Volume Doubling Times of Pulmonary Metastases in Patients With Bone and Soft Tissue Sarcomas: Associations With Subsequent New Metastases and Survival After Metastasectomy

Background: Pulmonary metastases of bone and soft tissue sarcoma are common and have a high recurrence rate after metastatectomy. Factors associated with post-metastatectomy recurrence are not well studied. Objective: To investigate the association of the volume doubling time (VDT) of pulmonary metastases with the subsequent development of new pulmonary nodules and survival after metastasectomy in patients with bone or soft tissue sarcoma. Methods: This retrospective study included patients with bone or soft tissue sarcoma who, between July 2020 and December 2020, underwent first complete metastasectomy of pulmonary nodules visualized on two sequential preoperative CT scans. Semi-automatic volumetric segmentation of the pulmonary metastases was performed on the two CT scans, and VDTs were calculated. VDT was compared between patients with and without subsequent new metastases after metastatectomy. Cox proportional hazards regression analyses were performed to determine risk factors for recurrence-free survival (RFS) after metastasectomy and for post-metastasectomy overall survival (OS). Results: Forty patients (21 women, 19 men; mean age, 51.1±14.3 years) were included. Of these patients, 23 (57.5%) developed new metastatic nodules after metastasectomy, and 10 (25%) died during follow-up. Median VDT was shorter in patients with, versus without, new metastases after metastasectomy (56 vs. 140 days, p=.002). Only four of 23 patients with new metastases had VDT ≥140 days. In multivariable analysis, older age [hazard ratio (HR), 1.06; p=.004), female sex (HR, 2.80; p=.03), and VDT <140 days (hazard ratio [HR], 4.22; p=.01) were independent predictors of worse RFS. Also in multivariable analysis, only older age (HR, 1.17; p=.005) and VDT <50 days (HR, 8.60; p=.02) were independent predictors of worse OS. OS was significantly worse in patients with VDT <140 days (10 deaths among 27 patients) than in patients with VDT ≥140 days (no deaths in 13 patients) (p=.01). Conclusions: In patients with bone and soft tissue sarcoma, shorter VDT of pulmonary metastases is independently associated with subsequent new metastases after metastasectomy and worse OS. Clinical Impact: VDT of pulmonary nodules may be considered in patient selection for pulmonary metastasectomy and in postoperative patient management.