Uveal Melanoma Metastatic to the Liver
Recent Medical Developments:
you don't have to "go home and die"
If you have recently been diagnosed with ocular/uveal melanoma and are considering enucleation, please go to this link.
This page is dedicated to my beloved father, John Brockman, who died June 29, 2000. Had we known the information on this page, he might have gotten one, perhaps two or more additional years of good quality life. Instead, we were advised by our oncologists that nothing could be done. This was the beginning of our search, within the medical community, for a cutting-edge treatment for this rare form of metastatic melanoma. Very few doctors are aware of the extraordinarily aggressive nature of this tumor, and even fewer are aware of recent developments which can at least significantly prolong life, if not cure the cancer.
For you reading this page, whether patient or loved one, your job is to keep the patient alive with good quality of life until something better than the palliative treatments cited here become available.
Ocular (uveal) melanoma patients who have had liver metastases and have undergone treatment have generously provided their stories here.
Time is of the essence.
When you find an appropriate treatment, you must convince your doctors to take action immediately. At each stage, as we discovered the next possible treatment, the tumor had already grown too large for it. My dad, who was otherwise in perfect health, was dead just eight weeks after diagnosis.
The Liver is the site of 95% of all uveal melanoma metastases.
Firstly, if a person has had ocular (uveal) melanoma, it is crucial that he have regularly scheduled CT scans of the liver. The standard liver enzyme tests are often normal, due to hepatic reserve, until the tumor is well advanced; these only catch ca. 70% of metastases. My dad was in the other 30%. The earlier this tumor is detected, the greater the patient's life expectancy.
Screening for metastatic malignant melanoma of the uvea revisited.
Liver function tests in metastatic uveal melanoma, Am J Ophthalmol.
Since the quality of MRI scans varies tremendously, you might be better off sticking with CT scans:
http://emedicine.medscape.com/article/369936-overview Updated: Dec 12, 2013
Medscape: In general, the imaging appearances of liver metastases are nonspecific, and biopsy specimens are required for histologic diagnosis. CT is the imaging modality of choice for evaluating liver metastases.
New York Times Article (Oct. 13, 2008): The Scan That Didn't Scan (excerpt): "Radiology centers send written reports to doctors, but the doctors may have no idea whether the M.R.I. was done well and interpreted well. “It’s a huge problem,” Dr. Black [professor of radiology and community and family medicine at Dartmouth Medical School] said.
Unlike C.T. scans or X-rays, which transmit radiation through the body to produce images, M.R.I.’s use powerful magnets and radio waves to manipulate protons in the body’s hydrogen atoms. The idea, said Dr. Andrew H. Haims, a diagnostic radiologist at Yale, is that protons in different types of tissue respond in distinctive ways to this pushing and prodding. The differing responses reveal the characteristics of the tissue.
Magnetic resonance machines, though, vary enormously, and not just in the strength of their magnets. Even more important, radiologists say, is the quality of the imaging coils they put around the body part being scanned and the computer programs they use to control the imaging and to analyze the images. And there is a huge variability in skill among the technicians doing the scans." © 2008 by The New York Times
Cutaneous and ocular melanoma are two different beasts.
Chemotherapy which may produce response in cutaneous melanoma has not been thought to be effective for ocular; ocular patients have long been excluded from melanoma trials. This has been questioned in the literature (Metastatic melanoma from intraocular primary tumors: the Southwest Oncology Group experience in phase II advanced melanoma clinical trials). Since the rate of occurrence of cutaneous melanoma is growing at 5% a year, there is much more research being done on it. However, ocular melanoma is extremely rare, and even more aggressive than cutaneous. So if your oncologist is treating you as though you had cutaneous melanoma, find another doc.
You're on your own--at least, we were.
This cancer is rare, and physicians are so specialized that they seldom know what is currently available at the next level, should it be too late for their own area of expertise.
Your first move should be to subscribe to the OCU-MEL Email List. This is where the mets survivors congregate. It's an extremely supportive and knowledgeable group. Feel free to ask questions about your case, their docs and treatment.
Regardless of whether you have any medical background, you can do significant research on the internet. Then, get on the telephone; you'll find that doctors, clinical nurses and other medical professionals are remarkably generous with time and information.
When writing or calling doctors, be sure to have all of the patient's lab reports organized in front of you: CT scan, Liver Function Test (blood test which will have the bilirubin level etc.), biopsy report etc. The liver CT scan report should list the size of tumor(s). If not, call the doc who wrote it, and ask to have the scan reviewed for this information.
When researching treatments, here are some questions to ask:
Ask what percentage of patients treated (for Ocular Melanoma which has metastasized to the liver) show a response? Response is defined as shrinkage of the tumor by 50% or more. If the response rate is similar to the placebo effect (ca. 15%), the treatment will produce futile suffering and compromise the patient's remaining time for good quality of life.
Precisely what is the method used for this treatment (duration of procedure, prep etc), and what are the chemochemicals used (if any)?
What are the side effects and how long will they last?
What is the average time before recurrence (if any)?
Can the procedure be safely repeated? Or what is the next line of treatment?
Be sure to get a 2nd, 3rd etc. opinion from doctors at reputable medical centers before deciding on a course of treatment.
I am not a medical doctor. The links and ideas here are the result of my search, presented in the hope that other lives may at least be prolonged.
Where to start: consider Immunoembolization, Isolated Liver Perfusion, Stereotactic Body Radiosurgery, Radiofrequency Ablation, or Chemoembolization.
These treatments are palliative. Tumor cells are seeded in the bloodstream, and will begin to grow again. Don't be greedy though, as these methods may have the highest response rate available.(Response rate is defined as tumor shrinkage of 50% or more.) With these procedures, you are buying time, in the hope that something better will have come of age when you need it. And the quality of prolonged life is good. These procedures can sometimes be repeated several times over a period of years. If you hear from your oncologist that a procedure is too dangerous, get a second, third or fourth opinion (but do it FAST), as some doctors are having success with these treatments. Bilirubin level seems to be the most important consideration regarding safety of the procedures.
Immunoembolization: Oncologist, Dr. Takami Sato (treats many of the patients on the Ocu-mel Email List) uses immunoembolization with GM-CSF etc. He is at the Kimmel Cancer Cancer at Thomas Jefferson University Hospital, Philadelphia, where they have a special Metastatic Uveal Melanoma Program. Website address is: http://www.KimmelCancerCenter.org/clinical/patients/sites/UvealMelanoma/UvealMelanoma.htm. Here is Dr. Sato's April 2002 article in Seminars in Oncology Online . Excerpt from the abstract:
Embolization of melanoma metastatic to the liver with a granulocyte-macrophage colony-stimulating factor (GM-CSF)/ethiodized oil emulsion resulted in control of liver metastases, as well as development of significant immune responses in remote extrahepatic metastases. A gene therapy designed to introduce foreign major histocompatibility complex (MHC) molecules in colorectal metastases has proven to be a safe and feasible approach. Larger scale clinical trials are mandatory to define the role of locoregional immunotherapy for metastatic tumors in the liver. Semin Oncol 29:160-167. Copyright 2002, Elsevier Science (USA). All rights reserved.
American Society of Clinical Oncology, October 14, 2008: "Immunoembolization safe, promising for liver metastases from uveal melanoma" Excerpt:
NEW YORK (Reuters Health) - A novel immunoembolization therapy using granulocyte-macrophage colony-stimulating factor (GM-CSF) safely achieved regression of unresectable liver metastases from uveal melanoma, according to a phase I study by U.S. researchers, published online by the Journal of Clinical Oncology.
Immunoembolization is a variation of chemoembolization, which involves infusing a cytotoxic agent into a tumor after mechanically or surgically disrupting the tumor's blood supply. (Most often, hepatic artery chemoembolization is performed to control hepatocellular carcinoma.)
Theoretically, the authors explain, the advantage of immunoembolization is that it could attract and stimulate antigen-presenting cells in liver tumors and improve the uptake of tumor antigens released from necrotic tumor cells, as well as potentially facilitate a systemic immune response against tumor cells and thereby suppress the growth of extrahepatic metastases.
Furthermore, recombinant human GM-CSF (these researchers used sargramostim) has been shown to stimulate macrophages and to increase the cytotoxicity of monocytes toward malignant melanoma cells in vitro. "As long as patients do not have any extra-hepatic metastasis, or as long as extra-hepatic metastases are small or controlled, our approach should work for other types of melanoma," Dr. Takami Sato of Thomas Jefferson University, Philadelphia, told Reuters Health.
Read the whole article.
IMC-A12, or Cixutumumab is another treatment presently being used by Dr. Sato and some others.
Stereotactic Body Radiosurgery: According to Dr. Robert T. Woodburn, M.D. (contact info below), this is a completely non-invasive procedure that eradicates tumors of the liver and lung. Stereotactic Body Radiosurgery uses multiple high energy beams converging to the tumor with extreme precision. Stereotactic Body Radiosurgery is 90% effective at eradicating the treated tumors. Treatments last about 30 minutes. There are virtually no side effects. The treatment is usually given in every other day for 3 sessions. Potential candidates have 5 tumors or less and must have enough remaining healthy liver/lung, as determined by the physician.
Robert T. Woodburn, M.D., Cancer Treatment Group at Methodist Hospital, Merrillville, IN (near Chicago) is currently performing stereotactic body radiosurgery for metastatic melanoma to the liver and lung. More information is here.
Radiofrequency Ablation: if the tumor is no larger than 3.5 cm in diameter (in some cases, 5 cm.) and the bilirubin level is still normal, consider RFA, a relatively safe laparoscopic procedure which zaps the neoplasm electronically.
Radiofrequency Waves Used to Kill Inoperable Liver Tumors
Among many sources for RFA treatment and info:
Daniel Brown, MD, Washington University School of Medicine, St. Louis, MO is currently performing both chemoembolization and radiofrequency ablation of ocular melanoma metastases in the division of interventional radiology. A formal treatment group is being developed consisting of William Harbour (ocular oncologist/ophthalmologist) and Gerry Linette an oncologist specializing in treatment of melanoma metastases. Dr. Brown's email: firstname.lastname@example.org and his nurse coordinators can be reached at 314-362-2353.
Anton Bilchik, MD, PhD, John Wayne Cancer Institute, Santa Monica, CA; ("Radiofrequency Ablation: A Minimally Invasive Technique with Multiple Applications", The CANCER Journal from Scientific American; first presented at the American Radium Society meeting, Kona Hawaii, April 17-21, 1999; reprint requests--contact Dr. Bilchik's office at JWCI). University of California at Davis. M.D. Anderson Cancer Center in Houston, TX (Radiofrequency Ablation of Malignant Liver Tumors) University of Minnesota Cancer Center "U of M physicians use heating device to treat liver cancer"
Radioembolization / Sir Spheres: here's a utube video of Dr. Dan Sze at Stanford explaining this procedure 7.21.2010
Sir Spheres: this treatment involves injecting tiny glass beads of radiation into the liver tumors via the hepatic artery. Ellen Buchanan has had much success with this treatment. She may be contacted though the Ocu-Mel email list (subscription instructions are below), and others on that list are trying it--so be sure to subscribe, and feel free to ask questions. See Ellen's story here.
There is now a support group for Spheres patients. To join, send an email to: email@example.com
Chemoembolization: Bilirubin level must not be higher than 2 or 2.5 for this treatment. This is localized chemotherapy, usually done in two or more treatments, ca. a month apart. If both lobes of the liver are involved, normally only one lobe is done at a time. Unlike conventional systemic chemotherapy, the drugs injected through the hepatic artery are confined to the liver. Side effects of chemotherapy are minimized as a result, and patient's recuperation time is only ca. one to two weeks. Also a palliative treatment.
Interventional Radiologists for this chemoembolization include:
See Daniel Brown, MD, Washington University School of Medicine, St. Louis, MO listed above under Radiofrequency Ablation.
Dr. Michael Soulen, University of PA Medical Center, Philadelphia (has much experience with ocular melanoma and chemoembolization). Penn Researchers Find Chemoembolization Effective for Liver Tumors Dr. Dan Sze and Dr. Mahmood Razavi,Stanford Medical Center, Stanford, CA. M.D. Anderson Cancer Center (Houston, TX) Liver Tumor Specialists Dr. Scott Foster, USAF Medical Center, Travis Air Force Base, CA (email: firstname.lastname@example.org).
See Links to Online Journals: Radiology World.com
If you have difficulty in locating someone in your area for this procedure, you might seek a referral from one of the radiologists above.
Some Important Articles and Ideas
Yervoy (Ipilimumab): The U.S. Food and Drug Administration today (Mar. 25, 2011) approved Yervoy (ipilimumab) to treat patients with late-stage (metastatic) melanoma. It may prove useful for ocular melanoma patients too. Read the FDA statement.
The MEK inhibitor AZD6244 is active in GNAQ mutant ocular melanoma cells
Presentation Time: Wednesday, Apr 21, 2010, 8:00 AM -11:00 AM
Author Block: Grazia Ambrosini, Gary K. Schwartz. Mem. Sloan-Kettering Cancer Ctr., New York, NY
Abstract Body: Uveal melanoma represents the most common intraocular malignancy in the United States. However, there are no effective treatments for this aggressive metastatic disease. While activating mutations in B-RAF are rare in ocular melanoma, oncogenic G protein alpha subunit q (GNAQ) mutations at codon 209 have been described in about 50% of uveal melanomas. Knock-down of GNAQ by siRNA inhibits p-ERK and the MEK inhibitor U0126 has been shown to inhibit growth of a GNAQ mutant cell line (Van Raamsdonk CD et al, Nature 2009). AZD6244 (ARRY-142886) is a MEK inhibitor now in clinical trials. Published phase I results have indicated clinical benefit in a patient with ocular melanoma (Adjei AA et al, J Clin Oncol. 2008). In view of this, we elected to test AZD6244 across a panel of ocular melanoma cell lines that differ in their GNAQ mutational status. Treatment with AZD4244 inhibited cell proliferation in a time- and dose-dependent manner, with IC50s in the 100-150nM range. This corresponded to the inhibition ERK phosphorylation and down-regulation of cyclin D1 in GNAQ mutant (both Q209L and P209L), but not in GNAQ wild-type cells. Over-expression of mutant GNAQ(Q209L) in wild type OCM290 cells, which are highly resistant to AZD6244, resulted in drug sensitization with inhibition of ERK phosphorylation. Depletion of GNAQ by siRNA in the GNAQ mutant cells resulted in inhibition of ERK phosphorylation and growth suppression. Interestingly, GNAQ depletion had no effect on ocular melanoma cells with wild type GNAQ or mutant B-RAF. We conclude that the GNAQ activating mutation in ocular melanoma can mediate sensitivity to AZD6244. This data provide a rationale for the clinical evaluation of AZD6244 in uveal melanoma.
Researchers Effectively Treat Tumors with Use of Nanotubes Jul 31, 2009
August 2009 issue: Proceedings of the National Academy of Sciences. (Not tested on humans yet) WINSTON-SALEM, N.C. By injecting man-made, microscopic tubes into tumors and heating them with a quick, 30-second zap of a laser, scientists have discovered a way to effectively kill kidney tumors in nearly 80 perce nt of mice. Researchers say that the finding suggests a potential future ca ncer treatment for humans.
The study appears in the August issue of PNAS (Proceedings of the National Academy of Sciences). It is the result of a collaborative effort between Wa ke Forest University School of Medicine, the Wake Forest University Center for Nanotechnology and Molecular Materials, Rice University and Virginia Tech.
When dealing with cancer, survival is the endpoint that you are se arching for said Suzy Torti, Ph.D., lead investigator for the study and professor of biochemistry at Wake Forest University School of Medicine. It's great if you can get the tumor to shrink, but the gold standard is to make the tumor shrink or disappear and not come back. It appears that we've found a way to do that.
Nanotubes are long, thin, sub-microscopic tubes made of carbon. For the stu dy, researchers used multi-walled nanotubes (MWCNTs), which contain several nanotubes nested within each other, prepared for the study by the Center for Nanotechnology and Molecular Materials. The tubes, when non-invasively exposed to laser-generated near-infrared radiation, respond by vibrating, creating heat. If enough heat is conducted, tumor cells near the tubes begin to shrink and die.
Using a mouse model, researchers injected kidney tumors with different quantities of MWCNTs and exposed the area to a three-watt laser for 30 seconds.
Researchers found that the mice who received no treatment for their tumors died about 30 days into the study. Mice who received the nanotubes alone or laser treatment alone survived for a similar length of time. However, in t he mice who received the MWCNTs followed by a 30-second laser treatment, re searchers found that the higher the quantity of nanotubes injected, the lon ger the mice lived and the less tumor regrowth was seen. In fact, in the gr oup that received the highest dose of MWCNTs, tumors completely disappeared in 80 percent of the mice. Many of those mice continued to live tumor-free through the completion of the study, which was about nine months later.
You can actually watch the tumors shrinking until, one day, they are gone, Torti said. Not only did the mice survive, but they maintained their weight, didn't have any noticeable behavioral abnormalities and experienced no obvious problems with internal tissues. As far as we can tell, other than a transient burn on the skin that didn't seem to affect the animals and eventually went away, there were no real downsides: that's very encouraging.
Current thermal ablation, or heat therapy, treatments for human tumors incl ude radiofrequency ablation, which applies a single-point source of heat to the tumor rather than evenly heating the tumor throughout, like the MWCNTs were able to. In addition to the MWCNTs used in this study, other nanomate rials, such as single-walled carbon nanotubes and gold nanoshells, are also currently undergoing experimental investigation as cancer therapies at oth er institutions.
MWCNTs are more effective at producing heat than other investigati onal nanomaterials, Torti said. Because this is a heat therapy rather than a biological therapy, the treatment works on all tumor ty pes if you get them hot enough. We are hopeful that we will be able to translate this into humans.
Before the treatment can be tested in humans, however, studies need to be d one to test the toxicity and safety, looking to see if the treatment causes any changes to organs over time, as well as the pharmacology of the treatm ent, looking at things such as what happens to the nanotubes, which are syn thetic materials, over time.
The treatment would need to be tested in larger animals before being tested in human trials, as well. Conceptually, however, Torti said there is no barrier to applying the therapy into humans to treat tumors close to the surf ace of the skin, such as in the oral cavity and bladder wall.
We're excited about this,Torti said. This is is the intersection between the physical and the medical sciences that represents the new frontier in modern medicine.
Co-authors on the study, funded by the National Cancer Institute, are Ravi Singh, Ph.D., Robert Kraft, Ph.D., Nicole Levi-Polyachenko, Ph.D., Heather Hatcher, Ph.D., Ralph D'Agostino, Jr., Ph.D., Nancy Kock, Ph.D., Steven Akman, M.D., Frank M. Torti, M.D. and Ph.D. students Andrew Burke and Xuanfeng Ding, all of the School of Medicine; David L. Carroll, Ph.D., dire ctor of the Wake Forest University Center for Nanotechnology and Molecular Materials; Marissa Rylander, Ph.D., Jon Whitney, M.S., Jessica Fisher, M.S. , and Ph.D. students Chris Szot and Cara Buchanan, of Virginia Polytechnic Institute and State University (Virginia Tech); and Pulickel Ajayan, Ph.D., of Rice University.
New Method of Gene Therapy Alters Immune Cells for Treatment of Advanced Melanoma; Technique May Also Apply to Other Common Cancers (National Institute of Health News August 31, 2006)
A team of researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, has demonstrated sustained regression of advanced melanoma in a study of 17 patients by genetically engineering patients’ own white blood cells to recognize and attack cancer cells. The study appears in the online edition of the journal Science on August 31, 2006*.
“These results represent the first time gene therapy has been used successfully to treat cancer. Moreover, we hope it will be applicable not only to melanoma, but also for a broad range of common cancers, such as breast and lung cancer,” said NIH Director Elias A. Zerhouni, M.D.
Autologous lymphocytes — a person’s own white blood cells — have previously been used to treat metastatic melanoma. In a process called adoptive cell transfer, lymphocytes are first removed from patients with advanced melanoma. Next, the most aggressive tumor-killing cells are isolated, multiplied in the lab, and then reintroduced to patients who have been depleted of all remaining lymphocytes. While reasonably successful, this method can only be used for melanoma patients and only for those who already have a population of specialized lymphocytes that recognize tumors as abnormal cells.
Thus, NCI researchers, led by Steven A. Rosenberg, M.D., Ph.D., sought an effective way to convert normal lymphocytes in the lab into cancer-fighting cells. To do this, they drew a small sample of blood that contained normal lymphocytes from individual patients and infected the cells with a retrovirus in the laboratory. The retrovirus acts like a carrier pigeon to deliver genes that encode specific proteins, called T cell receptors (TCRs), into cells. When the genes are turned on, TCRs are made and these receptor proteins decorate the outer surface of the lymphocytes. The TCRs act as homing devices in that they recognize and bind to certain molecules found on the surface of tumor cells. The TCRs then activate the lymphocytes to destroy the cancer cells.
In this study, newly engineered lymphocytes were infused into 17 patients with advanced metastatic melanoma. There were three groups of patients in this study. The first group consisted of three patients who showed no delay in the progression of their disease. As the study evolved, the researchers improved the treatment of lymphocytes in the lab so that the cells could be administered in their most active growth phase. In the remaining two groups, patients received the improved treatments. Two patients experienced cancer regression, had sustained high levels of genetically altered lymphocytes, and remained disease-free over one year. One month after receiving gene therapy, all patients in the last two groups still had 9 percent to 56 percent of their TCR-expressing lymphocytes. There were no toxic side effects attributed to the genetically modified cells in any patient. See the full NIH Press Release.
Hepatic resection for metastatic melanoma: distinct patterns of recurrence and prognosis for ocular versus cutaneous disease. * Pawlik TM, et al. (Ann Surg Oncol. 2006 May;13(5):712-20. Epub 2006 Mar 14.
Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 444, Houston 77030, USA.
BACKGROUND: Resection of melanoma metastatic to the liver remains controversial. We evaluated the efficacy of hepatic resection in patients with metastatic ocular and cutaneous melanoma and assessed factors that could affect survival after resection. METHODS: Forty patients with hepatic melanoma metastasis underwent resection at four major hepatobiliary centers. Clinicopathologic factors were evaluated with regard to recurrence and survival by using chi(2) and log-rank tests. RESULTS: The primary tumor was ocular in 16 patients and cutaneous in 24. The median disease-free interval from the time of primary tumor treatment to hepatic metastasis was the same for both groups (ocular, 62.9 months; cutaneous, 63.1 months; P .94). Most patients underwent either an extended hepatic resection (37.5%) or hemihepatectomy (22.5%). Twenty-six patients (65%) received perioperative systemic therapy. Thirty (75.0%) of 40 patients developed tumor recurrence. The median time to recurrence after hepatic resection was 8.3 months (ocular, 8.8 months; cutaneous, 4.7 months; P .3). Patients with primary ocular melanoma were more likely to experience recurrence within the liver (53.3% vs. 17.4%; P .015), whereas patients with a cutaneous primary tumor more often developed extrahepatic involvement. The 5-year survival rate for patients with a primary ocular melanoma was 20.5%, whereas there were no 5-year survivors for patients with cutaneous melanoma (P .03). CONCLUSIONS: Patterns of recurrence and prognosis after resection of hepatic melanoma metastasis differ depending on whether the primary melanoma is ocular or cutaneous. Resection should be performed as part of a multidisciplinary approach, because recurrence is common.
PMID: 16538410 [ PubMed - indexed for MEDLINE]
Study from Steven A. Rosenberg, M.D., Ph.D., of the National Cancer Institute (September 19, 2002): New Approach to Replacing Immune Cells Shrinks Tumors in Patients with Melanoma (Quoted from the press release.)
A new approach to cancer treatment that replaces a patient's immune system with cancer-fighting cells can lead to tumor shrinkage, researchers report today in the journal Science*. The study demonstrates that immune cells, activated in the laboratory against patients' tumors and then administered to those patients, can attack cancer cells in the body. The experimental technique, known as adoptive transfer, has shown promising results in patients with metastatic melanoma who have not responded to standard treatment. With further research, scientists hope this approach may have applications to many cancer types, as well as infectious diseases such as AIDS
In the study, 13 patients with metastatic melanoma (a deadly form of skin cancer) who had not responded to standard treatments were treated with immune cells produced in the laboratory specifically to destroy their tumors. The treatment resulted in at least 50 percent tumor shrinkage in six of the patients, with no growth or appearance of new tumors. Four additional patients had some cancer growths disappear. See full press release.
Important Article: "Tumor Doubling Times in Metastatic Malignant Melanoma of the Uvea: Tumor Progression Before and After Treatment" (Opthalmology Vol. 107, No. 8, August 2000, pp.1443-9)".
Based on their observation of the time it takes for tumors to double in size, the authors of this Finnish study speculate that perhaps when primary uveal melanoma is diagnosed in the eye, those that metastasize may be already present but undetectable in the liver. The authors point out that this hypothesis is complicated by the fact that tumors do not grow at a constant rate. They also found that chemoimmunotherapy slows down the growth rate of metastases, even if objective response does not result.
The opinions of the two physicians who wrote the accompanying guest editorial do not correlate with the information I was given by doctors at major cancer centers around the country regarding chemoembolization, and they do not mention radio-frequency ablation as a palliative treatment. By trying to provide here as much information as possible, I leave it to you, the reader, together with your doctors and the results of your own research, to draw your own conclusions. As the Finnish authors conclude, the state of knowledge in this area is rough, and must be confirmed by further studies.
This article summarizes results of many current treatments. Though ocular is mentioned regarding a couple of treatments, it mostly deals with cutaneous melanoma--there is still a question of how effective cutaneous melanoma treatments are on ocular patients. "Treating Melanoma: Old Myths and New Ideas"
Medscape coverage of: 38th Annual Meeting of the American Society of Clinical Oncology | Molecular Oncology (June 28, 2002). (You may need to complete their free registration in order to read this.)
We are on the brink of some extraordinary breakthroughs. Promising treatments include:
Immunotherapy (Used both as primary treatment and to prevent recurrence.)
December 2003 issue of Seminars in Cancer Biology is devoted to Immunotherapy of Melanoma
Volume 13, Issue 6, Pages 387-480 (December 2003)
Edited by: Soldano Ferrone and Francesco Marincola.
[Keep in mind that this information specifically refers to cutaneous melanoma, and what was said above about the differences between cutaneous and ocular melanoma.] Treating Cancer with Vaccine Therapy (National Cancer Institute) Biomedical Research: Immunology and Microbiology Melanoma Vaccines as a Therapeutic Option [South Med J 92(7):698-704, 1999]
Journal of Immunotherapy (requires subscription, or can purchase individual articles).
Because ocular melanoma is so highly vascular, inhibiting the growth of new blood vessels to the tumor makes good theoretical sense, and has been successful in mouse models. (Pioneered by Dr. Judah Folkman at Harvard/Boston Children's Hospital.) Results are not out though (as of this writing) on clinical trials in progress with Angiostatin, Endostatin (Entremed), Anti-VEGF (Genentech), and Thalidomide (Celgene), among others.
Thalidomide has been around since the 60s and is readily available. Here is a brief account of one patient's experience as posted on the OCU-MEL list.
See August 31, 2006 NIH News article above.
ASGT | American Society of Gene Therapy
Gene therapy runs into roadblocks (article):
"Fifteen years ago, scientists heralded gene therapy as a medical revolution that would quickly bring cures for crippling and deadly diseases.
Adenoviral-p53 therapy may benefit cancer patients (ASGT press release June 3, 2004)
After more than 900 clinical trials, however, gene scientists can claim few real successes, and even the technology's longtime supporters say gene therapy has developed far more slowly than they had expected." USA Today, April 2005 (more)
"Adenviral gene therapy with the p53 protein was safe and well tolerated in patients with advanced cancers, according to a study presented today at the 7 th Annual Meeting of the American Society of Gene Therapy (ASGT).
The p53 protein plays a central role in telling damaged cells to stop dividing or to give the damaged cell the signal to die. However, many tumors have mutated the p53 gene, resulting in its loss of function. In this study, researchers have developed an adenovirus vector that has had some of the adenovirus genes replaced with the p53 gene."
Among others, the Mayo Clinic (Rochester, Minn.) has a Molecular Medicine/Gene Therapy Center for cancer
Advances in Gene Therapy for Malignant Melanoma from Cancer Control: Journal of the Moffitt Cancer Center, Volume 9, Number 1 (April 2002).
Results: Clinical trials have shown the feasibility and safety of gene therapy against malignant melanoma. Although no major successes have been reported, the positive results observed in some patients support the potential for gene therapy in the management of this disease. (Read the article.)
Also, keep an eye out for developments regarding EGF (epithelial growth factors) and Erbitux. ImCLONE has had difficulty getting the FDA to approve Erbitux, (formerly known as IMC-C225) . Apparently there were questions about remarkable clinical trial results with the drug used in combination with chemotherapy. M.D. Anderson and others have been prescribing it for patients with metastatic lung, colon, pancreatic cancer on a compassionate use basis. What's New in Metastasis Prediction and Prevention? (Medscape requires free account setup.)
A reader sent me this account regarding Tetrathiomolybdate, a copper-chelator and angiogenesis inhibitor. Although it is new to me, this information is sufficiently well researched that I include it here, as it may be important.
Other Considerations--if you have symptoms:
It's crucial to keep the patient hydrated. Follow him/her around with water at all times. Crushed ice is also good for both hydration and nausea. Food Combining: making digestion as easy as possible. A complex subject, but applying the simple principles given here helped us a lot.
Food Combining Chart to print out--very useful
Principles of Combining Foods Properly. By Dr. Herbert M. Shelton, Reprinted from Dr. Shelton's Hygienic Review
Regardless of whether he/she appears to have difficulty breathing, if the patient says he/she can't seem to get enough oxygen, a rented oxygen concentrator may help tremendously.
CT vs. MRI Scans
Comparison Studies of CT and MRI in Patients With Hepatic Metastases
Other Important Links
OCU-MEL EMAIL LIST Your first move should be to subscribe to Pete Tustison's ocular melanoma liver mets list, OCU-MEL, for discussion with others in the trenches. These are the survivors, and they are often extremely knowledgeable. You can ask them questions about their docs and treatments.
To subscribe send an email to: OCU-MEL-subscribe-request@LISTSERV.ICORS.ORG
Leave the Subject blank. In the first line of the message body, type the following:
subscribe OCU-MEL firstname lastname [Type your actual first and last name.]
The command reference page can be found at: http://www.tustison.com/ocu-mel_listserv.shtml
This provides information and links for subscribing, signing off and other mail options for OCU-MEL.
OCU-MEL List-Archive & Help: http://listserv.icors.org/SCRIPTS/WA-ICORS.EXE?LISTOCU-MEL
Medscape (search for articles on all topics--free with registration)
PubMed (National Library of Medicine) This is what your doctor uses. You can get complete articles through Loansome Doc.
Melanoma Patients Information Page Excellent resource and message board/mailing list. Also has a medical dictionary and "glossifier" for translating "medicaleeze" in articles.
If you live in the UK, you can get info specific to treatment there at: Eye Cancer Forum UK
The Eye Cancer Network: Dr. Paul Finger's educational web-site about the diagnosis and treatment of ocular tumors, eye cancer, and orbital diseases for patients, their families and the health professionals who care for them.
Mike's Page: the Melanoma Resource Center is Pete Tustison's extensive source of information for every aspect of melanoma. He also moderates both the MEL-L and OCU-MEL email lists. See especially the Ocular Melanoma Links.
Cancerlinks.com's Ocular Melanoma section
Cancerlinks.com also has extensive links regarding every aspect of cancer.
The Society for Melanoma Research
The Foundation for Melanoma Research
CANSEARCH: Online Guide to Cancer Resources
The purpose of CanSearch is to assist online users in finding Internet cancer resources. CanSearch will take you step by step to each of the storehouses of cancer information.
Steve Dunn's Cancer Guide
Dedicated to helping you find the answers to your questions about cancer, and especially to helping you find the questions you need to ask. Also see: Researching the Medical Literature.
"An Online Zine for Cancer Patients and Professionals"
Treatment of Metastatic Choroidal Melanoma, by Dr. Bedikian (MD Anderson), Eye Cancer Network.
CancerNet (Information from the National Cancer Institute and National Institutes of Health)
American Liver Society: founded by caregivers and patients to help other caregivers and patients and those that may become affected by a liver disease by providing them with useful information on topics of the liver
A nonprofit organization whose mission is to provide free professional help to people with all cancers through counseling, education, information and referral, and direct financial assistance.
About Clinical Trials: My dad was not a candidate for these, but I was able to obtain useful information by contacting doctors and clinical nurses who are conducting these trials. Although it's becoming more difficult, it may be possible to obtain some new drugs outside of trials on a "compassionate use" basis, for example.
CancerTrials: A service of the National Cancer Institute
Cancer Treatment Studies - Clinical Trials
If you really want to know about the success of a new drug treatment or clinical trial: Check out the stock performance and financial news for the company which manufactures the drug. Company press releases (available on financial websites) may contain technical information which will give you an idea of a drug's performance in clinical trials.
Lastly, regardless of outcome, we found "The Tibetan Book of Living and Dying" by Sogyal Rinpoche (HarperSanFrancisco), with its message--if you know how to die, you know how to live--to be a remarkable resource. Death is the culmination of life.
Without the generosity of doctors and medical professionals all over the country, gathering the information here would not have been possible. I am exceptionally indebted to Dr. Elliot Eisenberg for instigating and directing my research--otherwise, we would never have known that there are alternatives to "go home and die". And, as he says, hope and belief are powerful forces.
Please feel free to email me, if I may be of help.
Last updated:Dec/ 12.2013
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