4 - Decreasing the Dose of Consolidation Radiation Therapy in DLBCL/HGBL: A Phase II Trial by the International Lymphoma Radiation Oncology Group
Presenter(s)
A. Ng1, D. Neish2, D. Niedzwiecki3, C. C. Pinnix4, H. I. Yoon5, M. Levis6, W. G. Rule7, J. L. Peterson8, K. W. Yeoh9, J. C. Yang10, L. S. Constine11, S. C. Lester12, I. M. Pashtan13, J. L. Leenstra12, K. Dedecková14, N. Shikama15, C. G. Patel16, B. Dabaja4, K. H. Kim17, and C. R. Kelsey2; 1Dana Farber Cancer Institute, Boston, MA, 2Duke University Medical Center, Durham, NC, 3Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC, 4Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 5Department of Radiation Oncology, Yonsei Cancer Center, Heavy Ion Therapy Research Institute, Yonsei University College of Medicine, Seoul, Korea, Republic of (South), 6Dept. of Oncology, University of Torino, Torino, Italy, 7Department of Radiation Oncology, Mayo Clinic, Phoenix, AZ, 8Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL, 9National Cancer Center, Singapore, Singapore, Singapore, 10WashU Medicine, Department of Radiation Oncology, St. Louis, MO, 11Department of Radiation Oncology and Pediatrics, University of Rochester Medical Center, Rochester, NY, 12Department of Radiation Oncology, Mayo Clinic, Rochester, MN, 13Department of Radiation Oncology, Dana-Farber Brigham Cancer Center, Boston, MA, 14Proton Therapy Center Czech Praha, Prague, Czech Republic, 15Division of Radiation Oncology, Department of Radiology, Juntendo University School of Medicine, Tokyo, Japan, 16Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 17Yonsei Cancer Center, Seoul, Korea, Republic of (South)
Purpose/Objective(s): Consolidation radiation therapy (RT) is often recommended for patients with diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL), depending upon the number of cycles of chemoimmunotherapy (ChI) administered, presence of bulky disease, double hit genetics/International Prognostic Index (IPI) risk factors, PET-CT response, and/or specific sites of involvement. Prior prospective studies utilizing 30-40 Gy reported crude local control rates ranging from 93-100%1,2,3,4. This phase II study tested whether a reduced dose of 20 Gy would provide outcomes comparable to historical observations in patients achieving a metabolic complete response (CR).
Materials/Methods: Patients with newly diagnosed DLBCL or HGBL achieving a CR by PET-CT (Deauville 1-3) after =3 cycles of ChI were eligible. Consolidation RT dose was 19.5-20 Gy in 1.5-2 Gy fractions using involved site principles. The primary endpoint was freedom from local recurrence (FFLR) defined as failure at a treated site and designed to test whether 5-year FFLR was =95% with a reduced dose of RT. Distant recurrence was defined as progression outside the RT field. An initial analysis was performed 2 years after the last patient was enrolled per the trial design.
Results: Patients (n=243) were enrolled between 2019-2023 from 16 institutions in Asia, Europe, and the US. Median age: 65 years (range, 19-91). Male: 47%; Female: 53%. Histology: DLBCL (n=207; 85%) and HGBL (n=36; 15%) with double hit genetics in 22 (9%). Stage distribution: I-II (n=161; 66%) and III-IV (n=82; 34%). Bulky disease (=7.5 cm) was present in 78 patients (32%). IPI: 0-1 (n=119; 49%), 2-3 (n=97; 40%), and 4-5 (n=27; 11%). ChI primarily consisted of R-CHOP (n=198, 82%) or R-EPOCH (n=19, 8%). Number of ChI cycles: 3 (n=55; 22%), 4 (n=19; 8%), and =5 (n=169; 70%). Most patients (n=196, 81%) had all sites of disease treated with only select sites treated in the remaining. RT modality: 3D (n=47, 19%), IMRT/VMAT (n=182, 75%), protons (n=14, 6%). With a median follow-up of 2.4 years (range, 0.1-5.6), 15/243 (6%) of patients progressed (1 local only recurrence, 3 local and distant recurrences, and 11 distant only recurrences). All 4 patients with a local recurrence had bulky disease at diagnosis (7.5 cm, 8 cm, 15 cm, and 13.7 cm), progressing 4, 5, 18, and 46 months after completing RT, respectively. FFLR at 3 years was 98.6% (95% CI 0.97-1). Progression-free and overall survival at 3 years were 91.4% (95% CI 0.88-0.95) and 95.7% (95% CI 0.93-0.99), respectively.
Conclusion: Results of this phase II study demonstrate high rates of local control with a lower dose of consolidation RT in a diverse population of patients with DLBCL/HGBL achieving a metabolic CR by post- ChI PET-CT. While guidelines currently recommend 30 Gy, this could be reduced to 20 Gy if high rates of local control are maintained with longer follow-up. A reduction in RT dose will decrease both acute and long-term toxicity.
1-4. ECOG 1484; GELA 93-4; GELA 93-1; LYSA/GOELAMS 02-03