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For BCC, consider curettage only
WAIKOLOA, HAWAII – Curettage alone for the treatment of basal cell carcinomas offers several distinct advantages over the widely accepted technique of curettage followed by electrodesiccation, Dr. David L. Swanson said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
When he asked for an audience show of hands as to who treats BCCs using curettage without electrodesiccation, the packed auditorium full of dermatologists remained hands-down. But there is good evidence that curettage alone provides cure rates similar to published rates for curettage and electrodesiccation, along with improved cosmesis, faster healing, and fewer problems with scarring and hypopigmentation, according to Dr. Swanson, a dermatologist at Mayo Clinic Arizona, Scottsdale.
He cited a persuasive study by other dermatologists at Mayo Clinic Arizona (J Am Acad Dermatol. 2006 Jun;54[6]:1039-45).
“This article was transformative for my practice,” said Dr. Swanson, who wasn’t involved in the study.
The investigators reviewed the records of 302 biopsy-proven BCCs in 136 patients. All were amenable to curettage and electrodesiccation but were instead treated by curettage alone during 1993-1998. The BCCs lacked histopathologic high-risk features; most were superficial or nodular lesions. Nearly one-quarter of the BCCs, however, were located on high-risk anatomic sites.
The 5-year cure rate was 96%. The authors’ review of 10 published series of BCCs treated using curettage and electrodesiccation showed recurrence rates mostly in the 3%-7% range.
Among the advantages cited by the investigators of going with curettage alone were its simplicity, reduced equipment requirement, cost effectiveness, lack of electrical interference with implantable cardiac devices, the avoidance of potentially hazardous viral smoke plumes, and reduced rates of hypopigmentation and scarring.
This was a retrospective study. Its other significant limitation was that all 302 BCCs were treated by the same dermatologist: Dr. Mark J. Zalla, who Dr. Swanson considers to be a dermatologic surgeon of exceptional talent.
“I’m not Mark Zalla. Nobody else in this room is Mark Zalla, so we can’t necessarily extrapolate from this study what your outcomes are going to be. That said, I’ve adopted this technique, and most of my colleagues do not do electrodesiccation anymore. I take off several basal cell carcinomas per day with curettage, and it’s my sense that I don’t have higher recurrence rates and that it does heal better with less scarring,” Dr. Swanson said.
He reported having no financial conflicts of interest regarding his presentation. SDEF and this news organization are owned by the same parent company.
WAIKOLOA, HAWAII – Curettage alone for the treatment of basal cell carcinomas offers several distinct advantages over the widely accepted technique of curettage followed by electrodesiccation, Dr. David L. Swanson said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
When he asked for an audience show of hands as to who treats BCCs using curettage without electrodesiccation, the packed auditorium full of dermatologists remained hands-down. But there is good evidence that curettage alone provides cure rates similar to published rates for curettage and electrodesiccation, along with improved cosmesis, faster healing, and fewer problems with scarring and hypopigmentation, according to Dr. Swanson, a dermatologist at Mayo Clinic Arizona, Scottsdale.
He cited a persuasive study by other dermatologists at Mayo Clinic Arizona (J Am Acad Dermatol. 2006 Jun;54[6]:1039-45).
“This article was transformative for my practice,” said Dr. Swanson, who wasn’t involved in the study.
The investigators reviewed the records of 302 biopsy-proven BCCs in 136 patients. All were amenable to curettage and electrodesiccation but were instead treated by curettage alone during 1993-1998. The BCCs lacked histopathologic high-risk features; most were superficial or nodular lesions. Nearly one-quarter of the BCCs, however, were located on high-risk anatomic sites.
The 5-year cure rate was 96%. The authors’ review of 10 published series of BCCs treated using curettage and electrodesiccation showed recurrence rates mostly in the 3%-7% range.
Among the advantages cited by the investigators of going with curettage alone were its simplicity, reduced equipment requirement, cost effectiveness, lack of electrical interference with implantable cardiac devices, the avoidance of potentially hazardous viral smoke plumes, and reduced rates of hypopigmentation and scarring.
This was a retrospective study. Its other significant limitation was that all 302 BCCs were treated by the same dermatologist: Dr. Mark J. Zalla, who Dr. Swanson considers to be a dermatologic surgeon of exceptional talent.
“I’m not Mark Zalla. Nobody else in this room is Mark Zalla, so we can’t necessarily extrapolate from this study what your outcomes are going to be. That said, I’ve adopted this technique, and most of my colleagues do not do electrodesiccation anymore. I take off several basal cell carcinomas per day with curettage, and it’s my sense that I don’t have higher recurrence rates and that it does heal better with less scarring,” Dr. Swanson said.
He reported having no financial conflicts of interest regarding his presentation. SDEF and this news organization are owned by the same parent company.
WAIKOLOA, HAWAII – Curettage alone for the treatment of basal cell carcinomas offers several distinct advantages over the widely accepted technique of curettage followed by electrodesiccation, Dr. David L. Swanson said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
When he asked for an audience show of hands as to who treats BCCs using curettage without electrodesiccation, the packed auditorium full of dermatologists remained hands-down. But there is good evidence that curettage alone provides cure rates similar to published rates for curettage and electrodesiccation, along with improved cosmesis, faster healing, and fewer problems with scarring and hypopigmentation, according to Dr. Swanson, a dermatologist at Mayo Clinic Arizona, Scottsdale.
He cited a persuasive study by other dermatologists at Mayo Clinic Arizona (J Am Acad Dermatol. 2006 Jun;54[6]:1039-45).
“This article was transformative for my practice,” said Dr. Swanson, who wasn’t involved in the study.
The investigators reviewed the records of 302 biopsy-proven BCCs in 136 patients. All were amenable to curettage and electrodesiccation but were instead treated by curettage alone during 1993-1998. The BCCs lacked histopathologic high-risk features; most were superficial or nodular lesions. Nearly one-quarter of the BCCs, however, were located on high-risk anatomic sites.
The 5-year cure rate was 96%. The authors’ review of 10 published series of BCCs treated using curettage and electrodesiccation showed recurrence rates mostly in the 3%-7% range.
Among the advantages cited by the investigators of going with curettage alone were its simplicity, reduced equipment requirement, cost effectiveness, lack of electrical interference with implantable cardiac devices, the avoidance of potentially hazardous viral smoke plumes, and reduced rates of hypopigmentation and scarring.
This was a retrospective study. Its other significant limitation was that all 302 BCCs were treated by the same dermatologist: Dr. Mark J. Zalla, who Dr. Swanson considers to be a dermatologic surgeon of exceptional talent.
“I’m not Mark Zalla. Nobody else in this room is Mark Zalla, so we can’t necessarily extrapolate from this study what your outcomes are going to be. That said, I’ve adopted this technique, and most of my colleagues do not do electrodesiccation anymore. I take off several basal cell carcinomas per day with curettage, and it’s my sense that I don’t have higher recurrence rates and that it does heal better with less scarring,” Dr. Swanson said.
He reported having no financial conflicts of interest regarding his presentation. SDEF and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR
New research institute to advance cancer immunotherapy
A new research institute launched by tech billionaire Sean Parker aims to advance the field of cancer immunotherapy by uniting the country’s top scientists, including Dr. Carl June, Dr. Jedd Wolchok, and Dr. James Allison, who are leaders in the field.
Best known for founding music-sharing service Napster, Mr. Parker has provided a $250 million grant to develop the Parker Institute for Cancer Immunotherapy, a collaboration between researchers, clinicians, and other stakeholders that focuses on expanding immunotherapy research efforts, according to an April announcement by the Parker Foundation.
“We are at an inflection point in cancer research and now is the time to maximize immunotherapy’s unique potential to transform all cancers into manageable diseases, saving millions of lives,” Mr. Parker said in a statement. “We believe that the creation of a new funding and research model can overcome many of the obstacles that currently prevent research breakthroughs. Working closely with our scientists and more than 30 industry partners, the Parker Institute is positioned to broadly disseminate discoveries and, most importantly, more rapidly deliver treatments to patients.”
The Parker Institute for Cancer Immunotherapy will include 40 laboratories and more than 300 researchers from leading cancer centers, including Memorial Sloan Kettering Cancer Center; Stanford Medicine; the University of California, Los Angeles; the University of California, San Francisco; the University of Pennsylvania; and the University of Texas MD Anderson Cancer Center. Each research center will receive comprehensive funding, clinical resources, and key technologies needed to accelerate research discoveries, according to the foundation. In a unique agreement, the administration of intellectual property will be shared between the research centers, allowing scientists to have immediate access to the broad spectrum of core discoveries.
Scientists involved with the institute call immunotherapy “one of the most important medical advances of our time,” and the first approach that could generate long-lasting remissions for all cancer types and stages. The relatively new treatment area mobilizes the body’s own defense systems to fight cancer cells.
“Immunotherapy represents a fundamentally new, breakthrough treatment paradigm in the fight against cancer – it harnesses the body’s own powerful immune system to mobilize its highly refined disease-fighting arsenal to engage and eliminate the cancer cells,” Parker Institute CEO and President Jeff Bluestone, Ph.D., said in a statement. “Our scientists are leaders in the field and will now work together to make discoveries to treat and potentially cure cancer.”
In the 1990s, Dr. Bluestone of the University of California, San Francisco, was one of two scientists who discovered that, to prevent autoimmunity and overreactions, a molecule called CTLA-4 acts as a “brake,” or checkpoint, on the immune response. The finding fueled a new class of checkpoint-blockade treatments for multiple cancers.
The Parker Institute will focus on several initial objectives, including developing novel approaches to modify T-cells to enhance function and creating a new generation of more effective T-cell therapies. Researchers also will work to improve the rates of durable responses and broaden the use of checkpoint-blocking agents, alone or in combination to treat more types of cancer. Finally, scientists will conduct research to advance DNA sequencing, antigenic peptide discovery efforts, and immune monitoring technologies. Their goal is to understand how to more effectively target tumors and ultimately develop new vaccines and T-cell therapies.
A major key of the institute is to remove competition among researchers that silo breakthroughs and instead enhance teamwork, said James P. Allison, Ph.D., of the University of Texas MD Anderson Cancer Center, Houston.
“One of the goals is to try to remove that competitive edge and have everybody bring their skills together,” Dr. Allison said in a video. “Still, you’re trying to do more than the other guy, but you’re doing it with them. So you use that competitive edge to an advantage.”
On Twitter @legal_med
A new research institute launched by tech billionaire Sean Parker aims to advance the field of cancer immunotherapy by uniting the country’s top scientists, including Dr. Carl June, Dr. Jedd Wolchok, and Dr. James Allison, who are leaders in the field.
Best known for founding music-sharing service Napster, Mr. Parker has provided a $250 million grant to develop the Parker Institute for Cancer Immunotherapy, a collaboration between researchers, clinicians, and other stakeholders that focuses on expanding immunotherapy research efforts, according to an April announcement by the Parker Foundation.
“We are at an inflection point in cancer research and now is the time to maximize immunotherapy’s unique potential to transform all cancers into manageable diseases, saving millions of lives,” Mr. Parker said in a statement. “We believe that the creation of a new funding and research model can overcome many of the obstacles that currently prevent research breakthroughs. Working closely with our scientists and more than 30 industry partners, the Parker Institute is positioned to broadly disseminate discoveries and, most importantly, more rapidly deliver treatments to patients.”
The Parker Institute for Cancer Immunotherapy will include 40 laboratories and more than 300 researchers from leading cancer centers, including Memorial Sloan Kettering Cancer Center; Stanford Medicine; the University of California, Los Angeles; the University of California, San Francisco; the University of Pennsylvania; and the University of Texas MD Anderson Cancer Center. Each research center will receive comprehensive funding, clinical resources, and key technologies needed to accelerate research discoveries, according to the foundation. In a unique agreement, the administration of intellectual property will be shared between the research centers, allowing scientists to have immediate access to the broad spectrum of core discoveries.
Scientists involved with the institute call immunotherapy “one of the most important medical advances of our time,” and the first approach that could generate long-lasting remissions for all cancer types and stages. The relatively new treatment area mobilizes the body’s own defense systems to fight cancer cells.
“Immunotherapy represents a fundamentally new, breakthrough treatment paradigm in the fight against cancer – it harnesses the body’s own powerful immune system to mobilize its highly refined disease-fighting arsenal to engage and eliminate the cancer cells,” Parker Institute CEO and President Jeff Bluestone, Ph.D., said in a statement. “Our scientists are leaders in the field and will now work together to make discoveries to treat and potentially cure cancer.”
In the 1990s, Dr. Bluestone of the University of California, San Francisco, was one of two scientists who discovered that, to prevent autoimmunity and overreactions, a molecule called CTLA-4 acts as a “brake,” or checkpoint, on the immune response. The finding fueled a new class of checkpoint-blockade treatments for multiple cancers.
The Parker Institute will focus on several initial objectives, including developing novel approaches to modify T-cells to enhance function and creating a new generation of more effective T-cell therapies. Researchers also will work to improve the rates of durable responses and broaden the use of checkpoint-blocking agents, alone or in combination to treat more types of cancer. Finally, scientists will conduct research to advance DNA sequencing, antigenic peptide discovery efforts, and immune monitoring technologies. Their goal is to understand how to more effectively target tumors and ultimately develop new vaccines and T-cell therapies.
A major key of the institute is to remove competition among researchers that silo breakthroughs and instead enhance teamwork, said James P. Allison, Ph.D., of the University of Texas MD Anderson Cancer Center, Houston.
“One of the goals is to try to remove that competitive edge and have everybody bring their skills together,” Dr. Allison said in a video. “Still, you’re trying to do more than the other guy, but you’re doing it with them. So you use that competitive edge to an advantage.”
On Twitter @legal_med
A new research institute launched by tech billionaire Sean Parker aims to advance the field of cancer immunotherapy by uniting the country’s top scientists, including Dr. Carl June, Dr. Jedd Wolchok, and Dr. James Allison, who are leaders in the field.
Best known for founding music-sharing service Napster, Mr. Parker has provided a $250 million grant to develop the Parker Institute for Cancer Immunotherapy, a collaboration between researchers, clinicians, and other stakeholders that focuses on expanding immunotherapy research efforts, according to an April announcement by the Parker Foundation.
“We are at an inflection point in cancer research and now is the time to maximize immunotherapy’s unique potential to transform all cancers into manageable diseases, saving millions of lives,” Mr. Parker said in a statement. “We believe that the creation of a new funding and research model can overcome many of the obstacles that currently prevent research breakthroughs. Working closely with our scientists and more than 30 industry partners, the Parker Institute is positioned to broadly disseminate discoveries and, most importantly, more rapidly deliver treatments to patients.”
The Parker Institute for Cancer Immunotherapy will include 40 laboratories and more than 300 researchers from leading cancer centers, including Memorial Sloan Kettering Cancer Center; Stanford Medicine; the University of California, Los Angeles; the University of California, San Francisco; the University of Pennsylvania; and the University of Texas MD Anderson Cancer Center. Each research center will receive comprehensive funding, clinical resources, and key technologies needed to accelerate research discoveries, according to the foundation. In a unique agreement, the administration of intellectual property will be shared between the research centers, allowing scientists to have immediate access to the broad spectrum of core discoveries.
Scientists involved with the institute call immunotherapy “one of the most important medical advances of our time,” and the first approach that could generate long-lasting remissions for all cancer types and stages. The relatively new treatment area mobilizes the body’s own defense systems to fight cancer cells.
“Immunotherapy represents a fundamentally new, breakthrough treatment paradigm in the fight against cancer – it harnesses the body’s own powerful immune system to mobilize its highly refined disease-fighting arsenal to engage and eliminate the cancer cells,” Parker Institute CEO and President Jeff Bluestone, Ph.D., said in a statement. “Our scientists are leaders in the field and will now work together to make discoveries to treat and potentially cure cancer.”
In the 1990s, Dr. Bluestone of the University of California, San Francisco, was one of two scientists who discovered that, to prevent autoimmunity and overreactions, a molecule called CTLA-4 acts as a “brake,” or checkpoint, on the immune response. The finding fueled a new class of checkpoint-blockade treatments for multiple cancers.
The Parker Institute will focus on several initial objectives, including developing novel approaches to modify T-cells to enhance function and creating a new generation of more effective T-cell therapies. Researchers also will work to improve the rates of durable responses and broaden the use of checkpoint-blocking agents, alone or in combination to treat more types of cancer. Finally, scientists will conduct research to advance DNA sequencing, antigenic peptide discovery efforts, and immune monitoring technologies. Their goal is to understand how to more effectively target tumors and ultimately develop new vaccines and T-cell therapies.
A major key of the institute is to remove competition among researchers that silo breakthroughs and instead enhance teamwork, said James P. Allison, Ph.D., of the University of Texas MD Anderson Cancer Center, Houston.
“One of the goals is to try to remove that competitive edge and have everybody bring their skills together,” Dr. Allison said in a video. “Still, you’re trying to do more than the other guy, but you’re doing it with them. So you use that competitive edge to an advantage.”
On Twitter @legal_med
FDA Proposes New Rule to Ban Use of Indoor Tanning Devices by Minors
The US Food and Drug Administration (FDA) has proposed 2 new rules to protect consumers from health risks associated with indoor tanning by banning use of indoor tanning devices by minors and imposing safety measures.
The first proposed rule restricts the use of indoor tanning devices to adults 18 years and older. It also requires indoor tanning facilities to inform adult users about the health risks of indoor tanning and obtain a signed risk acknowledgement from consumers before their first tanning session and every 6 months thereafter.
“Exposure to UV radiation from indoor tanning is a preventable cause of skin cancer,” explained Markham C. Luke, MD, PhD, deputy office director for the Office of Device Evaluation at the FDA’s Center for Devices and Radiological Health. “The FDA is committed to protecting public health by informing consumers of the risks of indoor tanning.”
The second proposed rule addresses performance standards, requiring manufacturers and indoor tanning facilities to take measures to improve the overall safety of tanning devices. Key changes would include:
- Make consumer warnings more prominent and easier to read on tanning devices.
- Require an easily accessible emergency shutoff switch (or panic button) on all tanning devices.
- Add requirements to limit the amount of light allowed through protective eyewear to protect the eyes.
- Improve labeling on replacement bulbs to ensure tanning facility operators use the proper bulbs to reduce risk for accidental burns.
- Prohibit tanning facilities from making dangerous device modifications (eg, installing stronger bulbs) without recertifying and reidentifying the device with the FDA.
The FDA reports that more than 1 million minors use indoor tanning facilities each year. According to the American Academy of Dermatology, consumers younger than 35 years who use indoor tanning facilities are 59% more likely to develop melanoma than those who have never tanned indoors. Because the effects of UV exposure are cumulative and add up over the course of one’s lifetime, minors who use indoor tanning devices are at an increased risk for developing melanoma and nonmelanoma skin cancers later in life.
In 2014 the FDA began requiring tanning devices to be labeled with a visible warning stating that individuals younger than 18 years should not use them. Additionally, several states have already passed laws prohibiting minors from indoor tanning; in Connecticut, New Jersey, New York, and Pennsylvania, tanning devices are banned in individuals younger than 17 years.
Dermatologists are in the position to discuss the health risks of indoor tanning with all patients regardless of age. Patients should be reminded that failure to wear appropriate protective eyewear can lead to short-term and long-term eye injury and that long exposures can lead to burning that may not be recognized until it is too late. It also is important to warn patients that tanning while using certain medications or cosmetics may cause increased sensitivity to UV radiation. Patients can be referred to the FDA website for more consumer updates about indoor tanning and the proposed rules.
The US Food and Drug Administration (FDA) has proposed 2 new rules to protect consumers from health risks associated with indoor tanning by banning use of indoor tanning devices by minors and imposing safety measures.
The first proposed rule restricts the use of indoor tanning devices to adults 18 years and older. It also requires indoor tanning facilities to inform adult users about the health risks of indoor tanning and obtain a signed risk acknowledgement from consumers before their first tanning session and every 6 months thereafter.
“Exposure to UV radiation from indoor tanning is a preventable cause of skin cancer,” explained Markham C. Luke, MD, PhD, deputy office director for the Office of Device Evaluation at the FDA’s Center for Devices and Radiological Health. “The FDA is committed to protecting public health by informing consumers of the risks of indoor tanning.”
The second proposed rule addresses performance standards, requiring manufacturers and indoor tanning facilities to take measures to improve the overall safety of tanning devices. Key changes would include:
- Make consumer warnings more prominent and easier to read on tanning devices.
- Require an easily accessible emergency shutoff switch (or panic button) on all tanning devices.
- Add requirements to limit the amount of light allowed through protective eyewear to protect the eyes.
- Improve labeling on replacement bulbs to ensure tanning facility operators use the proper bulbs to reduce risk for accidental burns.
- Prohibit tanning facilities from making dangerous device modifications (eg, installing stronger bulbs) without recertifying and reidentifying the device with the FDA.
The FDA reports that more than 1 million minors use indoor tanning facilities each year. According to the American Academy of Dermatology, consumers younger than 35 years who use indoor tanning facilities are 59% more likely to develop melanoma than those who have never tanned indoors. Because the effects of UV exposure are cumulative and add up over the course of one’s lifetime, minors who use indoor tanning devices are at an increased risk for developing melanoma and nonmelanoma skin cancers later in life.
In 2014 the FDA began requiring tanning devices to be labeled with a visible warning stating that individuals younger than 18 years should not use them. Additionally, several states have already passed laws prohibiting minors from indoor tanning; in Connecticut, New Jersey, New York, and Pennsylvania, tanning devices are banned in individuals younger than 17 years.
Dermatologists are in the position to discuss the health risks of indoor tanning with all patients regardless of age. Patients should be reminded that failure to wear appropriate protective eyewear can lead to short-term and long-term eye injury and that long exposures can lead to burning that may not be recognized until it is too late. It also is important to warn patients that tanning while using certain medications or cosmetics may cause increased sensitivity to UV radiation. Patients can be referred to the FDA website for more consumer updates about indoor tanning and the proposed rules.
The US Food and Drug Administration (FDA) has proposed 2 new rules to protect consumers from health risks associated with indoor tanning by banning use of indoor tanning devices by minors and imposing safety measures.
The first proposed rule restricts the use of indoor tanning devices to adults 18 years and older. It also requires indoor tanning facilities to inform adult users about the health risks of indoor tanning and obtain a signed risk acknowledgement from consumers before their first tanning session and every 6 months thereafter.
“Exposure to UV radiation from indoor tanning is a preventable cause of skin cancer,” explained Markham C. Luke, MD, PhD, deputy office director for the Office of Device Evaluation at the FDA’s Center for Devices and Radiological Health. “The FDA is committed to protecting public health by informing consumers of the risks of indoor tanning.”
The second proposed rule addresses performance standards, requiring manufacturers and indoor tanning facilities to take measures to improve the overall safety of tanning devices. Key changes would include:
- Make consumer warnings more prominent and easier to read on tanning devices.
- Require an easily accessible emergency shutoff switch (or panic button) on all tanning devices.
- Add requirements to limit the amount of light allowed through protective eyewear to protect the eyes.
- Improve labeling on replacement bulbs to ensure tanning facility operators use the proper bulbs to reduce risk for accidental burns.
- Prohibit tanning facilities from making dangerous device modifications (eg, installing stronger bulbs) without recertifying and reidentifying the device with the FDA.
The FDA reports that more than 1 million minors use indoor tanning facilities each year. According to the American Academy of Dermatology, consumers younger than 35 years who use indoor tanning facilities are 59% more likely to develop melanoma than those who have never tanned indoors. Because the effects of UV exposure are cumulative and add up over the course of one’s lifetime, minors who use indoor tanning devices are at an increased risk for developing melanoma and nonmelanoma skin cancers later in life.
In 2014 the FDA began requiring tanning devices to be labeled with a visible warning stating that individuals younger than 18 years should not use them. Additionally, several states have already passed laws prohibiting minors from indoor tanning; in Connecticut, New Jersey, New York, and Pennsylvania, tanning devices are banned in individuals younger than 17 years.
Dermatologists are in the position to discuss the health risks of indoor tanning with all patients regardless of age. Patients should be reminded that failure to wear appropriate protective eyewear can lead to short-term and long-term eye injury and that long exposures can lead to burning that may not be recognized until it is too late. It also is important to warn patients that tanning while using certain medications or cosmetics may cause increased sensitivity to UV radiation. Patients can be referred to the FDA website for more consumer updates about indoor tanning and the proposed rules.
Guidelines highlight revolution in advanced melanoma therapies
HOLLYWOOD, FLA. –The remarkable changes that have occurred in the treatment of advanced malignant melanoma over the last several years are reflected in revised National Comprehensive Cancer Network guidelines.
“Gone are the days where our active agents were interferon and dacarbazine,” said Dr. John A. Thompson of the Fred Hutchinson Cancer Research Center, Seattle.
“We’ve seen the approval by the FDA of the PD-1-targeted agents and also molecular-targeted agents to treat patients with mutations in the BRAF gene, and the rate of change continues apace,” he said at the annual conference of the National Comprehensive Cancer Network.
Among the changes in the 2016 guidelines are the addition of high-dose ipilimumab (Yervoy) as an option for stage III (node-positive) disease, and intralesional talimogene laherparepvec (T-VEC) for primary treatment of stage III in-transit disease.
Guidelines for first-line systemic therapy for metastatic or unresectable disease recommend treatment based on evaluation of individual patients and include:
• Monotherapy with an anti-PD-1 (programmed death-1) agent, either pembrolizumab (Keytruda) or nivolumab (Opdivo) (category 1 recommendation).
• Targeted therapy for BRAF-mutated disease with combinations (preferred) of either dabrafenib (Tafinlar) and trametinib (Mekinist) or vemurafenib (Zelboraf)and cobimetinib (Cotellic); both are category 1 recommendations.
• Single-agent therapy with either vemurafenib or dabrafenib (category 1), or clinical trial.
For patients with disease progression or those who have had their maximum clinical benefit from BRAF-targeted therapy and good performance status (0-2), the guidelines recommend second-line or subsequent therapy with anti-PD-1 agents as above, ipilimumab, or a combination of nivolumab and ipilimumab.
The guidelines note, however, that “nivolumab/ipilimumab combination therapy is associated with improved relapse-free survival compared with single-agent nivolumab or ipilimumab, at the expense of significantly increased toxicity. Compared to single-agent therapy, the impact of nivolumab/ipilimumab combination therapy on overall survival is not known.”
Also recommended are targeted therapy with the BRAF-inhibitor combinations listed above (preferred) or single-agent therapy with vemurafenib or dabrafenib.
“In previously untreated patients with unresectable stage IIIC or stage IV disease, the combination of vemurafenib/cobimetinib was associated with improved PFS [progression-free survival] and response rate when compared to vemurafenib alone. The impact on overall survival compared to single-agent vemurafenib is unknown,” the guidelines state.
Other second-line options for patients with good performance status include high-dose interleukin-2 (not suitable for patients with inadequate organ reserve, poor performance status, or untreated or active brain metastases), biochemotherapy and cytotoxic agents (dacarbazine or temozolomide, and cisplatin or carboplatin, with or without vinblastine or nitrosourea, and IL-2 and interferon alfa-2b; paclitaxel, albumin-bound paclitaxel).
For patients with poor performance status (3-4) the guidelines call for best supportive care according to guidelines for palliative care.
Oncolytic immunotherapy
For treatment of recurrent disease, the guidelines newly recommend use of T-VEC, a genetically modified herpes simplex-1 virus that is injected intralesionally into accessible tumors. The attenuated virus does not kill healthy cells, but replicates in tumors and causes the cells to secrete granulocyte macrophage–colony stimulating factor (GM-CSF), leading to lysis of the tumor cells.
“It is hypothesized that the GM-CSF works with the immune system to boost a resident immune response against the destroyed melanoma cells and antigens that are released from this process,” Dr. Thompson said.
In a recent clinical trial (J Clin Oncol. 2015;33:2780-8), patients with injectable melanoma that was not surgically resectable were randomized to either intralesional T-VEC injections on week 0, 3, and then every 2 weeks (295 patients), or subcutaneous GM-CSF 125 mcg/m2 on days 1 to 14 for every 28 days (141 patients).
T-VEC was associated with significantly more durables responses (16% vs. 2.1% for GM-CSF, P less than .001) and a significantly higher overall response rate (26.4% vs. 5.7%, respectively, P less than .001).
In the primary analysis in an intent-to-treat population, T-VEC had a borderline significant association with better overall survival (median 23.2 vs. 18.9 months, hazard ratio [HR] 0.70, log-rank P = .051).
In subanalyses of outcomes in patient subgroups, however, the benefits of T-VEC were seen in patients with stage IIIB IIIC, and IV M1a disease (HR 0.57, P less than .001), but not in patients with IV M1b or M1c disease. In addition, patients treated with T-VEC in first-line therapy had significantly better overall survival compared with GM-CSF (HR 0.50, P less than .001), but those who received it in second or subsequent lines of therapy saw no survival benefit from intralesional injection.
Future directions for the treatment of advanced melanoma include identification of predictive biomarkers to guide the choice of therapy, new immune agonist antibodies or checkpoint inhibitors to act in concert with PD-1 inhibitors, adaptive T-cell therapies, and lymphokines, cytokines, vaccines, and targeted therapies that can overcome mechanisms of resistance and work in combination with immunomodulators, Dr. Thompson said.
HOLLYWOOD, FLA. –The remarkable changes that have occurred in the treatment of advanced malignant melanoma over the last several years are reflected in revised National Comprehensive Cancer Network guidelines.
“Gone are the days where our active agents were interferon and dacarbazine,” said Dr. John A. Thompson of the Fred Hutchinson Cancer Research Center, Seattle.
“We’ve seen the approval by the FDA of the PD-1-targeted agents and also molecular-targeted agents to treat patients with mutations in the BRAF gene, and the rate of change continues apace,” he said at the annual conference of the National Comprehensive Cancer Network.
Among the changes in the 2016 guidelines are the addition of high-dose ipilimumab (Yervoy) as an option for stage III (node-positive) disease, and intralesional talimogene laherparepvec (T-VEC) for primary treatment of stage III in-transit disease.
Guidelines for first-line systemic therapy for metastatic or unresectable disease recommend treatment based on evaluation of individual patients and include:
• Monotherapy with an anti-PD-1 (programmed death-1) agent, either pembrolizumab (Keytruda) or nivolumab (Opdivo) (category 1 recommendation).
• Targeted therapy for BRAF-mutated disease with combinations (preferred) of either dabrafenib (Tafinlar) and trametinib (Mekinist) or vemurafenib (Zelboraf)and cobimetinib (Cotellic); both are category 1 recommendations.
• Single-agent therapy with either vemurafenib or dabrafenib (category 1), or clinical trial.
For patients with disease progression or those who have had their maximum clinical benefit from BRAF-targeted therapy and good performance status (0-2), the guidelines recommend second-line or subsequent therapy with anti-PD-1 agents as above, ipilimumab, or a combination of nivolumab and ipilimumab.
The guidelines note, however, that “nivolumab/ipilimumab combination therapy is associated with improved relapse-free survival compared with single-agent nivolumab or ipilimumab, at the expense of significantly increased toxicity. Compared to single-agent therapy, the impact of nivolumab/ipilimumab combination therapy on overall survival is not known.”
Also recommended are targeted therapy with the BRAF-inhibitor combinations listed above (preferred) or single-agent therapy with vemurafenib or dabrafenib.
“In previously untreated patients with unresectable stage IIIC or stage IV disease, the combination of vemurafenib/cobimetinib was associated with improved PFS [progression-free survival] and response rate when compared to vemurafenib alone. The impact on overall survival compared to single-agent vemurafenib is unknown,” the guidelines state.
Other second-line options for patients with good performance status include high-dose interleukin-2 (not suitable for patients with inadequate organ reserve, poor performance status, or untreated or active brain metastases), biochemotherapy and cytotoxic agents (dacarbazine or temozolomide, and cisplatin or carboplatin, with or without vinblastine or nitrosourea, and IL-2 and interferon alfa-2b; paclitaxel, albumin-bound paclitaxel).
For patients with poor performance status (3-4) the guidelines call for best supportive care according to guidelines for palliative care.
Oncolytic immunotherapy
For treatment of recurrent disease, the guidelines newly recommend use of T-VEC, a genetically modified herpes simplex-1 virus that is injected intralesionally into accessible tumors. The attenuated virus does not kill healthy cells, but replicates in tumors and causes the cells to secrete granulocyte macrophage–colony stimulating factor (GM-CSF), leading to lysis of the tumor cells.
“It is hypothesized that the GM-CSF works with the immune system to boost a resident immune response against the destroyed melanoma cells and antigens that are released from this process,” Dr. Thompson said.
In a recent clinical trial (J Clin Oncol. 2015;33:2780-8), patients with injectable melanoma that was not surgically resectable were randomized to either intralesional T-VEC injections on week 0, 3, and then every 2 weeks (295 patients), or subcutaneous GM-CSF 125 mcg/m2 on days 1 to 14 for every 28 days (141 patients).
T-VEC was associated with significantly more durables responses (16% vs. 2.1% for GM-CSF, P less than .001) and a significantly higher overall response rate (26.4% vs. 5.7%, respectively, P less than .001).
In the primary analysis in an intent-to-treat population, T-VEC had a borderline significant association with better overall survival (median 23.2 vs. 18.9 months, hazard ratio [HR] 0.70, log-rank P = .051).
In subanalyses of outcomes in patient subgroups, however, the benefits of T-VEC were seen in patients with stage IIIB IIIC, and IV M1a disease (HR 0.57, P less than .001), but not in patients with IV M1b or M1c disease. In addition, patients treated with T-VEC in first-line therapy had significantly better overall survival compared with GM-CSF (HR 0.50, P less than .001), but those who received it in second or subsequent lines of therapy saw no survival benefit from intralesional injection.
Future directions for the treatment of advanced melanoma include identification of predictive biomarkers to guide the choice of therapy, new immune agonist antibodies or checkpoint inhibitors to act in concert with PD-1 inhibitors, adaptive T-cell therapies, and lymphokines, cytokines, vaccines, and targeted therapies that can overcome mechanisms of resistance and work in combination with immunomodulators, Dr. Thompson said.
HOLLYWOOD, FLA. –The remarkable changes that have occurred in the treatment of advanced malignant melanoma over the last several years are reflected in revised National Comprehensive Cancer Network guidelines.
“Gone are the days where our active agents were interferon and dacarbazine,” said Dr. John A. Thompson of the Fred Hutchinson Cancer Research Center, Seattle.
“We’ve seen the approval by the FDA of the PD-1-targeted agents and also molecular-targeted agents to treat patients with mutations in the BRAF gene, and the rate of change continues apace,” he said at the annual conference of the National Comprehensive Cancer Network.
Among the changes in the 2016 guidelines are the addition of high-dose ipilimumab (Yervoy) as an option for stage III (node-positive) disease, and intralesional talimogene laherparepvec (T-VEC) for primary treatment of stage III in-transit disease.
Guidelines for first-line systemic therapy for metastatic or unresectable disease recommend treatment based on evaluation of individual patients and include:
• Monotherapy with an anti-PD-1 (programmed death-1) agent, either pembrolizumab (Keytruda) or nivolumab (Opdivo) (category 1 recommendation).
• Targeted therapy for BRAF-mutated disease with combinations (preferred) of either dabrafenib (Tafinlar) and trametinib (Mekinist) or vemurafenib (Zelboraf)and cobimetinib (Cotellic); both are category 1 recommendations.
• Single-agent therapy with either vemurafenib or dabrafenib (category 1), or clinical trial.
For patients with disease progression or those who have had their maximum clinical benefit from BRAF-targeted therapy and good performance status (0-2), the guidelines recommend second-line or subsequent therapy with anti-PD-1 agents as above, ipilimumab, or a combination of nivolumab and ipilimumab.
The guidelines note, however, that “nivolumab/ipilimumab combination therapy is associated with improved relapse-free survival compared with single-agent nivolumab or ipilimumab, at the expense of significantly increased toxicity. Compared to single-agent therapy, the impact of nivolumab/ipilimumab combination therapy on overall survival is not known.”
Also recommended are targeted therapy with the BRAF-inhibitor combinations listed above (preferred) or single-agent therapy with vemurafenib or dabrafenib.
“In previously untreated patients with unresectable stage IIIC or stage IV disease, the combination of vemurafenib/cobimetinib was associated with improved PFS [progression-free survival] and response rate when compared to vemurafenib alone. The impact on overall survival compared to single-agent vemurafenib is unknown,” the guidelines state.
Other second-line options for patients with good performance status include high-dose interleukin-2 (not suitable for patients with inadequate organ reserve, poor performance status, or untreated or active brain metastases), biochemotherapy and cytotoxic agents (dacarbazine or temozolomide, and cisplatin or carboplatin, with or without vinblastine or nitrosourea, and IL-2 and interferon alfa-2b; paclitaxel, albumin-bound paclitaxel).
For patients with poor performance status (3-4) the guidelines call for best supportive care according to guidelines for palliative care.
Oncolytic immunotherapy
For treatment of recurrent disease, the guidelines newly recommend use of T-VEC, a genetically modified herpes simplex-1 virus that is injected intralesionally into accessible tumors. The attenuated virus does not kill healthy cells, but replicates in tumors and causes the cells to secrete granulocyte macrophage–colony stimulating factor (GM-CSF), leading to lysis of the tumor cells.
“It is hypothesized that the GM-CSF works with the immune system to boost a resident immune response against the destroyed melanoma cells and antigens that are released from this process,” Dr. Thompson said.
In a recent clinical trial (J Clin Oncol. 2015;33:2780-8), patients with injectable melanoma that was not surgically resectable were randomized to either intralesional T-VEC injections on week 0, 3, and then every 2 weeks (295 patients), or subcutaneous GM-CSF 125 mcg/m2 on days 1 to 14 for every 28 days (141 patients).
T-VEC was associated with significantly more durables responses (16% vs. 2.1% for GM-CSF, P less than .001) and a significantly higher overall response rate (26.4% vs. 5.7%, respectively, P less than .001).
In the primary analysis in an intent-to-treat population, T-VEC had a borderline significant association with better overall survival (median 23.2 vs. 18.9 months, hazard ratio [HR] 0.70, log-rank P = .051).
In subanalyses of outcomes in patient subgroups, however, the benefits of T-VEC were seen in patients with stage IIIB IIIC, and IV M1a disease (HR 0.57, P less than .001), but not in patients with IV M1b or M1c disease. In addition, patients treated with T-VEC in first-line therapy had significantly better overall survival compared with GM-CSF (HR 0.50, P less than .001), but those who received it in second or subsequent lines of therapy saw no survival benefit from intralesional injection.
Future directions for the treatment of advanced melanoma include identification of predictive biomarkers to guide the choice of therapy, new immune agonist antibodies or checkpoint inhibitors to act in concert with PD-1 inhibitors, adaptive T-cell therapies, and lymphokines, cytokines, vaccines, and targeted therapies that can overcome mechanisms of resistance and work in combination with immunomodulators, Dr. Thompson said.
AT THE NCCN ANNUAL CONFERENCE
Key clinical point: Immunotherapies and targeted agents have revolutionized the treatment of advanced melanoma.
Major finding: Current therapies are associated with response rates ranging from 60% to 75%.
Data source: Review of NCCN melanoma guideline changes and evidence supporting the changes.
Disclosures: Dr. Thompson disclosed consulting fees or honoraria from Eisai, Genentech, and Seattle Genetics, and “other financial benefit” from Celidex Therapeutics.
Nevi, Melanoma, and the Ongoing Argument on Atypia
In a case study published online on March 2 in JAMA Dermatology, Geller et al examined the relationship between total nevi, atypical nevi, and melanoma thickness. The study included 566 patients with melanoma. They were administered written surveys and underwent skin examinations at academic centers in Michigan and California within 3 months of diagnosis, measuring current total nevus count and atypical nevus count in addition to cataloguing melanoma thickness, histologic subtype, patient age, sex, marital status, skin self-examination and physician skin examination tendency, other health care visits, and mode of melanoma discovery.
Many epidemiologic trends were noted, but in summary, most melanoma patients had 0 to 20 total nevi (66.4%) and no atypical nevi (73.3%), a trend most pronounced in older patients (≥60 years). In patients younger than 60 years, higher nevus count (>50) was associated with thinner melanomas (≤2.0 mm), and the presence of more than 5 atypical nevi was associated with thicker melanomas (>2.0 mm).
What’s the issue?Studies clarifying the overall clinical characteristics of patients with aggressive melanomas appear every month in reputable journals, touting that concurrent total nevus count is important; or nevus size is important; or atypia is important; or clinical stigmata, medical history, and family history are important. Who is correct? Is everyone correct? On the pathology arm of the argument, Rosendahl et al (J Am Acad Dermatol. 2015;73:507-512) highlighted the same dilemma in which clinicians do not agree on the histopathologic features of nevi that consistently put patients at risk for individual lesion or de novo melanoma.
For me, each clinic day involves performing many total-body skin examinations, and many of these patients have innumerable nevi and various scars from lesions removed over the years with “atypical mole,” “premelanoma,” “precancer,” and various other self-reported labels. Some lesions may have documented pathology reports, but many do not. Some reports refer to dysplasia as a gradient, some do not. Some reports include molecular testing or clinical markers to grade lesions, and each can vary between institutions and pathologists. On the macroscopic level, clinically atypical nevi do not have a widely agreed upon set of criteria or threshold for biopsy; some clinicians use dermoscopic markers, and others utilize some version of the ABCDE (a=asymmetry; b=border; c=color; d=diameter; e=evolving) features.
The Geller et al study supports that these melanoma patients did not necessarily have more total nevi, and younger patients with aggressive melanoma may have a tendency toward more clinically atypical nevi. Although the study establishes what those institutions and clinicians determined to be atypical, I’m not sure that this is something that most clinicians widely agree upon. Additionally, these features were not paired with histopathologic dysplasia because the lesions were not biopsied.
What I find in conversation with colleagues is that some agree with what Geller et al defined as atypical, but some clinicians do not even refer to nevi as clinically atypical in a medical record unless they have pathology evidence of atypia (or the term their pathologist may use), which may be to avoid controversy regarding legal implications of atypia or “open-note” misunderstanding that the patient may have about this term, likening it to Papanicolaou test premalignancy verbiage.
I am not aware of one dermatologist or dermatopathologist who does not find this quandary to be frustrating. How do any of us really know which patients to follow more often for melanoma surveillance? How does your practice or institution report atypia in the clinical and histopathologic setting, and what do you find are the most important markers for development of melanoma?
In a case study published online on March 2 in JAMA Dermatology, Geller et al examined the relationship between total nevi, atypical nevi, and melanoma thickness. The study included 566 patients with melanoma. They were administered written surveys and underwent skin examinations at academic centers in Michigan and California within 3 months of diagnosis, measuring current total nevus count and atypical nevus count in addition to cataloguing melanoma thickness, histologic subtype, patient age, sex, marital status, skin self-examination and physician skin examination tendency, other health care visits, and mode of melanoma discovery.
Many epidemiologic trends were noted, but in summary, most melanoma patients had 0 to 20 total nevi (66.4%) and no atypical nevi (73.3%), a trend most pronounced in older patients (≥60 years). In patients younger than 60 years, higher nevus count (>50) was associated with thinner melanomas (≤2.0 mm), and the presence of more than 5 atypical nevi was associated with thicker melanomas (>2.0 mm).
What’s the issue?Studies clarifying the overall clinical characteristics of patients with aggressive melanomas appear every month in reputable journals, touting that concurrent total nevus count is important; or nevus size is important; or atypia is important; or clinical stigmata, medical history, and family history are important. Who is correct? Is everyone correct? On the pathology arm of the argument, Rosendahl et al (J Am Acad Dermatol. 2015;73:507-512) highlighted the same dilemma in which clinicians do not agree on the histopathologic features of nevi that consistently put patients at risk for individual lesion or de novo melanoma.
For me, each clinic day involves performing many total-body skin examinations, and many of these patients have innumerable nevi and various scars from lesions removed over the years with “atypical mole,” “premelanoma,” “precancer,” and various other self-reported labels. Some lesions may have documented pathology reports, but many do not. Some reports refer to dysplasia as a gradient, some do not. Some reports include molecular testing or clinical markers to grade lesions, and each can vary between institutions and pathologists. On the macroscopic level, clinically atypical nevi do not have a widely agreed upon set of criteria or threshold for biopsy; some clinicians use dermoscopic markers, and others utilize some version of the ABCDE (a=asymmetry; b=border; c=color; d=diameter; e=evolving) features.
The Geller et al study supports that these melanoma patients did not necessarily have more total nevi, and younger patients with aggressive melanoma may have a tendency toward more clinically atypical nevi. Although the study establishes what those institutions and clinicians determined to be atypical, I’m not sure that this is something that most clinicians widely agree upon. Additionally, these features were not paired with histopathologic dysplasia because the lesions were not biopsied.
What I find in conversation with colleagues is that some agree with what Geller et al defined as atypical, but some clinicians do not even refer to nevi as clinically atypical in a medical record unless they have pathology evidence of atypia (or the term their pathologist may use), which may be to avoid controversy regarding legal implications of atypia or “open-note” misunderstanding that the patient may have about this term, likening it to Papanicolaou test premalignancy verbiage.
I am not aware of one dermatologist or dermatopathologist who does not find this quandary to be frustrating. How do any of us really know which patients to follow more often for melanoma surveillance? How does your practice or institution report atypia in the clinical and histopathologic setting, and what do you find are the most important markers for development of melanoma?
In a case study published online on March 2 in JAMA Dermatology, Geller et al examined the relationship between total nevi, atypical nevi, and melanoma thickness. The study included 566 patients with melanoma. They were administered written surveys and underwent skin examinations at academic centers in Michigan and California within 3 months of diagnosis, measuring current total nevus count and atypical nevus count in addition to cataloguing melanoma thickness, histologic subtype, patient age, sex, marital status, skin self-examination and physician skin examination tendency, other health care visits, and mode of melanoma discovery.
Many epidemiologic trends were noted, but in summary, most melanoma patients had 0 to 20 total nevi (66.4%) and no atypical nevi (73.3%), a trend most pronounced in older patients (≥60 years). In patients younger than 60 years, higher nevus count (>50) was associated with thinner melanomas (≤2.0 mm), and the presence of more than 5 atypical nevi was associated with thicker melanomas (>2.0 mm).
What’s the issue?Studies clarifying the overall clinical characteristics of patients with aggressive melanomas appear every month in reputable journals, touting that concurrent total nevus count is important; or nevus size is important; or atypia is important; or clinical stigmata, medical history, and family history are important. Who is correct? Is everyone correct? On the pathology arm of the argument, Rosendahl et al (J Am Acad Dermatol. 2015;73:507-512) highlighted the same dilemma in which clinicians do not agree on the histopathologic features of nevi that consistently put patients at risk for individual lesion or de novo melanoma.
For me, each clinic day involves performing many total-body skin examinations, and many of these patients have innumerable nevi and various scars from lesions removed over the years with “atypical mole,” “premelanoma,” “precancer,” and various other self-reported labels. Some lesions may have documented pathology reports, but many do not. Some reports refer to dysplasia as a gradient, some do not. Some reports include molecular testing or clinical markers to grade lesions, and each can vary between institutions and pathologists. On the macroscopic level, clinically atypical nevi do not have a widely agreed upon set of criteria or threshold for biopsy; some clinicians use dermoscopic markers, and others utilize some version of the ABCDE (a=asymmetry; b=border; c=color; d=diameter; e=evolving) features.
The Geller et al study supports that these melanoma patients did not necessarily have more total nevi, and younger patients with aggressive melanoma may have a tendency toward more clinically atypical nevi. Although the study establishes what those institutions and clinicians determined to be atypical, I’m not sure that this is something that most clinicians widely agree upon. Additionally, these features were not paired with histopathologic dysplasia because the lesions were not biopsied.
What I find in conversation with colleagues is that some agree with what Geller et al defined as atypical, but some clinicians do not even refer to nevi as clinically atypical in a medical record unless they have pathology evidence of atypia (or the term their pathologist may use), which may be to avoid controversy regarding legal implications of atypia or “open-note” misunderstanding that the patient may have about this term, likening it to Papanicolaou test premalignancy verbiage.
I am not aware of one dermatologist or dermatopathologist who does not find this quandary to be frustrating. How do any of us really know which patients to follow more often for melanoma surveillance? How does your practice or institution report atypia in the clinical and histopathologic setting, and what do you find are the most important markers for development of melanoma?
Targeted therapy, immunotherapy may benefit patients with leptomeningeal metastases from melanoma
Patients with leptomeningeal metastases (LM) from melanoma have a poor prognosis, but treatment with targeted therapy and immune checkpoint inhibitors increased overall survival and resulted in long-term remission in a few patients, according to researchers.
The median survival for 21 patients who were treated with a BRAF inhibitor and/or ipilimumab was 21.7 weeks (range 2 to 235+ weeks); 24.9 weeks for treatment including a BRAF inhibitor (with and without a MEK inhibitor); 15.8 weeks for treatment including ipilimumab; and 4.3 weeks for radiotherapy (RT) only (Annals of Oncology 2016 March 8. doi: 10.1093/annonc/mdw134).
“A remarkable and encouraging new finding in our study is the long-term survival of patients who were treated with targeted treatment or immunotherapy. Moreover, the median survival of 22 weeks following these new therapies compares favorably to reported results of [intrathecal] chemotherapy for LM from melanoma,” wrote Dr. Marnix Geukes Foppen of Netherlands Cancer Institute, Amsterdam, and colleagues.
The retrospective analysis evaluated 39 consecutive patients treated at the Netherlands Cancer Institute during 2010-2015. Because of rapid disease progression or poor performance status, 14 patients did not receive treatment for LM, and their median survival was 2.9 weeks. Among 25 patients who were treated for LM, 15 received cranial or spinal RT and 21 received systemic therapy, and the median survival was 16.9 weeks.
Patients with performance status of 2 or 3 had worse survival than did those with performance status of 0 or 1 (3.6 vs. 18.8 weeks, P less than .001), and treatment did not significantly improve survival in this group (median 1.9 weeks for untreated vs. 3.9 weeks for treated). Patients with increased serum levels of lactate dehydrogenase and/or S100B had poorer survival compared with patients with normal levels.
The investigators noted that ipilimumab increases anti-tumor T cell activation in the lymph nodes, and activated T cells can cross the blood-brain or blood-CSF barrier. RT combined with ipilimumab may increase responses. Among 10 patients whose treatment included ipilimumab, median survival was 15.8 weeks; median survival was 47 weeks for ipilimumab with RT, and 6 weeks for ipilimumab without RT. A patient who had lymph node and lung metastasis, and LM without brain metastasis, was treated with whole brain RT and four cycles of ipilimumab, resulting in a complete radiological and clinical remission beyond 54 months.
Combining systemic targeted therapy and immunotherapy may result in long-term remissions, according the investigators.
“Especially in LM patients with a good performance score and low serum LDH and S100B levels these treatment options should be considered,” they wrote.
Patients with leptomeningeal metastases (LM) from melanoma have a poor prognosis, but treatment with targeted therapy and immune checkpoint inhibitors increased overall survival and resulted in long-term remission in a few patients, according to researchers.
The median survival for 21 patients who were treated with a BRAF inhibitor and/or ipilimumab was 21.7 weeks (range 2 to 235+ weeks); 24.9 weeks for treatment including a BRAF inhibitor (with and without a MEK inhibitor); 15.8 weeks for treatment including ipilimumab; and 4.3 weeks for radiotherapy (RT) only (Annals of Oncology 2016 March 8. doi: 10.1093/annonc/mdw134).
“A remarkable and encouraging new finding in our study is the long-term survival of patients who were treated with targeted treatment or immunotherapy. Moreover, the median survival of 22 weeks following these new therapies compares favorably to reported results of [intrathecal] chemotherapy for LM from melanoma,” wrote Dr. Marnix Geukes Foppen of Netherlands Cancer Institute, Amsterdam, and colleagues.
The retrospective analysis evaluated 39 consecutive patients treated at the Netherlands Cancer Institute during 2010-2015. Because of rapid disease progression or poor performance status, 14 patients did not receive treatment for LM, and their median survival was 2.9 weeks. Among 25 patients who were treated for LM, 15 received cranial or spinal RT and 21 received systemic therapy, and the median survival was 16.9 weeks.
Patients with performance status of 2 or 3 had worse survival than did those with performance status of 0 or 1 (3.6 vs. 18.8 weeks, P less than .001), and treatment did not significantly improve survival in this group (median 1.9 weeks for untreated vs. 3.9 weeks for treated). Patients with increased serum levels of lactate dehydrogenase and/or S100B had poorer survival compared with patients with normal levels.
The investigators noted that ipilimumab increases anti-tumor T cell activation in the lymph nodes, and activated T cells can cross the blood-brain or blood-CSF barrier. RT combined with ipilimumab may increase responses. Among 10 patients whose treatment included ipilimumab, median survival was 15.8 weeks; median survival was 47 weeks for ipilimumab with RT, and 6 weeks for ipilimumab without RT. A patient who had lymph node and lung metastasis, and LM without brain metastasis, was treated with whole brain RT and four cycles of ipilimumab, resulting in a complete radiological and clinical remission beyond 54 months.
Combining systemic targeted therapy and immunotherapy may result in long-term remissions, according the investigators.
“Especially in LM patients with a good performance score and low serum LDH and S100B levels these treatment options should be considered,” they wrote.
Patients with leptomeningeal metastases (LM) from melanoma have a poor prognosis, but treatment with targeted therapy and immune checkpoint inhibitors increased overall survival and resulted in long-term remission in a few patients, according to researchers.
The median survival for 21 patients who were treated with a BRAF inhibitor and/or ipilimumab was 21.7 weeks (range 2 to 235+ weeks); 24.9 weeks for treatment including a BRAF inhibitor (with and without a MEK inhibitor); 15.8 weeks for treatment including ipilimumab; and 4.3 weeks for radiotherapy (RT) only (Annals of Oncology 2016 March 8. doi: 10.1093/annonc/mdw134).
“A remarkable and encouraging new finding in our study is the long-term survival of patients who were treated with targeted treatment or immunotherapy. Moreover, the median survival of 22 weeks following these new therapies compares favorably to reported results of [intrathecal] chemotherapy for LM from melanoma,” wrote Dr. Marnix Geukes Foppen of Netherlands Cancer Institute, Amsterdam, and colleagues.
The retrospective analysis evaluated 39 consecutive patients treated at the Netherlands Cancer Institute during 2010-2015. Because of rapid disease progression or poor performance status, 14 patients did not receive treatment for LM, and their median survival was 2.9 weeks. Among 25 patients who were treated for LM, 15 received cranial or spinal RT and 21 received systemic therapy, and the median survival was 16.9 weeks.
Patients with performance status of 2 or 3 had worse survival than did those with performance status of 0 or 1 (3.6 vs. 18.8 weeks, P less than .001), and treatment did not significantly improve survival in this group (median 1.9 weeks for untreated vs. 3.9 weeks for treated). Patients with increased serum levels of lactate dehydrogenase and/or S100B had poorer survival compared with patients with normal levels.
The investigators noted that ipilimumab increases anti-tumor T cell activation in the lymph nodes, and activated T cells can cross the blood-brain or blood-CSF barrier. RT combined with ipilimumab may increase responses. Among 10 patients whose treatment included ipilimumab, median survival was 15.8 weeks; median survival was 47 weeks for ipilimumab with RT, and 6 weeks for ipilimumab without RT. A patient who had lymph node and lung metastasis, and LM without brain metastasis, was treated with whole brain RT and four cycles of ipilimumab, resulting in a complete radiological and clinical remission beyond 54 months.
Combining systemic targeted therapy and immunotherapy may result in long-term remissions, according the investigators.
“Especially in LM patients with a good performance score and low serum LDH and S100B levels these treatment options should be considered,” they wrote.
FROM ANNALS OF ONCOLOGY
Key clinical point: Leptomeningeal metastases from melanoma yield a poor prognosis, but patients may benefit from systemic targeted therapy and immunotherapy.
Major finding: Median survival for patients treated with systemic targeted therapy and/or immunotherapy (n = 21) was 21.7 weeks (range 2 to 235+ weeks).
Data source: Retrospective analysis of 39 consecutive patients treated at the Netherlands Cancer Institute during 2010-2015.
Disclosures: Dr. Geukes Foppen and coauthors reported having no disclosures.
Intralesional interferon excels for challenging basal cell carcinomas
WAIKOLOA, HAWAII – Intralesional injection of interferon alfa-2b is an excellent option for the treatment of large problematic basal cell carcinomas in patients who aren’t interested in the higher-morbidity options, Dr. David L. Swanson said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
“This is a really effective way to treat basal cell carcinomas. These things just melt away before your eyes. It’s really quite amazing,” observed Dr. Swanson of Mayo Clinic Scottsdale (Ariz.).
He finds this therapy particularly useful in frail elderly patients who have a large BCC on the head or neck. A good example would be an 89-year-old with multiple comorbid conditions who has a 2-cm BCC on the tip of the nose and doesn’t want anything done about it. The patient declines the options of Mohs micrographic surgery or radiotherapy.
“This is the patient who just wants to be left alone. That’s fine if they’re going to be dead within a year, but if they’re going to be around for several years, that basal cell carcinoma could become a major issue for them,” the dermatologist continued.
He and his colleagues at the Mayo Clinic follow a treatment regimen similar to one laid out by Turkish investigators more than a decade ago in one of the few long-term outcome studies of intralesional interferon for treatment of BCCs.
Although interferon alfa-2b is approved for the intralesional treatment of genital warts and subcutaneously for Kaposi’s sarcoma and malignant melanoma, among other conditions, it’s off-label therapy for BCCs. The treatment entails thrice-weekly intralesional injections for 3 weeks. The dosing is 1.5 million units per injection for BCCs smaller than 2 cm and 3 million units per injection for BCCs that are 2 cm or larger. The injections are given without anesthesia, but premedication with 500-1,000 mg of acetaminophen is advisable to minimize aches and fever.
Interferon alfa-2b (Intron A) comes in a vial containing 10 million units with 1 mL of diluent. It’s important to reconstitute it carefully, similar to onabotulinumtoxin. Don’t shake it, Dr. Swanson advised.
The Turkish report included 20 patients with histopathologically proven BCCs on the head or neck. At clinical and dermatopathologic follow-up 8 weeks after the last interferon injection, 11 BCCs showed complete clinical and histopathologic cure, six showed partial remission, two showed no response, and one actually increased in size during treatment.
The 11 patients with an initial complete cure were followed for 7 years. During that period, only one of the 11 skin cancers recurred, at the fifth year (Clin Drug Investig. 2005;25[10]:661-7).
Dr. Swanson reported having no financial conflicts regarding his presentation. SDEF and this news organization are owned by the same parent company.
WAIKOLOA, HAWAII – Intralesional injection of interferon alfa-2b is an excellent option for the treatment of large problematic basal cell carcinomas in patients who aren’t interested in the higher-morbidity options, Dr. David L. Swanson said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
“This is a really effective way to treat basal cell carcinomas. These things just melt away before your eyes. It’s really quite amazing,” observed Dr. Swanson of Mayo Clinic Scottsdale (Ariz.).
He finds this therapy particularly useful in frail elderly patients who have a large BCC on the head or neck. A good example would be an 89-year-old with multiple comorbid conditions who has a 2-cm BCC on the tip of the nose and doesn’t want anything done about it. The patient declines the options of Mohs micrographic surgery or radiotherapy.
“This is the patient who just wants to be left alone. That’s fine if they’re going to be dead within a year, but if they’re going to be around for several years, that basal cell carcinoma could become a major issue for them,” the dermatologist continued.
He and his colleagues at the Mayo Clinic follow a treatment regimen similar to one laid out by Turkish investigators more than a decade ago in one of the few long-term outcome studies of intralesional interferon for treatment of BCCs.
Although interferon alfa-2b is approved for the intralesional treatment of genital warts and subcutaneously for Kaposi’s sarcoma and malignant melanoma, among other conditions, it’s off-label therapy for BCCs. The treatment entails thrice-weekly intralesional injections for 3 weeks. The dosing is 1.5 million units per injection for BCCs smaller than 2 cm and 3 million units per injection for BCCs that are 2 cm or larger. The injections are given without anesthesia, but premedication with 500-1,000 mg of acetaminophen is advisable to minimize aches and fever.
Interferon alfa-2b (Intron A) comes in a vial containing 10 million units with 1 mL of diluent. It’s important to reconstitute it carefully, similar to onabotulinumtoxin. Don’t shake it, Dr. Swanson advised.
The Turkish report included 20 patients with histopathologically proven BCCs on the head or neck. At clinical and dermatopathologic follow-up 8 weeks after the last interferon injection, 11 BCCs showed complete clinical and histopathologic cure, six showed partial remission, two showed no response, and one actually increased in size during treatment.
The 11 patients with an initial complete cure were followed for 7 years. During that period, only one of the 11 skin cancers recurred, at the fifth year (Clin Drug Investig. 2005;25[10]:661-7).
Dr. Swanson reported having no financial conflicts regarding his presentation. SDEF and this news organization are owned by the same parent company.
WAIKOLOA, HAWAII – Intralesional injection of interferon alfa-2b is an excellent option for the treatment of large problematic basal cell carcinomas in patients who aren’t interested in the higher-morbidity options, Dr. David L. Swanson said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
“This is a really effective way to treat basal cell carcinomas. These things just melt away before your eyes. It’s really quite amazing,” observed Dr. Swanson of Mayo Clinic Scottsdale (Ariz.).
He finds this therapy particularly useful in frail elderly patients who have a large BCC on the head or neck. A good example would be an 89-year-old with multiple comorbid conditions who has a 2-cm BCC on the tip of the nose and doesn’t want anything done about it. The patient declines the options of Mohs micrographic surgery or radiotherapy.
“This is the patient who just wants to be left alone. That’s fine if they’re going to be dead within a year, but if they’re going to be around for several years, that basal cell carcinoma could become a major issue for them,” the dermatologist continued.
He and his colleagues at the Mayo Clinic follow a treatment regimen similar to one laid out by Turkish investigators more than a decade ago in one of the few long-term outcome studies of intralesional interferon for treatment of BCCs.
Although interferon alfa-2b is approved for the intralesional treatment of genital warts and subcutaneously for Kaposi’s sarcoma and malignant melanoma, among other conditions, it’s off-label therapy for BCCs. The treatment entails thrice-weekly intralesional injections for 3 weeks. The dosing is 1.5 million units per injection for BCCs smaller than 2 cm and 3 million units per injection for BCCs that are 2 cm or larger. The injections are given without anesthesia, but premedication with 500-1,000 mg of acetaminophen is advisable to minimize aches and fever.
Interferon alfa-2b (Intron A) comes in a vial containing 10 million units with 1 mL of diluent. It’s important to reconstitute it carefully, similar to onabotulinumtoxin. Don’t shake it, Dr. Swanson advised.
The Turkish report included 20 patients with histopathologically proven BCCs on the head or neck. At clinical and dermatopathologic follow-up 8 weeks after the last interferon injection, 11 BCCs showed complete clinical and histopathologic cure, six showed partial remission, two showed no response, and one actually increased in size during treatment.
The 11 patients with an initial complete cure were followed for 7 years. During that period, only one of the 11 skin cancers recurred, at the fifth year (Clin Drug Investig. 2005;25[10]:661-7).
Dr. Swanson reported having no financial conflicts regarding his presentation. SDEF and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR
Tools for Diagnosing Skin Cancer Earlier: Report From the AAD Meeting
At the 74th Annual Meeting of the American Academy of Dermatology, Dr. Orit Markowitz discussed noninvasive imaging tools that can help dermatologists diagnose skin cancers earlier. She provides highlights from this session, including the use of dermoscopy and optical coherence technology to detect features of early melanoma and nonmelanoma skin cancers as well as monitor skin cancer management. A lesion that is pink clinically but shows pigment dermoscopically should be biopsied, Dr. Markowtiz advises, as it may be an early amelanotic melanoma. She also notes that noninvasive imaging tools can be used to detect residual tumor cells in treated skin that otherwise looks clinically normal.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
At the 74th Annual Meeting of the American Academy of Dermatology, Dr. Orit Markowitz discussed noninvasive imaging tools that can help dermatologists diagnose skin cancers earlier. She provides highlights from this session, including the use of dermoscopy and optical coherence technology to detect features of early melanoma and nonmelanoma skin cancers as well as monitor skin cancer management. A lesion that is pink clinically but shows pigment dermoscopically should be biopsied, Dr. Markowtiz advises, as it may be an early amelanotic melanoma. She also notes that noninvasive imaging tools can be used to detect residual tumor cells in treated skin that otherwise looks clinically normal.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
At the 74th Annual Meeting of the American Academy of Dermatology, Dr. Orit Markowitz discussed noninvasive imaging tools that can help dermatologists diagnose skin cancers earlier. She provides highlights from this session, including the use of dermoscopy and optical coherence technology to detect features of early melanoma and nonmelanoma skin cancers as well as monitor skin cancer management. A lesion that is pink clinically but shows pigment dermoscopically should be biopsied, Dr. Markowtiz advises, as it may be an early amelanotic melanoma. She also notes that noninvasive imaging tools can be used to detect residual tumor cells in treated skin that otherwise looks clinically normal.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Does sharing genetic risk change behavior?
In the era of individualized (or precision) medicine, we are presented with a unique opportunity to peer into the genetic “maps” of our patients. Through this window, we can envision the self-evident present or predict a possible future.
For the front-line provider, knowing that we could someday have a large amount of these data to deal with can be overwhelming. We may be loath to think that, amongst all the other daily battles we wage with current disease states, we may now need to understand and explain risk for future disease states.
But would we be more likely to use these data if we thought that they would change patient behavior? Maybe.
So does it?
Gareth Hollands, Ph.D., of the University of Cambridge, England, and his colleagues conducted a brilliantly timed and welcome systematic review of the literature assessing the impact of communicating DNA-based disease risk estimates on risk-reducing health behaviors and motivation to engage in such behaviors (BMJ. 2016 Mar 15;352:i1102).
Eighteen studies were found reporting on seven behavioral outcomes, including smoking cessation (six studies, n = 2,663), diet (seven studies, n = 1,784), and physical activity (six studies, n = 1,704). The smoking studies related genetic risk for lung or esophageal cancer; the diet studies related risk for diabetes, obesity, cardiovascular disease, hypertension, hyperlipidemia, and Alzheimer’s disease; and the physical activity studies related risks similar to the diet studies.
No evidence was found that communicating DNA-based risk increased smoking cessation or led to positive changes in diet or physical activity. Nor did the investigators find any effects on motivation to change behavior. Although this information is not motivating to patients, no evidence was found suggesting that it is demotivating, either.
If neither behavior nor motivation is modified by DNA-based risk assessment, what is it good for? As the authors pointed out, this information can be used for clinical risk stratification and for refining screening and treatment procedures.
It’s important to note that this puts the responsibility for the required action in response to DNA data in the hands of medical providers – sadly reminding us that the list of ways to motivate patients to change behavior remains frustratingly short.
Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author and do not necessarily represent the views and opinions of the Mayo Clinic. The opinions expressed in this article should not be used to diagnose or treat any medical condition nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician. Dr. Ebbert has no relevant financial disclosures about this article.
In the era of individualized (or precision) medicine, we are presented with a unique opportunity to peer into the genetic “maps” of our patients. Through this window, we can envision the self-evident present or predict a possible future.
For the front-line provider, knowing that we could someday have a large amount of these data to deal with can be overwhelming. We may be loath to think that, amongst all the other daily battles we wage with current disease states, we may now need to understand and explain risk for future disease states.
But would we be more likely to use these data if we thought that they would change patient behavior? Maybe.
So does it?
Gareth Hollands, Ph.D., of the University of Cambridge, England, and his colleagues conducted a brilliantly timed and welcome systematic review of the literature assessing the impact of communicating DNA-based disease risk estimates on risk-reducing health behaviors and motivation to engage in such behaviors (BMJ. 2016 Mar 15;352:i1102).
Eighteen studies were found reporting on seven behavioral outcomes, including smoking cessation (six studies, n = 2,663), diet (seven studies, n = 1,784), and physical activity (six studies, n = 1,704). The smoking studies related genetic risk for lung or esophageal cancer; the diet studies related risk for diabetes, obesity, cardiovascular disease, hypertension, hyperlipidemia, and Alzheimer’s disease; and the physical activity studies related risks similar to the diet studies.
No evidence was found that communicating DNA-based risk increased smoking cessation or led to positive changes in diet or physical activity. Nor did the investigators find any effects on motivation to change behavior. Although this information is not motivating to patients, no evidence was found suggesting that it is demotivating, either.
If neither behavior nor motivation is modified by DNA-based risk assessment, what is it good for? As the authors pointed out, this information can be used for clinical risk stratification and for refining screening and treatment procedures.
It’s important to note that this puts the responsibility for the required action in response to DNA data in the hands of medical providers – sadly reminding us that the list of ways to motivate patients to change behavior remains frustratingly short.
Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author and do not necessarily represent the views and opinions of the Mayo Clinic. The opinions expressed in this article should not be used to diagnose or treat any medical condition nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician. Dr. Ebbert has no relevant financial disclosures about this article.
In the era of individualized (or precision) medicine, we are presented with a unique opportunity to peer into the genetic “maps” of our patients. Through this window, we can envision the self-evident present or predict a possible future.
For the front-line provider, knowing that we could someday have a large amount of these data to deal with can be overwhelming. We may be loath to think that, amongst all the other daily battles we wage with current disease states, we may now need to understand and explain risk for future disease states.
But would we be more likely to use these data if we thought that they would change patient behavior? Maybe.
So does it?
Gareth Hollands, Ph.D., of the University of Cambridge, England, and his colleagues conducted a brilliantly timed and welcome systematic review of the literature assessing the impact of communicating DNA-based disease risk estimates on risk-reducing health behaviors and motivation to engage in such behaviors (BMJ. 2016 Mar 15;352:i1102).
Eighteen studies were found reporting on seven behavioral outcomes, including smoking cessation (six studies, n = 2,663), diet (seven studies, n = 1,784), and physical activity (six studies, n = 1,704). The smoking studies related genetic risk for lung or esophageal cancer; the diet studies related risk for diabetes, obesity, cardiovascular disease, hypertension, hyperlipidemia, and Alzheimer’s disease; and the physical activity studies related risks similar to the diet studies.
No evidence was found that communicating DNA-based risk increased smoking cessation or led to positive changes in diet or physical activity. Nor did the investigators find any effects on motivation to change behavior. Although this information is not motivating to patients, no evidence was found suggesting that it is demotivating, either.
If neither behavior nor motivation is modified by DNA-based risk assessment, what is it good for? As the authors pointed out, this information can be used for clinical risk stratification and for refining screening and treatment procedures.
It’s important to note that this puts the responsibility for the required action in response to DNA data in the hands of medical providers – sadly reminding us that the list of ways to motivate patients to change behavior remains frustratingly short.
Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author and do not necessarily represent the views and opinions of the Mayo Clinic. The opinions expressed in this article should not be used to diagnose or treat any medical condition nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician. Dr. Ebbert has no relevant financial disclosures about this article.
Low vitamin D linked with worse outcome in melanoma
Lower levels of vitamin D in patients with melanoma were associated with poorer survival, independent of effects from systemic inflammation indicated by simultaneous C-reactive protein (CRP) measures, according to researchers.
Multivariate analysis showed that vitamin D level was associated with overall survival (OS) (hazard ratio, 1.02 per unit decrease of vitamin D; 95% confidence interval, 1.01-1.04; P = .005), melanoma-specific survival (MSS) (HR, 1.02; 95% CI, 1.00-1.04; P = .048), and disease-free survival (DFS) (HR, 1.02; 95% CI, 1.00-1.04; P = .043). Patients with a vitamin D level less than 16 ng/mL* were 2.0 times more likely to die of all-cause disease than were patients with a higher level (95% CI, 1.50-2.66; P less than .001), investigators reported (J Clin Oncol. 2016 Mar 21. doi: 10.1200/JCO.2015.64.1357).
“Importantly, after adjustment for CRP, vitamin D remained an independent predictor of OS, MSS, and DFS. This suggests that, although blood levels of vitamin D and CRP are highly correlated with each other, each independently predicts clinical outcome in patients with melanoma,” wrote Dr. Shenying Fang of the University of Texas MD Anderson Cancer Center, Houston, and colleagues.
Although the role of the biomarkers in disease remains unclear and warrants further research, the authors added, “these data suggest that interventions to increase vitamin D or to reduce [systematic inflammatory response] and CRP could ultimately benefit patients with melanoma.”
Previous research has demonstrated an association between vitamin D deficiency and advanced melanoma stage, but investigations of vitamin D blood levels and melanoma risk have yielded inconsistent results. The researchers examined confounders, such as systemic inflammatory response (assessed by simultaneous CRP measurement), age, disease stage, and blood draw season to assess the relationship between vitamin D level and melanoma outcomes.
Decreased vitamin D was significantly associated with higher patient age, increased primary tumor thickness, ulcerated tumors, advanced-stage disease at blood draw, and increased CRP. Blood drawn in the fall/winter had lower vitamin D levels than that of spring/summer, reflecting average differences in sun exposure. These factors were included in the multivariable model.
A vitamin D level less than 20 ng/mL* is considered deficient, and deficient levels were significantly associated with poorer OS and DFS but not with poorer MSS. At levels below the optimal cutoff, determined by recursive partitioning, of 16 ng/mL*, patients had poorer OS (HR, 2.0; 95% CI, 1.50-2.66; P less than .001), MSS (HR, 1.76; 95% CI, 1.22-2.53; P = .003), and DFS (HR, 1.62; 95% CI, 1.04-2.53; P = .036) on univariate analysis, and associations remained significant on multivariable analysis.
The hospital-based investigation evaluated peripheral blood samples collected from 1,042 non-Hispanic white patients with melanoma from 1997 to 2009.
Dr. Fang reported having no disclosures. Several of his coauthors reported financial ties to industry sources.
*Correction: An earlier version of this article used an incorrect unit of measurement for vitamin D deficiency.
Lower levels of vitamin D in patients with melanoma were associated with poorer survival, independent of effects from systemic inflammation indicated by simultaneous C-reactive protein (CRP) measures, according to researchers.
Multivariate analysis showed that vitamin D level was associated with overall survival (OS) (hazard ratio, 1.02 per unit decrease of vitamin D; 95% confidence interval, 1.01-1.04; P = .005), melanoma-specific survival (MSS) (HR, 1.02; 95% CI, 1.00-1.04; P = .048), and disease-free survival (DFS) (HR, 1.02; 95% CI, 1.00-1.04; P = .043). Patients with a vitamin D level less than 16 ng/mL* were 2.0 times more likely to die of all-cause disease than were patients with a higher level (95% CI, 1.50-2.66; P less than .001), investigators reported (J Clin Oncol. 2016 Mar 21. doi: 10.1200/JCO.2015.64.1357).
“Importantly, after adjustment for CRP, vitamin D remained an independent predictor of OS, MSS, and DFS. This suggests that, although blood levels of vitamin D and CRP are highly correlated with each other, each independently predicts clinical outcome in patients with melanoma,” wrote Dr. Shenying Fang of the University of Texas MD Anderson Cancer Center, Houston, and colleagues.
Although the role of the biomarkers in disease remains unclear and warrants further research, the authors added, “these data suggest that interventions to increase vitamin D or to reduce [systematic inflammatory response] and CRP could ultimately benefit patients with melanoma.”
Previous research has demonstrated an association between vitamin D deficiency and advanced melanoma stage, but investigations of vitamin D blood levels and melanoma risk have yielded inconsistent results. The researchers examined confounders, such as systemic inflammatory response (assessed by simultaneous CRP measurement), age, disease stage, and blood draw season to assess the relationship between vitamin D level and melanoma outcomes.
Decreased vitamin D was significantly associated with higher patient age, increased primary tumor thickness, ulcerated tumors, advanced-stage disease at blood draw, and increased CRP. Blood drawn in the fall/winter had lower vitamin D levels than that of spring/summer, reflecting average differences in sun exposure. These factors were included in the multivariable model.
A vitamin D level less than 20 ng/mL* is considered deficient, and deficient levels were significantly associated with poorer OS and DFS but not with poorer MSS. At levels below the optimal cutoff, determined by recursive partitioning, of 16 ng/mL*, patients had poorer OS (HR, 2.0; 95% CI, 1.50-2.66; P less than .001), MSS (HR, 1.76; 95% CI, 1.22-2.53; P = .003), and DFS (HR, 1.62; 95% CI, 1.04-2.53; P = .036) on univariate analysis, and associations remained significant on multivariable analysis.
The hospital-based investigation evaluated peripheral blood samples collected from 1,042 non-Hispanic white patients with melanoma from 1997 to 2009.
Dr. Fang reported having no disclosures. Several of his coauthors reported financial ties to industry sources.
*Correction: An earlier version of this article used an incorrect unit of measurement for vitamin D deficiency.
Lower levels of vitamin D in patients with melanoma were associated with poorer survival, independent of effects from systemic inflammation indicated by simultaneous C-reactive protein (CRP) measures, according to researchers.
Multivariate analysis showed that vitamin D level was associated with overall survival (OS) (hazard ratio, 1.02 per unit decrease of vitamin D; 95% confidence interval, 1.01-1.04; P = .005), melanoma-specific survival (MSS) (HR, 1.02; 95% CI, 1.00-1.04; P = .048), and disease-free survival (DFS) (HR, 1.02; 95% CI, 1.00-1.04; P = .043). Patients with a vitamin D level less than 16 ng/mL* were 2.0 times more likely to die of all-cause disease than were patients with a higher level (95% CI, 1.50-2.66; P less than .001), investigators reported (J Clin Oncol. 2016 Mar 21. doi: 10.1200/JCO.2015.64.1357).
“Importantly, after adjustment for CRP, vitamin D remained an independent predictor of OS, MSS, and DFS. This suggests that, although blood levels of vitamin D and CRP are highly correlated with each other, each independently predicts clinical outcome in patients with melanoma,” wrote Dr. Shenying Fang of the University of Texas MD Anderson Cancer Center, Houston, and colleagues.
Although the role of the biomarkers in disease remains unclear and warrants further research, the authors added, “these data suggest that interventions to increase vitamin D or to reduce [systematic inflammatory response] and CRP could ultimately benefit patients with melanoma.”
Previous research has demonstrated an association between vitamin D deficiency and advanced melanoma stage, but investigations of vitamin D blood levels and melanoma risk have yielded inconsistent results. The researchers examined confounders, such as systemic inflammatory response (assessed by simultaneous CRP measurement), age, disease stage, and blood draw season to assess the relationship between vitamin D level and melanoma outcomes.
Decreased vitamin D was significantly associated with higher patient age, increased primary tumor thickness, ulcerated tumors, advanced-stage disease at blood draw, and increased CRP. Blood drawn in the fall/winter had lower vitamin D levels than that of spring/summer, reflecting average differences in sun exposure. These factors were included in the multivariable model.
A vitamin D level less than 20 ng/mL* is considered deficient, and deficient levels were significantly associated with poorer OS and DFS but not with poorer MSS. At levels below the optimal cutoff, determined by recursive partitioning, of 16 ng/mL*, patients had poorer OS (HR, 2.0; 95% CI, 1.50-2.66; P less than .001), MSS (HR, 1.76; 95% CI, 1.22-2.53; P = .003), and DFS (HR, 1.62; 95% CI, 1.04-2.53; P = .036) on univariate analysis, and associations remained significant on multivariable analysis.
The hospital-based investigation evaluated peripheral blood samples collected from 1,042 non-Hispanic white patients with melanoma from 1997 to 2009.
Dr. Fang reported having no disclosures. Several of his coauthors reported financial ties to industry sources.
*Correction: An earlier version of this article used an incorrect unit of measurement for vitamin D deficiency.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: After adjusting for C-reactive protein (CRP), lower vitamin D levels were independently associated with worse outcomes in melanoma patients.
Major finding: After adjusting for CRP and other confounders, vitamin D level was associated with overall survival (hazard ratio, 1.02 per unit decrease of vitamin D; 95% confidence interval, 1.01-1.04; P = .005), melanoma-specific survival (HR, 1.02; 95% CI, 1.00-1.04; P = .048), and disease-free survival (HR, 1.02; 95% CI, 1.00-1.04; P = .043).
Data sources: Peripheral blood samples from 1,042 non-Hispanic white patients with melanoma were collected from 1997 to 2009.
Disclosures: Dr. Fang reported having no disclosures. Several of his coauthors reported financial ties to industry sources.