Cliff Tatum

Transarterial Chemoembolization of Metastatic Colorectal Carcinoma with Drug-Eluting Beads, Irinotecan (DEBIRI): Multi-Institutional Registry

The purpose of this study was to evaluate the patient tolerance and efficacy of delivering locoregional chemotherapy to metastatic colorectal (MC) hepatic metastases via hepatic trans-arterial approach using irinotecan loaded drug eluting beads. This open-label, multi-center, single arm study included 30 MC patients, who had failed first line therapy. Of the 57 total embolization sessions, 12 (21% of sessions) were associated with adverse reactions during or after the treatment. After a median followup of 9 months, response rates by modified RECIST were 75% at 3 months and 66% at 6 months. Hepatic trans-arterial therapy using Irinotecan loaded DC BeadTM was safe and effective in the treatment of MCC as demonstrated by a minimal complication rate and acceptable tumor response.

Transarterial chemoembolisation (TACE) using irinotecan-loaded beads for the treatment of unresectable metastases to the liver in patients with colorectal cancer: an interim report

BackgroundFollowing failure of standard systemic chemotherapy, the role of hepatic transarterial therapy for colorectal hepatic metastasis continues to evolve as the experience with this technique matures. The aim of this study to gain a better understanding of the value of drug eluting bead therapy when administered to patients with unresectable colorectal hepatic metastasis.MethodsThis was an open-label, multi-center, single arm study, of unresectable colorectal hepatic metastasis patients who had failed standard therapy from 10/2006-10/2008. Patients received repeat embolizations with Irinotecan loaded beads(max 100 mg per embolization) per treating physicians discretion.ResultsFifty-five patients underwent 99 treatments using Irinotecan drug eluting beads. The median number of total treatments per patient was 2(range of 1-5). Median length of hospital stay was 23 hours(range 23 hours - 10 days). There were 30(30%) sessions associated with adverse reactions during or after the treatment. The median disease free and overall survival from the time of first treatment was 247 days and 343 days. Six patients(10%) were downstaged from their original disease status. Of these, four were treated with surgery and two with RFA.Neither number of liver lesions, size of liver lesions or extent of liver replacement(<= 25% vs >25%) were predictors of overall survival. Only the presence of extrahepatic disease(p = 0,001), extent of prior chemotherapy (failed 1st and 2nd line vs > 2 line failure)(p = 0,007) were predictors of overall survival in multivariate analysis.ConclusionChemoembolization using Irinotecan loaded beads was safe and effective in the treatment of patients as demonstrated by a minimal complication rate and acceptable tumor response.

Surgical downstaging and neo-adjuvant therapy in metastatic colorectal carcinoma with irinotecan drug-eluting beads: a multi-institutional study

BACKGROUND Neoadjuvant chemotherapy for potentially resectable metastatic colorectal cancer (MCC) is becoming a more common treatment algorithm. The aim of the present study was to evaluate the efficacy of precision hepatic arterial Irinotecan therapy in unresectable MCC. METHODS An open-label, multi-centre, multi-national single arm study of MCC patients, who received hepatic arterial irinotecan. Primary endpoints were safety, tolerance and metastatic tumour resection. RESULTS Fifty-five patients with metastatic colorectal to the liver underwent a total of 90 hepatic arterial irinotecan treatments. The extent of liver involvement was < 25% in 75% of the patients (n= 41), between 26 and 50% in 15% of the patients (n= 11) and >50% in 10% of the patients (n= 24). The median number of hepatic lesions was four (range 1-20), with a median total size of all target lesions of 9 cm (range 5.5-28 cm) with 50% of patients having bilobar tumour distribution. The median number of irinotecan treatments was two (range 1-5). The median treatment dose was 100 mg (range 100-200) with a median total hepatic treatment of 200 mg (range 200-650). The majority of treatments (86%) were performed as lobar infusion treatments, and 30% of patients were treated with concurrent simultaneous chemotherapy. Eleven (20%) patients demonstrated significant response and downstage of their disease or demonstrated stable disease without extra-hepatic disease progression allowing resection, ablation or resection and ablation. There were no post-operative deaths. Post-operative complications morbidity occurred in 18% of patients, with none of them hepatic related. Non-tumorous liver resected demonstrated no evidence of steatohepatitis from the irinotecan arterial infusion. CONCLUSIONS Hepatic arterial infusion irinotecan drug-eluting beads is safe and effective in pre-surgical therapy and helpful in evaluating the biology of metastatic colorectal cancer to the liver prior to planned hepatic resection.

Transarterial Chemoembolization and Selective Internal Radiation for the Treatment of Patients with Metastatic Neuroendocrine Tumors: A Comparison of Efficacy and Cost

BACKGROUND Hepatic arterial therapy (HAT) has been proven to be effective at palliation of hormonal symptoms of metastatic neuroendocrine tumors (NETs), as well as a means of cytoreduction. Recently, the newer modalities of yttrium-90 and drug-eluting beads with doxorubicin (DEBDOX) have been reported to be effective in the treatment of metastatic NETs. The aim of this study was to compare the safety, efficacy, and cost of selective internal radiation with DEB therapy. METHODS An institutional review board-approved, multicenter, multinational prospective treatment registry to investigate the safety and efficacy of yttrium-90 and doxorubicin microspheres was reviewed. RESULTS In all, 43 patients underwent a combined 69 HAT treatments, with 15 patients receiving 23 yttrium-90 treatments and 28 patients receiving 46 DEBDOX treatments. The extent of disease-based on the number of lesions, bilobar distribution, patient performance status, and size of largest lesion-was similar in both the yttrium-90 and DEBDOX groups. After a median follow-up of 12 months, response rates were similar with the two treatments, but then there was a significantly lower response rate in the yttrium-90 group at 12 months than in the DEBDOX group. In an evaluation of cost for the two treatments, the median cost for yttrium-90 was

Assessment of Chemotherapy Response in Colorectal Liver Metastases in Patients Undergoing Hepatic Resection and the Correlation to Pathologic Residual Viable Tumor

25,243 and the median cost for DEBDOX was

Hepatectomy after hepatic arterial therapy with either yttrium-90 or drug-eluting bead chemotherapy: is it safe?

13,400. CONCLUSION HAT is a safe and effective therapy in patients with unresectable NETs to the liver. The size of the lesions, total lesion volume, and expense of therapy need to be considered when choosing which HAT method is optimal.

Hepatic Arterial Infusion of Doxorubicin-Loaded Microsphere for Treatment of Hepatocellular Cancer: A Multi-Institutional Registry

BACKGROUND The Response Evaluation Criteria in Solid Tumors (RECIST), which evaluates maximum tumor diameter only, is commonly used to determine response to chemotherapy in patients with colorectal liver metastases. Limitations of RECIST include its inability to assess the changes in tumor enhancement. The aim of this study was to assess the correlation of these criteria as well as the modified RECIST (mRECIST) with pathologic tumor response. A novel semi-automated volumetric assessment of tumor size was also investigated. STUDY DESIGN A review of a 1,948-patient prospective hepatic database to assess response and pathologic criteria was performed. Patients undergoing preoperative chemotherapy before hepatic resection for colorectal liver metastases were reviewed. Radiographic responses according to RECIST and mRECIST were determined. The percentage of viable tumor cells compared with the total tumor area was determined from the pathologic specimens. RESULTS We identified 38 patients with adequate imaging who had undergone anatomic hepatic resection and full pathologic evaluation. The percentages of residual viable tumor in the resected specimens were significantly different across RECIST categories (p = 0.045), but not mRECIST (p = 0.305). For mRECIST, there were improved and significant linear trends for residual viable tumor, necrosis, and necrosis + fibrosis when compared with RECIST (p = 0.056). Neither RECIST nor mRECIST responses were predictive of residual viable tumor burden in regression analyses. A novel semi-automated volumetric assessment of tumor size correlated well with pathologic tumor size. CONCLUSIONS Neither RECIST nor mRECIST were predictive of residual viable burden, although the linear trend for mRECIST and residual necrosis + fibrosis compared favorably with RECIST. Continued evaluation for tumor enhancement and standardization of tumor size remain a critical unmet need in patients with solid organ disease.

Optimal technique and response of doxorubicin beads in hepatocellular cancer: bead size and dose

BACKGROUND The use of hepatic arterial therapy (HAT) with either yttrium-90 or drug-eluting bead therapy for initially unresectable hepatic malignancies has risen significantly. The safety of hepatic resection after hepatic arterial therapy (HAT) is not established. OBJECTIVE The present study evaluates the safety profile for hepatic resection after HAT. METHODS We identified 840 patients undergoing hepatectomy for primary or metastatic lesions. Forty patients underwent HAT before hepatectomy (pre-HAT). A 1:4 case-matched analysis compared three groups: (i) pre-HAT and pre-operative chemotherapy (n=40); (ii) pre-operative chemotherapy (n=160); and (iii) no pre-operative therapy (n=640). Controls were matched for age, resection type, maximal tumour size and magnitude of resection. Morbidity and mortality among groups were compared using a graded complication scale. RESULTS   There were no differences in post-operative complications, grade of complication or liver-specific complications among the groups. A proportional hazards model for all patients did not demonstrate any association between increased complications and either pre-HAT or pre-operative chemotherapy when compared with patients without pre-operative therapy (P=0.7). CONCLUSIONS Pre-HAT demonstrated similar morbidity, liver-specific morbidity and intra-operative complications when compared with patients undergoing pre-operative chemotherapy alone or without pre-operative chemotherapy. These results suggest that pre-HAT is safe and should not preclude hepatectomy in carefully selected patients.

Hepatic Arterial Therapy with Drug-Eluting Beads in the Management of Metastatic Bronchogenic Carcinoma to the Liver: A Multi-Institutional Registry

BACKGROUND Hepatic intra-arterial therapy for unresectable hepatocellular cancer (HCC) has been shown to improve overall survival, but can have significant toxicity. A recent prospective randomized controlled trial demonstrated superior response rates and significantly less morbidity and doxorubicin-related adverse events with drug-eluting beads with doxorubicin (DEBDOX) compared with conventional chemoembolization. The aim of this study was to confirm the efficacy of DEBDOX for the treatment of unresectable HCC. STUDY DESIGN This open-label, multicenter, multinational single-arm study included 118 intermediate-staged HCC patients who were not candidates for transplantation or resection. Patients received DEBDOX at each treatment. Complications and response rates to treatment were analyzed. RESULTS There were 118 patients who received a total of 186 DEBDOX treatments with a median total treatment dose of 75 mg (range 38 to 150 mg), and median overall total hepatic exposure of 150 mg (range 150 to 600 mg). Five lesions were targeted, with a median size of 5.3 cm (range 1.0 to 16.9 cm). Severe adverse events related to liver dysfunction were seen after 4% of treatments. Overall survival was a median of 14.2 months (range 5 to 30 months), with progression-free survival of 13 months and hepatic-specific progression-free survival of 16 months. Okuda class less than 1 at time of treatment, reduction of alpha-fetoprotein of 1,000 ng/mL at the first post-treatment evaluation, delivery of more than 200 mg doxorubicin, and less than 25% liver involvement were all predictors of favorable overall survival assessed by multivariable analyses. CONCLUSIONS Hepatic intra-arterial injection of DEBDOX is safe and effective in the treatment of HCC, as demonstrated by a minimal complication rate and robust and durable tumor response.

Comparison of tumor response assessment methods in patients with metastatic colorectal cancer after locoregional therapy

Background/Aims It has been shown that the drug-eluting beads loaded with doxorubicin (DEBDOX) are effective for the treatment of hepatocellular carcinoma (HCC). However, the optimal safety and efficacy still remain to be established by using various bead sizes, doxorubicin doses, and the degree of stasis.The aim of this study was to determine the optimal safety and efficacy of DEBDOX in the treatment of HCC. Methods Analysis of a 503-patient prospective, multicenter, multinational Bead Registry Database from 2007 to 2010 identified 206 patients who had been treated for HCC with DEBDOX. Primary endpoints were to compare safety, tolerance, response rates, and overall survival based on bead size (100-300, 300-500, 500-700, and 700-900 µm), number of vials, doxorubicin dose, and degree of stasis. Results In total, 206 patients underwent 343 treatments. The use of all four bead sizes was similar based on Child-Pugh class and Okuda stage, with a significantly higher use (50%) of beads of size 100-300 µm in patients with portal vein thrombosis (P=0.05). Significant differences were seen for the number of median treatments, median doxorubicin dose, lobar infusion), and degree of complete stasis. The rate of adverse events was higher for larger beads than for smaller beads (28% vs. 16%; P=0.02). Conclusions Bead size and dose may vary according to disease distribution. Smaller beads offer the opportunity for repeated treatments, a larger cumulative dose delivery, a lesser degree of complete stasis, and fewer adverse events.