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Mauri G, Monfardini L, Garnero A, Zampino MG, Orsi F, Della Vigna P, Bonomo G, Varano GM, Busso M, Gazzera C, Fonio P, Veltri A, Calandri M. Optimizing Loco Regional Management of Oligometastatic Colorectal Cancer: Technical Aspects and Biomarkers, Two Sides of the Same Coin. Cancers (Basel) 2021; 13:2617. [PMID: 34073585 PMCID: PMC8198296 DOI: 10.3390/cancers13112617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 05/21/2021] [Accepted: 05/22/2021] [Indexed: 11/23/2022] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide and has a high rate of metastatic disease which is the main cause of CRC-related death. Oligometastatic disease is a clinical condition recently included in ESMO guidelines that can benefit from a more aggressive locoregional approach. This review focuses the attention on colorectal liver metastases (CRLM) and highlights recommendations and therapeutic locoregional strategies drawn from the current literature and consensus conferences. The different percutaneous therapies (radiofrequency ablation, microwave ablation, irreversible electroporation) as well as trans-arterial approaches (chemoembolization and radioembolization) are discussed. Ablation margins, the choice of the imaging guidance as well as characteristics of the different ablation techniques and other technical aspects are analyzed. A specific attention is then paid to the increasing role of biomarkers (in particular molecular profiling) and their role in the selection of the proper treatment for the right patient. In conclusion, in this review an up-to-date state of the art of the application of locoregional treatments on CRLM is provided, highlighting both technical aspects and the role of biomarkers, two sides of the same coin.
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Affiliation(s)
- Giovanni Mauri
- Divisione di Radiologia Interventistica, Istituto Europeo di Oncologia, IRCCS, 20141 Milan, Italy; (G.M.); (F.O.); (P.D.V.); (G.B.); (G.M.V.)
- Dipartimento di Oncologia ed Emato-Oncologia, Università degli Studi di Milano, 20122 Milan, Italy
| | | | - Andrea Garnero
- Radiodiagnostica 1 U. A.O.U., San Luigi Gonzaga di Orbassano, Regione Gonzole 10, 10043 Orbassano, Torino, Italy; (A.G.); (M.B.); (A.V.); (M.C.)
- Department of Surgical Sciences, University of Turin, 10124 Torino, Italy;
| | - Maria Giulia Zampino
- Divisione di Oncologia Medica Gastrointestinale e Tumori Neuroendocrini, Istituto Europeo di Oncologia, IRCCS, 20141 Milan, Italy;
| | - Franco Orsi
- Divisione di Radiologia Interventistica, Istituto Europeo di Oncologia, IRCCS, 20141 Milan, Italy; (G.M.); (F.O.); (P.D.V.); (G.B.); (G.M.V.)
| | - Paolo Della Vigna
- Divisione di Radiologia Interventistica, Istituto Europeo di Oncologia, IRCCS, 20141 Milan, Italy; (G.M.); (F.O.); (P.D.V.); (G.B.); (G.M.V.)
| | - Guido Bonomo
- Divisione di Radiologia Interventistica, Istituto Europeo di Oncologia, IRCCS, 20141 Milan, Italy; (G.M.); (F.O.); (P.D.V.); (G.B.); (G.M.V.)
| | - Gianluca Maria Varano
- Divisione di Radiologia Interventistica, Istituto Europeo di Oncologia, IRCCS, 20141 Milan, Italy; (G.M.); (F.O.); (P.D.V.); (G.B.); (G.M.V.)
| | - Marco Busso
- Radiodiagnostica 1 U. A.O.U., San Luigi Gonzaga di Orbassano, Regione Gonzole 10, 10043 Orbassano, Torino, Italy; (A.G.); (M.B.); (A.V.); (M.C.)
| | - Carlo Gazzera
- Radiodiagnostica 1 U, A.O.U. Città della Scienza e della Salute, 10126 Torino, Italy;
| | - Paolo Fonio
- Department of Surgical Sciences, University of Turin, 10124 Torino, Italy;
- Radiodiagnostica 1 U, A.O.U. Città della Scienza e della Salute, 10126 Torino, Italy;
| | - Andrea Veltri
- Radiodiagnostica 1 U. A.O.U., San Luigi Gonzaga di Orbassano, Regione Gonzole 10, 10043 Orbassano, Torino, Italy; (A.G.); (M.B.); (A.V.); (M.C.)
- Department of Oncology, University of Turin, 10124 Torino, Italy
| | - Marco Calandri
- Radiodiagnostica 1 U. A.O.U., San Luigi Gonzaga di Orbassano, Regione Gonzole 10, 10043 Orbassano, Torino, Italy; (A.G.); (M.B.); (A.V.); (M.C.)
- Department of Oncology, University of Turin, 10124 Torino, Italy
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Chapelle N, Matysiak-Budnik T, Douane F, Metairie S, Rougier P, Touchefeu Y. Hepatic arterial infusion in the management of colorectal cancer liver metastasis: Current and future perspectives. Dig Liver Dis 2018; 50:220-225. [PMID: 29290599 DOI: 10.1016/j.dld.2017.12.004] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2017] [Revised: 12/04/2017] [Accepted: 12/06/2017] [Indexed: 12/11/2022]
Abstract
The technique of hepatic arterial infusion (HAI) for the treatment of liver metastases from colorectal cancer has been developed over more than 30 years. Although the indications and protocols for this technique have evolved with time, HAI is not routinely performed in clinical practice. Studies have been heterogeneous, with different regimens of intra-arterial drugs, associated or not with systemic chemotherapy, and with unconvincing outcomes. Technical difficulties for catheter placement have limited the implementation of this method in routine practice. The aim of this review is to present recent studies, highlighting technical improvements and promising combinations of oxaliplatin-based HAI with systemic treatments. HAI is being investigated in both the metastatic setting - in the first line and beyond - and in the adjuvant setting, and we will discuss its potential place in current and future patient management.
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Affiliation(s)
- Nicolas Chapelle
- University of Nantes, Nantes, France; Nantes University Hospital, Hôtel-Dieu, Digestive Disease Institute, Gastro-Enterology, Hepatology and Digestive Oncology Unit, France.
| | - Tamara Matysiak-Budnik
- University of Nantes, Nantes, France; Nantes University Hospital, Hôtel-Dieu, Digestive Disease Institute, Gastro-Enterology, Hepatology and Digestive Oncology Unit, France
| | | | | | - Philippe Rougier
- Nantes University Hospital, Hôtel-Dieu, Digestive Disease Institute, Gastro-Enterology, Hepatology and Digestive Oncology Unit, France
| | - Yann Touchefeu
- Nantes University Hospital, Hôtel-Dieu, Digestive Disease Institute, Gastro-Enterology, Hepatology and Digestive Oncology Unit, France
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Chimiothérapie intra-artérielle hépatique, chimioembolisation et radioembolisation : un apport important pour le traitement des métastases hépatiques des cancers colorectaux. ONCOLOGIE 2014. [DOI: 10.1007/s10269-014-2468-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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Sinn M, Nicolaou A, Ricke J, Podrabsky P, Seehofer D, Gebauer B, Pech M, Neuhaus P, Dörken B, Riess H, Hildebrandt B. Interventionally implanted port catheter systems for hepatic arterial infusion of chemotherapy in patients with primary liver cancer: a phase II-study (NCT00356161). BMC Gastroenterol 2013; 13:125. [PMID: 23927554 PMCID: PMC3751555 DOI: 10.1186/1471-230x-13-125] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2012] [Accepted: 08/01/2013] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Hepatic arterial infusion (HAI) of chemotherapy requires the implantation of a transcatheter application system which is traditionally performed by surgery. This procedure, but particularly the adjacent drug application via pump or port is often hampered by specific complications and device failure. Interventionally implanted port catheter systems (IIPCS) facilitate the commencement of HAI without need for laparatomy, and are associated with favorable complication rates. We here present an evaluation of the most important technical endpoints associated with the use of IIPCS for HAI in patients with primary liver cancers. METHODS 70 patients (pts) with hepatocellular (HCC, n=33) and biliary tract cancer (BTC, n=37) were enrolled into a phase II -study. Of those, n=43 had recurrent disease and n=31 suffered from liver-predominant UICC-stage IVb. All pts were provided with IIPCSs before being treated with biweekly, intraarterial chemotherapy (oxaliplatin, 5-Flourouracil, folinic acid). The primary objective of the trial was defined as evaluation of device-related complications and port duration. RESULTS Implantation of port catheters was successful in all patients. Mean treatment duration was 5.8 months, and median duration of port patency was not reached. Disease-progression was the most common reason for treatment discontinuation (44 pts., 63%), followed by chemotherapy-related toxicity (12 pts., 17%), and irreversible device failure (5 pts., 7%). A total of 28 port complications occurred in 21 pts (30%). No unexpected complications were observed. CONCLUSIONS HAI via interventionally implanted port catheters can be safely applied to patients with primary liver tumors far advanced or/and pretreated.
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Affiliation(s)
- Marianne Sinn
- CharitéCentrum für Tumormedizin, Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie, Campus Virchow Klinikum, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, D-13344 Berlin, Germany
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Benhaim L, Goéré D, Deschamps F, Dumont F, Bonnet S, Honoré C, Malka D, Boige V, De Baere T, Elias D. Placement of an arterial hepatic catheter after a major hepatectomy for colorectal liver metastases: Is this safe? EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2013; 39:640-7. [DOI: 10.1016/j.ejso.2013.02.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2012] [Revised: 12/20/2012] [Accepted: 02/01/2013] [Indexed: 11/25/2022]
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Baek YH, Kim KT, Lee SW, Jeong JS, Park BH, Nam KJ, Cho JH, Kim YH, Roh YH, Lee HS, Choi YM, Han SY. Efficacy of hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma. World J Gastroenterol 2012; 18:3426-34. [PMID: 22807613 PMCID: PMC3396196 DOI: 10.3748/wjg.v18.i26.3426] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2011] [Revised: 02/20/2012] [Accepted: 02/26/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the efficacy of hepatic arterial infusion chemotherapy (HAIC) using floxuridine (FUDR) in patients with advanced hepatocellular carcinoma (HCC) confined to the liver.
METHODS: Thirty-four patients who had advanced HCC with unresectability or unsuccessful previous therapy in the absence of extrahepatic metastasis were treated with intra-arterial FUDR chemotherapy at our hospital between March 2005 and May 2008. Among the 34 patients, 9 patients were classified as Child class C, and 18 patients had portal vein tumor thrombus (PVTT). One course of chemotherapy consisted of continuous infusion of FUDR (0.3 mg/kg during day 1-14) and dexamethasone (10 mg on day 1, 4, 7 and 11), and this treatment was repeated every 28 d.
RESULTS: Two patients (5.9%) displayed a complete response, and 12 patients (35.3%) had a partial response. The tumor control rate was 61.8%. The median overall survival times were 15.3 mo, 12.4 mo and 4.3 mo for the patients who were classified as Child class A, Child class B and Child class C, respectively (P = 0.0392). The progression-free survival was 12.9 mo, 7.7 mo and 2.6 mo for the patients who were classified as Child class A, Child class B and Child class C, respectively (P = 0.0443). The cumulative survival differed significantly according to the Child-Pugh classification and the presence of PVTT. In addition to hepatic reserve capacity and PVTT, the extent of HCC was an independent factor in determining a poor prognosis. The most common adverse reactions to HAIC were mucositis, diarrhea and peptic ulcer disease, but most of these complications were improved by medical treatment and/or a delay of HAIC.
CONCLUSION: The present study demonstrates that intra-arterial FUDR chemotherapy is a safe and effective treatment for advanced HCC that is recalcitrant to other therapeutic modalities, even in patients with advanced cirrhosis.
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Modern insights into hepatic arterial infusion for liver metastases from colorectal cancer. Eur J Cancer 2011; 47:2681-90. [PMID: 21783358 DOI: 10.1016/j.ejca.2011.06.037] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2010] [Revised: 05/05/2011] [Accepted: 06/17/2011] [Indexed: 01/21/2023]
Abstract
Hepatic arterial infusion (HAI) selectively achieves high drug exposure of liver metastases from colorectal cancer. Such pharmacologic advantage has doubled the response rate of liver metastases on fluoropyrimidines (FP) delivered as HAI rather than intravenously, in a meta-analysis of randomised clinical trials (RCT). However, the improvement in antitumour efficacy did not consistently translate into any significant survival advantage across all randomised studies. However, the results of this meta-analysis should be cautiously interpreted due to the heterogeneity of the studies, inadequate study designs, obsolete therapy and high rate of early treatment discontinuation due to HAI technical failures or hepato-biliary toxicity. Most studies actually were performed before year 2000 and did not integrate the considerable progresses accomplished in the management of CRC, such as multidrug regimens instead of single agent FP and secondary resection of metastases, a major contributing factor for prolonged survival. Furthermore, the systemic exposure of patients given HAI was low without concomitant IV therapy, facilitating extra-hepatic relapses. The role of HAI in liver metastases from CRC should, therefore, be revisited, using modern multidisciplinary therapeutic approaches and appropriate study designs. Recommendations for the design of future RCTs exploring HAI are provided.
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Percutaneous femoral implantation of an arterial port catheter for intraarterial chemotherapy: feasibility and predictive factors of long-term functionality. J Vasc Interv Radiol 2011; 21:1681-8. [PMID: 21029950 DOI: 10.1016/j.jvir.2010.08.003] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2009] [Revised: 07/08/2010] [Accepted: 08/02/2010] [Indexed: 02/07/2023] Open
Abstract
PURPOSE To evaluate the feasibility, functionality, and dysfunctions of an arterial port catheter implanted via the femoral artery. MATERIALS AND METHODS 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. RESULTS 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. CONCLUSIONS 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.
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Deschamps F, Elias D, Goere D, Malka D, Ducreux M, Boige V, Auperin A, de Baere T. Intra-arterial hepatic chemotherapy: a comparison of percutaneous versus surgical implantation of port-catheters. Cardiovasc Intervent Radiol 2010; 34:973-9. [PMID: 20936286 DOI: 10.1007/s00270-010-9996-6] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2010] [Accepted: 09/09/2010] [Indexed: 12/22/2022]
Abstract
PURPOSE To compare retrospectively the safety and efficacy of percutaneous and surgical implantations of port-catheters for intra-arterial hepatic chemotherapy (IAHC). MATERIALS AND METHODS Between January 2004 and December 2008, 126 consecutive patients (mean age 58 years) suffering from liver colorectal metastases were referred for intra-arterial hepatic chemotherapy (IAHC). Port-catheters were percutaneously implanted (P) through femoral access with the patient under conscious sedation when no other surgery was planned or were surgically implanted (S) when laparotomy was performed for another purpose. We report the implantation success rate, primary functionality, functionality after revision, and complications of IAHC. RESULTS The success rates of implantation were 97% (n = 65 of 67) for P and 98% (n = 58 of 59) for S. One hundred eleven patients received IAHC in our institution (n = 56P and n = 55S). Primary functionality was the same for P and S (4.80 vs. 4.82 courses), but functionality after revision was significantly higher for P (9.18 vs. 5.95 courses, p = 0.004) than for S. Forty-five complications occurred during 516 courses for P and 28 complications occurred during 331 courses for S. The rates of discontinuation of IAHC linked to complications of the port-catheters were 21% (n = 12 of 56) for P and 34% (n = 19 of 55) for S. CONCLUSION Overall, significantly better functionality and similar complication rates occurred after P versus S port-catheters.
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Affiliation(s)
- F Deschamps
- Department of Interventional Radiology, Gustave Roussy Institut, Villejuif, France.
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Carnaghi C, Santoro A, Rimassa L, Doci R, Rosati R, Pedicini V, Gullo G, Zuradelli M, Abbadessa G, Morenghi E, Marcon I, Garassino I. The efficacy of hybrid chemotherapy with intravenous oxaliplatin and folinic acid and intra-hepatic infusion of 5-fluorouracil in patients with colorectal liver metastases: a phase II study. Invest New Drugs 2007; 25:479-85. [PMID: 17492399 DOI: 10.1007/s10637-007-9048-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2007] [Accepted: 03/20/2007] [Indexed: 12/27/2022]
Abstract
Intra-arterial chemotherapy in patients with liver metastases from colorectal cancer has some limitations such as hepatic toxicity and extra-hepatic progression. With the aim of overcoming these limitations, a phase II trial was designed to assess the efficacy and tolerability of a hybrid chemotherapy regimen with systemic infusion of oxaliplatin and folinic acid associated with intra-arterial 5-fluorouracil. Thirty-nine patients with colorectal liver metastases were recruited. The median age was 59 years, 30 patients (77%) had synchronous metastases, and half of the patients were chemo-naive. A total of 313 chemotherapy cycles were administered (median number 8). Treatment was well tolerated and hepatic toxicity negligible. Out of 34 evaluable patients an ORR of 41%. was observed. Eight patients (21%) underwent radical liver surgery. The median time to progression (TTP) was 10 months (range 2-63) and the median overall survival (OS) 21 months (range 6-63). Extra-hepatic progression was observed in six patients. Our results suggest that this regimen is active even if technical complications are frequent. Our aim to reduce hepatic toxicity and extra-hepatic progression was reached.
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Affiliation(s)
- Carlo Carnaghi
- Department of Medical Oncology and Hematology, Istituto Clinico Humanitas, Via Manzoni 56, 20089 Rozzano (Milano), Italy.
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Vogl TJ, Zangos S, Eichler K, Yakoub D, Nabil M. Colorectal liver metastases: regional chemotherapy via transarterial chemoembolization (TACE) and hepatic chemoperfusion: an update. Eur Radiol 2006; 17:1025-34. [PMID: 16944163 DOI: 10.1007/s00330-006-0372-5] [Citation(s) in RCA: 98] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2006] [Revised: 05/26/2006] [Accepted: 06/19/2006] [Indexed: 01/15/2023]
Abstract
Liver metastasis is one of the main problems encountered in colorectal cancer management as the liver is the most common metastatic site. Several treatment options are available, among which transarterial chemotherapy has proved effective in achieving some local tumour control, improving the quality of life through symptomatic control as well as survival time. The present paper is intended to provide an overview of the techniques, indications and results of regional chemotherapy, which comprises transarterial chemoembolization (TACE) and chemoperfusion. This treatment approach has symptomatic, palliative, adjuvant and potentially curative objectives. We reviewed the studies involving TACE and chemoperfusion of colorectal liver metastases during the last few years to update the previous reviews published on this subject. The results achieved were so variable, due to the variations in patient selection criteria and regimens used between the different studies. The median survival ranged from 9 to 62 months and the morphological response ranged from 14 to 76%. Technical aspects, results, and complications of this modality will be demonstrated with a detailed analysis and comments.
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Affiliation(s)
- Thomas J Vogl
- Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Clinic, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany.
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Vogl TJ, Mack M, Eichler K, Lehnert T, Nabil M. Effect of laser-induced thermotherapy on liver metastases. Expert Rev Anticancer Ther 2006; 6:769-74. [PMID: 16759166 DOI: 10.1586/14737140.6.5.769] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Laser-induced thermotherapy, or laser ablation, is an established minimally invasive percutaneous technique of tumor ablation. It is performed routinely in hepatic tumors and in other indications. Most patients treated with laser-induced thermotherapy suffer from liver metastases from primary tumors, particularly colorectal cancer. In this review, the local control rate, including morphological response and local recurrence, is evaluated. Survival data, including median survival time and 1-, 2- and 3-year survival, are discussed; treatment complications are also explored. The method of treatment performance and evaluation, results, and the authors' views on the current status of treatment are outlined.
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Affiliation(s)
- Thomas J Vogl
- Institute of Diagnostic and Interventional Radiology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
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