Pathological Fractures Linked to Inferior OS in Adults With Osteosarcoma

Pathological fractures in adult patients with high-grade osteosarcoma of the extremities potentially correlates with inferior overall survival (OS), according to results of a retrospective analysis published in the Journal of Clinical Oncology.¹ However, this conclusion was not found in pediatric patients.

Results showed that, at a median time of potential follow-up of 10.8 years, the overall 5-year OS rate of patients with and without pathologic fractures, via univariable analysis, was 63.0% versus 70.6%, respectively (P = .007) and the 5-year event-free survival (EFS) rates were 50.9% and 58.4% (P = .026), respectively.

Specifically, in adults, the 5-year OS of patients with and without pathologic fractures was 45.9% versus 69.3% (P <.001) and the 5-year EFS was 35.9% versus 55.7% (P <.001). However, in pediatric patients, OS and EFS did not differ significantly between those with and without pathologic fractures, according to multivariable analysis.

In the retrospective study, investigators analyzed a total of 2847 patients registered in the Consecutive Cooperative Osteosarcoma Study Group database. Patients had primary central high-grade osteosarcoma of the extremities and were treated between 1980 and 2010.

A total 2193 patients were ≤18 years of age, of whom 11.3% (n = 321) previously had or developed pathologic fractures before or during neoadjuvant chemotherapy. Patients in their first decade of life (n = 370) as well as those >40 years old (n = 115) had the highest rate of pathologic fractures. Pathologic fractures were present in patients 0 to 10 years old (21.9%), 41 to 50 years (23.2%), and >50 years (>30%).

“The occurrence of pathologic fractures was highest in patients in their first decade of life—as well as those >40 years&mdash;possibly as a result of the earlier occurrence of main growth spurt in the humerus, where more pathologic fractures occur than in other bone sites,” the authors wrote. “Conversely, older patients are more likely to have degenerated bone structures, potentially making them more susceptible to a pathologic fracture when a tumor is present.”

A primary operation was performed upon 6.7% of patients, with the most frequent type of operation being limb salvage surgery (62.7%). Local surgical remission was achieved in 95.7% of patients; total surgical remission was achieved in 91.5% of patients.

Patients with pathologic fractures and without had osteosarcomas commonly located in the humerus (31.2% vs 8.4%; P <.001) and in the proximal part of the bone (50.8% vs 42.7%) as well as the diaphysis (6.0% vs 2.7%; P <.001). Patients with pathologic fractures were also more likely to have primary metastases than patients without pathologic fractures (19.0% vs 14.3%; P = .025).

Moreover, in adult patients with and without pathologic fractures , the 10-year OS rates were 36.8% and 62.1%, respectively (P <.001). The 10-year EFS rates were 34.2% and 49.5%, respectively (P <.001).

Variables associated with poorer OS in the total cohort were tumor site in the femur (HR, 0.764; P = .041), primary metastases (HR, 2.216; P <.001), poor response to chemotherapy (HR, 2.330; P <.001), failed achievement of total surgical remission (HR, 4.634; P <.001), and ablative surgery (HR, 1.289; P = .002). The presence of pathologic fractures leaned toward poorer OS (HR, 1.253; P = .081) but was not significant for EFS (HR, 1.033; P = .779). For EFS, the following variables resulted in poorer outcomes in multivariable analysis: age (HR, 1.011; P = .021), tumor site in the femur (HR, 0.744; P = .011), large relative tumor size (HR, 1.256; P = .002), primary metastasis (HR, 3.305; P <.001), and poor response to chemotherapy (HR, 2.207; P <.001).

Moreover, among adults, presence of pathologic fractures was associated with poorer OS (HR, 1.893; P = .013) but not with EFS (HR, 1.248; P = .360). In patients <18 years of age, presence of pathologic fractures was not associated with poorer OS (HR, 1.070; P = .664) or poorer EFS (HR, 0.968; P = .810).

In pediatric patients, results also showed that OS and EFS did not differ significantly between patients with and without pathologic fractures. Patients aged 0 to 18 years with pathologic fractures had estimated 5-year OS rates of 68.5% at 5 years and 64.8% at 10 years versus without pathologic fractures at 71.0% and 65.6%, respectively (P = .649).

“These results confirm those published in several previous studies that concluded that pathologic fractures are a predictor for worse survival in osteosarcoma,” the authors concluded in the study. “A decreased survival rate and a higher occurrence of [local recurrence] in patients with pathologic fractures was also found by our group. This study showed a significantly lower survival rate for adults with [pathologic fractures] and no significant survival difference in children with and without [pathologic fractures], as did our present study.”

Kelley LM, Schlegel M, Hecker-Nolting S, et al. Pathological fracture and prognosis of high-grade osteosarcoma of the extremities: an analysis of 2,847 consecutive cooperative osteosarcoma study group (COSS) patients [published online ahead of print January 13, 2020]. J Clin Oncol. doi:10.1200/JCO.19.00827.