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Diffusion-Weighted MRI for Lymphoma Restaging—Response

We thankAdams and colleagues (1) for their continued interest in our research.We feel that discussionswithin the community are a main source of innovation and vital for scientific advancement. Unfortunately, the core of Adams and colleagues' criticism of our publication is, obviously, basedon an incorrect use ofmedical terminology. Adams and colleagues criticize our use of F-fluoro-2-deoxy-Dglucose positron emission tomography/computed tomography (FDG-PET/CT) as reference standard for treatment response assessment in lymphoma (2), because previously "the value of both interim and end-of-treatment FDG-PET/CT in predicting outcome was demonstrated to be unsatisfactory." This statement suggests that Adams and colleagues are mixing up two oncological terms, and thus aremisinterpreting our study, by substituting (i) treatment response assessment with (ii) treatment outcome prediction. "Treatment response assessment" describes the assessment of changes in tumor burden at predefined time points after treatment initiation/completion, or after a predefined number of therapeutic interventions. This is the definition of treatment response on which the Lugano classification of the International Conference on Malignant Lymphoma (ICML; ref. [3]), and the Response Evaluation Criteria In Solid Tumors (RECIST), rely. FDG-PET/CT is the standard for response assessment in FDGavid lymphoma (3), and, hence, its use as reference standard is justifiable. "Treatment outcome prediction," on the other hand, refers to the ability of qualitative/quantitative measures to predict the future clinical course of a patient—here, overall, or progression-free, survival serves as endpoint. Nowhere in our article do we claim that diffusion-weighted magnetic resonance imaging (DWI) predicts treatment outcome/survival—this is an entirely different topic. We would also like to emphasize that our DWI criteria for lymphoma involvement are consistent with those recommended in the literature—for instance, see the recent publication by Toledano-Massiah and colleagues (4). Furthermore, a body of published evidence supports the observation that apparent diffusion coefficients (ADC) can differentiate between normal and malignant lymph nodes; lymphomatous nodes even show particularly low ADCs (5). These publications also contain cases that illustrate the visually assessable differences between benign and lymphomatous nodes on DWI (4, 5). Nevertheless, the 12 false-positive nodal regions observed in our study (2) suggest an overlap of DWI features between benign/ reactive and lymphomatous lymph nodes. This tendency for disease overestimation by DWI is mentioned several times throughout our article—most prominently, in the conclusive paragraph. In view of the above, we feel that the conclusions drawn from our article remain perfectly valid, as published, with actually little room for misinterpretation: DWI-MRI may be an alternative to FDG-PET/CT for treatment response assessment in lymphoma; nevertheless, size criteria or reference tissues may need to be incorporated to reduce falsepositive DWI results.