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Network for Organ Sharing database. Moreover, the chemoembolization (TACE) with a radiologically
[30]
optimal timing of transplantation (e.g., whether stable controlled percutaneous technique have been widely
disease needs to be observed for a certain amount of time) investigated and adopted during the past decade for the
and selection criteria (including development of patient- treatment of NETs LM. These strategies have generated
specific biomarkers to identify those who gain a long-term encouraging outcomes in term of survival, response, and
benefit from the procedure) are still debated. quality of life. Indications included well-differentiated or
[38]
moderately well-differentiated (Grade 1 or 2) unresectable
THERMAL ABLATION (TA) symptomatic liver lesions (due to tumor bulk), excessive
hormone production, and rapid progression of liver
The most widely applied TA modalities in the liver disease. Hepatic TAE, usually performed using lipiodol,
[39]
include radiofrequency (RF), microwave (MW), laser, obtains ischemia and necrosis of neoplastic cells by selective
cryoablation, and high-intensity focused ultrasonography. catheterization and obstruction of the hepatic artery
TA is often used alone or in conjunction with operative supplying tumor lesions. On radiologic evaluation, TAE
[40]
resection in the treatment of both primary and secondary has been shown to improve biophysical markers, palliate
hepatic malignancies. RF and MW ablation involves direct symptoms, and shrink tumor lesions. In contrast to TAE,
[41]
insertion of ablation probes into the region of a tumor, TACE combines blockage of the tumor blood supply with
followed by application of several cycles of hyperthermic intra-arterial administration of cytotoxic drugs. In clinical
energy to induce cell death. MW ablation is thought practice, TACE is preferred over TAE in patients with NET
to be more effective than RF ablation because a shorter with the worst prognostic factors, such as foregut origin
time is needed for each ablation, and higher intratumor (lung or pancreas) and poorly differentiated NETs.
[42]
temperatures can be reached. Use of TA requires real-time Several different chemotherapeutic agents have been used
ultrasonography guidance. The United States Food and in this setting (doxorubicin, streptozotocin, gemcitabine,
Drug Administration has approved TA for the treatment of mitomycin C, 5-FU, or cisplatin) along with either a
primary and metastatic tumors of the lung and liver. [31] transient or permanent embolic agent like ethiodized oil
or lipiodol. This treatment has shown effective results
[43]
RF ablation has been used for relief of symptoms of hepatic in patients with metastatic liver disease, with reported OS
metastases of insulin- or serotonin-secreting NETs [32] and values of 3-4 years and objective response of about 75%.
favorable 5-year survival rates after liver resection. Notably, response to TACE is higher when treatment is
[33]
More than a dozen lesions can be treated in a single used as a first-line therapy and liver involvement is lower.
patient, and many patients tolerated repeated ablations for Combining results obtained with TAE and TACE, the rates
recurrent disease. To date, no randomized trials have of symptomatic responses ranged from 39 to 95%. [44-47]
[33]
been undertaken to study whether surgical techniques such
as liver resection and/or RF ablation are more effective An accurate multicentric retrospective review on 100
than hepatic artery embolization or radio embolization, patients with NETs LM who submitted to TACE (n = 49)
peptide receptor radionuclide therapy (PRRT), or medical or TAE (n = 51) showed comparable rates of symptom
systemic treatments in patients with NET and LM. control (88% vs. 83%, respectively), similar toxicities,
and comparable survival outcomes (median OS: 25.7
PERCUTANEOUS LIVER- vs. 25.5 months, respectively). These data suggest that
DIRECTED TECHNIQUES WITH A the two techniques should be considered comparable.
[48]
CYTOREDUCTIVE AIM Future trials focusing on the evaluation of either the
efficacy of different intra-arterial techniques or the role of
In NET patients with liver disease only or with liver- a combination of loco-regional approaches with systemic
dominant metastases, loco-regional approaches such therapies are needed.
as ablative techniques or intra-arterial therapies can be
proposed in place of upfront surgery with a cytoreductive SELECTIVE INTERNAL RADIOTHERAPY
aim, leading to lesion resectability and a 5-year survival (SIRT)
rate of 50%. [34-36]
Percutaneous angiographic techniques should be used
In particular, it is well known that NET hepatic metastases in patients with Grade 1 or 2 tumors who have liver-
are characterized by a high rate of vascularization, predominant disease. The best treatment effect is
as opposed to many other liver primary or secondary achieved in patients with < 50% hepatic involvement
malignancies. Vascularization of NETs LM depends mostly and no extrahepatic disease. SIRT is a targeted approach
on the hepatic artery, whereas normal liver parenchyma has that delivers glass or resin microspheres labeled with
a unique dual blood supply from both the proper hepatic 90Yttrium (Y-90) that is primarily a beta particle emitter.
artery (20-40%) and the portal vein (60-80%). [37] Y-90 hepatic arterial administration is emerging as a
promising treatment modality in the management of NETs
Arterially directed interventional strategies, such as patients with LM. [49,50] Down-sizing/down-staging of
transarterial embolization (TAE) and transarterial hepatic tumors as a bridge to subsequent surgical treatment
296
Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ August 17, 2016 ¦