The International Council of Ophthalmology Highlights Fellowship Partnership with ECF

The Eye Cancer Foundation is proud to be joining forces with the International Council of Ophthalmology supporting and promoting eye cancer fellowship education for doctors from unserved and underserved countries.

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Since launching its ICO fellowship program in 2001, more than 920 Fellows have completed a three month subspecialty training and 28 ICO Fellows have completed their one year training.

This partnership between the ICO and the Eye Cancer Fellowship will expand and enhance ECF’s existing fellowship programs, focusing specifically on addressing the need to reduce world-wide mortality related to retinoblastoma by ensuring that more patients have ready access to a trained eye cancer specialist in their region.

The ICO highlighted the new in its recently released program report, Fifteen Years of ICO Fellowships. icofellowship15yearsscreenshot_1

“It is out mutual goal to decrease the high rates of world-wide mortality associated with the most common primary childhood eye cancer, retinoblastoma. Towards this goal, we agree that supplying subspecialty-trained retinoblastoma specialists to unserved and underserved countries is our priority,” The Eye Cancer Foundation Chairman Dr. Paul Finger wrote.

Together, the Eye Cancer Foundation and the ICO have set a goal of saving 1,000 children by 2020.


Drug Shows Promise in Eliminating Side-Effect of Retinoblastoma Chemotherapy

A study recently published in the Journal of Clinical Oncology showed revamping multi-drug chemotherapy for retinoblastoma to include tropotecan maintained high cure rates while preserving vision and reducing the risk of treatment related leukemia.

Retinoblastoma ranks as the most common intraocular childhood cancer. It affects approximately 300 children in the United States each year and more than 8,000 worldwide. Better than 96% of patients in North America and Europe are cured of retinoblastoma due to early detection and treatment.

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Multi-modal chemotherapy has proved to be an effective treatment, but the widely used triple-drug therapy includes etoposide, a drug that has been associated with secondary acute myeloid leukemia in some patients.

Ten years ago, Michael Dyer, Ph.D., chair of the St. Jude Department of Developmental Neurobiology, began laboratory research seeking a safer retinoblastoma therapy. Researchers began looking at topotecan because it had shown promise in the treatment of other solid tumors.

Working with retinoblastoma tumor cells grown in the laboratory and in mice, Dyer confirmed topotecan could possibly replace etoposide in retinoblastoma therapy and determined the effective dose. The laboratory findings led to a clinical trial including 26 children diagnosed with advanced, bilateral retinoblastoma that had not spread beyond their eyes.

In the trial, triple drug chemotherapy replacing etoposide with topotecan outperformed the standard chemotherapy treatment. Of the 51 diseased eyes included in the study, 78% of those treated with therapy including topotecan were salvaged. That compares to previous reports of 30 to 60% following chemotherapy that included etoposide and often required salvage radiation therapy.

Altogether, 10 eyes had to be surgically removed, including one eye removed at diagnosis prior to chemotherapy and three removed after radiation therapy failed to stop disease progression.

“Preservation of an eye is not synonymous with preservation of vision,” first and corresponding study author Rachel Brennan, M.D. said. “But this therapy provided significant improvement in survival of eyes and useful vision in patients with advanced retinoblastoma.”

Post-treatment vision screening of survivors identified 18 patients with vision of 20/40 or better in at least one eye.

“This 10-year follow-up study shows for the first time that topotecan can be used in front-line therapy to help reduce exposure of retinoblastoma patients to etoposide,” Brennan said first. “We expected patients to be cured, but we also found more than 80 percent of patients had measurable vision.”

The results of the study seem promising. Topotecan may well provide an alternative therapy that maintains or even exceed the effectiveness of traditional multi-modal chemotherapy for retinoblastoma while eliminating one potentially deadly treatment side-effect.


Newly Developed Test Shows Promise for Assessing Metastasis Risk in Uveal Melanoma Patients

Castle Biosciences, Inc. recently launched a new test to help doctors better asses the risk of uveal melanoma metastasis.

Uveal melanoma ranks as the most common eye cancer in adults. About half of patients diagnosed with uveal melanoma develop metastatic disease, primarily in the liver.

Researchers have found gene expression levels of PRAME (Preferentially Expressed Antigen in Melanoma) correlate with an increased risk of metastasis in patients diagnosed with uveal melanoma. The newly developed gene expression profile (GEP) test measures levels of PRAME.

“Our research shows that the expression of PRAME above a specific threshold in uveal melanoma is a strong predictor of increased metastatic risk in patients with a Class 1 uveal melanoma who otherwise would be assumed to be at low risk,” University of Miami School of Medicine Dr. J. William Harbour, said. “By combining results of the gene expression profile and PRAME tests, we believe we can enhance the accuracy of metastatic risk stratification in patients with uveal melanoma.”

The test is designed to be used in conjunction with DecisionDx-UM, the company’s primary uveal melanoma test.

“DecisionDx-UM is the standard of care to identify patients whose eye tumors are likely to spread and become deadly,” President and CEO of Castle Biosciences Derek Maetzold said. “We believe the DecisionDx-PRAME test used in conjunction with the results of the DecisionDx-UM test can enable further precision of a patient’s predicted risk for metastasis and help guide physicians and patients to the most appropriate follow-up care regimens.”

In a study published last March in Clinical Cancer Research, researchers found that PRAME could distinguish between GEP Class 1 tumors that would metastasize versus those that would not. Through the study, researchers were able to determine a threshold to signify positivity in uveal melanoma tumors. Tumors that metastasized in the study were all positive for PRAME expression according to this threshold.

Castle Biosciences went on to perform technical validation of the threshold in a 958 patient sample study. In addition, researchers found patients with high metastatic risk Class 2 tumors who were positive for PRAME expression may be at higher risk of earlier metastasis compared to patients with Class 2 tumors that were PRAME negative.

Dr. Paul Finger said that while more study is necessary, the new test shows promise.

“Though we all look forward to an independent GEP and PRAME validation study, these tests are promising developments for measurement of the risk for uveal melanoma metastasis,”he said. “Early treatment and therefore early detection is key to prolonging life. Therefore this new PRAME-test should help doctors better define an individual patients risk for choroidal melanoma metastasis.”


Experimental Treatment for Ocular Melanoma Liver Metastasis Shows Promise

A new experimental treatment offers some hope for patients with ocular melanoma that has metastasized to the liver.

Ocular melanoma is the most common eye cancer in adults. About 50% of patients diagnosed with ocular melanoma go on to develop metastatic disease. In 95% of cases, the liver is the first place metastases are discovered. This is because ocular melanoma spreads through the blood-stream as opposed to the lymphatic system, making the liver susceptible to metastasis.

liver-tumor

A patient’s prognosis is generally poor once the melanoma spreads. According to the Ocular Melanoma Foundation, median survival time is between two and eight months without treatment. Standard chemotherapy tends to be ineffective, but a new experimental therapy called percutaneous hepatic perfusion (PHP) shows promise. It is now undergoing clinical trials led by the National Cancer Institute.

In PHP, doctors isolate the liver and fill it with the chemotherapy drug Melphalan. During the procedure, a catheter with a balloon on either end is inserted through several needle punctures in the skin. The balloons are then inflated, sealing off the vein above and below the liver. Once isolated, high-dose, heated chemotherapy is infused through the liver. Charcoal filters remove chemotherapy from the blood as it is returned to the body through a second catheter in the neck.

A 2010 study published in the American Journal of Clinical Oncology revealed the potential benefits of using PHP to treat both ocular and skin melanomas that have metastasized in the liver. In the study, researchers concluded the treatment significantly improved progression-free survival rates compared to the best available options.

Clinical trials have reinforced cause for optimism. In one case, Sabrina Frey, 43, recently underwent PHP treatment at Moffitt Cancer Center in Tampa, Florida. She was featured in news reports across the country and says the treatment visibly reduced her tumors.

“Some tumors are not actually even visible on my MRI’s anymore,” Sabrina said.

While PHP seems to have reduced the size of metastatic ocular melanoma tumors in the liver, it is not a cure. Researchers say the earlier the treatment is started, the better the outcome. It seems to be most successful in patients with strong liver function and a limited number of metastatic tumors.


Research Shows Link Between Genetic Markers for Pigmentation and Uveal Melanoma

A recent study published in the journal Scientific Reports appears to establish a link between certain genetic factors relating to eye color and skin pigmentation, and the risk for uveal melanoma.

Uveal melanoma (UM) is the most common primary adult intraocular cancer involving the vascular layer within the eye between the retina and the sclera. Researchers have long suspected that people with light pigmentation and blue eyes have an increased risk of developing this type of eye cancer. Previous studies show that about 12% of uveal melanoma manifest within family circles, often involving a variety of other cancers including skin cancer. The co-occurrence of skin cancer and UM within some families suggests a shared predisposition to both types of cancer.

blue-eyes

But despite the suspicion that there are genetic risk factors involved in uveal melanoma, there has been little solid research establishing a firm link.

To study the possibility, researchers at the Perlmutter Cancer Center of the New York University School of Medicine selected 28 genetically based variations (SNPs) found within a given population of people. SNP variations have been shown to underly differences in susceptibility to diseases (such as sickle-cell anemia and cystic fibrosis) within different groups of people.

For the study, researchers conducted association analysis using 272 UM patients and 760 controls of European ancestry. Focusing on SNPs associated with skin cancer and related characteristics (including skin and eye pigmentation), they found five variants significantly associated with UM risk. In a nutshell, the study provides evidence that there is a link between light skin pigmentation (and blue eyes) and uveal melanoma:

“The identification of novel germline genetic loci involved in UM susceptibility in our study provides the first evidence of a link between the inherited genetics of pigmentation and UM risk. It has been established that lighter pigmentation and chronic sun exposure impact the development of choroid nevi, which occur in ~7% of the US population and are a known precursor for UM. Testing the associations in this study in the context of UM risk and the presence of ocular nevi will also be important in future analyses… Importantly, these genetic observations are also in clear alignment with previous epidemiological studies demonstrating that light eye color is indeed a UM risk factor.”

The association between skin cancer, uveal melanoma, and the emerging evidence of some genetic predisposition for the development of uveal melanoma underscores the importance of fair-skinned people protecting their eyes from sun exposure just like they do their skin. Since you can’t rub suntan lotion on your eyeballs, it’s important to wear sunglasses that provide 100% UV protection. Think of sunglasses as sunblock for your eyes. In fact, it’s a good idea for everybody to wear UV-cancelling sunglasses to protect their eyes from dangerous ultra-violet light rays.


Patient Stories

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