Image-Guided Transarterial Chemoembolization With Drug-Eluting Beads Loaded with Doxorubicin (DEBDOX) for Unresectable Hepatic Metastases from Melanoma: Technique and Outcomes.

PURPOSE: Hepatic metastasis from melanoma represents a therapeutic dilemma, with limited effective options for the 85% of cases deemed unresectable. Systemic agents confer toxicity and, along with traditional local hepatic arterial-directed therapies such as transarterial chemoembolization, have not led to a significant increase in survival. The aim of this study was to investigate the safety and dose-limiting toxicity of DEBDOX for the treatment of unresectable hepatic metastases from melanoma. METHODS: A multicenter (University of Louisville, Thomas Jefferson University, MD Anderson Cancer Center), prospective, non-controlled treatment trial (NCT01010984) of hepatic-directed therapy with DEBDOX for the treatment of melanoma liver metastasis was reviewed. Primary endpoints were response rates by modified response evaluation criteria in solid tumors, hepatic progression-free survival (PFS), and overall survival (OS). RESULTS: Twenty patients received a total of 61 DEBDOX treatments from January 2010 to March 2013. The median hepatic tumor burden was 40% (range 20-55), 18 patients (90%) had bilobar disease, and 13 patients (65%) had concomitant extrahepatic disease. At median assessment of 2.5 months, 11 patients (55%) exhibited a tumor response and 16 (80%) exhibited disease control. Median follow-up was 5 months (range 1.1-34.3 months). Median hepatic PFS was 3 months (95% CI 1.4, 3.4), and OS was 5 months (95% CI 3.3, 10.5). CONCLUSIONS: Directed arterial therapy with DEBDOX is effective in managing unresectable liver-dominant metastasis from melanoma and should be considered a therapeutic option in the multidisciplinary treatment of this disease. Concurrent systemic therapy is merited given the high rate of extrahepatic progression. CLINICAL TRIAL: NCT01010984.

Multi-disciplinary Concurrent Management of Recurrent Hepatocellular Therapy is Superior to Sequential Therapy.

BACKGROUND: Recurrent hepatocellular carcinoma after a patient's initial therapy, whether it is transplantation, resection, or ablation, remains a challenging clinical problem. Since recurrence occurs in 70% of all initially treated disease within 5 years, optimal management to treat this recurrence is needed. Currently, a bias exists toward mono-therapy (i.e., ablation alone, hepatic arterial therapy alone, or sorafenib therapy alone) instead of concurrent sequential therapy-as is common in other primary and metastatic disease to the liver. Thus, the aim of our study was to evaluate the overall survival of recurrent HCC based on either mono-therapy or multimodality therapy. METHODS: A review of our prospective 2245 patient hepato-pancreatico-biliary database was performed for all patients who underwent treatment with curative intent for hepatocellular carcinoma and had complete recurrence treatment data from June 2002 to May 2015. Mono-therapy was defined as initiation of a solitary therapy until disease progression or intolerance. Multimodality therapy was defined as at least 2 therapies that occurred simultaneously or within 4 weeks of each therapy. RESULTS: A total of 281 patients underwent treatment with curative intent for hepatocellular carcinoma, in which 192 experienced recurrence. These patients were treated with either thermal ablation or liver resection (LR) (N = 51), transarterial chemoembolization (TACE) or radiation (N = 68), systemic therapy (N = 26), or multimodality therapy (N = 47). The extent of the first recurrence was similar in regard to the number of tumors (median 1), the type of radiologic HCC, gender, BMI, and percentage of liver involvement. They differed in regard to size (MMT largest, median 5.6 cm, p = 0.02), and MMT had higher Hepatitis C involvement (37% of patients, p = 0.001). In evaluation of first recurrence treatment, after a median follow-up of 24 months, multimodality therapy has a significant improvement in overall survival (median 40 months, range 8-85), when compared to LR/Ablation (27 months, range 4-75), TACE/XRT (13 months, range 4-68), and systemic (26 months, range 3-59) (p = 0.003). CONCLUSION: Multimodality therapy should be considered in all patients with recurrent HCC based on tumor biology and underlying hepatic reserve. Hepatocellular cancer should be treated like other hepatic malignancies in which concurrent therapies are utilized simultaneously to optimize oncologic effects (response rates and overall survival) and minimize quality-of-life side effects. Multimodality therapy can lead to far superior overall survival and is well tolerated in the majority of recurrent HCC patients.

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

BACKGROUND: We evaluated the performance of the Response Evaluation Criteria in Solid Tumor (RECIST), modified RECIST, and the European Association for the Study of Liver (EASL) guidelines and correlated them with survival in patients with metastatic colorectal cancer (mCRC) treated with locoregional therapy (LRT). PATIENTS AND METHODS: Our LRT registry was evaluated from 2008 to 2013. 228 mCRC patients were treated with LRT (91% drug-eluting beads, 9% radioembolization) were evaluated. Cox regression and Kaplan-Meier (KM) statistics were utilized for survival analysis. RESULTS: Excellent inter-rater agreement between EASL/mRECIST (κ = 905) was seen. Correlations between RECIST/mRECIST (κ = 0.638) and EASL/RECIST were weaker (κ = 0.638 and 0.598, respectively). There were significant differences in KM and Cox regression survivals between responders and nonresponders with all three methods (all P < 0.0001). Multivariate analysis identified RECIST response, tumor extent, performance status, concomitant chemotherapy, and prior surgery/ablation as independent prognostic factors. EASL response and mRECIST response were not found to be independent prognostic factors. CONCLUSION: Imaging biomarkers are not efficient and do not represent ideal surrogates for survival; however, they all display prognostic significance. RECIST is superior to mRECIST/EASL given its ability to stratify survival benefit according to response category and demonstrate independent prognostic significance. J. Surg. Oncol. 2016;113:443-448. © 2016 Wiley Periodicals, Inc.

Assessment of chemotherapy response in colorectal liver metastases in patients undergoing hepatic resection and the correlation to pathologic residual viable tumor.

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.

Hepatic arterial therapy with drug-eluting beads in the management of metastatic pancreatic carcinoma to the liver: a multi-institutional registry.

Introduction. There has been limited reporting on the use of hepatic-directed therapy in liver dominant hepatic metastases arising from pancreatic cancer. Methods. An IRB-approved prospective multi-institutional treatment registry of 885 patients undergoing 1458 treatments for primary or secondary cancers in the liver was evaluated from January 2007 to January 2011. Results. Ten patients underwent a total of 17 treatment sessions with drug-eluting beads (DEBs). Six patients received concurrent chemotherapy while undergoing DEB with no severe adverse events. After a median followup of 16 months, the 6- and 12-month response rates were 80% and 75%, respectively, with a median overall survival of 9.3 months. Conclusion. Hepatic arterial therapy with DEB can be safely and effectively used in selected patients with liver predominant metastatic disease from pancreatic cancer. This therapy should be considered in combination with systemic chemotherapy as a possible second therapy given the limited response rates of second-line chemotherapy.

Hepatic arterial therapy with drug-eluting beads in the management of metastatic bronchogenic carcinoma to the liver: a multi-institutional registry.

Introduction. There has been limited information reported on the use of hepatic arterial therapy in liver dominant hepatic metastases arising from lung cancer. The aim of this study was to evaluate the safety and efficacy of hepatic arterial therapy in the treatment of liver dominant hepatic metastases arising from lung cancer. Methods. Thirteen patients underwent a total of 30 treatment sessions with Drug-Eluting Beads. Eight of the thirteen received only doxorubicin DEB (17 of the total treatments), and four patients received Irinotecan DEB (7 of the total treatments). Results. The planned preprocedural dosage was a median of 75 mg (range 19-200), with total hepatic dose exposure being a median of 150 mg (range 0-458), with a technical success rate of 97% in all 29 treatments. There were 4 adverse events related to treatment, but no evidence of hepatic insufficiency. Overall 6-month and 12-month response rates were 50%. After a median followup of 24 months, the median overall survival in this cohort was 14 months (range 7-48 months). Conclusion. Drug-eluting beads loaded with doxorubicin (DEBDOX) or irinotecan (DEBIRI) can be safely and effectively used in treatment of patients with liver predominant metastatic disease from lung cancer.

Hepatic arterial infusion of doxorubicin-loaded microsphere for treatment of hepatocellular cancer: 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.

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 $25,243 and the median cost for DEBDOX was $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.

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

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.

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

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.

Precision hepatic arterial irinotecan therapy in the treatment of unresectable intrahepatic cholangiocellular carcinoma: optimal tolerance and prolonged overall survival.

BACKGROUND: Unresectable intrahepatic cholangiocellular carcinoma (ICC) carries a poor prognosis, and there are few chemotherapeutic treatments to prolong survival. The purpose of this study was to assess the efficacy of drug-eluting bead (DEB) therapy by transarterial infusion for unresectable ICC. METHODS: A prospective multicenter study of ICC patients who received hepatic arterial DEB therapy. RESULTS: Twenty-four patients with unresectable ICC were treated with DEB. Ten patients (41.6%) had recurrent ICC after prior radiofrequency ablation (n = 3) or hepatectomy (n = 7). Twenty patients (80%) had received prior chemotherapy, mostly of gemcitabine (n = 8) or Eloxatin (n = 6). The percent of overall liver involvement was < 25% (n = 8), 26% to 50% (n = 11), and > 50% (n = 4). Ten patients (40%) had sites of extrahepatic disease located at lymph nodes (n = 5), bone (n = 2), peritoneum (n = 1), lung (n = 1), and mouth (n = 1). A total of 42 DEB treatments were administered. Eight were administered in combination with systemic chemotherapy of FOLFOX (n = 4) or Gemzar (n = 4). Twelve patients (48%) received a second treatment, and 4 patients (16%) received a third treatment. The median length of stay was 23 h (23-72 h). Eleven adverse reactions (26.2%) were reported. Of these, 7 (63.6%) were minor (less than grade 3). One patient died from hepatorenal syndrome. The disease of one patient was downstaged to resection. After a median follow-up of 13.6 months, the median overall survival of a multitherapeutic regimen with DEB therapy was significantly greater than chemotherapy alone (17.5 vs. 7.4 months; P = 0.02). CONCLUSIONS: Bead therapy is safe and effective in patients with unresectable ICC. There is a marked survival benefit when DEB therapy is used as adjunctive therapy.

Hepatic intra-arterial injection of drug-eluting bead, irinotecan (DEBIRI) in unresectable colorectal liver metastases refractory to systemic chemotherapy: results of multi-institutional study.

INTRODUCTION: Response rates and overall outcome for patients who have failed first-line and in some cases second-line chemotherapy are as low as 12% and 7 months, respectively. The aim of this study is to evaluate the efficacy of hepatic arterial sulfonate hydrogel microsphere (drug-eluting beads), irinotecan preloaded therapy (DEBIRI) in metastatic colorectal cancer refractory to systemic chemotherapy. METHODS: This was a multicenter multinational single-arm study of metastatic colorectal cancer patients who received DEBIRI after failing systemic chemotherapy from 10/2006 to 8/2008. Primary endpoints were safety, tolerance, tumor response rates, and overall survival. RESULTS: Fifty-five patients who had received prior systemic chemotherapy and who underwent a total of 99 DEBIRI treatments were reviewed. The median number of DEBIRI treatments was 2 (range 1-5), median treatment dose was 100 mg (range 100-200 mg), with total hepatic treatment of 200 mg (range 200-650 mg), with 86% of treatments performed as lobar infusion and 30% of patients treated with concurrent simultaneous chemotherapy. Adverse events occurred in 28% of patients with median grade of 2 (range 1-3) with no deaths at 30 days post procedure. Response rates were 66% at 6 months and 75% at 12 months. Overall survival in these patients was 19 months, with progression-free survival of 11 months. CONCLUSIONS: Hepatic arterial drug-eluting bead, irinotecan (DEBIRI) was safe and effective in treatment of metastatic colorectal cancer (MCC) refractory to multiple lines of systemic chemotherapy. DEBIRI is an acceptable therapy for treatment of metastatic colorectal cancer to the liver.

Safety of hepatic resection in metastatic disease to the liver after yttrium-90 therapy.

BACKGROUND: Unresectable hepatic metastases from aerodigestive cancers are common and in most cases herald a poor prognosis. A small percentage of patients maybe amenable to surgical resection or ablation once the biology of the disease and the burden of hepatic disease are better understood. The use of hepatic arterial resin microspheres containing the ß emitter, yttrium-90, has been reported in the treatment of unresectable hepatic metastases. The goal of this review was to evaluate the use of yttrium-90 hepatic arterial therapy in the management of hepatic metastases and surgical downstaging. METHODS: We reviewed our prospective hepatic arterial therapy registry and found 44 patients who had received Sir Sphere treatment for unresectable hepatic malignancies from 11/06 to 7/08. Response was assessed by using CT-imaging and characterized using modified response evaluation criteria in solid tumors (RECIST). All patients were managed in a multidisciplinary tertiary referral center specializing in hepatic malignancies. RESULTS: A total of 44 patients, 34 men and 10 women, with a median age of 60 y (range 44-8), received 67 treatments. The disease types treated were one adenosquamous tongue, one adrenal, nine carcinoid, three cholangiocarcinoma, four esophageal, one gastric, one gastrinoma, one GIST, four HCC, 15 colorectal, one melanoma, one non-small-cell lung, one occular, and one sarcoma. Four patients treated proceeded to resection because of downstaging of disease or no evidence of extrahepatic progression. The median age in these patients was 61 y (range 49-62). All of the patients had less than 25% tumor burden in the liver. Surgical therapy consisted of two patients undergoing right hepatic lobectomy, one patient who also underwent two wedge resections of segment 3, and one patient who had a left lateral hepatectomy with right lobe microwave ablation. The median length of postoperative stay was 7 d. There was no evidence of liver dysfunction following resection in any of the patients. None of the patients show evidence of recurrence in the liver following resection. One patient has had progression of disease in the lungs following resection, histologically confirmed as metastatic rectal carcinoma. All of the patients are currently alive with a median survival of 2 y. CONCLUSION: Hepatic directed yttrium-90 is a minimally invasive, highly effective therapy that can be utilized to downstage the hepatic burden and/or assess the biology of the disease to allow for appropriate treatment. The use of yttrium-90 microspheres for radio-embolization of metastases in the liver can successfully downstage the lesions to allow for surgical resection in patients with amenable predictors, and can provide a significantly better prognosis in these patients. This form of therapy for the purposes of downstaging tumors for resection merits more extensive study in order to provide the best possible outcomes for patients with metastatic liver disease.

Toxicity of irinotecan-eluting beads in the treatment of hepatic malignancies: results of a multi-institutional registry.

PURPOSE: To evaluate the predictors of toxicity of drug-eluting beads loaded with irinotecan (DEBIRI) in the treatment of hepatic malignancies. MATERIALS AND METHODS: A total of 330 patients were enrolled in a prospective, open-label, multicenter, multinational, single-arm study administering two types of drug-eluting beads (DEBIRI and drug-eluting beads loaded with doxorubicin). Complications were graded by Cancer Therapy Evaluation Program's Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. All events requiring additional physician treatment or requiring extended hospital stay or readmission within 30 days were included. RESULTS: A total of 109 patients received 187 DEBIRI treatments (range 1 to 5 per patient). The most common histology was metastatic colorectal cancer in 76% of patients, cholangiocarcinoma in 7% of patients, and other metastatic disease in 17% of patients. There were 35 patients (19%) with irinotecan treatments who sustained 158 treatment-related adverse events, with the median CTCAE event grade being CTCAE grade 2 (range 1 to 5). The most common adverse events were postembolic symptoms (42%). Multivariate analysis identified pretreatment and treatment-related risk factors as follows: lack of pretreatment with hepatic arterial lidocaine (p = 0.005), > or = 3 treatments (p = 0.05), achievement of complete stasis (p = 0.04), treatment with >100 mg DEBIRI in 1 treatment (p = 0.03), and bilirubin >2.0 microg/dl with >50% liver involvement (p = 0.05). These factors were predictive of adverse events and significantly greater hospital length of stay. CONCLUSIONS: DEBIRI is safe when appropriate technique and treatment are used. Adverse events can be predicted based on pretreatment- and treatment-related factors, and their occurrence can become part of the informed consent process. Continued standardization of this treatment will lead to fewer adverse events and improved patient quality of life.

Prior biliary tree instrumentation does not preclude hepatic arterial therapy for malignancy.

Hepatic arterial therapy (HAT) has become an accepted alternative for patients with unresectable hepatic malignancies. HAT has an acceptable toxicity profile, yet its safety for use in patients who have undergone significant biliary manipulation is undocumented. A retrospective review identified 18 consecutive patients with unresectable hepatic malignancies who had undergone significant prior biliary tree manipulation. All patients received peri-HAT antibiotics. Clinicopathologic, treatment-related, and outcomes data were collected and analyzed. Eighteen patients who had HAT were analyzed; 72 per cent were men, the median age was 61 years, and 61 per cent had greater than 25 per cent hepatic parenchymal replacement by tumor. Seventy-eight per cent of patients had an indwelling biliary stent and 22 per cent had undergone a hepaticojejunostomy. Twenty-two per cent of patients developed a complication, none of which were infectious, and there were no peri-HAT deaths. The majority of patients had evidence of either a partial response (55%) or stable disease (22%) upon follow-up. One patient had a complete response to HAT. The median survival was 27 months. Hepatic arterial therapy seems to be safe for patients with unresectable hepatic malignancies and a history of significant biliary instrumentation. There is no increased risk of infectious complications in this population after HAT.

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 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 Bead(TM) 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.

BACKGROUND: Following 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. METHODS: This 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 physician's discretion. RESULTS: Fifty-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%) 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. CONCLUSION: Chemoembolization using Irinotecan loaded beads was safe and effective in the treatment of patients as demonstrated by a minimal complication rate and acceptable tumor response.