New Data Provide Better Prognostic Information for Cutaneous Melanoma.
Did you know?
>> A better understanding of prognostic factors in cutaneous melanoma has evolved over the last decade. A revised melanoma staging system was approved by the American Joint Committee on Cancer (AJCC) in 2002 based on an analysis of prognostic factors that involved 17,600 patients with melanoma.
A recent review in Cancer Control looked at current data on several different prognostic factors and found that there are other factors not included in the revised staging system that may alter prognosis, survival and treatment.
Here is a sampling of some of the clinical and histologic factors related to outcomes in cutaneous melanoma.
>> One study found that patients younger than 30 years of age had a 5-year survival rate of 87% compared to 78%, 71%, and 60% for those in their 60s, 70s, and 80s, respectively.
Source: Balch CM, Soong SJ, Gershenwald JE, et al. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol. 2001;19:3622-3634.
>> Pathologically documented nodal metastases by either sentinel or elective node dissection are defined as microscopic. Clinically or radiologically documented nodal metastases are defined as macroscopic. Ten-year survival rates for the two groups are significantly different with 63% survival rate in the presence of a single microscopic node versus a 47% survival rate in the presence of a single macroscopic node.
Source: Balch CM, Soong SJ, Gershenwald JE, et al. Prognostic factors analysis of 17,600 melanoma patients; validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol. 2001;19:3622-3634.
>> The 5-year overall survival rate in patients with thin tumors without other adverse prognostic factors is 95% or greater.
Source: Balch CM, Buzaid AC, Soong SJ, et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol. 2001;19:3635-3648.
Clark WH Jr, Elder DE, Guerry D IV, et al. Model predicting survival in stage I melanoma base on tumor progression. J Natl Cancer Inst. 1989;81:1893-1904.
>> The presence of ulceration decreases survival in all tumor thickness categories. Thin ulcerated tumors have about a 4% decreased 5-year survival rate compared to non-ulcerated tumors. This survival decrement is as high as 22% in thick (>4-mm) tumors.
Source: Balch CM, Soong SJ, Gershenwald JE, et al. Prognostic factors analysis of 17,600 melanoma patients; validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol. 2001;19:3622-3634.
>> Vascular invasion was present in 57% of nodular melanomas with lymph node metastasis at the time of diagnosis compared with only 12% of those confined to the skin.
Source:Straume O, Akslen LA. Independent prognostic importance of vascular invasion in nodular melanomas. Cancer. 1996;78:122-1219.
>> Microsatellites are discrete tumor nests greater than 0.05 mm in diameter that are separated from the main body of the tumor by normal reticular dermal collagen or subcutaneous fat. Though rarely occurring in tumors less than 1.5 mm, the 5-year survival rate for patients with microsatellites was 36% compared to 89% for those without these microsatellites.
Source:Day CL Jr, Harrist TJ, Gorstein F, et al. Malignant melanoma. Prognostic significance of “microscopic satellites” in the reticular dermis and subcutaneous fat. Ann Surg. 1981;194:108-112.
>> In 1,158 patients with distant metastases, those with subcutaneous or distant lymph nodes had a better prognosis than those with lung or other visceral organ involvement (1-year survival rates were 59%, 57%, and 41%, respectively.)
Source: Balch CM, Soong SJ, Gershenwald JE, et al. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol. 2001;19:3622-3634.
Balch CM, Buzaid AC, Soong SJ, et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol. 2001;19:3635-3648.
>> One study reported an elevated lactate dehydrogenase (LDH) serum level to have 79% sensitivity and 92% specificity in detecting disease progression in stage IV melanoma.
Source: Dessureault S, Soong SJ, Ross MI, et al. Improved staging of node-negative patients with intermediate to thick melanomas (>1mm) with the use of lymphatic mapping and sentinel lymph node biopsy. Ann Surg Oncol. 2001;8:766-770. Erratum in Ann Surg Oncol. 2002;9:318.
Shivers SC, Wang X, Li W, et al. Molecular staging of malignant melanoma: correlation with clinical outcome. JAMA. 1998;280:1410-1415.
Treating Photodamage with ALA Plus IPL
Study results show significant improvement of skin damage with combination therapy.
In late October, Dusa Pharmaceuticals announced the final results of the first prospective, randomized, controlled split-face clinical study using 5% aminolevulinic acid HCI (Levulan) photodynamic therapy together with intense pulsed light (IPL) for the treatment of photodamaged skin.
Study Specifics
For this study, which was published in the Archives of Dermatology, 20 patients received a series of three treatments
3 weeks apart — half of each patient’s face was pretreated with 5-ALA for 45 minutes before IPL treatment, while the other half the face was treated with IPL alone.
After the initial 3-week treatment period, all patients received two full-face IPL treatments. Before each of these treatments, patients were assessed for signs of photodamage, including global photodamage, fine lines, mottled pigmentation, tactile roughness and sallowness. After 4 weeks, patients were again assessed for signs of photodamage.
Results
Pre-treatment with ALA during the first three treatments resulted in statistically significant improvement in global score for photaging (80% vs. 50%, p<0.02), mottled pigmentation (85% vs. 20%, p<0.0008), and fine lines (55% vs. 20%, p<0.008). There was a noticeable improvement from baseline scores with respect to tactile roughness and sallowness, but pre-treatment with
5-ALA did not seem to enhance the results of the IPL treatment.
The final investigator cosmetic evaluations (p=0.0002) and subject satisfaction scores (p=0.005) were significantly better for the side pretreated with 5-ALA.
Both treatments were well tolerated and there was little difference in the adverse effects on the two treatment sides.
Researchers concluded that the combination of 5-ALA and IPL improves the results of photorejuvenation and patient satisfaction.
Study Authors: Jeffrey S. Dover, M.D., F.R.C.P.C., Ashish C. Bhatia, M.D.,
Brigitte Stewart, and Kenneth A. Arndt, M.D.
Why Redheads’ Melanin Is More Susceptible to UV Damage
All types of melanin are not created equal. And researchers at Duke University have now offered solid proof of that.
People with red hair generate a different type of melanin than people with other hair colors. Scientists have long speculated that the melanin produced in people with red hair, which is known as pheomelanin, could be a key pathway in the formation of skin cancer.
Although a link between pheomelanin and skin cancer was not directly established, researchers from Duke University have now been the first to prove that pheomelanin is more susceptible to UV damage than other types of melanin, according to the Associated Press. (Blond hair also contains some pheomelanin.)
Using a special laser and microscope, the researchers observed an oxidative-stress causing reaction to pheomelanin when both UVA and UVB light was applied. In contrast, the type of melanin found in black hair, called eumelanin, did not adversely react to both types of UV light. Only UVB light caused an oxidative reaction with eumelanin.
Melanoma and UVB
Is it possible that ultraviolet B light is not associated with a greater risk for developing melanoma? A recent study in the Journal of the National Cancer Institute reported just this finding. UVB exposure was linked to a higher risk of developing basal cell and squamous cell carcinomas, but not melanoma.
In the study, 469 patients with skin cancer (231 with non-melanoma skin cancer and 238 with cutaneous malignant melanoma) were compared with 329 patients who were cancer-free.
Researchers focused on analyzing each patient’s mutagen sensitivity, which is a factor in susceptibility to a number of epithelial skin cancers. They assessed mutagen sensitivity by measuring the number of mutagen-induced chromatid breaks per cell in primary lymphocytes in vitro. They made this assessment after exposing the study participants to UVB radiation, waiting 24 hours, and then drawing blood to assess the number of chromatid breaks.
Here’s what the researchers discovered:
1. Patients who had more chromatid breaks per cell above the median of control subjects were three times as likely to be at risk for BCC and SCC.
2. Patients with more chromatid breaks per cell than the median were not at an increased risk for cutaneous malignant melanoma.
Source: Wang L, et al. In Vitro Sensitivity to Ultraviolet B Light and Skin Cancer Risk: A Case-Control Analysis. Journal of the National Cancer Institute, Dec. 21, 2005; 97(24):1822-1831.
Possible New Strategy for Treating Cancer
Typically, cancer research that focuses on treatments with chemotherapy have taken quite a different path than research seeking to develop vaccines for cancer. Historically, the thinking is that the two treatments are completely incompatible — chemotherapy usually weakens the immune system and vaccines work by relying on a strong immune system. But that could be changing.
Researchers reported in the Journal of the National Cancer Institute experimented with combining chemotherapy
(5-fluorouracil [5-FU]) and immunotherapy (a vaccine that targeted thymidylate synthase polyepitopic peptide) and found that the combination was much more successful in killing breast and colon cancer cells than the vaccine alone: 43.5% vs. 26.5% of breast cancer cells and 73.5% vs. 48.5% of colon cancer cells.
How did the combination work? Researchers chose to work with a thymidylate synthase (TS)-directed polyepitopic peptide vaccine because TS lies on the surface of the cancer cells and is typically an enzyme that is overexpressed in malignant cells. They chose 5-FU because — although this drug works by inhibiting expression of TS — the malignant cells overexpress TS at some point after being exposed to 5-FU. This combined process results in the malignant cells becoming a much larger target for the vaccine.
Although this study was only performed in mice, the concept of combining these therapies is promising.
Source: Correale P, et al. 5-Fluorouracil-Based Chemotherapy Enhances the Antitumor Activity of a Thymidylate Synthase-Directed Polyepitopic Peptide Vaccine. Journal of the National Cancer Institute, Oct. 5, 2005; 97(19):1437-1445.
Anti-Cancer Drugs Show Promise for Aging Disease
FTIs may help treat progeria patients
A class of experimental anti-cancer drugs may be effective in treating a fatal genetic disorder that causes premature aging, according to a research team led by the National Human Research Institute (NHGRI), part of the National Institutes of Health (NIH).
Researchers found that drugs knows as farnesyltransferase inhibitors (FTIs), which are currently being tested in people with myeloid leukemia, neurofibromatosis and other conditions, might also provide a potential therapy for children suffering from Hutchinson-Gilford Progeria Syndrome, commonly referred to as progeria.
Currently, there are no known treatments for progeria, a genetic disorder that is estimated to affect one in every 4 million children. Children with the disorder appear normal at birth, but experience growth retardation and show dramatically accelerated symptoms of aging, such as hair loss, skin wrinkling and fat loss, as the grow older. Accelerated cardiovascular disease is also common and typically death from heart attack or stroke occurs around the age of 12.
NHGRI Director Francis S. Collins, M.D., Ph.D., the study’s senior author, reported that they found that FTIs can reverse the nuclear structure abnormalities that are hallmark of cells from children with progeria. Researchers used FTIs to treat skin cells taken from patients with progeria and grown in laboratory conditions. Upcoming studies in a mouse model are pending. If these studies validate the results of the cell experiments and translate into improvements in the animals’ conditions, a clinical trial of FTIs in children with progeria may being as early as next spring.
Sun-Damage Skin Test
A new scientific test to assess the damage people have done to their skin through sun exposure was launched in November to public clinics throughout the United Kingdom. The test, called “skinphysical”, is able to reveal the extent of DNA damage caused by sun exposure. The test draws on work by skin cancer experts at the University of Newcastle upon Tyne combined with Canadian company Genesis Genomics.
Patients taking this test need to give a small sample of skin from just above their elbow that is sent off for laboratory testing. Patients must also complete a comprehensive, 10-page questionnaire about their lifestyles, skin types, sun protection regimes and more. The information from the skin test and questionnaire is analyzed to determine a patient’s skin’s molecular profile, genetic skin type and extent of damage. Researchers then provide patients with customized sun safety advice. Patients can repeat the test at a later date to see if changes in sun-safety behaviors have had an effect on their risk of skin cancer.
Professor Mark Birch-Machin of the Newcastle University’s School of Clinical Laboratory Sciences and Managing Director of Genesis Genomics UK said, in a statement, “The key issue with handing out general advice on sun safety is that it’s not specific enough for the individual. It’s human nature for people to assume that diseases like skin cancer happen to other people — and they tend not to make any adjustments to their behavior until they are threatened with the real possibility of it affecting them.”
For more information, visit www.skinphysical.co.uk.
New Data Provide Better Prognostic Information for Cutaneous Melanoma.
Did you know?
>> A better understanding of prognostic factors in cutaneous melanoma has evolved over the last decade. A revised melanoma staging system was approved by the American Joint Committee on Cancer (AJCC) in 2002 based on an analysis of prognostic factors that involved 17,600 patients with melanoma.
A recent review in Cancer Control looked at current data on several different prognostic factors and found that there are other factors not included in the revised staging system that may alter prognosis, survival and treatment.
Here is a sampling of some of the clinical and histologic factors related to outcomes in cutaneous melanoma.
>> One study found that patients younger than 30 years of age had a 5-year survival rate of 87% compared to 78%, 71%, and 60% for those in their 60s, 70s, and 80s, respectively.
Source: Balch CM, Soong SJ, Gershenwald JE, et al. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol. 2001;19:3622-3634.
>> Pathologically documented nodal metastases by either sentinel or elective node dissection are defined as microscopic. Clinically or radiologically documented nodal metastases are defined as macroscopic. Ten-year survival rates for the two groups are significantly different with 63% survival rate in the presence of a single microscopic node versus a 47% survival rate in the presence of a single macroscopic node.
Source: Balch CM, Soong SJ, Gershenwald JE, et al. Prognostic factors analysis of 17,600 melanoma patients; validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol. 2001;19:3622-3634.
>> The 5-year overall survival rate in patients with thin tumors without other adverse prognostic factors is 95% or greater.
Source: Balch CM, Buzaid AC, Soong SJ, et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol. 2001;19:3635-3648.
Clark WH Jr, Elder DE, Guerry D IV, et al. Model predicting survival in stage I melanoma base on tumor progression. J Natl Cancer Inst. 1989;81:1893-1904.
>> The presence of ulceration decreases survival in all tumor thickness categories. Thin ulcerated tumors have about a 4% decreased 5-year survival rate compared to non-ulcerated tumors. This survival decrement is as high as 22% in thick (>4-mm) tumors.
Source: Balch CM, Soong SJ, Gershenwald JE, et al. Prognostic factors analysis of 17,600 melanoma patients; validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol. 2001;19:3622-3634.
>> Vascular invasion was present in 57% of nodular melanomas with lymph node metastasis at the time of diagnosis compared with only 12% of those confined to the skin.
Source:Straume O, Akslen LA. Independent prognostic importance of vascular invasion in nodular melanomas. Cancer. 1996;78:122-1219.
>> Microsatellites are discrete tumor nests greater than 0.05 mm in diameter that are separated from the main body of the tumor by normal reticular dermal collagen or subcutaneous fat. Though rarely occurring in tumors less than 1.5 mm, the 5-year survival rate for patients with microsatellites was 36% compared to 89% for those without these microsatellites.
Source:Day CL Jr, Harrist TJ, Gorstein F, et al. Malignant melanoma. Prognostic significance of “microscopic satellites” in the reticular dermis and subcutaneous fat. Ann Surg. 1981;194:108-112.
>> In 1,158 patients with distant metastases, those with subcutaneous or distant lymph nodes had a better prognosis than those with lung or other visceral organ involvement (1-year survival rates were 59%, 57%, and 41%, respectively.)
Source: Balch CM, Soong SJ, Gershenwald JE, et al. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol. 2001;19:3622-3634.
Balch CM, Buzaid AC, Soong SJ, et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol. 2001;19:3635-3648.
>> One study reported an elevated lactate dehydrogenase (LDH) serum level to have 79% sensitivity and 92% specificity in detecting disease progression in stage IV melanoma.
Source: Dessureault S, Soong SJ, Ross MI, et al. Improved staging of node-negative patients with intermediate to thick melanomas (>1mm) with the use of lymphatic mapping and sentinel lymph node biopsy. Ann Surg Oncol. 2001;8:766-770. Erratum in Ann Surg Oncol. 2002;9:318.
Shivers SC, Wang X, Li W, et al. Molecular staging of malignant melanoma: correlation with clinical outcome. JAMA. 1998;280:1410-1415.
Treating Photodamage with ALA Plus IPL
Study results show significant improvement of skin damage with combination therapy.
In late October, Dusa Pharmaceuticals announced the final results of the first prospective, randomized, controlled split-face clinical study using 5% aminolevulinic acid HCI (Levulan) photodynamic therapy together with intense pulsed light (IPL) for the treatment of photodamaged skin.
Study Specifics
For this study, which was published in the Archives of Dermatology, 20 patients received a series of three treatments
3 weeks apart — half of each patient’s face was pretreated with 5-ALA for 45 minutes before IPL treatment, while the other half the face was treated with IPL alone.
After the initial 3-week treatment period, all patients received two full-face IPL treatments. Before each of these treatments, patients were assessed for signs of photodamage, including global photodamage, fine lines, mottled pigmentation, tactile roughness and sallowness. After 4 weeks, patients were again assessed for signs of photodamage.
Results
Pre-treatment with ALA during the first three treatments resulted in statistically significant improvement in global score for photaging (80% vs. 50%, p<0.02), mottled pigmentation (85% vs. 20%, p<0.0008), and fine lines (55% vs. 20%, p<0.008). There was a noticeable improvement from baseline scores with respect to tactile roughness and sallowness, but pre-treatment with
5-ALA did not seem to enhance the results of the IPL treatment.
The final investigator cosmetic evaluations (p=0.0002) and subject satisfaction scores (p=0.005) were significantly better for the side pretreated with 5-ALA.
Both treatments were well tolerated and there was little difference in the adverse effects on the two treatment sides.
Researchers concluded that the combination of 5-ALA and IPL improves the results of photorejuvenation and patient satisfaction.
Study Authors: Jeffrey S. Dover, M.D., F.R.C.P.C., Ashish C. Bhatia, M.D.,
Brigitte Stewart, and Kenneth A. Arndt, M.D.
Why Redheads’ Melanin Is More Susceptible to UV Damage
All types of melanin are not created equal. And researchers at Duke University have now offered solid proof of that.
People with red hair generate a different type of melanin than people with other hair colors. Scientists have long speculated that the melanin produced in people with red hair, which is known as pheomelanin, could be a key pathway in the formation of skin cancer.
Although a link between pheomelanin and skin cancer was not directly established, researchers from Duke University have now been the first to prove that pheomelanin is more susceptible to UV damage than other types of melanin, according to the Associated Press. (Blond hair also contains some pheomelanin.)
Using a special laser and microscope, the researchers observed an oxidative-stress causing reaction to pheomelanin when both UVA and UVB light was applied. In contrast, the type of melanin found in black hair, called eumelanin, did not adversely react to both types of UV light. Only UVB light caused an oxidative reaction with eumelanin.
Melanoma and UVB
Is it possible that ultraviolet B light is not associated with a greater risk for developing melanoma? A recent study in the Journal of the National Cancer Institute reported just this finding. UVB exposure was linked to a higher risk of developing basal cell and squamous cell carcinomas, but not melanoma.
In the study, 469 patients with skin cancer (231 with non-melanoma skin cancer and 238 with cutaneous malignant melanoma) were compared with 329 patients who were cancer-free.
Researchers focused on analyzing each patient’s mutagen sensitivity, which is a factor in susceptibility to a number of epithelial skin cancers. They assessed mutagen sensitivity by measuring the number of mutagen-induced chromatid breaks per cell in primary lymphocytes in vitro. They made this assessment after exposing the study participants to UVB radiation, waiting 24 hours, and then drawing blood to assess the number of chromatid breaks.
Here’s what the researchers discovered:
1. Patients who had more chromatid breaks per cell above the median of control subjects were three times as likely to be at risk for BCC and SCC.
2. Patients with more chromatid breaks per cell than the median were not at an increased risk for cutaneous malignant melanoma.
Source: Wang L, et al. In Vitro Sensitivity to Ultraviolet B Light and Skin Cancer Risk: A Case-Control Analysis. Journal of the National Cancer Institute, Dec. 21, 2005; 97(24):1822-1831.
Possible New Strategy for Treating Cancer
Typically, cancer research that focuses on treatments with chemotherapy have taken quite a different path than research seeking to develop vaccines for cancer. Historically, the thinking is that the two treatments are completely incompatible — chemotherapy usually weakens the immune system and vaccines work by relying on a strong immune system. But that could be changing.
Researchers reported in the Journal of the National Cancer Institute experimented with combining chemotherapy
(5-fluorouracil [5-FU]) and immunotherapy (a vaccine that targeted thymidylate synthase polyepitopic peptide) and found that the combination was much more successful in killing breast and colon cancer cells than the vaccine alone: 43.5% vs. 26.5% of breast cancer cells and 73.5% vs. 48.5% of colon cancer cells.
How did the combination work? Researchers chose to work with a thymidylate synthase (TS)-directed polyepitopic peptide vaccine because TS lies on the surface of the cancer cells and is typically an enzyme that is overexpressed in malignant cells. They chose 5-FU because — although this drug works by inhibiting expression of TS — the malignant cells overexpress TS at some point after being exposed to 5-FU. This combined process results in the malignant cells becoming a much larger target for the vaccine.
Although this study was only performed in mice, the concept of combining these therapies is promising.
Source: Correale P, et al. 5-Fluorouracil-Based Chemotherapy Enhances the Antitumor Activity of a Thymidylate Synthase-Directed Polyepitopic Peptide Vaccine. Journal of the National Cancer Institute, Oct. 5, 2005; 97(19):1437-1445.
Anti-Cancer Drugs Show Promise for Aging Disease
FTIs may help treat progeria patients
A class of experimental anti-cancer drugs may be effective in treating a fatal genetic disorder that causes premature aging, according to a research team led by the National Human Research Institute (NHGRI), part of the National Institutes of Health (NIH).
Researchers found that drugs knows as farnesyltransferase inhibitors (FTIs), which are currently being tested in people with myeloid leukemia, neurofibromatosis and other conditions, might also provide a potential therapy for children suffering from Hutchinson-Gilford Progeria Syndrome, commonly referred to as progeria.
Currently, there are no known treatments for progeria, a genetic disorder that is estimated to affect one in every 4 million children. Children with the disorder appear normal at birth, but experience growth retardation and show dramatically accelerated symptoms of aging, such as hair loss, skin wrinkling and fat loss, as the grow older. Accelerated cardiovascular disease is also common and typically death from heart attack or stroke occurs around the age of 12.
NHGRI Director Francis S. Collins, M.D., Ph.D., the study’s senior author, reported that they found that FTIs can reverse the nuclear structure abnormalities that are hallmark of cells from children with progeria. Researchers used FTIs to treat skin cells taken from patients with progeria and grown in laboratory conditions. Upcoming studies in a mouse model are pending. If these studies validate the results of the cell experiments and translate into improvements in the animals’ conditions, a clinical trial of FTIs in children with progeria may being as early as next spring.
Sun-Damage Skin Test
A new scientific test to assess the damage people have done to their skin through sun exposure was launched in November to public clinics throughout the United Kingdom. The test, called “skinphysical”, is able to reveal the extent of DNA damage caused by sun exposure. The test draws on work by skin cancer experts at the University of Newcastle upon Tyne combined with Canadian company Genesis Genomics.
Patients taking this test need to give a small sample of skin from just above their elbow that is sent off for laboratory testing. Patients must also complete a comprehensive, 10-page questionnaire about their lifestyles, skin types, sun protection regimes and more. The information from the skin test and questionnaire is analyzed to determine a patient’s skin’s molecular profile, genetic skin type and extent of damage. Researchers then provide patients with customized sun safety advice. Patients can repeat the test at a later date to see if changes in sun-safety behaviors have had an effect on their risk of skin cancer.
Professor Mark Birch-Machin of the Newcastle University’s School of Clinical Laboratory Sciences and Managing Director of Genesis Genomics UK said, in a statement, “The key issue with handing out general advice on sun safety is that it’s not specific enough for the individual. It’s human nature for people to assume that diseases like skin cancer happen to other people — and they tend not to make any adjustments to their behavior until they are threatened with the real possibility of it affecting them.”
For more information, visit www.skinphysical.co.uk.
New Data Provide Better Prognostic Information for Cutaneous Melanoma.
Did you know?
>> A better understanding of prognostic factors in cutaneous melanoma has evolved over the last decade. A revised melanoma staging system was approved by the American Joint Committee on Cancer (AJCC) in 2002 based on an analysis of prognostic factors that involved 17,600 patients with melanoma.
A recent review in Cancer Control looked at current data on several different prognostic factors and found that there are other factors not included in the revised staging system that may alter prognosis, survival and treatment.
Here is a sampling of some of the clinical and histologic factors related to outcomes in cutaneous melanoma.
>> One study found that patients younger than 30 years of age had a 5-year survival rate of 87% compared to 78%, 71%, and 60% for those in their 60s, 70s, and 80s, respectively.
Source: Balch CM, Soong SJ, Gershenwald JE, et al. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol. 2001;19:3622-3634.
>> Pathologically documented nodal metastases by either sentinel or elective node dissection are defined as microscopic. Clinically or radiologically documented nodal metastases are defined as macroscopic. Ten-year survival rates for the two groups are significantly different with 63% survival rate in the presence of a single microscopic node versus a 47% survival rate in the presence of a single macroscopic node.
Source: Balch CM, Soong SJ, Gershenwald JE, et al. Prognostic factors analysis of 17,600 melanoma patients; validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol. 2001;19:3622-3634.
>> The 5-year overall survival rate in patients with thin tumors without other adverse prognostic factors is 95% or greater.
Source: Balch CM, Buzaid AC, Soong SJ, et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol. 2001;19:3635-3648.
Clark WH Jr, Elder DE, Guerry D IV, et al. Model predicting survival in stage I melanoma base on tumor progression. J Natl Cancer Inst. 1989;81:1893-1904.
>> The presence of ulceration decreases survival in all tumor thickness categories. Thin ulcerated tumors have about a 4% decreased 5-year survival rate compared to non-ulcerated tumors. This survival decrement is as high as 22% in thick (>4-mm) tumors.
Source: Balch CM, Soong SJ, Gershenwald JE, et al. Prognostic factors analysis of 17,600 melanoma patients; validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol. 2001;19:3622-3634.
>> Vascular invasion was present in 57% of nodular melanomas with lymph node metastasis at the time of diagnosis compared with only 12% of those confined to the skin.
Source:Straume O, Akslen LA. Independent prognostic importance of vascular invasion in nodular melanomas. Cancer. 1996;78:122-1219.
>> Microsatellites are discrete tumor nests greater than 0.05 mm in diameter that are separated from the main body of the tumor by normal reticular dermal collagen or subcutaneous fat. Though rarely occurring in tumors less than 1.5 mm, the 5-year survival rate for patients with microsatellites was 36% compared to 89% for those without these microsatellites.
Source:Day CL Jr, Harrist TJ, Gorstein F, et al. Malignant melanoma. Prognostic significance of “microscopic satellites” in the reticular dermis and subcutaneous fat. Ann Surg. 1981;194:108-112.
>> In 1,158 patients with distant metastases, those with subcutaneous or distant lymph nodes had a better prognosis than those with lung or other visceral organ involvement (1-year survival rates were 59%, 57%, and 41%, respectively.)
Source: Balch CM, Soong SJ, Gershenwald JE, et al. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol. 2001;19:3622-3634.
Balch CM, Buzaid AC, Soong SJ, et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol. 2001;19:3635-3648.
>> One study reported an elevated lactate dehydrogenase (LDH) serum level to have 79% sensitivity and 92% specificity in detecting disease progression in stage IV melanoma.
Source: Dessureault S, Soong SJ, Ross MI, et al. Improved staging of node-negative patients with intermediate to thick melanomas (>1mm) with the use of lymphatic mapping and sentinel lymph node biopsy. Ann Surg Oncol. 2001;8:766-770. Erratum in Ann Surg Oncol. 2002;9:318.
Shivers SC, Wang X, Li W, et al. Molecular staging of malignant melanoma: correlation with clinical outcome. JAMA. 1998;280:1410-1415.
Treating Photodamage with ALA Plus IPL
Study results show significant improvement of skin damage with combination therapy.
In late October, Dusa Pharmaceuticals announced the final results of the first prospective, randomized, controlled split-face clinical study using 5% aminolevulinic acid HCI (Levulan) photodynamic therapy together with intense pulsed light (IPL) for the treatment of photodamaged skin.
Study Specifics
For this study, which was published in the Archives of Dermatology, 20 patients received a series of three treatments
3 weeks apart — half of each patient’s face was pretreated with 5-ALA for 45 minutes before IPL treatment, while the other half the face was treated with IPL alone.
After the initial 3-week treatment period, all patients received two full-face IPL treatments. Before each of these treatments, patients were assessed for signs of photodamage, including global photodamage, fine lines, mottled pigmentation, tactile roughness and sallowness. After 4 weeks, patients were again assessed for signs of photodamage.
Results
Pre-treatment with ALA during the first three treatments resulted in statistically significant improvement in global score for photaging (80% vs. 50%, p<0.02), mottled pigmentation (85% vs. 20%, p<0.0008), and fine lines (55% vs. 20%, p<0.008). There was a noticeable improvement from baseline scores with respect to tactile roughness and sallowness, but pre-treatment with
5-ALA did not seem to enhance the results of the IPL treatment.
The final investigator cosmetic evaluations (p=0.0002) and subject satisfaction scores (p=0.005) were significantly better for the side pretreated with 5-ALA.
Both treatments were well tolerated and there was little difference in the adverse effects on the two treatment sides.
Researchers concluded that the combination of 5-ALA and IPL improves the results of photorejuvenation and patient satisfaction.
Study Authors: Jeffrey S. Dover, M.D., F.R.C.P.C., Ashish C. Bhatia, M.D.,
Brigitte Stewart, and Kenneth A. Arndt, M.D.
Why Redheads’ Melanin Is More Susceptible to UV Damage
All types of melanin are not created equal. And researchers at Duke University have now offered solid proof of that.
People with red hair generate a different type of melanin than people with other hair colors. Scientists have long speculated that the melanin produced in people with red hair, which is known as pheomelanin, could be a key pathway in the formation of skin cancer.
Although a link between pheomelanin and skin cancer was not directly established, researchers from Duke University have now been the first to prove that pheomelanin is more susceptible to UV damage than other types of melanin, according to the Associated Press. (Blond hair also contains some pheomelanin.)
Using a special laser and microscope, the researchers observed an oxidative-stress causing reaction to pheomelanin when both UVA and UVB light was applied. In contrast, the type of melanin found in black hair, called eumelanin, did not adversely react to both types of UV light. Only UVB light caused an oxidative reaction with eumelanin.
Melanoma and UVB
Is it possible that ultraviolet B light is not associated with a greater risk for developing melanoma? A recent study in the Journal of the National Cancer Institute reported just this finding. UVB exposure was linked to a higher risk of developing basal cell and squamous cell carcinomas, but not melanoma.
In the study, 469 patients with skin cancer (231 with non-melanoma skin cancer and 238 with cutaneous malignant melanoma) were compared with 329 patients who were cancer-free.
Researchers focused on analyzing each patient’s mutagen sensitivity, which is a factor in susceptibility to a number of epithelial skin cancers. They assessed mutagen sensitivity by measuring the number of mutagen-induced chromatid breaks per cell in primary lymphocytes in vitro. They made this assessment after exposing the study participants to UVB radiation, waiting 24 hours, and then drawing blood to assess the number of chromatid breaks.
Here’s what the researchers discovered:
1. Patients who had more chromatid breaks per cell above the median of control subjects were three times as likely to be at risk for BCC and SCC.
2. Patients with more chromatid breaks per cell than the median were not at an increased risk for cutaneous malignant melanoma.
Source: Wang L, et al. In Vitro Sensitivity to Ultraviolet B Light and Skin Cancer Risk: A Case-Control Analysis. Journal of the National Cancer Institute, Dec. 21, 2005; 97(24):1822-1831.
Possible New Strategy for Treating Cancer
Typically, cancer research that focuses on treatments with chemotherapy have taken quite a different path than research seeking to develop vaccines for cancer. Historically, the thinking is that the two treatments are completely incompatible — chemotherapy usually weakens the immune system and vaccines work by relying on a strong immune system. But that could be changing.
Researchers reported in the Journal of the National Cancer Institute experimented with combining chemotherapy
(5-fluorouracil [5-FU]) and immunotherapy (a vaccine that targeted thymidylate synthase polyepitopic peptide) and found that the combination was much more successful in killing breast and colon cancer cells than the vaccine alone: 43.5% vs. 26.5% of breast cancer cells and 73.5% vs. 48.5% of colon cancer cells.
How did the combination work? Researchers chose to work with a thymidylate synthase (TS)-directed polyepitopic peptide vaccine because TS lies on the surface of the cancer cells and is typically an enzyme that is overexpressed in malignant cells. They chose 5-FU because — although this drug works by inhibiting expression of TS — the malignant cells overexpress TS at some point after being exposed to 5-FU. This combined process results in the malignant cells becoming a much larger target for the vaccine.
Although this study was only performed in mice, the concept of combining these therapies is promising.
Source: Correale P, et al. 5-Fluorouracil-Based Chemotherapy Enhances the Antitumor Activity of a Thymidylate Synthase-Directed Polyepitopic Peptide Vaccine. Journal of the National Cancer Institute, Oct. 5, 2005; 97(19):1437-1445.
Anti-Cancer Drugs Show Promise for Aging Disease
FTIs may help treat progeria patients
A class of experimental anti-cancer drugs may be effective in treating a fatal genetic disorder that causes premature aging, according to a research team led by the National Human Research Institute (NHGRI), part of the National Institutes of Health (NIH).
Researchers found that drugs knows as farnesyltransferase inhibitors (FTIs), which are currently being tested in people with myeloid leukemia, neurofibromatosis and other conditions, might also provide a potential therapy for children suffering from Hutchinson-Gilford Progeria Syndrome, commonly referred to as progeria.
Currently, there are no known treatments for progeria, a genetic disorder that is estimated to affect one in every 4 million children. Children with the disorder appear normal at birth, but experience growth retardation and show dramatically accelerated symptoms of aging, such as hair loss, skin wrinkling and fat loss, as the grow older. Accelerated cardiovascular disease is also common and typically death from heart attack or stroke occurs around the age of 12.
NHGRI Director Francis S. Collins, M.D., Ph.D., the study’s senior author, reported that they found that FTIs can reverse the nuclear structure abnormalities that are hallmark of cells from children with progeria. Researchers used FTIs to treat skin cells taken from patients with progeria and grown in laboratory conditions. Upcoming studies in a mouse model are pending. If these studies validate the results of the cell experiments and translate into improvements in the animals’ conditions, a clinical trial of FTIs in children with progeria may being as early as next spring.
Sun-Damage Skin Test
A new scientific test to assess the damage people have done to their skin through sun exposure was launched in November to public clinics throughout the United Kingdom. The test, called “skinphysical”, is able to reveal the extent of DNA damage caused by sun exposure. The test draws on work by skin cancer experts at the University of Newcastle upon Tyne combined with Canadian company Genesis Genomics.
Patients taking this test need to give a small sample of skin from just above their elbow that is sent off for laboratory testing. Patients must also complete a comprehensive, 10-page questionnaire about their lifestyles, skin types, sun protection regimes and more. The information from the skin test and questionnaire is analyzed to determine a patient’s skin’s molecular profile, genetic skin type and extent of damage. Researchers then provide patients with customized sun safety advice. Patients can repeat the test at a later date to see if changes in sun-safety behaviors have had an effect on their risk of skin cancer.
Professor Mark Birch-Machin of the Newcastle University’s School of Clinical Laboratory Sciences and Managing Director of Genesis Genomics UK said, in a statement, “The key issue with handing out general advice on sun safety is that it’s not specific enough for the individual. It’s human nature for people to assume that diseases like skin cancer happen to other people — and they tend not to make any adjustments to their behavior until they are threatened with the real possibility of it affecting them.”
For more information, visit www.skinphysical.co.uk.
