Long-term survival after aggressive resection of pulmonary metastases among children and adolescents with osteosarcoma
ABSTRACT Although survival without resection of pulmonary metastases from osteosarcoma is unlikely, not all surgeons agree on an aggressive surgical approach. We have taken an approach to attempt surgical resection if at all feasible regardless of number of metastases and disease-free interval (DFI). This study presents information on long-term follow-up after this aggressive approach to resection.
A single-institution retrospective cohort study of osteosarcoma patients younger than 21 years with pulmonary metastases, limited to the contemporary chemotherapeutic period (1980-2000), was conducted.
In 137 patients, synchronous (23.4%) or metachronous (76.6%) pulmonary nodules were identified. The median follow-up was 2.0 years (5 days to 20.1 years) for all patients. Overall survival among patients who had pulmonary nodules was 40.2% and 22.6% at 3 and 5 years, respectively. Ninety-nine patients underwent attempted pulmonary metastasectomy (mean survival, 33.6 months; 95% confidence interval, 25.1-42.1) and 38 patients did not (mean survival, 10.1 months; 95% confidence interval, 6.5-13.6; P < .001, t test). Characteristics that were associated with an increased likelihood of 5-year overall survival after pulmonary resection were primary tumor necrosis greater than 98% after neoadjuvant chemotherapy (P < .05) and DFI before developing lung metastases more than 1 year (P < .001). No statistically significant difference in overall survival or disease-free survival was found based on the number of pulmonary metastases resected. Characteristics including primary tumor size, site, or extension; chemotherapy; early vs late metastases; unilateral vs bilateral metastases; and resection margins did not significantly affect survival.
Most patient and tumor characteristics commonly used by surgeons to determine utility of resection of pulmonary metastases among patients with osteosarcoma are not associated with outcome. Biology of the particular tumor (response to preoperative chemotherapy, measured by tumor necrosis percentage, and DFI), as opposed to tumor burden, appears to influence survival more significantly. We would advocate considering repeat pulmonary resection for patients with recurrent metastases from osteosarcoma.
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ABSTRACT: Long non‑coding RNAs (lncRNAs) have recently been identified as novel modulators of malignant tumors. However, the function of lncRNAs in cancer stem cells (CSCs) remains to be elucidated. The present study aimed to investigate the regulating role of a novel lncRNA, hypoxia‑inducible factor‑2α (HIF‑2α) promoter upstream transcript (HIF2PUT), in osteosarcoma stem cells. The expression levels of HIF2PUT were assessed by quantitative polymerase chain reaction in 17 osteosarcoma tissue specimens, and the correlation between the expression of HIF2PUT and its host transcript‑HIF‑2α was determined. In functional experiments, HIF2PUT expression was knocked down by small interfering RNAs, or overexpressed by transfection with pcDNA‑HIF2PUT, in order to evaluate the effects of HIF2PUT on cell proliferation, migration, expression rate of osteosarcoma stem cell marker CD133, and stem sphere‑forming ability in MG63 cells. HIF2PUT expression levels were positively correlated with HIF‑2α in osteosarcoma tissues. Overexpression of HIF2PUT markedly inhibited cell proliferation and migration, decreased the percentage of CD133 expressing cells, and impaired the osteosarcoma stem sphere‑forming ability of the MG63 cells. Whereas, knockdown of HIF2PUT expression had the opposite effect. Furthermore, altering the expression of HIF2PUT resulted in a concomitant change to HIF‑2α mRNA expression. These results indicate that the lncRNA HIF2PUT may be a novel regulatory factor of osteosarcoma stem cells, which may exert its function partly by controlling HIF‑2α expression. Further studies regarding HIF2PUT may provide a novel therapeutic target of osteosarcoma in the future.Molecular Medicine Reports 12/2014; DOI:10.3892/mmr.2014.3024 · 1.48 Impact Factor
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ABSTRACT: Background:Late relapse and solitary lesion are positive prognostic factors in recurrent osteosarcoma.Methods:We reviewed the records of 39 patients treated at three major centres for recurrent osteosarcoma with a single pulmonary metastasis more than 1 year after diagnosis. We analysed their outcomes with respect to clinical factors and treatment with chemotherapy.Results:Median age at diagnosis was 14.6 years. Relapse occurred at a median of 2.5 years (range, 1.2-8.2 years) after initial diagnosis. At relapse, all patients were treated by metastasectomy; 12 (31%) patients also received chemotherapy. There was no difference in time to recurrence or nodule size between the patients who received or did not receive chemotherapy at relapse. Sixteen patients had no subsequent recurrence, 13 of whom survive without evidence of disease. The 5-year and 10-year estimates of post-relapse event-free survival (PREFS) were 33.0±7.5% and 33.0±9.6%, respectively, and of post-relapse survival (PRS) 56.8±8.6% and 53.0±11.0%, respectively. There was a trend for nodules <1.5 cm to correlate positively with PREFS (P=0.070) but not PRS (P=0.49). Chemotherapy at first relapse was not associated with PREFS or PRS.Conclusion:Approximately half of the patients with recurrent osteosarcoma presenting as a single pulmonary metastasis more than 1 year after diagnosis were long-term survivors. Metastasectomy was the primary treatment; chemotherapy did not add benefit.British Journal of Cancer advance online publication, 25 November 2014; doi:10.1038/bjc.2014.585 www.bjcancer.com.British Journal of Cancer 11/2014; DOI:10.1038/bjc.2014.585 · 4.82 Impact Factor
Article: Local control of metastatic sarcoma[Show abstract] [Hide abstract]
ABSTRACT: Survival rates for children with metastatic sarcoma have remained dismal despite intensified multiagent chemotherapy protocols. The local treatment of metastatic disease has been promoted as a way to eliminate colonies of genetically unstable, heterogeneous metastatic cells in an attempt to improve survival amongst this most unfortunate patient population. The survival benefit offered by pulmonary metastasectomies in patients with metastatic osteosarcoma is well substantiated. Utilization of other local treatment modalities, such as radiation therapy and percutaneous thermal ablation, offers the opportunity to intervene in a wide range of pulmonary and extrapulmonary metastatic disease. Patients who have the entirety of their identifiable disease addressed by local control modalities consistently demonstrate improved survival compared with patients who are treated with systemic therapy in isolation. The current state of the literature prevents a definitive conclusion about the utility of local control for metastatic sarcoma. The retrospective trials are clouded by selection bias and the prospective studies are designed to address alternative questions. However, the techniques utilized for local control impart minimal risk to the patient and, in amenable cases, have been shown to provide an opportunity to effect a cure in children with an otherwise dismal prognosis.Current Opinion in Pediatrics 12/2014; 27(1). DOI:10.1097/MOP.0000000000000170 · 2.74 Impact Factor