Intraarterial chemotherapy and osmotic blood-brain barrier disruption for patients with embryonal and germ cell tumors of the central nervous system

Kristoph Jahnke, Dale Kraemer, Kristin Knight, David Fortin, Susan Bell, Nancy Doolittle, Leslie Muldoon, Edward Neuwelt

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

BACKGROUND. The rate of durable responses in embryonal and certain germ cell tumors of the central nervous system (CNS) is unsatisfactory. Intraarterial chemotherapy and osmotic blood-brain barrier disruption (IA/BBBD) increases drug delivery to the CNS. METHODS. Data of patients treated with carboplatin or methotrexate-based IA/BBBD on prospective phase 2 trials conducted at 3 centers were collected. Study outcomes included overall survival (OS), time to progression (TTP), and toxicity. RESULTS. Fifty-four patients were treated. Twenty-seven patients received IA/BBBD as salvage treatment. The median OS was 2.8 years for all patients, 2.5 years for supratentorial and disseminated primitive neuroectodermal tumors (PNETs, n = 29), 1.7 years for medulloblastomas (n = 12), and 5.4 years for germ cell tumors (n = 13). OS and TTP for all patients were better with a Karnofsky Performance Status ≥70% (P = .0013 and .0070) and IA/BBBD as first-line treatment (P = .0059 and .029). In PNETs, OS was higher with pineal location (P = .045) and IA/BBBD as first-line treatment (P = .0036), and TTP was improved with radiotherapy before IA/BBBD (P = .036) and IA/BBBD as first-line treatment (P = .0079). Seventeen of 54 patients (31%) are alive, and 16 are alive at 4+ to 18+ years. Three survivors were not treated with radiotherapy and 4 were treated with focal radiotherapy only. The patients who were not irradiated did not develop dementia. CONCLUSIONS. Survival and toxicity data appear promising, considering the cohort's adverse prognostic profile. A plateau in survival curves suggests a cure for some patients. Long-term survival may be achieved with focal or reduced-dose radiotherapy in some IA/BBBD patients.

Original languageEnglish (US)
Pages (from-to)581-588
Number of pages8
JournalCancer
Volume112
Issue number3
DOIs
StatePublished - Feb 1 2008

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Nervous System Neoplasms
Germ Cell and Embryonal Neoplasms
Blood-Brain Barrier
Central Nervous System
Drug Therapy
Survival
Primitive Neuroectodermal Tumors
Radiotherapy
Karnofsky Performance Status
Salvage Therapy
Medulloblastoma
Carboplatin
Methotrexate
Survivors
Dementia
Therapeutics
Outcome Assessment (Health Care)

Keywords

  • Blood-brain barrier disruption
  • Embryonal tumors
  • Germ cell tumors

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Intraarterial chemotherapy and osmotic blood-brain barrier disruption for patients with embryonal and germ cell tumors of the central nervous system. / Jahnke, Kristoph; Kraemer, Dale; Knight, Kristin; Fortin, David; Bell, Susan; Doolittle, Nancy; Muldoon, Leslie; Neuwelt, Edward.

In: Cancer, Vol. 112, No. 3, 01.02.2008, p. 581-588.

Research output: Contribution to journalArticle

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T1 - Intraarterial chemotherapy and osmotic blood-brain barrier disruption for patients with embryonal and germ cell tumors of the central nervous system

AU - Jahnke, Kristoph

AU - Kraemer, Dale

AU - Knight, Kristin

AU - Fortin, David

AU - Bell, Susan

AU - Doolittle, Nancy

AU - Muldoon, Leslie

AU - Neuwelt, Edward

PY - 2008/2/1

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N2 - BACKGROUND. The rate of durable responses in embryonal and certain germ cell tumors of the central nervous system (CNS) is unsatisfactory. Intraarterial chemotherapy and osmotic blood-brain barrier disruption (IA/BBBD) increases drug delivery to the CNS. METHODS. Data of patients treated with carboplatin or methotrexate-based IA/BBBD on prospective phase 2 trials conducted at 3 centers were collected. Study outcomes included overall survival (OS), time to progression (TTP), and toxicity. RESULTS. Fifty-four patients were treated. Twenty-seven patients received IA/BBBD as salvage treatment. The median OS was 2.8 years for all patients, 2.5 years for supratentorial and disseminated primitive neuroectodermal tumors (PNETs, n = 29), 1.7 years for medulloblastomas (n = 12), and 5.4 years for germ cell tumors (n = 13). OS and TTP for all patients were better with a Karnofsky Performance Status ≥70% (P = .0013 and .0070) and IA/BBBD as first-line treatment (P = .0059 and .029). In PNETs, OS was higher with pineal location (P = .045) and IA/BBBD as first-line treatment (P = .0036), and TTP was improved with radiotherapy before IA/BBBD (P = .036) and IA/BBBD as first-line treatment (P = .0079). Seventeen of 54 patients (31%) are alive, and 16 are alive at 4+ to 18+ years. Three survivors were not treated with radiotherapy and 4 were treated with focal radiotherapy only. The patients who were not irradiated did not develop dementia. CONCLUSIONS. Survival and toxicity data appear promising, considering the cohort's adverse prognostic profile. A plateau in survival curves suggests a cure for some patients. Long-term survival may be achieved with focal or reduced-dose radiotherapy in some IA/BBBD patients.

AB - BACKGROUND. The rate of durable responses in embryonal and certain germ cell tumors of the central nervous system (CNS) is unsatisfactory. Intraarterial chemotherapy and osmotic blood-brain barrier disruption (IA/BBBD) increases drug delivery to the CNS. METHODS. Data of patients treated with carboplatin or methotrexate-based IA/BBBD on prospective phase 2 trials conducted at 3 centers were collected. Study outcomes included overall survival (OS), time to progression (TTP), and toxicity. RESULTS. Fifty-four patients were treated. Twenty-seven patients received IA/BBBD as salvage treatment. The median OS was 2.8 years for all patients, 2.5 years for supratentorial and disseminated primitive neuroectodermal tumors (PNETs, n = 29), 1.7 years for medulloblastomas (n = 12), and 5.4 years for germ cell tumors (n = 13). OS and TTP for all patients were better with a Karnofsky Performance Status ≥70% (P = .0013 and .0070) and IA/BBBD as first-line treatment (P = .0059 and .029). In PNETs, OS was higher with pineal location (P = .045) and IA/BBBD as first-line treatment (P = .0036), and TTP was improved with radiotherapy before IA/BBBD (P = .036) and IA/BBBD as first-line treatment (P = .0079). Seventeen of 54 patients (31%) are alive, and 16 are alive at 4+ to 18+ years. Three survivors were not treated with radiotherapy and 4 were treated with focal radiotherapy only. The patients who were not irradiated did not develop dementia. CONCLUSIONS. Survival and toxicity data appear promising, considering the cohort's adverse prognostic profile. A plateau in survival curves suggests a cure for some patients. Long-term survival may be achieved with focal or reduced-dose radiotherapy in some IA/BBBD patients.

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KW - Embryonal tumors

KW - Germ cell tumors

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