Long-term survival after aggressive resection of pulmonary metastases among children and adolescents with osteosarcoma

Department of Surgery, University of Texas Medical Sciences Center, Houston, TX 77030, USA.
Journal of Pediatric Surgery (Impact Factor: 1.39). 02/2006; 41(1):194-9. DOI: 10.1016/j.jpedsurg.2005.10.089
Source: PubMed


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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    • "However, the prognosis for patients with lung metastasis after sarcoma has remained mixed, with a 5-year survival rate varying from 30% to 40% [2,3]. Patient care consists of combined treatment with chemotherapies and multiple recurring lung resections [4]. "
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    ABSTRACT: Background The aim of our study was to assess the postoperative course of bilateral anterior sternothoracotomy (BAT) in children with sarcoma metastases, in a curative care perspective. Methods We reviewed the records of seven patients younger than 18 years old, who underwent surgical procedures for sarcoma metastasis to the lung between 2000 and 2012. We compared the postoperative course of the BAT group with that of patients who underwent unilateral posterolateral thoracotomies (PLTs) for the same etiology. Results Of 17 surgical procedures, there were seven BAT and 10 unilateral PLT. Mean ages at the time of the procedures were 12.9 ± 5.4 years old for BAT, and 17.4 ± 1.9 years old for PLT. Mean operative time was 173 ± 37 minutes in the BAT group, and 145 ± 39 minutes in the PLT group (P = 0.19). Patients received epidural analgesia in all cases; this was for a mean time of 3.8 ± 1.3 days in the BAT group, and 3.21 ± 4 days in the PLT group (P = 0.36). Chest tubes were removed after 3.6 ± 1.3 days in the BAT group, and 3 ± 1.2 days in the PLT group (P = 0.69). Total hospital stay was 7.7 ± 6.6 days in the BAT group, and 7 ± 1.2 days in the PLT group (P = 0.72). Conclusion In our experience, BAT seems suitable and shows outcomes similar to those of PLT for sarcoma metastasis resection. The BAT procedure allows the manual exploration of both lungs during a single surgical intervention, and so reduces the delay of further therapies.
    World Journal of Surgical Oncology 07/2014; 12(1):233. DOI:10.1186/1477-7819-12-233 · 1.41 Impact Factor
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    • "[2], [3] However in those with metastasis and in those who relapse, prognosis remains poor with survival rates of only 20–30%. [4], [5] There has been no improvement in the survival of osteosarcoma patients in the last 20 years and therefore new therapeutic options are urgently needed. "
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    ABSTRACT: Survival rates from childhood cancer have improved dramatically in the last 40 years, such that over 80% of children are now cured. However in certain subgroups, including metastatic osteosarcoma, survival has remained stubbornly poor, despite dose intensive multi-agent chemotherapy regimens, and new therapeutic approaches are needed. Hypoxia is common in adult solid tumours and is associated with treatment resistance and poorer outcome. Hypoxia induces chemotherapy resistance in paediatric tumours including neuroblastoma, rhabdomyosarcoma and Ewing's sarcoma, in vitro, and this drug resistance is dependent on the oxygen-regulated transcription factor hypoxia inducible factor-1 (HIF-1). In this study the effects of hypoxia on the response of the osteosarcoma cell lines 791T, HOS and U2OS to the clinically relevant cytotoxics cisplatin, doxorubicin and etoposide were evaluated. Significant hypoxia-induced resistance to all three agents was seen in all three cell lines and hypoxia significantly reduced drug-induced apoptosis. Hypoxia also attenuated drug-induced activation of p53 in the p53 wild-type U2OS osteosarcoma cells. Drug resistance was not induced by HIF-1α stabilisation in normoxia by cobalt chloride nor reversed by the suppression of HIF-1α in hypoxia by shRNAi, siRNA, dominant negative HIF or inhibition with the small molecule NSC-134754, strongly suggesting that hypoxia-induced drug resistance in osteosarcoma cells is independent of HIF-1α. Inhibition of the phosphoinositide 3-kinase (PI3K) pathway using the inhibitor PI-103 did not reverse hypoxia-induced drug resistance, suggesting the hypoxic activation of Akt in osteosarcoma cells does not play a significant role in hypoxia-induced drug resistance. Targeting hypoxia is an exciting prospect to improve current anti-cancer therapy and combat drug resistance. Significant hypoxia-induced drug resistance in osteosarcoma cells highlights the potential importance of hypoxia as a target to reverse drug resistance in paediatric osteosarcoma. The novel finding of HIF-1α independent drug resistance suggests however other hypoxia related targets may be more relevant in paediatric osteosarcoma.
    PLoS ONE 06/2013; 8(6):e65304. DOI:10.1371/journal.pone.0065304 · 3.23 Impact Factor
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    • "When administered preoperatively, generally in preparation for limb salvage, and postoperatively as adjuvant therapy, survival was escalated to 60%–75% [26]. In addition with multimodal intervention comprising the possible administration of alternate agents and surgical resection to remove local recurrence and persistent or recurrent metastases, survival was escalated by an additional 10%−15% [27]. The discovery of effective chemotherapy was instrumental in implementing aggressive surgical sustained attacks (principally thoracotomies) to ablate recurrent and persistent tumor. "
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    ABSTRACT: This paper reviews the contribution of chemotherapy in the conquest of osteosarcoma. It discusses how the treatment of osteosarcoma has evolved over the last five decades, resulting in a more than fivefold increase in survival. Though the initial improvements in survival were dramatic, essentially there has been no change in the outlook for this disease over the past 30 years. The paper also highlights the necessity of a multidisciplinary approach to combat this disease and stresses the need to explore newer treatment agents in order to build on the lessons learnt from the past while striving to achieve greater levels of success.
    Sarcoma 05/2013; 2013:203531. DOI:10.1155/2013/203531
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