Radiation Therapy for Burkitt Lymphoma: Multi-Decade Insights from a Single Center

Introduction: Burkitt Lymphoma (BL) is an aggressive B-cell neoplasm with high pediatric incidence in sub-Saharan Africa and historical significance in providing evidence for the MYC oncogene translocation pathway to oncogenesis. First-line treatment for both pediatric and adult patients includes high dose chemotherapy regimens. Most patients achieve a durable remission, but patients with relapsed/refractory disease experience poor survival outcomes. Secondary treatment options are not standardized and may include additional lines of chemotherapy, stem cell transplantation (SCT), or, more recently, chimeric antigen receptor T-cell (CAR-T) therapy. Radiation therapy (RT) is a well-established treatment modality in other lymphoma subtypes, however the role of RT for patients with BL is understudied with limited published data in 40 years, and none focused on modern diagnostic criteria. Given the high proliferative index of BL, there is rationale for utilizing RT for local control, including a potential to leverage the radiobiologic advantage of hyperfractionation. We sought to characterize our experience treating BL with RT and the role RT may play in the treatment paradigm. Methods: We identified patients that were diagnosed with BL and who received radiation therapy between 2000-2024 at Memorial Sloan Kettering Cancer Center. Each case was individually reviewed by a team of specialized hematopathologists to confirm BL histology using updated, modern diagnostic criteria, with careful consideration of those initially reviewed to have “Burkitt-like” features. Patient demographic, pathologic, imaging, and treatment characteristics were extracted from the electronic medical record. Results: We identified 140 patients before hematopathology review, and 116 were excluded, leading to a final cohort of 24 BL patients who received RT. The median age was 34 (range 4-81), and 20 patients (83%) were ≥18 years old. At the time of RT delivery, all patients had received at least one line of systemic therapy, 18 (75%) had advanced disease (Ann Arbor stage III/IV), and 22 (92%) had received intrathecal methotrexate before RT. 6 (25%) patients had a known history of central nervous system and/or leptomeningeal involvement. Patients received RT with different treatment intents: consolidation to sites with residual disease (n=4, 17%), palliation for symptom control (n=10, 42%), bridging in anticipation of SCT or CAR-T therapy (n=9, 37%), and prophylaxis in the setting of testicular primary site (n=1, 4%). All patients receiving consolidative RT had residual PET active disease following chemotherapy. The range of delivered dose was 9 Gy to 55 Gy in a range of 3 to 30 fractions. The median follow-up time was four months (range 0.5 - 134). Following RT, ten patients (42%) went on to receive additional lines of chemotherapy, five (21%) received a SCT, five (21%) received CAR-T cell therapy, and three (13%) received additional RT after the initial RT event. Of note, three of four patients (all with localized disease) who received consolidative RT did not require further therapy. After RT, 33% (n=8) achieved a complete metabolic response. Six-month overall survival was 100% for the consolidative/prophylaxis groups, 75% for the bridging group, 10% for the palliative group. One-year overall survival was 63% for the bridging group, 67% for the consolidative group, 0% for the palliative group, and 100% for the prophylaxis group. Conclusions: In this largest modern series to study the role of RT for BL, we found significant heterogeneity in referred cases but that RT can be an effective strategy for treating patients with either curative or palliative intent. Bridging and consolidative strategies were associated with more favorable survival outcomes, with the potential for durable remissions after RT delivery. Further analysis is warranted to understand patterns of failure and best practices.