Reply to A. Hüttmann et al
Authors: Craig H. Moskowitz, Andrew D. Zelenetz, Heiko Schoder
Journal: Journal of Clinical Oncology (2010)

Hu ¨ttmann et al 1 raise the issue of the design of our clinical trial as well as the analysis of [ 18 F]fluorodeoxyglucose (FDG) positron emission tomography (PET) scans in our prospective dose-dense immunochemotherapy program for patients with advanced-stage diffuse large B-cell lymphoma (DLBCL).We understand some of the criticisms described in the correspondence; however, we disagree with their critique. 2,3Our results are not at variance with the modern rituximab-based chemotherapy programs for DLBCL.In fact, a number of recent studies using rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) administered every 21 days; rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone; rituximab plus CHOP administered every 14 days; or rituximab, etoposide, doxorubicin, vincristine, cyclophosphamide, and prednisolone as primary therapy found a similar falsepositive rate of interim FDG-PET as did our report, and there was no difference in progression-free survival between interim FDG-PETpositive and FDG-PET-negative patients. 4-12Of note, in Hodgkin's lymphoma, where a regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine every 2 weeks is used, the role of interim FDG-PET is better substantiated, 13 and FDG-PET is more accurate when performed 10 to 12 days after chemotherapy cycle 2B. 14There are no standard criteria for the evaluation of interim FDG-PET scans.We used the standard at the time, and in fact, it may still be the standard.Some research studies are using a 5-point scale (St Thomas Hospital Criteria) where a negative scan is no uptake, less than or equal to mediastinal blood pool, and greater than mediastinal blood pool but less than liver and a positive scan is either moderately or markedly greater than the liver with or without new lesions; this is clearly an investigational scale. 15 Several groups, including ours, are investigating the potential utility of change in standardized uptake value (SUV) as a predictive factor compared with visual analysis. 16,17This remains work in progress; Hu ¨ttmann et al 1 overstate the case for SUV-based analysis in the interim assessment of large-cell lymphoma.Two of the studies they cite in support of their point of view are either small or preliminary.The third study references the work by a group who suggested that a 66% decline in SUV after two cycles of chemotherapy or a 73% decline after four cycles of chemotherapy are suitable predictors for patient outcome.Patients in these studies were treated with four different regimens. 18,19Interestingly, percent change in SUV had a higher positive predictive value only for scans performed after two cycles of chemotherapy, but the positive predictive value of SUVbased analysis was in fact lower than that of visual analysis after four cycles of chemotherapy.Finally, the guidelines paper only states, "it is possible that semiquantitative assessment…may prove to be necessary for a more uniform and potentially more accurate assessment of midtherapy PET studies." 20In short, therefore, the issue of how to best interpret these scans currently remains unsettled. 21We have addressed these questions in more detail elsewhere.