Patients with osteosarcoma at axial sites have an increased risk for local recurrence after surgery relative to peers with osteosarcoma at nonproximal limb sites, according to a new analysis of the EURAMOS-1 study published in BMJ Open.

The analysis also showed an increased risk of new metastatic disease in patients with a poor histological response to neoadjuvant chemotherapy. In addition, patients younger than 12 years of age had a lower risk of local recurrence but a higher risk of death if they experienced local recurrence.

EURAMOS-1 is a phase 3 randomized controlled trial (ClinicalTrials.gov Identifier: NCT00134030) designed to optimize treatment strategies for resectable osteosarcoma based on histological response to preoperative chemotherapy.


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In previous analyses of EURAMOS-1 data, researchers investigated the relationship between various predictors and survival outcomes. However, they did not take into consideration disease evolution and how patient history might affect the final prognosis. 

With the current analysis, researchers set out to determine the effect of prognostic factors on survival using a multistate model. The model took into account 6 disease states that a patient may transition to after surgical resection of the primary tumor: local recurrence, new metastatic disease, local recurrence with new metastatic disease, secondary malignancy, second new metastatic disease occurring after remission, and death.

The analysis was based on a subset of 1631 metastasis-free patients who participated in the EURAMOS-1 study. Overall, 3% of patients had tumors in axial sites (ribs, pelvis, or sacrum), 13% in proximal limb sites (femur or humerus), and 84% in other limb sites. 

Of the 1631 patients, 526 experienced an intermediate event, moving to the states of local recurrence (61 patients), new metastatic disease (407 patients), local recurrence with new metastatic disease (35 patients), or secondary malignancy (23 patients). By the end of follow-up, 305 patients had died. 

When compared with any other limb site except proximal, an axial tumor site was associated with an increased risk for local recurrence after surgery (hazard ratio [HR], 10.84; 95% CI, 8.46-13.86) and death after local recurrence (HR, 11.54; 95% CI, 6.11-21.78). On the other hand, patients with axial tumors were less likely to develop new metastatic disease after surgery (HR, 0.70; 95% CI, 0.56-0.87).

A poor histological response to neoadjuvant chemotherapy was linked to an elevated risk for new metastatic disease (HR, 5.81; 95% CI, 5.31-6.36), which declined 3 years after surgery. 

Patients who underwent intralesional surgical excision (HR, 0.33) or marginal surgical excision (HR, 0.38) were less likely than those who underwent wide/radical excision to experience progression from local recurrence to death.

Compared with adolescents aged 12 to 18 years, patients younger than 12 years had a reduced risk for local recurrence (HR, 0.66), new metastasis (HR, 0.80), secondary malignancy (HR, 0.61), and event-free death (HR, 0.56). However, patients younger than 12 years had an increased risk for death after local recurrence (HR, 2.40).

Patients older than 18 years had a decreased risk for death after local recurrence (HR, 0.35), death after local recurrence with new metastatic disease (HR, 0.47), and death after second new metastatic disease following remission (HR, 0.53). 

On the basis of these findings, the researchers suggested that patients with axial tumors should be monitored for local recurrence, and patients with poor histological response should be monitored for new metastatic disease. For patients younger than 12 years of age who have local recurrence, additional treatment options are needed.

Reference

Hazewinkel AD, Lancia C, Anninga J, et al. Disease progression in osteosarcoma: A multistate model for the EURAMOS-1 (European and American Osteosarcoma Study) randomised clinical trial. BMJ Open. 2022;12(3):e053083. doi:10.1136/bmjopen-2021-053083