolated pulmonary recurrence. Therefore, new treatment strategies are needed. Cancer 2003. © 2003 American Cancer Society.

Treatment and outcome of recurrent osteosarcoma: Experience at Rizzoli in 235 patients initially treated with neoadjuvant chemotherapy

“…This discrepancy probably reflects the fact that several factors complicate the analysis of the published literature regarding the post-relapse survival. In fact, as noted by Hawkins and Arndt [6]: (1) some series represent selected cohorts of patients amenable to surgical excision thereby excluding patients with unresectable, and therefore unfavorable outcome [5,14 Á/16]; (2) some series included patients who had not received adjuvant or neoadjuvant chemotherapy as part of their primary osteosarcoma therapy [5,17 Á/20]; (3) most series reported only survival rates, often at different times, and only few series reported DFS or EFS rates after disease recurrences [1,21,22]. However, the data concerning the post-relapse event-free survival are also really contrasting, and range between 7% [1] and 27% [21].…”

“…There are many studies which report the outcome of patients who relapse, but their results are contrasting. In fact the overall post recurrence survival (OPRS) rate for patients with osteosarcoma initially treated by combined treatment ranges between 13% [5] and 61% [6] and the event free post recurrence survival (EFPRS), reported in only a few series, between 6% [6] and 27% [7]. These discrepancies can be explained by the lack of homogeneity of these series and the small number of patients these reports are based on.…”

Pirarubicin inhibits multidrug-resistant osteosarcoma cell proliferation through induction of G2/M phase cell cycle arrest

“…Multiagent chemotherapy, commonly including doxorubicin (ADM), cisplatin (DDP) and high-dose methotrexate (MTX), has improved patient survival from 11% with surgical resection alone to 70% for localized disease. Unfortunately, the longterm survival for the remaining patients with recurrent disease is less than 20% [1][2][3] . Studies designed to identify novel active agents and implement strategies to overcome chemoresistance will likely be important for improving survival [1] .…”

High expression of tumor endothelial marker 7 is associated with metastasis and poor survival of patients with osteogenic sarcoma

“…The introduction of multiagent chemotherapy in addition to surgery has dramatically increased long-term survival for patients with OGS, with a disease-free 5-year survival reaching 65-70% for patients with localized disease (Link et al, 1986;Meyers and Gorlick, 1997;Arndt and Crist, 1999;Hawkins and Arndt, 2003). However, patients who develop metastatic disease still have an extremely dismal prognosis despite its contemporary treatment.…”

“…However, patients who develop metastatic disease still have an extremely dismal prognosis despite its contemporary treatment. Recently, the 4-year disease free survival for patients with metastatic disease was reported to be only 6% (Hawkins and Arndt, 2003). Therefore, new treatment strategies are needed.…”