Neither Posttreatment PET/CT Nor Interim PET/CT Using Deauville Criteria Predicts Outcome in Pediatric Hodgkin Lymphoma

TO THE EDITOR: With interest we read the article by Bakhshi et al. (1) that was recently published online ahead of print. Their study aimed to assess the value of interim ¹⁸F-FDG PET (after 2 cycles of chemotherapy) and posttreatment ¹⁸F-FDG PET in predicting treatment failure, event-free survival, and overall survival. The study prospectively included 57 patients with early- or advanced-stage Hodgkin lymphoma treated with doxorubicin, bleomycin, vinblastine, and dacarbazine with or without additional radiation therapy. ¹⁸F-FDG PET scans were interpreted according to both the Revised International Workgroup criteria (2) and the Deauville criteria (3). Interim ¹⁸F-FDG PET, according to either the Revised International Workgroup criteria or the Deauville criteria, had no value in predicting event-free survival or overall survival. End-of-treatment ¹⁸F-FDG PET, interpreted according to the Revised International Workgroup criteria, was positive in only 7 patients and had a sensitivity of 25% and specificity of 88% in predicting treatment failure. This group of 7 patients included 4 patients with progressive disease according to end-of-treatment ¹⁸F-FDG PET, 3 of whom (75%) had false-positive findings (2 biopsy-confirmed and 1 determined by follow-up imaging), and 3 patients with partial remission according to end-of-treatment ¹⁸F-FDG PET, all 3 of whom (100%) were considered to have false-positive findings as determined by follow-up imaging. According to the Deauville criteria (which apply a higher threshold to determine positivity), only 3 of 52 patients (5.8%) were considered positive at end-of-treatment ¹⁸F-FDG PET. Two of these 3 cases (66%) were considered false-positive. Bakhshi et al. (1) concluded that posttreatment ¹⁸F-FDG PET using the Deauville criteria predicts outcome in Hodgkin lymphoma, particularly considering the high specificity of this imaging modality.

However, we strongly disagree with this conclusion. First, the fact that posttreatment ¹⁸F-FDG PET had a sensitivity of only 25% indicates that most patients who are not cured actually have negative posttreatment ¹⁸F-FDG PET findings. This is due to the limited spatial resolution of PET, as a result of which residual disease can never be excluded (4), as has been shown by several studies (5). The diagnostic performance of a test comprises both sensitivity and specificity. Any test with such a low sensitivity can generate a high specificity if the threshold to define positivity is simply raised. The combination of the very low sensitivity and the generally good prognosis of patients with Hodgkin lymphoma underlines that the number of patients needed to be scanned in order to detect one case of residual disease is actually quite high. ¹⁸F-FDG PET scans are expensive, are not available in all institutions, provide ionizing radiation, and cause discomfort to the patient. Furthermore, according to the study of Bakhshi et al. and several other studies (6), the false-positive rate of posttreatment ¹⁸F-FDG PET is actually very high. This applies to both the Revised International Workgroup criteria and the Deauville criteria, with false-positive rates of 85.7% and 66.7%, respectively, in the study by Bakhshi et al. (1). Awareness of this high false-positive rate is of the utmost importance, because it may result in unjustified initiation of second-line therapies and erroneous prognostication (if biopsy confirmation of ¹⁸F-FDG–avid lesions is not possible), lead to a high number of unnecessary conformational biopsies, and cause unnecessary patient anxiety. The fact that an early ¹⁸F-FDG PET–based detection of residual disease has not been proven to improve patient outcome further nullifies the need to acquire posttreatment ¹⁸F-FDG PET scans (7).

In conclusion, interim ¹⁸F-FDG PET fails to predict outcome in Hodgkin lymphoma, and posttreatment ¹⁸F-FDG PET scans have a strikingly low sensitivity for the detection of residual disease. Furthermore, most ¹⁸F-FDG–avid lesions seen on posttreatment ¹⁸F-FDG PET scans appear to be false-positive findings. Therefore, neither interim nor posttreatment ¹⁸F-FDG PET predicts outcome in Hodgkin lymphoma.

• © 2017 by the Society of Nuclear Medicine and Molecular Imaging.