Impact of radiation in limited stage diffuse large B-cell lymphoma in the modern era

Abstract Background: The current approach of limited-stage (LS) DLBCL consists of a short course of chemoimmunotherapy (3-4 cycles) followed by radiation therapy (XRT) or observation, which results in high responses and excellent outcomes. We are reporting the impact of XRT in this patient population from a single institution. Methods: We conducted a retrospective study of adult patients with stage I/II (LS) DLBCL of any tumor bulk, IPI, regardless of B-symptom presence, diagnosed from 2019-2024 at the Moffitt Cancer Center and treated with 3 or 4 of RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) with and without the use of XRT. Patients with PMBCL, PTLD, receiving non-standard dose RCHOP for cycle (C) 1 were excluded. The primary endpoints were progression-free survival and overall survival. Secondary endpoints were overall response rate (ORR) and complete response (CR). Results: The study included 46 patients. The median age was 57 years old (range: 21-83), with 43.4% being 60 years or older. Half were male, 82.6% were non-Hispanic White, 67.4% had Stage I disease, 33.3% had elevated LDH, 13% had ECOG performance status of 1 or higher, 9% presented with B symptoms, and 22.7% had extranodal disease. Cell of origin (by Hans algorithm) was germinal center (GCB) in 65.2% and non-GCB in 21.7%. Most had de novo DLBCL (91%), with the remaining cases being transformed follicular lymphoma (6.52%) and from marginal zone lymphoma (2.17%). MYC and BCL2 rearrangements (double hit) were identified on FISH analysis in 8.7% of cases. Efficacy outcomes: 42/46 (91.3%) patients achieved CR after R-CHOP therapy (regardless of 3 or 4 cycles of R-CHOP). About 6.5% of patients received prophylactic CNS-directed therapy. 18 of the 46 (39.1%) had radiation therapy completed following R-CHOP therapy (11 patients had 3 cycles of R-CHOP; 7 patients had 4 cycles of R-CHOP). After all treatments, the CR rates in XRT and non-XRT groups were 88.9% and 61.9% Interim PETs were done in 58.7% of total cases (70.3% achieving CR and 26% achieving PR). Complications from the data set include 12 patients (26.1%) developing neutropenia, and 2 (4.6%) developing an infectious process. 4 progression events occurred at distant sites and occurred in a range of 1.2-5 years after treatment. There were 3 deaths without prior progression, and the causes of death were all unrelated to the underlying lymphoma. At a median follow-up of 2.45 years (range: 0.47-5.8 years), the median PFS and OS were not reached. The 36-month PFS and OS were 90% and 95%, respectively. For patients who received XRT, the 36-month PFS and OS were 87% and 100%. For those who did not receive XRT, the PFS and OS were 89% and 92%, respectively, which were not statistically different. Conclusion: In patients with limited-stage DLBCL cohort from a single center treated with short R-CHOP therapy with or without adjunct radiation therapy, the outcomes are very good. It appears that those who have received radiation therapy have better outcomes and survived longer than those patients who did not receive RT, without reaching a statistical difference.