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ORIGINAL ARTICLE
Year : 2017  |  Volume : 13  |  Issue : 4  |  Page : 642-646

A retrospective analysis of the efficacy of microparticle-mediated chemoembolization in liver metastases arising from gastrointestinal tumors


1 Department of Intervention, The Affiliated Zhongshan Hospital of Dalian University, Dalian, China
2 Department of Hepatopancreatobiliary Interventional Radiology, Beijing Tsinghua Changgeng Hospital, Beijing, China

Date of Web Publication13-Sep-2017

Correspondence Address:
Jun Zhou
Department of Intervention, The Affiliated Zhongshan Hospital of Dalian University, Dalian
China
Yue-Wei Zhang
Department of Hepatopancreatobiliary Interventional Radiology, Beijing Tsinghua Changgeng Hospital, No. 268, Li Tang Road, Changping District, Beijing
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_213_17

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 > Abstract 

Purpose: We evaluated the clinical efficacy of gelatin sponge microparticle (GSM) -mediated chemoembolization for the treatment of patients with liver metastases following surgery for gastrointestinal tumors.
Materials and Methods: In a retrospective analysis of 37 patients who were treated at our hospital with GSM-mediated chemoembolization for liver metastases over 13 years, we evaluated outcomes using a modified response evaluation criteria in solid tumors system and also assessed liver function and adverse effects. All patients had previously undergone surgery for gastrointestinal tumors.
Results: Treatment produced various degrees of necrosis and shrinkage of lesions among our patients. Two patients achieved a complete response (CR), 27 showed a partial response (PR), five had stable disease, and three had progressive disease. The overall response rate (CR + PR) was 78%, and no severe adverse effects were observed.
Conclusion: GSM-mediated chemoembolization showed good clinical efficacy in the treatment of liver metastases after gastrointestinal tumor surgery. However, larger cohort and clinical controlled studies are warranted.

Keywords: Chemoembolization, gastrointestinal tumor, gelatin sponge microparticles, liver metastases


How to cite this article:
Li C, Liu Y, Zhou J, Zhang YW. A retrospective analysis of the efficacy of microparticle-mediated chemoembolization in liver metastases arising from gastrointestinal tumors. J Can Res Ther 2017;13:642-6

How to cite this URL:
Li C, Liu Y, Zhou J, Zhang YW. A retrospective analysis of the efficacy of microparticle-mediated chemoembolization in liver metastases arising from gastrointestinal tumors. J Can Res Ther [serial online] 2017 [cited 2018 Aug 16];13:642-6. Available from: http://www.cancerjournal.net/text.asp?2017/13/4/642/214467


 > Introduction Top


Liver metastases commonly arise from gastrointestinal tumors. The hepatic artery and portal vein are connected to the lymphatic drainage system; hence, malignant tumor infiltration is commonly observed in gastric and colorectal cancers.[1] Metastases are already present in 20%–50% of patients with colorectal cancer at clinical diagnosis.[2],[3] Moreover, 2.0%–9.9% of gastric cancer patients have liver metastases that are detected before or during surgery, and 13.5%–30.0% of these metastases are discovered after radical surgery.[4],[5] Surgical resection is the mainstay of treatment for colorectal cancer patients with liver metastases;[6] however, only 15%–30% of these patients are eligible.[7] Surgical resection for liver metastases arising from gastric cancers remains controversial.[8]

Transcatheter arterial chemoembolization (TACE) is emerging as an effective method for the treatment of liver metastases from gastrointestinal tumors.[9] We investigated the efficacy and outcomes of TACE with gelatin sponge microparticles (GSMs) in patients with liver metastases following surgery for gastrointestinal tumors from December 2012 to December 2015.


 > Materials and Methods Top


Patient information

We included 37 patients treated at our institution between December 2012 and December 2015 in this study. These patients had liver metastases with progression after radical surgery for their gastrointestinal tumors; all were refractory to systemic chemotherapy. The patients' characteristics are provided in [Table 1].
Table 1: General information of patients

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Embolization agent

GSMs (Registration Number: CFDA 3770360 (2006), product standard: YZB/National 2518-77-2004 [gelatin sponge particles embolic agent]) were produced by Alicon Pharmaceuticals Pvt. Ltd., (Hangzhou, China). The diameters of the GSMs used in this study were 350–560 μm.

Chemotherapeutic drug

Injectable lobaplatin (10 mg/ampoule) was produced by Hainan Chang'an International Pharmacy Limited Company.

Interventional therapy

The Seldinger technique was used to insert a catheter through the femoral artery for selective digital subtraction angiography (DSA) to determine the source of the arterial blood supply into tumors, as well as the number of tumors and their staining intensities. Next, 50 mg of lobaplatin with GSMs (350–560 μm) was injected into an artery located in the tumor blood supply zone for chemoembolization until the artery was completely blocked. Embolization was then stopped. Eight patients received one course of interventional therapy while seven patients received two courses.

Evaluation criteria for efficacy

Three to seven days after surgery, routine blood examination, liver and kidney function, and tumor marker levels were examined. Liver computed tomography (CT) was performed on day 3 and at 1 and 3 months postsurgery. The 2009 modified response evaluation criteria in solid tumors (mRECIST) were used for evaluating the target and nontarget lesions in each patient. Target lesions were evaluated as follows: complete response (CR), disappearance of any intratumoral arterial enhancement in all target lesions; partial response (PR), a ≤30% decrease in the sum of the longest diameters (arterial enhancement) of the target lesions; progressive disease (PD), an increase of ≥20% in the sum of the longest lesion diameters from baseline or the appearance of new lesions; and stable disease (SD), a decrease or increase in the sum of the longest lesion diameters from baseline that did not attain the scope of a PR or PD, respectively. Nontarget lesions were evaluated as follows: CR, disappearance of any intratumoral arterial enhancement in all target lesions and normal levels of tumor markers; SD, persistence of intratumoral arterial enhancement in one or more nontarget lesions, or else tumor marker levels above normal; and PD, appearance of one or more new lesions or the progression of existing nontarget lesions. At various time points, the objective response rate (calculated as [CR + PR]/total number of patients treated during the time period) and the disease control rate (calculated as [CR + PR + SD]/total number of patients treated during the time period) were calculated.

Survival analysis

The Kaplan–Meier method and life table were used to analyze the survival rates. The overall survival time was calculated in months and was based on the duration between the date of the first GSM-TACE treatment and death or the most recent follow-up.


 > Results Top


Presentations of metastases

DSA showed diverse presentations of liver metastases from gastrointestinal tumors. Metastases with rich blood supplies were similar in appearance to hepatocellular carcinoma, with thickened and tortuous hepatic arteries and significant staining of the tumor parenchyma. Liver metastases with poor blood supplies only showed enhancement of the tumor circumference. Liver metastases that lacked blood supplies showed fewer and thinner blood vessels that were stiff or wrapped, and the edges of the tumor parenchyma were also enhanced. Twenty patients had tumors with rich blood supplies; 11 had tumors with poor blood supplies and six had tumors devoid of blood supply. Eleven patients had single lesions and 26 had multiple lesions.

Efficacy

The number of TACE courses and mRECIST outcomes is shown in [Table 2]. The liver function in all patients recovered to presurgical levels within 7 days. Liver CT was performed on day 3 and at 1, 3, and 6 months after surgery; different degrees of necrosis and shrinkage of tumors were observed [Figure 1] and [Figure 2].
Table 2: Treatment outcomes

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Figure 1: Digital subtraction angiography of the transcatheter arterial chemoembolization site. (a) A large tumor is stained in the left liver lobe. (b) After embolization, the tumor staining has disappeared

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Figure 2: Computed tomography images pre- and post-transcatheter arterial chemoembolization. (a) Enhancement of a tumor's circumference before embolization. (b) Honeycomb necrosis can be observed on computed tomography 3 days after embolization. (c) One month after embolization, there is no increase in lesion enhancement, and tumor shrinkage is observed. (d) Six months after embolization, there is no increase in lesion enhancement, and tumor shrinkage is more pronounced. (e) After partial removal of the left half of the liver, complete tumor necrosis was verified by pathology

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Adverse events

All patients experienced various degrees of fever, mild gastrointestinal discomfort, upper abdominal pain, nausea, and vomiting. There were no incidences of liver or kidney failure, liver abscesses, bilomas, or other severe complications. The results of liver function tests pre- and post-TACE are shown in [Figure 3].
Figure 3: Mean results of liver function tests before and 7 days after transcatheter arterial chemoembolization. Levels of (a) total bilirubin, (b) albumin, (c) alanine transaminase, and (d) aspartate transaminase

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Survival time

The follow-up period ranged from 4 to 55 months; the last follow-up was in December 2015. The median survival time was 32 months (95% confidence interval: 22.29–41.70). The 6-month, 1-year, and 2-year survival rates were 91.6%, 82.5%, and 50.3%, respectively [Figure 4].
Figure 4: Kaplan–Meier curve showing patient survival

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 > Discussion Top


Liver metastases are a common presentation in gastrointestinal tumors; 60%–71% of deaths among colorectal cancer patients are the result of liver metastases, and the 5-year survival rate of patients with such metastases is 3.6%.[7] Furthermore, the 5-year survival rate of gastric cancer patients with liver metastases is <10%.[5] Surgical resection of liver metastases is the mainstay of treatment in these patients and is aimed at prolonging survival. The 5-year survival rate is 35.6% after resection, which is markedly better than that of patients who do not undergo resection.[10] However, because of surgical contraindications, as well as fear of surgery in some patients, only 15%–30% of colorectal cancer patients undergo surgery,[11] and only 0.3%–2.4% of gastric cancer patients are eligible for radical surgery.[5],[12] Effective therapy for patients with liver metastases who do not undergo surgical resection is an urgent unmet need. In recent years, TACE has gained a more important role in combined therapy for liver metastases of gastrointestinal tumors.[9],[13] Studies of malignant liver tumors (including liver metastases) have shown that 90% of the tumors' blood supply is derived from the hepatic artery.[14] Hence, injection of high concentrations of chemotherapeutic agents through the hepatic artery can directly target tumor cells while the selection of suitable embolic agents to obstruct the tumors' blood supply may increase the local control rate of liver metastases and further increase the patients' quality of life and survival.[15]

The arterial embolic agents used during TACE can be classified as permanent or absorbable. Iodized oil is one of the commonly used permanent embolic agents in clinical practice and has more pronounced effects against parenchymal tumors with rich blood supplies. However, iodized oil shows poor efficacy against tumors that lack a blood supply; moreover, it can cause severe damage to the liver and kidney owing to the mass effect [16] and complete embolization of large liver tumors is not possible. There are also reports of iodized oil being associated with higher risks of lung embolisms, brain embolisms, and other severe complications.[17],[18]

Recently, the use of particle embolic agents in intervention therapy has attracted attention. Many clinical studies have demonstrated the efficacy of drug-eluting beads in the treatment of liver metastases.[19],[20],[21] Martin et al.[22] used irinotecan-eluting beads with diameters of 50–200 μm in 30 patients with metastatic colorectal cancer (MCC) and found that 15 patients achieved a PR, 14 had SD, and 1 had PD. After a median follow-up period of 9 months, the survival rates were 75% at 3 months and 66% at 6 months. Among their thirty patients with MCC, approximately 50% showed significant decreases in carcinoembryonic antigen levels at 3 and 6 months posttreatment, with some patients attaining normal levels. Their study also showed that embolization using drug-eluting beads in MCC significantly controlled tumor progression and increased both the survival rates of patients and their quality of life. Nitta et al.[23] reported the use of cisplatin-releasing GSMs (diameter 50–100 μm) alone for TACE in nine patients with liver metastases; two of their patients achieved a CR, one had a PR, and six had SD. However, complete embolization cannot be performed with permanent embolic agents, as it increases the risk of liver failure, gallbladder necrosis, liver abscesses, and other severe complications.[24],[25]

GSMs with diameters of 350–560 μm showed good efficacy when used in combination with chemotherapeutic agents for the embolization of primary liver tumors and liver metastases arising from colorectal tumors.[26] Such GSMs can be reabsorbed in 7–14 days with few adverse effects on liver function; we successfully used them for complete embolization of the tumor-supplying artery, and tumors lacking blood supplies also showed significant necrosis. CT performed 3 days postsurgery revealed large honeycomb necrosis within the tumors, and liver function returned to normal levels at 7 days postsurgery. Follow-up visits after surgery showed necrosis and shrinkage of tumors to various extents as well as effective tumor control rates. Moreover, patients showed differing degrees of gastrointestinal discomfort and fever in response to the procedure although no severe complications were observed.

As our 37 patients with liver metastases were all refractory to systemic chemotherapy (including FOLFOX, FOLFIR, CAPEOX, etc.), lobaplatin was selected because of its good water solubility, lack of cross-resistance with other platinum drugs, and low toxicity.[27] Lobaplatin was combined with GSMs for the TACE procedure to achieve better therapeutic efficacy. From our experience, GSMs can completely block the arteries supplying liver metastases and also show high rates of tumor necrosis, no mass effect, low liver damage, rapid recovery of liver function after surgery and have other advantages as well. In this study, good clinical efficacy was attained; however, further investigations in larger cohorts are warranted as are clinical controlled studies.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 > References Top

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2]



 

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