Therapy Response Assessment of Pediatric Tumors with Whole-Body Diffusion-weighted MRI and FDG PET/MRI

Abstract

Background Whole-body diffusion-weighted (DW) MRI can help detect cancer with high sensitivity. However, the assessment of therapy response often requires information about tumor metabolism, which is measured with fluorine 18 fluorodeoxyglucose (FDG) PET. Purpose To compare tumor therapy response with whole-body DW MRI and FDG PET/MRI in children and young adults. Materials and Methods In this prospective, nonrandomized multicenter study, 56 children and young adults (31 male and 25 female participants; mean age, 15 years ± 4 [standard deviation]; age range, 6-22 years) with lymphoma or sarcoma underwent 112 simultaneous whole-body DW MRI and FDG PET/MRI between June 2015 and December 2018 before and after induction chemotherapy (ClinicalTrials.gov identifier: NCT01542879). The authors measured minimum tumor apparent diffusion coefficients (ADCs) and maximum standardized uptake value (SUV) of up to six target lesions and assessed therapy response after induction chemotherapy according to the Lugano classification or PET Response Criteria in Solid Tumors. The authors evaluated agreements between whole-body DW MRI- and FDG PET/MRI-based response classifications with Krippendorff α statistics. Differences in minimum ADC and maximum SUV between responders and nonresponders and comparison of timing for discordant and concordant response assessments after induction chemotherapy were evaluated with the Wilcoxon test. Results Good agreement existed between treatment response assessments after induction chemotherapy with whole-body DW MRI and FDG PET/MRI (α = 0.88). Clinical response prediction according to maximum SUV (area under the receiver operating characteristic curve = 100%; 95% confidence interval [CI]: 99%, 100%) and minimum ADC (area under the receiver operating characteristic curve = 98%; 95% CI: 94%, 100%) were similar (P = .37). Sensitivity and specificity were 96% (54 of 56 participants; 95% CI: 86%, 99%) and 100% (56 of 56 participants; 95% CI: 54%, 100%), respectively, for DW MRI and 100% (56 of 56 participants; 95% CI: 93%, 100%) and 100% (56 of 56 participants; 95% CI: 54%, 100%) for FDG PET/MRI. In eight of 56 patients who underwent imaging after induction chemotherapy in the early posttreatment phase, chemotherapy-induced changes in tumor metabolism preceded changes in proton diffusion (P = .002). Conclusion Whole-body diffusion-weighted MRI showed significant agreement with fluorine 18 fluorodeoxyglucose PET/MRI for treatment response assessment in children and young adults. © RSNA, 2020 Online supplemental material is available for this article.

Figures

Graphical abstract

Figure 1:

Flowchart shows study cohort with inclusion criteria. DW = diffusion weighted, 18F-FDG = fluorine 18 fluorodeoxyglucose, WB = whole body.

Figure 2:

Concordant information with fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/MRI and whole-body (WB) diffusion-weighted (DW) MRI for monitoring treatment of diffuse large B-cell lymphoma. A, Coronal color-encoded fused FDG PET/MRI scan and, B, color-encoded fused whole-body DW MRI scan obtained before chemotherapy in a 13-year-old boy with diffuse large B-cell lymphoma show FDG- and DWI-positive mediastinal lymph nodes (arrows). C, Coronal color-encoded fused FDG PET/MRI scan and, D, color-encoded fused whole-body DW MRI image obtained after induction therapy show complete treatment response.

Figure 3:

Discordant information with fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/MRI and whole-body (WB) diffusion-weighted (DW) MRI for monitoring treatment of Hodgkin lymphoma. A, Schematic overview of different signal kinetics of FDG PET/MRI and whole-body DW MRI before, during, and after chemotherapy. Before therapy, tumor cells show increased FDG metabolism (orange cells) and restricted diffusion (blue hydrogen protons). After induction chemotherapy, tumor cells demonstrate decreased FDG metabolism (blue cells) but still restricted diffusion. At the end of treatment, tumor cells show decreased FDG metabolism and unrestricted diffusion (blue hydrogen protons with arrows). B, Axial color-encoded fused FDG PET/MRI scan in a 22-year-old man with Hodgkin lymphoma before the start of therapy shows an FDG-avid lymph node in right inguinal region (arrow). C, Corresponding color-encoded fused whole-body DW MRI scan of same lymph node demonstrates increased DW signal (arrow). D, Axial color-encoded fused FDG PET/MRI scan after induction chemotherapy shows FDG signal resolution of the lymph node (arrow). E, Axial color-encoded fused whole-body DW MRI scan of same lymph node demonstrates decreased but still positive DW signal (arrow). F, Axial color-encoded fused FDG PET/MRI scan at the end of therapy shows complete FDG signal resolution (arrow). G, Axial color-encoded fused whole-body DW MRI scan at the end of therapy shows complete DW signal resolution (arrow). Of note, patient had increased FDG signal at the anus (* in F) on FDG PET/MRI scan at the end of therapy, suggesting bowel inflammation. This resolved completely at further follow-up without any treatment.

Figure 4:

Receiver operating characteristic curves of the true-positive rate (sensitivity) plotted as a function of the false-positive rate (1 – specificity) for different cut-off points of tumor maximum standardized uptake value (SUV) and tumor minimum apparent diffusion coefficient (ADC). Prediction of clinical response using change in maximum SUV (100%; 95% confidence interval [CI]: 99%, 100%) and using change in minimum ADC (98%; 95% CI: 94%, 100%) was not significantly different (P = .37). AUC = area under the receiver operating characteristic curve.