Radiation-induced occult insufficiency fracture or bone metastasis after radiotherapy for cervical cancer? The nomogram based on quantitative apparent diffusion coefficients for discrimination

Abstract

Background: Radiation-induced insufficiency fractures (IF) is frequently occult without fracture line, which may be mistaken as metastasis. Quantitative apparent diffusion coefficient (ADC) shows potential value for characterization of benign and malignant bone marrow diseases. The purpose of this study was to develop a nomogram based on multi-parametric ADCs in the differntiation of occult IF from bone metastasis after radiotherapy (RT) for cervical cancer.

Methods: This study included forty-seven patients with cervical cancer that showed emerging new bone lesions in RT field during the follow-up. Multi-parametric quantitative ADC values were measured for each lesion by manually setting region of interests (ROIs) on ADC maps, and the ROIs were copied to adjacent normal muscle and bone marrow. Six parameters were calculated, including ADC_mean, ADC_min, ADC_max, ADC_std, ADC_mean ratio (lesion/normal bone) and ADC_mean ratio (lesion/muscle). For univariate analysis, receiver operating characteristic curve (ROC) analysis was performed to assess the performance. For combined diagnosis, a nomogram model was developed by using a multivariate logistic regression analysis.

Results: A total of 75 bone lesions were identified, including 48 occult IFs and 27 bone metastases. There were significant differences in the six ADC parameters between occult IFs and bone metastases (p < 0.05), the ADC ratio (lesion/ muscle) showed an optimal diagnostic efficacy, with an area under ROC (AUC) of 0.887, the sensitivity of 95.8%, the specificity of 81.5%, respectively. Regarding combined diagnosis, ADC_std and ADC_mean ratio (lesion/muscle) were identified as independent factors and were selected to generate a nomogram model. The nomogram model showed a better performance, yielded an AUC of 0.92, the sensitivity of 91.7%, the specificity of 96.3%, positive predictive value (PPV) of 97.8% and negative predictive value (NPV) of 86.7%, respectively.

Conclusions: Multi-parametric ADC values demonstrate potential value for differentiating occult IFs from bone metastasis, a nomogram based on the combination of ADC_std and ADC_mean ratio (lesion/muscle) may provide an improved classification performance.

Keywords: Apparent diffusion coefficient; Cervical cancer; Insufficiency fracture; Nomogram; Radiotherapy.