K. R. Tringale1,2, C. Grommes3, B. A. Ucpinar4, A. Reiner4, J. Yahalom5, G. Cederquist5, L. Schaff3, R. J. Young6, V. Hatzoglou6, M. Payinkay6, G. Bartlett6, M. Scordo7, J. Schefflein6, and B. S. Imber2; 1University of California, San Diego, La Jolla, CA, 2Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 3Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, 4Memorial Sloan Kettering Cancer Center, New York, NY, 5Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 6Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 7Department of Medicine, Bone Marrow Transplant Division, Memorial Sloan Kettering Cancer Center, New York, NY
Purpose/Objective(s): Post-methotrexate (MTX) consolidation strategies are selected to minimize toxicity while optimizing survival, yet patients with PCNSL remain at risk of neurotoxicity. Toxicity concerns from standard-dose whole-brain radiotherapy (SD-WBRT >24Gy) have led to declining use. Cerebral atrophy is an established surrogate for neurotoxicity; however, the extent to which modern consolidation strategies (reduced-dose [RD]-WBRT =24Gy, autologous hematopoietic cell transplantation [AHCT]) contribute to cerebral atrophy is unclear. Materials/
Methods: Patients with PCNSL from 2000-2020 who achieved complete response to consolidation after induction were identified (n=283). An expert neuroradiologist segmented ventricular volume (VV) on 458 MRIs then measured parenchymal volume loss longitudinally via VV change. Inclusion criteria were pre-consolidation MRI (baseline) and = 1 MRI showing sustained remission at 1, 3, 5, or 10 years. We assessed factors associated with annual VV change-rates and compared cerebral atrophy in patients with a published healthy cohort of aging adults (Fujita et al, 2023). Multivariable linear mixed effects models were performed. Results: Of 139 patients (median follow-up 4.5 years), all had MTX-anchored induction, most were MSKCC RPA class 2 (age >50, KPS = 70), and median baseline VV was 36.9 cm3. Consolidation was mostly non-myeloablative chemotherapy with cytarabine (NMC; n=57, 41%), high-dose myeloablative chemotherapy with AHCT (n=50, 36%), and RD-WBRT with cytarabine (n=28, 20%). Higher RPA class was associated with greater median baseline VV (p<0.001). Overall adjusted annual VV-change rates post-consolidation were greater than healthy adults (4.3% vs 1.8%) and generally increased by age-decade: 40-49-year-olds 1.8% (95%CI -1.4-5.0), 50-59-year-olds 3.1% (95%CI 0.7-5.5), 60-69-year-olds 4.8% (95%CI 2.4-7.3), 70-79-year-olds 7.2% (95%CI 4.3-10.2), and 80-89-year-olds 4.2% (95%CI -1.1-9.6). These values were higher and accelerated faster than healthy adults by age-decade. Despite larger baseline VV, patients who received RD-WBRT did not accelerate statistically significantly faster than AHCT or NMC (p=0.23). There were no associations between consolidation strategy and annual VV-change rates accounting for KPS, age, gender, baseline VV, and interaction between age and consolidation. Conclusion: Patients with PCNSL experience accelerated cerebral atrophy after consolidation compared to healthy aging adults; however, the rate of atrophy was similar among standard consolidation strategies. Given the progression-free survival benefit compared to observation and acceptable neurotoxicity with RD-WBRT on RTOG 1114, our findings of similar cerebral atrophy across consolidation regimens confirm that RD-WBRT should have greater consideration.
