Primary metastatic osteosarcoma: results of a prospective study in children given chemotherapy and interleukin-2

Abstract

To improve the poor prognosis for children with metastatic osteosarcoma (OS), interleukin-2 (IL-2) was added to the standard treatment due to its capacity to activate lymphocytes and differentiate lymphocyte subsets into lymphokine-activated killer (LAK) cells that are capable of recognizing and killing various tumor cells. This study concerns a cohort of unselected patients aged < 18 years with metastatic OS, who were treated with IL-2, high-dose methotrexate, doxorubicin, cisplatin, ifosfamide, LAK reinfusion, and surgery, between 1995 and 2010. Thirty-five patients aged 4-17 years were involved. Thirty-two of the 35 patients underwent surgery on their primary tumor, and 25 had surgery on lung metastases too. Twenty-seven patients received IL-2 plus LAK reinfusion. The median follow-up was 130 months (77-228), and the 3-year event-free and overall survival rates were 34.3 and 45.0%, respectively. Eleven patients remained alive, all of whom achieved a complete surgical removal of the primary tumor and lung metastases (1 patient did not receive lung resections due to complete lung metastases remission). Patients who had a complete surgical remission of the primary and metastatic sites and who responded well to chemotherapy had a better event-free survival. These results confirm the importance of complete surgical remission and point to a noteworthy (though still be ameliorate) survival rate in our series of patients, underling a potential role for immunotherapy with IL-2 and LAK/NK cell activation.

Understanding and Modeling Metastasis Biology to Improve Therapeutic Strategies for Combating Osteosarcoma Progression

“…In one study, Meazza and colleagues reported the outcomes of 35 pediatric OS patients with macroscopic OS treated with surgery and combinatorial chemoimmunotherapy comprised of IL-2, MAP, ifosfamide, and lymphokine-activated killer (LAK) cell infusion. While the study was not designed to determine the immunobiologic benefit derived from IL-2 and LAK cell infusion, adverse effects associated with IL-2 therapy were tolerable (grade I and II) with most common side effects being fever, flu-like symptoms, hypotension, and cytokine release syndrome (248). In a different study, Schwinger and colleagues reported the tolerability and activity of single-agent, high-dose IV IL-2 therapy in 10 pediatric patients, in which 4 adolescents had metastatic OS (249).…”

Current and Emerging Targets in Immunotherapy for Osteosarcoma

“…Although responses to IL-2 have been reported in clinical trials in patients with various malignancies, only clinical trials for renal cell carcinoma and melanoma observed efficacy of IL-2 [34]. Only a few clinical trials of IL-2 for sarcomas have been reported [35, 36]. In a clinical trial using IL-2 with or without reinfusion of LAK for patients with metastatic osteosarcoma, 3-year event-free and overall survival rates were 34% and 45%, respectively [35].…”

“…Only a few clinical trials of IL-2 for sarcomas have been reported [35, 36]. In a clinical trial using IL-2 with or without reinfusion of LAK for patients with metastatic osteosarcoma, 3-year event-free and overall survival rates were 34% and 45%, respectively [35]. Immunotherapy using a monoclonal antibody against the tumor-associated disialoganglioside GD2, granulocyte macrophage colony-stimulating factor (GM-CSF), and IL-2 was associated with a significantly improved outcome as compared with standard treatment in patients with neuroblastoma [36].…”

A population-based propensity-matched study of regional dissections in patients with metastatic osteosarcoma

“…Osteosarcoma is the most common primary malignant bone tumour in children and adolescents [1]. It is characterized by rapid progression, early pulmonary metastasis, poor prognosis and recurrence [2][3][4]. While the 5-year survival rate of patients with osteosarcoma is approximately 65%, that of patients with metastatic osteosarcoma is only 25% [5].…”

“…However, whether surgery is beneficial for stage IV osteosarcoma patients with extensive metastases remains unclear. There have been studies that have favoured non-resection therapies, such as chemotherapy or radiotherapy, for patients with multiple unresectable metastases [2,12]. Surgical resection is not always feasible due to challenges such as large tumours, various sites of origin, poor physical condition, and various complications after resection.…”