Page 222 - 18F-FDG PET as biomarker in aggressive lymphoma; technical and clinical validation

Chapter 8
5 criteria [3], which were higher than the PPV of 30.5% for DS4-5–positive patients at I-PET2 in this study. This difference can be explained by the fact that 40.3% of the patients with an I-PET scan after 2 cycles were from the PETAL trial, and the PPV of DS4-5 in the PETAL trial was 26.4% (data not shown). Nyilas et al [23] retrospectively included mainly patients with an I-PET after 4 cycles and reported a PPV of 48%, which is slightly higher than our PPV of 42.6% at I-PET4. The PPV of ∆SUVmax–positivity criteria was higher in our study, which confirms the higher PPV using ∆SUVmax positivity criteria in the PETAL trial [24]. For all PET-positivity criteria, PPVs are rather low, but both PPV and NPV are dependent on the prevalence of the outcome. Because the prior probability (ie, prevalence) of progression is 21.9% in our data, it is hard to reach a high PPV. After I-PET scans, the posterior probability increases for poor responders (ie, increase in PPV ) and decreases for good responders (ie, high NPV ), further stratifying risk groups.
These results show that I-PET scans have the potential to guide risk adapted therapy. By detecting suboptimal response, therapy can be adapted earlier, potentially leading to higher cure rates and lower toxicity. DS5 patients have the worst response and can be identified as early as I-PET2 because PPV at I-PET2 is similar to that at I-PET4. For ∆SUVmax positive and DS4 patients, I-PET4 would be the optimal timing, because the discriminative power is higher at I-PET4. However, I-PET4 is quite late for an I-PET–based strategy, so the importance of a high predictive value should be balanced with the reduced potential for early treatment escalation in the case of ineffective chemotherapy. In clinical trials, I-PET can be used to power new trials that investigate the potential of new drugs for treating patients who have DLBCL and a DS5 at I-PET2 or with a poor response using ∆SUVmax criteria at I-PET4. So far, I-PET2–based treatment escalation has not been effective in DLBCL [13]. When detecting good response from I-PET scans, de-escalation of therapy might be considered. For treatment de-escalation, I-PET2 seems to be the optimal timing. A recent trial showed that treatment de-escalation seems feasible for patients with DLBCL between ages 18 and 60 years who have a favorable prognosis, because treatment with 4 cycles of R-CHOP plus 2 cycles of rituximab was noninferior to 6 cycles of R-CHOP [25]. Moreover, interim-PET–guided treatment in limited-stage nonbulky de novo DLBCL resulted in high survival rates for poor responders and good responders at I-PET [26]. Similar approaches could be considered for all DLBCL patients with a good response at I-PET2.
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