Treatment of 120 adult osteosarcoma patients with metachronous and synchronous metastases: A retrospective series of the French Sarcoma Group

Abstract

Treatment options for metastatic osteosarcomas are scarce. Following failure of standard first line therapy, patients who relapse present a challenging treatment dilemma, and have a poor prognosis. Surgical removal of all metastases is essential. A retrospective analysis of patients with metastatic osteosarcomas was conducted in 15 French Sarcoma Group centers. From January 2009 to December 2018, we identified 120 adult patients; 36 with synchronous and 84 with metachronous metastases with 74 males and 46 females. Mean age was 30 years (18‐53). Metastatic sites were lung, bone and other in 91, 11 and 24 patients, respectively. Mean time to first metachronous metastases was 22 months (4‐97). All patients except 13 (10.8%) with metachronous metastases received a first line systemic treatment for relapse, and 39 patients (32.5%) were included in a clinical trial. Eighty‐one patients (67.5%) had local treatment of distant metastases. Median progression free survival (PFS) and overall survival (OS) were 5.5 (95% CI 4.6‐6.4) and 20.5 months (95% CI 13.2‐27.7) respectively for the overall group. In multivariate analysis, more than five metastases, time to first metastases <24 months, were statistically significant negative prognostic factors for OS and PFS (P = .002, ≤.001 and P = .006, ≤.001, respectively). Surgery of metastases was associated with better prognosis on OS and PFS (P = .001 and .037, respectively). The presence of bone metastases was a negative prognostic factor on OS but not on PFS (P = .021). In reference sarcoma centers, relapsed osteosarcoma patients with more than one metastasis commonly receive more than one line of systemic therapy, and are included in clinical trial if available.

Metastatic Progression of Osteosarcomas: A Review of Current Knowledge of Environmental versus Oncogenic Drivers

“…Complete remission is achieved only in patients with full surgical resection of all the metastasis. Second-line chemotherapy associated with surgery can increase survival as compared with surgery alone, but its exact modality is still debated [ 26 , 44 , 45 ]. In a recent review, Gazouli et al evaluated 56 phase I and II trials for new treatment strategies in recurrent/metastatic osteosarcoma over the last 2 decades; strategies included cytotoxic chemotherapy, targeted agents, such as tyrosine kinase, and mammalian target of rapamycin inhibitors, immunotherapy, and combination approaches [ 44 ].…”

Challenges of Systemic Therapy Investigations for Bone Sarcomas

“…However, if recurrence or metastasis occurs, the prognosis of osteosarcoma patients remains poor; the 5-year overall survival (OS) rate of patients with recurrent or metastatic osteosarcoma has been unchanged at <20% since the 1980s [ 16 , 17 ]. Most long-term survivors of metastatic osteosarcoma have been patients who had limited pulmonary metastatic lesions and underwent a successful metastasectomy [ 18 , 19 , 20 ], and patients with bone lesions at recurrence have been suggested to have poor OS [ 21 ]. Clinical evidence of standard salvage chemotherapy that improves the overall survival of recurrent/metastatic osteosarcoma patients has not been obtained.…”

“…Although lung metastases are highly observed, as described in Section 2 , lung metastatic lesions could be the target of salvage surgery for bone sarcoma patients if their sizes are measurable and their numbers are limited [ 110 ], so the percentage of “not surgically resectable” bone sarcoma patients receiving salvage chemotherapy and requiring new drugs with lung metastases of measurable size is even lower. Bone sarcomas with bone metastases are known to have a poor prognosis [ 21 ], and despite the high demand for clinical trials, it is undesirable that bone lesions are not adequately evaluated in clinical trials. A time-to-event outcome with a control group is required when evaluating the efficacy of a treatment for bone sarcoma.…”

Europium-doped hybrid nano-complexes: a potential strategy for metastasis prevention in osteosarcoma

“…4 In particular, osteosarcoma presents a notable case with a less than 30% five-year survival rate, primarily attributed to distant lung metastasis. 5,6 Despite patients receiving surgery combined with adjuvant radiotherapy and chemotherapy in the early stage, the outcomes were not satisfactory. Therefore, it is essential to develop new therapeutic agents to inhibit the initial tumor metastasis.…”