In melanoma, sentinel node results will drive targeted therapies

VANCOUVER, B.C. – Why should dermatologists care about the role of sentinel lymph node biopsy in melanoma patients? Because SNLB results will inform the use of an explosion of immunotherapies and targeted therapies emerging for melanoma and – because even after melanoma patients have been referred to a comprehensive cancer center – patients will continue to view dermatologists as the primary care providers with respect to the cancer, Dr. Timothy M. Johnson said in a plenary address at the World Congress of Dermatology.

“I guarantee you of that” scenario, predicted Dr. Johnson, professor of dermatology and clinical director of the multidisciplinary melanoma program at the University of Michigan, Ann Arbor, where more than 2,000 melanoma patients are seen each year.

Bruce Jancin/Frontline Medical News

New melanoma therapies are “coming in waves. They seem to be coming weekly,” he said. In June, the National Cancer Institute listed 218 therapeutic clinical trials for advanced melanoma in the United States alone. And some of these new treatments for stage IV melanoma are already starting to make their way into the adjuvant setting for stage III melanoma.

“The first round of adjuvant therapy trials has been done, and the data are being analyzed now. A new round is coming like gangbusters,” Dr. Johnson said. “This is one of the most exciting times ever in melanoma.”

Should some of these novel agents prove safe and effective as adjuvant therapy, SLNB results will determine the need for such therapy based upon individualized patient prognosis. And the SLNB results will determine the type of adjuvant therapy that’s most appropriate based upon the tumor molecular profile.

“Once we have effective adjuvant therapy, it will eradicate the need for total lymph node dissection in patients with a positive node on SLNB. Those with a positive node will likely undergo systemic therapy based on a personalized approach,” he predicted.

For the present, in Dr. Johnson’s view, much of the best guidance on when and how to employ SLNB in melanoma patients comes from the landmark National Cancer Institute–sponsored Multicenter Selective Lymphadenectomy Trial (MSLT-1).

The MSLT-1 results (N Engl J Med. 2014 Feb 13;370:599-609) are deemed controversial by some, Dr. Johnson noted. But they provide a strong case for widespread application of SLNB for accurate staging and regional control of the nodal basin based upon the findings in 1,270 participants with intermediate-thickness melanomas of 1.2-3.5 mm and 290 others with melanomas greater than 3.5 mm thick, he said. Both groups showed significant benefit in terms of 10-year melanoma-specific survival if randomized to SLNB with immediate total lymph node dissection if SLNB positive, as opposed to watchful waiting for an occult nodal metastasis to become clinically evident.

An important finding was that roughly 27% of patients in the observation arms who experienced a clinically evident nodal metastasis during follow-up and then underwent completion total lymph node dissection had four or more positive nodes at that time, compared to 1.6% of those with a positive SLNB who underwent immediate completion dissection.

“If an occult metastasis is present in the lymph node it’s going to grow to the point of becoming clinically evident in an average of 2-3 years. You can deal with it now or you can deal with it later, but you’re likely going to have to deal with it. Failure to detect and treat that disease early will result in increased tumor burden upon completion lymph node dissection, increased morbidity and side effects in order to remove those nodes, and a small but increased likelihood of dying from that disease. That’s a very powerful conversation to have with patients and families to help them make the best informed decision for themselves,” Dr. Johnson said.

At the University of Michigan melanoma program – the nation’s largest – patients are counseled to seriously consider SLNB if they have a clinically localized melanoma 1 mm or more in thickness provided their functional status is favorable. In contrast, there is essentially no evidence to support SLNB in patients with a melanoma less than 0.75 mm in thickness.

In patients with a melanoma thickness of 0.75-0.99 mm, however, Dr. Johnson and his colleagues may recommend SLNB in the presence of certain predictors of increased likelihood of a positive biopsy: ulceration, angiolymphatic invasion, younger age, a positive deep margin on a shave biopsy, extensive dermal regression in excess of 1 mm, and/or a mitotic rate of at least 1 mm². Age and mitotic rate are continuous variables: The younger the patient and the higher the mitotic rate, the greater the likelihood of a positive SLNB in the setting of a thin melanoma.

At present, the decision regarding whether to recommend SLNB in a patient with a thin melanoma is based upon a general gestalt, said Dr. Johnson. He and his colleagues have received a grant to study more than 2,000 cases of thin melanoma in an effort to develop a system for weighting the individual risk factors.

“As dermatologists – you, me, we – should be one of the lead dogs with respect to melanoma advancement, knowledge, management, and guidance. To do that most effectively, you must learn from and work closely with other specialists – collegially, collaboratively, and humbly,” he concluded.

Dr. Johnson reported having no financial conflicts of interest regarding his talk.

[email protected]

VANCOUVER, B.C. – Why should dermatologists care about the role of sentinel lymph node biopsy in melanoma patients? Because SNLB results will inform the use of an explosion of immunotherapies and targeted therapies emerging for melanoma and – because even after melanoma patients have been referred to a comprehensive cancer center – patients will continue to view dermatologists as the primary care providers with respect to the cancer, Dr. Timothy M. Johnson said in a plenary address at the World Congress of Dermatology.

“I guarantee you of that” scenario, predicted Dr. Johnson, professor of dermatology and clinical director of the multidisciplinary melanoma program at the University of Michigan, Ann Arbor, where more than 2,000 melanoma patients are seen each year.

Bruce Jancin/Frontline Medical News

New melanoma therapies are “coming in waves. They seem to be coming weekly,” he said. In June, the National Cancer Institute listed 218 therapeutic clinical trials for advanced melanoma in the United States alone. And some of these new treatments for stage IV melanoma are already starting to make their way into the adjuvant setting for stage III melanoma.

“The first round of adjuvant therapy trials has been done, and the data are being analyzed now. A new round is coming like gangbusters,” Dr. Johnson said. “This is one of the most exciting times ever in melanoma.”

Should some of these novel agents prove safe and effective as adjuvant therapy, SLNB results will determine the need for such therapy based upon individualized patient prognosis. And the SLNB results will determine the type of adjuvant therapy that’s most appropriate based upon the tumor molecular profile.

“Once we have effective adjuvant therapy, it will eradicate the need for total lymph node dissection in patients with a positive node on SLNB. Those with a positive node will likely undergo systemic therapy based on a personalized approach,” he predicted.

For the present, in Dr. Johnson’s view, much of the best guidance on when and how to employ SLNB in melanoma patients comes from the landmark National Cancer Institute–sponsored Multicenter Selective Lymphadenectomy Trial (MSLT-1).

The MSLT-1 results (N Engl J Med. 2014 Feb 13;370:599-609) are deemed controversial by some, Dr. Johnson noted. But they provide a strong case for widespread application of SLNB for accurate staging and regional control of the nodal basin based upon the findings in 1,270 participants with intermediate-thickness melanomas of 1.2-3.5 mm and 290 others with melanomas greater than 3.5 mm thick, he said. Both groups showed significant benefit in terms of 10-year melanoma-specific survival if randomized to SLNB with immediate total lymph node dissection if SLNB positive, as opposed to watchful waiting for an occult nodal metastasis to become clinically evident.

An important finding was that roughly 27% of patients in the observation arms who experienced a clinically evident nodal metastasis during follow-up and then underwent completion total lymph node dissection had four or more positive nodes at that time, compared to 1.6% of those with a positive SLNB who underwent immediate completion dissection.

“If an occult metastasis is present in the lymph node it’s going to grow to the point of becoming clinically evident in an average of 2-3 years. You can deal with it now or you can deal with it later, but you’re likely going to have to deal with it. Failure to detect and treat that disease early will result in increased tumor burden upon completion lymph node dissection, increased morbidity and side effects in order to remove those nodes, and a small but increased likelihood of dying from that disease. That’s a very powerful conversation to have with patients and families to help them make the best informed decision for themselves,” Dr. Johnson said.

At the University of Michigan melanoma program – the nation’s largest – patients are counseled to seriously consider SLNB if they have a clinically localized melanoma 1 mm or more in thickness provided their functional status is favorable. In contrast, there is essentially no evidence to support SLNB in patients with a melanoma less than 0.75 mm in thickness.

In patients with a melanoma thickness of 0.75-0.99 mm, however, Dr. Johnson and his colleagues may recommend SLNB in the presence of certain predictors of increased likelihood of a positive biopsy: ulceration, angiolymphatic invasion, younger age, a positive deep margin on a shave biopsy, extensive dermal regression in excess of 1 mm, and/or a mitotic rate of at least 1 mm². Age and mitotic rate are continuous variables: The younger the patient and the higher the mitotic rate, the greater the likelihood of a positive SLNB in the setting of a thin melanoma.

At present, the decision regarding whether to recommend SLNB in a patient with a thin melanoma is based upon a general gestalt, said Dr. Johnson. He and his colleagues have received a grant to study more than 2,000 cases of thin melanoma in an effort to develop a system for weighting the individual risk factors.

“As dermatologists – you, me, we – should be one of the lead dogs with respect to melanoma advancement, knowledge, management, and guidance. To do that most effectively, you must learn from and work closely with other specialists – collegially, collaboratively, and humbly,” he concluded.

Dr. Johnson reported having no financial conflicts of interest regarding his talk.

[email protected]

VANCOUVER, B.C. – Why should dermatologists care about the role of sentinel lymph node biopsy in melanoma patients? Because SNLB results will inform the use of an explosion of immunotherapies and targeted therapies emerging for melanoma and – because even after melanoma patients have been referred to a comprehensive cancer center – patients will continue to view dermatologists as the primary care providers with respect to the cancer, Dr. Timothy M. Johnson said in a plenary address at the World Congress of Dermatology.

“I guarantee you of that” scenario, predicted Dr. Johnson, professor of dermatology and clinical director of the multidisciplinary melanoma program at the University of Michigan, Ann Arbor, where more than 2,000 melanoma patients are seen each year.

Bruce Jancin/Frontline Medical News

New melanoma therapies are “coming in waves. They seem to be coming weekly,” he said. In June, the National Cancer Institute listed 218 therapeutic clinical trials for advanced melanoma in the United States alone. And some of these new treatments for stage IV melanoma are already starting to make their way into the adjuvant setting for stage III melanoma.

“The first round of adjuvant therapy trials has been done, and the data are being analyzed now. A new round is coming like gangbusters,” Dr. Johnson said. “This is one of the most exciting times ever in melanoma.”

Should some of these novel agents prove safe and effective as adjuvant therapy, SLNB results will determine the need for such therapy based upon individualized patient prognosis. And the SLNB results will determine the type of adjuvant therapy that’s most appropriate based upon the tumor molecular profile.

“Once we have effective adjuvant therapy, it will eradicate the need for total lymph node dissection in patients with a positive node on SLNB. Those with a positive node will likely undergo systemic therapy based on a personalized approach,” he predicted.

For the present, in Dr. Johnson’s view, much of the best guidance on when and how to employ SLNB in melanoma patients comes from the landmark National Cancer Institute–sponsored Multicenter Selective Lymphadenectomy Trial (MSLT-1).

The MSLT-1 results (N Engl J Med. 2014 Feb 13;370:599-609) are deemed controversial by some, Dr. Johnson noted. But they provide a strong case for widespread application of SLNB for accurate staging and regional control of the nodal basin based upon the findings in 1,270 participants with intermediate-thickness melanomas of 1.2-3.5 mm and 290 others with melanomas greater than 3.5 mm thick, he said. Both groups showed significant benefit in terms of 10-year melanoma-specific survival if randomized to SLNB with immediate total lymph node dissection if SLNB positive, as opposed to watchful waiting for an occult nodal metastasis to become clinically evident.

An important finding was that roughly 27% of patients in the observation arms who experienced a clinically evident nodal metastasis during follow-up and then underwent completion total lymph node dissection had four or more positive nodes at that time, compared to 1.6% of those with a positive SLNB who underwent immediate completion dissection.

“If an occult metastasis is present in the lymph node it’s going to grow to the point of becoming clinically evident in an average of 2-3 years. You can deal with it now or you can deal with it later, but you’re likely going to have to deal with it. Failure to detect and treat that disease early will result in increased tumor burden upon completion lymph node dissection, increased morbidity and side effects in order to remove those nodes, and a small but increased likelihood of dying from that disease. That’s a very powerful conversation to have with patients and families to help them make the best informed decision for themselves,” Dr. Johnson said.

At the University of Michigan melanoma program – the nation’s largest – patients are counseled to seriously consider SLNB if they have a clinically localized melanoma 1 mm or more in thickness provided their functional status is favorable. In contrast, there is essentially no evidence to support SLNB in patients with a melanoma less than 0.75 mm in thickness.

In patients with a melanoma thickness of 0.75-0.99 mm, however, Dr. Johnson and his colleagues may recommend SLNB in the presence of certain predictors of increased likelihood of a positive biopsy: ulceration, angiolymphatic invasion, younger age, a positive deep margin on a shave biopsy, extensive dermal regression in excess of 1 mm, and/or a mitotic rate of at least 1 mm². Age and mitotic rate are continuous variables: The younger the patient and the higher the mitotic rate, the greater the likelihood of a positive SLNB in the setting of a thin melanoma.

At present, the decision regarding whether to recommend SLNB in a patient with a thin melanoma is based upon a general gestalt, said Dr. Johnson. He and his colleagues have received a grant to study more than 2,000 cases of thin melanoma in an effort to develop a system for weighting the individual risk factors.

“As dermatologists – you, me, we – should be one of the lead dogs with respect to melanoma advancement, knowledge, management, and guidance. To do that most effectively, you must learn from and work closely with other specialists – collegially, collaboratively, and humbly,” he concluded.

Dr. Johnson reported having no financial conflicts of interest regarding his talk.

[email protected]