As treatment failure occurs in 1 in 4 PET-negative patients with bulky/advanced DLBCL after R-CHOP, and aggressive salvage therapies are toxic, often ineffective, and not suitable for frail or elderly patients, there remains significant room for improvement. This is important information for both current practice and for guiding further research into the selection of patients for additional therapies. 5,6 These data, together with multiple other nonrandomized and population-based studies, consistently suggest a possible overall benefit of up to 15% associated with adjuvant RT after R-CHOP.įreeman and colleagues’ data confirm that a policy of no radiation in EOT PET-negative patients delivers acceptable results for many patients. 4 Notable among nonrandomized studies, the RICOVER trial reported a 26% higher EFS with RT after R-CHOP for elderly patients with bulky disease (per protocol analysis) and an MDACC study reported a 15% higher 5-year PFS associated with the addition of RT in 295 patients in complete response (CR) after R-CHOP. As EFS included RT given for residual masses (which do not always represent disease), applicability in the PET era is not straightforward. This study reported a 16% increase in event-free survival (EFS) ( P =. 3 In the R-CHOP era, the only randomized trial of RT for bulky DLBCL, “UNFOLDER,” was not PET-guided and has been reported only in abstract form. “Proof of principle” for the efficacy of RT was provided by Eastern Cooperative Oncology Group-1484, a randomized trial in which RT following CHOP increased PFS by 16%. The benefit of adjuvant RT for bulky/advanced DLBCL has been debated for 2 decades. This is particularly important given the very poor outcome of relapsed DLBCL post –R-CHOP, even in the chimeric antigen receptor T-cell era. 2 With 25% of EOT PET-negative patients experiencing treatment failure, potentially effective adjuvant therapies, including RT, remain a relevant consideration. Although the 83% 3-year TTP for PET-negative patients was good, an eventual progression rate of at least 25% was observed (Figure 1A in Freeman et al), consistent with previous reports of a 70% to 75% progression-free survival (PFS) for EOT PET-negative patients. However, this recommendation requires careful consideration, particularly as this was not a randomized trial addressing that question. Based on the 83% 3-year TTP and subset analyses showing near identical outcomes for patients with or without bulky disease (>10 cm), or with or without skeletal disease at diagnosis, the authors recommend that RT should be routinely avoided for such patients. This study provides a robust benchmark for outcomes of EOT PET-negative patients after R-CHOP without adjuvant radiation.
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