Blood-brain barrier disruption and intra-arterial methotrexate-based therapy for newly diagnosed primary CNS lymphoma: A multi-institutional experience

Lilyana Angelov, Nancy Doolittle, Dale Kraemer, Tali Siegal, Gene H. Barnett, David M. Peereboom, Glen Stevens, John McGregor, Kristoph Jahnke, Cynthia A. Lacy, Nancy A. Hedrick, Edna Shalom, Sandra Ference, Susan Bell, Lisa Sorenson, Rose Marie Tyson, Marianne Haluska, Edward Neuwelt

Research output: Contribution to journalArticle

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Abstract

Purpose: Primary CNS lymphoma (PCNSL) is confined to the CNS and/or the eyes at presentation and is usually initially treated with intravenous methotrexate-based chemotherapy and whole-brain radiotherapy (WBRT). However, the intact blood-brain barrier (BBB) can limit diffusion of methotrexate into brain and tumor. With BBB disruption (BBBD), enhanced drug delivery to the tumor can be achieved. Patients and Methods: This report summarizes the multi-institutional experience of 149 newly diagnosed (with no prior WBRT) patients with PCNSL treated with osmotic BBBD and intra-arterial (IA) methotrexate at four institutions from 1982 to 2005. In this series, 47.6% of patients were age ≥ 60 years, and 42.3% had Karnofsky performance score (KPS) less than 70 at diagnosis. Results: The overall response rate was 81.9% (57.8% complete; 24.2% partial). Median overall survival (OS) was 3.1 years (25% estimated survival at 8.5 years). Median progression-free survival (PFS) was 1.8 years, with 5-year PFS of 31% and 7-year PFS of 25%. In low-risk patients (age <60 years and KPS ≥ 70), median OS was approximately 14 years, with a plateau after approximately 8 years. Procedures were generally well tolerated; focal seizures (9.2%) were the most frequent side effect and lacked long-term sequelae. Conclusion: This large series of patients treated over a 23-year period demonstrates that BBBD/IA methotrexate-based chemotherapy results in successful and durable tumor control and outcomes that are comparable or superior to other PCNSL treatment regimens.

Original languageEnglish (US)
Pages (from-to)3503-3509
Number of pages7
JournalJournal of Clinical Oncology
Volume27
Issue number21
DOIs
StatePublished - Jul 20 2009
Externally publishedYes

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Blood-Brain Barrier
Methotrexate
Lymphoma
Disease-Free Survival
Survival
Radiotherapy
Therapeutics
Drug Therapy
Brain
Brain Neoplasms
Neoplasms
Seizures
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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Blood-brain barrier disruption and intra-arterial methotrexate-based therapy for newly diagnosed primary CNS lymphoma : A multi-institutional experience. / Angelov, Lilyana; Doolittle, Nancy; Kraemer, Dale; Siegal, Tali; Barnett, Gene H.; Peereboom, David M.; Stevens, Glen; McGregor, John; Jahnke, Kristoph; Lacy, Cynthia A.; Hedrick, Nancy A.; Shalom, Edna; Ference, Sandra; Bell, Susan; Sorenson, Lisa; Tyson, Rose Marie; Haluska, Marianne; Neuwelt, Edward.

In: Journal of Clinical Oncology, Vol. 27, No. 21, 20.07.2009, p. 3503-3509.

Research output: Contribution to journalArticle

Angelov, L, Doolittle, N, Kraemer, D, Siegal, T, Barnett, GH, Peereboom, DM, Stevens, G, McGregor, J, Jahnke, K, Lacy, CA, Hedrick, NA, Shalom, E, Ference, S, Bell, S, Sorenson, L, Tyson, RM, Haluska, M & Neuwelt, E 2009, 'Blood-brain barrier disruption and intra-arterial methotrexate-based therapy for newly diagnosed primary CNS lymphoma: A multi-institutional experience', Journal of Clinical Oncology, vol. 27, no. 21, pp. 3503-3509. https://doi.org/10.1200/JCO.2008.19.3789
Angelov, Lilyana ; Doolittle, Nancy ; Kraemer, Dale ; Siegal, Tali ; Barnett, Gene H. ; Peereboom, David M. ; Stevens, Glen ; McGregor, John ; Jahnke, Kristoph ; Lacy, Cynthia A. ; Hedrick, Nancy A. ; Shalom, Edna ; Ference, Sandra ; Bell, Susan ; Sorenson, Lisa ; Tyson, Rose Marie ; Haluska, Marianne ; Neuwelt, Edward. / Blood-brain barrier disruption and intra-arterial methotrexate-based therapy for newly diagnosed primary CNS lymphoma : A multi-institutional experience. In: Journal of Clinical Oncology. 2009 ; Vol. 27, No. 21. pp. 3503-3509.
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abstract = "Purpose: Primary CNS lymphoma (PCNSL) is confined to the CNS and/or the eyes at presentation and is usually initially treated with intravenous methotrexate-based chemotherapy and whole-brain radiotherapy (WBRT). However, the intact blood-brain barrier (BBB) can limit diffusion of methotrexate into brain and tumor. With BBB disruption (BBBD), enhanced drug delivery to the tumor can be achieved. Patients and Methods: This report summarizes the multi-institutional experience of 149 newly diagnosed (with no prior WBRT) patients with PCNSL treated with osmotic BBBD and intra-arterial (IA) methotrexate at four institutions from 1982 to 2005. In this series, 47.6{\%} of patients were age ≥ 60 years, and 42.3{\%} had Karnofsky performance score (KPS) less than 70 at diagnosis. Results: The overall response rate was 81.9{\%} (57.8{\%} complete; 24.2{\%} partial). Median overall survival (OS) was 3.1 years (25{\%} estimated survival at 8.5 years). Median progression-free survival (PFS) was 1.8 years, with 5-year PFS of 31{\%} and 7-year PFS of 25{\%}. In low-risk patients (age <60 years and KPS ≥ 70), median OS was approximately 14 years, with a plateau after approximately 8 years. Procedures were generally well tolerated; focal seizures (9.2{\%}) were the most frequent side effect and lacked long-term sequelae. Conclusion: This large series of patients treated over a 23-year period demonstrates that BBBD/IA methotrexate-based chemotherapy results in successful and durable tumor control and outcomes that are comparable or superior to other PCNSL treatment regimens.",
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AU - Kraemer, Dale

AU - Siegal, Tali

AU - Barnett, Gene H.

AU - Peereboom, David M.

AU - Stevens, Glen

AU - McGregor, John

AU - Jahnke, Kristoph

AU - Lacy, Cynthia A.

AU - Hedrick, Nancy A.

AU - Shalom, Edna

AU - Ference, Sandra

AU - Bell, Susan

AU - Sorenson, Lisa

AU - Tyson, Rose Marie

AU - Haluska, Marianne

AU - Neuwelt, Edward

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N2 - Purpose: Primary CNS lymphoma (PCNSL) is confined to the CNS and/or the eyes at presentation and is usually initially treated with intravenous methotrexate-based chemotherapy and whole-brain radiotherapy (WBRT). However, the intact blood-brain barrier (BBB) can limit diffusion of methotrexate into brain and tumor. With BBB disruption (BBBD), enhanced drug delivery to the tumor can be achieved. Patients and Methods: This report summarizes the multi-institutional experience of 149 newly diagnosed (with no prior WBRT) patients with PCNSL treated with osmotic BBBD and intra-arterial (IA) methotrexate at four institutions from 1982 to 2005. In this series, 47.6% of patients were age ≥ 60 years, and 42.3% had Karnofsky performance score (KPS) less than 70 at diagnosis. Results: The overall response rate was 81.9% (57.8% complete; 24.2% partial). Median overall survival (OS) was 3.1 years (25% estimated survival at 8.5 years). Median progression-free survival (PFS) was 1.8 years, with 5-year PFS of 31% and 7-year PFS of 25%. In low-risk patients (age <60 years and KPS ≥ 70), median OS was approximately 14 years, with a plateau after approximately 8 years. Procedures were generally well tolerated; focal seizures (9.2%) were the most frequent side effect and lacked long-term sequelae. Conclusion: This large series of patients treated over a 23-year period demonstrates that BBBD/IA methotrexate-based chemotherapy results in successful and durable tumor control and outcomes that are comparable or superior to other PCNSL treatment regimens.

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