PHILADELPHIA (Ivanhoe Newswire) - Did you know melanoma can affect the eyes? In fact, it's the most common and most dangerous form of eye cancer in adults. Half the time it spreads and if that happens it's almost 100 percent fatal. Now, a new breakthrough therapy gives patients more time.
Molly Larkin's kids are the focus of her life, but eye cancer could keep her from watching them grow up.
"I just, I just, don't dwell on the what-ifs," Molly Larkin, uveal melanoma patient, told Ivanhoe.
Molly was diagnosed with ocular melanoma ten years ago. She was treated and thought she was in the clear.
"By the time we got to eight years I wasn't too worried about it anymore," Larkin said.
However, a routine exam showed Molly was among the 50 percent of patients in whom the fatal cancer spreads to the liver. Once that happens, Dr. Carin Gonsalves said the outlook is grim.
"Their overall survival is less than 6 months with a one year survival of about 13%," Carin F. Gonsalves, MD, at Thomas Jefferson University Hospital, told Ivanhoe.
Now a new therapy, immunoembolization, could improve those odds. Doctors inject an immune system booster directly into the arteries that supply blood to tumors in the liver. The booster blocks blood flow and starves the tumor.
"This GM-CSF stimulates the body's immune system to recognize the tumor as foreign and therefore kill it," Dr. Gonsalves stated.
The technique is prolonging life expectancy from less than six months without treatment to an average of two years, time this mom is thankful for.
Thomas Jefferson University Hospital developed the therapy and is the only hospital in the world offering it. The injection is not a cure. Patients come in once a month for the treatment and must stay overnight for observation. Because of the aggressive nature of this cancer, patients often require treatment for life.
RESEARCH SUMMARY
BACKGROUND: Melanoma is a type of cancer that develops in melanin producing cells, cells that pigment your skin. The eyes also can develop melanoma because they have melanin-producing cells. Eye melanoma, also called ocular melanoma, is difficult to detect because it forms in part of the eye that you can't see when looking into the mirror and it does not usually cause any symptoms. When symptoms do occur, they can include: a growing dark spot on the iris, a change in the shape of the pupil, a sensation of flashing lights, loss of peripheral vision, blurry vision in one eye, and specs of dust in your vision (floaters). (Source:www.mayoclinic.com)
CAUSES: Doctors do not know exactly what causes eye melanoma. It occurs when errors develop in the DNA of healthy eye cells. The DNA errors tell the cells to grow and multiply. Then they accumulate in the eye and turn into eye melanoma. Eye melanoma mostly develops in the cells of the vascular layer of the eye (uvea), which is between the retina and the sclera (the white area of the eye). It can develop in the front part of the uvea, the iris, or the back part, the choroid layer. Also, eye melanoma can develop in the conjunctiva, the outer layer on the front of the eye, in the socket that surrounds the eyeball and on the eyelid; however, these types are very rare. Some risk factors for developing melanoma include: light eye color, being Caucasian, certain inherited skin disorders, increasing age, and exposure to ultraviolet light. (Source: www.mayoclinic.com)
TREATMENT: Eye melanoma can cause certain complications. It increases pressure within the eye, which is called glaucoma. It can also lead to vision loss that can also cause retinal detachment. It can spread to other areas of the body, like the liver, bones, and lungs. Treatment options will depend on the size and location of the eye melanoma. For small melanomas, surgery can be done to remove the melanoma and a tiny area of the healthy tissue. Surgery to remove small melanoma in the iris is called iridectomy. Surgery to remove it in the choroid is called choroidectomy. For large eye tumors, surgery can be done to remove the entire eye, called enucleation. Radiation therapy can also be used to treating small to medium-sized melanomas. Laser treatment can also be used to kill the melanoma cells and extreme cold treatments, called cryotherapy. However, cryotherapy is not a common one. (Source:www.mayoclincic.com)
NEW TECHNOLOGY: Among patients who have eye melanoma, 50 percent of patients will have it lead to liver cancer. Physicians at Thomas Jefferson University Hospital developed a new therapy to treat these patients, called Immunoembolization. They inject drugs that stimulate or modulate the immune responses, called cytokines, into the arteries that supply the liver, along with the embolization of the hepatic artery. Conventional treatment only offers a five month survival rate, but Immunoembolization offers an average 14.5 month survival rate. (Source:www.jeffersonhospital.org) During the phase I study of the safety of immunoembolization, 39 patients with malignant liver tumors with 34 of them having primary uveal melanoma were enrolled. They were given an infusion dose of GM-CSF every four weeks. Patients who completed two cycles of treatments were monitored for hepatic antitumor response and survival rates. Results showed that 31 patients with uveal melanoma demonstrated two complete responses, eight partial responses, and ten occurrences of stable disease in their hepatic metastases. Multivariate analyses indicated that female sex, high doses of GM-CSF and regression of hepatic metastases (complete and partial responses) were related to longer overall survival. (Source: www.ncbi.nlm.nih.gov)
INTERVIEW
Carin F. Gonsalves, MD, Associate Professor of Radiology, Division of Interventional Radiology at Thomas Jefferson University Hospital and Jefferson's Kimmel Cancer Center, talks about a new therapy for uveal melanoma.
What is ocular melanoma?
Dr. Gonsalves: Uveal melanoma is a malignant tumor of a part of the eye known as the uvea. It typically strikes people who have inability to tan or people with light-colored eyes, such as blue or green eyes.
It is a deadly form of cancer?
Dr. Gonsalves: It is a very deadly form of cancer if it escapes the eye. But fortunately, it is a rare tumor. Only twenty five hundred cases are diagnosed each year in the United States. However, up to fifty percent of patients can develop tumors outside of the liver known as metastatic disease and at that point it becomes a very deadly disease.
So it can spread to the liver. Can you talk about what happens once it does spread?
Dr. Gonsalves: What's unique about uveal melanoma is that when it metastasizes, it most commonly spreads to the liver. Seventy to ninety percent of patients will develop only liver metastasis. Once the tumor metastasizes to the liver, the overall survival is less than six months with a one year survival of about thirteen percent. Therefore, it's very critical to control the growth of the liver metastases in order to prolong the survival of patients with metastatic uveal melanoma.
I know this drug has been around for a while but with the dosage you're actually helping increase survival. Can you talk about how this is changing things for people?
Dr. Gonsalves: We have been performing immunoembolization for several years now with GMCSF. Initially, our first immunoembolization study looked at dosing of GMCSF and the maximum tolerated dose. In other words, we increased the dose from 25 micrograms all the way up to 2,000 micrograms. In that study, we found that the overall survival increased to a median overall survival of 14.5 months, with a one year survival of 62 percent. In more recent years we've been using a higher dose, 1,500 micrograms or more, to treat patients with liver metastases. What we found was that patients seem to have a better overall survival, with a higher dose of GMCSF, increasing median overall survival to greater than 25 months.
What is the mechanism behind it?
Dr. Gonsalves: Immunoembolization is an approach that was developed by Dr. Takami Sato. He's one of our medical oncologists who specialize in metastatic uveal melanoma. As an interventional radiologist, I perform the procedure. I place a hollow tube or catheter from an artery in the groin all the way up to the liver using X-ray. The hepatic arteries supply the liver as well as the liver tumors. GMCSF is injected into the hepatic artery. GMCSF is an immune system modulator, which stimulates the body's immune system to recognize the tumor as foreign; therefore, the immune system kills it or prevents tumor growth. Following the injection of GMCSF, blood flow to the tumors is blocked. The blockage of blood flow is called embolization. Embolization deprives tumors of oxygen causing death of tumor cells.
Does the catheter go into the groin?
Dr. Gonsalves: It goes right into an artery in the groin known as the common femoral artery. It's not painful. We give patients sedation to make them comfortable, but it's really not a painful procedure and it usually takes less than an hour to perform.
So they are awake?
Dr. Gonsalves: They are sedated but we can wake them up so they can hold their breath so we can take pictures of the liver. The medication we use makes them very comfortable.
Is that the new direction of medicine, to work with the body's own immune system?
Dr. Gonsalves: Yes, manipulating the immune system to fight cancer is an important aspect of medicine especially with uveal melanoma, which is resistant to intravenous chemotherapy.
Is the tumor reabsorbed or is it removed?
Dr. Gonsalves: The body can eventually resorb the dead tissue. It is not removed. This can take time. Therefore, we can often see tumor on post procedure imaging, but it may not have any viable tissue, meaning that it's not alive.
Is this basically a death sentence for most people?
Dr. Gonsalves: Yes. This is not a cure. There is no cure for metastatic uveal melanoma. Our goal is to prolong the survival of these patients and provide them with good quality of life between treatments for as long as possible.
How much longer is this drug letting people live?
Dr. Gonsalves: Right now we're looking at more than two years instead of less than six months. If patients progress through this particular treatment, we do have other treatments similar to this one that are slightly more aggressive than immunoembolization. However, we have managed to keep people alive and provide them with a good quality of life for years, which is very encouraging for patients with this disease.
Is there a way that they could have a transplant?
Dr. Gonsalves: No, because it's such an aggressive tumor. Also, there is a limited amount of livers available for transplantation and patients do not have time to wait for one to become available. So, they are not a candidate for transplantation. In addition, less than 10 percent of patients are eligible for resection of uveal melanoma liver metastases because patients usually have multiple tumors at the time of diagnosis.
If they were able to get a transplant, would that help or is the cancer so aggressive it would end up attacking that new healthy liver?
Dr. Gonsalves: The theory is that micro-metastases have already been released into the circulation when the primary eye tumor is treated. So even though you remove the liver, the micro-metastases are still circulating in the bloodstream. Therefore, tumors would likely grow within the transplanted liver especially because transplanted patients require drugs that suppress the immune system to prevent rejection. A weak immune system will allow tumor to grow.
If you catch it early enough, is there a way to stop it in its tracks?
Dr. Gonsalves: There are institutions working on this. Unfortunately, there are no drugs that can be given to prevent metastatic disease. Up to 50 percent of patients will get metastatic disease of the liver and elsewhere in the body, but the liver is the organ that most commonly decreases survival more than other areas of the body. Therefore, treatment of liver tumors is very important.
Can you talk about Molly's case?
Dr. Gonsalves: Molly is wonderful. She has two small children and a very supportive husband. I met her about a year ago. However, she knew Dr. Sato for several years when she was first diagnosed with her eye tumor. Unfortunately, approximately a year ago she was found to have four tumors within her liver. We have been treating her ever since with immunoembolization. She has had 12 treatments so far and is doing quite well. Currently, we can only see three out of four tumors. We are hoping her next set of imaging will show even better results.
What size would you say Molly's tumors were?
Dr. Gonsalves: They are about two centimeters, about the size of a nickel. She was discovered early because she was already seeing Dr. Sato after her primary eye tumor was treated. He followed her with MR imaging of her liver so he detected the tumors within her liver early.
What is the drug called?
Dr. Gonsalves: GMCSF stands for granulocyte macrophage colony stimulating factor. For the most part, it is a very easy treatment. As you will see today, Molly will go home and take care of her two little kids without any problems. She handles this treatment extremely well. Patients stay overnight after the procedure so that we can monitor them for any kind of side effects such as pain. Typically they don't require much medication.
FOR MORE INFORMATION, PLEASE CONTACT:
Carin F. Gonsalves, MD
Associate Professor of Radiology, Division of Interventional Radiology
Thomas Jefferson University Hospital
Jefferson's Kimmel Cancer Center
Carin.gonsalves@jefferson.edu
