Combined-Modality Treatment for Resectable Metastatic Colorectal Carcinoma to the Liver: Surgical Resection of Hepatic Metastases in Combination With Continuous Infusion of Chemotherapy—An Intergroup Study

2002 ◽  
Vol 20 (6) ◽  
pp. 1499-1505 ◽  
Author(s):  
M. Margaret Kemeny ◽  
Sudeshna Adak ◽  
Bruce Gray ◽  
John S. Macdonald ◽  
Thomas Smith ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Hepatic Resection ◽  
Continuous Infusion ◽  
Median Survival ◽  
Hepatic Metastases ◽  
Combined Modality Treatment ◽  
Long Term Outcome ◽  
Chemotherapy Group ◽  
Time To Recurrence ◽  
Free Rate

PURPOSE: Despite technical improvements that have minimized the morbidity and mortality of hepatic surgery, the long-term outcome of resection of hepatic metastases of colorectal cancer remains poor, with the majority of patients experiencing treatment failure in the liver. Because arterial chemotherapy regimens targeted to the liver have demonstrated high response rates, an intergroup trial of adjuvant therapy for patients undergoing hepatic resection of liver metastases from colorectal cancer was initiated. PATIENTS AND METHODS: Patients with one to three potentially resectable metastases were randomized preoperatively to receive no further therapy (control arm, 56 patients) or postoperative hepatic arterial floxuridine combined with intravenous continuous-infusion fluorouracil (chemotherapy arm, 53 patients). After exclusion of patients identified as ineligible for the planned treatment at the time of surgery, there were 45 control patients and 30 on the chemotherapy arm. The study was powered to evaluate improvement in time to recurrence and hepatic disease-free survival, not overall survival. RESULTS: The 4-year recurrence-free rate was 25% for the control arm and 46% for the chemotherapy group (P = .04). The 4-year liver recurrence-free rate was 43% in the control group and 67% in the chemotherapy group (P = .03). The median survival of the 75 assessable patients was 49 months for the control arm and 63.7 months for the chemotherapy arm (P = .60). The median survival of all 109 patients was 47 months for the control arm compared with 34 months for the chemotherapy arm (P = .19) CONCLUSION: These data demonstrate that adjuvant intra-arterial and intravenous chemotherapy was beneficial in prolonging time to recurrence and pre-venting hepatic recurrence after hepatic resection of colorectal cancer.

Association of DNA repair inhibition and radiofrequency ablation in the treatment of xenografted colorectal cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 215-215
Author(s):  
Flavien Devun ◽  
Julian Biau ◽  
Jian-sheng Sun ◽  
Alban Denys ◽  
Marie Dutreix
Keyword(s):  
Colorectal Cancer ◽  
Dna Repair ◽  
Radiofrequency Ablation ◽  
Median Survival ◽  
Tumor Resection ◽  
Hepatic Metastases ◽  
Colon Adenocarcinoma ◽  
Human Colon ◽  
Heat Sensitivity

215 Background: Most of the patients with advanced colorectal cancer will develop liver metastasis, even after primary tumor resection. Although surgical resection remains the gold standard treatment of hepatic metastases, only few patients are eligible to curative resection. Radiofrequency ablation (RFA) is the most common curative alternative. Dbait are new molecules that inhibit DNA double-strand breaks repair. In vitro, Dbait has shown to increase cell death after hyperthermia. Here, we have assessed the combination of Dbait and RFA in the treatment of human colorectal cancer model xenografted in nude mice. Methods: 98 mice were flank-grafted with HT29 (human colon adenocarcinoma). When tumor reached 500 mm3, mice were sham treated (n=19), treated by Dbait via local injections (n=20), treated by RFA using an incomplete ablation scheme (n=20) or treated by combination of Dbait and RFA (n=39 separated in two Dbait regimens). After RFA, 39 mice were sacrificed for blinded pathological study, and 59 others were followed for survival analysis. Results: Mice treated by RFA-Dbait had significantly longer survival as compared to RFA alone (median survival: 56 vs 39 days, p<0.05) while RFA improved survival as compared to controls (median survival: 39 vs 28 days, p<0.05). Pathological studies of tumor slice have demonstrated significant decrease of tumor area and cancer cell viability in the RFA-Dbait group. Conclusions: While the implication of DNA repair activity in heat sensitivity remains unclear, our results show that the addition of Dbait to RFA enhances the antitumor response in this model and provide an experimental basis for the use of Dbait as an additional therapy to RFA. [Table: see text]

Feasibility of Intraportal Chemotherapy with Fluorouracil and Folinic Acid Immediately after Hepatic Resection for Colorectal Metastases

1995 ◽  
Vol 81 (2) ◽  
pp. 96-101 ◽  
Author(s):  
Paola Bignami ◽  
Roberto Doci ◽  
Fabrizio Montalto ◽  
Susanna Fissi ◽  
Maria Di Bartolomeo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Hepatic Resection ◽  
Folinic Acid ◽  
Postoperative Period ◽  
Systemic Chemotherapy ◽  
Hepatic Metastases ◽  
Systemic Toxicity ◽  
Colorectal Metastases ◽  
Control Group ◽  
Consecutive Series

Background About 50% of recurrence after resection of hepatic metastases from colorectal cancer remain confined to the liver. Adjuvant locoregional treatments could reduce the failure rate, but these treatments have been scantily investigated. Experimental models have shown that both intra-arterial chemotherapy (IAC) and intraportal chemotherapy (IPC) in adjuvant setting were able to reduce metastatic growth, but IPC should be initiated in the immediate postoperative period. Aims To evaluate the feasibility of immediate postoperative IPC of fluorouracil (5-FU) plus folinic acid (FA) in a consecutive series of patients undergoing hepatic resection for metastatic colorectal cancer. Methods Forty-three consecutive patients underwent hepatic resection. The first 25 (Control Group = CG) received only surgery; the latter 18 (Treated Group = TG) were candidate to postoperative IPC of 5-FU 750 mg/m2 plus FA 20 mg/m2/day continuous infusion for 8 days. One patient was not treated owing to bleeding, thus only 17 received the treatment. Results Postoperative morbidity was 14%, equally distributed in both groups. Biochemical hepatic parameters of TG were not statistically different from those of CG. Five patients (29%) developed systemic toxicity: one hematologic grade 4; 3 mucositis grade 3 and one allergic erythema. Three of these patients had been treated by systemic chemotherapy less than one year before. Discussion IPC of 5-FU plus FA in the immediate postoperative period has not yet been tested. The schedule we have investigated neither affected the postoperative outcome, nor influenced hepatic function and regeneration. Systemic toxicity was evident and severe mainly in patients already pretreated by systemic chemotherapy. In these patients, however, toxicity did not affect further outcome. This study confirms the feasibility of immediate intraportal chemotherapy after hepatic resection.

Five-year survival analysis of liver metastasis of colorectal cancer after hepatic resection

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14571-14571
Author(s):  
J. Xu ◽  
Y. Zhong ◽  
J. Fan ◽  
J. Zhou ◽  
J. Zhou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Survival Rate ◽  
Liver Metastasis ◽  
Hepatic Resection ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Operative Therapy ◽  
Metachronous Liver Metastasis ◽  
First Choice

14571 Background: To evaluate the relation between hepatic resecion and survival rate of liver metastasis of colorectal cancer ( LMCC). Methods: Use retrograde case analysis method, 133 cases of LMCC received hepatic resection from 1/1/2000 to 31/12/2005 were included,with attention to the relation between hepatic resection and survival rate. Results: There were 133 cases underwent curative hepatic resection in all 470 LMCC cases, of which 30 cases (30/196,15.3%) in synchronous liver metastasis (SLM) group and 103 cases (103/274,37.6%) in metachronous liver metastasis (MLM) group, P<0.01. Mortality rate related to operation was 3.3%(1/30) in SLM and 1.9%(2/103) in MLM(P<0.05). Until 31/6/2006, all 133 cases were followed-up, 1,3,5 years survival rate and median survival time of SLM (81.0%, 40.3%, 16.5%, 22 months) is similar to that of MLM (88.2%, 49.1%, 31.7%, 25 months, P > 0.05), but the recurrence rate is higher(36.7% vs 20.4%,P=0.03). Compared to 49 cases whose liver metastases focus can be resected but chosen non- operative therapy, 1, 3, 5 years survival rate of 133 resected cases is higher (55.6%, 11.0%, 0 vs 86.2%, 39.2%, 29.4%, P=0.0034). In SLM, 22 cases received I stage resection of the primary colorectal tumor and liver metastasis and 8 cases received liver metastasis resection after the primary surgery (II stage operation). 1, 2, 3 years survival are 90.0% vs 87.5%(P > 0.05),61.4% vs 55.3%(P > 0.05)and 35.4% vs 30.0%(P > 0.05) and the median survival time is 28 months vs 26months(P > 0.05).COX multivariate analysis was used to analyze the prognositic factors. Incision margin =1cm(β=-0.8351,P=0.0363)and reoperation after recurrence(β=- 0.9428,P=0.0411)were protective survival factors, and postoperation recurrence (β=0.6471,P=0.0226) was survival risk factor. Conclusions: Curative hepatic resection is the first choice of liver metastasis of colorectal cancer and can improve survival. No significant financial relationships to disclose.

American Society of Clinical Oncology 2009 Clinical Evidence Review on Radiofrequency Ablation of Hepatic Metastases From Colorectal Cancer

2010 ◽  
Vol 28 (3) ◽  
pp. 493-508 ◽  
Author(s):  
Sandra L. Wong ◽  
Pamela B. Mangu ◽  
Michael A. Choti ◽  
Todd S. Crocenzi ◽  
Gerald D. Dodd ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Radiofrequency Ablation ◽  
Hepatic Resection ◽  
Clinical Oncology ◽  
Clinical Evidence ◽  
Hepatic Metastases ◽  
Disease Free Survival ◽  
Cochrane Collaboration ◽  
Evidence Review ◽  
American Society

PurposeTo review the evidence about the efficacy and utility of radiofrequency ablation (RFA) for hepatic metastases from colorectal cancer (CRHM).MethodsThe American Society of Clinical Oncology (ASCO) convened a panel to conduct and analyze a comprehensive systematic review of the RFA literature from Medline and the Cochrane Collaboration Library.ResultsBecause data were considered insufficient to form the basis of a practice guideline, ASCO has instead published a clinical evidence review. The evidence is from single-arm, retrospective, and prospective trials. No randomized controlled trials have been included. The following three clinical issues were considered by the panel: the efficacy of surgical hepatic resection versus RFA for resectable tumors; the utility of RFA for unresectable tumors; and RFA approaches (open, laparoscopic, or percutaneous). Evidence suggests that hepatic resection improves overall survival (OS), particularly for patients with resectable tumors without extrahepatic disease. Careful patient and tumor selection is discussed at length in the literature. RFA investigators report a wide variability in the 5-year survival rate (14% to 55%) and local tumor recurrence rate (3.6% to 60%). The reported mortality rate was low (0% to 2%), and the major complications rate was commonly reported to be between 6% and 9%. RFA is currently performed with all three approaches.ConclusionThere is a compelling need for more research to determine the efficacy and utility of RFA to increase local recurrence-free, progression-free, and disease-free survival as well as OS for patients with CRHM. Clinical trials have established that hepatic resection can improve OS for patients with resectable CRHM.

Randomized trial of hepatic arterial floxuridine, mitomycin, and carmustine versus floxuridine alone in previously treated patients with liver metastases from colorectal cancer.

1993 ◽  
Vol 11 (2) ◽  
pp. 330-335 ◽  
Author(s):  
N Kemeny ◽  
A Cohen ◽  
K Seiter ◽  
J A Conti ◽  
E R Sigurdson ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Therapy ◽  
Median Survival ◽  
Systemic Chemotherapy ◽  
Response Rate ◽  
Hepatic Metastases ◽  
Prior Therapy ◽  
Significant Difference ◽  
Previously Treated Patients ◽  
Previously Treated

PURPOSE This study was designed to determine if hepatic arterial therapy with floxuridine (F), mitomycin, and carmustine (BCNU) (FMB) is superior to hepatic arterial therapy with F alone in previously treated patients with hepatic metastases from colorectal cancer. PATIENTS AND METHODS Ninety-five patients were randomized to intrahepatic FMB versus intrahepatic F. All patients had tumor progression after systemic chemotherapy (either therapeutic or adjuvant). RESULTS There was no significant difference in response rate (47% FMB v 33% F; P = .17). Median survival was similar in the two groups, 19.1 months for the FMB group compared with 14.0 months for the F group (P = .23). The overall median survival was 16.8 months. In patients who received prior adjuvant therapy, there was no difference between the two groups, but response rate was high in both (50% FMB v 62% F). The response rate for all patients who had received only prior adjuvant therapy versus all those who had received prior therapy for metastatic disease was 57% and 35%, respectively (P = .066). In the subset of patients whose disease had progressed with prior systemic chemotherapy, the response rate to FMB was greater than that to F (47% v 23%; P = .035). CONCLUSION The overall partial response rate of 39% and the overall survival of 16.8 months from initiation of intrahepatitis therapy show that hepatic arterial therapy is a reasonable treatment option for patients whose tumor does not respond to systemic therapy or whose disease progresses after adjuvant therapy for colorectal cancer.

Intrahepatic Chemotherapy with Floxuridine, Leucovorin and Dexamethasone in Continuous Infusion and Mitomycin-c Bolus in Unresectable Hepatic Metastases from Colorectal Cancer: A Phase II Study

1999 ◽  
Vol 85 (6) ◽  
pp. 473-477 ◽  
Author(s):  
Maurizio Bertuccelli ◽  
Alfredo Falcone ◽  
Silvana Campoccia ◽  
Monica Conti ◽  
Isa Brunetti ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Continuous Infusion ◽  
Mitomycin C ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Hepatic Metastases

Outcomes after a Hepatic Resection for Multiple Hepatic Metastases from Colorectal Cancer

2008 ◽  
Vol 24 (2) ◽  
pp. 100 ◽  
Author(s):  
Pyong Wha Choi ◽  
Hee Cheol Kim ◽  
Sang Hun Jung ◽  
Dae Dong Kim ◽  
In Ja Park ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Hepatic Resection ◽  
Hepatic Metastases

Analysis of the p53/BAX Pathway in Colorectal Cancer: Low BAX Is a Negative Prognostic Factor in Patients With Resected Liver Metastases

1999 ◽  
Vol 17 (5) ◽  
pp. 1364-1364 ◽  
Author(s):  
Isrid Sturm ◽  
Claus-Henning Köhne ◽  
Gerhard Wolff ◽  
Henrik Petrowsky ◽  
Timo Hillebrand ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Relative Risk ◽  
Protein Expression ◽  
Liver Metastases ◽  
Prognostic Marker ◽  
Median Survival ◽  
Prognostic Value ◽  
Hepatic Metastases ◽  
Wild Type ◽  
Frameshift Mutations

PURPOSE: To determine the prognostic value of the central downstream apoptosis effector BAX in relation to its upstream regulator p53 in R0-resected hepatic metastases of colorectal cancer. PATIENTS AND METHODS: Retrospective analysis of 41 patients who underwent potentially curative resection of liver metastases from colorectal cancer was performed. Tumor DNA was screened for p53 mutations by single-stranded conformational polymorphism polymerase chain reaction and for BAX frameshift mutations by fragment length analysis. Protein expression of BAX, p21, and p53 was investigated by immunohistochemistry. RESULTS: Overall median survival was 40.2 months. Tumors with BAX frameshift mutations were considered microsatellite mutator phenotype–positive and were excluded from further prognostic analyses. Patients with high BAX protein expression had a median survival of 53.6 months compared with 35.4 months for patients with low BAX expression (P < .05). The negative prognostic value of low BAX expression was more evident in those patients with wild-type p53 (median survival, 54.0 v 23.3 months for BAX-negative tumors; P < .01). Low BAX expression was an independent negative prognostic marker in multivariate regression analysis for all patients independent of the p53 status (relative risk, 3.03, P = .03), especially for p53 wild-type tumors (relative risk, 8.21; P = .0095). CONCLUSION: We conclude that low BAX expression is an independent negative prognostic marker in patients with hepatic metastases of colorectal cancer. The best survival was seen in patients with an intact p53-to-BAX pathway; ie, wild-type p53- and BAX-positive tumors. Thus, analysis of apoptosis signaling pathways (here, p53 in concert with its downstream death effector, BAX) might yield more prognostic power in future studies as compared with analysis of single genes such as p53 alone.

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