Page 136 - 18F-FDG PET as biomarker in aggressive lymphoma; technical and clinical validation

Chapter 6a
(interquartile range, 8.3-46.3) for I-PET-negatives. The corresponding PPV and NPV for 2-y PFS were 38% (95%CI, 30%-47%) and 85% (95%CI, 81%-88%), respectively.
Optimal I-PET4 response criterion
For various DS cutoffs, NPVs ranged between 82% and 85% for I-PET4 (Table 2). PPVs varied widely for different cutoffs (22%-68%); the highest PPV was seen for the DS5 cutoff in I-PET4 (68%). Also, the univariate HR of 7.4 was highest for the DS1-4 cutoff versus DS5, yielding the best separation between good and poor outcome (Supplemental Fig. 2). However, only 25 of 513 patients (5%) had a DS5.
∆SUVmax analysis was feasible in 367 of 574 patients (64%; Fig. 1). In patients with no more than a 70% ∆SUVmax reduction between baseline and I-PET4 (n=38, 10%) the 2-y PFS was 47% (95%CI, 31%-63%), versus 83% (95%CI, 78%-87%) for patients with more than a 70% reduction (Fig. 2b, P<0.001) with a univariate HR of 4.8 (95%CI, 2.9-8.0). Corresponding PPVs and NPVs for 2-y PFS were 53% (95%CI, 37%-68%) and 83% (95%CI, 78%-86%), respectively (Table 2). Repeating these comparisons in the 296 patients with complete metrics on baseline MTV yielded similar results (Supplemental Table 3).
PPV and HRs were better for ∆SUVmax than for the most commonly used cutoff, DS4-5 (53% vs. 38% and 4.8 vs. 3.1, respectively). NPV was above 80% for all applied criteria. When ∆SUVmax was compared with the most commonly used DS cutoff, DS4-5, ∆SUVmax was preferred for prediction of 2-y PFS, but the highest PPV and HR were found for the DS5 cutoff.
Combined baseline and I-PET4 analysis
Statistically significant prognostic factors for 2-y PFS in univariate Cox regression analyses were a ∆SUVmax of 70% or less, a high-intermediate or high aaIPI, and B-symptoms. In multivariable analysis, a high-intermediate or high aaIPI and no more than a 70% reduction of ∆SUVmax were independently associated with 2-y PFS (Supplemental Table 4). A Low or low-intermediate aaIPI and a ∆SUVmax of more than 70% (37% of patients) resulted in an NPV of 93% (95%CI, 87%-96%), whereas a high-intermediate or high aaIPI and a ∆SUVmax of 70% or less (6% of patients) resulted in a PPV of 65% (95%CI, 45%-81%, Supplemental Fig. 3).
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