Hepatic metastases—a physiological approach to treatment

Abstract

Hepatic metastases derived from primary malignancy of the gastrointestinal tract have a grave prognosis, with median survival rates varying from 3 to 11 months. Surgery for isolated metastases and intrahepatic artery chemotherapy are the most effective treatment options currently available. We have explored the potential use of radioactive microspheres delivered into the liver by the hepatic artery as a form of internally irradiating metastatic liver cancer. Microspheres containing radioactive Yttrium injected into the hepatic artery concentrate in the metastases rather than normal liver parenchyma, due to the fact that the blood supply of metastases is derived preferentially from the hepatic artery. Using a rabbit tumour model, radioactive microspheres delivered into the hepatic artery have been shown to lodge preferentially in tumour tissue. The therapeutic application of this phenomenon is that metastases may receive many times the radiation dose delivered to normal liver parenchyma when radioactive microspheres are delivered into the hepatic artery. This would mean that a mean dose of 30 Gy delivered to normal liver tissue would result in greater than 150 Gy being delivered to tumour tissue. Current results in experiments suggest that this form of treatment may have considerable potential for prolonging survival of patients with hepatic metastases.

90Y Radioembolization for Metastatic Neuroendocrine Liver Tumors

“…Finally, medical therapy used solely for symptom control also has survival rates of 76% and 39% at 1 and 3 years from initiation of therapy respectively. 6 Palliative embolization therapies have yielded mixed results. Studies of TAE using polyvinyl alcohol particles or gelfoam report survival rates of 60% to 94% (1 year) and 14% to 51% (5 year).…”

“…Unfortunately, Ն90% of patients present with multiple hepatic metastatic lesions excluding them from surgical cure. 4,5 Therapies for unresectable metastatic NET include (a) medical (eg, somatostatin analogues) 6 ; (b) ablative such as cryotherapy 7 or radiofrequency ablation (RFA) 8,9 ; (c) systemic chemotherapy, 10 and; (d) transcatheter arterial embolization (TAE) or chemoembolization (TACE). 4,11,12 These therapies have been effective at improving patient symptomatology but lack robust clinical trial data, long-term survival Ͼ5 years (cryotherapy, RFA, or medical therapy), or have 5-year survival percentages widely ranging from 14% to 60% (TAE/TACE).…”

Randomised phase 2 trial of SIR‐Spheres® plus fluorouracil/leucovorin chemotherapy versus fluorouracil/leucovorin chemotherapy alone in advanced colorectal cancer

“…The SIR-Spheres are embolised into the hepatic artery and result in high doses of radiation being selectively targeted to tumours, regardless of their number or position within the liver. The technique of SIRT, dosimetry, and preclinical studies have all been previously reported [2][3][4][5][6][7]. Injection of specific vasoactive drugs into the hepatic arterial circulation has been shown to greatly enhance tumour targeting with SIR-Spheres [8][9][10][11][12].…”

Intra-hepatic-arterial infusion of misonidazole – an experimental study of regional radiosensitisation by intraarterial embolisation

“…Microspheres of 30-40 tm (range 10-90 jLm) in diameter should lodge in the hepatic-arterial microvasculature when injected into the common hepatic artery. Chamberlain and Gray (1983) demonstrated that in rabbit VX2 liver tumours, the concentration of microspheres was 30-fold higher than in the normal liver tissues. Therefore in hypervascular regions of tumours the aterial capillary obstruction and the slowdown of blood flow rate result in the entrapment of a greater volume of drug solution than in normal liver.…”