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

Kemeny, M. Margaret; Adak, Sudeshna; Gray, Bruce N.; Macdonald, John S.; Smith, Thomas J.; Lipsitz, Stuart R.; Sigurdson, Elin R.; O’Dwyer, Peter J.; Benson, Al B.

doi:10.1200/jco.2002.20.6.1499

Cited by 222 publications

(137 citation statements)

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“…Presently, there is no standard guideline for CLM patients after liver resection. There are a few randomised clinical trials published that evaluate the survival effects of HAI of FUdR and/or intravenous systemic chemotherapy after hepatic resection (Lygidakis et al, 1995;Asahara et al, 1998;Lorenz et al, 1998;Lorenz and Muller, 2000;Tono et al, 2000;Kemeny et al, 2002;Kemeny and Gonen, 2005;Portier et al, 2006). Most of these studies, however, have limited statistical power due to small sample sizes (less than 100 subjects) or slow accrual.…”

Section: Discussionmentioning

confidence: 99%

“…Most of these studies, however, have limited statistical power due to small sample sizes (less than 100 subjects) or slow accrual. Among five studies in which HAI with FUdR chemotherapy was compared with resection alone, disease-free survival was reported to be better in patients with adjuvant HAI of FUdR after resection in three studies (Lygidakis et al, 1995;Asahara et al, 1998;Kemeny et al, 2002). An overall survival benefit was observed in two of these studies (Lygidakis et al, 1995;Asahara et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, while systemic chemotherapy is frequently administered after resection, the optimal regimen and its contributions to survival outcomes are inconclusive (Kemeny et al, 2002;Portier et al, 2006;Yoshida et al, 2006). We, therefore, conducted a population-based study to investigate the impact of demographic, clinical, and treatment characteristics on survival after hepatic resection for CLMs.…”

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Predictors of survival after hepatic resection among patients with colorectal liver metastasis

et al. 2007

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Studies suggest improved survival following resection of colorectal cancer liver metastases (CLMs). We investigated predictors of survival among patients with CLM who underwent hepatic resection using the SEER-Medicare database to identify patients X65 years diagnosed with CLM, 1991CLM, -2003, who underwent hepatectomy. Cox proportional hazards models were used to identify factors associated with survival after hepatectomy. Of 923 patients with CLM who underwent hepatectomy, 514 were stages I -III and developed CLM46 months after diagnosis (metachronous), and 409 were stage IV with CLM at diagnosis (synchronous). From the date of hepatectomy, 5 year survival was 22%; younger age, being married, female gender, surgery in an NCI-designated cancer centre, fewer comorbidities, fewer positive lymph nodes, and lower grade were associated with improved survival. Both 5-fluorouracil (5FU)-based chemotherapy and hepatic arterial infusion (HAI) of floxuridine-based chemotherapy following hepatectomy improved survival (HR ¼ 0.62, 95% CI: 0.50 -0.78; HR ¼ 0.51, 95% CI: 0.28 -0.97, respectively) in the synchronous, but not metachronous, group. The HR for overall mortality was higher in hospitals with a high vs low procedure volume (0.75, 95% CI: 0.58 -0.94). A substantial subgroup of patients with CLM who undergo hepatectomy experiences long-term survival. High hospital procedure volume and use of 5FU-based or HAI-based chemotherapy after resection were associated with improved prognosis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Predictors of survival after hepatic resection among patients with colorectal liver metastasis

et al. 2007

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“…Postsurgical chemotherapy is used; however, its effectiveness needs to be determined. 1,2,32,33 Infusion of 5-fluorouracil directly into the hepatic artery has increased the clinical response rate. 33 However, its use is limited by severe complications, and there is no overall long-term survival benefit so far.…”

Section: Discussionmentioning

confidence: 99%

Induction of antigen-specific CD4- and CD8-mediated T-cell responses by fusions of autologous dendritic cells and metastatic colorectal cancer cells

et al. 2005

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Human metastatic colorectal carcinomas (CRCAs) express carcinoembryonic antigen (CEA) and/or MUC1 tumor-associated antigens as potential targets for the induction of active specific immunity. In the present study, freshly isolated metastatic CRCA cells were successfully fused with immature autologous human monocyte-derived dendritic cells (DCs). The created heterokaryons (DC/CRCA) coexpress the CRCA-derived CEA and MUC1 antigens and DC-derived MHC class II and costimulatory molecules. The fusion cells were functional in stimulating the proliferation of autologous T cells. In addition, both CD4 1 and CD81 T cells were activated by fusion cells, as demonstrated by the production of high levels of IFN-c. More importantly, coculture of fusion cells with patient-derived peripheral blood mononuclear cells (PBMCs) resulted in the induction of antigen-specific cytotoxic T lymphocytes (CTLs). CTLs were effective at lysis of not only autologous CRCA cells but also the CEA and/or MUC1-positive and HLA partially matched target cells. Antigen-specific CTL responses were confirmed by tetrameric analysis. Coculture of PBMCs with fusion cells resulted in increased frequency of CEAand MUC1-specific CTLs simultaneously. Taken together, these results indicate that freshly isolated human metastatic CRCA cells expressing the CEA and/or MUC1 may represent a potential partner for the creation of DC/tumor fusion cells targeting induction of antigen-specific CTL responses. Our report demonstrates the simultaneous induction of CRCA-specific CTL responses restricted by HLA-A2 and -A24. ' 2005 Wiley-Liss, Inc.Key words: dendritic cell; cytotoxic T lymphocyte; cytokine; MHC; tumor immunity CRCA is one of the most common malignancies and often metastasizes to the liver, lymph nodes and lung. At diagnosis, 15-20% of patients with CRCA have presented with metastatic liver disease. 1 Surgical resection is the treatment of choice for colorectal liver metastasis. However, tumor recurrence in the liver occurs in up to 60% of patients who undergo surgical resection.2 Therefore, therapy to prevent the recurrence of liver metastasis is needed. In this context, immunotherapy represents a potential approach for the prevention of recurrence of colorectal metastases. In support of the immunotherapy approach is the finding that CRCA cells overexpress the CEA, MUC1, Ep-CAM and Her-2/ neu antigens.3-8 CRCA cells also express mutated forms of the p53 and adenomatous polyposis coli 5,9 tumor-suppressor genes. In fact, there is increasing evidence that tumor-reactive and antigenspecific CTLs exist in patients with CRCA and have been expanded from tumor-infiltrating lymphocytes and PBMCs in CRCA patients. 7,8,10 These results indicate that active specific immunotherapy can be developed in patients with metastatic CRCA.DCs are potent professional APCs capable of priming naive T cells and inducing antigen-specific CTLs.11,12 DCs derive their potency from the expression of MHC class I and II, and costimulatory molecules that provide secondary signals for the acti...

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“…It delivers the dose directly to the tumor on the premise that macrometastases (Ͼ0.5 cm) derive Ͼ80% of their blood supply from the hepatic artery, in contrast to hepatocytes, which are supplied by the portal circulation [70]. Table 3 shows results from randomized studies of HAI chemotherapy [73][74][75][76][77]. A systematic review of seven studies involving 592 patients receiving HAI chemotherapy in the adjuvant setting did not find any OS benefit (HR, 1.089; 95% CI, 0.887-1.334) [71].…”

Section: The Role Of Local Treatments For Liver Metastasesmentioning

confidence: 99%

Curative Strategies for Liver Metastases from Colorectal Cancer: A Review

et al. 2012

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After completing this course, the reader will be able to:1. Among patients with liver metastases from colorectal cancer, determine which would benefit from liver resection, the timing for surgery, and an appropriate perioperative chemotherapy regimen.2. Determine which patients are candidates for perioperative chemotherapy and the appropriate timing of chemotherapy, and describe the relevant toxicities and their impact on morbidity and mortality.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME ABSTRACTColorectal cancer is a very common malignancy and frequently manifests with liver metastases, often without other systemic disease. Margin-negative (R0) resection of limited metastatic disease, in conjunction with systemic antineoplastic agents, is the primary treatment strategy, leading to long survival times for appropriately selected patients. There is debate over whether the primary tumor and secondaries should be removed at the same time or in a staged manner. Chemotherapy is effective in converting some unresectable liver metastases into resectable disease, with a correspondingly better survival outcome. However, the ideal chemotherapy with or without biological agents and when it should be administered in the course of treatment are uncertain. The role of neoadjuvant chemotherapy in initially resectable liver metastases is controversial. Local delivery of chemotherapy, with and without surgery, can lead to longer disease-free survival times, but it is not routinely used with curative intent. This review focuses on methods to maximize the disease-free survival interval using chemotherapy, surgery, and local methods. The Oncologist 2012;17:201-211

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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

Abstract: 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.

Cited by 222 publications

References 20 publications

Predictors of survival after hepatic resection among patients with colorectal liver metastasis

Predictors of survival after hepatic resection among patients with colorectal liver metastasis

Induction of antigen-specific CD4- and CD8-mediated T-cell responses by fusions of autologous dendritic cells and metastatic colorectal cancer cells

Curative Strategies for Liver Metastases from Colorectal Cancer: A Review

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