Diagnostic value of PET-CT for early detection of MRONJ in breast cancer patients.

Abstract

e13112 Background: Antiresorptive therapy with denosumab is standard care for patients with osseous metastasized breast cancer. One of the most important toxicities of this class of drugs is medication-related osteonecrosis of the jaw (MRONJ). MRONJ represents a major medical burden, impairs quality of life and may necessitate discontinuation of treatment. Currently diagnosis of MRONJ includes symptoms like pain, swelling or infection of the jaw. The objective of this study was to assess the possibility of early detection of MRONJ by imaging, specifically PET/CTs (positron emission tomography with computed tomography). Methods: This study included all patients with metastasized breast cancer receiving denosumab, diagnosed with MRONJ between 2000 and 2020 at the Department of Obstetrics and Gynecology Innsbruck, who received continuous PET/CTs. To each of these patients we matched two patients with similar characteristics as a control group. Control patients with metastasized breast cancer also received denosumab and regular PET/CTs but developed no MRONJ. Two senior radiologist then separately examined all PET/CTs of these patients starting from the beginning of treatment with antiresorptive therapy until first appearance of lesion in the jaw or present time. In cases of differing assessments, a consensus was reached through joint re-evaluation. Results: The baseline characteristics were well balanced regarding age, menopausal status and duration of antiresorptive therapy. Presence of jaw lesion depending on group is shown in the table. Median time to develop MRONJ was 36 months (7-78) during which patients received 120 mg denosumab once per month subcutaneously without de-escalation of therapy. Sensitivity to predict MRONJ in case of detection of jaw lesions was 91% (19 of 21 MRONJ cases). Lead time of imaging by demonstrating lesion in the jaw was in median 238 days (11-1118) prior to MRONJ diagnosis. Moreover, in 68% of the MRONJ cases the radiology physicians were able to predict the exact tooth location of the MRONJ with a deviation of no more than two teeth. In the control group a lesion was found in 28.6% (12 of 42) patients without development of MRONJ so far. Conclusions: This study showed that imaging has a very high sensitivity and excellent negative predictive value for early detection of MRONJ. These results are highly relevant for clinical practice as many patients receive regular PET/CTs and this provides the opportunity to detect MRONJ with a lead time that allows for early intervention. Presence of jaw lesion. MRONJ (N = 21) NO MRONJ (N= 42) Jaw Lesion 19 12 Positive predictive value* 30.16% No lesion in the jaw 2 30 Negative predictive value* 98.21% Sensitivity 91% Specificity 71% *These values were adjusted assuming disease prevalence of 11.6% according to Brunner et al JCO August 2024, https://doi.org/10.1200/JCO.24.00171.