The role of whole-brain radiotherapy (WBRT) in primary central nervous system lymphoma: is it an alternative to ASCT for consolidation following HD-methotrexate based induction in low-income settings?

Autor: de Pádua Covas Lage LA; Department of Hematology, Hemotherapy and Cell Therapy, Faculty of Medicine, University of São Paulo (FM-USP), São Paulo, Brazil. luis.lage@hc.fm.usp.br.; Laboratory of Medical Investigation in Pathogenesis and Directed Therapy in Onco-Immuno-Hematology (LIM-31), University of São Paulo (USP), Cerqueira César, Avenue Dr. Enéas de Carvalho Aguiar, 155 - Ambulatory building - 1st. Floor, Room 61, São Paulo (SP), 05403-000, Brazil. luis.lage@hc.fm.usp.br., Araújo Soares V; Department of Hematology, Hemotherapy and Cell Therapy, Faculty of Medicine, University of São Paulo (FM-USP), São Paulo, Brazil., Meneguin TD; Department of Hematology, Hemotherapy and Cell Therapy, Faculty of Medicine, University of São Paulo (FM-USP), São Paulo, Brazil., Culler HF; Department of Hematology, Hemotherapy and Cell Therapy, Faculty of Medicine, University of São Paulo (FM-USP), São Paulo, Brazil.; Laboratory of Medical Investigation in Pathogenesis and Directed Therapy in Onco-Immuno-Hematology (LIM-31), University of São Paulo (USP), Cerqueira César, Avenue Dr. Enéas de Carvalho Aguiar, 155 - Ambulatory building - 1st. Floor, Room 61, São Paulo (SP), 05403-000, Brazil., Reichert CO; Department of Hematology, Hemotherapy and Cell Therapy, Faculty of Medicine, University of São Paulo (FM-USP), São Paulo, Brazil.; Laboratory of Medical Investigation in Pathogenesis and Directed Therapy in Onco-Immuno-Hematology (LIM-31), University of São Paulo (USP), Cerqueira César, Avenue Dr. Enéas de Carvalho Aguiar, 155 - Ambulatory building - 1st. Floor, Room 61, São Paulo (SP), 05403-000, Brazil., Jacomassi MD; Department of Hematology, Hemotherapy and Cell Therapy, Faculty of Medicine, University of São Paulo (FM-USP), São Paulo, Brazil., Reis DGC; Department of Hematology, Hemotherapy and Cell Therapy, Faculty of Medicine, University of São Paulo (FM-USP), São Paulo, Brazil., Zerbini MCN; Department of Pathology, Faculty of Medicine, University of São Paulo (FM-USP), São Paulo, Brazil., de Oliveira Costa R; Department of Hematology and Hemotherapy, Faculty of Medical Sciences Santos (FCMS), Centro Universitário Lusíadas (Unilus), Santos, Brazil., Rocha V; Department of Hematology, Hemotherapy and Cell Therapy, Faculty of Medicine, University of São Paulo (FM-USP), São Paulo, Brazil.; Laboratory of Medical Investigation in Pathogenesis and Directed Therapy in Onco-Immuno-Hematology (LIM-31), University of São Paulo (USP), Cerqueira César, Avenue Dr. Enéas de Carvalho Aguiar, 155 - Ambulatory building - 1st. Floor, Room 61, São Paulo (SP), 05403-000, Brazil.; Fundação Pró-Sangue, Blood Bank of São Paulo, São Paulo, Brazil.; Churchill Hospital, Oxford University, Oxford, UK., Pereira J; Department of Hematology, Hemotherapy and Cell Therapy, Faculty of Medicine, University of São Paulo (FM-USP), São Paulo, Brazil.; Laboratory of Medical Investigation in Pathogenesis and Directed Therapy in Onco-Immuno-Hematology (LIM-31), University of São Paulo (USP), Cerqueira César, Avenue Dr. Enéas de Carvalho Aguiar, 155 - Ambulatory building - 1st. Floor, Room 61, São Paulo (SP), 05403-000, Brazil.; Hospital Alemão Osvaldo Cruz, São Paulo, Brazil.
Jazyk: angličtina
Zdroj: Radiation oncology (London, England) [Radiat Oncol] 2022 Oct 22; Vol. 17 (1), pp. 171. Date of Electronic Publication: 2022 Oct 22.
DOI: 10.1186/s13014-022-02142-y
Abstrakt: Background: Primary central nervous system lymphoma (PCNSL) is a rare and aggressive malignancy. Although potentially curable, its prognosis remains dismal. Its treatment is based on high-doses of methotrexate (HD-MTX) and rituximab, followed by consolidation therapy with whole-brain radiotherapy (WBRT) or autologous stem cell transplantation (ASCT). Currently, there is no consensus about the best consolidation strategy, but better outcomes with ASCT are obtained with conditioning regimens based on thiotepa, a high-cost drug with restricted use in resource-constrained settings. Latin American data on clinical outcomes, prognostic factors, and therapeutic management in PCNSL are virtually unknown.
Methods: This is a retrospective, observational, and single-center study involving 47-Brazilian patients with PCNSL. We aim to assess outcomes, determine predictors of survival, and compare responses, as well as toxicities in patients consolidated with chemotherapy alone versus chemotherapy plus WBRT.
Results: The median age at diagnosis was 59 years (24-88 years), and 53.1% were male. LDH ≥ UVN occurred in 44.7%, ECOG ≥ 2 in 67.6%, and 34.1% had multifocal disease. Hemiparesis was the main clinical presentation, observed in 55.3%, 51.0% had intermediate-/high-risk IELSG prognostic score, and 57.6% had an ABC-like phenotype by IHC. With a median follow-up of 24.4 months, estimated 5-year OS and PFS were 45.5% and 36.4%, respectively. Among 40 patients treated with HD-MTX-based induction, estimated 2-year OS was 85.8% for those consolidated with WBRT plus HIDAC versus only 41.5% for those consolidated with HIDAC alone (p < 0.001). Hematologic and non-hematologic toxicities were not significant, and severe cognitive impairment occurred in only 6.3% (3/47) of cases, all of them treated with WBRT. Age < 60 years, Hb ≥ 120 g/L and WBRT consolidation were associated with increased OS, however, LDH ≥ UVN, hypoalbuminemia, ECOG ≥ 2, Karnofsky PS < 70 and intermediate-/high-risk Barcelona score were associated with decreased OS.
Conclusion: Combined consolidation therapy (CCT) based on WBRT plus HIDAC was associated with increased OS in PCNSL compared to isolated consolidation therapy (ICT) based on HIDAC alone. Here, severe late neurotoxicity was uncommon with this approach. These data suggest that WBRT may be an effective and safe alternative to ASCT for consolidation therapy in PCNSL, particularly in resource-constrained settings, where access to thiotepa for pre-ASCT conditioning is not universal.
(© 2022. The Author(s).)
Databáze: MEDLINE
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