Capillary physiology of human medulloblastoma: impact on chemotherapy.
BACKGROUND
Advances in the treatment of medulloblastoma have largely been attributed to the introduction of chemotherapy, although Phase III trials have shown advantages for chemotherapy only in subgroups. Because the efficacy of chemotherapy depends on tumor vascularization, the vascular physiology of human medulloblastomas was evaluated.


METHODS
Seven patients with histologically proven medulloblastomas underwent measurements of capillary permeability and vascular plasma volume using contrast-enhanced dynamic computer tomography. Regional blood flow was measured in 5 patients using xenon computed tomography (CT).


RESULTS
The capillary permeability-surface product for water-soluble compounds ranged from 1.7 +/- 5.5 to 17.6 +/- 12.3 muL/g/min with a mean of 10.5 +/- 6.3 microL/g/min. The vascular plasma volume ranged from 0.02 +/- 0.021 to 0.045 +/- 0.049 mL/g with a mean of 0.03 +/- 0.01 mL/g. The efflux rate ranged from 0.012 +/- 0.007 to 0.065 +/- 0.064 1/min with a mean of 0.039 +/- 0.020 1/min. Regional tumoral blood flow showed a mean of 19.86 +/- 6.8 mL/100g/min as compared with normal cerebellum with 45.4 +/- 12.03 mL/100g/min (P < .005).


CONCLUSIONS
The current study demonstrated a low capillary permeability and blood flow in medulloblastomas that could explain the limited response rates of partially resected tumors even after aggressive high-dose chemotherapy, as recently reported.
Warnke
Peter C
PC
Department of Neurological Science, Clinical Sciences Centre for Research and Education, University of Liverpool, Liverpool, Merseyside, United Kingdom. pwarnke@bidmc.harvard.edu
Kopitzki
Klaus
K
Timmer
Jens
J
Ostertag
Christoph B
CB
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002196:Capillaries / Q000503:physiopathology*; D002199:Capillary Permeability; D002528:Cerebellar Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000503:physiopathology*; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000098:blood supply* / Q000188:drug therapy / Q000503:physiopathology*