A Multifaceted Approach 
to Treating Melanoma at Montefiore Einstein Center for Cancer Care

Wednesday, May 1, 2013

Montefiore Einstein Center for Cancer Care’s Melanoma/Sarcoma Program offers leading-edge treatments for the most deadly form of skin cancer.

At  Montefiore Einstein Center for Cancer Care, a multidisciplinary team of medical, surgical and radiation oncologists, as well as dermatologists, collaborates with nutritionists, pathologists, palliative care providers, plastic surgeons, nuclear medicine specialists and social workers to provide customized treatment plans that meet the comprehensive needs of each patient who enters the Melanoma/Sarcoma Program. After the group identifies the most appropriate treatment path, a specialist from medical, surgical or radiation oncology — whichever is appropriate — takes over as the patient’s lead physician, with experts from the group contributing as necessary.

“Our goal here is to try to attack the cancer in as many different ways as possible. Before treatments become standard clinical practice, they must go through clinical trials in a place dedicated to that kind of clinical research — like Montefiore Einstein Center for Cancer Care.”
— Stuart Packer, M.D., Clinical Director, Weiler Oncology
Service and Director, Melanoma/Sarcoma Program, Montefiore Einstein Center for Cancer Care, and assistant professor, Department of Medicine (Oncology), Albert Einstein College of Medicine

Targeted Medical Treatments

Stuart Packer, M.D., Clinical Director, Weiler Oncology Service and Director, Melanoma/Sarcoma Program, Montefiore Einstein Center for Cancer Care, and assistant professor, Department of Medicine (Oncology), Albert Einstein College of Medicine, takes the lead when the team deems medical management the most appropriate course of treatment for a patient. The partnership between Montefiore Medical Center and Albert Einstein College of Medicine enables Dr. Packer and the team to provide both traditional treatments, such as interferon and chemotherapy, and innovative targeted therapies and immunotherapies that only an experienced team can offer because of associated side effects and specific administration guidelines. A wide variety of clinical trials and experimental treatment modalities are available as well.

“One capability that makes us unique is that we have continued our program of IL-2 [interleukin-2], which has been around since the early 1990s,” Dr. Packer explains. “Because this therapy requires specialized techniques and care, not many institutions provide it.”

Stuart Packer
Stuart Packer, M.D., examines a patient.

The United States Food and Drug Administration (FDA) approved IL-2 in 1992 after clinical trials — in which Montefiore Einstein Center for Cancer Care participated — demonstrated the drug’s efficacy. IL-2 is the only therapy recognized as producing durable remissions, and some patients have even experienced remissions lasting more than 20 years, according to Dr. Packer. The Montefiore team is experienced and equipped to offer high-dose IL-2 and address its potential side effects, such as capillary leak syndrome, chills, fever and low blood pressure.

“Albert Einstein College of Medicine was part of the original IL-2 trials, and we have made a recommitment to use IL-2,” Dr. Packer says. “It’s one option for treatment, and we felt that, being a multidisciplinary, full-service, tertiary care center, it was necessary to offer its benefits to appropriate patients.”

Commonly administered intravenously for 15 minutes every eight hours, IL-2 treatment takes place in two or three five-day courses separated by a seven- to 10-day rest period. IL-2 activates the immune system’s T-lymphocyte (T-cell) response to stave off or slow cancer cell growth in patients with stage 4 metastatic melanoma.

Karthik Krishnamurthy
Karthik Krishnamurthy, D.O., performs a skin biopsy with Patricia Keys, LPN.

Dr. Packer explains that exclusion criteria for IL-2 therapy are predicated on the patient’s performance status and stage of disease. Patients in good overall health with no significant cardiac or pulmonary disease may be candidates for IL-2 therapy. The results from IL-2 therapy are almost always seen within several weeks, and most important, treatment with IL-2 doesn’t affect whether the patient can go on to receive more standard treatments.

Unchecking the Immune System

While IL-2 works to augment the immune system, ipilimumab works to keep it going. CTLA-4 is a molecule located on T-cells that prevents them from assaulting the body’s normal healthy tissues. The problem is CTLA-4 can suppress the immune system’s attack on cancer as well. Approved by the FDA in 2011, ipilimumab blocks the CTLA-4 response, enabling the immune system to effectively identify, target and attack melanoma tumor cells.

Ipilimumab is typically administered via four courses of intravenous infusion once every three weeks. Although response rates with ipilimumab are modest, some patients may achieve long-lasting, durable remissions. Ipilimumab can result in side effects, such as colitis, diarrhea, endocrine deficiencies, fatigue and skin rash, due to its potency. Montefiore Einstein Center for Cancer Care’s experienced providers are trained to identify and manage these side effects.

Innovation for Gene Mutations

A subgroup of patients with melanoma has tumors that express the BRAF V600E gene mutation. BRAF proteins are typically involved in the regulation of cell growth, but in nearly half of all patients with late-stage melanomas, a mutation of this gene causes the tumor cells to grow quickly, according to the American Cancer Society (ACS). In 2011, the FDA approved vemurafenib, a drug that targets melanoma cells with the mutated BRAF gene, along with a companion diagnostic test that identifies whether or not patients’ tumors had the mutation.

Multidisciplinary Tumor Board
The Multidisciplinary Tumor Board includes physicians, residents and a patient navigator.

In approximately half of patients whose melanoma had the BRAF mutation, vemurafenib shrank the tumors and in some patients extended the period of time before tumors began growing again, thus extending those patients’ lives, according to the ACS. Dr. Packer collaborates with pathologists to be certain all melanomas undergo appropriate genetic testing. Karthik Krishnamurthy, D.O., a dermatologist at Montefiore Einstein Center for Cancer Care and assistant professor, Department of Medicine (Dermatology), Albert Einstein College of Medicine, closely monitors patients following vemurafenib administration, as the drug can increase the risk of developing other types of skin cancer, such as squamous cell carcinoma and keratoacanthoma.

Surgical Options for All Stages

When physicians catch melanoma before it progresses and metastasizes elsewhere in the body, Katia Papalezova, M.D., a surgical oncologist, Melanoma/Sarcoma Program, Montefiore Einstein Center for Cancer Care, and assistant professor, Department of Surgery, Division of General Surgery, Albert Einstein College of Medicine, performs traditional wide local excision of the melanoma site. For melanoma that has progressed to later stages, she calls upon the full gamut of surgical options.

Patients whose melanoma measures greater than 1 mm in thickness and whose lymph nodes are normal upon clinical examination are candidates for sentinel lymph node biopsy (SLNB).

“A physician injects a radioactive substance directly adjacent to the melanoma or biopsy scar, as well as a blue dye,” says Dr. Papalezova, who co-founded the Melanoma/Sarcoma Program with Dr. Krishnamurthy. “The dye travels along the lymph channels to the sentinel lymph node. Once identified, this lymph node is removed, and we perform a microscopic exam to determine whether cancer cells are present. If we find none, it is unlikely the cancer has spread to other lymph nodes, and usually no other treatment is necessary.”

Dr Packer And Katia Papalezova
Dr. Packer and Katia Papalezova, M.D., collaborate on a patient case.

If the team pathologist finds cancer in the lymph node, Dr. Papalezova discusses with the patient a procedure called complete lymph node dissection (CLND), which is offered to determine the extent of the melanoma’s progression. Both SLNB and CLND are conducted to determine the subsequent course of treatment.

“We offer sentinel lymph node biopsy for prognostic and staging purposes,” Dr. Papalezova says. “After this procedure, we know what stage the patient’s disease is, so we can then see if he or she qualifies for clinical trials, which patients in general cannot enroll in unless we assess the status of their lymph nodes.”

Nitin Ohri, M.D., is a radiation oncologist at the Montefiore Einstein Center for Cancer Care and assistant professor, Department of Radiation Oncology, Albert Einstein College of Medicine, who specializes in the treatment of skin cancer with radiation therapy.

“Radiotherapy is often used for locally advanced skin cancers after surgery to decrease the risk of disease recurrence,” Dr. Ohri says. “We also use radiotherapy as a definitive treatment for patients for whom surgery would be unsafe or yield poor cosmetic outcomes.”

Recent advances in target definition, treatment planning and setup verification allow Dr. Ohri and his team to aggressively treat tumors while minimizing the exposure of healthy tissues to radiation, which in turn minimizes the side effects his patients experience during and after radiotherapy. In some cases, this also allows radiotherapy to be delivered during one to two weeks rather than the traditional five- to six-week course.

Chemotherapy, Confined and Effective

While chemotherapy may be an appropriate treatment option for other cancers that have spread beyond the point of origin, Dr. Packer says this is a lesser option for patients with melanoma.

Michelle Padua
The patient navigator, Michelle Padua, N.P., schedules an appointment for one of her patients.

“One of the problems with melanoma is that it’s in a group of cancers that have not been effectively treated with chemotherapy,” Dr. Packer says. “Chemotherapy for metastatic melanoma is a very unsatisfying treatment because the cancer is not chemotherapy responsive. Treatment with chemotherapy is often associated with significant side effects, and to date, there has been no evidence it prolongs survival. In the past three years, there has been an explosion of information and knowledge about melanoma, and several effective treatments have been approved by the FDA.”

One treatment offered by Montefiore Einstein Center for Cancer Care’s Melanoma/Sarcoma Program is isolated limb perfusion (ILP). For a local recurrence after adequate wide excision and in the absence of extraregional disease, surgery to remove the tumor is recommended. Approximately half of newly diagnosed cases of melanoma are isolated to the upper or lower limbs, and in as many as 10% of these cases, melanoma recurs in the same limb the primary diagnosis was made. For patients with recurrent melanoma that is confined to a limb and cannot be cured by surgical means, ILP can be offered.

ILP provides an alternative to amputation. This method allows for large doses of chemotherapy to be delivered to the limb only, leaving the rest of the body unaffected. Montefiore is among a select group of medical centers nationwide to offer ILP and isolated limb infusion (ILI), a simplified, minimally invasive procedure offered to poor surgical candidates as an alternative to ILP.

Dr Packer And Nitin Ohri
Dr. Packer and Nitin Ohri, M.D., review a PET/CT scan for a patient with melanoma.

“We offer ILP to patients who have multiple lesions between the primary site of the melanoma and the regional lymph node basin,” Dr. Papalezova explains. “It’s offered when the disease cannot be removed by surgery, so the only alternative for the patient is an amputation. We know that systemic chemotherapy has a poor response rate, so for people to whom surgery cannot be offered, this is an attractive option. Short of amputation, this procedure has a response rate of up to 80%, and we offer it to salvage the limb.”

For patients who cannot tolerate the operation because of comorbidities such as poor cardiac condition, Dr. Papalezova offers ILI, a less invasive form of ILP that features no incisions because blood vessels are accessed percutaneously. The response rate is a little lower than that of ILP, Dr. Papalezova says, but patients may find it preferable to amputation.

Hospitable Treatment for All

While patients are in the expert care of specialists at the Montefiore Einstein Center for Cancer Care’s Melanoma/Sarcoma Program, they are provided leading-edge treatments and cared for by readily accessible ancillary staff. A nurse navigator is available to answer patients’ questions, tend to any needs they may have, and coordinate patients’ appointments and transition back to their primary dermatologists.

Dr. Krishnamurthy says the central location of the center’s specialists is convenient for patients, who avoid adding miles to their cars and stress to their lives by having to visit multiple offices for specialty appointments.

Krishnamurthy And Papalezova
Drs. Krishnamurthy and Papalezova review dermascopic features of a suspicious lesion.

“For such a devastating disease, it is best to refer these patients to a place where they can receive immediate, advanced care,” Dr. Krishnamurthy says. “Many times, physicians send a patient to a surgeon, and then after surgery, the patient may need an oncologist, and so on. This leads to a delay in overall assessment and initiation of treatment. Utilizing a ‘one-stop shop’ like we do at Montefiore Einstein Center for Cancer Care averts this issue.”

In addition, a team of social workers, aid officers and clerical staff work to provide patients with low incomes or no insurance a path for care by taking advantage of special aid provided by Medicaid or grants from drug companies themselves. This and other measures ensure that, at Montefiore Einstein Center for Cancer Care, all patients with melanoma are able to receive the appropriate care.

For more information about the Melanoma/Sarcoma Program, please visit www.montefiore.org/cancer.