Unresectable Hepatic Colorectal Metastases Research Articles

Transarterial radioembolization with Iodine-131-Lipiodol for hepatic metastases from gastrointestinal malignancies - Experience in tertiary care oncology center in India.

Context:Unresectable colorectal hepatic metastases can be treated with radioembolization.Aims:The aim of this study is to analyze the response and survival benefits of transarterial radioembolization (TARE) with Iodine-131 (131I) Lipiodol for hepatic metastases from gastrointestinal malignancies.Settings and Design:Retrospective study of 20 patients with pathologically proven hepatic metastases from primary gastrointestinal malignancies referred for palliative therapy with TARE.Subjects and Methods:At baseline, standard laboratory and imaging data were recorded. All patients fulfilling the inclusion/exclusion criteria underwent TARE with 131I Lipiodol. Post procedure, the patients were reviewed after 1 month with follow-up positron emission tomography–computed tomography and tumor marker levels to evaluate treatment response with continued follow-up till December 2016 and overall survival calculated.Statistical Analysis Used:Data were analyzed using a statistical analysis package (Social sciences, version 15.0 for Windows; SSPS Inc.). Survival data were plotted using Kaplan–Meier survival curves.Results:At the end of follow-up period, 15 of 20 patients were alive. The mean and median survival was 38.88 ± 5.0 months (95% confidence interval [CI], 29.03–48.74 months, P = 0.17) and 49.3 ± 12.4 months (95% CI, 25.0–73.7 months, P = 0.17), respectively. 66 months survival was 75%. Response evaluation in 10 patients showed partial response in 3 (30%), stable disease in 2 (20%) and progressive disease in 5 (50%) patients. All patients with partial response showed a reduction in serum tumor marker levels.Conclusions:TARE with 131I-Lipiodol is highly effective with a significant survival benefit in refractory cases of hepatic metastases from gastrointestinal malignancies.

Partial response after transcatheter arterial infusion chemotherapy in a patient with systemic chemotherapy-resistant unresectable colon cancer and hepatic metastasis: (case report)

We report here a case of partial response to hepatic arterial infusion chemotherapy in a patient who developed serious hepatic failure due to unresectable colorectal cancer and hepatic metastasis and showed resistance to systemic chemotherapy with molecular targeted drugs, mFOLFOX6, and FOLFIRI. The patient was a 60-year-old woman who underwent sigmoidectomy for sigmoid colon cancer, lateral posterior hepatic segmentectomy for metastatic liver cancer, and postoperative radiation therapy for metastatic lung cancer. As first-line systemic chemotherapy, mFOLFOX6 (oxaliplatin, 5-fluorouracil, and leucovorin), bevacizumab + FOLFIRI (irinotecan, 5-fluorouracil, leucovorin), and anti-epidermal growth factor receptor antibody + irinotecan were administered, in that order. However, recurrent hepatic metastasis was exacerbated, which induced serious hepatic failure manifested by general malaise, jaundice, abnormal hepatic function, difficulty in walking due to bilateral lower extremity edema, and decreased appetite. The patient was admitted in a serious condition. After hospitalization, the patient received hepatic arterial infusion chemotherapy with 5-fluorouracil and l-leucovorin. After two complete courses, the symptoms improved. The patient’s performance status also improved, and she was discharged from the hospital. Four months after discharge, the patient had continued outpatient chemotherapy and maintained excellent performance status. Although HAIC is not presently considered an alternative to systemic chemotherapy, it is sometimes effective in patients who show resistance to molecular targeted drug therapy, FOLFOX, and FOLFIRI, and in whom hepatic metastasis is a key factor in determining prognosis and serious hepatic failure. Further studies should be performed in the future to verify these findings.

Radiofrequency ablation for unresectable colorectal hepatic metastases: Prognostic factors and the effect of postoperative chemotherapy on survival.

581 Background: Radiofrequency ablation (RFA) is a recognized treatment modality in the management of patients with colorectal cancer liver metastasis (CRCLM). Our goal was to assess factors affecting long-term survival of patients undergoing RFA of CRCLM. Methods: We prospectively evaluated patients with unresectable CRCLM that underwent laparoscopic RFA. Patients were assessed pre- and postoperatively using triphasic computed tomography (CT) and intraoperatively using laparoscopic ultrasound. All information was entered into an IRB approved database. Pre-operative predictors were identified using Cox modeling. Postoperative chemotherapy was analyzed for its affect on survival. Results: 312 patients underwent 397 RFA sessions from 1999 to 2010. Patients averaged 2.7 lesions, with a dominant diameter of 3.4 cm and a preoperative CEA of 76. 28% had preoperative extrahepatic disease. Median survival on Kaplan-Meier analysis was 32 months, with 3 and 5 years survivals of 44% and 22%, respectively. The following were statistically significant on univariate and multivariable analysis: number of tumors (hazard ratio (HR) of 1.13 per tumor p=0.0002), dominate tumor diameter (HR 1.14 per cm p=0.03), pre-operative CEA (HR of 1.002 per one point rise p<.0001), and pre-operative extrahepatic disease (HR 1.4 p=0.05). Post-operative chemotherapy was shown to improve survival after controlling for the presence of new disease in follow-up. Conclusions: To our knowledge, this is both the largest and longest follow-up of RFA for unresectable CRCLM. The number and size of tumors, and preoperative CEA value are strong predictors of survival whereas pre-operative extrahepatic disease had mild impact on survival. Post-operative chemotherapy was shown to improve survival after controlling for other factors.

Percutaneous Femoral Implantation of an Arterial Port Catheter for Intraarterial Chemotherapy: Feasibility and Predictive Factors of Long-term Functionality

To evaluate the feasibility, functionality, and dysfunctions of an arterial port catheter implanted via the femoral artery. From November 2001 to May 2008, 93 consecutive patients (mean age 57 years old) with unresectable hepatic colorectal metastases were referred for intraarterial chemotherapy. The arterial port catheters were percutaneously implanted via the femoral artery. The catheter tips were placed as "free-floating" in the common hepatic artery (technique 1), "fixed" in the gastroduodenal artery (technique 2), or inserted in a segmental hepatic artery (technique 3). Embolization of the right gastric artery was always attempted. The technical success rate of the femoral approach was 94% (n = 88 of 93). Intraarterial chemotherapy (average 7.3 courses) was administered to 84 patients. Migration and occlusion of the catheters occurred in 12% (n = 10 of 84) and 11% (n = 9 of 84) of patients, and extrahepatic perfusion occurred in 30% (n = 25 of 84) of patients. Catheter migration occurred significantly more frequently with technique 1 (50%; n = 3 of 6) than with technique 2 (11%; n = 7 of 64; P = .03) or technique 3 (0%; n = 0 of 14; P = .02). Occurrence of gastroduodenal ulcerations was significantly lower (P = .01) when embolization of the right gastric artery was performed (8%; n = 4 of 48) than when it was not (28%; n = 11 of 36). The success rate of embolization of the right gastric artery significantly improved (P = .006) from the first half of patients treated to the second half, resulting in a significant (P = .02) decrease in the occurrence of ulcerations from 28% (n = 12 of 42) in the first half of patients treated to 7% (n = 3 of 42) in the second half. Percutaneous femoral placement of an arterial port catheter is highly feasible. Right gastric artery embolization and use of techniques 2 and 3 are good predictive factors for long-term functionality.

Effectiveness of positron emission tomography for predicting chemotherapy response in colorectal cancer liver metastases.

Chemotherapeutic agents may be able to convert unresectable colorectal hepatic metastasis to resectable disease, therefore changing the surgical options. The role of positron emission tomography (PET) for patients undergoing chemotherapy remains unclear. We hypothesize that recent chemotherapy treatment could result in false-negative PET results. Case-control study evaluating PET findings. The University of Texas M. D. Anderson Cancer Center. From May 1, 2006, through August 31, 2008, data for 224 consecutive patients were entered into a prospective database for evaluation of hepatic metastasis of colorectal carcinoma. One hundred thirty-eight patients underwent PET and conventional imaging (a combination of computed tomography, magnetic resonance imaging, and ultrasonography). All had oncologically sound colorectal operations. Liver resection or ablation for colorectal liver metastases. To determine the accuracy of PET scans to detect residual viable colorectal cancer liver metastases after a significant response to systemic chemotherapy. Patients with biopsy-proven disease underwent hepatic resection (120 patients [87.0%]), radiofrequency ablation (2 [1.4%]), or resection with radiofrequency ablation (7 [5.1%]). Nine patients (6.5%) had inoperable disease that was found intraoperatively. When performed within 4 weeks of chemotherapy, PET had a negative predictive value of 13.3% and a positive predictive value of 94.3%. The sensitivity was 89.9%, the specificity was 22.2%, and the accuracy was 85.5%. Positron emission tomography within 4 weeks of chemotherapy is not a useful test for evaluation of colorectal hepatic metastases. The high rate of false-negative results is likely due to metabolic inhibition caused by chemotherapeutic drugs. We recommend that physicians not use PET in patients recently completing chemotherapy; they should undergo the appropriate oncologic hepatic operation based on the high probability of viable malignant disease.

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 physician's 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.

Radioembolization of colorectal hepatic metastases using yttrium‐90 microspheres

: The objective of the current study was to determine the safety and efficacy of Yttrium-90 (Y90) microsphere treatment in patients with liver-dominant colorectal metastases. : Seventy-two patients with unresectable hepatic colorectal metastases were treated at a targeted absorbed dose of 120 Gray (Gy). Safety and toxicity were assessed using version 3 of the National Cancer Institute Common Terminology Criteria. Response was assessed by anatomic imaging and positron emission tomography (PET). Survival from the diagnosis of hepatic metastases and first treatment were estimated using the Kaplan-Meier method. Substratification analyses were performed. : The median dose delivered was 118 Gy. Treatment-related toxicities included fatigue (61%), nausea (21%), and abdominal pain (25%). Grade 3 and 4 bilirubin toxicities were observed in 9 of 72 patients (12.6%). The tumor response rate was 40.3%. The median time to hepatic progression was 15.4 months, and the median response duration was 15 months. The PET response rate was 77%. Overall survival from the first Y90 treatment was 14.5 months. Tumor replacement (< or =25% vs >25%) was associated with significantly greater median survival (18.7 months vs 5.2 months). The presence of extrahepatic disease was associated negatively with overall survival (7.9 months vs 21 months). Overall survival from the date of initial hepatic metastases was 34.6 months. A subset analysis of patients who had an Eastern Cooperative Oncology Group performance status of 0 demonstrated a median survival of 42.8 months and 23.5 months from the time of hepatic metastases and Y90 treatment, respectively. : Y90 liver therapy appears to provide sustained disease stabilization with acceptable toxicity. Asymptomatic patients with preserved liver function at the time of Y90 appeared to benefit most from treatment. Cancer 2009. (c) 2009 American Cancer Society.

Hepatic arterial infusion plus systemic irinotecan in patients with unresectable hepatic metastases from colorectal cancer previously treated with systemic oxaliplatin: a retrospective analysis

Response rates to systemic chemotherapy are low after tumor progression on oxaliplatin regimens. Hepatic arterial infusion (HAI) therapy in patients with tumor progression is a viable alternative. Thirty-nine heavily pre-treated patients (all receiving prior oxaliplatin) with unresectable colorectal hepatic metastases were treated with systemic CPT-11 and concurrent HAI floxuridine (FUDR) and dexamethasone (DEX). Partial responses were seen in 44% of patients. Median time to hepatic progression was 8.6 months, and median time to overall progression was 6.5 months. Median survival from time of initiation of HAI was 20.1 months [95% confidence interval (CI) 16.9-21.4] and from the initiation of treatment of metastatic disease, 32.01 months (95% CI 29.1-34.6). After a median follow-up of 19.1 months, seven patients (18%) proceeded to potentially curative surgery. Grade 3/4 toxic effects included neutropenia (13%), diarrhea (15%), intra-abdominal hemorrhage (2%), and bleeding duodenal ulcer (2%). Elevated liver function tests were seen, including bilirubin concentration >3 mg/dl (7%), alkaline phosphatase 2X baseline (20%), and aspartate aminotransferase >3X baseline (26%). HAI FUDR/DEX plus systemic CPT-11 achieves a response rate of 44% and a median overall survival of 20 months in heavily pre-treated patients with colorectal hepatic metastases all receiving previous oxaliplatin; 18% of patients proceeded to surgical resection or ablation.

90Y Microsphere (TheraSphere) Treatment for Unresectable Colorectal Cancer Metastases of the Liver: Response to Treatment at Targeted Doses of 135–150 Gy as Measured by [ 18F]Fluorodeoxyglucose Positron Emission Tomography and Computed Tomographic Imaging

The purpose of this phase II study was to determine the safety and efficacy of TheraSphere treatment (90Y microspheres) in patients with liver-dominant colorectal metastases in whom standard therapies had failed or were judged to be inappropriate. Twenty-seven patients with unresectable hepatic colorectal metastases were treated at a targeted absorbed dose of 135-150 Gy. Safety and toxicity were assessed according to the National Cancer Institute's Common Toxicity Criteria, version 3.0. Response was assessed with use of computed tomography (CT) and was correlated with response on [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET). Survival from first treatment was estimated with use of the Kaplan-Meier method. Tumor response measured by FDG PET imaging exceeded that measured by CT imaging for the first (88% vs 35%) and second (73% vs 36%) treated lobes. Tumor replacement of 25% or less (vs >25%) was associated with a statistically significant increase in median survival (339 days vs 162 days; P = .002). Treatment-related toxicities included mild fatigue (n = 13; 48%), nausea (n = 4; 15%), and vague abdominal pain (n = 5; 19%). There was one case of radiation-induced gastritis from inadvertent deposition of microspheres to the gastrointestinal tract (n = 1; 4%). Three patients (11%) experienced ascites/pleural effusion after treatment with TheraSphere as a consequence of liver failure in advanced-stage metastatic disease. With the exception of these three patients whose sequelae were not considered to be related to treatment, all observed toxicities were transient and resolved without medical intervention. TheraSphere administration appears to provide stabilization of liver disease with minimal toxicity in patients in whom standard systemic chemotherapy regimens have failed.

Second-look hepatectomy after pharmacokinetic modulating chemotherapy (PMC) combination with hepatic arterial 5FU infusion and oral UFT in patients with unresectable hepatic colorectal metastases

Second-look hepatectomy after pharmacokinetic modulating chemotherapy (PMC) combination with hepatic arterial 5FU infusion and oral UFT in patients with unresectable hepatic colorectal metastases

Second-look hepatectomy after pharmacokinetic modulating chemotherapy (PMC) combination with hepatic arterial 5FU infusion and oral UFT in patients with unresectable hepatic colorectal metastases

3739 Background:In order to improve prognosis we carried out hepatectomy on patients with initially unresectable hepatic metastases, where the metastic lesions had shrunk and resection subsequently became possible (second-look hepatectomy: s-l hepatectomy) after neoadjuvant chemotherapy by HAI plus the oral anticancer drug UFT (pharmacokinetic modulating chemotherapy by HAI: HAI-PMC). Methods:Since 1993, 51 patients with unresectable hepatic metastases for colorectal carcinoma without extra hepatic diseases received HAI-PMC. The regimen of HAI-PMC is a combination of intra-arterial infusion of 5FU for 2 consecutive days per week at 600mg/m2/day and oral administration of UFT at 400 mg/day for 5 days per week for 6 months. Results:The response rate to HAI-PMC was 78.4%, but 6 months after starting HAI-PMC we judged thirty-one of the 51 patients(61%) to be cases where s-l hepatectomy was possible. Twenty-four of the 31 patients agreed to undergo s-l hepatectomy (A group) while 8 patients chose to go on HAI-PMC (B group). The two-year, three-year and five-year survival rates of patients in the A group were 84%, 58% and 42%, and for those in the B group, 62%, 25% and 0%. The survival rate of patients in the A group was significantly higher than for those the B group.(P=0.039) (median follow-up period, 42 months) Conclusions:These results indicate that there is no hope of a cure by chemotherapy for unresectable hepatic metastases, but that there is the possibility of a cure with s-l hepatectomy after HAI-PMC. No significant financial relationships to disclose.

Second-look hepatectomy after 5FU arterial infusion in patients with primary unresectable hepatic colorectal metastases

We treated primary unresectable hepatic colorectal metastases by hepatic arterial chemotherapy (HAC) combined with resection of the tumor. Patients underwent a resection of the primary colorectal tumor and a placement of HAC system, and received a 5-fluorouracil (5FU) administration once a week (320 mg/m(2)/day). Five patients underwent a 'second-look' hepatectomy in this series. Their shrinkage rate of the primary lesion ranged from 80-99%, as seen by computed tomography. The resected liver tumors were characterized as p53-positive and proliferating cell nuclear antigen-positive. The levels of fluorodeoxyuridylate (FdUMP) and thymidylate synthetase inhibition were low in the tumor tissue. These results might reflect a kind of resistance to 5FU therapy. Hepatectomy is one of the possible options to eradicate the residual SFU-resistant component of the malignancy. Our preliminary experience possibly indicates longer survival from combination approach than from HAC alone.

P53 Mutations as a possible predictor of response to chemotherapy in metastatic colorectal cancers

Although intrahepatic infusion therapy with 5-fluorouracil for unresectable colorectal liver metastases may lead to improved overall survival for some patients, it is not clear why a response is not observed in others. Gene alterations in oncogenes or tumor-suppressor genes are critical events in tumor formation, and some of them could play a role in the process of drug resistance. The tumor-suppressor gene p53, which is known to trigger cell arrest or apoptosis in response to DNA damage, is found to be mutated in a wide range of human tumors. The aim of this work is to establish whether a relationship is found between p53 mutations and survival in patients undergoing adjuvant chemotherapy for advanced Dukes' D colorectal cancers. Seventeen tumors from patients treated with 5-fluorouracil regimen via intrahepatic infusion for unresectable colorectal hepatic metastasis were considered. p53 mutations from tumor DNA were detected, after amplification by PCR of exons 5 to 8, by non-radioactive single-strand conformation polymorphism and direct DNA sequencing. Patients with mutated p53 colorectal tumors had short survival, whereas prolonged survival was associated with the presence of wild-type p53 (p = 0.0 19). Our data suggest that mutated p53 colorectal tumors had a weak response, or even no response, to chemotherapeutic treatment. Routine assessment of p53 status would be helpful in selecting patients with only wild-type p53 gene who have a predictably better response to chemotherapy. o 1996 Wilq-Liss, Inc. The outcome of patients with unresectable liver metastasis from colorectal cancer is poor. The median survival time for patients without treatment is estimated to be 6 to 9 months

Serum carcinoembryonic antigen (CEA) correlates with the survival time during 5-FU hepatic arterial infusion chemotherapy for unresectable colorectal hepatic metastases

We investigated whether carcinoembryonic antigen (CEA) could be used to predict the response and survival of patients treated with 5-FU. Between 1984 and 1994, 58 patients with unresectable hepatic metastases from colorectal carcinoma were enrolled in this study. Forty-three patients underwent resection of the primary colorectal malignancy, and a catheter was inserted into the hepatic artery during the operation (HAI group). Fifteen patients received no adjuvant therapy (non-HAI group). Patients with CEA values reduced by greater than or equal to 30% at 2 months after the start of 5-FU infusion had a significantly longer survival period than patients with a decrease of <30%. Terminal cases in CEA reduced by greater than or equal to 30% group revealed that CEA re-elevation was observed at 7 months, and the patients died 8 months later at 15 months. Our findings suggest that serum CEA monitoring is useful for predicting the survival time following 5-FU hepatic arterial infusion.

Percutaneous hepatic venous isolation and extracorporeal charcoal hemoperfusion for high-dose intraarterial chemotherapy in patients with colorectal hepatic metastases.

The results of treating 12 consecutive patients with unresectable colorectal hepatic metastases with a hepatic arterial infusion of high-dose Adriamycin, 100-120 mg/m2, using hepatic venous isolation (HVI) and charcoal hemoperfusion (CHP) are reported herein. Adriamycin was administered over 5-15 min under extracorporeal drug elimination by HVI-CHP. HVI was percutaneously accomplished by either the double-balloon technique using a Fogarty occlusion catheter (8/22F) or a balloon-tipped catheter (16F). During the infusion, isolated hepatic venous blood was filtered by CHP and pumped into the left axillary vein. There were no lethal complications, and good hemodynamic tolerance to HVI-CHP was confirmed. Tumor liquefaction accompanied by a sharp decrease in serum carcinoembryonic antigen levels by more than 50% of pretreatment levels was observed in 6 of the 12 patients 1 month after treatment. Apart from chemical hepatitis, which developed in 11 (92%) of the patients, the Adriamycin toxicities were well controlled following the development of nausea and vomiting in 2 patients (17%), leukopenia < 2,000/mm3 in 3 (25%), and gastric ulcer in 1 (8%). These results indicate that this method is a safe and useful procedure for otherwise hazardous high-dose intra-arterial chemotherapy in patients with unresectable hepatic tumors.