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Can a positive positron emission tomography scan be positive news?

Response assessment is of paramount importance in lymphoma therapy. It is no surprise that patients who achieve a complete response (CR) by computed tomographic (CT) assessment do better than patients who achieve a lesser response. Several studies have reported that a negative positron emission tomography (PET) scan after treatment of Hodgkin’s lymphoma or aggressive non-Hodgkin’s lymphoma correlates with a good patient outcome when the scan is obtained during or after treatment. For example, in patients with aggressive lymphoma, we found that a PET-negative partial response resulted in a similar outcome to a CR by CT, suggesting that PET improves the prognostic ability of CT response assessment [1]. A positive PET scan may be indicative of malignancy, immune response, or both. This raises the question: is a positive PET scan ever positive? Several prior studies suggest that an immune response can be generated to lymphoma using patient specific vaccines or dendritic cell therapies, and that disease control after chemotherapy may be prolonged by patient specific vaccination strategies [2]. Phase III trials of patient specific vaccines have been completed and the outcome data are eagerly anticipated, and assessment of dendritic cell approaches also continues. In this issue of Leukemia and Lymphoma, Baudard et al. [3] report on the PET and CT responses of six patients treated with a dendritic cell vaccine on a clinical trial. Three of these patients had measurable disease at the time of vaccination. One of the three patients with macroscopic disease responded to vaccine therapy with an increase in [F]fluorodeoxyglucose (FDG) uptake after the fifth vaccination, followed later by resolution of the previously measurable node with no FDG uptake. An increase in the size and number of lymph nodes, and an increase in FDG uptake, was noted in the other two patients with macroscopic disease. Similarly, one patient in CR prior to vaccination progressed by CT and PET criteria after vaccination. This report describes a number of interesting findings. The increase in FDG uptake in the responding patient during vaccination suggests that PET may be able to identify the migration of immune cells to tumor. The response seems to be specific to patient tumor because no unexpected sites of FDG uptake were reported. Conversely, an increase in FDG uptake at new sites, as well as increase in FDG uptake in sentinel lesions, was associated with increase in nodal size and number by CT imaging in the non-responding patients. The study used standard criteria for measurable disease and considered a PET to be positive when the Standard Uptake Value (SUV) was 2.5 or greater, a value that is controversial but used in other studies [4]. Despite these findings, the present study has a number of limitations. The responding patient had the smallest macroscopic tumor burden of the three patients reported and, presently, there is no indication that the subject’s response correlates with induction of a cellular or humoral anti-lymphoma response. The very small sample size must be viewed as interesting but anecdotal, and a more detailed report from a larger cohort of patients is necessary to confirm the hypothesis that PET imaging can be useful in monitoring immunotherapy. Nevertheless, the report is interesting and supports further study. Several studies have suggested that immune cells migrate to the site of malignancy. Ridolfi et al. [5]