Page 33 - 18F-FDG PET as biomarker in aggressive lymphoma; technical and clinical validation

Interim PET as biomarker of response in HL and DLBCL?
depends on patient age, fitness, disease distribution and, most importantly, the individual assessment of that risk in the decision-making process.
The recently published US Intergroup Trial of response adapted therapy for stage III-IV Hodgkin lymphoma used early interim PET after 2 cycles of ABVD to escalate therapy for patients with Deauville score 4 or 5 to BEACOPP escalated. The authors concluded that response-adapted therapy based on iPET imaging seemed promising with a 2-year PFS of 64% for PET2-positive patients compared to historical series with 2-year PFS of 15%-30% for PET-positive patients treated with ABVD [11].
Unpublished data presented in early and advanced disease from the EORTC H10 and the recently published UK Response Adapted Therapy in Advanced Hodgkin Lymphoma (RATHL) studies [12] also suggest that escalation from ABVD to BEACOPP may be beneficial in patients with an inadequate response on iPET after 2 cycles. In RATHL, patients randomized to receive AVD rather than ABVD on the basis of CMR on iPET had less pulmonary toxicity but no significant difference in 3-year PFS/OS. Published data are awaited for the EORTC H10 trial but in the meantime, at least in centers that participated in RATHL, this strategy is being offered to patients in clinical practice.
The H10 and RAPID trials used the mediastinal blood pool (equivalent to DS 2) as the reference region for CMR; the RATHL study used the liver (DS 3). To avoid under-treatment, it may be desirable to use the mediastinal blood pool in trials testing de-escalation. The RATHL study, which tested both treatment escalation and de-escalation, used DS 3 as a cutoff for CMR. The liver is a more reliable threshold for reporting iPET with respect to inter-reporter agreement and there was good agreement amongst reporters in local PET centers with expert central reviewers in RATHL [4]. This supports the use of DS 3 for assessment of CMR in patients undergoing standard treatment but, in the authors’ opinion, in early stage disease for de-escalation it is still prudent to use DS2. It is imperative that those reporting PET results and clinicians understand how the DS should be used for response-adaptation in clinical practice. Nowadays, many imaging specialists are educated in using DS not only for clinical trials, but also for clinical practice.
31
2