Long-Term Evaluation of Combination Treatment of Single Agent HD-MTX Chemotherapy up to Three Cycles and Moderate Dose Whole Brain Irradiation for Primary CNS Lymphoma

2019 ◽  
Vol 31 (1) ◽  
pp. 35-41
Author(s):  
Hiroyuki Kobayashi ◽  
Shigeru Yamaguchi ◽  
Hiroaki Motegi ◽  
Sadahiro Kaneko ◽  
Shogo Endou ◽  
...  
Keyword(s):  
Combination Treatment ◽  
Single Agent ◽  
Primary Cns Lymphoma ◽  
Cns Lymphoma ◽  
Moderate Dose ◽  
Whole Brain Irradiation ◽  
Whole Brain ◽  
Brain Irradiation ◽  
Term Evaluation

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]

Treatment of Primary CNS Lymphoma with Induction High-Dose Methotrexate, Temozolomide, Rituximab Followed by Consolidation Cytarabine/Etoposide: A Pilot Study with Biomarker Analysis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1364-1364 ◽  
Author(s):  
Samar Issa ◽  
Arthur Shen ◽  
Jon Karch ◽  
Cigall Kadoch ◽  
Marc Shuman ◽  
...  
Keyword(s):  
Overall Survival ◽  
Performance Status ◽  
Primary Cns Lymphoma ◽  
Immunohistochemical Analysis ◽  
Cns Lymphoma ◽  
High Dose ◽  
Whole Brain Irradiation ◽  
Whole Brain ◽  
Brain Irradiation ◽  
Biomarker Analysis

Abstract Background: There is no consensus on the optimal treatment for patients diagnosed with primary CNS lymphoma (PCNSL). The goals of this study were: to determine the safety and efficacy of a methotrexate (MTX)-based induction therapy followed by high-dose consolidation chemotherapy and the elimination or deferral of whole brain irradiation, to identify molecular markers in PCNSL which predict sensitivity to chemotherapy and outcome. Methods: 23 newly diagnosed, CD20-positive, immunocompetent PCNSL patients were treated with combination high-dose intravenous MTX (8 gm/m2), temozolomide (150 mg/m2/day) and intravenous rituximab (375 mg/m2) (MTR). Patients in complete remission (CR) after eight courses of MTX were offered consolidation with high-dose cytarabine (2 g/m2 x 8 doses) and etoposide (40 mg/kg over 96 hours) (AE). Candidate markers of outcome in PCNSL were identified by gene expression profile analysis of an independent, multicenter dataset of PCNSL tumors. Immunohistochemical analysis of one of these markers, death-associated protein-1 (DAP-1), was performed on paraffin sections of tumors from 18 of the patients treated with the MTR regimen. Results: MTR induction followed by AE consolidation was well tolerated with no treatment-related mortality or evidence for neurotoxicity. Thirteen patients (56.5%) attained CR with induction; 8 received consolidation; 5 in CR refused AE. Median progression-free (PFS) and overall survival (OS) has not yet been reached with a median follow-up of 33 months. Karnovsky performance status (KPS) correlated with improved survival (p<0.0281). Expression by lymphoma cells of DAP-1, a regulator of apoptosis, was associated with improved progression-free survival (p<0.03) and overall survival (p<0.038). Conclusions: Combination MTR followed by AE is well tolerated in PCNSL. PFS appears at least similar to regimens that contain whole brain irradiation. A multi-center study has been initiated to further evaluate this regimen. DAP-1 may be a tumor suppressor whose expression in PCNSL predicts a favorable response to MTX-based therapy.

Primary central nervous system lymphoma

1985 ◽  
Vol 62 (4) ◽  
pp. 522-527 ◽  
Author(s):  
Yasuto Kawakami ◽  
Kazuo Tabuchi ◽  
Rinkichi Ohnishi ◽  
Shoji Asari ◽  
Akira Nishimoto
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Subtotal Resection ◽  
Cns Lymphoma ◽  
Whole Brain Irradiation ◽  
Whole Brain ◽  
Content Type ◽  
Brain Irradiation

✓ A retrospective analysis of 21 cases of primary central nervous system (CNS) lymphoma is reported. All patients presented with a solitary mass in the supratentorial region. None had previously received immunosuppressive therapy. Neuroradiological studies included technetium-99m-pertechnetate brain scanning in eight cases, cerebral arteriography in all 21 cases, and computerized tomography (CT) in 14 cases. The characteristic features were increased uptake in brain scans, mass effect in arteriograms, and marked contrast enhancement on CT scans. Abnormal tumor vessels were occasionally seen on arteriography, and subtraction films were usually required to appreciate tumor stain. All patients underwent craniotomy, and histological studies of the tumors showed a diffuse type of lymphoma in all cases. Immunoglobulin testing was performed in 19 cases and a monoclonal spike was verified in 10, suggesting a B cell origin. All patients were followed until their death except one who was still alive 12 months from onset of symptoms. Therapy included subtotal resection in all 21 cases, whole-brain irradiation in six cases, chemotherapy in two cases, and a combination of whole-brain irradiation and chemotherapy in nine cases. Three different forms of chemotherapy were used. The results suggest that chemotherapy is an important addition to subtotal resection and whole-brain irradiation in the treatment of primary CNS lymphoma.

scholarly journals Mpv Salvage Regimen Followed by Hdt/Asct and Whole Brain Irradiation for Secondary Cns Lymphoma: a Follow-Up Data

2014 ◽  
Vol 25 ◽  
pp. v83
Author(s):  
Ikuo Shimizu ◽  
Naoaki Ichikawa ◽  
Wataru Takeda ◽  
Toshimitsu Ueki ◽  
Yuki Hiroshima ◽  
...  
Keyword(s):  
Cns Lymphoma ◽  
Whole Brain Irradiation ◽  
Salvage Regimen ◽  
Whole Brain ◽  
Brain Irradiation

scholarly journals Rituximab, Methotrexate, Procarbazine, and Vincristine Followed by Consolidation Reduced-Dose Whole-Brain Radiotherapy and Cytarabine in Newly Diagnosed Primary CNS Lymphoma: Final Results and Long-Term Outcome

2013 ◽  
Vol 31 (31) ◽  
pp. 3971-3979 ◽  
Author(s):  
Patrick G. Morris ◽  
Denise D. Correa ◽  
Joachim Yahalom ◽  
Jeffrey J. Raizer ◽  
David Schiff ◽  
...  
Keyword(s):  
Primary Cns Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Cns Lymphoma ◽  
Karnofsky Performance Score ◽  
Whole Brain ◽  
Long Term Outcome ◽  
Reduced Dose ◽  
Brain Radiotherapy

Purpose A multicenter phase II study was conducted to assess the efficacy of rituximab, methotrexate, procarbazine, and vincristine (R-MPV) followed by consolidation reduced-dose whole-brain radiotherapy (rdWBRT) and cytarabine in primary CNS lymphoma. Patients and Methods Patients received induction chemotherapy with R-MPV (five to seven cycles); those achieving a complete response (CR) received rdWBRT (23.4 Gy), and otherwise, standard WBRT was offered (45 Gy). Consolidation cytarabine was given after the radiotherapy. The primary end point was 2-year progression-free survival (PFS) in patients receiving rdWBRT. Exploratory end points included prospective neuropsychological evaluation, analysis of magnetic resonance imaging (MRI) white matter changes using the Fazekas scale, and evaluation of the apparent diffusion coefficient (ADC) as a prognostic factor. Results Fifty-two patients were enrolled, with median age of 60 years (range, 30 to 79 years) and median Karnofsky performance score of 70 (range, 50 to 100). Thirty-one patients (60%) achieved a CR after R-MPV and received rdWBRT. The 2-year PFS for this group was 77%; median PFS was 7.7 years. Median overall survival (OS) was not reached (median follow-up for survivors, 5.9 years); 3-year OS was 87%. The overall (N = 52) median PFS was 3.3 years, and median OS was 6.6 years. Cognitive assessment showed improvement in executive function (P < .01) and verbal memory (P < .05) after chemotherapy, and follow-up scores remained relatively stable across the various domains (n = 12). All examined MRIs (n = 28) displayed a Fazekas score of ≤ 3, and no patient developed scores of 4 to 5; differences in ADC values did not predict response (P = .15), PFS (P = .27), or OS (P = .33). Conclusion R-MPV combined with consolidation rdWBRT and cytarabine is associated with high response rates, long-term disease control, and minimal neurotoxicity.

scholarly journals An Updated Review on Memantine Efficacy in Reducing Cognitive Dysfunction of Whole-brain Irradiation for Adult Patients with Brain metastasis

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Anya jafari ◽  
Zahra Siavashpour ◽  
Mohammad Houshyari
Keyword(s):  
Brain Metastasis ◽  
Verbal Learning ◽  
Whole Brain Radiotherapy ◽  
Protective Effects ◽  
Whole Brain Irradiation ◽  
Whole Brain ◽  
Brain Irradiation ◽  
Brain Radiotherapy ◽  
Delayed Recognition

Context: Increased survival of patients with cancer raises the need to pay attention to long-term side effects. Patients with brain metastasis experienced cognition failure after whole-brain radiotherapy. This review aimed at concluding the efficacy of Memantine in preserving cognitive function by reducing the brain toxicity of whole-brain radiotherapy for metastatic brain cancers. Evidence Acquisition: Published studies evaluating memantine protective effects during brain metastasis radiotherapy were searched for in scientific databases (e.g., Embase, PubMed, Cochrane database, Google Scholar, Scopus) using keywords including whole-brain radiotherapy and Memantine. Results: A total of 4 prospective clinical trials were included in the review. Effects of Memantine on cognition tests were evaluated in these trials. A significantly better Hopkins Verbal Learning Test-Revised (HVLT-R) delayed recognition at months 6 was achieved in RTOG 0614 and NRG CC001. Longer time to cognitive decline was found in the memantine arm of the RTOG trial and was statistically significant. Memantine effects were not statistically significant before 2 months. Conclusions: It seems reasonable to consider Memantine during radiation to prevent long-term cognitive failure in patients with brain metastasis due to the current results. Memantine improves cognition function during whole-brain radiotherapy (WBRT) without adding irreparable complications.

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