In the Clinic

On Cancer: Rare Medical Phenomenon: Melanoma Patient’s Tumors Disappear throughout the Body after Radiation of One Tumor

By Media Staff  |  Thursday, March 8, 2012
Pictured: Jedd Wolchok Medical oncologist and immunologist Jedd Wolchok

Researchers at Memorial Sloan Kettering have reported a rarely seen phenomenon in cancer patients: Metastatic melanoma tumors disappeared throughout the body after a patient received radiation focused on one tumor.

The patient had radiation therapy after treatment with ipilimumab (trade name YervoyTM), a type of immunotherapy that harnesses the body’s own immune system to attack cancer. The phenomenon, known as the abscopal effect, occurs when localized radiation therapy to a single tumor in patients with advanced disease results in tumor disappearance outside of the irradiated area. Though the abscopal effect is extremely rare, it has been described in several cancers including melanoma, lymphoma, and kidney cancer.

Findings from a multidisciplinary research team led by Memorial Sloan Kettering medical oncologist and immunologist Jedd Wolchok are published in the March 8 edition of the New England Journal of Medicine. This unique single-patient study could help shed light on the immune system’s role in fighting cancer.

“We are excited about these results, and what we have seen in this one patient proves the principle that adding radiation therapy to immunotherapy may be a promising combination approach to treatment for advanced cancer,” explains senior author Dr. Wolchok, while noting that this patient’s response to the radiation treatment might be unusual. The researchers cannot tell whether other patients receiving ipilimumab might benefit from radiation therapy until studies have been conducted in more patients.

Focusing Radiation Therapy on One Tumor

Dr. Wolchok and colleagues treated a patient with advanced melanoma whose disease had spread from a mole on her back to other parts of the body. The patient was enrolled in a clinical trial and received ipilimumab, which was approved by the US Food and Drug Administration in March 2011, as part of her treatment. The drug did not initially prevent the disease from worsening over time, with metastatic tumors growing in the spleen, lymph nodes, and an area near the spine.

As her disease progressed, the patient received localized radiation therapy to the tumor near the spine to help with pain relief. The radiation caused the tumor near the patient’s spine to shrink significantly.

Unexpectedly, the tumors growing in the patient’s spleen and lymph nodes also shrunk, even though they were not directly targeted by the radiation therapy, which is consistent with the abscopal effect. The patient continues to do well more than one year after radiation therapy.

“What we think is happening here is that the immune system’s cancer fighting response is turned up a notch with the addition of focused radiation,” Dr. Wolchok says.

Another Success for Immunotherapy

Ipilimumab is the first drug ever shown to improve overall survival for patients with advanced melanoma. The therapy, which targets a protein called CTLA-4, was developed by James P. Allison, Chair of the Sloan Kettering Institute's Immunology Program.

For more than 20 years, Dr. Allison’s research has focused on the mechanisms by which immune cells called T cells mediate the body’s defense against infections and cancer, with an emphasis on how T cell responses might be manipulated therapeutically to attack tumors. Dr. Wolchok was the principal investigator in a pivotal phase III study of ipilimumab in patients with metastatic melanoma.

Scientists are not certain how the abscopal effect works to eliminate cancer in patients. Studies in mice suggest that the effect may depend upon activation of the immune system. In this case study, changes in the patient’s immune system were measured over the course of treatment. At the time the abscopal effect occurred, the team observed changes in the patient’s immune system. Their findings support the idea that radiation may help stimulate the immune system to fight cancer.    

This patient’s dramatic response provides new insight into how radiation may help activate the immune system to fight cancer, encouraging investigation of novel therapeutic strategies. Clinical trials to explore the approach of combining radiation therapy with ipilimumab for the treatment of melanoma are expected to begin soon at Memorial Sloan Kettering Cancer Center.

In a March 7 interview with NBC News, Dr. Wolchok explains, “We’re very excited about this result because we treated just one tumor with radiation therapy in this patient, and as a result, distant tumors regressed.”

Comments

how is this for rare. I had a melanoma appear last year. I was the size of half a pencil eraser. I thought it was a freckle. However after several months I noticed it had grown in diameter. it scared the mess out of me. I told my sister and a few friends about it. I was worried that if I had to get chemo, it might effect me having kids. I mentioned it to my doctor, however, I had some other things going on medically, so we never readdressed it. To be honest I was afraid too. I looked online and found some interesting research on new cancer discoveries. 1. the use of L-Arginine, 2. grape juice, 3. Brocolli, 4. Garlic. Earlier this year, in March, I began ingesting 16 oz of Minced garlic per 2 weeks, drinking 2 gallons of grape juice per week, Eating 3 lbs of brocolli per week, and taking 1000mg of L-Arginine per day. During this time, the melanoma started growing, had dark areas, with light brown, and some pink irritated areas. By April it had grown to the size of a Nickle. I looked online at the different characteristics of skin melanomas.. This had all the signs of something bad. It was located in my left region of the pelvis, just below my belt line. One morning I woke up on a Saturday, May 26, 2012 to be exact, was getting ready to take a shower, and looked down and the melanoma was completely gone, not even a scar. Immediately called my sister and also friends.. No one can believe this..

What did your doctor have to say about this?

Glycine is reported to inhibit VEGF activated angiogenesis in melanoma in vivo [rats], and arginine reported to be used by melanoma for NO production, possibly for enabling angiogenesis as well. What would be the expected effect of combining these two for prevention of metastasis in excised cutaneous melanoma patients beyond in situ stages: e.g. T1b with 0-1 mitosis/HPF. Relevant because of the very long subclinical latent period to clinical metastasis [10 years], and the fact that mets ≤2mm survive by diffusion alone but without signs or symptoms until angiogenesis permits their promotion.

Need a Hail Mary treatment for my friend who has metastatic melanoma spread to pelvic area and grown since clinical trials done in Pittsburgh. Intestinal blockage caused her to have tube to colon to drain. PLEASE,give us hope. They say they can't can't radiate redistribute it sounds like you do and it works. What should we do?

Dear Patty, we are sorry to hear about your friend. We can't answer personal medical questions on the blog. If she would like to make an appointment with one of our specialists, please have her call our Physician Referral Service at 800-525-2225. The staff there can refer her to the most appropriate physician, who can then explain what treatment options exist for her.
Thanks for your comment.

I have advanced metastatic melanoma with multiple subcutaneous and intramuscular tumors diagnosed in August 2012. So far I've participated in 2 clinical trials. The first was IL-21 combined with Ipilimumab . I developed pancreatitis after the 2nd combo treatment and had to stop. I have since had two rounds of treatment with IL-12 with electroporation. Repeated scans have shown relative stability in most of the tumors with some disappearing completely. A few months ago, however, I had a tumor appear on my left flank which grew much more rapidly and caused pain now 50x23 mm. My oncologists termed it a rogue tumor and suggested radiation. After debate with radiation oncologist, I am having 6 ex-ray radiation treatments (6 greys each) directed at the tumor. While all the oncologist mentioned the abscopal effect, none suggested that it would have any bearing the decision for my treatment course.
In my wildest dreams, I hope that it will wipe out all the tumors, but would be content if it stabilizes the one 'rogue" and allows me en extended prognosis with good quality of life! I am so grateful for all the research that is being done on melanoma and that I am near a research facility where I can easily take advantage of it!
Just finished my 3rd treatment

Thank you for your comment. We're wishing you all the best, Mary!

My husband was recently diagnosed with malignant mucosal melanoma of the right maxillary sinus with metastatic lesion at T6 spine. He had surgery to debulk tumor with no clean margins and is presently on Yervoy infusions, SBRT radiation to lesion on spine (one treatment) and IMRT and arc radiation to the sinus and face area. We were told to look for clinical trials and also just heard about the Merck EAP of the MK 3475 drug. Is this something Sloan Kettering participates in and how do I go about getting into a program like this. He is 57 years old and was in good health. This started with a nose bleed in November. Any information you can offer would be appreciated. He is presently being treated a Jefferson in Phila but they do not participate in clinical trials and although In the process of the paperwork for the EAP program, I am concerned that time is of the essence with my husband's diagnosis.

Linda, we are sorry to hear about your husband's diagnosis. Memorial Sloan Kettering is conducting several trials for melanoma. If you'd like to make an appointment with a doctor at MSK to find out if we have a trial that is right for your husband, please call our Physician Referral Service at 800-525-2225 or go to http://www.mskcc.org/cancer-care/appointment for more information. Thank you for your comment.

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