Survival and prognosis with osteosarcoma: outcomes in more than 2000 patients in the EURAMOS-1 (European and American Osteosarcoma Study) cohort

Abstract

Background High-grade osteosarcoma is a primary malignant bone tumour mainly affecting children and young adults. The European and American Osteosarcoma Study (EURAMOS)-1 is a collaboration of four study groups aiming to improve outcomes of this rare disease by facilitating randomised controlled trials. Methods Patients eligible for EURAMOS-1 were aged ≤40 years with M0 or M1 skeletal high-grade osteosarcoma in which case complete surgical resection at all sites was deemed to be possible. A three-drug combination with methotrexate, doxorubicin and cisplatin was defined as standard chemotherapy, and between April 2005 and June 2011, 2260 patients were registered. We report survival outcomes and prognostic factors in the full cohort of registered patients. Results For all registered patients at a median follow-up of 54 months (interquartile range: 38–73) from biopsy, 3-year and 5-year event-free survival were 59% (95% confidence interval [CI]: 57–61%) and 54% (95% CI: 52–56%), respectively. Multivariate analyses showed that the most adverse factors at diagnosis were pulmonary metastases (hazard ratio [HR] = 2.34, 95% CI: 1.95–2.81), non-pulmonary metastases (HR = 1.94, 95% CI: 1.38–2.73) or an axial skeleton tumour site (HR = 1.53, 95% CI: 1.10–2.13). The histological subtypes telangiectatic (HR = 0.52, 95% CI: 0.33–0.80) and unspecified conventional (HR = 0.67, 95% CI: 0.52–0.88) were associated with a favourable prognosis compared with chondroblastic subtype. The 3-year and 5-year overall survival from biopsy were 79% (95% CI: 77–81%) and 71% (95% CI: 68–73%), respectively. For patients with localised disease at presentation and in complete remission after surgery, having a poor histological response was associated with worse outcome after surgery (HR = 2.13, 95% CI: 1.76–2.58). In radically operated patients, there was no good evidence that axial tumour site was associated with worse outcome. Conclusions In conclusion, data from >2000 patients registered to EURAMOS-1 demonstrated survival rates in concordance with institution- or group-level osteosarcoma trials. Further efforts are required to drive improvements for patients who can be identified to be at higher risk of adverse outcome. This trial reaffirms known prognostic factors, and owing to the large numbers of patients registered, it sheds light on some additional factors to consider.

Risk factors associated with delayed methotrexate clearance and increased toxicity in pediatric patients with osteosarcoma

“…There was a male predominance and variation in race/ethnicity among patients with OS consistent with what has previously been reported in the literature . The overall survival of 73% in this cohort is similar to reported outcomes for pediatric OS …”

Outcomes for pediatric patients with osteosarcoma treated with palliative radiotherapy

“…The prognosis for pediatric patients with OS has not changed significantly over three decades . Despite intensive multiagent neoadjuvant chemotherapy and primary tumor resection, three‐year event‐free and overall survival are 59% and 71%, respectively, for nonmetastatic disease, whereas patients with metastatic disease at initial diagnosis fare considerably worse . Optimal management of symptomatic metastatic or locally recurrent disease is unclear, with a lack of data to guide decision‐making.…”

“…9,10 Despite intensive multiagent neoadjuvant chemotherapy and primary tumor resection, three-year event-free and overall survival are 59% and 71%, respectively, for nonmetastatic disease, whereas patients with metastatic disease at initial diagnosis fare considerably worse. 11 Optimal management of symptomatic metastatic or locally recurrent disease is unclear, with a lack of data to guide decision-making. However, even when not curative, treatment of locally recurrent or symptomatic metastatic disease may lengthen survival, control symptoms, and improve quality of life.…”

Circular RNA LARP4 correlates with decreased Enneking stage, better histological response, and prolonged survival profiles, and it elevates chemosensitivity to cisplatin and doxorubicin via sponging microRNA‐424 in osteosarcoma

“…After the neoadjuvant chemotherapy, patients were re‐assessed by the X‐ray, PET, or bone scan, and then, definitive surgery (limb salvage or amputation) was performed. The histological response to the neoadjuvant chemotherapy was evaluated on the basis of the tumor cell necrosis rate in the resected specimen, and a good response was defined as tumor cell necrosis rate (TCNR) ≥90%; accordingly, a poor response was defined as TCNR <90% . Postoperative chemotherapy was based on histological response to neoadjuvant chemotherapy.…”

“…The histological response to the neoadjuvant chemotherapy was evaluated on the basis of the tumor cell necrosis rate in the resected specimen, and a good response was defined as tumor cell necrosis rate (TCNR) ≥90%; accordingly, a poor response was defined as TCNR <90%. 14…”