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ABSTRACT |
Wednesday, May 9, 1:30 PM–3:30 PM
Abstracts 187-195
Moderator(s): David Madoff
1:30 PM
Keynote Address: Vascular Interventions in Oncology
David Maddoff, The University of Texas MD Anderson Cancer Center, Houston, TX
2:00 PM
187. Pilot Study with Intraarterial Doxorubicin-eluting Microspheres (GelSpheres) in Patients with Unresectable Hepatocellular Carcinoma: Experience in the US
Kamel I. R.*; Reyes D. K.; Wahlin T.; Georgiades C.; Hong K.; Geschwind J. H. Johns Hopkins Hospital, Baltimore, MD
Address correspondence to I. Kamel (ikamel{at}jhmi.edu)
Objective: This pilot study under an investigator IDE was conducted to gather preliminary data using GelSphere beads loaded with doxorubicin to treat patients with unresectable HCC. The endpoints measured were tumor response and adverse events.
Materials and Methods: Between 11/05 and 06/06, 10 patients (7 men and 3 women, mean age, 64 years) were treated with 2 vials of GelSphere beads (100–300 and/or 300–500 microns), each loaded with 50 mg of doxorubicin. Functional perfusion and diffusion MR imaging studies before and 1 month after single selective treatment were evaluated by consensus of 2 MR radiologists to assess treatment response. Tumor size, arterial and venous enhancement, and apparent diffusion coefficient (ADC) values were recorded before and after treatment. One targeted tumor in the treated lobe of the liver was included in each patient. Immediate adverse events, reported toxicities and serious adverse events at 1 month follow-up were recorded.
Results: Mean tumor size was 8.7 cm. Targeted tumors had mean decrease in arterial enhancement of 60% (p = 0.002), decrease in venous enhancement of 62% (p < 0.001), and increase in ADC of 38% (p = 0.0056). Targeted tumors had no change in size after treatment (p = 0.489). The ADC values for liver and spleen were unchanged (p = 0.398 and 0.401, respectively). The procedures were well tolerated without significant side effects. Toxicities reported 1 month following initial treatment were: fatigue (n = 6), abdominal pain (n = 3), decreased appetite (n = 3), decreased libido (n = 2), impotency (n = 2), weight loss (n = 2), pedal edema (n = 2), and 1 patient for each of the following (vomiting, chest pain, unilateral edema in leg, belching, fever, hypothermia, hypotension, and insomnia). One patient died from progression of liver disease within 30 days of the procedure but was judged to be unrelated.
Conclusion: This pilot study demonstrated that GelSphere beads mixed with doxorubicin result in significant reduction in arterial and venous enhancement of HCC, without a significant change in tumor size, at 1 month after therapy. Treated lesions have significant increase in ADC due to tumor necrosis. Our data also suggest that this new drug-delivery device is effective and well tolerated.
188. Radiofrequency Ablation of Hepatocellular Carcinoma: A Comparison of Tolerance and Recovery Between Open and Percutaneous Methods
Teh H.*; Tan E.; Tan S.; Ibrahim S.; Tay K.; Fock K. Changi General Hospital, Singapore
Address correspondence to H. Teh (cyber_xray{at}yahoo.com)
Objective: Radiofrequency ablation of hepatocellular carcinoma can be performed by various methods, including percutaneously, at laparoscopy, or surgery. The study aims to compare the tolerance and recovery between open laparotomy and percutaneous techniques, in patients with hepatocellular carcinoma (HCC) who underwent radiofrequency ablation.
Materials and Methods: Thirty-six HCC nodules (27 <3 cm and 8 between 3–5 cm, 1 >5 cm) in 25 patients (20 men and 5 women) ablated between October 2004 and September 2006 were included in the analysis. Tolerance and recovery were measured by using an objective pain assessment score (Wong Baker), and length of stay (LOS) in hospital, respectively.
Results: A total of 39 ablations were performed under ultrasound imaging guidance. Seventeen ablations were performed percutaneously, and 22 by open laparotomy. Technique effectiveness (defined as complete ablation of macroscopic tumor as evidenced at CT imaging follow-up at 3 weeks postablation) was achieved in 94% of ablations using percutaneous technique, and 91% with open laparotomy. Average pain score was 0.1 and length of stay in hospital was 2.1 days for patients who underwent percutaneous technique, compared to a pain score of 1.5 and length of stay in hospital of 10.6 days for those who had ablation performed with open laparotomy. There was no major complication encounter in either group.
Conclusion: Percutaneous imaging guided radiofrequency ablation of hepatocellular carcinoma nodules is a safe and effective technique, with benefits of reduced postprocedural pain and length of stay in hospital.
190. Perfusion and Diffusion-weighted MR Imaging After TheraSpheres Treatment for Patients with Metastatic Colon Cancer: Multiparametric Assessment of Tumor Response
Kamel I. R.*; Reyes D. K.; Liapi E.; Hong K.; Bluemke D. A.; Geschwind J. H. Johns Hopkins Hospital, Baltimore, MD
Address correspondence to I. Kamel (ikamel{at}jhmi.edu)
Objective: To assess the utility of multiparametric MR imaging in assessing early (1 month) response of patients with metastatic colon cancer to Yttrium-90 labeled microspheres (TheraSpheres).
Materials and Methods: MR imaging studies before and 1 month after single selective TheraSpheres treatment were evaluated. All patients had pathologically proven colon cancer that was metastatic to the liver. Patients were imaged using a 1.5-T MR scanner and a phased array torso coil. Imaging protocol included T2-weighted FSE images (matrix, 256 x 256; thickness, 8 mm; gap, 2 mm; TR, 5000; TE 100), BH diffusion-weighted echoplanar images (matrix, 128 x 128; thickness, 8 mm; gap, 2 mm; B value, 500; TR, 5000-6500; TE, 110), and BH unenhanced and contrast-enhanced T1-weighted 3D fat-suppressed GRE (matrix, 192 x 160; thickness, 4–6 mm; TE 1.2; flip angle, 15) in the arterial (20 sec) and portal venous (60 sec) phases. Images were evaluated by consensus of 2 MR radiologists. Tumor size, venous enhancement, and ADC values were recorded before and after treatment.
Results: The study included a total of 41 lesions (mean size, 5.7 cm) present in 18 patients (14 men and 4 women; mean age, 58 years). Mean tumor burden was 28% of the total liver volume, and mean TheraSperes dose was 177 Gy. Mean tumor size was 5.8 cm after treatment (p = 0.500), relatively unchanged. Mean tumor enhancement in the venous phase before and after treatment was 46% and 41%, respectively. The difference was small (5%) and was of borderline significance (p = 0.032). Mean tumor ADC value before treatment was 1.59 E-3 mm2/sec, and increased after treatment to 1.90 mm2/sec. The difference in ADC was statistically significant (20%, p < 0.0001). Mean ADC values for the liver and spleen were relatively unchanged before and after treatment (p = 0.287 and 0.185, respectively).
Conclusion: Hepatic metastases from colon cancer are typically hypovascular before treatment, and may not change in size or enhancement in the early (1 month) follow-up period after TheraSpheres. However, the significant increase in tumor ADC value may be used as a surrogate marker for assessing early response to therapy.
191. Functional MR Imaging Assessment of Tumor Response Following TheraSpheres Treatment in Patients with Unresectable Hepatocellular Carcinoma
Vossen J. A. *; Buijs M. A.; Kamel I. R.; Reyes D. K.; Liapi E.; Hebert J.; Bluemke D. A.; Geschwind J. H. Johns Hopkins Hospital, Baltimore, MD
Address correspondence to M. Buijs (M.Buijs{at}Student.Unimaas.NL)
Objective: To assess the utility of functional perfusion and diffusion MR imaging in assessing early (1 month) response of unresectable HCC to a single treatment with Yttrium-90 labeled microspheres (TheraSpheres).
Materials and Methods: MR Imaging studies before and 1 month after single selective TheraSphere treatment on 13 consecutive patients were evaluated. All patients had cirrhosis and pathologically proven HCC. Patients were imaged using a 1.5-T MR scanner and a phased array torso coil. Images were evaluated by consensus of 2 MR radiologists. Tumor size, arterial and venous enhancement, and apparent diffusion coefficient (ADC) values were recorded before and after treatment. One targeted tumor in the treated lobe of the liver was included in each patient. In patients who also had lesions in the contralateral lobe of the liver a second tumor was included as non-targeted tumor for comparison of tumor response.
Results: A total of 21 tumors (mean size, 9.4 cm) were evaluated in 13 male patients (mean age, 62 years). Mean tumor burden was 25% of the total liver volume, and mean TheraSpheres dose was 127 Gy. Targeted tumors (n = 13) demonstrated mean decrease in arterial enhancement of 22% (p = 0.013), mean decrease in venous enhancement of 25% (p = 0.012), and mean increase in ADC value of 18% (p < 0.001). Targeted tumors had no change in size after treatment (p = 0.492), and therefore, were considered nonresponders based on size criteria. Six patients had contralateral non-targeted tumors. These tumors had no change in size (p = 0.100), arterial enhancement (p = 0.182), venous enhancement (p = 0.182), or ADC value (p = 0.105) after treatment.
Conclusion: Early after treatment with TheraSpheres, tumors demonstrated decrease in arterial and venous enhancement and increase in ADC, without statistically significant change in tumor size. These MR imaging findings suggest that molecular and cellular changes (tumor enhancement and water mobility) precede anatomical (size) changes after therapy and may serve as useful surrogate markers of tumor response in the early post-treatment period.
192. Role of Functional MR Imaging in Assessing Treatment Response to Transarterial Chemoembolization (TACE) in Patients with Hepatic Metastases
Buijs M. A.*; Vossen J. A.; Georgiades C.; Hong K.; Geschwind J. H.; Kamel I. R. Johns Hopkins Hospital, Baltimore, MD
Address correspondence to M. Buijs (M.Buijs{at}Student.Unimaas.NL)
Objective: To assess the utility of functional MR imaging in assessing treatment response after TACE in patients with unresectable hepatic metastases.
Materials and Methods: MR imaging studies before and after selective TACE on 32 patients (mean age, 59 years) with hepatic metastatic were evaluated. The primary cancer was breast, soft tissue sarcoma, and melanoma in 14, 10, and 8 patients, respectively. Patients were imaged using a 1.5-T MR scanner and a phased array torso coil. Imaging protocol included T2-weighted FSE images (matrix, 256 x 256; thickness, 8 mm; gap, 2 mm; TR, 5000; TE 100), BH diffusion-weighted echoplanar images (matrix, 128 x 128; thickness, 8 mm; gap, 2 mm; B value, 500; TR, 5000–6500; TE, 110), and BH unenhanced and contrast-enhanced T1-weighted 3D fat-suppressed GRE (matrix, 192 x 160; thickness, 4–6 mm; TE 1.2; flip angle, 15) in the arterial (20 sec) and portal venous (60 sec) phases. Images were evaluated by consensus of 2 MR radiologists. Tumor size, arterial and venous enhancement, and ADC values were recorded before and after treatment.
Results: A total of 78 lesions (mean size 5.2 cm) were evaluated. The average number of chemoembolizations per patient was 2 (range 1–3) and the average duration between pre- and postprocedural MR imaging was 58 days. Arterial and venous enhancement decreased after TACE by 36% (p < 0.0001) and 49% (p < 0.0001), respectively. Mean tumor ADC increased after TACE by 30% (p < 0.0001), whereas the ADC remained unchanged in non-tumorous liver and spleen. Although mean tumor size decreased to 4.4 cm (16%; p = 0.002) after TACE, it did not meet RECIST for complete response (i.e., disappearance of all measurable disease). Based on these results, all patients in our cohort would have been considered nonresponders to TACE, using size criteria. These trends were true for each of the primary tumor subtypes.
Conclusion: Hepatic metastases that were treated with TACE demonstrated decrease in arterial and venous enhancement due to interruption of the tumor blood supply. In addition, increase in tumor ADC indicated increasing cellular necrosis after therapy. These functional MR imaging features may be used as surrogate markers for assessing response to therapy before morphological changes in tumor size occur.
193. Serial Molecular and Cellular Changes After TACE as Detected by Perfusion and Diffusion-weighted MR Imaging in Patients with Unresectable HCC
Kamel I. R.*; Liapi E.; Reyes D. K.; Wahlin T.; Hebert J.; Bluemke D. A.; Geschwind J. H. Johns Hopkins Hospital, Baltimore, MD
Address correspondence to I. Kamel (ikamel{at}jhmi.edu)
Objective: To assess serial changes in perfusion and diffusion MR imaging values early (1 month) after TACE in patients with unresectable HCC.
Materials and Methods: MR Imaging studies were obtained before and immediately (within 24 hours) after TACE in 24 patients (mean age, 60 years) with HCC. Serial MR imaging was subsequently performed at 1, 2, 3 and 4 weeks after therapy. Patients were imaged using a 1.5-T MR scanner and a phased array torso coil. Imaging protocol included T2-weighted FSE images (matrix, 256 x 256; thickness, 8 mm; gap, 2 mm; TR, 5000; TE 100), BH diffusion-weighted echoplanar images (matrix, 128 x 128; thickness, 8 mm; gap, 2 mm; B value, 500; TR, 5000-6500; TE, 110), and BH unenhanced and contrast-enhanced T1-weighted 3D fat-suppressed GRE (matrix, 192 x 160; thickness, 4-6 mm; TE 1.2; flip angle, 15) in the arterial (20 sec) and portal venous (60 sec) phases. Images were evaluated by consensus of 2 MR radiologists. Tumor size, enhancement, and ADC values were recorded before and sequentially after treatment.
Results: A single tumor was included in each patient, and mean tumor size was 7.0 cm. No change in tumor size was detected at 4 weeks after therapy (p = 0.372). Reduction of tumor enhancement at 24 hours, 1, 2, 3, and 4 weeks was 37%, 47%, 41%, 37%, and 34%, respectively. Paired T-test was statistically significant at all 5 time points (p = 0.0001, 0.0004, 0.0004, 0.003, and 0.002, respectively). Increase in tumor ADC value at 24 hours, 1, 2, 3, and 4 weeks was 6%, 29%, 24%, 20%, and 7%, respectively. Paired T-test was statistically significant at 1, 2 and 3 weeks (p = 0.01, 0.005, 0.06, respectively). However, no change in ADC was detected at 24 hours and 4 weeks after therapy (p = 0.22 and 0.29, respectively).
Conclusion: Successful tumor embolization resulted in significant reduction in tumor enhancement, occurring within 24 hours after TACE, and persisting up to 4 weeks after treatment. Destruction of the cellular membranes and tumor necrosis resulted in a more delayed increase in ADC values, which appeared one week after therapy, persisted through the second and third weeks, and became less apparent at 4 weeks. These temporal findings precede tumor regression in size, and indicate that perfusion and diffusion MRI can detect early therapeutic response.
194. Radiofrequency Ablation of Hepatic Colorectal Carcinoma Metastases: Patient Survival, Local Metastasis Progression-Free Survival, and Factors for Failure of Treatment Effectiveness
Lehmann E. D.*; Kachura J. R.; Ho C. S.; Beecroft J. R.; Tomlinson G. A.; Wei A. C. Toronto General Hospital and Mount Sinai Hospital (University of Toronto), Toronto, Canada
Address correspondence to E. Lehmann (Eldon.Lehmann{at}uhn.on.ca)
Objective: To determine patient survival, local metastasis progression rates, and risk factors for failure of primary treatment effectiveness following radiofrequency ablation (RFA) of hepatic colorectal carcinoma metastases (HCRCM).
Materials and Methods: At our 2 hospitals we have maintained a prospective RFA database since November 1999. This was analyzed to September 2006 to identify treatment effectiveness, local metastasis progression, and patient survival in HCRCM. We reviewed 106 procedures on 90 metastases in 61 patients. Metastases were treated with LeVeen electrodes (Boston Scientific, Natick, MA) n = 98, 92.5%; Berchtold electrodes (Integra LifeSciences, Plainsboro, NJ) n = 4, 3.8%; and Cool-tip electrodes (Tyco Healthcare, Mansfield, MA) n = 4, 3.8%. RFA was performed percutaneously on 64 occasions and at surgery on 42 occasions. Image guidance was used as follows: US 23%, CT 12%, CT+US 26%, open US at surgery without liver resection 17% and with liver resection 22%. Failure of primary treatment effectiveness was defined as local viable metastasis on the first CT/MRI scan done >24 hours and <3 months (mo) from the treatment date. Data were analyzed using the freeware "R Project for Statistical Computing" program (www.r-project.org).
Results: Data are given as numbers, mean (SD) or ± SEM. Mean patient age was 64.5 (12.5) years (43 M, 18 F). Patients had on average 1.5 metastases, and 1.7 procedures. Each metastasis received on average 1.2 treatments. Mean maximum metastasis diameter was 2.3 (1.1) cm. Primary treatment effectiveness was 92.1%. Complications requiring treatment occurred in 14.2% of procedures; 1 of 64 percutaneous RFAs (1.6%), and 14 of 42 open RFAs at surgery (33.3%). Mean follow-up was 18 months (range 0–67 months). Overall Kaplan-Meier estimates of 1-year, 2-year, 3-year, and 4-year survival were 93.1 ± 3.9%, 71.1 ± 8.5%, 66.7 ± 9.0% and 57.2 ± 11.7%, respectively. In patients with primarily effectively ablated metastases, 1 year, 2 year, 3 year, 4 year and 5 year local metastasis progression-free survival was 70.7 ± 6.4%, 60.3 ± 7.3%, 55.3 ± 8.3%, 55.3 ± 8.3% and 47.4 ± 10.2%, respectively. In univariate analyses the strongest predictor of primary treatment effectiveness was metastasis size (p < 0.03).
Conclusion: In the treatment of colorectal carcinoma liver metastases, RFA was less likely to be primarily effective the larger the metastasis. However, survival rates with RFA are similar to those reported following surgical resection. Most complications were related to open RFA at surgery, with a <2% complication rate for percutaneous RFA.
195. Tumor Response Following Yttrium-90 Radioembolization for Hepatocellular Carcinoma: Comparison of Diffusion-weighted Functional MRI with Anatomic MRI
Rhee T. K.*; Naik N. K.; Deng J.; Atassi B.; Mulcahy M. F.; Kulik L. M.; Ryu R. K.; Miller F. H.; Larson A. C.; Salem R.; Omary R. A. Northwestern University Feinberg School of Medicine, Chicago, IL
Address correspondence to T. Rhee (t-rhee{at}northwestern.edu)
Objective: Anatomic MRI assessment of hepatocellular carcinoma (HCC) response to yttrium-90 (90Y) radioembolization may require up to 3 months before size changes are detected. Diffusion-weighted MRI (DWI) detects changes in cellular microstructures and cell membrane integrity post 90Y, but the relationship between anatomic and DWI MRI changes post 90Y therapy is unclear. We tested the hypothesis that apparent diffusion coefficient (ADC) values on DWI at 1 month precede anatomic tumor size change at 3 months post 90Y.
Materials and Methods: In this IRB-approved prospective study, patients with histologically confirmed HCC underwent standard 90Y therapy. On a 1.5-T MR scanner, anatomic MRI (gadolinium enhanced T1-weighted GRE with fat suppression in arterial and venous phases) and DWI (single-shot spin-echo EPI; TR/TE 2,500/82 msec; b values 0, 500 sec/mm2) were performed at baseline (0–3 weeks pre 90Y), 1 and 3 months post 90Y. Tumor size and ADC values were measured on an axial image with largest tumor diameter for the largest single treated HCC lesion. Tumor size was measured using WHO criteria while DWI ADC values were measured by drawing an ROI around the tumor. We compared ADC to tumor size and percent change [(follow-up value-baseline value)/baseline value] (PC) in ADC to tumor size (minimum >5% change in size) using a paired t-test (p = 0.05).
Results: Out of 32 consecutive patients (age 62 ± 13 years), 20 patients successfully completed the MRI protocol. Mean baseline ADC of 1.64 x 10-3 mm2/sec ± 0.30 increased to 1.81 x 10-3 mm2/sec ± 0.37 at 1 month, and to 1.82 x 10-3 mm2/sec ± 0.23 at 3 months. Compared to baseline, increases in ADC at 1 month (p = 0.02) and 3 months (p = 0.02) were statistically significant. However, mean baseline tumor size of 83.0 ± 63.7 cm2 did not statistically change at 1 month (84.1 ± 62.1 cm2; p = 0.75) or 3 months (74.0 ± 57.0 cm2 (p = 0.10). Overall mean ADC PC (1 month) of 10.5 ± 23.1% preceded overall mean tumor size PC (3 months) of -18.5 ± 31.5% (p = 0.03). For the ADC PC values, sensitivity/specificity was 93%/100% and positive/negative predictive value was 100%/80%.
Conclusion: HCC tumor response assessed with DWI at 1 month correlates to anatomic size changes at 3 months post 90Y. DWI may assist in early determination of HCC 90Y therapy response or failure which then may allow patients to undergo additional or alternative therapies earlier than 3 months. Future studies should assess how DWI affects patient outcome following 90Y therapy.
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