Cognitive Outcomes and Long-term Follow-up Results after Enhanced Chemotherapy Delivery for Primary Central Nervous System Lymphoma

Abstract

BBBD-enhanced chemotherapy delivery, without subsequent radiotherapy, resulted in favorable survival and cognitive outcomes for patients with primary central nervous system lymphomas who had not previously undergone irradiation. A cooperative multicenter study of intravenous chemotherapy without radiotherapy versus BBBD-enhanced chemotherapy would address the feasibility and necessity of performing a Phase III study for these rare central nervous system malignancies.

Combined systemic and intraventricular chemotherapy in primary CNS lymphoma: a pilot study

“…Employing systemic high dose MTX alone Guha-Thakurta et al reported a 100% response rate; however, median progression free survival was 16.7 and median overall survival only 30.4 months in 31 patients 57. However, this treatment modality is invasive, requires general anaesthesia, and is associated with potential acute neurotoxicity (seizures in 6% to 8% of the procedures, strokes in 6.8% of the patients) 7.…”

“…In 74 patients treated with intra-arterial cyclophophamide and high dose MTX after blood-brain barrier opening a median overall survival of 40.7 months has been reported without long term neurotoxicity as documented by serial neurosychological testing in 23 out of these 74 patients with ongoing complete remission 7. However, this treatment modality is invasive, requires general anaesthesia, and is associated with potential acute neurotoxicity (seizures in 6% to 8% of the procedures, strokes in 6.8% of the patients) 7. In a combined pilot/phase II study on 14 patients treated with systemic high dose MTX, thiotepa, vincristine, dexamethasone, and intraventricular MTX and ara-C a 79% complete remission has been achieved with a median progression free survival of 16.5 months and a projected minimum median overall survival of 40 months 6…”

“…In these studies, health related quality of life assessment5 and neuropsychological testing7 showed no significant long term neurotoxicity. However, more than half of the patients in the study of Guha-Thakurta et al relapsed within 17 months,5 and the rationale for blood-brain barrier opening, as employed by McAllsiter et al ,7 remains controversial, because PCNSL are potentially widespread infiltrative tumours that are not always identifiable by neuroimaging 18 Here we report on the therapeutic results of 20 patients with PCNSL enrolled in a pilot study evaluating the efficacy and toxicity of a novel combined intraventricular and systemic chemotherapy regimen without radiotherapy.…”

“…Chemotherapy alone based on systemic MTX greater than1g/m 2 is efficient in terms of tumour response and extended survival 56 Complete response rates (median overall survival) were 65% (30.4 months) in 31 patients treated with high dose (3.5 to 8 g/m 2 /cycle) systemic MTX alone,5 and 65% (40.7 months) in 74 patients treated with intra-arterial cyclophosphamide and MTX (2.5 g/m 2 /cycle) after osmotic blood-brain barrier opening 7. In these studies, health related quality of life assessment5 and neuropsychological testing7 showed no significant long term neurotoxicity.…”

“…6 Complete response rates (median overall survival) were 65% (30.4 months) in 31 patients treated with high dose (3.5 to 8 g/m 2 /cycle) systemic MTX alone,5 and 65% (40.7 months) in 74 patients treated with intra-arterial cyclophosphamide and MTX (2.5 g/m 2 /cycle) after osmotic blood-brain barrier opening 7. In these studies, health related quality of life assessment5 and neuropsychological testing7 showed no significant long term neurotoxicity. However, more than half of the patients in the study of Guha-Thakurta et al relapsed within 17 months,5 and the rationale for blood-brain barrier opening, as employed by McAllsiter et al ,7 remains controversial, because PCNSL are potentially widespread infiltrative tumours that are not always identifiable by neuroimaging 1…”