Despite improvements in cure rates for patients with diffuse large B-cell lymphoma (DLBCL), up to 40% relapse after achieving initial remission, mostly within 18 months from treatment. There is no consensus as to role, or most appropriate form of post-remission surveillance. Our aim was to explore the role of Positron Emission Tomography combined with computer tomography (PET-CT) scanning in the follow up of patients with diffuse large B-cell lymphoma (DLBCL) achieving complete metabolic response (CMR) after primary therapy, identify patterns of relapse and define a risk-adapted strategy.
We included 116 patients with de novo DLBCL treated at our centre between 2002 and 2009 with a negative post-treatment PET-CT, and at least one surveillance PET-CT scan. International Prognostic Index (IPI) was <3 in 77 (66%) and ≥3 in 37 (32%) patients. With a median follow up of 53 months (range 8–133), 456 surveillance scans were performed (range 1–10 per patient). 13 patients (11%) relapsed, with an actuarial 5 year relapse free survival of 86%. Two-thirds of relapses occurred in the first 18 months following completion of treatment. In seven cases (54%), the relapse was suspected based on symptoms and in six (46%) the relapse was subclinical and detected with PET. There was no difference in survival (P=0.76) or second line IPI (P=1.00) between the groups, as the number of relapses was small.
PET-CT had very high sensitivity (100%), specificity (98%) and negative predictive value (NPV, 100%) with positive predictive value (PPV) 56% in the cohort of patients with a low IPI (<3) compared with 80% if the IPI was ≥3. Across the entire cohort, the average number of patients in remission needed to scan to detect one subclinical relapse within the first 18 months was 42. However, for those with an IPI ≥3 the number needed to scan to detect one subclinical relapse was 22. Surveillance PET-CT had a very low yield after 18 months had elapsed from the conclusion of primary therapy (1 true positive among 170 scans). Interim response PET-CT was performed in 81 (70%) patients; achieving CMR was not a predictor of time to relapse (P=0.65) or having a positive surveillance scan, irrespective of IPI (P=1.00). Second malignancies were detected by PET-CT in eight patients (7%).
The achievement of CMR at the completion of primary therapy identifies a group of patients with favourable outlook and a low risk of relapse. Surveillance PET-CT scanning within this select cohort has high sensitivity, specificity and NPV and despite the low number of relapses retains a high PPV, particularly in patients with IPI≥3. Surveillance PET-CT is useful in the first 18 months following completion of primary therapy in patients in whom IPI at diagnosis is ≥3. We feel that such a strategy would be appropriate to evaluate in a prospective comparative trial.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.