indications were dialysis catheter placement (n;;;5) and facial and/or extremity edema in the presence of a dial­ysis shunt (n=5). The average length of the occlusion was 3.5 cm (range 1.0 cm to 10.0 cm ). The location of the occlusion was SVC (n=3), right brachiocephalic vein (n=3), left brachiocephalic ve in (n=2), right subclavian vein (n=1), and left iliac vein (n=1). All procedures were attempted with a 21G needle using a loop snare as a tar­get introduced from a remote access s ite.

RESULTS: Sharp recanalization was successful in 9 out of 10 cases with resolution of edema in 4 out of 5 cases and successful placement of a dialysis catheter in all 5 cases. There were no immediate procedure related com­plications. In the patiems with edema, 1 patient remains asymptomatic at 12 momh follow-u p, 2 patients under­went kidney transplamation at a mean of 4 months after the procedure and remained asymptomatic. The final patiem remained asymptomatic for 3 months al which time a new dia lysis gra[( was placed in the comralatera l limb due to peripheral venous outflow disease.

Two initially placed dialysis catheters in this patient group are still in place and functioning well (>300 cc/min) at a mean of 5 months follow-up. At 3 months, one patiem developed catheter infection requi ring re­moval and subsequently had a translumbar rvc catheter placed. The final patient developed catheter infect ion requiring removal at 14 momhs, w ith placemem of a second catheter via a d ifferem site which is now fu nc­tioning well at 4 months.

CONCLUSION: Sharp recana lization of venous occlu­

sions is fea sible and safe for obtaining and preserving dialysis access in se lected patients.

4d2pm Abstract No. 40

Intervention in Axillary Necklace Dialysis Grafts-­an Institutional Experience

].N. Pappas, Durham, NC · JI Hl?Weli • ].M. Ryan. P. V. Suhocki • T.P Smith

PURPOSE This study describes our experience with inter ~ ventional procedures in patients with hemodialysis access grafts from axillary artery to; axillary vein, or subclavian vein, or internal jugular vein, so-called 'necklace grafts'.The purpose of this study is to determine how intervention in these grafts affects graft patency and longeVity, and com­pare the results with other types of dialysis gra[(.

METHOD: All grafts were surgica lly placed at our insti­tution. 'fhe srudy was performed retrospectively from information in the dialysis/vascular radiology database and from the patients medical records . The patients age, sex, the type of graft, and previou s access history was recorded. The number and type of interventions were recorded, and patency rates determined.

RESULTS: Of 27 grafts placed, 14 remained patent, 10 were occluded, 2 patients d ied (with patent graf(s), and

1 patient was lost [Q follow up. 71 intervenrional proce­dures were perfo rmed .The average time from graft

placement to firs t intervention was 108 days (range 6-416 days). Average duration of secondary patency was

273 days Crange 15-425 days).Of the 14 grafts that re­mained patent, 4 had no intervention and 32 procedures had been performed. 'fhe avemge duration of graft pa­

tency in this group was 286 daysCrange 16-1075 days).

CONG'LUSJONS: The 'necklace' graft is a useful alterna­tive in patients who have exhausted other arm graft sites. These grafts show similar patency rales to conven­tional arm grafts. Radiologic intervent ion for lhrombosis

or decreased flow rates is e ffective.

Scientific Session 6 Cancer Therapy: Chemoembolization Moderators:Jae-Hyung Park, MD

Michael C. Sou/en, 111D

Sunday, March 26, 2000 3:15 pm-4:45 pm

Abstraet No. 41

Determinants of Post-Embolization Syndrome

Following Hepat1c Chemoembolization

D.A. Leung, PhiiadelphU:i. PA • IE. Goin • C. Sickles · M .e. Soulen

PURPOSE: Post-emboliza tion syndrome occurs in up to

9Q01o of patients undergOing hepatiC chemoembolization, and is the major reason for hospilalization a[(er the proce­

dure. It is difficult to predict the severily of symptoms for anyone procedure or patient. Prediction of severi ty would be useful to 1) counsel patients, 2) alter procedural

variables to minimize toxicity, and 3) plan outpatient vs. inpatient therapy. We analysed several procedural vari­ables for their impact on (he post-embolization syndrome.

METHODS: 66 chemoembo liza tion procedures were performed on 31 patients with hep:noma . Segmenra l or lobar chemoembol iza tion was performed with CA..l\.1/Ethiodol/PVA emu lsion. Toxicity was scored ac­cording ro \'(fHO/SWOG criteria. The following vari ­ables were retrospectively assessed and correlated with toxicity: gallbladder embolizat ion, lobe embolized, % liver volume embolized, %embolized volume occupied by tumor, prior embolization of same territory, and dose administered. Stepwise logistic regreSSion of significa nt variables was performed to determine relative effect.

RESULTS: Prior embol ization was an overwhelming neg­ative predictor for post-embolization syndrome (odds ratio 0.02, p= 0.01). Whe n prior embolization was in­cluded in the logistiC regreSSion, a ll other variables dropped out. Among 41 chemoembolizations of vessels thal had not been previously emboli zed, significant pre­dictors of the severity of post-embolization syndrome included gallbladder embolization (odds ratio 6.4, p=0.04) and dose Codds ratio 4.0, p=0.04). A trend 185

CONCLUSION: Sharp recanalization of venous occlu­

sions is feasible and safe for oblaining and preservingdialysis access in selected patients.

Intervention in Axillary Necklace Dialysis Grafts--­an Institutional Experience

IN. Pappas, Durham, NC· II Hl!Weti • 1M. Ryan.P. V. Suhocki • T.P Smith

185

Abstract No. 41

Determinants of Post-Embolization Syndrome

Following Hepatic Chemoembolization

D.A. Leung, Philadelphia, PA • IE Goin • C. Sickles·

M.e. Sou/en

Sunday, March 26, 20003:15 pm-4:45 pm

RESULTS: Prior embolization was an overwhelming neg­ative predictor for post-embolization syndrome (oddsratio 0.02, p"" 0.01). When prior embolization was in­cluded in the logistiC regression, all mher variablesdropped out Among 41 chemoembolizations of vesselsLhal had not been preViously embolized, significant pre­dictors of the severity of post-embolization syndromeincluded gallbladder embolization (odds ratio 6.4,p=0.04) and dose (odds ratio 4.0, p=0.04). A trend

METHODS: 66 chemoembolization procedures wereperformed on 31 patients with heparoma. Segmental orlobar chemoembolization was performed withCA..l\1/Ethiodol/PVA emulsion. 'foxiciry was scored ac­cording to WHO/SWaG criteria. The following vari­ables were retrospectively assessed and correlated withtoxicity: gallbladder embolization, lobe embolized, %

liver volume embolized, %embolized volume occupiedby tumor, prior embolization of same territoIY, and doseadministered. Stepwise logistic regression of significantvariables was performed to determine relative effect.

PURPOSE: Post-embolization syndrome occurs in up [0

90% of patients undergoing hepatiC chemoembolization,

and is the major reason for hospitalization after the proce­dure. It is djfficult to predict the severity of symptoms foranyone procedure or patient. Prediction of severitywould be useful to 1) counsel patients, 2) alter procedural

variables to minimize toxiciry, and 3) plan outpatient vs.inpatient therapy. We analysed several procedural vari­

ables for their impact on the post-embolization syndrome.

Scientific Session 6Cancer Therapy: ChemoembolizationModerators: ;ae-Hyung Park, MD

Michael C. Soulen, MD

placement to first intervention was 108 days (range6---416 days). Average duration of secondary patency was

273 days (range 15-425 days).Of the 14 grafts that re­mained patent, 4 had no intervention and 32 procedureshad been performed. The avcragc duration of graft pa­

tency in this group was 286 daysCrange 16-1075 days).

CONCLUSIONS: The 'necklace' graft is a useful alterna­rive in patients who have exhausted other arm graftsites. These grafts show similar patency rates to conven­tional arm grafts. Radiologic intelvention for thrombosis

or decreased flow ra tes is effective.

Abstract No. 404d2prn

RESULTS: Sharp recanalization was successful in 9 out of10 cases with resolution of edema in 4 out of 5 casesand successful placement of a dialysis catheter in all 5cases. There were no irrunediate procedure related com­plications. In the patients with edema, 1 patient remainsasymptomatic at 12 month follow-up, 2 patients under­went kidney transplantation at a mean of 4 months afterthe procedure and remained asymptomatic. The finalpatient remained asympwmatic for 3 momhs al whichtime a new dialysis grah was placed in the contralaterallimb due to peripheral venous outflow disease.

Two initially placed dialysis catheters in this patientgroup are still in place and functioning well (>300cc/min) at a mean of 5 months follow-up. At 3 months,one patient developed cameter infection requiring re­moval and subsequenrly had a translumbar NC catheterplaced. The final patient developed catheter infectionreqUiring removal at 14 months, with placement of asecond catheter via a different site which is now func­tioning well at 4 months.

PURPOSE ills study describes our experience with inter­ventional procedures in patients with hemodialysis accessgrafts from axilIaIY aneIY to; axillary vein, or subclavianvein, or internal jugular vein, so-caJled 'necklace grafrs'.Thepurpose of this study is to determine how intervention inthese grafts affects graft patency and longcviry, and com­pare the results with other types of dialysis graft.

METHOD: All grafts were surgically placed at our insti­tution. 'The study was performed rctrospectively frominformation in the dialysis/vascular radiology databaseand from the pmients medical records. The patients age,sex, the type of graft, and previous access history wasrecorded. The number and type of interventions wererecordcd, and patency rates determined.

RESUlTS: Of 27 grafts placed, 14 remained patent, 10were occluded, 2 patients died (with patent grafts), and

1 parient was lost to follow up. 71 interventional proce­dures were performed.The average time from graft

indications were dialysis catheter placement (0':;;5) andfacial and/or extremity edema in the presence of a dial­ysis shunt (n="'5). The average length of the occlusionwas 3.5 cm (range 1.0 cm to 10.0 cm ). The location ofthe occlusion was SVC (n=",3), right brachiocephalic vein(n=3), left brachiocephalic vein (n=2), right subclavianvein (n=",1), and left: iliac vein (n=1). All procedures wereauempted with a 21G needle using a loop snare as a tar­get introduced from a remote access site.

186

existed for %liver volume embolized (odds ratio 2.0, p=0.3). Other variables did not correlate with toxicity. Logistic regression revealed that gallbladder emboliza­tion was the dominant variable, with the impact of dose declining to an odds ratio of 3.0, p=0.12.

CONCLUSION Significant, clinically relevant predictors

of severity of post-embolization syndrome exist. Avoid­

ing embolization of the gallbladder reduces post-em­bolization syndrome. Re-treatment of previously em­

bolized vessels results in minimal toxicity, and can

likely be performed on an out-patient basis. Dose ad­

ministration is of prognostic value.

3:26 pm Abstract No. 42

A Comparative Study For Long-term Results in the Management of Single Nodular Hepatocellular Carcinoma: Chemoembolization vs. Surgical Resection j. Park, Seoul, South Korea • j. W Chung • H.E. Kim •

Y H. Ko • K. U. Lee

PURPOSE: To compare chemoembolization (TACE) with surgical resection (SR) for the long-term results in the

management of single nodular (SN) hepatocellular ca r­cinoma (HCC)

MATERIALS AND METHODS: A retrospective analysis was done for the 121 patients with SN HCC « 5 cm) for

5 years from January 1993 to December 1997. Group A (SR) is for 58 patients with surgical resection after chemoembolization . Group B (TACE) is for 63 patients with TACE. The two groups were demographically not Significantly different except age distribution and liver fu nction reservoir. The two groups were subdivided ac­cording to Child-Pugh scoring system (5 to 12) to com­pare the two groups of same liver function reservoir. The mean age of group A (SR) was 52 years, younger than that of group B (TACE), 57 years. The two groups were compared in the long-term survival, disease-free survival, local recurrence rate and remote recurrence and metastasis rate by Kaplan-Mayer method.

RESULTS: Long-term survival in patients with Child's A5 (Child 's A with score 5) in SR group was 97.1%, 97.1% and 92.5% at 1-, 2- and 3-year resp ectively. Those were significantly better than those in patients

with A5 in TACE group ; 100%, 94.4% and 72.4% (p<0.05). However, there was no significant statistical

difference of long-te rm survival in other subgroups with A6, B7 and the worse liver funct ion reservoir. There was no sign ificant difference in disease-free sur­vival of each subgroup between SR group and TACE group , and no significant difference of remote recur­rence and metastasis rates e ither. TACE group showed 34.7% local recurrence rate at 3-year, significantly dif­

ferent with SR grou p (p<O. OOl).

CONCLUSION In comparison of the long-term results in the management SN HCC, SR group shows betler results of long-term survival only in A5 subgroup with good

liver function reservoir. Other long-term resu lts are all

comparable in both SR and TACE groups except local recurrence rate.

3:37 pm Abstract No. 43

Targeting Study o f Magnetic Targeted Carriers (MTCs) In Swine and Canine j.A . Hill, Los Angeles, C4 • S.M. Bon illa ·

A X . Bonneville · S.e. Goodwin

PURPOSE: To determine targeting efficiency of intravas­cular delivery of MTCs to lung, brain, and other organs in swine and canine models.

lv'L4TERlALS AND METHODS: MTCs are a proprietary mi­crosphere composite of elemental iron and activated carbon. Intravascular infusion of MTCs was performed in swine and canine to various sites including lung, brain, kidney, and mammary gland. MTCs were deliv­ered via selective arterial catheterization and retained in the desired site with the application of a 1 kilogauss ex­ternal magnetic field. Angiography was performed be­fore and after each infusion of MTCs to verify catheter location and arterial patency. In order to confirm target­ing, the particles were labeled with 99Tc followed by gamma camera imaging and/or animals were sacrificed for histopathologic verification of targeting.

RESULTS: Selec tive ca theterization with infus ion of

99Tc-labeled MTCs was achieved in the pulmonary ar­teries of swine and internal carotid arte ry of canine , al­lowing for speCific delivery to the targeted organ. High tracer activity was seen in the region underlying the magnet with minimal to no tracer activity seen else­where. In the bronchial arteries, only a single branch feeding both the right and left lung could be accessed. Despite limited selective access with bronchial arterial infusions, high tracer activity was found in the region of lung where the magnet was placed, with only mild ac­tivity seen in the non-targeted lung. As shown by gamma camera imaging and/or by histopathology, se­lective targeting to the mammary gland and kidney was also possible with minimal to no MTC delivelY to non­selected areas of the organ and other organs.

CONCLUSION MTC particles can be targeted to the lung, brain, mammalY gland, and kidney in swine and canines with minimal or no delivery to non-targeted regions. As MTCs have been coupled to Doxorubicin for the treat­ment of hepatoce llular carcinoma, magnetic targeting may lead to improved eft'icacy and decreased toxicity of chemotherapeutic agents used in solid tumor therapy .

3:48pm Abstract No. 44

Pharmacokinetics of Mitomycin-C in Hepatic Chemoembolization for Metastatic Co lon Cancer M. Sehgal, Philadelphia, PA • N.A . Kumar • I.E. Daliis •

M.e. Soulen

PURPOSE: To evaluate the pharmacokinetic disposition and systemic exposu re o f mitomycin-C (MMC) in

existed for %liver volume embolized (odds ratio 2.0,p=0.3). Other variables did not correlate with toxicity.Logistic regression revealed that gallbladder emboliza­tion was the dominant variable, with the impact of dosedeclining to an odds ratio of 3.0, p=0.12.

CONCLUSION Significant, clinically relevant predictors

of severity of post-embolization syndrome exist. Avoid­

ing embolization of the gallbladder reduces post-em­bolization syndrome. Re-treatment of previously em­

bolized vessels results in minimal toxicity, and can

likely be performed on an out-patient basis. Dose ad­

ministration is of prognostic value.

liver function reservoir. Other long-term results are all

comparable in both SR and TACE groups except localrecurrence rate.

3:37 pm Abstract No. 43

Targeting Study of Magnetic Targeted Carriers(MTCs) In Swine and Caninej.A. Hill, Los Angeles, C4 • S.M. Bonilla·

AX. Bonneville· S.c. Goodwin

PURPOSE: To determine targeting efficiency of intravas­cular delivery of MTCs to lung, brain, and other organsin swine and canine models.

PURPOSE: To compare chemoembolization (TACE) withsurgical resection (SR) for the long-term results in the

management of single nodular (SN) hepatocellular car­cinoma (HCC)

A Comparative Study For Long-term Resultsin the Management of Single NodularHepatocellular Carcinoma: Chemoembolizationvs. Surgical Resectionj. Park, Seoul, South Korea· j. W Chung. H.B. Kim·

YH. Ko • K. U. Lee

MATERIALS AND METHODS: A retrospective analysiswas done for the 121 patients with SN HCC «5 cm) for

5 years from January 1993 to December 1997. Group A(SR) is for 58 patients with surgical resection afterchemoembolization. Group B (TACE) is for 63 patientswith TACE. The two groups were demographically notSignificantly different except age distribution and liverfunction reservoir. The two groups were subdivided ac­cording to Child-Pugh scoring system (5 to 12) to com­pare the two groups of same liver function reservoir.The mean age of group A (SR) was 52 years, youngerthan that of group B (TACE), 57 years. The two groupswere compared in the long-term survival, disease-freesurvival, local recurrence rate and remote recurrenceand metastasis rate by Kaplan-Mayer method.

RESULTS: Long-term survival in patients with Child'sA5 (Child's A with score 5) in SR group was 97.1%,97.1% and 92.5% at 1-, 2- and 3-year respectively.Those were significantly better than those in patients

with A5 in TACE group; 100%, 94.4% and 72.4%(p<0.05). However, there was no significant statistical

difference of long-term survival in other subgroupswith A6, B7 and the worse liver function reservoir.There was no significant difference in disease-free sur­vival of each subgroup between SR group and TACEgroup, and no significant difference of remote recur­rence and metastasis rates either. TACE group showed34.7% local recurrence rate at 3-year, significantly dif­

ferent with SR group (p<O.OOl).

CONCLUSION In comparison of the long-term results inthe management SN HCC, SR group shows better resultsof long-term survival only in A5 subgroup with good

PURPOSE: To evaluate the pharmacokinetic dispositionand systemic exposure of mitomycin-C (MMC) in

Abstract No. 443:48pm

Pharmacokinetics of Mitomycin-C in HepaticChemoembolization for Metastatic Colon CancerM. Sehgal, Philadelphia, PA • N.A. Kumar. I.E. Dads •

M.C. Soulen

CONCLUSION MTC particles can be targeted to the lung,brain, mammary gland, and kidney in swine and canineswith minimal or no delivery to non-targeted regions. AsMTCs have been coupled to Doxorubicin for the treat­ment of hepatocellular carcinoma, magnetic targetingmay lead to improved eftlcacy and decreased toxicity ofchemotherapeutic agents used in solid tumor therapy.

lvL4TERIALS AND METHODS: MTCs are a proprietary mi­crosphere composite of elemental iron and activatedcarbon. Intravascular infusion of MTCs was performedin swine and canine to various sites including lung,brain, kidney, and mammary gland. MTCs were deliv­ered via selective arterial catheterization and retained inthe desired site with the application of a 1 kilogauss ex­ternal magnetic field. Angiography was performed be­fore and after each infusion of MTCs to verify catheterlocation and arterial patency. In order to confirm target­ing, the particles were labeled with 99Tc followed bygamma camera imaging and/or animals were sacrificedfor histopathologic verification of targeting.

RESULTS: Selective catheterization with infusion of

99Tc-labeled MTCs was achieved in the pulmonary ar­teries of swine and internal carotid artery of canine, al­lowing for specific delivery to the targeted organ. Hightracer activity was seen in the region underlying themagnet with minimal to no tracer activity seen else­where. In the bronchial arteries, only a single branchfeeding both the right and left lung could be accessed.Despite limited selective access with bronchial arterialinfusions, high tracer activity was found in the region oflung where the magnet was placed, with only mild ac­tivity seen in the non-targeted lung. As shown bygamma camera imaging and/or by histopathology, se­lective targeting to the mammary gland and kidney wasalso possible with minimal to no MTC delivery to non­selected areas of the organ and other organs.

Abstract No. 423:26 pm

186

patients with hepatic metastases from colon cancer. We postu late that the peak and total systemic exposure of MMC wi ll be lower in chemoembolization patients as compared to prior pharmacokinetic studies of intra­venous (N) infusion of MMC.

METHODS: 6 patients were enrolled. Patients were chemoembolized with up to 10 mg of MMC, 100 mg of cispla tin, 50 rng of doxorubicin , iodized o il and PVA particles via selective injection into the right or left he­patic artery. Vessels were chernoembolized to 90% sta­sis. 14 blood samples were drawn from a cemral ve­nous catheter up to 8 hours after chemoembolization. The samples were analyzed by a phannacokineticist.

RESULTS: The mean injected dose of MMC was 7.2 ± 1.9 mg (range 5--9.5 mg, median 7.3 mg), which normalized for body surface area (BSA) was 3.8 ± 0.93 mg/m' (range 2.7-4.9, median 3.9 mg/m2). The maximal serum concen­tration (Cmax) of MMC was 119.9 ± 61.3 ng/ml (range 36.0-192.5 ng/ml, median 126.4 ng/mJ). The mean T!l2b was 180 ± 283 min (range 25-757 min, median 80 min). The mean total clearance was 759.7 ± 358.8 mllmin (range 214 .1-1150.5 ml/min, median 798.6 mVmin), nor­malized for BSA 396.7 ± 172.6 ml/min'm' (range 119.6-{j18.5 mVmin'm', median 387.8 ml/ min'm'). The mean area under the curve (AUC) using a non-compart­mental model was 8.03 ± 2.71 mcg*min/ ml (ra nge

4.14-11. 11 mcg'minlml , median 8.61 mcg'minlml).

CONCLUSiONS: The Cmax for hepatic chemoemboliza­tion is 3.2 times less than that reported for IV adminis­{fation (31.5 ng*m2/mg*mt versus 100 ng*m2Img*ml) .

The total systemic exposure to MMC is reduced to 56% of published levels for patients with IV infusion of equivalent doses of l'vlMC. This is probably due to first pass extraction by the liver. The systemic clearance of MMC is the same as compared to IV infus ion (396.7 rnJJmin·m2 versus 400 mllmin*m2). Chemoembolization

with this drugiEthiodollPVA emulsion substantially re­duces systemic exposure to MMC compared to previ­ously published data for IV administration.

369 pm Abstract No. 45

Sarcomas Metastatic to the Liver: Response and Survival Following CAMlEthlodol!PVA ChernoemboUzation D.K. Rajan, Philadelphia, PA • M.C Soulen • R.A. Baum • ZI Helskat • D.A. Freiman. RD. Shlansky-Goldberg

PURPOSE: To evaluate the response to and survival after CAM/Ethiodol!PVA chemoembolization for pa­tients with sarcomas metastatic to the liver.

MATERlAIS AND METHODS: 16 patients were treated. Primary tumors included eleven gastrointestinal leiomyosarcomas, two splenic angiosarcomas, one leiomyosarcoma of the broad ligamem, one leiomyosar­coma of the inferior vena cava and one malignant fibrous histiocytoma of the colon. Chemoembolization with cis-

platin, doxorubicin, mitomycin-C, Ethiodol and polyvinyl alcohol particles was performed at approximately monthly intervals for 1-5 sessions (mean 2.7). Pre and

post trea tment cross-sectional imaging was performed one month afte r completion of treatment and then every three months. Response was graded according to \xrHO criteria. Survival was calculated using life table analysis.

RESULTS: FoUowup is pending on one patient «30 days) . 20% (n=3) exhibited partial morphological response, 60% of patients were morphologically stable (n=9), and 20% demonstrated progression of disease (n=3) th irty days foll owing completion of treatment. Among 12 respon­ders, 6 developed intrahepatic progression at a median time of 11.5 months. Five developed extrahepatic pro­gression at a median time of 6 months, of whom two un­derwent surgical resection. One patient has had no pro­gression to date. The cumulative survival using liie table analysis was 87% at 1 year, 56% at 2 years and 400/0 at 3 years. One patient developed necrosis of the right he­patiC lobe and a biliary fisnila requiring sustained perCll­taneous draLnage. Thirty day mortality was zero.

CONCLUSION Durable tumor response with chemoem­bolization is possible in this form of metastatic disease, which is highly resistant to systemic chemotherapy.

4:10 pm Abstract No. 46

Technical Feasibility and Complication Rate Associated With Indwelling Transbrach1aJ, Hepatic Artery Chemotherapy Infusion Catheters in Metastatic Liver Disease M.K. Varma, Ann Arbor, Mi • M. W Schunk. N. Dasika • D. Williams

PURPOSE: Retrospective analysis of technical success and complication rates associated with indwelling percutaneous transbrachiaJ , hepatiC artery infusion cathete rs (THAC) for chemotherapy of metastatic liver disease.

MATERIAL AND METHODS: The records of 93 consec­utive patients referred over a two year period for per­cutaneous placement of a 5 Fr. THAC for cont inuous 14 day infu sion of a chemotherape utic agent were re­viewed. A detailed record of a) hepatiC arteria l anatomy b) successful catheter tip placement c) rein­te rvention for re position of a displaced tip d) addi­tional interve ntion to achieve redis tribution o f he patiC al1eria l flow to a Single feeding artery and to prevent extrahepatic fl ow of chemotherapeutic agent and e) Intra- and postproced ura l com plicat ions was made.

Complicat ions requiring additional surgery, discont in­uation of infUSion, neurologic or ischemic complica­lions were graded as major.

RESULTS: Successful catheter tip pla cement was achieved in all the 93 patients. Of these 93 patients, 50 returned for a second session of 1A chemotherapy folowing a 4-week interval, and 6 patients returned for more than 2 procedures. 23 patients required reposi- 187

PURPOSE: To evaluate the response to and survivalafter CAM/EthiodollPVA chemoembolization for pa~

tients with sarcomas metastatic to the liver.

Sarcomas Metastatic to the Uver: Response andSurvival Following CAMlEthiodollPVAChemoemboUzationD.K. Rajan, Philadelphia, PA • M.C Sou/en •R.A. Baum • Z}. Haskal • D.A. Freiman.RD. Sblansky-Goldherg

MATERlAIS AND METHODS: 16 patients were treated.Primary tumors included eleven gastrointestinalleiomyosarcomas, two splenic angiosarcomas, oneleiomyosarcoma of the broad ligamem, one leiomyosar­coma of the inferior vena cava and one malignant fibroushistiocytoma of the colon. Chemoembolization with cis- 187

Abstract No. 464:10 pm

PURPOSE: Retrospective analysis of technical successand complication rates associated with indwellingpercutaneous transbrachial, hepatiC artery infusioncatheters (THAC) for chemotherapy of metastaticliver disease.

Technical Feasibility and Complication RateAssociated With Indwelling Transbrachial, HepaticArtery Chemotherapy Infusion Catheters inMetastatic Liver DiseaseM.K. Varma, Ann Arbor. Mi • M. W Schunk.lV". Dasika • D. Williams

RESULTS: FoUowup is pending on one patient «30 days).20% (n=3) exhibited partial morphological response. 60%of patients were morphologically stable (n=9), and 20%demonstrated progression of disease (n=3) thirty daysfollOWing completion of treatment. Among 12 respon­ders, 6 developed intrahepatic progression at a mediantime of 11.5 monrhs. Five developed extrahepatic pro­gression at a median time of 6 months, of whom two un­derwent surgical resection. One patient has had no pro­gression to date. The cumulative survival using life tableanalysis was 87% at 1 year, 56% at 2 years and 40010 at 3years. One patient developed necrosis of the right he~

patic lobe and a biliary fisnda requiring sustained percu­taneous drainage. Thirty day mortality was zero.

CONCLUSiON Durable tumor response with chemoem­bolization is possible in this form of metastatic disease,which is highly resistant to systemic chemotherapy.

placin, doxorubicin, mitomycin-C, Ethiodol and polyvinylalcohol particles was performed at approximatelymonthly intervals for 1-5 sessions (mean 2.7). Pre andpost treatment cross-sectional imaging was performedone month after completion of treatment and then everythree months. Response was graded according to \'VHOcriteria. Survival was calculated using life table analysis.

M.4.TERJAL AND METHODS: The records of 93 consec­utive patients referred over a two year period for per­cutaneous placement of a 5 Fe. THAC for continuous14 day infusion of a chemmherapeutic agent were re­viewed. A detailed record of a) hepatic arterialanatomy b) successful catheter tip placemem c) rein­tervention for repOSition of a displaced rip d) addi­tional imelvention to achieve redistribution of hepaticarterial flow to a single feeding artery and to preventextrahepatic flow of chemotherapeutic agent and e)Intra- and postprocedural complications was made.Complications requiring additional surgery, discontin­uation of infusion, neurologic or ischemic complica­tions were graded as major.

RESULTS: Successful catheter tip placement wasachieved in all the 93 patients. Of these 93 patients, 50returned for a second session of lA chemotherapyfolowing a 4-week interval, anti 6 patienrs returned formore than 2 procedures. 23 patients required reposi-

Abstract No. 45369 pm

patients with hepatic metastases from colon cancer. Wepostulate that the peak and total systemic exposure ofMMC will be lower in chemoembolization patients ascompared to prior pharmacokinetic snldies of intra­venous (N) infusion of MMC.

ME7110DS: 6 patients were enrolled. Patients werechemoembolized with up [Q 10 mg of MMC, 100 mg ofcisplatin, 50 mg of doxombicin, iodized oil and PVAparticles via selective injection into the right or lefl he­patic artery. Vessels were chemoembolized [Q 90010 sta­sis. 14 blood samples were drawn from a central ve­nous catheter up to 8 hours after chemoembolization.The samples were analyzed by a pharmacokineticist.

RESULTS: The mean injected dose of MMC was 7.2 ± 1.9mg (range s-9.5 mg, median 7.3 mg), which normalizedfor body surface area (BSA) was 3.8 ± 0.93 mg/m' (range2.7-4.9, median 3.9 mg/m2). The maximal serum concen­tration (Cmax) of M!,1C was 119.9 ± 61.3 ng/ml (range36.0-192.5 ng/m1, median 126.4 ng/mJ). The mean TI/2bwas 180 ± 283 min (range 25-757 min, median 80 min).The mean total clearance was 759.7 ± 358.8 ml/min(range 214.1-1150.5 mVrnin, median 798.6 mVrnin), nor­

malized for BSA 396.7 ± 172.6 ml/min'm' (range119.6-<i18.5 mVrnin'm', median 387.8 m1/min'm'). Themean area under the curve (AUC) using a non-compart­mental model was 8.03 ± 2.71 mcg+min/ml (range4.1+-11.11 meg'minlml, median 8.61 meg'minlmD.

CONCLUSiONS: The Cmax for hepatic chemoemboliza­tion is 3.2 times less than that reported for IV adminis­tration (31.5 ng*m 2/mg*mJ versus ]00 ng*m2Img*ml).

The total systemic exposure to MMC is reduced to 56%of published levels for patients with IV infusion ofequivalent doses of MMC. TIlis is probably due to firstpass extraction by the liver. The systemic clearance ofMMC is the same as compared to N infusion (396.7mJlmin*m2 versus 400 mllmin"m2). Chemoembolizationwith this dnlg/EthiodollPVA emulsion substantially re­duces systemic exposure to MMC compared to previ­ously published data for IV administration.

188

tioning of the displaced catheter tip , diagnosed by Tc-99NIAA hepatic scan during infusion. Additional imer­ventions included coil embolization of a branch artery to prevent non-targel infusion (n=20), coil occlusion of a hepatic artery branch to achieve redistribution to a single feeding artery (n=21). Complications C7 major and 40 minor) were noted in 39 patients during the 149 infusions. 5 of the 149 infusions were prematurely ter­minated. No procedure rela ted mortality was noted.

CONCLUSION: Percutaneous, transbrachial, intra-arte­rial chemotherapy with indwelling catheters over a

14-day period is technically feasible . 95% of the pa­tients had successfully completed the infusion. The

major (5%) and minor (26%) complication rate for 149 procedures is higher than the reported complications for diagnostic transbrachial arterial catheterization. No increase in the complication rate is noted with addi­

tiona l procedures for reposition of the tip and coil embolization of branch arteries.

4,21 pm Abstract No. 47

Phase I/U Cohort Trial to Determine Maximum Tolerated Dose of Doxorubicin Adsorbed to Magnetic Targeted Carriers (MTC· DOX) In Patients With Hepatocellular Carcinoma S.C Goodwin, Los Angeles, C4 . }.A. Hill • RL Gordon· R.K. Kerlan • E.M. Walser . P. Suhocki, et at

PURPOSE: To determine the maximum tolerated dose, safety, and phannacokinetic profile of MTC-DOX ad­ministered by hepatic intra-arteria l del ivery in patients with hepatocellular carcinoma.

MATERiALS AND METHODS .. Up to 24 patients with ad·

vanced or recurrent hepatocellular carcinoma were to be entered into lhis trial to receive a single dose of doxoru­bicin adsorbed to MTCs via intra-arteria l infusion into a segmental hepatic. artery proximal to the tumor lesion. Doses ranged from 3 mg doxorubicin / 37.5mg MTCs to 18 mg doxombic.in / 225 mg MTC. Delivery was targeted to one lesion in a specifiC hepatic segment with the ap­plication of a 5 kilogauss external magnetiC field. An­giography was performed prior to dosing and at the end of the dosing procedure. Patients were evaluated over a 28 day follow-up period for treatment related Side-ef­fects. Patiems underv.rent baseline and 28-day follow-up CT and MRl scans to document tumor size and number of lesions as well as MTC particle distribution. In those patients with multiple lesions, non-targeted lesions were used as controls within the same patient. In this ongoing study, 8 patients have been treated to date.

RFSUL7S: MR imaging has shown deposition of the par­ticles in the selected site only. After 28 days, MRI results show that the particles remain in the targeted site with no redistribution. No Significant arterial embolization has been visualized by angiography. No srudy related deaths have occurred to date. End-srudy imaging results will be shown here. Additionally, a preliminary dose response curve has been generated. TIle maximum tolerated dose

for a single lesion has also been determined, which will lead to dosing per volume of tumor in furure studies.

CONCLUSION In this phase 1/IJ clinical study, the safety profile and 10Iembility of MTC-DOX has been evalu­ated, and a maximum tolcmted dose determined . This novel technique of regional drug delivery may improve efficacy while limiting toxicity of chemotherapeutic agent'; in the treatment of hepatocellular carcinoma.

4,32 pm Abstract No. 48

DR. GARY J. BECKER YOUNG INVESTIGATOR AWARD

Chemoetnbolization of liver Tumor in a Rabbit Model: Assessment of Tumor Cell Death With Diffusion·Weighted MRI and Histologic Analysis j.H. Geschwind, Baltimore, MD • D. Artemov • S. Abraham. D. Omdal • C JvlCGee • G. Lund, et al

PURPOSE: To assess the efficacy of chemoemboliza­tion on liver rumors by determining the frac:tion of vi­able tumor cells re,maining after treatment, to create a regional map of the rumor bed by identifying areas of cellular death using diffusion MRI and to measure BcI:.

2 expression (inhibitor of apoptosis) within the nlmor.

MATERIAlS A/liD ,Will·IODS Tumor ceUs halVested from a

rabbit c:3Irier were injected into the left lobe of the liver of 12 rabbits and grown for 14 days. Animals were divided

into a chemoemb.:Jlization (n~ and a no treatment or con­trol group (n=6). Chemoembolization was pe1fonned "ith carboplatio, ethiodo! and ivalon. Conventional, perfusion and diffusion l\.1R imaging was perfonned on all rabbits 19-21 clays after tumor implantation i.e. 7-9 days JX6t­chemoernlxilization for the treated -group. Histopa.thologic analysis of explanted livel> was pelfonned with standard

and immuno staining to docwnent tumor ceil death and measure & 1-2 levels-respectively.

RESULTS: Diffusion-weighted MRI was able to clearly delineate zones of rumor cell death within the rumor as regions of lower Signal intensity, with the -area of tumor necrosis Significantly greater in the treated than -in the control group. Apparent diffusion coefficients calcu­lated from reconstructed maps were significantly ' greater in the area of rumor necrosis than in the area of viable cells, indicating the presence of leakier rumor cell membranes. Histologic analysis conftrmed that the fraction of viable cells identified within me treated tumor (<1%) was Significantly lower than in the control group (55%). Bd-2 expression detected within the vi­able areas of the tumor \vas Significantly greater in the treated than in tile control group.

CONCLUSIONS: Chemoembolization causes signifi­cant tumor cell destruction since tumor cell viability was less than 1% after treatmem. DiffUSion-weighted IvlRl is able to detect tumor cell- death and can be used to assess the efficacy of chemoembolization . Overexpression of Bcl-2 in the treated group ind i­cates a greater degree of tumor resistance to cellular apoptosis -which may ultimately be detrimenta l to

the efficacy of chemoembolization.

tioning of the displaced catheter tip, diagnosed by Tc­99NIAA_ hepatic scan during infusion. Additional imer­ventions included coil embolization of a branch artery[Q prevent non-target infusion (n=20), coil occlusion ofa hepatic arteIY branch to achieve redistribution to asingle feeding artelY (n=21). Complications C7 majorand 40 minor) were noted in 39 patients during the 149infusions. 5 of the 149 infusions were prematurely ter­minated. No procedure related mortality was noted.

for a single lesion has also been determined, which willlead to dosing per volume of tumOr in future studies.

CONCLUSION In trus phase UIJ clinical study, Lhe safetyprofile and tolerability of MTC-DOX has been evalu­ated, and a maximum tolerated dose determined. Thisnovel technique of regional drug delivery may improveefficacy while limiting toxicity of chemotherapeuticagents in the treatment of hepatOcellular carcinoma.

DR. GARY J. BECKER YOUNG INVESTIGATOR AWARD

ChemoeInbolization of liver Tumor in a RabbitModel: Assessment ofTmnor Cell Death WithDiffusion-Weighted MID and Histologic Analysisj.H. Geschwind, Baltimore, i\l!D • D. ArleniOV •

S. Abraham .-D. Omdal. C. lv[cGee • G. Lund, eta!

PURPOSE: To assess the efficacy of chemoemboliza­tion on liver rumors by delermining the fraction of vi·able tumor cells r~maining after treatment, to create aregional map of the tumor bed by identifying areas 0fcellular deat,h using diffusion MRI and to measure Bct­2 expression (inhibitor of apoptosis) within the nlmor.

MATERIAlSAND II1Iill-IODS.· Tumor ceUs halVested from arabbit carrier were injecrecl into the left lobe of the liver of12 rabbits and grown for 14 days. Animals were dividedinto a cheITK>Cf11b,:Jlization (n~ and a no treatment or coo- .001 group (n=Q). Chemoembolizati9n was pe1formed withcad::x)platin, ethiexiol and ivalon. Conventional, perfLisionand diffusion ~1R imaging was perfolmed on all rabbitS19-21 clays after tumor implantation i.e. 7....fJ days post­

chemoerl1oolization for the treated -group. Histopa_thologicanalysis of explanted livel' was pe1formed with standardand immuno Slaining to docwnent tumor cell cleath andmeasure &1-2 levelsTespectively.

RESULTS: Diffusion-weighted MRI was able to clearlydelineate zones of tumor cell death within the tumQr asregions of lower Signal intensity, with the-area of tumornecrosis significantly greater in the treated than -in thecontrol group. Apparent diffusion coeffi~ients caJcu­lated from reconstructed maps were significantlygreater in the area of tUmor necrosis than in the area ofviable cells, indicating the presence of leakier tumorcell membranes. Histologic analysis confirmed that thefraction of via-ble cells identified within the tre~tedtumor (<1%) was significantly lower than in the controlgroup (55%). Bd-2 expression detected within the vi­able areas· of the Ulmor \vas Significantly greater in thetreated than in tile control group.

CONCLUSIONS: Chemoembolization causes signifi­cant tumor cell destnIction since rumor cell viabilitywas less than 1o/~ after treatmeOl. DiffUSion-weightedMRI is able to detect tumor cell· death and can beused .to assess the efficacy of chemoernbolization.Overexpression of BcI-2 in the treated group indi~

cates a greater degree of tumor resistance to cellularapoptosis-which may ultimately be detrimental lO

the efficacy of chemoembo1ization.188

CONCLUSION: Percutaneous, transbrachial, intra-arte­rial chemotherapy with indwelling catheters over a

lA-day period is technically feasible. 95% of the pa­tients had successfully completed the infusion. The

major (5%) and minor (26%) complication rate for 149procedures is higher than the reponed complicationsfor diagnostic transbrachial arterial catheterization. Noincrease in the complication rate is noted with addi­

tional procedures for reposition of the tip and coilembolization of branch arteries.

Abstract No. 47

Phase I/U Cohort Trial to Determine MaximumTolerated Dose of Doxorubicin Adsorbed toMagnetic Targeted Carriers (MTC·DOX) In PatientsWith Hepatocellular Carcinomas.c. GoodWin, Los Angeles, C4 • j.A. Hill • R.L. Gordon·R.K. Kerlan • E.M. Walser. P. Suhocki, et a!

PURPOSE: To determine the maximum tolerated dose,safety, and pharmacokinetic profile of MTC-DOX ad­ministered by hepatic intra·anerial delivery in patientswith hepatocellular carcinoma.

MATElUAL5' AND METHODS.. Up to 24 patients wid, ad­vanced or recurrent hepatocellular carcinoma were to beentered into this trial to receive a single dose of doxoru­bicin adsorbed to MTCs via intra-arterial infusion into asegmental hepatiC artery proximal to the tumor lesion.Doses ranged from 3 mg doxorubicin / 37.5mg MTCs to

18 mg doxorubicin / 225 mg MTC. Delivery was targetedto one lesion in a specifiC hepatic segment with the ap­plication of a 5 kilogauss external magnetiC field. An­

giography was performed prior to dosing and at the endof the dosing procedure. Patients were evaluated over a28 day follow-up period for treatment related side-ef­fects. Patients underv.rent baseline and 28-day foHow-upcr and MRJ scans to document tumor size and numberof lesions as well as MTC particle distribution. In chosepatients with multiple lesions, non-targeted lesions wereused as controls within the same patient. In this ongoingstudy, 8 patients have been treated to date.

RFSUL7S: MR imaging has shown deposition of the par­ticles in the selected site only. After 28 days, Mill resultsshow that the particles remain in the targeted site withno redistribution. No significant arterial emboli:zation hasbeen visualized by angiography. No srudy related deathshave occurred to date. End-srudy imaging results will beshown here. Additionally, a preliminaly dose responsecurve has been generated. TIle maximum tolerated dose

4<32 pm Abstract No. 48