PET/CT assessment in follicular lymphoma using standardized criteria: central review in the PRIMA study

Purpose

We aimed to compare the standardized central review of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT scans performed after induction therapy for follicular lymphoma (FL) in the PRIMA study (Salles et al., Lancet 377:42–51, 2011; Trotman et al., J Clin Oncol 29:3194–3200, 2011) to scan review at local centres.

Methods

PET/CT scans were independently evaluated by two nuclear medicine physicians using the 2007 International Harmonization Project (IHP) criteria (Cheson et al., J Clin Oncol 25:579–586, 2007; Juweid et al., J Clin Oncol 25:571–578, 2007; Shankar et al., J Nucl Med 47:1059–1066, 2006) and Deauville 5-point scale (5PS) criteria (Meignan et al., Leuk Lymphoma 50:1257–1260, 2009; Meignan et al., Leuk Lymphoma 51:2171–2180, 2010; Barrington et al., Eur J Nucl Med Mol Imaging 37:1824–1833, 2010). PET/CT status was compared with prospectively recorded patient outcomes.

Results

Central evaluation was performed on 119 scans. At diagnosis, 58 of 59 were recorded as positive, with a mean maximum standardized uptake value (SUV_max) of 11.7 (range 4.6–35.6). There was no significant association between baseline SUV_max and progression-free survival (PFS). Sixty post-induction scans were interpreted using both the IHP criteria and 5PS. Post-induction PET-positive status failed to predict progression when applying the IHP criteria [p?=?0.14; hazard ratio (HR) 1.9; 95 % confidence interval (CI) 0.8–4.6] or 5PS with a cut-off ≥3 (p?=?0.12; HR 2.0; 95 % CI 0.8–4.7). However, when applying the 5PS with a cut-off ≥4, there was a significantly inferior 42-month PFS in PET-positive patients of 25.0 % (95 % CI 3.7–55.8 %) versus 61.4 % (95 % CI 45.4–74.1 %) in PET-negative patients (p?=?0.01; HR 3.1; 95 % CI 1.2–7.8). The positive predictive value (PPV) of post-induction PET with this liver cut-off was 75 %. The 42-month PFS for patients remaining PET-positive by local assessment was 31.1 % (95 % CI 10.2–55.0 %) vs 64.6 % (95 % CI 47.0–77.6 %) for PET-negative patients (p?=?0.002; HR 3.3; 95 % CI 1.5–7.4), with a PPV of 66.7 %.

Conclusion

We confirm that FDG PET/CT status when applying the 5PS with a cut-off ≥4 is strongly predictive of outcome after first-line immunochemotherapy for FL. Further efforts to refine the criteria for assessing minimal residual FDG uptake in FL should provide a reproducible platform for response assessment in future prospective studies of a PET-adapted approach.