Page 157 - 2021_07-Haematologica-web

Meta-analysis of radiotherapy for DLBCL
to improve the outcome of the first-line treatment11,12,17,22 or as a salvage option for patients who achieved only a partial remission after chemotherapy.14,21 As the Korean “ASPIRE” trial was unfortunately later withdrawn (clini- caltrials gov. Indentifier: NCT02054559; three times R- CHOP + radiotherapy vs. six times R-CHOP for stage 1 and 2 DLBCL), there is currently no randomized trial sup- porting the widely used, recently updated and safe approach to give less chemotherapy and PET-guided radiotherapy to patients with localized DLBCL.5,23,30-33 Also the data on limited stage DLBCL which accounts for 30 % of the cases, harbor significant variability as different definitions for limited stage, bulky disease as well as risk stratification and extrapolations were used.2,34 This ren-
ders the integration of all available results difficult. Furthermore, a detailed view goes beyond the possibili- ties of a meta-analysis analyzing population level data. Although we do not have information on the stage-mod- ified-IPI20,35 for all trials included in our analysis, we assume that many patients with localized disease of this meta-analysis had a low risk disease. They have an excel- lent prognosis, regardless of radiotherapy.36 The FLYER trial established four cycles of R-CHOP to be sufficient for patients with favorable risk (and non-bulky) DLBCL.37 Radiotherapy in this trial was limited to the contralateral testis in case of testicular involvement. In the yet unpub- lished OPTIMAL>60 trial (clinicaltrials gov. Identifier: NCT014778542), radiotherapy (and two additional cycles
Figure 2. Effect of consolidation radiotherapy on progression-free survival. Circles are proportional to trial size i.e., number of patients; retracted trials are displayed with hollow circles.
Table 2. Outcome data of the individual trials used for the meta-analysis. Correlation between progression-free and overall survival were done for the GELA trial. The superscript number in the study column refers to the number of the references in the manuscript.
Trial
(with reference)
Aviles et al.13 Engelhard et al.18 ECOG 148419 Aviles et al.14 SWOG 873620 GELA 93-111 GELA 93-412 Aviles et al.15 Aviles et al.16 UNFOLDER17,22 GOELAMS 02 0321
Overall survival Hazard ratio
0.33
2.09 0.81 0.35 0.64 1.98 1.08 0.21 0.28 1.2 0.52
Progression-free survival ln HR (SE)
-1.11 (0.44)
0.74 (0.58) -0.21 (0.28) -1.04 (0.25) -0.44 (0.23) 0.68 (0.20) 0.07 (0.14) -1.54 (0.29) -1.27 (0.32) 0.18 (0.38) -0.66 (0.45)
Hazard ratio
0.31
n/a 0.66 0.36 0.63 1.92 1.09 0.31 0.4 0.7 0.58
ln HR (SE)
?-1.17 (0.36)
n/a ?-0.41 (0.24) -1.02 (0.22) -0.46 (0.19) 0.65 (0.16) 0.09 (0.13) -1.16 (0.28) -0.92 (0.28) -0.36 (0.20) -0.54 (0.43)
HR: hazard ratio; ln: natural logarithm; SE: standard error.
haematologica | 2021; 106(7)
1927