Faculty Opinions recommendation of High-dose methotrexate with or without whole brain radiotherapy for primary CNS lymphoma (G-PCNSL-SG-1): a phase 3, randomised, non-inferiority trial.

2011 ◽  
Author(s):  
Jeffrey Raizer ◽  
Priya Kumthekar
Keyword(s):  
Primary Cns Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Cns Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Phase 3 ◽  
Whole Brain ◽  
Brain Radiotherapy ◽  
Dose Methotrexate

Treatment of primary CNS lymphoma with induction high-dose methotrexate, temozolomide, rituximab followed by consolidation cytarabine/etoposide: A pilot study with biomarker analysis

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7595-7595 ◽  
Author(s):  
S. Issa ◽  
J. Hwang ◽  
J. Karch ◽  
J. Fridlyand ◽  
M. Prados ◽  
...  
Keyword(s):  
Induction Therapy ◽  
Primary Cns Lymphoma ◽  
Cns Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Whole Brain Irradiation ◽  
Whole Brain ◽  
Brain Irradiation ◽  
Dose Methotrexate ◽  
Biomarker Analysis

7595 Background: There is currently no consensus on the optimal treatment for patients diagnosed with primary CNS lymphoma (PCNSL). Between 2001–2004, UCSF PCNSL patients were treated with combination high-dose methotrexate, temozolomide, rituximab (MTR) as induction therapy. Patients in CR with this regimen were treated with high-dose cytarabine plus etoposide as consolidation. The purposes of this study were: (1) Pilot analysis to determine the safety and efficacy of intensive methotrexate-based induction therapy followed by high-dose consolidation with elimination of whole brain irradiation; (2) Analysis of molecular markers in PCNSL which predict sensitivity to chemotherapy and outcome. Methods: 21 untreated, CD20 +, immunocompetent PCNSL patients were treated with combination methotrexate (8 gm/m²), temozolomide (150 mg/m²/day)and rituximab (375 mg/m²). Patients in CR received consolidation cytarabine (2 g/ m² x 8 doses) plus etoposide (40 mg/kg over 96 hours). IHC analysis of potential biomarkers predictive of outcome was performed on paraffin sections from these patients. Candidate markers for validation were selected by gene expression analysis of an independent, multicenter dataset of 20 cases. Results: Mean age was 58.6 y (range 40–81). Median KPS was 60. MTR and cytarabine/etoposide consolidation was well-tolerated with no treatment-related mortality or evidence for neurotoxicity. One case of post-remission cytopenia occurred after consolidation and resolved spontaneously. Eleven patients (52.4%) attained CR with induction; eight received consolidation; three patients in CR deferred consolidation. Median PFS was 11.5 months. Median OS for all 21 patients has not yet been reached with median follow-up of 27.5 months. Expression of the apoptotic regulator DAP-1 by lymphoma cells as determined by IHC was associated with improved PFS (p<0.028) and OS (p<0.021). Conclusions: Combination MTR followed by intensive consolidation appears to be well tolerated in PCNSL. PFS appears at least similar to regimens that contain whole brain irradiation. A larger phase II study has been initiated to evaluate this regimen in a multicenter setting. [Table: see text]

scholarly journals NQPC-5 Does high-dose methotrexate-based chemotherapy for relapsed primary CNS lymphoma increase a risk of leukoencephalopathy with prior whole brain radiotherapy?

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi22-vi22
Author(s):  
Keiichi Kobayashi ◽  
Nobuyoshi Sasaki ◽  
Kuniaki Saito ◽  
Yuki Yamagishi ◽  
Naomi Hanayama ◽  
...  
Keyword(s):  
Performance Status ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Progression Free Survival ◽  
Cns Lymphoma ◽  
High Dose ◽  
Whole Brain ◽  
Brain Radiotherapy ◽  
Study Results

Abstract Backgrounds: Standard care for primary central nervous system lymphoma (PCNSL) comprises high-dose (HD) methotrexate (MTX) -based chemotherapy with or without consolidation whole brain radiotherapy (WBRT). HD-MTX administration following WBRT has been suggested to increase a risk of leukoencephalopathy. However, given that there are no other agents with efficacy similar to or better than MTX, patients with relapsed PCNSL may often be treated with regimens containing HD-MTX if the initial MTX treatment achieved a long-term complete remission. Here, we retrospectively analyzed prevalence and an extent of white mater damages in association with prior WBRT in patients with relapsed PCNSL treated with HD-MTX based therapy. Patients & methods: Among 79 patients with relapsed/refractory PCNSL in a total of 162 patients with newly-diagnosed PCNSL treated in our institution from April, 2000 to February, 2021, 35 patients were identified with evaluable KPS, MMSE, and Fazekas scale data at both baseline and follow-up periods. Of the 35 patients, 22 were treated with chemotherapy at a relapse (10 with prior WBRT, while 12 without WBRT), and were included in this preliminary study. Results: In the WBRT group (male/female: 5/5), median age was 65 years (range, 45–73), initial median KPS was 70 (40–90), and median WBRT dose was 27 Gy (23.4–40). Median progression-free survival (mPFS) was 11.8 months, and median overall survival (mOS) was not reached. In the non-WBRT group (M/F 8/4), median age 75 (62–84), initial mKPS 80 (50–90), mPFS 16.2 m, and mOS not reached. Initial KPS and MMSE score tended to be worse in WBRT group, presumably due to enrichment of patients with poorer performance status and more comorbidities. A decline in the Fazekas score was not associated with MMSE deterioration.Conclusions: The preliminary analysis was not informative enough, and further extensive imaging analysis will be exploited.

Whole Brain Radiotherapy and Ara-C In Consolidation Post High-Dose Methotrexate Is Important In Establishing Durable Disease Control In the Treatment of Primary CNS Lymphoma: A Single Centre Observational Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1776-1776
Author(s):  
Hang Quach ◽  
Melody Abikhair ◽  
Michael MacManus ◽  
Ron Freilich ◽  
Beena Kumar ◽  
...  
Keyword(s):  
Disease Control ◽  
Cell Lymphoma ◽  
Whole Brain Radiotherapy ◽  
B Cell Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Single Centre ◽  
Whole Brain ◽  
Brain Radiotherapy ◽  
Dose Methotrexate

Abstract Abstract 1776 While the survival benefits of high-dose methotrexate (MTX) based chemotherapy for primary central nervous system lymphoma (PCNSL) are well documented, the place for adjunctive cytarabine, and whole brain radiotherapy (WBRT) in consolidation remains uncertain. Due to the potential significant risk of treatment delayed neurotoxicity, the delivery of WBRT is often omitted at the physician's discretion in the treatment of PCNSL, especially in elderly patients. In the absence of randomised control trials comparing survival outcomes between patients receiving high dose MTX with or without WBRT in consolidation, we performed a retrospective study assessing the impact of these treatment modalities and other prognostic factors on the overall survival in a heterogeneously treated population with PCNSL. Forty-five patients with newly diagnosed PCNSL were identified at Monash Medical Centre, Australia between 1995 and 2009. Twenty patients were treated with palliative intent and were removed from analysis. The remaining 25 patients had a median age of 59 (range 31–79). Twenty-four patients had diffuse large B cell lymphoma, one T-cell lymphoma. Positive CSF cytology for lymphoma was found in 4 patients. All actively treated patients received chemotherapy; 16 patients received high-dose MTX-based combination chemotherapy, 5 patients received single-agent high-dose MTX, and 3 other. Eleven patients (median age 48, range 31–79) received WBRT in consolidation. The median dose of RT delivered was 39.6 Gy (range 20–45 Gy). After a median follow up of 2.1 years (range 0.3 – 11.6 years), the 5 year PFS was 27% and 5 year OS was 40% for all patients in the actively treated group. On univariate analysis, Age <60 years at diagnosis was significantly associated with both increased in PFS (p=0.002) and OS (p=0.04). Patients who received WBRT in consolidation tended to have a longer PFS (5 year PFS 49% vs. 12% p=0.098) compared to patients who did not receive WBRT. However, OS in both groups were similar (5 year OS 47% (consolidation WBRT) vs. 42%, p=0.31). Importantly, no relapses were observed in patients receiving WBRT who survived 2.7 years. Although formal neuropsychiatric assessment was not performed, examination of the records identified no significant cognitive impairment in survivors. Adjunctive cytarabine was associated with improved OS (p<0.001), however use of cytarabine was correlated with age<60 (Fishers exact test). Nonetheless, on multivariate analysis, the use of cytarabine was the only covariate associated with improved PFS and OS (p<0.001, Cox regression). Conclusion. The potential of cure in a proportion of patients as a result of initial therapy is suggested in this single centre experience by the plateau in the PFS and OS curve. This study underscores the potential role of both WBRT and AraC in consolidation after high dose MTX-based chemotherapy, in establishing durable disease control, and supports such an approach particularly in young patients with good performance status. The lack of overt neurotoxicity associated with moderate dose radiotherapy is of particular interest; although long-term formal cognitive assessments are lacking in this case. Disclosures: No relevant conflicts of interest to declare.

Long-Term Follow-Up of High-Dose Methotrexate-Based Therapy With and Without Whole Brain Irradiation for Newly Diagnosed Primary CNS Lymphoma

2006 ◽  
Vol 24 (28) ◽  
pp. 4570-4574 ◽  
Author(s):  
Igor T. Gavrilovic ◽  
Adília Hormigo ◽  
Joachim Yahalom ◽  
Lisa M. DeAngelis ◽  
Lauren E. Abrey
Keyword(s):  
Overall Survival ◽  
Whole Brain Radiotherapy ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Whole Brain ◽  
Brain Radiotherapy ◽  
Dose Methotrexate ◽  
Long Term Follow Up

Purpose We previously reported a series of patients treated with high-dose methotrexate (MTX) -based chemotherapy, with or without whole brain radiotherapy. The purpose of this report is to update the initial results and provide long-term data regarding overall survival, patterns of relapse, and the risk of treatment-related neurotoxicity. Patients and Methods Fifty-seven patients with an average age of 65 and median Karnofsky performance score of 70 were treated; all patients have been observed longitudinally with serial magnetic resonance imaging scans and neurologic examinations. Results The overall median survival was 51 months with a median follow-up of 115 months for surviving patients. Twenty-five patients relapsed or developed progressive disease; median progression-free survival was 129 months. Seventeen patients developed treatment-related neurotoxicity; all but one had received whole brain radiotherapy as a component of treatment. Seventy-four percent of patients younger than 60 years who received both MTX-based chemotherapy and whole brain radiotherapy were alive at last follow-up. Median survival for patients older than 60 years was 29 months regardless of whether or not they received whole brain radiotherapy. Conclusion Long-term follow-up of our initial cohort confirms the observation of excellent overall survival, particularly for those patients younger than age 60 at diagnosis. For older patients, it appears to be reasonable to defer whole brain radiotherapy in an effort to minimize treatment-related neurotoxicity.

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