This study aims to determine the prognostic value of interim 18F-FDG PET/CT in DLBCL. Actually, there are many controversies until now.
Multiple studies have proved that interim PET/CT can predict the outcomes of patients with DLBCL (12
). Yang DH et al.
evaluated the prognostic significance of interim PET/CT in the treatment of DLBCL. SUVmax
3.0 was defined as the cut-off value of interim PET/CT. Patients who continued to have positive interim PET/CT showed a significantly high relapse rate (62.8%) compared to those with a negative PET/CT (12.1%) (P<0.01). After a median follow-up period of 30.8 months, the positivity of interim PET/CT was found to be a prognostic factor for both OS and PFS. This study concluded interim PET/CT scanning had a significant predictive value for disease progression and survival of DLBCL (12
). However, other studies have drawn different conclusions (14
). The study performed by Yoo C et al.
demonstrated that there was no difference in PFS (P=0.07) and OS (P=0.24) between interim PET/CT positive and negative groups (14
In the present study, we also evaluated the correlation of interim PET/CT with the outcomes of patients with DLBCL. PET/CT results were affected by different machines, observers, and interpretation criteria. A more direct index in PET/CT is urgently needed to guide clinical treatment. A study has applied SUVmax
cut-off value to define PET/CT as negative or positive (12
), but there is still controversy. In our study, we set SUVmax
2.0, 2.5 and 3.0 as cut-off value of interim PET/CT, respectively. If SUVmax
2.0 and 3.0 were applied as cut-off value, there was no difference in 2-year PFS rates between interim PET/CT negative and positive patients (P=0.360; P=0.113). However, if we applied SUVmax
2.5 as the cut-off value, the 2-year PFS rates differed between the negative and positive patients (P=0.039). Unfortunately, we cannot analyze patients’ OS because of the small sample size and short follow-up time.
Recently, the role of SUVmax
reduction becomes more important in predicting outcomes of patients with DLBCL (16
). Casasnovas RO et al.
assessed whether SUVmax
can predict the survival of DLBCL. Eighty-five high-risk patients underwent PET/CT scans at baseline (PET0), after 2 (PET2) and 4 cycles (PET4) chemotherapy, respectively. ΔSUVmax
was calculated between PET2 and PET0 (ΔSUVmaxPET0-2
) or PET4 (ΔSUVmaxPET0-4
≤66%) analysis identified patients with significantly different 2-year PFS and OS rates (P=0.0282; P<0.0001). ΔSUVmaxPET0-4
≤70%) seemed even more predictive for 2-year PFS and OS rates (P<0.0001; P<0.0001) (16
). In this study, we also calculated SUVmax
reduction of interim PET/CT scan compared to the baseline result, and applied 70% and 90% as the cut-off value of SUVmax
reduction. But we did not find the correlation of SUVmax
reduction and the outcomes of DLBCL, and this may be attributed to the small sample size and short follow-up time.
The interim PET/CT cannot predict outcomes of DLBCL accurately, and the reasons are as following:
Difficulty in determining the exact timing of interim PET/CT scan
If patients underwent interim PET/CT too early (after 1-2 cycles of treatment), 2/3 interim positive patients will be turned to negative after the following treatment (15
), and it has reached agreement that post-treatment PET/CT negative patients have a good prognosis (6
). The outcomes of this group of interim PET/CT positive patients are similar to that of interim negative patients (14
). In this study, about half of the interim PET/CT positive patients turned to negative after the following treatment, and these patients did not relapse till now, indicating the treatment after interim PET/CT can affect the prognosis of patients. If patients underwent interim PET/CT too late (after 4 cycles for patients planning for receiving 6 cycles of treatment, after 6 cycles for the patients planning for receiving 8 cycles of treatment), the interim PET/CT loses its significance for predicting prognosis early.
High false-positive rate
FDG as a marker does not have such a high specificity because it is also taken up in infections and inflammatory processes (18
). Rituximab is a kind of immunotherapy drug, and antibody-mediated cellular cytotoxicity and complement activity are important mechanisms in rituximab’s activity. Both processes are able to attract mediators of inflammation to tumor sites (21
). Although a study recommended to exclude false-positive cases by biopsy (21
), it is hard in a clinical setting to perform biopsies on every lesion showing residual FDG uptake, and these may cause unwanted procedure-related complications or interruptions of treatment.
Absence of uniform interpretation criteria
Currently, there are many PET interpretation criteria, but most of these criteria are defined for post-treatment assessment. Recently, Horning et al.
reported only a moderate reproducibility among the observer in interim PET interpretation (23
). To minimize the affection of immunochemotherapy on the PET result, PET scans should not be performed for at least 3 weeks, and preferably 6-8 weeks, after completion of therapy (9
). This is easy for the post-treatment PET scan. However, it is difficult for the interim PET scan, because the time interval of the regimen for lymphoma is 2-3 weeks. To ensure the following treatment on time, the interim PET is always within 3 weeks. So it is inevitable of the affection of immunochemotherapy on the interim PET result.
In conclusion, using a SUVmax cut-off value of 2.5, interim PET/CT can predict the 2-year PFS rate of patients with DLBCL. But this is a small retrospective study. We should treat this result cautiously, and cannot adjust the following treatment according to the interim PET/CT. In the future, larger prospective trials are needed to assess the real prognostic value of interim PET/CT in patients with DLBCL.