S1597 PET-DRIVEN RADIOTHERAPY IN PATIENTS WITH LOW RISK DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL): THE DLCL10 MULTICENTER PHASE 2 TRIAL BY FONDAZIONE ITALIANA LINFOMI (FIL)
Authors: M. Balzarotti, M. Spina, C. Monagheddu, S. Chauvie, A. Tucci, F. Cavallo, M. Zanni, A. Arcari, C. Rusconi, R. Sartori, F. Merli, F. Re, U. Vitolo, L. Melis, P. Navarria, G. Gini, D. Dessì, A. Chiti, A. Santoro, G. Ciccone, U. Ricardi, M.G. Cabras
Journal: HemaSphere (2019)

Background: The role of consolidation radiotherapy (RT) after rituximab-chemotherapy (R-CT) in DLBCL is not completely defined. Historically, bulky sites at diagnosis are irradiated after R-CT, whereas residual disease at other sites is considered as treatment failure. Since 2007, complete remission (CR) is defined as PET negativity and some groups postulated that PET negative areas after R-CT do not need consolidation RT. Aims: To assess the role of RT in PET-negative and in PET-positive low-risk DLBCL patients after R-CT Methods: The DLCL10 trial was a phase II study of patients > = 18 years with DLBCL defined at low risk according to the MiNT study,(aa IPI 0 and bulky, aa IPI 1 with/without bulky) conducted in 19 FIL centers. Patients were treated with 6 courses of RCHOP-14 or R-CHOP-21 and final response was evaluated with FDG-PET. Both pre and post treatment PET scans were centrally reviewed through the Widen web platform by a panel of five nuclear medicine experts. Positive scans were those centrally classified with Deauville score 3-4-5 .The first 2 concordant reviewers decided the final results. Patients with one residual FDG-uptaking area (RUA) were planned to receive RT, 36 Gray involved-field, regardless of the presence of bulky disease at diagnosis, while patients with multiple RUA were shifted to salvage systemic therapy. Primary aim was to obtain 2-year PFS of at least 85% for PET negative patients observed after R-CT; secondary endpoints were overall survival and response Results: From January 2012 to December 2017, 115 consecutive patients were enrolled, and 109 were evaluable. Patients had a median age of 58 yrs (47–65); M:F 60/49; 90% DLBCL de novo. Fifteen patients presented with aa IPI 0, and 94 with aa IPI 1, among whom 20 with bulky disease; 72 patients received RCHOP-14 and 37 RCHOP-21. The median follow-up was 36 months and 6 patients died (2 lymphoma, 3 toxicitiy, 1 unknown). A total of 105 patients completed the chemotherapy program, while four were discontinued for lymphoma progression (1), toxicity (2, both died) and unknown cause (1). At the end of treatment 83 patients had negative PET, whereas 17 had single RUA and received RT. In PET-negative patients, PFS was 90.6% (95% CI 81.1–95.4) at 2 years and 88.7% (95% CI 78.4–94.3) at 3 years. After RT, 15 out of 16 evaluable cases reached CR, one PR and one was not evaluable. None of them relapsed. Thus, all patients with positive focal findings after R-CT were cured with focal RT. Concerning the 35 patients with bulky disease, 20 reached negative PET and 15 had RUA after R-CT (1 PD). There were two relapses in the negative PET/non irradiated group and none in the positive PET /RT group. In the total population, 3-year PFS and OS are 85.1% (95%CI 76.4–89.3) and 94% (95% CI 87.3–97.7), respectively. Summary/Conclusion: Our data suggest that irradiating only sites of unique residual PET uptake, regardless of bulky at onset, can be considered as a reasonable strategy for low risk DLBCL patients. In patients with bulky disease, PET-driven RT allowed RT sparing in approximately half of patients. Moreover, consolidation RT in those with focal residual PET positivity, guaranteed excellent prognosis (17/17 cured) and has to be recommended as a valid option.