Reduced-dose whole brain radiotherapy is an effective consolidation strategy for parenchymal-only secondary cns lymphoma

Abstract Introduction: While optimal consolidation strategies for patients with secondary central nervous system lymphoma (SCNSL) remain debated, autologous stem cell transplant (ASCT) is commonly used in eligible patients. However, effective alternatives are needed for those who are ineligible for high-dose chemotherapy. Whole brain radiotherapy (WBRT) has demonstrated consolidative efficacy in primary CNS lymphoma but has not been well-studied in SCNSL, particularly when given at reduced doses (≤25 Gy). Methods: We retrospectively analyzed SCNSL patients who received consolidative brain radiotherapy (RT) after achieving a complete (CR) or partial response (PR) to induction therapy by International PCNSL Collaborative Group criteria. Patients who underwent ASCT were excluded. Reduced-dose RT was defined as ≤25 Gy. CNS relapse was assessed by magnetic resonance imaging, and overall survival (OS) was calculated from the start of RT using Kaplan-Meier estimates. Results: Eight patients met inclusion criteria (median age 65, range 34–73; median KPS 90). All had diffuse large B-cell lymphoma histology; two presented with treatment-naïve (de novo) SCNSL, and six developed CNS involvement at relapse. Seven received methotrexate (MTX)-based induction regimens. The median interval from last MTX dose to RT was 51 days (range 21–115). At the time of RT, five patients were in CR and three in PR. No patients had leptomeningeal or extracranial disease at the time of RT. RT fields included WBRT in seven patients and partial brain RT in one. The median RT dose was 24 Gy (range 23.4–45 Gy) delivered over a median of 13 fractions (range 10–25); five patients received reduced-dose RT. Additional consolidative systemic therapy was delivered after RT in five patients, which included cytarabine (n=4) and rituximab (n=1). With a median follow-up of 49 months (range 15–198), median OS was not reached. The estimated 5-year OS was 60% (95% CI, 25–96%). All three patients initially in PR converted to CR. There were no CNS failures within the radiation field, which includes patients who received reduced-dose RT. CNS relapse occurred in two patients at sites outside the RT field (lumbar nerve root and ocular); one of these recieved salvage therapy with MTX. Two patients experienced extracranial relapse; one of these received salvage therapy with polatuzumab vedotin/bendamustine/rituximab. Conclusions: This cohort suggests that consolidative reduced-dose WBRT may be a valuable consolidation option for certain transplant-ineligible chemo-responsive SCNSL patients, with encouraging and sometimes durable responses. The absence of leptomeningeal and systemic disease at the time of RT may help guide patient selection. These findings support further prospective evaluation and raise the possibility of a new, previous-underexplored role for RT in the management of SCNSL.