2815 - Response-Directed Radiotherapy after Methotrexate-Based Systemic Therapy for Patients with Primary CNS Lymphoma
Presenter(s)
A. Nalin1, T. Lin1, O. Saifi1, M. Hamilton2, A. Lionel2, C. C. Nze2, R. Nair2, S. Ahmed2, P. Strati2, P. Fang1, L. Fayad2, D. Chihara2, C. Flowers2, J. R. Gunther1, B. Dabaja1, J. Westin2, A. Chauhan2, C. C. Pinnix1, and S. Y. Wu1; 1Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 2Department of Lymphoma-Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
Purpose/Objective(s): The role of radiation (RT) in the management of primary central nervous system lymphoma (PCNSL) has evolved with improvements in high-dose MTX-based systemic therapy (HD-MTX ST) and has been further refined by increased use of consolidative autologous stem cell transplant in eligible patients. However, the optimal RT approach for patients (pts) who do not achieve a complete response (CR) following MTX remains poorly defined. We hypothesize that a response-directed approach, with a boost to residual sites of disease, may offer durable control in pts with PCNSL.
Materials/Methods: We performed an IRB-approved retrospective study of 52 consecutive pts who received whole brain RT (WBRT) for biopsy-proven PCNSL after HD-MTX ST between 3/2007-3/2025. Pts with secondary CNS lymphoma and primary intraocular lymphoma were excluded. Progression-free survival (PFS) was defined from the date of completion of RT using the Kaplan-Meier method.
Results: The median age at diagnosis was 62 years (IQR 53-69). 52% were male, 85% were white, and 15% were Hispanic. Three pts were HIV+. At diagnosis 62% of patients had an ECOG performance status of 0-1, 39/51 pts (75%) had multiple lesions on initial MRI, 26/51 (50%) had deep brain involvement, and 7/52 (13%) presented with orbital involvement. The median Ki-67 on initial biopsy was 90% (IQR 70-90). The most common ST regimen was HD-MTX, Procarbazine, and Vincristine (MPV) +/- Rituximab (R) in 32/52 (62%) of pts, while 13/52 (25%) received HD-MTX +/- R, and 7/52 (13%) received other HD-MTX-based regimens. 16/52 pts (31%) received consolidative cytarabine. Following a median of 5 cycles of HD-MTX-based ST, 14/52 pts (27%) achieved a CR, 23/52 (44%) a partial response (PR), and 15/52 (29%) had stable/progressive disease.
All pts in CR at the time of RT received WBRT to 23.4 Gy in 13 fractions (fx). Among 43 pts with residual disease at RT (including 5 who had previously achieved a CR and were observed), the median WBRT dose was 23.4 Gy in 13 fx (IQR 23.4-30 Gy in 11-15 fx). 17/43 pts (40%) received an intermediate dose boost (targeting FLAIR or original extent of disease) to 36.4 Gy EQD2 a/b 10 in 19 fx (IQR 33.0-38.6 Gy in 17-20 fx), and 30/43 pts (70%) received a boost to residual disease to 42.2 Gy EQD2 a/b 10 in 22 fx (IQR 39.6-45 Gy in 19-23 fx). Following RT, 38 of 50 evaluable pts (76%) achieved CR. 21 pts experienced progression at a median of 7 months following RT (IQR 3-26); in 11 pts, progression involved original sites of disease. The median PFS for all pts was 36 months (95% CI 23-44). Among pts with residual disease at RT, a boost was associated with improved median PFS compared with no boost (44 vs 3 months, p=0.005). PFS among patients who received a boost was comparable to those treated in CR (39 months, p=0.53).Conclusion: In pts with PCNSL treated with HD-MTX-based ST, an RT approach incorporating a boost to residual disease is associated with improved PFS. Further investigation into optimal consolidative strategies in pts with a PR following HD-MTX-based induction is warranted.