Prospective Evaluation of FDG-PET Imaging of Treatment Response in Relapsed Follicular Lymphoma.
Authors: Brown Jennifer R. , Rastarhuyeva Iryna , Jagannathan Jyothi , Stevenson Kristen , Neuberg Donna , Melenevsky Yulia , Phillips Kimberly S. , Clark Jennifer C. , Takvorian Ronald W. , Fisher David C. , Freedman Arnold S. , Van den Abbeele Annick D. 
Published: April 2020

Abstract
Follicular lymphoma is the most common low-grade lymphoma and incurable with conventional therapies. In recent years, increased use of FDG-PET (PET) scanning in aggressive lymphomas has led to its application in follicular lymphoma, despite a lack of information on its predictive value. We undertook a prospective study to evaluate PET scanning prior to and following therapy (tx) in relapsed follicular lymphoma patients. Eligibility criteria included follicular grade I or II disease in 1st or 2nd relapse, with planned tx for at least stage 2 disease. Pre- and post-tx PET and CT scans were read by different blinded radiologists. 24 pts were enrolled; of these, two were ineligible and one was later found to have lung cancer. 21 pts were therefore analyzed. The median age at diagnosis was 57 (34–72), with a median time from diagnosis to pre-treatment PET scan of 2.8 yrs (0.6–9.0); 15 pts were in 1st relapse (71%), and 13 had follicular grade 1 (62%). By clinical staging, 4 were stage 2 (19%), 8 stage 3 (38%) and 9 stage 4 (43%). PET resulted in upstaging compared to CT in 5 pts (24%), 3 due to bone lesions and 2 due to nodal sites; however 3 of these 5 pts were also upstaged by bone marrow biopsy. The median of the highest SUVmax on the pre-tx PET scans was 12.1 (1.9–20.7). The mean SUVmax of all identified lesions on each pre-tx PET scan had a median value of 5.7 (1.9–8.4). A trend toward a correlation between the highest SUVmax on the initial PET scan and the bidimensional area of the largest CT lesion was observed (p=0.059). The tx received during the study included chemotherapy for 8 pts (38%) and antibody tx for 13 pts (62%). The objective response rate using Cheson criteria was 52%, with 5 CR/CRu, 6 PR, 7 SD and 3 PD. Using EORTC PET response criteria, 4 CR, 12 PR, 1 SD and 1 PD were observed. Thus 84% had evidence of response by PET, but 79% remained PET positive on their post-tx scan. The median value of the highest residual SUVmax on the post-tx scans was 5.13 (0.5–18.1); no correlation of residual SUVmax and bidimensional area of the largest residual CT lesion was observed. At 1-year follow-up, 48% of pts have relapsed, with a median time to relapse of 0.7 years (0.07–1.6). No pt who was PET negative on the post-tx scan has relapsed; of these 4 pts, 3 were also CRs by CT, and one had SD by CT criteria. PFS was not predicted by age, stage, or follicular subtype; a trend toward shorter PFS for pts in 2nd relapse was observed (p=0.055). Of CT and PET measures on initial and post-tx scans, only a residual SUVmax ≥ 5 predicted shorter PFS (p=0.0009); bidimensional area of the largest residual CT lesion was not predictive of PFS. Among pts with PR by PET criteria, CT responses by Cheson criteria (CRu, PR, SD) were not predictive of PFS (p=0.18). We conclude that PET imaging is highly sensitive for detection of follicular lymphoma, which commonly has high SUVmax values. A large fraction of relapsed follicular NHL pts who respond to tx by standard criteria have evidence of residual disease on FDG-PET, and positive lesions with SUVmax ≥ 5 are associated with a shorter PFS. The overall value of FDG-PET imaging in the management of pts with relapsed follicular lymphoma remains to be determined.