We read with interest the study by Mayerhoefer and colleagues (1) that included 51 patients who underwent interim and 48 patients who underwent end-of-treatment 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) and diffusion-weighted magnetic resonance imaging (DWI). FDG-PET/CT and DWI were reported to agree in 99.4% of cases on a region-based level, and in 97.1% of cases with regard to treatment response assessment. Mayerhoefer and colleagues (1) concluded DWI to be a feasible alternative to FDG-PET/CT for follow-up and treatment response assessment. However, we believe their data do not support the clinical implementation of DWI in these settings.

An important weakness of the study by Mayerhoefer and colleagues (1) is that FDG-PET/CT was used as reference standard. Although DWI and FDG-PET/CT showed very good agreement, the value of both interim and end-of-treatment FDG-PET/CT in predicting outcome was demonstrated to be unsatisfactory in various lymphoma subtypes by recent meta-analyses (2–4), with a high proportion of FDG-PET/CT-negative patients developing relapsed disease during follow-up (2–4). Of interest, a recently published large-scale randomized controlled trial in which patients with negative interim FDG-PET/CT results were randomized to standard or less intensive treatments was ceased prematurely due to the notable higher numbers of disease relapses in interim FDG-PET/CT-negative patients receiving less intensive treatment (5). Only prospective studies with homogeneous patient populations and treatments that correlate DWI results to patient outcome measures will provide reliable evidence.

Another concern is the DWI interpretation criteria that were used. Mayerhoefer and colleagues (1) describe that regions were rated as positive for lymphoma when at least one lymph node or lesion showed restricted diffusion on DWI, defined as a high signal on the b = 50 s/mm2 images (relative to the surrounding tissues), and persistence or increase of the signal on the b = 1,000 s/mm2 images (relative to the b = 50 s/mm2 images); or a high signal on the b = 50 s/mm2 images and low signal on the apparent diffusion coefficient (ADC) map (relative to the surrounding tissues). However, both lymphomatous and normal lymph nodes fulfill these criteria, and it is unclear how Mayerhoefer and colleagues (1) were able to differentiate these two lymph node conditions with such high interobserver agreement.

In conclusion, Mayerhoefer and colleagues (1) have not proven DWI to be a useful technique for response evaluation in lymphoma, the main reason being the use of FDG-PET/CT as unsatisfactory reference standard. Moreover, the proposed DWI interpretation criteria cannot differentiate between lymphomatous and normal lymph nodes.

See the Response, p. 3809

No potential conflicts of interest were disclosed.

This project was financially supported by an Alpe d'HuZes/Dutch Cancer Society Bas Mulder Award for T.C. Kwee (grant number 5409). Data collection, data analysis, and interpretation of data, writing of the paper, and decision to submit were left to the authors' discretion and were not influenced by Alpe d'HuZes/Dutch Cancer Society.

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