Hepatic arterial90Yttrium glass microspheres (Therasphere) for unresectable hepatocellular carcinoma: Interim safety and survival data on 65 patients

Abstract

Hepatocellular carcinoma (HCC) generally arises in a cirrhotic liver and, in most cases, is multifocal and bilobar. Although trans-hepatic artery chemoembolization (TACE) can be highly affective in shrinking tumors, it is limited by virtue of the damage that it can cause to the liver that is already damaged by chronic disease. A high priority in HCC research, after primary prevention and early detection, is to find new treatment modalities that are both effective and non-toxic to the underlying cirrhotic liver. A cohort of 65 patients with biopsy-proven unresectable HCC have been treated with hepatic arterial 90 Yttrium microspheres (Therasphere), and the interim results are reported here. Only 1 cycle of Therasphere treatment ever was performed on 46 patients, 17 patients had 2 cycles, and 2 patients had 3 cycles of therapy. The median dose delivered was 134 Gy, typically as either 5 or 10 GBq (2-4 million microspheres). Clinical toxicities include 9 episodes of abdominal pain and 2 episodes of acute cholecystitis, requiring cholecystectomy. A main lab toxicity was elevated bilirubin which increased by more than 200 % in 25 patients (30.5 %) during 6 months of therapy, although 18 of these patients had only transient elevation. A prominent finding was prolonged and profound (> 70%) lymphopenia in more than 75% of the patients, but without clinical significance. Forty-two patients (64.6%) had a substantial decrease in tumor vascularity in response to therapy, and 25 patients (38.4%) had a partial response, by computed tomography scan. Median survival for Okuda stage I patients (n ‫؍‬ 42) was 649 days (historical comparison 244) and for Okuda stage II patients (n ‫؍‬ 23) was 302 days (historical comparison 64 days). All patients were followed after therapy for a minimum of 6 months. There were 42 deaths, 21 due to liver failure, 6 from HCC progression, and 3 from metastases. Therasphere appears to be a relatively safe and effective therapy for advanced-stage unresectable HCC. (Liver Transpl 2004;10:S107-S110.)

Safety and efficacy of 90Y radiotherapy for hepatocellular carcinoma with and without portal vein thrombosis

“…9,10 This device may be indicated as a radiation treatment, or as a neoadjuvant to surgery or transplantation in patients with unresectable HCC. It also may be used for the treatment of unresectable HCC in patients with branch/partial portal vein thrombosis.…”

Radiotherapy Dose Optimization in Target Tissues Using Internal Radiation-Generating Devices and Microspheres

“…As an initial example of the internal device concept, a spectrum of eight proton groups (i.e., 10,20,30,40,50,60,70, and 80 MeV) is selected to be the output of the device. A spectrum of energies facilitates the irradiation of the entire tumor volume.…”

“…Each device is assumed to radiate isotropically. The results of irradiating this water volume with 27 internal devices generating an output of 10,20,30,40,50,60,70, and 80 MeV protons are illustrated in Figure 1. The luence at each proton energy is selected to be the same.…”

“…However, treatment procedures will utilize many spheres with the actual number determined by the cancer type and its progression. Although microsphere delivery methods other than the usual catheter approach [2-6] may be feasible, initial eforts will likely focus on the traditional delivery method [17][18][19][20][21][22][23].…”

“…A number of authors [15,16] have proposed a therapy approach that prevents the development of the tumor's vascular supply. Vascular disruption agents incorporate both chemotherapy [17,18] as well as radiotherapy [18][19][20][21][22][23][24][25][26][27]. Radiotherapy vascular disruption techniques utilizing 90 Y microspheres, including anti-angiogenic and radioembolization therapies, are used to treat liver cancers [18][19][20][21][22][23].…”