Consolidation regimen and cerebral atrophy in patients with primary central nervous system lymphoma Journal Article
| Authors: | Tringale, K. R.; Grommes, C.; Ucpinar, B. A.; Reiner, A. S.; Yahalom, J.; Cederquist, G. Y.; Schaff, L. R.; Hatzoglou, V.; Young, R. J.; Payinkay, M.; Bartlett, G.; Scordo, M.; Imber, B. S.; Schefflein, J. |
| Article Title: | Consolidation regimen and cerebral atrophy in patients with primary central nervous system lymphoma |
| Abstract: | Purpose: In primary central nervous system lymphoma (PCNSL), the extent to which post-methotrexate consolidation contributes to neurotoxicity is unclear. Concerns for neurotoxicity from standard dose whole-brain radiation therapy (WBRT) have led to declining use. Cerebral atrophy is an established surrogate for neurotoxicity; however, the relative extent to which modern consolidation (ie, reduced-dose [RD-]WBRT ≤24 Gy, autologous hematopoietic cell transplant) contributes to cerebral atrophy is unclear. Methods and Materials: Patients with PCNSL from 2000-2020 who achieved a complete response to consolidation following methotrexate-based induction were included. Inclusion criteria were preconsolidation magnetic resonance imaging (baseline) and ≥1 magnetic resonance imaging showing sustained remission at 1, 3, 5, or 10 years. An expert neuroradiologist longitudinally measured parenchymal volume loss via ventricular volumetric change. Linear mixed-effects models were performed to estimate absolute and annual volumetric change rates. Results: Of 139 patients (median follow-up, 4.5 years), most were Memorial Sloan Kettering Cancer Center (MSK) recursive partitioning analysis (RPA) class 2 (age ≤50 years, Karnofsky performance score (KPS) ≥70). Consolidation therapies included nonmyeloablative chemotherapy (n = 57; 41%), high-dose myeloablative chemotherapy with autologous hematopoietic cell transplant (n = 50; 36%), and RD-WBRT (n = 28; 20%). A higher MSK RPA class was associated with greater baseline ventricular volume (P < .001). Overall adjusted annual ventricular volume change rates were greater than those published in healthy controls (4.3% vs 1.8%) and generally increased by age/decade at diagnosis: 40 to 49-year-olds 1.8% (95% CI, −1.4% to 5.0%), 50 to 59-year-olds 3.1% (95% CI, 0.7%-5.5%), 60 to 69-year-olds 4.8% (95% CI, 2.4%-7.3%), 70 to 79-year-olds 7.2% (95% CI, 4.3%-10.2%), and 80 to 89-year-olds 4.2% (95% CI, −1.1% to 9.6%). There were no significant associations between consolidation strategy and ventricular volume change rates accounting for age, KPS, gender, baseline ventricular volume, or interaction between age and consolidation. Conclusions: These findings demonstrate accelerated cerebral atrophy in PCNSL after consolidation compared with healthy adults. However, atrophy did not differ by consolidation strategy. These long-term results suggest acceptable neurotoxicity following RD-WBRT. © 2024 Elsevier Inc. |
| Keywords: | adult; controlled study; treatment response; aged; middle aged; major clinical study; busulfan; cancer patient; cancer radiotherapy; chemotherapy; primary central nervous system lymphoma; cytarabine; methotrexate; rituximab; drug megadose; neuroimaging; neurotoxicity; follow up; magnetic resonance imaging; radiotherapy; cohort analysis; lung cancer; cyclophosphamide; vincristine; retrospective study; procarbazine; thiotepa; age; cancer center; cancer regression; karnofsky performance status; brain ventricle; quantitative analysis; hematopoietic cell; central nervous systems; autologous hematopoietic stem cell transplantation; performance; induction chemotherapy; longitudinal study; brain size; whole brain radiotherapy; gadolinium chelate; brain atrophy; recursive partitioning analysis; diffuse large b cell lymphoma; recursive partitioning; consolidation chemotherapy; methods and materials; very elderly; human; male; female; article; neuroradiologist; whole brain radiation therapies; volumetric changes; t2 weighted imaging; volume change; cell transplants |
| Journal Title: | International Journal of Radiation Oncology, Biology, Physics |
| Volume: | 121 |
| Issue: | 5 |
| ISSN: | 0360-3016 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2025-04-01 |
| Start Page: | 1248 |
| End Page: | 1257 |
| Language: | English |
| DOI: | 10.1016/j.ijrobp.2024.11.088 |
| PUBMED: | 39615656 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Kathryn R. Tringale -- Source: Scopus |
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