The extranodal stage I patients in this analysis included patients with testicular and breast disease, which are associated with a peculiar clinical course (eg, contralateral and central nervous system relapses) 10 based on compelling retrospective data, these patients should be treated differently than patients with extranodal disease. There was variability in time of PET performance after chemoimmunotherapy. The small number of patients with nodal presentation and PET positivity after chemotherapy did not allow an analysis of the role of RT in these patients. The small number of patients in individual treatment groups prevented comparison of outcomes between patients treated with an abbreviated vs a full course of chemotherapy. The chemotherapy was not uniform, and patient treatments were selected by physicians based on clinical presentation and other unknown but potentially confounding considerations. There are several limitations to this retrospective study. However, there was no difference in PFS and OS, indicating that additional studies addressing the role of RT in extranodal DLBCL may be needed. The reduced EFS in patients without RT was linked to a higher rate of partial responses that triggered additional treatment. 9 The 3-year event-free survival (EFS) was superior in patients who received RT. In the rituximab era, 2 randomized trials demonstrated that (1) RT may not be necessary in nonbulky (7.5 cm) disease or IPI of 1 were randomly assigned to R-CHOP with or without RT to bulky and/or extranodal disease. However, with longer follow-up, this survival advantage disappeared due to continuous late relapses, which were also observed in other studies. 2 The initial report showed an OS advantage with 3 cycles of CHOP combined with RT over 8 cycles of CHOP. The SWOG study S8736 enrolled stage I (including bulky ) and nonbulky stage II patients without any restrictions based on the sm-IPI. In the pre-rituximab era, 4 randomized trials in limited-stage DLBCL patients have compared chemotherapy with combined modality treatment 2, 4 - 6 but did not establish the best treatment approach. 3Ĭonsequently, the optimal therapy for limited-stage DLBCL patients in general and risk-stratified patient subgroups remains unclear. While extranodal involvement, a risk factor in the original IPI, is not included in the sm-IPI, there are reports suggesting that extranodal presentation may be associated with inferior outcomes. Differences in survival can also be attributed to the presence of unfavorable clinical characteristics that constitute the stage-modified International Prognostic Index (sm-IPI) 2 (age >60 years, elevated lactate dehydrogenase, performance status ≥2, and stage II), bulky disease, and biological heterogeneity. Variability in outcomes in limited-stage DLBCL patients stems from different definitions of limited stage (stage I or both stage I and II), tumor bulk, and whether staging was performed by PET computed tomography. Retrospective analyses and clinical trials in these patients demonstrated favorable but markedly variable outcomes following short- or full-course chemotherapy with or without rituximab with or without RT. Limited-stage presentation accounts for ∼30% to 40% of DLBCL cases. The figure has been adapted from Figures 3A and 4 in the article by Bobillo et al that begins on page 39. A small number of events did not allow analysis of the value of radiotherapy in patients with nodal presentation and positive PET after chemoimmunotherapy. Based on these findings, a depicted treatment algorithm can be proposed. Radiotherapy was associated with longer OS and PFS in patients with extranodal DLBCL. Bobillo et al demonstrated that in stage I DLBCL patients, OS and PFS were shorter in patients with extranodal disease than in patients with nodal involvement.
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