Strikingly high false positivity of surveillance FDG‐PET/CT scanning among patients with diffuse large cell lymphoma in the rituximab era

Abstract

Predictive value (PV) of surveillance fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with diffuse large B-cell lymphoma (DLBCL) treated with chemotherapy-rituximab (R) versus chemotherapy only, remains unclear. The aim of the current study was to compare the performance of surveillance PET in DLBCL patients receiving CHOP (cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, and prednisone) alone versus CHOP-R. Institutional database was retrospectively searched for adults with newly diagnosed DLBCL, receiving CHOP or CHOP-R, who achieved complete remission and underwent surveillance PETs. Follow-up (FU) PET was considered positive for recurrence in case of an uptake unrelated to physiological or known benign process. Results were confirmed by biopsy, imaging and clinical FU. One hundred nineteen patients, 35 receiving CHOP and 84 CHOP-R, who underwent 422 FU-PETs, were analyzed. At a median PET-FU of 3.4 years, 31 patients relapsed (17 vs. 14, respectively; P 5 0.02). PET detected all relapses, with no false-negative studies. Specificity and positive PV (PPV) were significantly lower for patients receiving CHOP-R vs. CHOP (84% vs. 87%, P 5 0.023; 23% vs. 74%, P < 0.0001), reflecting a higher false-positive (FP) rate in subjects receiving CHOP-R (77% vs. 26%, P < 0.001). In the latter group, FP-rate remained persistently high up to 3 years post-therapy. Multivariate analysis confirmed rituximab to be the most significant predictor for FP-PET. In conclusion, routine surveillance FDG-PET is not recommended in DLBCL treated with rituximab; strict criteria identifying patients in whom FU-PET is beneficial are required. Am. J. Hematol. 88:400-405,

Utility of Routine Post-Therapy Surveillance Imaging in Diffuse Large B-Cell Lymphoma

“…11 However, our results are in agreement with the five previous studies that have failed to show a survival benefit when relapses are detected before development of symptoms or physical examination abnormalities. 11,12,14,25,31 Due to the small number of patients with asymptomatic relapse detected solely via surveillance scan in this cohort, we were unable to identify a subgroup of patients where surveillance may be useful. Determining the optimal follow-up strategy and potentially a group of patients where scans may be beneficial is difficult outside of a prospective, randomized trial.…”

“…32 Imaging studies, particularly PET scans, may have false-positive results and lead to further testing including unnecessary biopsies. 20,25 Patients' quality of life may be negatively affected, as the anticipation of a scan is associated with increased anxiety levels for lymphoma survivors. 22 Lastly, imaging costs money.…”

“…[10][11][12] One recent study from El-Galaly et al 21 reported a reduced risk of death in patients with DLBCL detected solely via imaging, however, this association was no longer significant after excluding those who relapsed with an indolent lymphoma histology and those with relapse before first surveillance imaging. Furthermore, scans have potential downsides-patient anxiety, 22 radiation exposure, 23,24 false-positive results leading to more testing, 9,20,25 and cost. In this study, we examined the utility of posttherapy surveillance imaging in a large, prospectively enrolled cohort of patients with DLBCL predominantly from the upper Midwest of the United States and confirmed our results in an independent cohort of patients from France.…”

Reply: Interim PET in Hodgkin Lymphoma: Is It So Useless?

“…However, both studies had a major (12)(13)(14)(15). Posttreatment and follow-up 18 F-FDG PET/CT studies have a strikingly high number of false-positive results, as has been reported for several lymphoma subtypes (16)(17)(18)(19), including Hodgkin lymphoma (20). Consequently, the studies by Gallamini et al (12,13) are methodologically seriously biased.…”

The Role of Functional Imaging in Lymphoma: Current Controversies and Future Directions

“…Multivariate analysis showed rituximab administration was the most significant predictor of FP PET. 10 Guidelines state that PET should be avoided within 10 days of chemotherapy, 2 weeks of granulocyte-colony stimulating factor (G-CSF) treatment, or 3 months of radiotherapy in order to minimize false positives. 9 Allogeneic stem cell transplantation (alloSCT) can also result in persistent reactive FDG positivity.…”