Critical considerations on the utility of <sup>18</sup>F‐fluoro‐2‐deoxy‐D‐glucose positron emission tomography/computed tomography for posttreatment restaging of the bone marrow in diffuse large B‐cell lymphoma
Authors: Hugo J.A. Adams, Thomas C. Kwee
Journal: American Journal of Hematology (2014)

To the Editor: We read with interest the article written by Jackson et al. 1 that was recently published in the Journal. Jackson et al. 1 aimed to investigate whether bone marrow assessment by restaging 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) could obviate the need for a repeat bone marrow biopsy (BMB) in diffuse large B-cell lymphoma (DLBCL). Their study included a retrospective series of 34 patients with a positive BMB at diagnosis and who had undergone posttreatment FDG-PET/CT and BMB (with 33 patients having both negative bone marrow FDG-PET/CT and BMB examinations, and one patient with both positive bone marrow FDG-PET/CT and BMB examinations), and a prospective series of four patients with a positive BMB at diagnosis and who had undergone posttreatment FDG-PET/CT and BMB (with all four patients having both negative bone marrow FDG-PET/CT and BMB examinations). Jackson et al. 1 reported that FDG-PET/CT had a 100% negative predictive value to exclude residual bone marrow disease in DLBCL patients after frontline therapy, using BMB as reference standard. In addition, repeat bone marrow biopsy may not provide additional information beyond that of a restaging FDG-PET/CT. Although Jackson et al.'s results sound very promising 1, they should be viewed with caution. First, the reported negative predictive value was positively biased due to the fact that only one case was found positive at posttreatment BMB 2. Any other diagnostic (imaging) test for bone marrow assessment can achieve a similarly high negative predictive value with such low (assumed) disease prevalence. Second, it should be realized that the sensitivity of pretreatment FDG-PET/CT for the detection of lymphomatous bone marrow involvement has been found to be far from optimal in DLBCL. Although a recent meta-analysis reported sensitivity values ranging between 70 and 95% for FDG-PET/CT 3, the studies included in that meta-analysis used both BMB and follow-up FDG-PET/CT scans as reference standard 3. However, FDG decrease at follow-up studies may not be sufficient proof to confirm pretreatment bone marrow involvement because benign bone marrow lesions may also demonstrate a decrease in FDG uptake after therapy. Thus, the actual diagnostic value of FDG-PET/CT in this setting may be lower than previously reported 3. A recent study published in the Journal supports this hypothesis, because it showed that, unlike pretreatment BMB findings, pretreatment bone marrow FDG-PET/CT findings were of no prognostic value in DLBCL 4. Moreover, recent studies showed that pretreatment FDG-PET/CT can be negative in even up to 30–50% of cases with a positive BMB 4, 5. The suboptimal sensitivity of pretreatment FDG-PET/CT is very likely also applicable to the posttreatment FDG-PET/CT-based evaluation of the bone marrow. In conclusion, due to the low prevalence of positive posttreatment BMBs in DLBCL, any diagnostic (imaging) test for posttreatment restaging of the bone marrow can achieve a high negative predictive value when BMB is used as reference standard. On a level of intrinsic test characteristics, recent evidence suggests that the sensitivity of FDG-PET/CT for the detection of lymphomatous bone marrow involvement is suboptimal in the pretreatment setting, and this is likely also applicable to the posttreatment setting. 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. Hugo J.A. Adams and Thomas C. Kwee* Department of Radiology and Nuclear Medicine, University Medical Center Utrecht Utrecht, The Netherlands