Efficacy of the Nordic and the MSKCC chemotherapy protocols on the overall and progression-free survival in intracranial PCNSL

Broi, Michele Da; Jahr, Guro; Beiske, Klaus; Holte, Harald; Meling, Torstein R.

doi:10.1016/j.bcmd.2018.08.005

Cited by 4 publications

(5 citation statements)

References 44 publications

(40 reference statements)

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“…With a MS of 45.0 months, our results are on par with the results obtained by the EORTC, using high-dose MTX+ WBRT (35). Recently, Da Broi et al reported the results of 57 patients treated over 12 years with chemotherapy (14). Overall, a median OS of 35.4 months, and a PFS of 15.7 months were observed.…”

Section: Discussionsupporting

confidence: 79%

“…Over the years, high-dose methotrexate (HD-MTX) has become the backbone of PCNSL treatment and is recommended by the European Association of Neuro-Oncology (EANO) guidelines (9). Many variations of protocols built around HD-MTX have been designed among which the Nordic protocol (14), the memorial Sloan-Kettering Cancer Center (MSKCC) protocol (14) and the Matrix protocol (15), to name only a few. In most recent protocols, investigators tend to postpone or even avoid the use of radiotherapy; indeed, its use has become controversial with findings of associated severe neuro-toxicity, especially in elderly patients (9,16,17).…”

Section: Introductionmentioning

confidence: 99%

“…Preventing most drugs from entering into the CNS, the BBB poses several challenges to the treatment of CNS pathologies (18) (19)(20)(21). It is presumably the reason behind the fact that most protocols for systemic non-Hodgkin lymphomas such as CHOP or CHOD have a low efficacy in primary CNS lymphomas (9,14,22,23). Although the BBB is partially breached at disease presentation, as exemplified by the florid contrast enhancement, it closes as the disease responds to the first cycles of treatment, re-establishing its impermeability (24,25).…”

Section: Introductionmentioning

confidence: 99%

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Management of Primary Central Nervous System Lymphoma Using Intra-Arterial Chemotherapy With Osmotic Blood-Brain Barrier Disruption: Retrospective Analysis of the Sherbrooke Cohort

et al. 2021

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BackgroundPrimary central nervous system lymphomas (PCNSL) are rare and aggressive CNS tumors. Current management involves high-dose methotrexate (HD-MTX) typically administered intravenously (IV), despite the existence of the blood-brain barrier (BBB), which significantly decreases its bioavailability. Cerebral intra-arterial chemotherapy (CIAC) coupled with osmotic BBB disruption (OBBBD) can theoretically circumvent this issue.MethodsWe performed a retrospective analysis of patients with newly diagnosed PCNSL treated with HD-MTX-based CIAC+OBBBD at our center between November 1999 and May 2018. OBBBD was achieved using a 25% mannitol intra-arterial infusion. Patients were followed clinically and radiologically every month until death or remission. Demographics, clinical and outcome data were collected from the medical record. All imaging studies were reviewed for evidence of complication and outcome assessment. Kaplan-Meier analyses were used to compute remission, progression-free survival (PFS) as well as overall survival times. Subgroup analyses were performed using the log rank test.ResultsForty-four patients were included in the cohort. Median follow-up was 38 months. Complete response was achieved in 34 patients (79%) at a median of 7.3 months. Actuarial median survival and PFS were 45 months and 24 months, respectively. Age, ECOG and lesion location did not impact outcome. Complications included thrombocytopenia (39%), neutropenia (20%), anemia (5%), seizures (11%), stroke (2%), and others (20%).ConclusionCIAC using HD-MTX-based protocols with OBBBD is a safe and well-tolerated procedure for the management of PCNSL. Our data suggests better PFS and survival outcomes compared to IV protocols with less hematologic toxicity and good tolerability, especially in the elderly.

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Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Management of Primary Central Nervous System Lymphoma Using Intra-Arterial Chemotherapy With Osmotic Blood-Brain Barrier Disruption: Retrospective Analysis of the Sherbrooke Cohort

et al. 2021

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“…Over the years, different protocols of IV high-dose Methotrexate have shown encouraging results. Indeed, Da Broi et al reported the results of 57 patients treated over 12 years with chemotherapy [44]. Overall, they found a median OS of 35.4 months, and a PFS of 15.7 months.…”

Section: Clinical Resultsmentioning

confidence: 99%

Drug Delivery Technology to the CNS in the Treatment of Brain Tumors: The Sherbrooke Experience

Fortin

2019

Pharmaceutics

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Drug delivery to the central nervous system (CNS) remains a challenge in neuro-oncology. Despite decades of research in this field, no consensus has emerged as to the best approach to tackle this physiological limitation. Moreover, the relevance of doing so is still sometimes questioned in the community. In this paper, we present our experience with CNS delivery strategies that have been developed in the laboratory and have made their way to the clinic in a continuum of translational research. Using the intra-arterial (IA) route as an avenue to deliver chemotherapeutics in the treatment of brain tumors, complemented by an osmotic breach of the blood-brain barrier (BBB) in specific situations, we have developed over the years a comprehensive research effort on this specialized topic. Looking at pre-clinical work supporting the rationale for this approach, and presenting results discussing the safety of the strategy, as well as results obtained in the treatment of malignant gliomas and primary CNS lymphomas, this paper intends to comprehensively summarize our work in this field.

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“…Several retrospective and single-arm prospective studies have been published of which many [19][20][21][22][23][24][25][26][27][28][29], but not all [24,[30][31][32], suggested improved progression-free survival with rituximab in comparison with historic controls or previously published results without rituximab (Table 1). All these studies reported that combination treatment is feasible.…”

Section: Introductionmentioning

confidence: 99%

The Role of Rituximab in Primary Central Nervous System Lymphoma

2020

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Purpose of Review The treatment of primary central nervous system lymphoma (PCNSL) is still under debate. One of the issues is the role of rituximab in improving the outcome. Here, we summarize the existing evidence, and comment on the literature on this topic. Recent Findings Two randomized controlled studies have been published recently, with conflicting results. Although the evidence of the benefit of rituximab is limited, it is already incorporated into many treatment regimens, both in studies and in standard clinical practice. Summary The use of rituximab in PCNSL is still a matter of debate. A positive effect on the outcome is uncertain. However, there are no clinical signs of significantly increased toxicity. The uncertain positive effect should therefore be weighed against the increased costs of the treatment.

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Efficacy of the Nordic and the MSKCC chemotherapy protocols on the overall and progression-free survival in intracranial PCNSL

Abstract: In univariate analysis, the MSKCC with RTX achieved significantly longer median OS compared to the Nordic protocol. However, in multivariate analysis, the only prognostic factor for survival of statistical significance was deep brain involvement.

Cited by 4 publications

References 44 publications

Management of Primary Central Nervous System Lymphoma Using Intra-Arterial Chemotherapy With Osmotic Blood-Brain Barrier Disruption: Retrospective Analysis of the Sherbrooke Cohort

Management of Primary Central Nervous System Lymphoma Using Intra-Arterial Chemotherapy With Osmotic Blood-Brain Barrier Disruption: Retrospective Analysis of the Sherbrooke Cohort

Drug Delivery Technology to the CNS in the Treatment of Brain Tumors: The Sherbrooke Experience

The Role of Rituximab in Primary Central Nervous System Lymphoma

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