The role of ¹⁸F-FDG PET/CT in early detection and risk assessment of medication-related osteonecrosis of the jaw

Objectives: Medication-related osteonecrosis of the jaw (MRONJ) is a significant side effect of antiresorptive and antiangiogenic drugs prescribed for advanced cancer patients. Because MRONJ is intractable, the early detection and risk assessment before the development of stage 2 MRONJ are crucial and have been attempted by various methods. However, the role of ¹⁸F-fluorodeoxyglucose (FDG) positron-emission tomography (PET)/computed tomography (CT) in the early detection and risk assessment of MRONJ is not yet fully understood. The aim of this study was to validate a diagnostic ability of FDG PET/CT for early-stage MRONJ.

Methods: We evaluated a total of 53 cancer patients who underwent FDG PET/CT for oncologic surveillance at our hospital retrospectively. In the MRONJ group, all 12 patients were diagnosed as stage 2 MRONJ by experienced dentists according to the American Association of Oral and Maxillofacial Surgeons staging system between August 2011 and May 2016, and underwent FDG PET/CT 3 months (the average 3.3 ± 1.8 months, range 0.7 to 5.7) before the first diagnosis of stage 2 MRONJ. The types of cancer of the patients were breast (83%), lung (8%), and prostate (8%). Regarding risk drugs of MRONJ, 9 (75%) patients had several drugs, 8 (67%) had zoledronic acid, 8 (67%) had denosumab, and 5 (42%) had bevacizumab. The average duration of risk drugs was 3.4 ± 2.5 years, ranged from 0.5 to 9.0 at the time of the first diagnosis of stage 2 MRONJ. MRONJ developed in the mandible and maxilla in 8 (66%) and 4 (33%) patients, respectively. Four (33%) patients underwent dental extraction less than 1 year (average 4.0 ± 3.6 months) before the diagnosis of stage 2 MRONJ. As the control group, we evaluated 41 consecutive breast cancer patients who had never received risk drugs of MRONJ (i.e., zoledronic acid, denosumab, and bevacizumab) and underwent FDG PET/CT between January 2014 and February 2014. There was no significant difference in age between the groups (63.2 ± 10.2 and 57.2 ± 11.3 years in the MRONJ group and the control group, respectively). Tracer uptakes in the jaw were analyzed by maximum standardized uptake value (SUVmax). We evaluated the screening accuracy of MRONJ based on SUVmax by receiver operating characteristic (ROC) analysis. The significance of high SUVmax for the prediction of early-stage MRONJ was calculated by Fisher’s exact test.

Results: The average SUVmax in the jaw of patients who developed stage 2 MRONJ was 6.4 ± 2.1 (range 3.4 to 9.7), 3 months before the diagnosis. In contrast, the average SUVmax in the jaw of patients who did not develop MRONJ was 3.6 ± 0.8 (range 2.2 to 6.3). The SUVmax in the jaw was significantly higher in patients who developed MRONJ than in those who did not, 3 months before the first diagnosis of stage 2 MRONJ (p < 0.001). The ROC analysis showed the area under the curve of 0.89. Using the cutoff value of 5.2, SUVmax for predicting stage 2 MRONJ showed sensitivity and specificity of 75 and 98%, respectively, at 3 months before the diagnosis. The SUVmax greater than 5.2 in the jaw were much more frequently observed in patients who subsequently developed stage 2 MRONJ 3 months after the FDG PET/CT than in those who did not (p < 0.0001 and odds ratio = 120).

Conclusion: For predicting occurrence of MRONJ, the threshold of SUVmax = 5.2 in the jaw may be used. A differential diagnosis including MRONJ is recommended when we incidentally detect regions with high ¹⁸F-FDG uptake in the jaw during routine oncologic surveillance. Research Support: