Pretreatment intratumoral susceptibility signals correlate with response to high-dose methotrexate and progression-free survival in primary central nervous system lymphoma

Abstract OBJECTIVE To evaluate the efficacy and safety of high-dose methotrexate combined with temozolomide in the treatment of newly diagnosed primary central nervous system lymphoma. METHODS A retrospective study was performed to analyze the clinical data of patients with primary central nervous system lymphoma treated with high-dose methotrexate plus temozolomide in the Department of Neuro-oncology, Capital Medical University, Sanbo Brain Hospital from May 2010 to December 2018. RESULTS A total of 41 patients were identified. Median age was 57 years (range, 27–76 years). The maximal extent of surgery was total resection in 6, partial resection in 8, and biopsy in 27 patients. Of the 35 patients with evaluable lesions, 32 achieved complete response (CR) and 3 achieved partial response. CR rate was 91.4%. The median follow-up time was 36.5 months (range, 4.9–115.4 months). After treatment, the median progression-free survival (PFS) was 45.1 months. PFS rate at 1, 2, 5 years were 85.4%, 70.1% and 43.8%, respectively. The OS rate at 1, 2, 5 years were 92.7%, 82.4% and 66.5%, respectively. The median PFS of patients younger than 65 years was better than that of patients ≥65 years (98.8 months vs 27.9 months, p=0.039). There was no association between efficacy and extent of resection (p=0.836). After disease progression, 6 of the 21 patients received radiotherapy. There was no statistical difference in OS between the patients with or without radiotherapy (36.9 months vs 28.4 months). The main severe adverse events were myelosuppression (36.6%) and elevated transaminase (34.1%). Three patients were discontinued due to drug-related toxicities. CONCLUSIONS High-dose methotrexate combined with temozolomide is effective in the treatment of primary central nervous system lymphoma, with a low incidence of severe adverse reactions. This efficacy may be better than the historical control of methotrexate alone or methotrexate plus rituximab.

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High-dose methotrexate-based regimens with or without vincristine for the treatment of primary central nervous system lymphoma

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa077 ◽

2020 ◽

Vol 2 (1) ◽

Author(s):

Tracelyn Freeman ◽

Carlo S Legasto ◽

M Alexandra Schickli ◽

Eric M McLaughlin ◽

Pierre Giglio ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Treatment Options ◽

Group Versus ◽

Central Nervous System Lymphoma ◽

Progression Free Survival ◽

Adverse Event Rate ◽

High Dose ◽

High Dose Methotrexate ◽

Dose Methotrexate

Abstract Background Primary central nervous system lymphoma (PCNSL) is a rare malignancy with few treatment options. One regimen used for induction is rituximab, high-dose methotrexate (HD-MTX), procarbazine, and vincristine (R-MPV). A common institutional practice is removing vincristine (VCR) from this regimen due to its poor CNS penetration and associated toxicities. The aim of this study was to evaluate how the omission of VCR from HD-MTX-based induction impacted clinical outcomes. Methods In a retrospective review, patients with PCNSL who received HD-MTX-based induction therapy between January 1, 2010 and May 31, 2018 were evaluated. Patients were stratified according to treatment into 2 groups, VCR-containing therapy versus no VCR. The primary endpoint was complete response (CR) rate following the completion of induction chemotherapy. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and adverse event rate. Results Twenty-nine patients were included: 16 patients in the VCR group and 13 in the non-VCR group. A CR was achieved in 7 (44%) and 5 (38%) (odds ratio [OR] = 1.24; 95% confidence interval [CI]: 0.28–5.53) patients, respectively. Median OS was 85.3 (95% CI: 20.2–85.3) versus 67.1 months (95% CI: 10.5–NR) and median PFS was 60.7 (95% CI: 9.4–NR) versus 23.7 months (95% CI: 4.7–NR) in the VCR group versus non-VCR group, respectively. The incidence of any grade peripheral neuropathy was higher in the VCR group. Conclusions CR rate, OS, and PFS were similar between groups regardless of VCR inclusion. Adverse events were higher in the VCR group. Larger studies are required to further evaluate the efficacy of VCR in PCNSL induction regimens.

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Primary central nervous system lymphoma: Retrospective analysis of 34 cases in a single centre

Journal of International Medical Research ◽

10.1177/0300060517734395 ◽

2017 ◽

Vol 46 (2) ◽

pp. 883-894 ◽

Cited By ~ 3

Author(s):

Huafeng Wang ◽

Ming Wang ◽

Juying Wei ◽

Lei Wang ◽

Liping Mao ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Poor Prognosis ◽

Central Nervous System Lymphoma ◽

Progression Free Survival ◽

High Dose ◽

Single Centre ◽

Free Survival ◽

Median Progression Free Survival ◽

Dose Methotrexate

Objective To retrospectively analyse outcomes in patients with primary central nervous system lymphoma (PCNSL), which is a malignant CNS non-Hodgkin’s lymphoma with a poor prognosis. Methods This study retrospectively analysed the treatment and outcomes of patients with PCNSL, which were divided into two groups: surgery (S) group and surgery/biopsy+chemotherapy (SC) group. The latter group was further subdivided into four cohorts based on the treatment regimen: cyclophosphamide, epidoxorubicin, vincristine and prednisone (CHOP), high-dose methotrexate (HDM)+dexamethasone+rituximab (HDM+D+R), HDM+D+temozolomide (HDM+D+T), and HDM+D+R+T. Results The study enrolled 34 patients; 10 of which received surgery only. Between the S and SC groups, the median progression-free survival (PFS) and overall survival (OS) of intracranial PCNSLs ( n = 32) were 8.5 months versus 29 months, respectively; and 8.5 months versus 54 months, respectively (5-year OS: 10.0% versus 48.7%, respectively; 2-year PFS: 0.0% versus 52.6%, respectively). Comparing the CHOP and HDM-based chemotherapy cohorts, the median PFS and OS were 15 months versus not achieved, respectively, and 25 months versus not achieved, respectively (5-year OS: 20.0% versus 60.8%, respectively; 2-year PFS: 20.0% versus 62.7%, respectively). Conclusion Chemotherapy appears to provide a better OS and PFS for patients with PCNSLs compared with surgery alone. HDM+D+T and HDM+D+R+T may be effective choices for PCNSL treatment.

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