8 10 Intracarotid Chemotherapy of Glioblastoma after Induced Blood-Brain Barrier Disruption Cha rl es T. Bonst elle,1 Shashidhar H. Kori,2 and Harold Rekate 3 Intracarotid chemotherapy has been suggested as an addi- tional mode of therapy in patients with brain tumors. Seven comatose patients received intracarotid 5-fluorouracil and adria- mycin after intracarotid infusion of 25% mannitol to open the blood-b rain barrier at the tumor site. Five of seven patients became fully functional for 3-12 months . Another 11 patients ent ered the study , of which nine are currently receiving therapy and are f unctional , and two have died , one from brain herniation. The results are encouraging and support the need for further research of this therapeutic method . The end results .o f mali gnant brain tumars are unifarmly paar. The present therapies invalving radiatian therapy and/ ar chema- therapy have been unifarmly disa ppainting. These tumars have an early devastating eff ect because, nat .only da they gr aw within limited space, but th eir infiltrative natur e disturbs functi .on, ca using related symptams and (ultimately) death. The blaad-brain barrier prevents the passage .o f ce rtain chematherapies int.o the brain parenchyma s urr aunding the tumar. The blaad-brain barrier is, .o f ca urse, absent in the cent ral part .o f the tumar. Hawever, this part .of the tumar is usually nec ratic and nat respansive ta chematherapy. The wa rk by Rapa part et al. [1- 4] has shawn that the bl aad-brain barrier can be temp.o rarily .ope ned ta a ll aw the passage .o f s ub- stances usua ll y nat all awed past the bl aad- br ain barrier, including certain chematherapeutic drugs. The wa rk by Neuwelt et al. [5 -9 ] has demanstrated that this .o pening .o f the bla.o d- brain barrier in pa ti ent s far subsequent chematherapy can be perfarmed safely. Subjects and Methods The seven initial patients in .o ur stu dy were all ca matase and were be li eved ta be ter mina l. All had rec eived surgery and radiati.on therapy. Twa had received high-dase BCNU chematherapy with b.one marraw transplant. One patient had r eceived intrath eca l T- Iymph.ocyte therapy. All patie nt s had tissue canfirmatian .o f the diagnasis. All had an art er iagram ta delineate the bl.oad s uppl y ta the tumar. The next 11 patients ent ered the st udy at an earl ier phase .of their tu mars . All had received radiatian thera py and surge ry. Fi ve had received chematherapy. All were believed ta have exhausted the narmal therapeutic regimens. CT sc ans .of these patient s all de m- anstrated tu mars with assaciated mass eff ec ts. The therapy pro tacal was canstant far all pa ti ents (table 1). Immediately befare intracaratid chem.otherapy, 25% mannital was rapidly infused inta the internal carotid artery t.o cause .osm.oti c disruptian .of the bl .oad- brain barrier at the tumar site far 20- 30 min [10]. Infusi.on .of 5-fluar.ouracil and adriamycin inta the internal carotid artery .occ urred within 30 min .of the mannital infusian. The th erapy sessians were repeated every 6 weeks until the patient had received the maximum d.ose .of adriamycin. In same cases the dase .of chematherapy was redu ce d bec ause .of leuk.openia after ' wiaus therapy . Results Table 2 lists the results. Six .of the first seven patients awake and had 3 -12 manths .of additi.onal functianallife, being ambulatary and self-caring. One .of th ese six patients was limited by c.ontractures that develaped befare ther apy. One patient was withdrawn fr .om the study by the family. One patient was still alive and func tianing well after mare than 1 year with na evidence .o f tum.o r an CT. He devel.oped herpes encephalitis and was ca nfined t.o a nursing hame. Only .one patient died with knawn brain death. CT scans durin g the peri ad .of tr eatment shawed diminuti .o n in tumar mass size in l Oaf 13 pati ent s (fig. 1). In thase patients wha were aut apsied, residual tumar was pr ese nt ta a small deg ree in all cases. H.owever, m.ost .o f the mass present was necratic tissue. The next 11 patients wer e m.ore recent additian s t.o th e study (table 2, cases 8 -1 8). Twa died, .one .o f pulm.onary causes and .one .o f brain herniatian. Nine patients have been ambulat ary and self- caring. These patients have n.ot been fallawed lang enaugh ta yield dat a abaut the use .of this therapy in patients whase disease prace ss has nat pr.og ressed ta the p.oint .of unc .onsciausness. The ca mplicatians in .o ur group are listed in table 3. All seiz ures were ca ntralled. The twa patients wha develaped brain swelling after their first ch ematherapy were treated with steroids and had furth er therapy pa stpaned until the brain swelling regressed . The develapment .of f.ourth cranial nerve palsy appeared ta be related ta the mannital infusian bec ause this devel .o pment cauld be seen during mannital infusian. Discussion The wark .of Rapapart, Neuwelt, et al. [1 -1 0] has sugg ested that .o pening .o f the blaad-brain ba rrier .o ff ers great pat ential in the treatment .o f patients with br ain tumars. We underta.ok t.o verify their , Departmenl of Radiology, University Hospit als of Cleveland. 2074 Abington Rd ., Cleveland, OH 44 160. Add ress repri nt requests to C. T. Bonstelle. 2 Department of Neurol ogy , University Hospitals of Cleveland, Cleveland, OH 44 106. 3 Deparlment of Surgery, University Hos pitals of Cleveland, Cleveland, OH 44106 . AJNR 4:810-8 12, May/ June 1983 0195 - 6108 / 83 /0 403- 08 10 $00 .00 © American Roenlgen Ray Society