1061 - Optimizing Low Dose Radiotherapy for Indolent Lymphomas: Comparing 4 Gy x 2 vs. 2 Gy x 2

J. F. Burlile¹, W. S. Harmsen², O. Saifi³, B. Laughlin⁴, S. Kosydar⁵, Y. Sharifzadeh¹, K. M. Frechette¹, T. M. Habermann⁶, J. Villasboas Bisneto⁶, Y. Wang⁶, P. Hampel⁶, J. Paludo⁶, B. S. Hoppe³, W. G. Rule⁴, J. L. Peterson³, T. Witzig⁶, I. N. Micallef⁶, W. Breen¹, and S. C. Lester¹; ¹Department of Radiation Oncology, Mayo Clinic, Rochester, MN, ²Department of Biostatistics and Health Sciences Research, Mayo Clinic, Rochester, MN, ³Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL, ⁴Department of Radiation Oncology, Mayo Clinic, Phoenix, AZ, ⁵Department of Internal Medicine, Mayo Clinic, Rochester, MN, ⁶Division of Hematology, Mayo Clinic, Rochester, MN

Purpose/Objective(s): Approximately 30% of patients treated with 4 Gy delivered at 2 Gy/fraction (4Gy) will experience local progression at 18 months after treatment. In 2020, we introduced 8 Gy delivered at 4 Gy/fraction (8Gy) into routine clinical practice at our institution. We hypothesized that 8 Gy would result in less local recurrences (LR) and more complete responses (CR) compared to 4 Gy, and herein report early outcomes. Materials/

Methods: This was an IRB-approved retrospective review of patients treated from 2013 to 2024 with 4 Gy or 8 Gy for low grade B-cell lymphomas including follicular (FL) and marginal zone lymphoma (MZL). The reverse Kaplan Meier method was utilized to calculate cumulative incidence of local recurrence (LR) and CR, with death and initiation of systemic therapy as competing risks. Univariate and multivariable Cox models were performed to identify any patient, disease, or treatment factors associated with LR and with CR.

Results: 77 sites of disease (68 patients) were treated with 4 Gy and 56 sites (49 patients) were treated with 8 Gy. The majority (71%) of 4 Gy was administered between 2013-2020, while 95% of 8 Gy was delivered from 2020-2023. Therefore, median follow up was 2.1, 5.8, and 1.2 years for the overall cohort, 4 Gy, and 8 Gy groups, respectively. The two treatment groups were balanced with respect to prior systemic therapy receipt, previous non-local radiation for lymphoma, and size of GTV (gross tumor volume, cm). FL represented a larger proportion of the 8 Gy group (64%) than the 4 Gy group (35%), which approached statistical significance (p=0.058). More patients with orbital tumors were treated with 4 Gy: 40% of the 4 Gy vs 4% of the 8 Gy group. There were 20 local recurrences in the 4 Gy group (26.0%) and four in the 8 Gy group (7.1%) (HR 2.63, 0.74 – 9.30, p=0.134). The 2, 3, and 5-year cumulative incidences of LR after 4 Gy were 19%, 25%, and 30%. The 2-year cumulative incidence of LR after 8 Gy was 14%. On univariate analysis, nodal sites of disease were more likely to recur (HR 3.63, 1.30 – 10.11, p=0.014): 2-year cumulative incidence of nodal LR was 32.6%. Larger tumors were also more likely to recur (HR 1.25 per 1 cm size, p=0.010). There was no difference in LC between 4 Gy and 8 Gy within the FL and MZL groups when examined individually (p=0.336 and p=0.251, respectively). The cumulative incidence of CR at one year after treatment was 58.5% for the 4 Gy group and 83.5% for the 8 Gy group. On univariate analysis, 4 Gy was associated with a lower chance of CR (HR 0.53, 0.32 – 0.89, p=0.016), which on multivariable analysis did not differ depending on size of GTV. For MZL, 4 Gy produced an inferior CR (HR 0.47, 0.23 – 0.95, p=0.037), while for FL there was no difference in CR between the two doses.

Conclusion: Early outcomes of utilizing 8 Gy for indolent lymphomas compare favorably to 4 Gy, with better CR rates and encouraging local control rates. Longer follow-up and additional studies are needed, and toxicity data are forthcoming.