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 care cited here comes of age.

Ocular (uveal) melanoma patients who have had liver metastases and have undergone treatment have generously provided their stories here.

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.

Firstly, if a person has had ocular (uveal) melanoma, it is crucial that he have regularly scheduled MRI or 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.

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 recently 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. Ocular melanoma is rare, and even more aggressive than cutaneous.

Most oncologists will never see this rare tumor in a lifetime, 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.

What is the response rate? You are asking what percentage of patients treated (for this precise tumor) 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, avoid choosing a treatment which will produce futile suffering and waste 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.

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 are inaugurating a special Metastatic Uveal Melanoma Program (Sept. 2003). . Website address is: http://www.KimmelCancerCenter.org/clinical/patients/sites/UvealMelanoma/UvealMelanoma.htm. Tel: 1-800 JEFF NOW. Email: JEFF.NOW@mail.tju.edu.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.

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.

Isolated Heat Perfusion: Dr. H. Richard Alexander has an isolated heat perfusion trial at NIH in Bethesda MD, about which several patients have written to me. The liver is actually isolated from the body and given its own blood supply while it is flooded with chemochemicals. Apparently this drastic method (6 1/2 hour surgery) is quite successful with patients whose lesions are extremely small. Patients over 65 are not eligible for this trial and the metastasis must be only in the liver. Dr. Alexander's nurse: cynthiahelsabeck@nih.gov

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: brownda@mir.wustl.edu 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"

Livercancer.com/ablation.html

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 treatment 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: scott.foster@60mdg.travis.af.mil).

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

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.

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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)".