2
MATERIALS AND METHODS: The four dogs with radioactive balloon dilation immediately after stent placement were sacrificed four weeks (group I, n=2) or eight weeks (group II, n=2) later. Five dogs with radioactive balloon dilation two weeks after stent placement were sacrificed four weeks following stent placement (group III). The remaining five dogs witb conventional balloon dilation immediately after stent placement were sacrificed four weeks later; control group (group IV). We obtained retrograde urethrography (RGU) during follow-up and histologic findings (number of epithelial layers, tbickness of granulation tissue and papillary projection, and degree of submucosal inflammatory cell infiltration) at botb the in-stent and out-stent areas for each stent after sacrificing each dog. The Mann-Whitney U test was performed to test the significant difference of the RGU or pathologic findings between radioactive balloon dilation (group J to III) and conventional balloon dilation (group TV). When all four groups were compared, the Kruskal-Wallis test was used to test for a difference among the means. RESUL TS: There were no complications such as stent migration or blockage of the stent. RGU and the histologic findings showed less tissue hyperplasia in the radioactive balloon group than in the conventional balloon group in all comparisons with statistical significance in six of eight pathologic comparisons. There were significant differences in five of eight pathologic comparisons wben the mean values of each pathologic item were compared among the four groups. Group II showed the least tissue byperplasia in the histologic fmdings. CONCLUSION: Beta-irradiation using 188Re-MAG3-filled balloon dilation was feasible and effective in reducing tissue hyperplasia secondary to stent placement in a canine urethral model. Scientific Session 26 Oncology Sunday, March 28, 2004 12:30 PM ·2:00 PM Moderator(s): Andreas Adam, ME, BS, FRCR Marshall Hicks, MD 12:30 PM Abstract No, 133 Relative Thermosensitivity of Cytotoxic Drugs Commonly Used in Transarterial Chemoembolization of Liver Tumors. K. Ahrar, M D. Anderson Cancer Center, Houston, TX, USA 'R.A. Newman-MJ. Wallace'S. Gupta'F.A. Morello K C Wright PURPOSE: There is a trend towards multimodality treatment ofiarge hepatocellular carcinoma tumors with combination of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA). Cytotoxic activity of anticancer drugs used in TACE may be adversely affected by high temperatures attained during RFA. Our goal is to report the relative thermosensitivity of anticancer agents commonly used in TACE. MATERiALS AND METHODS: We examined the relative cytotoxicity of cisplatin, doxorubicin HCL, and mitomycin on human colon (HT 29) and human lung (A 549) adenocarcinoma cells before and after heating each chemotherapeutic agent. The drugs were exposed to 120°C for a period of2 hours. Drugs were then cooled and added to cells. To assess the effect of absolute temperature on the relative cytotoxioity of doxorubicin HCL and mitomycin, each drug was exposed to various temperatures (60, 80, 100, and 120°C) for 2 hours. Drugs were then cooled and added to cells. Finally, to evaluate the effect of exposure duration on S 190 relative cytotoxicity of doxorubicin HCL and mitomycin, each drug was heated to 120°C for a variable period of time (15,30, 60,90, and 120 minutes). Drugs were then cooled and added to cells. After 72 hours of incubation, cell growth inhibition was assessed by MTT assay and IC 50 was calculated for each cytotoxic agent in each experiment. RESULTS: After heating the drugs to 120°C for a period of 2 hours, the relative cytotoxic activity of cisplain, doxorubicin HCL, and mitomycin decreased by a factor of 1.35 (range, I to 1.75),9.5 (range, 8.5 to 10.5), and 7.05 (range, 3.5 to 12), respectively. With incremental increases in temperature, the cytotoxic activity of doxorubicin HCL and mitomycin decreased. Similarly, with incremental increases in duration mf exposure to heat, the cytotxic activity of the two drugs decreased. CONCLUSION: Cytotoxic activity of cisplatin is not affected by exposure to heal. In contrast, cytotoxicity of doxorubicin HCL and mitomycin was adversely affected by temperature and duration of exposure to heat. 12:41 PM Abstract No, Combined Chemoembolization and Radiofrequency Ablation of Liver Tumors: One-Year Follow-Up, R. Agarwal, University of Pennsylvania, Philadelphia, PA , USA-MC Soulen-T.W Clark'CM Tuite'S.W Stavropoulos 'J.I. Mondschein PURPOSE: Radiofrequency ablation (RFA) has a high local failure rate for liver tumors >2.5 cm. We evaluated the one- year outcome after chemoembolization and RFA ofliver tumors up to 6 cm in diameter. MATERiALS AND METHODS: 32 tumors (18 HCC, 14 metastases) in 26 patients were chemoembolized with CAM} EthiodoVPYA, followed by RFA the next day. Patients with bilobar disease had the other lobe treated one month later. 21 patients had one tumor, 4 had two, and one had three tumors ablated. 14/32 tumors were treated using a 3.5 cm radial array and a 90W generator (Radiotherapeutics), 18/32 were treated with a second-generation 4 cm array and a 200W generator. 5 tumors were treated with one burn, 27 with mUltiple overlapping burns. Follow-up laboratory studies, tumor markers, clinical assessment, and imaging were performed at one month, then every 3 montbs. All patients have been followed until transplant, death, or a minimum of 12 months. RESULTS: Technical success was 100%, with rolloff achieved in all cases. Complications requiring rehospitalization included 2 cases of bacteremia, one patient developed a bilocutaneous fistula, and one left lobe infarction. One patient developed a large groin hematoma that did not require intervention. Tumor markers were evaluable in 18 patients; there were 3 CR 's, 11 PRlMR's, 2 remained stable, and 2 progressed. Lesion size was 4.3 ± 1.1 cm initially, 5.8 ±1.4 cm one month after RFA (p<0.05, paired t-test), 5.0 ± 1.2 cm at4 months, and 5.5± 0.9 cm at 7 months. 4/32 tumors had residual viable tissue on post-treatment imaging, and 2 developed local failure at 10 and 11 months. Four patients underwent transplantation within 6 months. 64% of the remaining 22 patients progressed elsewhere within 12 months; 9 had intrahepatic progression at new sites, 3 had extrahepatic progression, and 2 had both intra-and extrahepatic progression. One non-transplanted patient had liver recurrence after 37 months. With a mean follow-up of 13 months, overall and disease-free survival at one year are 50% and 18%. CONCLUSION: Chemoembolization and RFA provided durable local control of26 /32 liver tumors up to 6 cm (81 %). In the absence of a transplant, progression at other sites remains a therapeutic challenge.

Scientific Session 26 Oncology

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Page 1: Scientific Session 26 Oncology

MATERIALS AND METHODS: The four dogs with radioactive balloon dilation immediately after stent placement were sacrificed four weeks (group I, n=2) or eight weeks (group II, n=2) later. Five dogs with radioactive balloon dilation two weeks after stent placement were sacrificed four weeks following stent placement (group III). The remaining five dogs witb conventional balloon dilation immediately after stent placement were sacrificed four weeks later; control group (group IV). We obtained retrograde urethrography (RGU) during follow-up and histologic findings (number of epithelial layers, tbickness of granulation tissue and papillary projection, and degree of submucosal inflammatory cell infiltration) at botb the in-stent and out-stent areas for each stent after sacrificing each dog. The Mann-Whitney U test was performed to test the significant difference of the RGU or pathologic findings between radioactive balloon dilation (group J to III) and conventional balloon dilation (group TV). When all four groups were compared, the Kruskal-Wallis test was used to test for a difference among the means.

RESUL TS: There were no complications such as stent migration or blockage of the stent. RGU and the histologic findings showed less tissue hyperplasia in the radioactive balloon group than in the conventional balloon group in all comparisons with statistical significance in six of eight pathologic comparisons. There were significant differences in five of eight pathologic comparisons wben the mean values of each pathologic item were compared among the four groups. Group II showed the least tissue byperplasia in the histologic fmdings.

CONCLUSION: Beta-irradiation using 188Re-MAG3-filled balloon dilation was feasible and effective in reducing tissue hyperplasia secondary to stent placement in a canine urethral model.

Scientific Session 26 Oncology

Sunday, March 28, 2004 12:30 PM ·2:00 PM Moderator(s): Andreas Adam, ME, BS, FRCR

Marshall Hicks, MD

12:30 PM Abstract No, 133

Relative Thermosensitivity of Cytotoxic Drugs Commonly Used in Transarterial Chemoembolization of Liver Tumors. K. Ahrar, M D. Anderson Cancer Center, Houston, TX, USA 'R.A. Newman-MJ. Wallace'S. Gupta'F.A. Morello K C Wright

PURPOSE: There is a trend towards multimodality treatment ofiarge hepatocellular carcinoma tumors with combination of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA). Cytotoxic activity of anticancer drugs used in TACE may be adversely affected by high temperatures attained during RFA. Our goal is to report the relative thermosensitivity of anticancer agents commonly used in TACE.

MATERiALS AND METHODS: We examined the relative cytotoxicity of cisplatin, doxorubicin HCL, and mitomycin on human colon (HT 29) and human lung (A 549) adenocarcinoma cells before and after heating each chemotherapeutic agent. The drugs were exposed to 120°C for a period of2 hours. Drugs were then cooled and added to cells. To assess the effect of absolute temperature on the relative cytotoxioity of doxorubicin HCL and mitomycin, each drug was exposed to various temperatures (60, 80, 100, and 120°C) for 2 hours. Drugs were then cooled and added to cells. Finally, to evaluate the effect of exposure duration on

S 190 relative cytotoxicity of doxorubicin HCL and mitomycin, each

• drug was heated to 120°C for a variable period of time (15,30, 60,90, and 120 minutes). Drugs were then cooled and added to cells. After 72 hours of incubation, cell growth inhibition was assessed by MTT assay and IC 50 was calculated for each cytotoxic agent in each experiment.

RESULTS: After heating the drugs to 120°C for a period of 2 hours, the relative cytotoxic activity of cisplain, doxorubicin HCL, and mitomycin decreased by a factor of 1.35 (range, I to 1.75),9.5 (range, 8.5 to 10.5), and 7.05 (range, 3.5 to 12), respectively. With incremental increases in temperature, the cytotoxic activity of doxorubicin HCL and mitomycin decreased. Similarly, with incremental increases in duration mf exposure to heat, the cytotxic activity of the two drugs decreased.

CONCLUSION: Cytotoxic activity of cisplatin is not affected by exposure to heal. In contrast, cytotoxicity of doxorubicin HCL and mitomycin was adversely affected by temperature and duration of exposure to heat.

12:41 PM Abstract No, 1~4

Combined Chemoembolization and Radiofrequency Ablation of Liver Tumors: One-Year Follow-Up, R. Agarwal, University of Pennsylvania, Philadelphia, PA, USA-MC Soulen-T.W Clark'CM Tuite'S.W Stavropoulos 'J.I. Mondschein

PURPOSE: Radiofrequency ablation (RFA) has a high local failure rate for liver tumors >2.5 cm. We evaluated the one­year outcome after chemoembolization and RFA ofliver tumors up to 6 cm in diameter.

MATERiALS AND METHODS: 32 tumors (18 HCC, 14 metastases) in 26 patients were chemoembolized with CAM} EthiodoVPYA, followed by RFA the next day. Patients with bilobar disease had the other lobe treated one month later. 21 patients had one tumor, 4 had two, and one had three tumors ablated. 14/32 tumors were treated using a 3.5 cm radial array and a 90W generator (Radiotherapeutics), 18/32 were treated with a second-generation 4 cm array and a 200W generator. 5 tumors were treated with one burn, 27 with mUltiple overlapping burns. Follow-up laboratory studies, tumor markers, clinical assessment, and imaging were performed at one month, then every 3 montbs. All patients have been followed until transplant, death, or a minimum of 12 months.

RESULTS: Technical success was 100%, with rolloff achieved in all cases. Complications requiring rehospitalization included 2 cases of bacteremia, one patient developed a bilocutaneous fistula, and one left lobe infarction . One patient developed a large groin hematoma that did not require intervention. Tumor markers were evaluable in 18 patients; there were 3 CR 's, 11 PRlMR's, 2 remained stable, and 2 progressed. Lesion size was 4.3 ± 1.1 cm initially, 5.8 ±1.4 cm one month after RFA (p<0.05 , paired t-test), 5.0 ± 1.2 cm at4 months, and 5.5± 0.9 cm at 7 months. 4/32 tumors had residual viable tissue on post-treatment imaging, and 2 developed local failure at 10 and 11 months. Four patients underwent transplantation within 6 months. 64% of the remaining 22 patients progressed elsewhere within 12 months; 9 had intrahepatic progression at new sites, 3 had extrahepatic progression, and 2 had both intra-and extrahepatic progression. One non-transplanted patient had liver recurrence after 37 months. With a mean follow-up of 13 months, overall and disease-free survival at one year are 50% and 18%.

CONCLUSION: Chemoembolization and RFA provided durable local control of26/32 liver tumors up to 6 cm (81 %). In the absence of a transplant, progression at other sites remains a therapeutic challenge.

Page 2: Scientific Session 26 Oncology

12:52 PM Abstract No_ 135

Intrahepatic Cholangiocarcinoma: 10-Year Experience with Treatment with CAM/Ethiodol/PVA Chemoembolization_ G.K. Lai, University of Pennsylvania, Philadelphia, PA, USA -Me. SoulewT.W Clark-J.I. MondscheiwR.D. Shlansky-Goldberg

PURPOSE: To evaluate response and survival after CAM! EthiodollPVA chemoembolization in patients with intrahepatic cholangiocarcinoma.

MATERIALS AND J'vfETHODS: From 1993-2002,8 patients were treated . Six patients had pathologically proven cholangiocarcinoma and two had poorly differentiated adenocarcinoma of unknown primary possibly cholangiocarcinoma. Chemoembolization with cisplatinum, doxorubicin, mitomycin-C, Ethiodol, and polyvinyl alcohol paJticles was performed at approximately monthly intervals for 1-3 sessions. Cross-sectional imaging, clinical and laboratory evaluation was performed before treatment,one month after and then every 3 months. In patients with elevated CA 19-9, tumor markers were obtained.

RESULTS: 18 chemoembolizations (mean 2.25/pt .) were performed. There were two major complications: pulmonary edema and left lobe infarction in one patient each. 30 day mortality was 0%. CA 19-9 was elevated in three patients; two dropped to normal and one remained stable after chemoembolization. Seven of the 8 patients had follow-up imaging. The treated tumor regressed in four, was 'stable in two, and progressed in one. One patient died at 13 months due to a motor vehicle accident, two others died of disease progression 15 and 16 months after chemoembolization. The remaining 5 patients are alive at a mean of 19 months (range, 7 ·50 mo) from diagnosis and 13 months (range, 4-38 mo) from first chemoembolization.

CONCLUSION: A decade 's experience with this rare disease suggests that objective responses are achieved in most patients with intrahepatic cholangiocarcinoma after chemoembolization, with encouraging long-term survival.

1:03 PM Abstract No_ 136

Chemoembolization of Hepatic Metastasis from Neuroendocrine Tumors_ MM Odelowo, Hospital of the University of Pennsylvania, Philadelphia, PA, USA -Me. SoulewMF Giroux-R.D. Shlansky-Goldberg

PURPOSE: To evaluate response and survival after hepatic chemoembolization with cisplatin, doxorubicin, mitomycin­C ethiodol and polyvinyl alcohol in patients with liver metastasis from neuroendocrine tumors.

MATERIALS AND METHODS: 43 patients were treated between 1991 and 2003 for hormonal symptoms and lor progressive liver dominant disease. On average liver metastasis was diagnosed 46 months before commencing liver directed therapy. 9/43 patients (20.9%) were previously treated with systemic chemotherapy and 15 % with sandostatin. Chemoembolization was performed monthly in a lobar distribution until the entire tumor burden was treated. All patients received sandostatin 500 mcg prophylaxis for the procedures. Pretreatment and post treatment cross-sectional imaging and clinical and laboratory follow up were obtained at one month and every three months thereafter. Recurrent intrahepatic disease was treated with additional chemoembolization as needed.

RESULTS: 144 chemoembolizations (mean 3.3, range 1-13) were performed. Major complications occurred after 5 procedures (3.4%). There was one death within 30-days, from liver failure . Two patients were not imaged due to death or loss to follow-up. Morphologic regression occurred in 28/43 patients (65%), 9/43 patients had stability of the lesions and 4/43 patients showed morphologic progression of the liver lesions. 16 patients (37%) died at a mean of24 months (range 1-86 months) from first embolization. Crude one- and fIve­year survival is 87% and 83% respectively.

CONCLUSION: Chemoembolization can be performed safely in patients with metastatic neuroendocrine tumors. Durable responses with 5-year survival >80% are achieved.

1:14 PM Abstract No_ 137

Robotic Guided Placement of Ablation Probes for Multiple Overlapping Ablations_ SB. Solomon, Johns Hopkins Hospital, Baltimore, MD, USA -M Awad-A. Patriciu -D. Stoianovici-M Choti

PURPOSE: Tumor targets for ablation may be large or eccentrically shaped preventing easy, complete targeting with a single ablation. In these cases multiple, overlapping volumes of ablation are performed. The purpose of this study was to show the feasibility of pre-procedure mapping of needle tip placements for multiple ablations and then using a robot to precisely place the needle tip at the pre-determined coordinates to obtain appropriate overlapping ablations.

MATERIALS AND METHODS: Pre-ablation software was created that allowed 3-D simulation volumes of ablation to be overlayed on CT images ofthe patient's tumor. This simulation was done to create approximately 25% overlap between volumes. The simulation determined the necessary location of the needle tip for each ablation. These coordinates were then transferred to a CT mounted robot that could hold and direct the needle placement.

RESULTS: Hepatic lesions requiring more than one ablation were treated using the simulation software and robotic guidance system. Overlapping ablations appeared appropriate by the operator assessment and the ultimate coverage of the lesions as seen on post-contrast exams. Contrast CT or MR images after ablation showed successful lesion treatment.

CONCLUSION: Pre-ablation 3-D simulation for multiple, overlapping ablations and then robotic guidance for needle placement according to the simulation appears feasible. Additional study is necessary to compare clinical results with simulation versus without simulation.

S191