Shift in treatment modalities associated with improved outcomes in uveal melanoma patients with liver metastasis

PHILADELPHIA – Uveal melanoma – a cancer found in the eye – is rare, comprising less than 5% of all melanomas. Despite successful treatment of the primary tumor in the eye, up to 50% of patients will develop systemic spread (metastasis), most commonly in the liver.  A recent study from Massachusetts Eye and Ear Infirmary reported that prognosis of uveal melanoma patients with metastasis is very poor with a median survival of 3.9 months after diagnosis. They also suggested there has been no improvement in care over decades of treatment of metastatic disease.  In contrast, new research from The Sidney Kimmel Cancer Center (SKCC) – Jefferson Health investigating uveal melanoma patients with liver metastasis treated at Jefferson showed that outcomes of these patients significantly improved with changes in treatment.

Currently, there is no FDA-approved treatment for metastatic uveal melanoma. Systemic chemotherapy rarely induces a response in patients with metastatic disease. Likewise, while developments in new immunotherapy have improved outcomes of metastatic skin melanoma, a similar benefit has not been seen in metastatic uveal melanoma. In response, physician researchers at Jefferson have been experimenting with treatments directed to the liver. Rather than exposing the entire body to the treatment, localized therapy targeting one organ, the liver, allows the delivery of higher doses of medication to tumors. Furthermore, cutting blood supply to the liver metastasis after delivering the medications by the technique called “embolization” gives additional damage to the tumors.

“We recognized the poor prognosis associated with liver metastasis and we shifted from systemic chemotherapies to the use of various liver-directed treatments,’ says Takami Sato, MD, PhD, Director of the Metastatic Uveal Melanoma Program at SKCC. “We wanted to analyze patient outcomes before and after this shift.” The study was published in Cancers on Jan 1^st, 2020.

The researchers performed a retrospective review on uveal melanoma patients with liver metastasis who were treated at Thomas Jefferson University Hospital during three time periods over five decades: 1971-1993 (Cohort 1), 1998-2007 (Cohort 2), and 2008-2017 (Cohort 3). 70% of patients in Cohort 1 received only systemic chemotherapy, while 98% of patients in Cohort 2 and 3 received liver-directed treatments either alone or in combination with systemic therapy. The study found that overall survival was shortest in Cohort 1 (5.3 months), longer in Cohort 2 (13.6 months) and longest in the more recent Cohort 3 (17.8 months). The researchers suggest that the shift of treatment modalities from systemic chemotherapy (Cohort 1) to liver-directed treatments (Cohorts 2 and 3) improved the survivals of uveal melanoma patients with liver metastasis.

“Approximately  650 liver-directed treatments annually have been given to metastatic uveal melanoma patients at Thomas Jefferson University Hospital”, says David Eschelman, MD,  Co-Director of Interventional Radiology at Jefferson and co-author of the study. 

The researchers also suggest potential benefits of combining liver-directed therapies with newly emerging systemic therapies.

“We believe that our study is one of the largest studies showing extended survival in uveal melanoma patients with liver metastasis,” says Dr. Sato. “We are also hoping that the addition of newly developed systemic therapies, especially immunotherapy, to liver-directed treatments will further increase the survival of patients with this devastating disease”.

Article Reference: Rino S. Seedor, David J. Eschelman, Carin F. Gonsalves, Robert D. Adamo, Marlana Orloff, Anjum Amjad, Erin Sharpe-Mills, Inna Chervoneva, Carol L. Shields, Jerry A. Shields, Michael J. Mastrangelo, Takami Sato, “An Outcome Assessment of a Single Institution’s Longitudinal Experience with Uveal Melanoma Patients with Liver Metastasis”, DOI:10.3390/cancers12010117, Cancers, 2020

By Karuna Meda

Media Contacts: Edyta Zielinska, 215-955-7359, [email protected]; Karuna Meda, 267-624-4792, [email protected].

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