Photodynamic Therapy Guidelines Suggest Its Use as First-Line Treatment for Some Nonmelanoma Skin Cancers
An international team of colleagues supports photodynamic therapy (PDT) as a first-line treatment for actinic keratoses (AK) and Bowen’s disease (BD), and recommends methyl aminolevulinate MAL-PDT for nodular basal cell carcinoma (nBCC) lesions.
GUIDELINE DEVELOPMENT
The recently published guidelines of the group led by Lasse R Braathen, M.D., Ph.D., M.H.A, are for PDT treatment for non-melanoma skin cancers (NMCA) and are based on major clinical trials conducted with 5-aminolevulinic acid (ALA) (Levulan) and or methyl aminolevulinate (MAL) (Metvix) in the treatment of actinic keratoses (AK), Bowen’s disease (BD) and basal cell carcinoma (BCC) — both superficial (s)BCC and nodular (n)BCC.
These guidelines for the use of PDT, which involves the use of light to activate a photosensitizer localized in diseased tissues, were originally developed during a January 2005 meeting of the International Society for Photodynamic Therapy in Dermatology, on whose behalf the report was prepared. Recommendations were based on the quality of evidence for efficacy, safety/tolerability, cosmetic outcome, and patient satisfaction/preference. They are detailed in the January issue of the Journal of the American Academy of Dermatology. (Braathen LR et al. J Am Acad Dermatol. 2007;56:125-143.)
CONCLUSIONS
They concluded that PDT is highly effective in the treatment of AK, BD, (s)BCC and (n)BCC, with cosmesis typically superior to that achieved with existing standard therapies; they also determined that PDT may also be a means of preventing certain nonmelanoma skin cancers in immunosuppressed patients.
RECOMMENDATIONS
Their guidelines, summarized below, use a scoring system with letters (A-E) to indicate the strength of the recommendation — with A being strongest — and numbers (I-IV) to indicate the quality of the evidence — breaking down the quality of evidence in category II further into II-i-iii.
Actinic Keratosis — As PDT with either ALA or MAL is highly effective and offers excellent cosmetic outcome, it should be considered as a first-line therapy for AK (Rating: AI); MAL-PDT has a superior cosmetic outcome compared cryotherapy (Rating: AI).
Bowen’s Disease — Topical PDT is effective in BD, achieving good cosmesis, and is at least as effective as cryotherapy or 5-fluorouracil, but with fewer adverse events; topical PDT should be considered as a first-line therapy for BD (Rating: AI).
Squamous Cell Carcinoma — There is insufficient evidence to support the routine use of topical PDT for SCC (Rating: CIIiii).
Superficial Basal Cell Carcinoma — PDT is an effective and reliable treatment option for sBCC that offers excellent cosmetic outcomes (Rating: AI); PDT offers an advantage in the treatment of large, extensive and multiple lesions (Rating: AI); MAL-PDT has demonstrated long-term efficacy, with 5-year follow-up data (Rating: AI).
Nodular Basal Cell Carcinoma — MAL-PDT is an effective and reliable treatment option for nBCC less than 2 mm in depth with the advantage of good cosmetic outcome (Rating: AI); MAL-PDT has demonstrated long-term efficacy, with 5-year follow-up data (Rating: AI).
Cancer Prevention in Immunosuppressed Patients — PDT may be considered as a means for preventing AK in Immunosuppressed transplant patients (Rating: BI); and as a means of preventing SCC (Rating: CIII) and BCC (Rating: CIIiii) in Immunosuppressed patients.
Study finds 100% target lesion clearance twice as likely when AK cryosurgery is followed by diclofenac sodium 3% gel treatment
According to a prospective, double-arm, multi-center, open- label, Phase IV study, “treating the field” for actinic keratosis (AK) after cryosurgery doubles a patient’s chance of achieving 100% target lesion clearance compared to cryosurgery alone.
Noting that that the vast majority of AK lesions are treated with destructive therapies designed for well-defined lesions, investigators sought to test a topical treatment alternative to inhibit the formation of new, early AK lesions in addition to providing targeted treatment of clearly visible lesions. Toward that end, their main study objective was to evaluate the effectiveness of diclofenac sodium 3% gel when applied for 90 days subsequent to cryosurgery, compared to cryosurgery alone. Their secondary objective was to evaluate the preparation’s safety and tolerability.
Study Description
This study involved 714 patients who had first undergone cryosurgery for removal of visible lesions from 82 community dermatologic centers in the United States. Among the original patients enrolled, 521 completed treatment with either cryosurgery alone or cryosurgery followed by the topical treatment 15 days after cryosurgery, for a period of 90 days. Lesion counts for the cryosurgery alone group were assessed at baseline and 135 days after cryosurgery. Lesion counts for the cryosurgery followed by diclofenac sodium 3% gel group were assessed at baseline, then at 45, 75, 105, and 135 days after cryosurgery, with the day 135 visit being 30 days after topical therapy completion.
Results
At the completion of the study on day 135, 46% of the subjects in the cryosurgery followed by diclofenac sodium 3% gel arm had achieved 100% cumulative (target plus new) lesion clearance compared to 21% of subjects in the cryosurgery alone arm. Of the participants in the active arm, 64% had achieved 100% target lesion clearance compared to 21% in the cryosurgery alone arm. The average percent reduction of both cumulative and target lesions started at day 45 in the diclofenac sodium 3% gel arm, reaching an 80% average cumulative lesion reduction at day 135 and an 89% average target lesion reduction at day 135. The average percent reduction for the cryosurgery alone arm of target lesions were 68% and 43%, respectively, for the cumulative lesions.
Conclusion
Presenters concluded that their efficacy and safety findings establish diclofenac sodium 3% gel as an evidence-based therapeutic option that allows for treatment of large hyperkeratotic AK lesions as well as early, subclinical lesions, with minimaI cutaneous side effects.
Poster Authors: Darrell S. Rigel, M.D., Joshua M. Berlin, M.D.
Scientists Link Inherited Gene to BRAF-Mutant Melanoma
Researchers at the National Cancer Institute (NCI) in collaboration with colleagues from the University of California at San Francisco, the University of Pennsylvania, Philadelphia, and Bufalini Hospital in Cesena, Italy, have identified a link between inherited and acquired genetic factors that dramatically increase the chance of developing BRAF-mutant melanoma.
A combined total of 197 subjects from the Italian and American groups was made up of patients with little or no signs of chronic sun damage. Scientist then sequenced MC1 R genes in normal cells and BRAF in tumor cells and found that BRAF mutations were more frequent in non-chronic sun-induced melanoma cases with hereditary genetic variant forms of melanocortin-1 receptor (MC1 R) gene.
Skin Cancer Increasing in Under-40 Population
The incidence of all types of skin cancers are increasing in children and young adults, according to Clinical Cancer Advances, a report issued by the American Society of Clinical Oncology.
The report noted the following statistics:
• The incidence of melanoma in people under age 20 increased 2.9% per year from 1973 to 2001, based on an analysis of the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) database.1
• Nonmelanoma skin cancers are also increasing in people under the age of 40. Researchers at the Mayo Clinic, who gathered data on people in Olmstead, MN, between 1976 and 2003, found the following:
• The incidence of basal cell carcinoma increased from 18.2 cases to 29.1 cases per 100,000 people.
• Squamous cell carcinoma cases also rose, with 0.9 cases reported in 1976 to 4.1 cases reported in 2003 per 100,000 people.2
Researchers expressed the need for larger studies before determining whether these increases will be seen on a larger scale.
References
1. Strouse JJ et al. Pediatric melanoma: Risk factor and survival analysis of the Surveillance, Epidemiology and End Results Database. J Clin Oncol. 2005;23:4735-4741.
2. Christenson LJ et al. Incidence of basal cell and squamous cell carcinomas in a population younger than 40 years. JAMA. 2005;294:681-690.
Visual Screening for Malignant Melanoma Found to Be Cost-Effective
An examination of various melanoma screening strategies using a computer simulation Markov model found one-time melanoma screening of the general population older than 50 years to be very cost-effective compared with other cancer screening programs in the United States, according to a study published in the January issue of Archives of Dermatology.
Other strategies considered included background screening only, and screening 1 time, every 2 years, and annually, all beginning at age 50 years. Screening every 2 years in siblings of patients with melanoma was also deemed cost-effective based on outcome measures including life expectancy, quality-adjusted life expectancy, and lifetime costs.
Fast-Growing Melanomas Don’t Fit ABCD Rule
According to Australian researchers led by Dr. Wendy Liu of the Alfred Hospital in Melbourne, rapidly growing melanomas don’t conform to the ABCD rule. They are instead thicker, redder, symmetrical or elevated, have regular borders, and often itch or bleed. What’s more, they don’t occur in the usual suspects — people who have large numbers of moles and freckles.
This is of course troublesome because these quickly growing tumors are not only much more lethal, their contradictory features make it more difficult for patients aware of the ABCD rule to spot them.
The study involved 404 subjects with invasive melanomas. All had skin examinations and pathology reviews and were interviewed about their melanoma and medical history. Researchers developed a "rate of growth index" based on the melanoma’s thickness and the time it took for the melanoma to develop. Faster rates of growth were associated with faster mitotic rates, or the rates at which the cancer cells multiplied.
These finding, published in the December issue of the Archives of Dermatology, also found that such melanomas were more likely to occur in men older than 70 and people with few freckles or moles.
The take-home message here: Any rapidly growing lesion of any description should be assessed promptly.
Red Hair Gene Ups Skin Cancer Risk — Regardless of Person’s Hair Color
Even patients with dark hair and olive skin but who carry the “red hair color gene” — the melanocortin 1 receptor (MC1R) gene — are at increased risk for developing skin cancer, according to an article by Reuters Health, which was based on a study published in the International Journal of Cancer.
In fact, researchers found that women who had medium or olive skin — not fair skin — and who had the MC1R gene were at the highest risk for skin cancer. Researchers studied three variants of this gene that are linked to red hair, fair skin and resistance to tanning. These variations are known as red hair color (RHC) variants. They also studied four other variants of the gene that were not as closely linked to red hair (non-red hair variants [NRHC]).
Using the Nurse’s Health Study, researchers identified groups of women with and without cancer, including the following:
- 219 women with melanoma
- 286 women with squamous cell carcinoma (SCC)
- 300 women with basal cell carcinoma (BCC)
- 873 women without skin cancer.
Researchers concluded the following after they controlled for the effects of skin type and other skin cancer risk factors:
• Women with the variant 151 Cys were at a 65% increased risk for melanoma.
• Women with the 151 Cys variant also had a 67% greater risk for developing SCC.
• Women with the 151 Cys variant were 56% more likely to develop BCC.
• Women who had one RHC gene, one NRHC gene, and medium to olive skin were at the greatest risk for melanoma.
• Women who had red hair and the 151 Cys variant were also at an increased risk for melanoma
• However, women without red hair who had the variant 151 Cys were not at a greater risk for developing melanoma, but women who had red hair and the variant 151 Cys were.
Source: Han J, Kraft P, Colditz GA, Wong J, Hunter DJ. Melanocortin 1 receptor variants and skin cancer risk. Int J Cancer. 2006 Oct 15; 119:1976-84.
Diphtheria Toxin-containing Drug Triggers Immune System to Fight Melanoma
Ateam of researchers at the James Graham Brown Cancer Center have discovered that a drug combination of diphtheria toxin and interleukin 2 appears to prompt the immune system to recognize and kill cancer cells in patients with advanced melanoma.
Preliminary results of a Phase II clinical trial showed that five out of seven patients with stage IV disease experienced significant regression or stabilization of both tumors and the spread of cancer.
Dr. Jason Chesney, Associate Director for translational research at the Brown Cancer Center led the investigation. He postulates that by wiping out the T-regulator cells, the drug prevents the immune system from shutting down, thus priming the body to mount a continuous attack against cancer.
Telephone Triage System Flags and Promptly Treats Patients with Suspicious Skin Lesions
A telephone screening method designed to reduce appointment wait times for patients with high-risk skin lesions has been developed by group of Kansas physicians — Drs. Jeff Graves, Mark H. Fleischman, and Glenn D. Goldstein.
The goal of their Derm Access strategy was to allow for the most suspicious lesions to be seen within 72 hours, if desired. This entailed leaving open slots in appointment schedules to accommodate these patients.
To evaluate the effectiveness of this approach, a total of 233 patients were studied; their wait time, procedure, and treatment data were collected and compared against national wait-time data.
Among these patients, a total of 146 (63%) were diagnosed with a cancerous or precancerous lesion. The mean wait time in actual working days was 7.44 during this same period.
This program was considered successful in that it substantially decreased patient anxiety and increased patient satisfaction. Additional benefits included public relations for the practice and public awareness of skin cancer.
Photodynamic Therapy Guidelines Suggest Its Use as First-Line Treatment for Some Nonmelanoma Skin Cancers
An international team of colleagues supports photodynamic therapy (PDT) as a first-line treatment for actinic keratoses (AK) and Bowen’s disease (BD), and recommends methyl aminolevulinate MAL-PDT for nodular basal cell carcinoma (nBCC) lesions.
GUIDELINE DEVELOPMENT
The recently published guidelines of the group led by Lasse R Braathen, M.D., Ph.D., M.H.A, are for PDT treatment for non-melanoma skin cancers (NMCA) and are based on major clinical trials conducted with 5-aminolevulinic acid (ALA) (Levulan) and or methyl aminolevulinate (MAL) (Metvix) in the treatment of actinic keratoses (AK), Bowen’s disease (BD) and basal cell carcinoma (BCC) — both superficial (s)BCC and nodular (n)BCC.
These guidelines for the use of PDT, which involves the use of light to activate a photosensitizer localized in diseased tissues, were originally developed during a January 2005 meeting of the International Society for Photodynamic Therapy in Dermatology, on whose behalf the report was prepared. Recommendations were based on the quality of evidence for efficacy, safety/tolerability, cosmetic outcome, and patient satisfaction/preference. They are detailed in the January issue of the Journal of the American Academy of Dermatology. (Braathen LR et al. J Am Acad Dermatol. 2007;56:125-143.)
CONCLUSIONS
They concluded that PDT is highly effective in the treatment of AK, BD, (s)BCC and (n)BCC, with cosmesis typically superior to that achieved with existing standard therapies; they also determined that PDT may also be a means of preventing certain nonmelanoma skin cancers in immunosuppressed patients.
RECOMMENDATIONS
Their guidelines, summarized below, use a scoring system with letters (A-E) to indicate the strength of the recommendation — with A being strongest — and numbers (I-IV) to indicate the quality of the evidence — breaking down the quality of evidence in category II further into II-i-iii.
Actinic Keratosis — As PDT with either ALA or MAL is highly effective and offers excellent cosmetic outcome, it should be considered as a first-line therapy for AK (Rating: AI); MAL-PDT has a superior cosmetic outcome compared cryotherapy (Rating: AI).
Bowen’s Disease — Topical PDT is effective in BD, achieving good cosmesis, and is at least as effective as cryotherapy or 5-fluorouracil, but with fewer adverse events; topical PDT should be considered as a first-line therapy for BD (Rating: AI).
Squamous Cell Carcinoma — There is insufficient evidence to support the routine use of topical PDT for SCC (Rating: CIIiii).
Superficial Basal Cell Carcinoma — PDT is an effective and reliable treatment option for sBCC that offers excellent cosmetic outcomes (Rating: AI); PDT offers an advantage in the treatment of large, extensive and multiple lesions (Rating: AI); MAL-PDT has demonstrated long-term efficacy, with 5-year follow-up data (Rating: AI).
Nodular Basal Cell Carcinoma — MAL-PDT is an effective and reliable treatment option for nBCC less than 2 mm in depth with the advantage of good cosmetic outcome (Rating: AI); MAL-PDT has demonstrated long-term efficacy, with 5-year follow-up data (Rating: AI).
Cancer Prevention in Immunosuppressed Patients — PDT may be considered as a means for preventing AK in Immunosuppressed transplant patients (Rating: BI); and as a means of preventing SCC (Rating: CIII) and BCC (Rating: CIIiii) in Immunosuppressed patients.
Study finds 100% target lesion clearance twice as likely when AK cryosurgery is followed by diclofenac sodium 3% gel treatment
According to a prospective, double-arm, multi-center, open- label, Phase IV study, “treating the field” for actinic keratosis (AK) after cryosurgery doubles a patient’s chance of achieving 100% target lesion clearance compared to cryosurgery alone.
Noting that that the vast majority of AK lesions are treated with destructive therapies designed for well-defined lesions, investigators sought to test a topical treatment alternative to inhibit the formation of new, early AK lesions in addition to providing targeted treatment of clearly visible lesions. Toward that end, their main study objective was to evaluate the effectiveness of diclofenac sodium 3% gel when applied for 90 days subsequent to cryosurgery, compared to cryosurgery alone. Their secondary objective was to evaluate the preparation’s safety and tolerability.
Study Description
This study involved 714 patients who had first undergone cryosurgery for removal of visible lesions from 82 community dermatologic centers in the United States. Among the original patients enrolled, 521 completed treatment with either cryosurgery alone or cryosurgery followed by the topical treatment 15 days after cryosurgery, for a period of 90 days. Lesion counts for the cryosurgery alone group were assessed at baseline and 135 days after cryosurgery. Lesion counts for the cryosurgery followed by diclofenac sodium 3% gel group were assessed at baseline, then at 45, 75, 105, and 135 days after cryosurgery, with the day 135 visit being 30 days after topical therapy completion.
Results
At the completion of the study on day 135, 46% of the subjects in the cryosurgery followed by diclofenac sodium 3% gel arm had achieved 100% cumulative (target plus new) lesion clearance compared to 21% of subjects in the cryosurgery alone arm. Of the participants in the active arm, 64% had achieved 100% target lesion clearance compared to 21% in the cryosurgery alone arm. The average percent reduction of both cumulative and target lesions started at day 45 in the diclofenac sodium 3% gel arm, reaching an 80% average cumulative lesion reduction at day 135 and an 89% average target lesion reduction at day 135. The average percent reduction for the cryosurgery alone arm of target lesions were 68% and 43%, respectively, for the cumulative lesions.
Conclusion
Presenters concluded that their efficacy and safety findings establish diclofenac sodium 3% gel as an evidence-based therapeutic option that allows for treatment of large hyperkeratotic AK lesions as well as early, subclinical lesions, with minimaI cutaneous side effects.
Poster Authors: Darrell S. Rigel, M.D., Joshua M. Berlin, M.D.
Scientists Link Inherited Gene to BRAF-Mutant Melanoma
Researchers at the National Cancer Institute (NCI) in collaboration with colleagues from the University of California at San Francisco, the University of Pennsylvania, Philadelphia, and Bufalini Hospital in Cesena, Italy, have identified a link between inherited and acquired genetic factors that dramatically increase the chance of developing BRAF-mutant melanoma.
A combined total of 197 subjects from the Italian and American groups was made up of patients with little or no signs of chronic sun damage. Scientist then sequenced MC1 R genes in normal cells and BRAF in tumor cells and found that BRAF mutations were more frequent in non-chronic sun-induced melanoma cases with hereditary genetic variant forms of melanocortin-1 receptor (MC1 R) gene.
Skin Cancer Increasing in Under-40 Population
The incidence of all types of skin cancers are increasing in children and young adults, according to Clinical Cancer Advances, a report issued by the American Society of Clinical Oncology.
The report noted the following statistics:
• The incidence of melanoma in people under age 20 increased 2.9% per year from 1973 to 2001, based on an analysis of the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) database.1
• Nonmelanoma skin cancers are also increasing in people under the age of 40. Researchers at the Mayo Clinic, who gathered data on people in Olmstead, MN, between 1976 and 2003, found the following:
• The incidence of basal cell carcinoma increased from 18.2 cases to 29.1 cases per 100,000 people.
• Squamous cell carcinoma cases also rose, with 0.9 cases reported in 1976 to 4.1 cases reported in 2003 per 100,000 people.2
Researchers expressed the need for larger studies before determining whether these increases will be seen on a larger scale.
References
1. Strouse JJ et al. Pediatric melanoma: Risk factor and survival analysis of the Surveillance, Epidemiology and End Results Database. J Clin Oncol. 2005;23:4735-4741.
2. Christenson LJ et al. Incidence of basal cell and squamous cell carcinomas in a population younger than 40 years. JAMA. 2005;294:681-690.
Visual Screening for Malignant Melanoma Found to Be Cost-Effective
An examination of various melanoma screening strategies using a computer simulation Markov model found one-time melanoma screening of the general population older than 50 years to be very cost-effective compared with other cancer screening programs in the United States, according to a study published in the January issue of Archives of Dermatology.
Other strategies considered included background screening only, and screening 1 time, every 2 years, and annually, all beginning at age 50 years. Screening every 2 years in siblings of patients with melanoma was also deemed cost-effective based on outcome measures including life expectancy, quality-adjusted life expectancy, and lifetime costs.
Fast-Growing Melanomas Don’t Fit ABCD Rule
According to Australian researchers led by Dr. Wendy Liu of the Alfred Hospital in Melbourne, rapidly growing melanomas don’t conform to the ABCD rule. They are instead thicker, redder, symmetrical or elevated, have regular borders, and often itch or bleed. What’s more, they don’t occur in the usual suspects — people who have large numbers of moles and freckles.
This is of course troublesome because these quickly growing tumors are not only much more lethal, their contradictory features make it more difficult for patients aware of the ABCD rule to spot them.
The study involved 404 subjects with invasive melanomas. All had skin examinations and pathology reviews and were interviewed about their melanoma and medical history. Researchers developed a "rate of growth index" based on the melanoma’s thickness and the time it took for the melanoma to develop. Faster rates of growth were associated with faster mitotic rates, or the rates at which the cancer cells multiplied.
These finding, published in the December issue of the Archives of Dermatology, also found that such melanomas were more likely to occur in men older than 70 and people with few freckles or moles.
The take-home message here: Any rapidly growing lesion of any description should be assessed promptly.
Red Hair Gene Ups Skin Cancer Risk — Regardless of Person’s Hair Color
Even patients with dark hair and olive skin but who carry the “red hair color gene” — the melanocortin 1 receptor (MC1R) gene — are at increased risk for developing skin cancer, according to an article by Reuters Health, which was based on a study published in the International Journal of Cancer.
In fact, researchers found that women who had medium or olive skin — not fair skin — and who had the MC1R gene were at the highest risk for skin cancer. Researchers studied three variants of this gene that are linked to red hair, fair skin and resistance to tanning. These variations are known as red hair color (RHC) variants. They also studied four other variants of the gene that were not as closely linked to red hair (non-red hair variants [NRHC]).
Using the Nurse’s Health Study, researchers identified groups of women with and without cancer, including the following:
- 219 women with melanoma
- 286 women with squamous cell carcinoma (SCC)
- 300 women with basal cell carcinoma (BCC)
- 873 women without skin cancer.
Researchers concluded the following after they controlled for the effects of skin type and other skin cancer risk factors:
• Women with the variant 151 Cys were at a 65% increased risk for melanoma.
• Women with the 151 Cys variant also had a 67% greater risk for developing SCC.
• Women with the 151 Cys variant were 56% more likely to develop BCC.
• Women who had one RHC gene, one NRHC gene, and medium to olive skin were at the greatest risk for melanoma.
• Women who had red hair and the 151 Cys variant were also at an increased risk for melanoma
• However, women without red hair who had the variant 151 Cys were not at a greater risk for developing melanoma, but women who had red hair and the variant 151 Cys were.
Source: Han J, Kraft P, Colditz GA, Wong J, Hunter DJ. Melanocortin 1 receptor variants and skin cancer risk. Int J Cancer. 2006 Oct 15; 119:1976-84.
Diphtheria Toxin-containing Drug Triggers Immune System to Fight Melanoma
Ateam of researchers at the James Graham Brown Cancer Center have discovered that a drug combination of diphtheria toxin and interleukin 2 appears to prompt the immune system to recognize and kill cancer cells in patients with advanced melanoma.
Preliminary results of a Phase II clinical trial showed that five out of seven patients with stage IV disease experienced significant regression or stabilization of both tumors and the spread of cancer.
Dr. Jason Chesney, Associate Director for translational research at the Brown Cancer Center led the investigation. He postulates that by wiping out the T-regulator cells, the drug prevents the immune system from shutting down, thus priming the body to mount a continuous attack against cancer.
Telephone Triage System Flags and Promptly Treats Patients with Suspicious Skin Lesions
A telephone screening method designed to reduce appointment wait times for patients with high-risk skin lesions has been developed by group of Kansas physicians — Drs. Jeff Graves, Mark H. Fleischman, and Glenn D. Goldstein.
The goal of their Derm Access strategy was to allow for the most suspicious lesions to be seen within 72 hours, if desired. This entailed leaving open slots in appointment schedules to accommodate these patients.
To evaluate the effectiveness of this approach, a total of 233 patients were studied; their wait time, procedure, and treatment data were collected and compared against national wait-time data.
Among these patients, a total of 146 (63%) were diagnosed with a cancerous or precancerous lesion. The mean wait time in actual working days was 7.44 during this same period.
This program was considered successful in that it substantially decreased patient anxiety and increased patient satisfaction. Additional benefits included public relations for the practice and public awareness of skin cancer.
Photodynamic Therapy Guidelines Suggest Its Use as First-Line Treatment for Some Nonmelanoma Skin Cancers
An international team of colleagues supports photodynamic therapy (PDT) as a first-line treatment for actinic keratoses (AK) and Bowen’s disease (BD), and recommends methyl aminolevulinate MAL-PDT for nodular basal cell carcinoma (nBCC) lesions.
GUIDELINE DEVELOPMENT
The recently published guidelines of the group led by Lasse R Braathen, M.D., Ph.D., M.H.A, are for PDT treatment for non-melanoma skin cancers (NMCA) and are based on major clinical trials conducted with 5-aminolevulinic acid (ALA) (Levulan) and or methyl aminolevulinate (MAL) (Metvix) in the treatment of actinic keratoses (AK), Bowen’s disease (BD) and basal cell carcinoma (BCC) — both superficial (s)BCC and nodular (n)BCC.
These guidelines for the use of PDT, which involves the use of light to activate a photosensitizer localized in diseased tissues, were originally developed during a January 2005 meeting of the International Society for Photodynamic Therapy in Dermatology, on whose behalf the report was prepared. Recommendations were based on the quality of evidence for efficacy, safety/tolerability, cosmetic outcome, and patient satisfaction/preference. They are detailed in the January issue of the Journal of the American Academy of Dermatology. (Braathen LR et al. J Am Acad Dermatol. 2007;56:125-143.)
CONCLUSIONS
They concluded that PDT is highly effective in the treatment of AK, BD, (s)BCC and (n)BCC, with cosmesis typically superior to that achieved with existing standard therapies; they also determined that PDT may also be a means of preventing certain nonmelanoma skin cancers in immunosuppressed patients.
RECOMMENDATIONS
Their guidelines, summarized below, use a scoring system with letters (A-E) to indicate the strength of the recommendation — with A being strongest — and numbers (I-IV) to indicate the quality of the evidence — breaking down the quality of evidence in category II further into II-i-iii.
Actinic Keratosis — As PDT with either ALA or MAL is highly effective and offers excellent cosmetic outcome, it should be considered as a first-line therapy for AK (Rating: AI); MAL-PDT has a superior cosmetic outcome compared cryotherapy (Rating: AI).
Bowen’s Disease — Topical PDT is effective in BD, achieving good cosmesis, and is at least as effective as cryotherapy or 5-fluorouracil, but with fewer adverse events; topical PDT should be considered as a first-line therapy for BD (Rating: AI).
Squamous Cell Carcinoma — There is insufficient evidence to support the routine use of topical PDT for SCC (Rating: CIIiii).
Superficial Basal Cell Carcinoma — PDT is an effective and reliable treatment option for sBCC that offers excellent cosmetic outcomes (Rating: AI); PDT offers an advantage in the treatment of large, extensive and multiple lesions (Rating: AI); MAL-PDT has demonstrated long-term efficacy, with 5-year follow-up data (Rating: AI).
Nodular Basal Cell Carcinoma — MAL-PDT is an effective and reliable treatment option for nBCC less than 2 mm in depth with the advantage of good cosmetic outcome (Rating: AI); MAL-PDT has demonstrated long-term efficacy, with 5-year follow-up data (Rating: AI).
Cancer Prevention in Immunosuppressed Patients — PDT may be considered as a means for preventing AK in Immunosuppressed transplant patients (Rating: BI); and as a means of preventing SCC (Rating: CIII) and BCC (Rating: CIIiii) in Immunosuppressed patients.
Study finds 100% target lesion clearance twice as likely when AK cryosurgery is followed by diclofenac sodium 3% gel treatment
According to a prospective, double-arm, multi-center, open- label, Phase IV study, “treating the field” for actinic keratosis (AK) after cryosurgery doubles a patient’s chance of achieving 100% target lesion clearance compared to cryosurgery alone.
Noting that that the vast majority of AK lesions are treated with destructive therapies designed for well-defined lesions, investigators sought to test a topical treatment alternative to inhibit the formation of new, early AK lesions in addition to providing targeted treatment of clearly visible lesions. Toward that end, their main study objective was to evaluate the effectiveness of diclofenac sodium 3% gel when applied for 90 days subsequent to cryosurgery, compared to cryosurgery alone. Their secondary objective was to evaluate the preparation’s safety and tolerability.
Study Description
This study involved 714 patients who had first undergone cryosurgery for removal of visible lesions from 82 community dermatologic centers in the United States. Among the original patients enrolled, 521 completed treatment with either cryosurgery alone or cryosurgery followed by the topical treatment 15 days after cryosurgery, for a period of 90 days. Lesion counts for the cryosurgery alone group were assessed at baseline and 135 days after cryosurgery. Lesion counts for the cryosurgery followed by diclofenac sodium 3% gel group were assessed at baseline, then at 45, 75, 105, and 135 days after cryosurgery, with the day 135 visit being 30 days after topical therapy completion.
Results
At the completion of the study on day 135, 46% of the subjects in the cryosurgery followed by diclofenac sodium 3% gel arm had achieved 100% cumulative (target plus new) lesion clearance compared to 21% of subjects in the cryosurgery alone arm. Of the participants in the active arm, 64% had achieved 100% target lesion clearance compared to 21% in the cryosurgery alone arm. The average percent reduction of both cumulative and target lesions started at day 45 in the diclofenac sodium 3% gel arm, reaching an 80% average cumulative lesion reduction at day 135 and an 89% average target lesion reduction at day 135. The average percent reduction for the cryosurgery alone arm of target lesions were 68% and 43%, respectively, for the cumulative lesions.
Conclusion
Presenters concluded that their efficacy and safety findings establish diclofenac sodium 3% gel as an evidence-based therapeutic option that allows for treatment of large hyperkeratotic AK lesions as well as early, subclinical lesions, with minimaI cutaneous side effects.
Poster Authors: Darrell S. Rigel, M.D., Joshua M. Berlin, M.D.
Scientists Link Inherited Gene to BRAF-Mutant Melanoma
Researchers at the National Cancer Institute (NCI) in collaboration with colleagues from the University of California at San Francisco, the University of Pennsylvania, Philadelphia, and Bufalini Hospital in Cesena, Italy, have identified a link between inherited and acquired genetic factors that dramatically increase the chance of developing BRAF-mutant melanoma.
A combined total of 197 subjects from the Italian and American groups was made up of patients with little or no signs of chronic sun damage. Scientist then sequenced MC1 R genes in normal cells and BRAF in tumor cells and found that BRAF mutations were more frequent in non-chronic sun-induced melanoma cases with hereditary genetic variant forms of melanocortin-1 receptor (MC1 R) gene.
Skin Cancer Increasing in Under-40 Population
The incidence of all types of skin cancers are increasing in children and young adults, according to Clinical Cancer Advances, a report issued by the American Society of Clinical Oncology.
The report noted the following statistics:
• The incidence of melanoma in people under age 20 increased 2.9% per year from 1973 to 2001, based on an analysis of the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) database.1
• Nonmelanoma skin cancers are also increasing in people under the age of 40. Researchers at the Mayo Clinic, who gathered data on people in Olmstead, MN, between 1976 and 2003, found the following:
• The incidence of basal cell carcinoma increased from 18.2 cases to 29.1 cases per 100,000 people.
• Squamous cell carcinoma cases also rose, with 0.9 cases reported in 1976 to 4.1 cases reported in 2003 per 100,000 people.2
Researchers expressed the need for larger studies before determining whether these increases will be seen on a larger scale.
References
1. Strouse JJ et al. Pediatric melanoma: Risk factor and survival analysis of the Surveillance, Epidemiology and End Results Database. J Clin Oncol. 2005;23:4735-4741.
2. Christenson LJ et al. Incidence of basal cell and squamous cell carcinomas in a population younger than 40 years. JAMA. 2005;294:681-690.
Visual Screening for Malignant Melanoma Found to Be Cost-Effective
An examination of various melanoma screening strategies using a computer simulation Markov model found one-time melanoma screening of the general population older than 50 years to be very cost-effective compared with other cancer screening programs in the United States, according to a study published in the January issue of Archives of Dermatology.
Other strategies considered included background screening only, and screening 1 time, every 2 years, and annually, all beginning at age 50 years. Screening every 2 years in siblings of patients with melanoma was also deemed cost-effective based on outcome measures including life expectancy, quality-adjusted life expectancy, and lifetime costs.
Fast-Growing Melanomas Don’t Fit ABCD Rule
According to Australian researchers led by Dr. Wendy Liu of the Alfred Hospital in Melbourne, rapidly growing melanomas don’t conform to the ABCD rule. They are instead thicker, redder, symmetrical or elevated, have regular borders, and often itch or bleed. What’s more, they don’t occur in the usual suspects — people who have large numbers of moles and freckles.
This is of course troublesome because these quickly growing tumors are not only much more lethal, their contradictory features make it more difficult for patients aware of the ABCD rule to spot them.
The study involved 404 subjects with invasive melanomas. All had skin examinations and pathology reviews and were interviewed about their melanoma and medical history. Researchers developed a "rate of growth index" based on the melanoma’s thickness and the time it took for the melanoma to develop. Faster rates of growth were associated with faster mitotic rates, or the rates at which the cancer cells multiplied.
These finding, published in the December issue of the Archives of Dermatology, also found that such melanomas were more likely to occur in men older than 70 and people with few freckles or moles.
The take-home message here: Any rapidly growing lesion of any description should be assessed promptly.
Red Hair Gene Ups Skin Cancer Risk — Regardless of Person’s Hair Color
Even patients with dark hair and olive skin but who carry the “red hair color gene” — the melanocortin 1 receptor (MC1R) gene — are at increased risk for developing skin cancer, according to an article by Reuters Health, which was based on a study published in the International Journal of Cancer.
In fact, researchers found that women who had medium or olive skin — not fair skin — and who had the MC1R gene were at the highest risk for skin cancer. Researchers studied three variants of this gene that are linked to red hair, fair skin and resistance to tanning. These variations are known as red hair color (RHC) variants. They also studied four other variants of the gene that were not as closely linked to red hair (non-red hair variants [NRHC]).
Using the Nurse’s Health Study, researchers identified groups of women with and without cancer, including the following:
- 219 women with melanoma
- 286 women with squamous cell carcinoma (SCC)
- 300 women with basal cell carcinoma (BCC)
- 873 women without skin cancer.
Researchers concluded the following after they controlled for the effects of skin type and other skin cancer risk factors:
• Women with the variant 151 Cys were at a 65% increased risk for melanoma.
• Women with the 151 Cys variant also had a 67% greater risk for developing SCC.
• Women with the 151 Cys variant were 56% more likely to develop BCC.
• Women who had one RHC gene, one NRHC gene, and medium to olive skin were at the greatest risk for melanoma.
• Women who had red hair and the 151 Cys variant were also at an increased risk for melanoma
• However, women without red hair who had the variant 151 Cys were not at a greater risk for developing melanoma, but women who had red hair and the variant 151 Cys were.
Source: Han J, Kraft P, Colditz GA, Wong J, Hunter DJ. Melanocortin 1 receptor variants and skin cancer risk. Int J Cancer. 2006 Oct 15; 119:1976-84.
Diphtheria Toxin-containing Drug Triggers Immune System to Fight Melanoma
Ateam of researchers at the James Graham Brown Cancer Center have discovered that a drug combination of diphtheria toxin and interleukin 2 appears to prompt the immune system to recognize and kill cancer cells in patients with advanced melanoma.
Preliminary results of a Phase II clinical trial showed that five out of seven patients with stage IV disease experienced significant regression or stabilization of both tumors and the spread of cancer.
Dr. Jason Chesney, Associate Director for translational research at the Brown Cancer Center led the investigation. He postulates that by wiping out the T-regulator cells, the drug prevents the immune system from shutting down, thus priming the body to mount a continuous attack against cancer.
Telephone Triage System Flags and Promptly Treats Patients with Suspicious Skin Lesions
A telephone screening method designed to reduce appointment wait times for patients with high-risk skin lesions has been developed by group of Kansas physicians — Drs. Jeff Graves, Mark H. Fleischman, and Glenn D. Goldstein.
The goal of their Derm Access strategy was to allow for the most suspicious lesions to be seen within 72 hours, if desired. This entailed leaving open slots in appointment schedules to accommodate these patients.
To evaluate the effectiveness of this approach, a total of 233 patients were studied; their wait time, procedure, and treatment data were collected and compared against national wait-time data.
Among these patients, a total of 146 (63%) were diagnosed with a cancerous or precancerous lesion. The mean wait time in actual working days was 7.44 during this same period.
This program was considered successful in that it substantially decreased patient anxiety and increased patient satisfaction. Additional benefits included public relations for the practice and public awareness of skin cancer.
