Quantitative Whole-Body Diffusion-weighted MRI after One Treatment Cycle for Aggressive Non-Hodgkin Lymphoma Is an Independent Prognostic Factor of Outcome

Abstract

Purpose: To evaluate the prognostic utility of apparent diffusion coefficient (ADC) changes at whole-body diffusion-weighted (WB-DW) MRI after one treatment cycle for aggressive non-Hodgkin lymphoma (NHL) compared with response assessment at interim and end-of-treatment fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT.

Materials and methods: This was a secondary analysis of a prospective study (ClinicalTrials.gov identifier: NCT01231269) in which participants with aggressive NHL were recruited between March 2011 and April 2015 and underwent WB-DW MRI before and after one cycle of immunochemotherapy. Volunteers were recruited for test-retest WB-DW MRI (ClinicalTrials.gov identifier: NCT01231282) to assess ADC measurement repeatability. Response assessment was based on ADC change after one treatment cycle at WB-DW MRI and Deauville criteria at 18F-FDG PET/CT. To evaluate prognostic factors of disease-free survival (DFS), Kaplan-Meier survival analysis and univariable and multivariable Cox regression were performed; intraclass correlation coefficient (ICC) and mean difference with limits of agreement were calculated to determine inter- and intraobserver repeatability of ADC measurements.

Results: Forty-five patients (mean age, 58 years ± 17 [standard deviation]; 31 men) and nine volunteers (mean age, 22 years ± 3; seven men) were enrolled. Median DFS was 48 months (range, 2-48 months). Outcome prediction accuracy was 86.7% (39 of 45), 71.4% (30 of 42), and 73.8% (31 of 42) for WB-DW MRI and interim and end-of-treatment 18F-FDG PET/CT, respectively. WB-DW MRI (hazard ratio [HR], 17.8; P < .001) and interim (HR, 5; P = .008) and end-of-treatment (HR, 4.3; P = .017) 18F-FDG PET/CT were prognostic of DFS. After multivariable analysis, WB-DW MRI remained an independent predictor of outcome (HR, 26.8; P = .002). Intra- and interobserver agreement for ADC measurements were excellent (ICC = 0.85-0.99).

Conclusion: Quantitative WB-DW MRI after only one cycle of immunochemotherapy predicts DFS in aggressive NHL and is noninferior to routinely performed interim and end-of-treatment 18F-FDG PET/CT.Keywords: MR-Diffusion Weighted Imaging, Lymphoma, Oncology, Tumor Response, Whole-Body ImagingSupplemental material is available for this article.© RSNA, 2021.

Keywords: Lymphoma; MR-Diffusion Weighted Imaging; Oncology; Tumor Response; Whole-Body Imaging.

Conflict of interest statement

Disclosures of Conflicts of Interest: K.N.D.P. disclosed no relevant relationships. C.A.V.K. disclosed no relevant relationships. G.M.A. disclosed no relevant relationships. F.D.K. disclosed no relevant relationships. O.G. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: author received consultancy fees from IBA and payment for lectures including service on speakers bureaus from Pfizer. Other relationships: disclosed no relevant relationships. O.B. disclosed no relevant relationships. P.W. disclosed no relevant relationships. D.D. disclosed no relevant relationships. A.J. disclosed no relevant relationships. G.V. disclosed no relevant relationships. R.O. disclosed no relevant relationships. M.K. disclosed no relevant relationships. V.V. disclosed no relevant relationships.

2021 by the Radiological Society of North America, Inc.

Figures

Figure 1:

A, Whole-body short-tau inversion-recovery (STIR) image in a 21-year-old female volunteer and overlay of a color-scaled diffusion-weighted image. A region-growing segmentation tool with adaptable threshold allows for the identification of lymph nodes, such as the axillary nodes in this patient (arrow). B, Whole-body STIR image and color-scaled diffusion-weighted image overlay in a 50-year-old man with stage IV mantle cell lymphoma. The large mediastinal mass (arrow) was segmented using a high threshold to include only the most hyperintense component of the mass, excluding the central necrotic portion of the tumor (*). Also shown is a large solid retroperitoneal mass (arrowhead).

Figure 2:

Consolidated Standards of Reporting Trials diagram of patient inclusion. FDG = fluorodeoxyglucose, WB-DWI = whole-body diffusion-weighted imaging.

Figure 3:

Example of a 41-year-old woman with stage I primary mediastinal B-cell lymphoma. A, Mediastinal mass (arrow) with high fluorine 18 (18F) fluorodeoxyglucose (FDG) uptake at 18F-FDG PET/CT (left), high b1000 signal at diffusion-weighted (DW) imaging (middle), and low signal on apparent diffusion coefficient (ADC) map (right). B, After 2 weeks, 18F-FDG uptake of the mass (arrow) was in keeping with good partial response. DW imaging shows decreased signal on the b1000 images and marked increase of ADC (from 1.02 to 1.80 × 10−3 mm2/sec), confirmed on, C, the ADC histogram, indicating good outcome. D, End-of-treatment 18F-FDG PET/CT shows inflammatory changes (arrowhead), yet complete remission, which was maintained until the end of follow-up.

Figure 4:

Example of a 59-year-old male patient with stage IV diffuse large B-cell lymphoma with recurrent disease. A, At baseline, fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT (left), b1000 diffusion-weighted (DW) imaging (middle), and corresponding apparent diffusion coefficient (ADC) map (right) demonstrate involvement of right cervical lymph nodes (arrow). B, After 3 weeks of therapy, the 18F-FDG PET/CT scan was negative to disease, but at DW imaging the nodes (arrow) still show high b1000 signal intensity and low ADC. C, Although the ADC-derived histogram shows a marked volume decrease, there is also a decrease in ADCmean (from 1.16 to 1.07 × 10−3 mm2/sec), rendering this a poor outcome. D, End 18F-FDG PET/CT still shows complete remission. E, After 20 months, a follow-up 18F-FDG PET/CT shows recurrent disease in multiple lymph node regions above and below the diaphragm.

Figure 5:

Kaplan-Meier survival curves of disease-free survival on the basis of whole-body diffusion-weighted (WB-DWI) MRI and interim and end-of treatment fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT assessment of treatment response.