1039 - Identifying Patients with Bone Metastases at Highest Risk of Skeletal-Related Events and Understanding Underuse of Bone Modifying Agents: A Retrospective Analysis

L. R. Narra^1,2, T. Gutschenritter^2,3, J. Leu², T. Gooley⁴, J. T. Yang⁵, and E. F. Gillespie²; ¹Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, ²Department of Radiation Oncology, University of Washington, Seattle, WA, ³Radiation Medicine Associates, Oklahoma City, OK, ⁴Translational Science and Therapeutics, Fred Hutchinson Cancer Center, Seattle, WA, ⁵New York University School of Medicine, New York, NY

Purpose/Objective(s): Skeletal-related events (SRE) are a common cause of morbidity in patients with bone metastases. Guidelines recommend bone modifying agents (BMA), though underuse is common. In a recent phase 2 randomized controlled trial, radiation prevented SRE in patients with widespread high-risk asymptomatic bone metastases. The objectives of this study are: 1) estimate the incidence of high-risk lesions among patients with bone metastases, 2) evaluate the phase 2 trial definition of “high risk”, and 3) evaluate reasons for BMA non-use. Materials/

Methods: Patients diagnosed with bone metastases and a systemic imaging report available from Feb-March 2022 at a single academic center were included. Patients were categorized as phase 2 trial eligible or not, where trial eligibility included non-oligometastatic disease with at least one asymptomatic lesion in a high-risk location (defined as hip/SI joints, long bones, and junctional spine). Fisher’s exact test, Chi-square, and multivariable analysis with a nominal logistic model were used.
Results: Among 415 patients with bone metastases from solid tumors, 184 (44%) had at least one asymptomatic high-risk lesion. With a median follow-up of 12 months (IQR:8-14), a total of 57 (13.7%) patients developed SRE, which was more common among patients meeting prior trial eligibility than those who did not (19.5% vs 9%, p=0.002). Factors associated with SRE included non-oligometastatic disease (p<0.001, OR=4.6, 95% CI: 1.94-11.2), and lesion location (p<0.001), but not age, sex, BMA use, histology or prior SRE. Among 203 patients with lesion-level SRE outcomes available, SRE occurred in 13/34 (38%) lesions in non-junctional spine, 6/23 (26%) hips/SI joint, 10/43 (23%) junctional spine, 5/21 (23%) chest wall/ribs/sternum, 5/51 (12%) long bones, and 1/31(3%) pelvis. BMA use was more common among patients with high-risk disease per phase 2 criteria compared to those without (71% vs 56%, p=0.002). Among patients not on BMAs (n=153), reasons for non-use were not documented (n=114, 75%), clinician considered but deferred (n=17, 11%) including for "limited disease" in 3 patients and "good response to systemic therapy" in 1 patient, pending dental evaluation (n=12, 7.8%), and previous discontinuation for side effects (n=6, 3.9%) including 3 with bone pain and 3 with renal dysfunction, and patient refusal (n=2, 1.3%).
Conclusion: Although our prior phase 2 trial definition appears to discriminate patients at higher risk of SRE, overall incidence of SRE is still low. Additionally, lesions in non-junctional spine appear at no lower risk than junctional spine. Patients deemed at high risk of SRE are more often prescribed BMAs, but still 1 in 4 patients are not, and reasons are multifactorial. Further research is needed to refine the definition of “high risk” to facilitate targeted interventions to prevent SRE.