Page 32 - 18F-FDG PET as biomarker in aggressive lymphoma; technical and clinical validation

Chapter 2
clinical trials is to achieve optimal efficacy in terms of progression-free survival (PFS) and overall survival (OS), and to reduce long-term adverse effects.
The first reports using iPET to de-escalate therapy in responding individuals with early-stage disease have been published. The UK RAPID study [8] and the EORTC H10 study [9] have randomized patients with complete metabolic response (CMR) on iPET after 2-4 cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) treatment to receive radiotherapy (RT) or no further treatment (NFT). Both were non-inferiority studies, with a slightly different design. Involved field was used in RAPID and involved node RT in H10. RAPID investigators accepted that by abandoning RT some loss of disease control was inevitable, whereas H10 investigators designed their trial to demonstrate that patients could be spared RT without any compromise in disease control. Both studies demonstrated a modest PFS advantage for patients receiving RT (Table 1).
In the RAPID trial, the 3-year PFS was 97.1% using RT versus 90.8% for NFT in a per-protocol analysis (HR 2.36; 1.13, 4.95). There was no significant difference in 3-year OS: 97.1% (RT) versus 99.0% (NFT). In the H10 study, 1-year PFS was 100% (favorable disease) and 97.3% (unfavorable disease) using RT versus 94.9% (favorable) and 94.7% (unfavorable) for NFT.The H10 study was halted early for patients with CMR as it was felt unlikely to demonstrate non-inferiority for the NFT option with a 10% decrease in 5-year PFS where the threshold for non-inferiority was set at a hazard ratio of respectively 3.2 and 2.1 for the favorable and unfavorable subgroups. Nonetheless, patients had excellent outcomes in both trials whether or not they received RT. However, follow up in both trials is still short, and (late) adverse effects of radiotherapy may become apparent over time [10]. Results from the HD16 and HD17 trials of the German Hodgkin Study Group are currently awaited. Both trials are comparing standard combined modality treatment with a PET-directed regimen, omitting radiotherapy for patients with complete metabolic response after chemotherapy (www.ghsg.org).
So de-escalation has become a real option in clinical practice, but requires detailed discussions between patients, hematologists and radiation oncologists. Balancing the risks and benefits of chemotherapy alone versus combined modality treatment
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