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M.D. Berger et al.
to be cancer-free. Trial 2 would be a superiority design testing whether radiotherapy is able to improve the out- come residual DLBCL after chemo-immunotherapy. Assuming a 2-year PFS, an appropriate and pragmatic endpoint in DLBCL49,50 of 80%, an alpha of 0.025 for the non-inferiority (one-sided) and 0.05 (two-sided) for the superiority trial, a power of 80% and enrolment over 5 years, we calculated the following sample size: trial 1 (failure rate of 24% [HR 1.23]), would require 1,916 over- all or 384 patients per year; trial 2 (and a HR of 0.75 or an improvement of the 2-year PFS to 85%) would need 1,098 patients or 220 patients per year. Assuming an end- of-therapy PET-positivity of 25-30%,45 4,000 or 5,000 patients respectively have to be screened. Clearly, such numbers need a global and fully committed academic effort. However, otherwise the important question on the role of consolidation radiotherapy in DLBCL, which with the current data, regularly gives rise to unsatisfacto- ry and futile discussions at lymphoma boards, will never be answered convincingly. Based on this meta-analysis and other data,21 we favor a superiority trial that first allocates a role of consolidation radiotherapy in DLBCL. Then, one may also test the use of smaller irradiation volumes according to the concept of involved node ver-
sus involved site radiotherapy using modern techniques (intensity modulated radiotherapy [IMRT]) to reduce doses to organs at risk.31,51 New trials could also approach unanswered questions on the role of consolidation radio- therapy in other subpopulations like patients with inter- im PET positive disease, or in limited stage disease of high risk histologies such as double hit lymphomas although the prognosis of the later may be better than previously perceived.52
Disclosures
No conflicts of interest to disclose.
Contributions
MDB performed research, analyzed data and wrote parts of the paper; ST analyzed data, contributed vital material and wrote parts of the paper; AEB and SJ performed research and analyzed data; CI analyzed data; TL contributed vital material; UN had the idea, designed research, analyzed data, contributed vital material, and wrote the paper.
Acknowledgments
We thank Doris Kopp for the literature search, as well as Matthias Egger and Emanuele Zucca for valuable comments.
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