Liver-dominant Disease Research Articles

Efficacy and tolerability of second-line intra-arterial 5FU or mitomycine C after intra-arterial oxaliplatin failure in patients with colorectal cancer and unresectable liver metastases.

e15061 Background: Hepatic arterial infusion (HAI) chemotherapy of oxaliplatin is an option in the management of metastatic colorectal cancers (mCRC) with dominant liver metastases (LM). However, despite prolonged control some patients (pts) experience disease progression or dose-limiting toxicity. In these cases, the use of a second-line HAI with an alternative drug has never been reported to date. This pilot study is evaluating treatment outcomes in pts receiving HAI of 5-FU or mitomycine C (MMC), after HAI oxaliplatin (HAI-ox) in heavily pretreated pts. Methods: 24 pts with unresectable mCRC were enrolled, metastases were exclusively or dominant in the liver (≥80% of overall total metastatic tumour burden in the liver), all pts received prior HAI-ox. They were treated with either biweekly HAI 5-FU with dose ranging from 600 to 1200mg/m2 over 2 hours (17 patients), or monthly MMC 7mg/m2 over 1 hour (7 patients). Results: Mean age was 62 years. 42% of pts (10/24) had extra-hepatic metastases and 75% (18/24) had 8 LM or more. Including prior HAI-ox, pts had previously received a median of 3 prior lines of treatment (range:2 to 5). Previous HAI-ox was stopped for toxicity in 17 pts (allergy, neuropathy or abdominal pain) or progression in 7 pts. At baseline, 62% of pts had progressive disease. All pts but one received concomitant systemic therapies together with HAI 5FU or MMC. The overall RECIST V1.1 objective response rate and disease control rate were respectively 42% (10/24) and 71% (17/24). Median progression free survival (PFS) and overall survival (OS) were respectively 5.6 and 25.8 months; hepatic PFS was 8.5 months. 3 pts benefited from further curative intent treatments after 2nd line HAI (2 radiofrequency, 1 surgery). No toxic death occurred and toxicity profile was acceptable, with only 2 grade 3 events reported (diarrhea and thrombocytopenia). Conclusions: 2nd line HAI with 5-FU or MMC seems feasible and efficient in heavily pretreated mCRC with liver dominant disease when progressing or not tolerating oxaliplatin HAI. A phase II study is going to be performed to confirm these first results.

Y90 Radioembolization in chemo-refractory metastastic, liver dominant colorectal cancer patients: outcome assessment applying a predictive scoring system.

BackgroundIn treatment-refractory liver dominant metastatic colorectal cancer, the role of liver directed therapies still is unclear. We sought to determine a prognostic score for Y90 radioembolization in these patients.MethodsWe analyzed 106 patients with refractory liver dominant mCRC who had undergone a total of 178 Y90 radioembolizations with resin microspheres was collected. Potential factors influencing survival were analyzed using a Cox regression. The Log rank test served to establish prognostic factors and to form a clinical score for outcome prediction after Y90 radioembolization.ResultsMedian survival of all patients was 6.7 months. Neither age nor prior surgical or systemic therapy nor metastatic spread had an effect on survival. In contrast, hepatic tumor load, Karnofsky index as well as CEA and CA19-9 serums level had a significant influence (p < 0.001, p = 0.037, p = 0.023 and p < 0.001, respectively). These three factors formed a score with 1 point each for tumor load >20 %, CEA >130 ng/ml or CA19-9 > 200U/ml and Karnofsky index <80 %. Patients with a score of 0 and 1 displayed a median OS of 10.4 months. Patients with a score of 2 and 3 demonstrated a median OS of 5.1 months only (p < 0.001).ConclusionOveraggressive patient selection for Y90 radioembolization of liver dominant chemorefractory mCRC is of questionable benefit. A scoring system comprising hepatic tumor load, CEA and CA19-9 serum levels and Karnofsky index (TuCK-score) may support an improved patient selection. In our cohort of liver only versus liver dominant disease, extrahepatic lung or lymphatic metastases did not significantly alter the prognosis.

Protocol and early results of a retrospective clinical trial in pediatric pancreatitis (PINEAPPLE-R – Pain IN EArly phase of Pediatric Pancreatitis)

Data suggest selective internal radiotherapy (SIRT) in third-line or subsequent therapy for metastatic colorectal cancer has clinical benefit in patients with colorectal liver metastases with liver-dominant disease after chemotherapy. The FOXFIRE, SIRFLOX, and FOXFIRE-Global randomised studies evaluated the efficacy of combining first-line chemotherapy with SIRT using yttrium-90 resin microspheres in patients with metastatic colorectal cancer with liver metastases. The studies were designed for combined analysis of overall survival.FOXFIRE, SIRFLOX, and FOXFIRE-Global were randomised, phase 3 trials done in hospitals and specialist liver centres in 14 countries worldwide (Australia, Belgium, France, Germany, Israel, Italy, New Zealand, Portugal, South Korea, Singapore, Spain, Taiwan, the UK, and the USA). Chemotherapy-naive patients with metastatic colorectal cancer (WHO performance status 0 or 1) with liver metastases not suitable for curative resection or ablation were randomly assigned (1:1) to either oxaliplatin-based chemotherapy (FOLFOX: leucovorin, fluorouracil, and oxaliplatin) or FOLFOX plus single treatment SIRT concurrent with cycle 1 or 2 of chemotherapy. In FOXFIRE, FOLFOX chemotherapy was OxMdG (oxaliplatin modified de Gramont chemotherapy; 85 mg/m2 oxaliplatin infusion over 2 h, L-leucovorin 175 mg or D,L-leucovorin 350 mg infusion over 2 h, and 400 mg/m2 bolus fluorouracil followed by a 2400 mg/m2 continuous fluorouracil infusion over 46 h). In SIRFLOX and FOXFIRE-Global, FOLFOX chemotherapy was modified FOLFOX6 (85 mg/m2 oxaliplatin infusion over 2 h, 200 mg leucovorin, and 400 mg/m2 bolus fluorouracil followed by a 2400 mg/m2 continuous fluorouracil infusion over 46 h). Randomisation was done by central minimisation with four factors: presence of extrahepatic metastases, tumour involvement of the liver, planned use of a biological agent, and investigational centre. Participants and investigators were not masked to treatment. The primary endpoint was overall survival, analysed in the intention-to-treat population, using a two-stage meta-analysis of pooled individual patient data. All three trials have completed 2 years of follow-up. FOXFIRE is registered with the ISRCTN registry, number ISRCTN83867919. SIRFLOX and FOXFIRE-Global are registered with ClinicalTrials.gov, numbers NCT00724503 (SIRFLOX) and NCT01721954 (FOXFIRE-Global).Between Oct 11, 2006, and Dec 23, 2014, 549 patients were randomly assigned to FOLFOX alone and 554 patients were assigned FOLFOX plus SIRT. Median follow-up was 43·3 months (IQR 31·6–58·4). There were 411 (75%) deaths in 549 patients in the FOLFOX alone group and 433 (78%) deaths in 554 patients in the FOLFOX plus SIRT group. There was no difference in overall survival (hazard ratio [HR] 1·04, 95% CI 0·90–1·19; p=0·61). The median survival time in the FOLFOX plus SIRT group was 22·6 months (95% CI 21·0–24·5) compared with 23·3 months (21·8–24·7) in the FOLFOX alone group. In the safety population containing patients who received at least one dose of study treatment, as treated, the most common grade 3–4 adverse event was neutropenia (137 [24%] of 571 patients receiving FOLFOX alone vs 186 (37%) of 507 patients receiving FOLFOX plus SIRT). Serious adverse events of any grade occurred in 244 (43%) of 571 patients receiving FOLFOX alone and 274 (54%) of 507 patients receiving FOLFOX plus SIRT. 10 patients in the FOLFOX plus SIRT group and 11 patients in the FOLFOX alone group died due to an adverse event; eight treatment-related deaths occurred in the FOLFOX plus SIRT group and three treatment-related deaths occurred in the FOLFOX alone group.Addition of SIRT to first-line FOLFOX chemotherapy for patients with liver-only and liver-dominant metastatic colorectal cancer did not improve overall survival compared with that for FOLFOX alone. Therefore, early use of SIRT in combination with chemotherapy in unselected patients with metastatic colorectal cancer cannot be recommended. To further define the role of SIRT in metastatic colorectal cancer, careful patient selection and studies investigating the role of SIRT as consolidation therapy after chemotherapy are needed.Bobby Moore Fund of Cancer Research UK, Sirtex Medical.

DEBIRI and capecitabine in refractory prevalently liver metastases of colorectal cancer: A phase II study.

724 Background: Treatment options for metastatic colorectal cancer (mCRC) patients refractory to chemotherapy are limited and clinical outcome is poor. In mCRC patients with liver-dominant disease hepatic locoregional therapy might be a treatment option. In this pilot study we evaluated the safety, tolerance, and efficacy of drug-eluting beads irinotecan (DEBIRI) in combination with capecitabine in the treatment of patients with mCRC with predominally liver disease. Methods: Twenty patients affected by liver metastasis of colorectal cancer were included in this study. All patients had progression of disease after two or more lines of chemotherapy and liver was the major or the predominant site of disease. DEBIRI, beads loaded with 100 mg irinotecan, was administered biweekly via hepatic artery. All patients assumed capecitabine 1,000 mg/m2 twice daily on days 1 to 14 every 3 weeks, until disease progression. Primary endpoints were safety, tolerance and overall responce rate (ORR); secondary endpoints were progression free servival (PFS) and overall survival (OS). Results: Twenty patients underwent a total of 54 DEBIRI treatments of the 66 planned; the median number was 3 (range 2-4) administrated for patients. Grade 1-2 toxic effects included fatigue (70%), diarrhea (45 %), anemia (45%), elevated liver enzymes (45%), nausea (40%), neutropenia (35%) and thrombocytopenia (25%). One grade 3 diarrhea and a case of acute vasospastic angina were observed and required patient hospitalization, but no deaths at 30 days post occurred. Two partial responses were reported (10%) with ORR of 60%. PFS and OS were 4 and 7, 3 months respectively. Univariate analysis showed that patients with KRAS wild-type, good ECOG performance status and single lobe metastases have a better prognosis. Multivariate analysis confirmed that only the good clinical conditions represent an important positive prognostic factor (p=0.03). Conclusions: DEBIRI with capecitabine seem to be a safe, technically feasible and well-tolerated treatment in chemotherapy refractory mCRC with prevalently liver metastases. It has a moderate but not negligible activity in this heavily treated group of patients and deserves further studies in a larger series.

Intrahepatic therapy for liver-dominant metastatic colorectal cancer.

In patients with metastatic colorectal cancer, the liver is the most common site of metastatic disease. In patients with liver-dominant disease, consideration needs to be given to locoregional treatments such as hepatic arterial infusion chemotherapy, transarterial chemoembolisation and selective internal radiation therapy because hepatic metastases are a major cause of liver failure especially in chemorefractory disease. In this review we provide insights on the published literature for locoregional treatment of liver metastases in metastatic colorectal cancer.

GEP-NETS UPDATE: Interventional radiology: role in the treatment of liver metastases from GEP-NETs

Neuroendocrine tumors from gastro-pancreatic origin (GEP-NET) can be responsible for liver metastases. Such metastases can be the dominant part of the disease as well due to the tumor burden itself or the symptoms related to such liver metastases. Intra-arterial therapies are commonly used in liver only or liver-dominant disease and encompass trans-arterial chemoembolization (TACE), trans-arterial embolization (TAE), and radioembolization (RE). TACE performed with drug emulsified in Lipiodol has been used for the past 20 years with reported overall survival in the range of 3-4 years, with objective response up to 75%. Response to TACE is higher when treatment is used as a first-line therapy and degree of liver involvement is lower. Benefit of TACE over TAE is unproven in randomized study, but reported in retrospective studies namely in pancreatic NETs. RE provides early interesting results that need to be further evaluated in terms of benefit and toxicity. Radiofrequency ablation allows control of small size and numbered liver metastases, with low invasiveness. Ideal metastases to target are one metastasis <5 cm, or three metastases <3 cm, or a sum of diameter of all metastases below 8 cm. Ablation therapies can be applied in the lung or in the bones when needed, and more invasive surgery should be probably saved for large-size metastases. Even if the indication of image-guided therapy in the treatment of GEP-NET liver metastases needs to be refined, such therapies allow for manageable invasive set of treatments able to address oligometastatic patients in liver, lung, and bones. These treatments applied locally will save the benefit and the toxicity of systemic therapy for more advanced stage of the disease.

Hepatic yttrium-90 radioembolization for metastatic melanoma

The aim of the study was to analyze the safety and efficacy of yttrium-90 ((90)Y) radioembolization in the treatment of unresectable hepatic melanoma metastases refractory to previous systemic/locoregional therapy. Between February 2004 and April 2010, 16 patients with hepatic melanoma metastases (ocular=7, skin=4, other sites=5) were treated with (90)Y radioembolization at a single center. Toxicity was assessed using the National Cancer Institute Common Terminology Criteria, version 3.0. Response to therapy was assessed by size and necrosis criteria. Progression-free survival (hepatic) and overall survival were calculated using the Kaplan-Meier method. The median dose to the treatment site was 108.57 Gy. Grade 1 and 2 clinical toxicities included fatigue (44%), nausea (19%), and vomiting (12%). Grade 3 absolute lymphocyte toxicity and aspartate aminotransferase toxicity were noted in 2 (12%) and 1 (7%) patients, respectively. Grade 4 bilirubin toxicity was observed in 1 (7%) patient. Overall, 13 (81%) patients showed disease control (response+stable disease) according to WHO, European Association for the Study of the Liver, and Response Evaluation Criteria for Solid Tumors. Progressive disease was observed in 3 (19%) patients according to WHO, European Association for the Study of the Liver, and Response Evaluation Criteria for Solid Tumors. The median overall and hepatic progression-free survival times were 7.63 and 4.23 months. Patients with disease control (responders+stable disease) survived longer than those with progressive disease (9.97 vs. 2.13 months, P<0.0001). Results from this small and single-center experience show that radioembolization is a safe therapy and its potential for being an efficacious therapy for hepatic melanoma metastases should be explored further. Radioembolization should be considered for liver-dominant disease refractory to other forms of systemic therapies.

Current role of transarterial chemoembolization and radioembolization in the treatment of metastatic colorectal cancer.

In this article, we review two liver-directed therapies that are currently used for the palliative treatment of primary and secondary hepatic malignancies, transcatheter arterial chemoembolization (TACE), including a new type of TACE with drug-eluting beads, and radioembolization. Important developments and administration techniques for all therapies are discussed, as well as their integration into the current routine clinical care for management of metastatic colorectal cancer. According to published data from clinical trials, as presented in this review, both radioembolization and TACE/TACE with drug-eluting beads have been proven to be safe and effective in selected patients with chemorefractory liver metastases from colorectal cancer. For patients with unresectable liver-only or liver-dominant disease who have failed standard chemotherapy options or for whom chemotherapy is contraindicated, new modalities, such as those discussed, are particularly valid and promising if clinical guidelines for patient selection and treatment administration are followed.

Pilot Study of Angiogenic Response to Yttrium-90 Radioembolization with Resin Microspheres

PurposeTo investigate the impact of radioembolization with yttrium-90 resin microspheres on the regulation of angiogenesis through observation of serial changes in a spectrum of angiogenic markers and other cytokines after therapy. Materials and MethodsThis prospective pilot study enrolled 22 patients with liver-dominant disease deriving from biopsy-proven hepatocellular carcinoma (HCC) (n = 7) or metastatic colorectal carcinoma (mCRC) (n = 15). Circulating angiogenic markers were measured from serum samples drawn at baseline and at time points after therapy ranging from 6 hours to 120 days. Using multiplex enzyme-linked immunosorbent assay, several classic angiogenesis factors (vascular endothelial growth factor [VEGF], angiopoietin-2 [Ang-2], basic fibroblast growth factor [bFGF], platelet-derived growth factor subunit BB [PDGF-BB], thrombospondin-1 [Tsp-1]) and nonclassic factors (follistatin, leptin, interleukin [IL]-8) were evaluated. ResultsIncreases in cytokine levels ≥ 50% over baseline were observed in more than half of all patients studied for many cytokines, including classic angiogenic factors such as VEGF, Ang-2, and Tsp-1 as well as nonclassic factors IL-8 and follistatin (range, 36%–82% for all cytokines). Baseline cytokine levels in patients with overall survival (OS) < 6 months differed significantly from patients with longer survival for Ang-2 (P = .033) and IL-8 (P = .041). Patients with OS ≤ 6 months exhibited transient increases in VEGF and PDGF-BB after therapy compared with patients with OS > 6 months. ConclusionsRadioembolization is associated with early transient increases in many angiogenic cytokines. In this small sample size, some of these changes were associated with worse OS. This research has important implications for future studies of radioembolization with antiangiogenic therapy performed during and after the procedure.

Hepatic arterial infusion pump chemotherapy for colorectal liver metastases: an old technology in a new era

Aggressive treatment of colorectal cancer (crc) liver metastases can yield long-term survival and cure. Unfortunately, most patients present with technically unresectable metastases; conventional therapy in such patients consists of systemic therapy. Despite advances in the effectiveness of systemic therapy in the first-line setting, the tumour response rate and median survival remain low in the second-line setting. The preferential blood supply from the hepatic artery to crc liver metastases allows for excellent regional delivery of chemotherapy. Here, we review efficacy and safety data for hepatic artery infusion (hai) pump chemotherapy in patients with metastatic crc from the 5-fluorouracil era and from the era of modern chemotherapy. In selected patients with liver-only or liver-dominant disease who have progressed on first-line chemotherapy, hai combined with systemic agents is a viable therapeutic option when performed at experienced centres. Furthermore, significantly improved survival has been demonstrated with adjuvant hai therapy after liver resection in the phase iii setting. The complication rates and local toxicities associated with hai pump therapy are infrequent at experienced centres and can be managed with careful follow-up and early intervention. The major obstacles to the wide adoption of hai therapy include technical expertise for pump insertion and maintenance, and for floxuridine dose modification. The creation of formal preceptor-focused education and training in hai therapy for interdisciplinary medical professionals might encourage the creation and expansion of this liver-directed approach.

The prognostic value of quantitative parameters of 18F-FDG PET/CT in the evaluation of response to internal radiation therapy with yttrium-90 in patients with liver metastases of colorectal cancer

The aim of this study was to evaluate tumor response using fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in patients who received yttrium-90 selective internal radiation therapy (SIRT) for colorectal liver metastases. The initial and sixth-week tumor lesion glycolysis values were calculated to evaluate the success of the treatment and compare it with patient survival. Thirty-five patients (15 female, 20 male, mean age: 61.9 ± 9.0 years, range: 33-76 years) who received SIRT treatment for unresectable colorectal cancer liver metastases in our hospital between June 2008 and May 2011 were included in the study. All patients included in the study had liver-only or liver-dominant disease. The treatment response was evaluated by 18F-FDG PET/CT in the sixth week after treatment. Response was evaluated according to the change in total lesion glycolysis (ΔTLG). The ΔTLG was calculated using the following formula: ΔTLG=100 ×[standardized uptake value (SUV) mean1 × total functional tumor volumes (FTVs)1-SUV mean2 × FTV2]/SUV mean1 × FTV1. Mean FTV1 and FTV2 values were calculated to be 235.7 ± 203 and 107.3 ± 67 mm3, respectively (P=0.04). The mean ΔTLG was 43 ± 35 (range: 0-100). Mean overall survival time was 12.7 ± 8.0 months (range: 3-31 months). The cutoff value of ΔTLG was calculated to be 26.5 using receiver operating characteristic analysis (sensitivity 64%; specificity 85%; AUC=0.717 ± 0.087, P=0.034). Patients were allocated into those having values greater than the cutoff value (group 1) and those having values lower than the cutoff value (group 2) in order to calculate the effect of ΔTLG on survival. Survival was 11.32 ± 1.18 (95% CI 9.02-13.62) months in group 2 and 20.76 ± 2.71 (95% CI 15.46-26.06) months in group 1 (P=0.016). ΔTLG was found to be a significant factor in univariate analysis (P=0.01). An 18F-FDG PET/CT scan with calculation of ΔSUVmax3, ΔFTV, and ΔTLG before and at the sixth week after SIRT may play an important role in evaluating early tumor response and survival expectancy in these patients and help decide whether these patients should be referred to other treatment modalities or to follow-up.

Added value of FDG-PET imaging in the diagnostic workup for yttrium-90 radioembolisation in patients with colorectal cancer liver metastases

Yttrium-90 radioembolisation (Y90-RE) is recommended for unresectable, chemorefractory liver-dominant disease; however, the incidence of extrahepatic disease (EHD) is high. FDG-PET may have additional value to CT in demonstrating EHD. Our aim was to evaluate the added diagnostic value of FDG-PET to abdominal CT and study the influence of FDG-PET findings on treatment decisions. All consecutive patients with colorectal cancer liver metastases (CRCLM) referred for Y90-RE were included. Patients who underwent both CT and FDG-PET in the diagnostic workup were selected. Imaging reports were scrutinised for documented sites of EHD, and changes of management due to FDG-PET findings were determined. A total of 42 patients were included. Findings on CT and FDG-PET matched in 20 patients (no EHD, n = 15; identical EHD, n = 5). In 4 patients, lesions detected on CT were not FDG-avid, and in 18 patients, FDG-PET showed more lesions than CT (P < 0.05). In 7/42 patients (17 %) a change of management was made based on the additional FDG-PET findings, i.e. exclusion from Y90-RE treatment (n = 6) and change in treatment plan (whole liver rather than segmental treatment, n = 1). In patients with CRCLM referred for Y90-RE, FDG-PET showed significantly more EHD and led to a considerable change of management.

Systemic Therapy for Advanced Carcinoid Tumors: Where Do We Go From Here?

Carcinoid tumors are relatively indolent, but the treatment of advanced disease remains a challenge. Liver-directed therapies are a consideration in patients with liver-dominant disease. Somatostatin analogs (SSTa) are routinely used to control hormone-mediated symptoms (carcinoid syndrome), but the identification of systemic agents with antitumor efficacy has proven difficult. Aside from octreotide for small bowel carcinoid (which is associated with delayed progression), no treatment has proven antitumor activity. Chemotherapy seems to be of limited value. The role of interferon is also controversial; it is typically used after failure of octreotide. Peptide receptor radionuclide therapy may have activity in patients with SST receptor-expressing tumors, but randomized controlled trials are lacking. Advances in the understanding of the mechanisms underlying tumor progression have led to the identification of several potential therapeutic targets (including the vascular endothelial growth factor [VEGF] and mammalian target of rapamycin [mTOR] signaling pathways), but none has been definitively validated in carcinoid. Everolimus is associated with a trend toward improved progression-free survival in patients with progressive carcinoid, but is not approved for this indication. Therefore, a serious unmet need remains for additional therapeutic strategies for patients with advanced disease. Several avenues are under study, including the use of novel SSTa; VEGF and mTOR inhibitors; and agents that interfere with insulin growth factor 1 receptor and AKT signaling. Moving forward, optimizing patient selection based on clinical features or biomarkers holds promise for identifying individuals most likely to benefit from therapy.

Research Reporting Standards for Radioembolization of Hepatic Malignancies

Primary Liver Tumors Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver; its incidence is increasing worldwide. It ranks as the sixth most common tumor and third most common cause of cancer-related mortality (1,2). Primary liver tumors include HCC and intrahepatic cholangiocarcinoma. Surgical resection is preferred over transplantation and is considered potentially curative in patients with resectable HCC and normal liver function (3). Transplantation is considered the gold standard for patients with unresectable HCC and whose disease is within the Milan criteria (4). Resection and transplantation have limited roles, given advanced disease (chronic liver disease and/or tumor extent) at presentation and limited organ availability (5–7). Chemoembolization and radiofrequency ablation represent standard therapies in treating patients and serve as a bridge to transplantation in selected patients (8,9). Radioembolization has an emerging role in “bridging” patients within criteria by delaying tumor progression. It has also been shown to downstage disease beyond the Milan, to within, transplant criteria (10–12). A recent study has demonstrated that radioembolization leads to longer time-to-progression and better toxicity profile when compared with chemoembolization (13). Patients with macrovascular tumor involvement have also exhibited evidence of clinical benefit after radioembolization (14).

Hepatic complications of breast cancer

Hepatic disease associated with breast cancer is common and can result from metastatic spread of the tumour to the liver, or can be caused by systemic treatment with chemotherapeutic or antiendocrine agents. Metastatic disease to the liver can present clinically and pathologically in various ways. Little is known as to why breast cancer can sometimes present as liver dominant disease or with liver involvement as a late event in the disease course. However, there are many postulations involving metastasis organotropism, which might offer future insight. The mainstay of treatment for hepatic metastases continues to be systemic therapy, but several locoregional adjunct therapies exist. Despite these therapies, liver metastasis from breast cancer is associated with a poor prognosis. Ongoing research of the mechanisms and tropism of liver metastasis from breast cancer will hopefully result in improved targeted therapies to reduce their incidence and improve outcomes when they arise.

Chemoembolization for hepatic metastases

Liver metastases are one of the most difficult therapeutic challenges in modern oncologic practice. Few systemic therapies are effective for solid tumors in the liver. Resection is possible in a minority of patients and usually not curative. Image-guided therapies such as chemoembolization offer substantial intensification of treatment by combining tumor ischemia, increased drug concentrations, prolonged dwell time, and reduced systemic toxicity. Although not a curative therapy, durable responses are seen in most adenocarcinomas, which may contribute to prolongation and preservation of quality of life by delaying liver failure in patients with liver-dominant disease. Copyright 2002, Elsevier Science (USA). All rights reserved.

Colorectal cancer. Are adjuvant therapies beneficial?

The American Cancer Society's recommendations for screening the population at normal risk for colorectal cancer have been promoted since 1983. Additional study of the effectiveness of these recommendations is in progress, but the medical community has generally endorsed them and urges their implementation in office practice. To date, chemotherapy is not clearly indicated as adjuvant therapy, but enrollment of patients in cooperative group protocols is recommended. Use of second-look surgery to resect selected recurrent tumors has increased in recent years, in part because of the contribution of the computed tomographic scan and carcinoembryonic antigen assay to follow-up of postoperative patients. For advanced disease, technologic advances have improved the technique of hepatic artery perfusion with chemotherapeutic agents, but evidence of a survival advantage afforded by this method is still lacking. Single-agent chemotherapy with fluorouracil remains the best choice for palliating advanced disease, but hepatic artery perfusion with floxuridine also may relieve liver-dominant disease.