LM from lung cancer represent advanced and incurable disease and thus local therapies are usually contraindicated, because it is without any shown benefit in survival or quality of life. Murthy et al. (2008) described a cohort of six patients with unresectable LM from lung cancer treated with ⁹⁰Y resin-microspheres after having failed systemic chemotherapy, RF ablation, or arterial embolization. RE was administered as second- to sixth-line therapy. A median dose of 36.1 mCi (range, 12.9–54 mCi) was delivered. A decrease in the size of LM (one patient) and stable disease (two patients) were reported. One patient had a mixed response, and two patients had progression of disease. One grade 3 and one grade 4 liver toxicity occurred. All patients experienced grade 1/2 fatigue. Time to progression of liver disease ranged from 3 to 9 months. The authors concluded that, when the treatment was deemed effective, the duration of local disease control after one treatment seem to equal or exceed what would be expected with chemotherapy.

Over 200,000 gastrointestinal malignancies are diagnosed annually in the United States, and the liver is the predominant site of metastasis in most of them. Although there have been significant advances in systemic chemotherapy, most patients will eventually succumb to their disease. As a result, much effort has been put forward to develop methods of local liver tumor ablation aimed to achieve improved outcomes.

With the exception of gastric cancer, surgical results for other gastrointestinal primaries remain highly disappointing. The distinctive natural histories and the lower chemoresponsiveness of these tumors turn into a shorter projected survival for advanced disease than for CRC. Therefore, alternative approaches are eagerly awaited in order to bring some hope of long-term survival. For this reason, RE is being increasingly incorporated into treatment strategies, since its effectiveness may rely more on the dependence of a given tumor on its vascular supply than strictly on its chemosensitivity. Moreover, it may be possible to overcome steep dose-response curves for chemotherapy effect by attaining more protracted and locally concentrated levels of radiation near the tumor.

Ocular melanoma is an aggressive disease that usually metastasizes to the liver. Overall survival rates have been reported to decrease to less than 1 year after the development of metastases. Although some rare long-term survivors have been reported after hepatectomy, most patients present with unresectable liver disease (Lejeune et al. 1992). Kennedy et al. (2009) reported their experience on 11 patients treated with RE with a mean activity of 1.55 GBq. PET-CT at 3 months showed a response in all patients. More recently, Klingestein et al. (2012) retrospectively evaluated the outcome of 13 metastatic uveal melanoma patients after RE as salvage therapy. Most patients had already undergone dacarbazine-based chemotherapy. The mean activity administered was 1.7 MBq. Eight patients achieved a partial response, and the median survival time after RE was 7 months.

For renal tumors (Wilms’ or adenocarcinoma), the survival times after hepatectomy are close to those achieved for colorectal primaries (Schwartz 1995). Surgical resection of LM in this disease remains a component of total oncologic treatment in carefully selected patients. Factors significant for positive outcome benefit usually include complete resection and a large interval from primary resection to the development of subsequent hepatic metastases. Since these factors are only found in a minority of patients, the role of alternative liver-directed therapies is being actively investigated. A recent report investigated the safety and efficacy of yttrium-90 RE in six patients with liver-dominant renal cell carcinoma refractory to immunotherapy and targeted agents. The median dose delivered was 1.89 GBq. Three patients achieved a complete response, and one additional patient had a partial response. These patients are alive at 64, 55, 17, and 7 months after treatment, respectively, (Abdelmakssoud et al. 2012).

Jakobs et al. (2007) reported results on 39 treated patients that included metastatic pancreatic cancer, carcinoma of unknown primary, ICC, thymus carcinoma, malignant melanoma, and choroid melanoma. Some evidence of activity was noted, with a median time to progression of 8 months (range 3–11 months). Lim et al. (2005) prospectively evaluated the efficacy and safety of ⁹⁰Y microspheres in 46 patients with unresectable primary or secondary hepatic malignancies. Tumor types included patients with adenocarcinoma of unknown primary and single cases of hepatic angiosarcoma, gastrointestinal stromal tumor (GIST), ocular melanoma, gastric cancer, pulmonary carcinoid, cholangiocarcinoma, and prostate cancer. With the exception of the single patient with a GIST, activity was not seen in any other tumor type. Popperl et al. (2005) reported on 23 patients with unresectable hepatic malignancies who were not suitable for resection and were no longer responding to polychemotherapy and/or other local forms of treatment. Primary tumors in the mixed group included thymic carcinoma and choroidal melanoma. The mean activity of treatment was 2,270 MBq. Follow-up data showed a marked decrease of FDG uptake, a decrease in tumor marker levels, and unchanged or slightly decreasing lesion size (on CT) in 10 of 13 patients. Wong et al. (2005) described 19 patients with unresectable chemotherapy-refractive hepatic metastatic disease of various origins treated with SIR-Spheres. The median absorbed dose for the tumor was 76 Gy. By PET criteria, 15 of patients (79 %) showed response to therapy, whereas four (21 %) showed no response. Yu et al. (2006) reported on 49 patients with CRC, pancreatic, breast, carcinoid, lung, thyroid, squamous cell, renal-cell, gastrointestinal stromal tumor, and endometrial cancer who underwent 78 administrations of SIR-Spheres. All patients had undergone previous multiple-agent chemotherapy, which had failed. The mean dose of resin-microspheres administered was 0.83 GBq, which translates to 42 Gy absorbed dose. A RECIST response rate of 29 % and a PET response rate of 79 % were noted. Mean and median survival times were 305 and 175 days, respectively. Jakobs et al. (2006) presented midterm results on 88 patients who received 118 administrations of SIR-Spheres. Forty-five of them had CRC, whereas the remaining cases comprised pancreatic, breast, NET, lung thyroid, squamous-cell, GIST, thymus, melanoma, and endometrial cancers, and HCC. All patients had undergone prior chemotherapy. The mean dose infused was 0.83 GBq for lobar and whole-liver treatments. The mean absorbed dose was 42 Gy. The response rate according to RECIST criteria was 18 %, whereas the functional response rate according to PET was 62 %. Mean and median survival times were 285 days and 180 days, respectively. Unfortunately, the inclusion of such a heterogeneous tumor types in these studies adds little to the data on efficacy and reinforce the need for specific disease directed-trials.