Treatment of uveal melanoma metastatic to the liver. A review of the M. D. Anderson cancer center experience and prognostic factors

Abstract

Background. Liver metastasis develops in approximately two‐thirds of patients with recurrent uveal melanoma. Despite therapy, the median survival of those with liver metastasis is 5 to 7 months. The recognition of a grave prognosis associated with liver metastasis has led to evaluation of new modalities of therapy, including the use of regional therapies such as intrahepatic arterial chemotherapy and either embolization or chemoembolization of hepatic metastases. In this study, the results of an institutional experience over the past 2 decades are reviewed and prognostic factors that affect survival from the time the liver metastasis is diagnosed are assessed. Methods. In this study of 201 patients with uveal melanoma involving the liver who were treated at M. D. Anderson Cancer Center between 1968 and 1991, the authors retrospectively reviewed the cases and compared the results of systemic therapies, hepatic infra‐arterial chemotherapies, and chemoembolization of liver metastases. Cox's multivariate analysis and stepwise logistic regression were then computed to determine significant prognostic variables. Results. The systemic therapies produced a response rate of less than 1%. Chemoembolization was the most effective treatment, inducing responses in 36% of patients. Survival curves were calculated using the life‐table method of Kaplan and Meier. Patient‐and tumor‐related characteristics were examined and their relation to on survival from the time of diagnosis of liver metastasis was determined. Levels of serum alkaline phosphatase, total bilirubin, and lactic dehydrogenase plus response to treatment showed a strong relation to survival. In contrast, univariate analysis showed that patient age and gender, metastasis free interval, presence of extrahepatic metastasis, and type of therapy for liver metastasis did not influence survival. Multivariate stepwise regression analysis identified serum alkaline phosphatase and metastasis free interval as the main independent prognostic factors for survival after liver metastasis diagnosis. Conclusions. Of the three modalities of therapy used for choroidal melanoma metastatic to the liver, only chemoembolization using cisplatin‐based regimens produced a meaningful response rate. Information from this analysis can be used to predict the outcome of patients with uveal melanoma metastatic to the liver. Patients with metastatic ocular melanoma confined to the liver should be treated with chemoembolization and should not be included in chemotherapy trials designed for cutaneous melanoma. Cancer 1995; 76:1665–70.

Inflammation in uveal melanoma

“…The average survival time after diagnosis of liver metastasis is about 8 months. 10 Treatment only rarely prolongs survival, because metastases are highly resistant to most chemotherapeutic agents and because they are not usually resectable. Tumours with a high risk of metastasis can be identified by many techniques.…”

Treatment of disseminated ocular melanoma with sequential fotemustine, interferon α, and interleukin 2

“…Indeed, until recently, there had been no effective systemic treatment for metastatic uveal melanoma (Nathan et al, 1997). The largest series reported with treatment by DTIC, usually in combination with other drugs and bioactive agents, had a response rate of below 1% with no improvement of survival noted (Bedikian et al, 1995;Woll et al, 1999).…”

“…To this end, intraarterial chemoembolisation or perfusion has been reported to induce both complete and partial responses in patients with metastatic uveal melanoma. Bedikian reported a 36% objective response rate induced by cisplatin-based chemoembolisation (Bedikian et al, 1995). The group of Leyvraz treated 31 patients by the intraarterial administration of fotemustine, a nitrosurea that is characterised by a high hepatic extraction rate (Leyvraz et al, 1997).…”

Isolated Hepatic Perfusion with Melphalan for Primary or Metastatic Unresectable Cancers of the Liver: Safety and Feasibility in A U.S. Academic Medical Center

“…In many cancers, the finding of liver metastases is indicative of widespread disease present in several organs. But specific cancers, such as colorectal cancer, ocular melanoma, and neuroendocrine carcinoma commonly metastasize to the liver, without spread to other organs [1][2][3][4][5]. Systemic therapy remains the mainstay of treatment for patients with these conditions; however, because of systemic-toxicity related dosage limitations the efficacy is generally limited.…”

“…Systemic therapy remains the mainstay of treatment for patients with these conditions; however, because of systemic-toxicity related dosage limitations the efficacy is generally limited. For example, even with aggressive treatment, the median survival in patients with liver metastases from ocular melanoma is between 2 and 7 months [4,6]. While neuroendocrine carcinoma liver metastases sometimes have an indolent biology with a slow rate of growth, poorly differentiated neuroendocrine carcinomas are much more aggressive and are generally associated with a very poor prognosis.…”