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Ionizing radiation linked to BCC
SAN DIEGO – Patients treated with ionizing radiation were 2.65 to 3.78 times more likely to develop basal cell carcinoma than were controls, and exposure at younger ages or relatively high doses further increased that risk, according to a pooled analysis presented at the annual meeting of the American Society for Dermatologic Surgery.
“Concomitant exposure to ultraviolet radiation may potentiate this effect,” said Dr. Min Deng, a dermatology resident at the University of Chicago. “With newer treatment protocols and improved shielding, it would be interesting to see if the effect of ionizing radiation has changed, or whether we as dermatologists should more actively screen this at-risk population.”
Basal cell carcinoma (BCC) is the most common skin cancer worldwide, but relatively few dermatology papers have assessed the effects of ionizing radiation on the incidence of BCC, said Dr. Deng and coauthor Dr. Diana Bolotin, also of the University of Chicago.
To better understand the link, the researchers searched PubMed for controlled studies on the topic by using the terms “radiation,” “risk,” and “basal cell carcinoma.” They excluded case reports, animal studies, studies published in languages other than English, and trials of radiation as a treatment of BCC, they said. They also excluded studies of atomic bomb survivors, because exposure was uncontrolled and methods to estimate exposure in this group have changed over time, they noted.
In all, six studies published between 1991 and 2012 met the inclusion criteria, and all six showed a statistically significant relative risk or odds of BCC with ionizing radiation exposure, the investigators reported. Three analyses calculated the relative risk of BCC in patients who received radiation for tinea capitis or who underwent total-body irradiation before hematopoietic cell transplantation, they said. Two studies evaluated the odds of BCC in patients with a past history of radiation exposure, and one study assessed time to subsequent BCCs in patients with a history of BCC.
For the three studies that calculated relative risk, the researchers calculated a pooled RR of BCC after ionizing radiation treatment of 2.65 (95% confidence interval, 1.22-5.72) compared with controls. The study of total-body irradiation (TBI) did not report or control for the primary disease for which patients were treated, “which may have confounded the results,” they said. When they excluded that study from their calculation, the overall RR rose to 3.78 (95% CI, 2.62 to 5.44).
Notably, in the two studies of patients with tinea capitis, the relative risk of BCC fell by 12% to 16% for every additional year of age at which patients received radiation treatment, the researchers said. Similarly, risk of BCC dropped by 10.9% for every 1-year increase in age at total-body irradiation prior to cell transplantation.
The combined odds ratio for the next two studies was 4.28 (1.45-12.63). “Likewise, both studies found an elevated odds ratio with younger age at radiation exposure,” the researchers added. One study that stratified patients by type of medical condition detected a “markedly elevated” 8.7 odds of BCC after radiation treatment for acne (2.0 to 38.0), they noted.
The sixth study was a nested case-control analysis that found a statistically significant increase in the odds of BCC starting at a 1-Gy dose of ionizing radiation, and rising linearly up to doses of 35-63.3 Gy. “The risk for developing multiple BCCs also appears to be elevated in patients with a history of radiation therapy,” the researchers said. Patients who had been exposed to ionizing ratio were 2.3 times more likely to develop new BCCs compared with unexposed patients (1.7 to 3.1), they said.
The investigators reported no funding sources or conflicts of interest.
SAN DIEGO – Patients treated with ionizing radiation were 2.65 to 3.78 times more likely to develop basal cell carcinoma than were controls, and exposure at younger ages or relatively high doses further increased that risk, according to a pooled analysis presented at the annual meeting of the American Society for Dermatologic Surgery.
“Concomitant exposure to ultraviolet radiation may potentiate this effect,” said Dr. Min Deng, a dermatology resident at the University of Chicago. “With newer treatment protocols and improved shielding, it would be interesting to see if the effect of ionizing radiation has changed, or whether we as dermatologists should more actively screen this at-risk population.”
Basal cell carcinoma (BCC) is the most common skin cancer worldwide, but relatively few dermatology papers have assessed the effects of ionizing radiation on the incidence of BCC, said Dr. Deng and coauthor Dr. Diana Bolotin, also of the University of Chicago.
To better understand the link, the researchers searched PubMed for controlled studies on the topic by using the terms “radiation,” “risk,” and “basal cell carcinoma.” They excluded case reports, animal studies, studies published in languages other than English, and trials of radiation as a treatment of BCC, they said. They also excluded studies of atomic bomb survivors, because exposure was uncontrolled and methods to estimate exposure in this group have changed over time, they noted.
In all, six studies published between 1991 and 2012 met the inclusion criteria, and all six showed a statistically significant relative risk or odds of BCC with ionizing radiation exposure, the investigators reported. Three analyses calculated the relative risk of BCC in patients who received radiation for tinea capitis or who underwent total-body irradiation before hematopoietic cell transplantation, they said. Two studies evaluated the odds of BCC in patients with a past history of radiation exposure, and one study assessed time to subsequent BCCs in patients with a history of BCC.
For the three studies that calculated relative risk, the researchers calculated a pooled RR of BCC after ionizing radiation treatment of 2.65 (95% confidence interval, 1.22-5.72) compared with controls. The study of total-body irradiation (TBI) did not report or control for the primary disease for which patients were treated, “which may have confounded the results,” they said. When they excluded that study from their calculation, the overall RR rose to 3.78 (95% CI, 2.62 to 5.44).
Notably, in the two studies of patients with tinea capitis, the relative risk of BCC fell by 12% to 16% for every additional year of age at which patients received radiation treatment, the researchers said. Similarly, risk of BCC dropped by 10.9% for every 1-year increase in age at total-body irradiation prior to cell transplantation.
The combined odds ratio for the next two studies was 4.28 (1.45-12.63). “Likewise, both studies found an elevated odds ratio with younger age at radiation exposure,” the researchers added. One study that stratified patients by type of medical condition detected a “markedly elevated” 8.7 odds of BCC after radiation treatment for acne (2.0 to 38.0), they noted.
The sixth study was a nested case-control analysis that found a statistically significant increase in the odds of BCC starting at a 1-Gy dose of ionizing radiation, and rising linearly up to doses of 35-63.3 Gy. “The risk for developing multiple BCCs also appears to be elevated in patients with a history of radiation therapy,” the researchers said. Patients who had been exposed to ionizing ratio were 2.3 times more likely to develop new BCCs compared with unexposed patients (1.7 to 3.1), they said.
The investigators reported no funding sources or conflicts of interest.
SAN DIEGO – Patients treated with ionizing radiation were 2.65 to 3.78 times more likely to develop basal cell carcinoma than were controls, and exposure at younger ages or relatively high doses further increased that risk, according to a pooled analysis presented at the annual meeting of the American Society for Dermatologic Surgery.
“Concomitant exposure to ultraviolet radiation may potentiate this effect,” said Dr. Min Deng, a dermatology resident at the University of Chicago. “With newer treatment protocols and improved shielding, it would be interesting to see if the effect of ionizing radiation has changed, or whether we as dermatologists should more actively screen this at-risk population.”
Basal cell carcinoma (BCC) is the most common skin cancer worldwide, but relatively few dermatology papers have assessed the effects of ionizing radiation on the incidence of BCC, said Dr. Deng and coauthor Dr. Diana Bolotin, also of the University of Chicago.
To better understand the link, the researchers searched PubMed for controlled studies on the topic by using the terms “radiation,” “risk,” and “basal cell carcinoma.” They excluded case reports, animal studies, studies published in languages other than English, and trials of radiation as a treatment of BCC, they said. They also excluded studies of atomic bomb survivors, because exposure was uncontrolled and methods to estimate exposure in this group have changed over time, they noted.
In all, six studies published between 1991 and 2012 met the inclusion criteria, and all six showed a statistically significant relative risk or odds of BCC with ionizing radiation exposure, the investigators reported. Three analyses calculated the relative risk of BCC in patients who received radiation for tinea capitis or who underwent total-body irradiation before hematopoietic cell transplantation, they said. Two studies evaluated the odds of BCC in patients with a past history of radiation exposure, and one study assessed time to subsequent BCCs in patients with a history of BCC.
For the three studies that calculated relative risk, the researchers calculated a pooled RR of BCC after ionizing radiation treatment of 2.65 (95% confidence interval, 1.22-5.72) compared with controls. The study of total-body irradiation (TBI) did not report or control for the primary disease for which patients were treated, “which may have confounded the results,” they said. When they excluded that study from their calculation, the overall RR rose to 3.78 (95% CI, 2.62 to 5.44).
Notably, in the two studies of patients with tinea capitis, the relative risk of BCC fell by 12% to 16% for every additional year of age at which patients received radiation treatment, the researchers said. Similarly, risk of BCC dropped by 10.9% for every 1-year increase in age at total-body irradiation prior to cell transplantation.
The combined odds ratio for the next two studies was 4.28 (1.45-12.63). “Likewise, both studies found an elevated odds ratio with younger age at radiation exposure,” the researchers added. One study that stratified patients by type of medical condition detected a “markedly elevated” 8.7 odds of BCC after radiation treatment for acne (2.0 to 38.0), they noted.
The sixth study was a nested case-control analysis that found a statistically significant increase in the odds of BCC starting at a 1-Gy dose of ionizing radiation, and rising linearly up to doses of 35-63.3 Gy. “The risk for developing multiple BCCs also appears to be elevated in patients with a history of radiation therapy,” the researchers said. Patients who had been exposed to ionizing ratio were 2.3 times more likely to develop new BCCs compared with unexposed patients (1.7 to 3.1), they said.
The investigators reported no funding sources or conflicts of interest.
Key clinical point: Ionizing radiation therapy significantly increased risk of basal cell carcinoma, especially when patients were younger or were treated at relatively high doses.
Major finding: The pooled relative risk of BCC after ionizing radiation treatment was 2.65 (95% confidence interval, 1.22-5.72) compared with controls.
Data source: Pooled analysis of six studies of ionizing radiation exposure and risk or odds of basal cell carcinoma.
Disclosures: The researchers reported no funding sources or conflicts of interest.
A Team Approach to Nonmelanotic Skin Cancer Procedures
For many decades, the treatment of choice for nonmetastatic but locally invasive nonmelanotic basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) has been complete surgical excision that ensures minimal tissue waste, yet retains adequate tumor-free resection margins. From early on, the primary challenge has been assessing the appropriateness of those margins at the time of the initial surgical procedure, rather than having to recall the patient later for an additional surgery to excise involved margins.
In 1953, Steven Mohs, MD, envisioned the use of a vital dye to distinguish benign from malignant skin tissue at the time of surgery.1-3 At that point intraoperative consultation with a pathologist and the process of examining frozen sections (FS) for diagnosis were not standards of care in oncologic surgery. This process allowed Mohs, with limited success, to excise tumors with negative margins. Mohs repeatedly revised and improved his procedure, including the utilization of intraoperative FS to examine the entire specimen margin, a process that is at the core of the Mohs micrographic surgery.1-3
Currently, the Mohs procedure is one of the most popular approaches to definitive skin cancer surgery, especially in the head and neck region where tissue preservation can be critical. It is usually performed as an outpatient or clinic procedure by a specially trained dermatologist who acts both as a surgeon and a pathologist, excising the lesion and processing it for FS diagnosis.4-6 In a hospital setting, other practitioners (surgeons and pathologists) often use the standard approach of limited sampling of resection margins for FS by serially sectioning a specimen that had already been inked or marked for the appropriate margins and freeze-sectioning representative portions of those margins. Reports published by experienced operators using these different approaches indicate variable cancer recurrence rates of 1% to 6%.7-9
At the VA it is a priority to deliver the same quality health care at a much lower price. In this setting it is prudent to periodically reexamine alternative approaches to patient care delivery that utilize existing resources or excess capacity to achieve comparable, if not superior, outcomes to the usually more costly private sector outsourcing contractual arrangements.
With that goal in mind, a few years ago Robley Rex VAMC (RRVAMC) embarked on a new team approach for resectable nonmelanotic skin cancer cases. The team consisted of a plastic surgeon and a pathologist with the appropriate technical and nursing support (histotechnicians, surgical nurse practitioners, and/or nurse anesthsesists) staff. None of the team members were exclusively dedicated to the procedure but were afforded adequate time and material resources to handle all such cases. In this report, the authors describe their experience and the impact of their approach on the affected patients.
Methods
At RRVAMC, primary care providers were encouraged to refer patients suspected of nonmelanotic skin cancer directly to a hospital-based plastic surgeon, who schedules them for a FS-controlled surgical excision of the suspected lesion. The plastic surgeon also plans to cover the resulting wound, if too large for primary closure, with a micrograft during the same procedure. The procedure is usually performed under local anesthesia. A general surgeon or surgical fellow with basic training in plastic surgery may substitute for the plastic surgeon. When not performing this procedure, the surgeon carries on other routine surgical duties.
A dedicated FS room was set up next to an operating room (OR), which was designated for this specialized skin cancer surgery, among other surgeries. The pathologist could walk into the OR anytime to assess the lesion, its location, and the surgeon’s plan of resection, and both physicians could discuss the best strategy for the initial resection or any subsequent margin reexcision. Both could also discuss whether a permanent section would be more appropriate under the conditions.
A small window separated the FS room from the OR, allowing two-way communication and the delivery of specimens. If the specimen was more complex in terms of margin definition, the pathologist could personally take the specimen after its excision directly from the surgeon who could offer further explanation of the special attributes of the specimen. The specimen was usually placed on a topographic drawing of the body region with one or more permanent marks that denoted specific landmarks for orientation.
Once the specimen was in the FS room, the pathologist proceeded with standard gross description followed by color inking of the margins and sampling, according to the following rules:
- Small specimen (< 0.5 cm): Embed as is; FSs may be cut parallel to epidermal surface and examined until no more tumor is seen.
- Medium specimen (0.5-3.0 cm): Serially cross-section and embed all in ≥ 1 blocks; ≥ 6 FSs (cuts) examined from each block.
- Large specimen (> 3.0 cm): Peripheral margins shaved; few central sections taken through deep margin.
For the very small specimens excised from cosmetically or biologically critical areas, such as the head and neck region, the pathologist could use the classic Mohs sampling technique of freezing the entire specimen as is and sectioning parallel to the skin surface until free margins were reached or the entire specimen was exhausted. The pathologist could use serial cross-sectioning at 2 mm intervals in medium-sized excisions, or limited sampling of peripheral and deep margins in very large specimens. In these latter sampling approaches, at least 6 sections are cut from each slice (block), each 5 µm to 10 µm thick. The sections were mounted on glass slides, stained with hematoxylin-eosin (H&E), and examined thoroughly under a microscope before rendering a diagnosis (assessment of the resection margin).
The diagnosis was communicated directly to the surgeon by the pathologist who walked into the OR or while viewing the slides with the surgeon at a double-headed microscope located in the FS room. Remnants of any frozen or unprocessed tissue were submitted for permanent section, and the findings of both the FS and permanent diagnosis were compared the following day. Similar to the main laboratory procedures, 10% of cases were subjected to retroactive peer review for quality assurance.
Freeze section duty was handled by a pathologist and a histotechnician. Once the FS case was completed, the pathologist and histotechnician returned to the main laboratory to attend to other routine duties.
The patient’s state of comfort and satisfaction was assessed informally but routinely by the surgical team before discharge and at the follow-up visit. The patient was asked about the overall experience and invited to submit written comments to the RRVAMC patient representative. A generic mailback card was also available for feedback.
For the cost analysis, budgeting for the recurrent annual cost of labor and supplies was based on a presumed maximum workload of 300 cases/year (3-4 cases/day; 2 days/week or 0.4 full-time equivalent employee [FTEE] for each member of the team) and estimated additional OR and histology laboratory supplies of about $500/case. At the end of the fiscal year, the budgeted estimates were reconciled with the actual expenses or the added financial burden that was associated with the program to calculate the expense per case, which then was compared with the average CMS (Centers for Medicare and Medicaid Services) reimbursement rate for Mohs procedures as usually billed by private practitioners.
Results
From 2006 to 2007, 439 procedures were performed at the RRVAMC program. Patients were followed up for recurrence or other complications through the end of 2012. No serious complications were encountered during any of these procedures. Patients’ comments after each procedure indicated complete satisfaction with the process, and no negative feedback or complaint was received. More than 5 years of follow-up on the initial 439 procedures yielded a rate of cancer recurrence of about 0.5% (2 patients, a 30-year-old woman and a 77-year-old man, both with basal cell carcinoma [BCC] of the nose), which is comparable or slightly better than that reported in relevant literature for the various methods, including the classic Mohs.10,11
Table 1 shows the distribution of the cases by age, gender, specimen size, and type of cancer. Most patients were white men (98.5%), and almost all (99%) cancers were from the head and neck region. Basal cell carcinoma was the diagnosis in 80% of the cases; the remainder were squamous cell carcinomas (SCCs). Both types of cancer were prevalent in the older age groups (> 50 years). Basal cell carcinoma was more prevalent in the group aged 51 to 70 years, whereas SCC predominated in patients aged > 70 years. The patients ranged in age from 30 to 89 years. The majority of specimens were medium sized (86%); 11% were large and the remaining 3% were small specimens. These demographics of patient’s age, cancer location, and prevalent diagnosis, were comparable to those of most VAMCs.
All acrediatation standards of the Clinical Laboratory Improvement Amendments of 1988 (CLIA 88) and College of American Pathologists (CAP) were observed in the RRVAMC FS laboratory, including monitoring frozen vs permanent tissue diagnosis and 10% retroactive peer review. Those indicators were always well below established thresholds or reasonable pathology practice community standards. The RRVAMC laboratory overall error (major discrepancy) rate has been < 0.2%. The FS laboratory has also been in compliance with the technical quality CAP accreditation standards, such as those for equipment, reagents, personnel, and environment controls.
Cost analysis data are presented in Table 2. The data are based on realistic estimates in a hospital setting. The provided numbers for the FTEE salaries are average local estimates (based on VA-wide pay scale for employees according to their grades and within grade steps), though actual salary structure varied widely among institutions. Although budgeted estimates suggest an average expense of about $1,500 per case (including cases with multiple lesions that could be removed at the same session), the actual or realistic expense is far less, because some of the resources were preexisting or shared across the Surgical and Pathology Services, including FTEE time commitments. The RRVAMC planning strategy assumed 200 to 300 cases/year at $1,000 to $2,000/case.
Discussion
The RRVAMC approach of direct patient referral to the in-house plastic surgeon often spared the patient 2 additional clinical visits or procedures, which might otherwise have been required. Often, the primary care provider referred the patient to a dermatologist who would perform a shave or punch biopsy, awaiting a pathologist’s diagnosis before scheduling definitive (eg, Mohs) surgery with a separate provider. After that, the patient might be scheduled for reconstructive surgery, if necessary, by a plastic surgeon. With the RRVAMC approach, not only were the number of visits/procedures reduced, but the total time was shortened by several weeks, sparing the patient discomfort and uncertainty.
The RRVAMC cost analysis data show an average realistic cost at this setting (considering already available resources) of far less than $2,000 ($1,000-$1,500). This is substantially below the $2,000 to $10,000 cost per case (or lesion in patients with multiple lesions) that would have been required for a private sector referral, based on CMS reimbursement rates for Mohs procedures (CPT codes 17311-17315).
An important element in the cost-effectiveness, quality assurance, and time use in this approach is the flexibility of the key operators (surgery and pathology staff) and the sampling technique. For the latter, the pathologist can use the most efficient technique, depending on specimen source and size: The classic Mohs technique for very small (head and neck area) specimens, but serial cross-sectioning or limited sampling of peripheral and deep margins in other situations. All 3 sectioning approaches in the RRVAMC practice proved reliable in assessing the margins, as they were always verified either on permanent sections and/or through retroactive peer review. Furthermore, in a mostly elderly patient population, there is rarely a need for extremely conservative resection of the margins, as the skin often shows wrinkling or redundancy that allows for a more generous healthy rim around the lesion. In such cases, it may be indeed superfluous to apply the protracted and expensive Mohs procedural variant.
The quality assurance aspect of the RRVAMC approach is also important. Examining permanent sections as well as retroactive peer review can uncover diagnostic or processing errors even in the best of laboratories. That error rate in the surgical pathology community may reach more than 1% to 2%.12 In the RRVAMC practice, the major discrepancy rate is usually below 0.2%. There is a reason for concern in any FS laboratory where such monitoring is not done, considering that even BCC can be occasionally confused on FS with other small blue cell malignancies, such as lymphoma or Merkel cell carcinoma.
Conclusion
The authors offer the RRVAMC pathologist-plastic surgeon team approach to definitive skin cancer surgery as a reliable and less expensive in-house alternative to contractual outsourcing for those VA (or non-VA) medical centers that have a plastic surgeon (or trained equivalent) and a surgical pathologist on staff.
Acknowledgements
This material is the result of work supported with resources and the use of facilities at the Robley Rex VAMC in Louisville, Kentucky.
Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.
Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.
1. Robins P, Albom MJ. Mohs’ surgery—fresh tissue technique. J Dermatol Surg. 1975;1(2):37-41.
2. Mohs FE. Mohs micrographic surgery. A historical perspective. Dermatol Clin. 1989;7(4):609-611.
3. Mohs FE. Origin and progress of Mohs micrographic surgery. In: Mikhail GR, ed. Mohs Micrographic Surgery. Philadelphia, PA: WB Saunders; 1991:1-10.
4. Rowe DE, Carroll RJ, Day CL Jr. Prognostic factors for local recurrence, metastasis, and survival rates in squamous cell carcinoma of the skin, ear, and lip. Implications for treatment modality selection. J Am Acad Dermatol. 1992;26(6):976-990.
5. Rowe DE. Comparison of treatment modalities for basal cell carcinoma. Clin Dermatol. 1995;13(6):617-620.
6. Smeets NW, Krekels GA, Ostertag JU, et al. Surgical excision vs Mohs’ micrographic surgery for basal-cell carcinoma of the face: Randomised controlled trial. Lancet. 2004;364(9447):1766-1772.
7. Bentkover SH, Grande DM, Soto H, Kozlicak BA, Guillaume D, Girouard S. Excision of head and neck basal cell carcinoma with a rapid, cross-sectional, frozen-section technique. Arch Facial Plast Surg. 2002;4(2):114-119.
8. Kimyai-Asadi A, Goldberg LH, Jih MH. Accuracy of serial transverse cross-sections in detecting residual basal cell carcinoma at the surgical margins of an elliptical excision specimen. J Am Acad Dermatol. 2004;53(3):469-474.
9. Dhingra N, Gajdasty A, Neal JW, Mukherjee AN, Lane CM. Confident complete excision of lid-margin BCCs using a marginal strip: An alternative to Mohs’ surgery. Brit J Ophthalmol. 2007;91(6):794-796.
10. Minton TJ. Contemporary Mohs surgery applications. Curr Opin Otolaryngol Head Neck Surg. 2008;16(4):376-380.
11. Mosterd K, Krekels GA, Nieman FH, et al. Surgical excision versus Mohs’ micrographic surgery for primary and recurrent basal-cell carcinoma of the face: A prospective randomised controlled trial with 5-years’ follow-up. Lancet Oncol. 2008;9(12):1149-1156.
12. Weiss MA. Analytic variables; diagnostic accuracy. In: Nakhleh RE, Fitzgibbons PL, eds. Quality Management in Anatomic Pathology. Northfield, IL: College of American Pathologists; 2005:50-76.
For many decades, the treatment of choice for nonmetastatic but locally invasive nonmelanotic basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) has been complete surgical excision that ensures minimal tissue waste, yet retains adequate tumor-free resection margins. From early on, the primary challenge has been assessing the appropriateness of those margins at the time of the initial surgical procedure, rather than having to recall the patient later for an additional surgery to excise involved margins.
In 1953, Steven Mohs, MD, envisioned the use of a vital dye to distinguish benign from malignant skin tissue at the time of surgery.1-3 At that point intraoperative consultation with a pathologist and the process of examining frozen sections (FS) for diagnosis were not standards of care in oncologic surgery. This process allowed Mohs, with limited success, to excise tumors with negative margins. Mohs repeatedly revised and improved his procedure, including the utilization of intraoperative FS to examine the entire specimen margin, a process that is at the core of the Mohs micrographic surgery.1-3
Currently, the Mohs procedure is one of the most popular approaches to definitive skin cancer surgery, especially in the head and neck region where tissue preservation can be critical. It is usually performed as an outpatient or clinic procedure by a specially trained dermatologist who acts both as a surgeon and a pathologist, excising the lesion and processing it for FS diagnosis.4-6 In a hospital setting, other practitioners (surgeons and pathologists) often use the standard approach of limited sampling of resection margins for FS by serially sectioning a specimen that had already been inked or marked for the appropriate margins and freeze-sectioning representative portions of those margins. Reports published by experienced operators using these different approaches indicate variable cancer recurrence rates of 1% to 6%.7-9
At the VA it is a priority to deliver the same quality health care at a much lower price. In this setting it is prudent to periodically reexamine alternative approaches to patient care delivery that utilize existing resources or excess capacity to achieve comparable, if not superior, outcomes to the usually more costly private sector outsourcing contractual arrangements.
With that goal in mind, a few years ago Robley Rex VAMC (RRVAMC) embarked on a new team approach for resectable nonmelanotic skin cancer cases. The team consisted of a plastic surgeon and a pathologist with the appropriate technical and nursing support (histotechnicians, surgical nurse practitioners, and/or nurse anesthsesists) staff. None of the team members were exclusively dedicated to the procedure but were afforded adequate time and material resources to handle all such cases. In this report, the authors describe their experience and the impact of their approach on the affected patients.
Methods
At RRVAMC, primary care providers were encouraged to refer patients suspected of nonmelanotic skin cancer directly to a hospital-based plastic surgeon, who schedules them for a FS-controlled surgical excision of the suspected lesion. The plastic surgeon also plans to cover the resulting wound, if too large for primary closure, with a micrograft during the same procedure. The procedure is usually performed under local anesthesia. A general surgeon or surgical fellow with basic training in plastic surgery may substitute for the plastic surgeon. When not performing this procedure, the surgeon carries on other routine surgical duties.
A dedicated FS room was set up next to an operating room (OR), which was designated for this specialized skin cancer surgery, among other surgeries. The pathologist could walk into the OR anytime to assess the lesion, its location, and the surgeon’s plan of resection, and both physicians could discuss the best strategy for the initial resection or any subsequent margin reexcision. Both could also discuss whether a permanent section would be more appropriate under the conditions.
A small window separated the FS room from the OR, allowing two-way communication and the delivery of specimens. If the specimen was more complex in terms of margin definition, the pathologist could personally take the specimen after its excision directly from the surgeon who could offer further explanation of the special attributes of the specimen. The specimen was usually placed on a topographic drawing of the body region with one or more permanent marks that denoted specific landmarks for orientation.
Once the specimen was in the FS room, the pathologist proceeded with standard gross description followed by color inking of the margins and sampling, according to the following rules:
- Small specimen (< 0.5 cm): Embed as is; FSs may be cut parallel to epidermal surface and examined until no more tumor is seen.
- Medium specimen (0.5-3.0 cm): Serially cross-section and embed all in ≥ 1 blocks; ≥ 6 FSs (cuts) examined from each block.
- Large specimen (> 3.0 cm): Peripheral margins shaved; few central sections taken through deep margin.
For the very small specimens excised from cosmetically or biologically critical areas, such as the head and neck region, the pathologist could use the classic Mohs sampling technique of freezing the entire specimen as is and sectioning parallel to the skin surface until free margins were reached or the entire specimen was exhausted. The pathologist could use serial cross-sectioning at 2 mm intervals in medium-sized excisions, or limited sampling of peripheral and deep margins in very large specimens. In these latter sampling approaches, at least 6 sections are cut from each slice (block), each 5 µm to 10 µm thick. The sections were mounted on glass slides, stained with hematoxylin-eosin (H&E), and examined thoroughly under a microscope before rendering a diagnosis (assessment of the resection margin).
The diagnosis was communicated directly to the surgeon by the pathologist who walked into the OR or while viewing the slides with the surgeon at a double-headed microscope located in the FS room. Remnants of any frozen or unprocessed tissue were submitted for permanent section, and the findings of both the FS and permanent diagnosis were compared the following day. Similar to the main laboratory procedures, 10% of cases were subjected to retroactive peer review for quality assurance.
Freeze section duty was handled by a pathologist and a histotechnician. Once the FS case was completed, the pathologist and histotechnician returned to the main laboratory to attend to other routine duties.
The patient’s state of comfort and satisfaction was assessed informally but routinely by the surgical team before discharge and at the follow-up visit. The patient was asked about the overall experience and invited to submit written comments to the RRVAMC patient representative. A generic mailback card was also available for feedback.
For the cost analysis, budgeting for the recurrent annual cost of labor and supplies was based on a presumed maximum workload of 300 cases/year (3-4 cases/day; 2 days/week or 0.4 full-time equivalent employee [FTEE] for each member of the team) and estimated additional OR and histology laboratory supplies of about $500/case. At the end of the fiscal year, the budgeted estimates were reconciled with the actual expenses or the added financial burden that was associated with the program to calculate the expense per case, which then was compared with the average CMS (Centers for Medicare and Medicaid Services) reimbursement rate for Mohs procedures as usually billed by private practitioners.
Results
From 2006 to 2007, 439 procedures were performed at the RRVAMC program. Patients were followed up for recurrence or other complications through the end of 2012. No serious complications were encountered during any of these procedures. Patients’ comments after each procedure indicated complete satisfaction with the process, and no negative feedback or complaint was received. More than 5 years of follow-up on the initial 439 procedures yielded a rate of cancer recurrence of about 0.5% (2 patients, a 30-year-old woman and a 77-year-old man, both with basal cell carcinoma [BCC] of the nose), which is comparable or slightly better than that reported in relevant literature for the various methods, including the classic Mohs.10,11
Table 1 shows the distribution of the cases by age, gender, specimen size, and type of cancer. Most patients were white men (98.5%), and almost all (99%) cancers were from the head and neck region. Basal cell carcinoma was the diagnosis in 80% of the cases; the remainder were squamous cell carcinomas (SCCs). Both types of cancer were prevalent in the older age groups (> 50 years). Basal cell carcinoma was more prevalent in the group aged 51 to 70 years, whereas SCC predominated in patients aged > 70 years. The patients ranged in age from 30 to 89 years. The majority of specimens were medium sized (86%); 11% were large and the remaining 3% were small specimens. These demographics of patient’s age, cancer location, and prevalent diagnosis, were comparable to those of most VAMCs.
All acrediatation standards of the Clinical Laboratory Improvement Amendments of 1988 (CLIA 88) and College of American Pathologists (CAP) were observed in the RRVAMC FS laboratory, including monitoring frozen vs permanent tissue diagnosis and 10% retroactive peer review. Those indicators were always well below established thresholds or reasonable pathology practice community standards. The RRVAMC laboratory overall error (major discrepancy) rate has been < 0.2%. The FS laboratory has also been in compliance with the technical quality CAP accreditation standards, such as those for equipment, reagents, personnel, and environment controls.
Cost analysis data are presented in Table 2. The data are based on realistic estimates in a hospital setting. The provided numbers for the FTEE salaries are average local estimates (based on VA-wide pay scale for employees according to their grades and within grade steps), though actual salary structure varied widely among institutions. Although budgeted estimates suggest an average expense of about $1,500 per case (including cases with multiple lesions that could be removed at the same session), the actual or realistic expense is far less, because some of the resources were preexisting or shared across the Surgical and Pathology Services, including FTEE time commitments. The RRVAMC planning strategy assumed 200 to 300 cases/year at $1,000 to $2,000/case.
Discussion
The RRVAMC approach of direct patient referral to the in-house plastic surgeon often spared the patient 2 additional clinical visits or procedures, which might otherwise have been required. Often, the primary care provider referred the patient to a dermatologist who would perform a shave or punch biopsy, awaiting a pathologist’s diagnosis before scheduling definitive (eg, Mohs) surgery with a separate provider. After that, the patient might be scheduled for reconstructive surgery, if necessary, by a plastic surgeon. With the RRVAMC approach, not only were the number of visits/procedures reduced, but the total time was shortened by several weeks, sparing the patient discomfort and uncertainty.
The RRVAMC cost analysis data show an average realistic cost at this setting (considering already available resources) of far less than $2,000 ($1,000-$1,500). This is substantially below the $2,000 to $10,000 cost per case (or lesion in patients with multiple lesions) that would have been required for a private sector referral, based on CMS reimbursement rates for Mohs procedures (CPT codes 17311-17315).
An important element in the cost-effectiveness, quality assurance, and time use in this approach is the flexibility of the key operators (surgery and pathology staff) and the sampling technique. For the latter, the pathologist can use the most efficient technique, depending on specimen source and size: The classic Mohs technique for very small (head and neck area) specimens, but serial cross-sectioning or limited sampling of peripheral and deep margins in other situations. All 3 sectioning approaches in the RRVAMC practice proved reliable in assessing the margins, as they were always verified either on permanent sections and/or through retroactive peer review. Furthermore, in a mostly elderly patient population, there is rarely a need for extremely conservative resection of the margins, as the skin often shows wrinkling or redundancy that allows for a more generous healthy rim around the lesion. In such cases, it may be indeed superfluous to apply the protracted and expensive Mohs procedural variant.
The quality assurance aspect of the RRVAMC approach is also important. Examining permanent sections as well as retroactive peer review can uncover diagnostic or processing errors even in the best of laboratories. That error rate in the surgical pathology community may reach more than 1% to 2%.12 In the RRVAMC practice, the major discrepancy rate is usually below 0.2%. There is a reason for concern in any FS laboratory where such monitoring is not done, considering that even BCC can be occasionally confused on FS with other small blue cell malignancies, such as lymphoma or Merkel cell carcinoma.
Conclusion
The authors offer the RRVAMC pathologist-plastic surgeon team approach to definitive skin cancer surgery as a reliable and less expensive in-house alternative to contractual outsourcing for those VA (or non-VA) medical centers that have a plastic surgeon (or trained equivalent) and a surgical pathologist on staff.
Acknowledgements
This material is the result of work supported with resources and the use of facilities at the Robley Rex VAMC in Louisville, Kentucky.
Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.
Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.
For many decades, the treatment of choice for nonmetastatic but locally invasive nonmelanotic basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) has been complete surgical excision that ensures minimal tissue waste, yet retains adequate tumor-free resection margins. From early on, the primary challenge has been assessing the appropriateness of those margins at the time of the initial surgical procedure, rather than having to recall the patient later for an additional surgery to excise involved margins.
In 1953, Steven Mohs, MD, envisioned the use of a vital dye to distinguish benign from malignant skin tissue at the time of surgery.1-3 At that point intraoperative consultation with a pathologist and the process of examining frozen sections (FS) for diagnosis were not standards of care in oncologic surgery. This process allowed Mohs, with limited success, to excise tumors with negative margins. Mohs repeatedly revised and improved his procedure, including the utilization of intraoperative FS to examine the entire specimen margin, a process that is at the core of the Mohs micrographic surgery.1-3
Currently, the Mohs procedure is one of the most popular approaches to definitive skin cancer surgery, especially in the head and neck region where tissue preservation can be critical. It is usually performed as an outpatient or clinic procedure by a specially trained dermatologist who acts both as a surgeon and a pathologist, excising the lesion and processing it for FS diagnosis.4-6 In a hospital setting, other practitioners (surgeons and pathologists) often use the standard approach of limited sampling of resection margins for FS by serially sectioning a specimen that had already been inked or marked for the appropriate margins and freeze-sectioning representative portions of those margins. Reports published by experienced operators using these different approaches indicate variable cancer recurrence rates of 1% to 6%.7-9
At the VA it is a priority to deliver the same quality health care at a much lower price. In this setting it is prudent to periodically reexamine alternative approaches to patient care delivery that utilize existing resources or excess capacity to achieve comparable, if not superior, outcomes to the usually more costly private sector outsourcing contractual arrangements.
With that goal in mind, a few years ago Robley Rex VAMC (RRVAMC) embarked on a new team approach for resectable nonmelanotic skin cancer cases. The team consisted of a plastic surgeon and a pathologist with the appropriate technical and nursing support (histotechnicians, surgical nurse practitioners, and/or nurse anesthsesists) staff. None of the team members were exclusively dedicated to the procedure but were afforded adequate time and material resources to handle all such cases. In this report, the authors describe their experience and the impact of their approach on the affected patients.
Methods
At RRVAMC, primary care providers were encouraged to refer patients suspected of nonmelanotic skin cancer directly to a hospital-based plastic surgeon, who schedules them for a FS-controlled surgical excision of the suspected lesion. The plastic surgeon also plans to cover the resulting wound, if too large for primary closure, with a micrograft during the same procedure. The procedure is usually performed under local anesthesia. A general surgeon or surgical fellow with basic training in plastic surgery may substitute for the plastic surgeon. When not performing this procedure, the surgeon carries on other routine surgical duties.
A dedicated FS room was set up next to an operating room (OR), which was designated for this specialized skin cancer surgery, among other surgeries. The pathologist could walk into the OR anytime to assess the lesion, its location, and the surgeon’s plan of resection, and both physicians could discuss the best strategy for the initial resection or any subsequent margin reexcision. Both could also discuss whether a permanent section would be more appropriate under the conditions.
A small window separated the FS room from the OR, allowing two-way communication and the delivery of specimens. If the specimen was more complex in terms of margin definition, the pathologist could personally take the specimen after its excision directly from the surgeon who could offer further explanation of the special attributes of the specimen. The specimen was usually placed on a topographic drawing of the body region with one or more permanent marks that denoted specific landmarks for orientation.
Once the specimen was in the FS room, the pathologist proceeded with standard gross description followed by color inking of the margins and sampling, according to the following rules:
- Small specimen (< 0.5 cm): Embed as is; FSs may be cut parallel to epidermal surface and examined until no more tumor is seen.
- Medium specimen (0.5-3.0 cm): Serially cross-section and embed all in ≥ 1 blocks; ≥ 6 FSs (cuts) examined from each block.
- Large specimen (> 3.0 cm): Peripheral margins shaved; few central sections taken through deep margin.
For the very small specimens excised from cosmetically or biologically critical areas, such as the head and neck region, the pathologist could use the classic Mohs sampling technique of freezing the entire specimen as is and sectioning parallel to the skin surface until free margins were reached or the entire specimen was exhausted. The pathologist could use serial cross-sectioning at 2 mm intervals in medium-sized excisions, or limited sampling of peripheral and deep margins in very large specimens. In these latter sampling approaches, at least 6 sections are cut from each slice (block), each 5 µm to 10 µm thick. The sections were mounted on glass slides, stained with hematoxylin-eosin (H&E), and examined thoroughly under a microscope before rendering a diagnosis (assessment of the resection margin).
The diagnosis was communicated directly to the surgeon by the pathologist who walked into the OR or while viewing the slides with the surgeon at a double-headed microscope located in the FS room. Remnants of any frozen or unprocessed tissue were submitted for permanent section, and the findings of both the FS and permanent diagnosis were compared the following day. Similar to the main laboratory procedures, 10% of cases were subjected to retroactive peer review for quality assurance.
Freeze section duty was handled by a pathologist and a histotechnician. Once the FS case was completed, the pathologist and histotechnician returned to the main laboratory to attend to other routine duties.
The patient’s state of comfort and satisfaction was assessed informally but routinely by the surgical team before discharge and at the follow-up visit. The patient was asked about the overall experience and invited to submit written comments to the RRVAMC patient representative. A generic mailback card was also available for feedback.
For the cost analysis, budgeting for the recurrent annual cost of labor and supplies was based on a presumed maximum workload of 300 cases/year (3-4 cases/day; 2 days/week or 0.4 full-time equivalent employee [FTEE] for each member of the team) and estimated additional OR and histology laboratory supplies of about $500/case. At the end of the fiscal year, the budgeted estimates were reconciled with the actual expenses or the added financial burden that was associated with the program to calculate the expense per case, which then was compared with the average CMS (Centers for Medicare and Medicaid Services) reimbursement rate for Mohs procedures as usually billed by private practitioners.
Results
From 2006 to 2007, 439 procedures were performed at the RRVAMC program. Patients were followed up for recurrence or other complications through the end of 2012. No serious complications were encountered during any of these procedures. Patients’ comments after each procedure indicated complete satisfaction with the process, and no negative feedback or complaint was received. More than 5 years of follow-up on the initial 439 procedures yielded a rate of cancer recurrence of about 0.5% (2 patients, a 30-year-old woman and a 77-year-old man, both with basal cell carcinoma [BCC] of the nose), which is comparable or slightly better than that reported in relevant literature for the various methods, including the classic Mohs.10,11
Table 1 shows the distribution of the cases by age, gender, specimen size, and type of cancer. Most patients were white men (98.5%), and almost all (99%) cancers were from the head and neck region. Basal cell carcinoma was the diagnosis in 80% of the cases; the remainder were squamous cell carcinomas (SCCs). Both types of cancer were prevalent in the older age groups (> 50 years). Basal cell carcinoma was more prevalent in the group aged 51 to 70 years, whereas SCC predominated in patients aged > 70 years. The patients ranged in age from 30 to 89 years. The majority of specimens were medium sized (86%); 11% were large and the remaining 3% were small specimens. These demographics of patient’s age, cancer location, and prevalent diagnosis, were comparable to those of most VAMCs.
All acrediatation standards of the Clinical Laboratory Improvement Amendments of 1988 (CLIA 88) and College of American Pathologists (CAP) were observed in the RRVAMC FS laboratory, including monitoring frozen vs permanent tissue diagnosis and 10% retroactive peer review. Those indicators were always well below established thresholds or reasonable pathology practice community standards. The RRVAMC laboratory overall error (major discrepancy) rate has been < 0.2%. The FS laboratory has also been in compliance with the technical quality CAP accreditation standards, such as those for equipment, reagents, personnel, and environment controls.
Cost analysis data are presented in Table 2. The data are based on realistic estimates in a hospital setting. The provided numbers for the FTEE salaries are average local estimates (based on VA-wide pay scale for employees according to their grades and within grade steps), though actual salary structure varied widely among institutions. Although budgeted estimates suggest an average expense of about $1,500 per case (including cases with multiple lesions that could be removed at the same session), the actual or realistic expense is far less, because some of the resources were preexisting or shared across the Surgical and Pathology Services, including FTEE time commitments. The RRVAMC planning strategy assumed 200 to 300 cases/year at $1,000 to $2,000/case.
Discussion
The RRVAMC approach of direct patient referral to the in-house plastic surgeon often spared the patient 2 additional clinical visits or procedures, which might otherwise have been required. Often, the primary care provider referred the patient to a dermatologist who would perform a shave or punch biopsy, awaiting a pathologist’s diagnosis before scheduling definitive (eg, Mohs) surgery with a separate provider. After that, the patient might be scheduled for reconstructive surgery, if necessary, by a plastic surgeon. With the RRVAMC approach, not only were the number of visits/procedures reduced, but the total time was shortened by several weeks, sparing the patient discomfort and uncertainty.
The RRVAMC cost analysis data show an average realistic cost at this setting (considering already available resources) of far less than $2,000 ($1,000-$1,500). This is substantially below the $2,000 to $10,000 cost per case (or lesion in patients with multiple lesions) that would have been required for a private sector referral, based on CMS reimbursement rates for Mohs procedures (CPT codes 17311-17315).
An important element in the cost-effectiveness, quality assurance, and time use in this approach is the flexibility of the key operators (surgery and pathology staff) and the sampling technique. For the latter, the pathologist can use the most efficient technique, depending on specimen source and size: The classic Mohs technique for very small (head and neck area) specimens, but serial cross-sectioning or limited sampling of peripheral and deep margins in other situations. All 3 sectioning approaches in the RRVAMC practice proved reliable in assessing the margins, as they were always verified either on permanent sections and/or through retroactive peer review. Furthermore, in a mostly elderly patient population, there is rarely a need for extremely conservative resection of the margins, as the skin often shows wrinkling or redundancy that allows for a more generous healthy rim around the lesion. In such cases, it may be indeed superfluous to apply the protracted and expensive Mohs procedural variant.
The quality assurance aspect of the RRVAMC approach is also important. Examining permanent sections as well as retroactive peer review can uncover diagnostic or processing errors even in the best of laboratories. That error rate in the surgical pathology community may reach more than 1% to 2%.12 In the RRVAMC practice, the major discrepancy rate is usually below 0.2%. There is a reason for concern in any FS laboratory where such monitoring is not done, considering that even BCC can be occasionally confused on FS with other small blue cell malignancies, such as lymphoma or Merkel cell carcinoma.
Conclusion
The authors offer the RRVAMC pathologist-plastic surgeon team approach to definitive skin cancer surgery as a reliable and less expensive in-house alternative to contractual outsourcing for those VA (or non-VA) medical centers that have a plastic surgeon (or trained equivalent) and a surgical pathologist on staff.
Acknowledgements
This material is the result of work supported with resources and the use of facilities at the Robley Rex VAMC in Louisville, Kentucky.
Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.
Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.
1. Robins P, Albom MJ. Mohs’ surgery—fresh tissue technique. J Dermatol Surg. 1975;1(2):37-41.
2. Mohs FE. Mohs micrographic surgery. A historical perspective. Dermatol Clin. 1989;7(4):609-611.
3. Mohs FE. Origin and progress of Mohs micrographic surgery. In: Mikhail GR, ed. Mohs Micrographic Surgery. Philadelphia, PA: WB Saunders; 1991:1-10.
4. Rowe DE, Carroll RJ, Day CL Jr. Prognostic factors for local recurrence, metastasis, and survival rates in squamous cell carcinoma of the skin, ear, and lip. Implications for treatment modality selection. J Am Acad Dermatol. 1992;26(6):976-990.
5. Rowe DE. Comparison of treatment modalities for basal cell carcinoma. Clin Dermatol. 1995;13(6):617-620.
6. Smeets NW, Krekels GA, Ostertag JU, et al. Surgical excision vs Mohs’ micrographic surgery for basal-cell carcinoma of the face: Randomised controlled trial. Lancet. 2004;364(9447):1766-1772.
7. Bentkover SH, Grande DM, Soto H, Kozlicak BA, Guillaume D, Girouard S. Excision of head and neck basal cell carcinoma with a rapid, cross-sectional, frozen-section technique. Arch Facial Plast Surg. 2002;4(2):114-119.
8. Kimyai-Asadi A, Goldberg LH, Jih MH. Accuracy of serial transverse cross-sections in detecting residual basal cell carcinoma at the surgical margins of an elliptical excision specimen. J Am Acad Dermatol. 2004;53(3):469-474.
9. Dhingra N, Gajdasty A, Neal JW, Mukherjee AN, Lane CM. Confident complete excision of lid-margin BCCs using a marginal strip: An alternative to Mohs’ surgery. Brit J Ophthalmol. 2007;91(6):794-796.
10. Minton TJ. Contemporary Mohs surgery applications. Curr Opin Otolaryngol Head Neck Surg. 2008;16(4):376-380.
11. Mosterd K, Krekels GA, Nieman FH, et al. Surgical excision versus Mohs’ micrographic surgery for primary and recurrent basal-cell carcinoma of the face: A prospective randomised controlled trial with 5-years’ follow-up. Lancet Oncol. 2008;9(12):1149-1156.
12. Weiss MA. Analytic variables; diagnostic accuracy. In: Nakhleh RE, Fitzgibbons PL, eds. Quality Management in Anatomic Pathology. Northfield, IL: College of American Pathologists; 2005:50-76.
1. Robins P, Albom MJ. Mohs’ surgery—fresh tissue technique. J Dermatol Surg. 1975;1(2):37-41.
2. Mohs FE. Mohs micrographic surgery. A historical perspective. Dermatol Clin. 1989;7(4):609-611.
3. Mohs FE. Origin and progress of Mohs micrographic surgery. In: Mikhail GR, ed. Mohs Micrographic Surgery. Philadelphia, PA: WB Saunders; 1991:1-10.
4. Rowe DE, Carroll RJ, Day CL Jr. Prognostic factors for local recurrence, metastasis, and survival rates in squamous cell carcinoma of the skin, ear, and lip. Implications for treatment modality selection. J Am Acad Dermatol. 1992;26(6):976-990.
5. Rowe DE. Comparison of treatment modalities for basal cell carcinoma. Clin Dermatol. 1995;13(6):617-620.
6. Smeets NW, Krekels GA, Ostertag JU, et al. Surgical excision vs Mohs’ micrographic surgery for basal-cell carcinoma of the face: Randomised controlled trial. Lancet. 2004;364(9447):1766-1772.
7. Bentkover SH, Grande DM, Soto H, Kozlicak BA, Guillaume D, Girouard S. Excision of head and neck basal cell carcinoma with a rapid, cross-sectional, frozen-section technique. Arch Facial Plast Surg. 2002;4(2):114-119.
8. Kimyai-Asadi A, Goldberg LH, Jih MH. Accuracy of serial transverse cross-sections in detecting residual basal cell carcinoma at the surgical margins of an elliptical excision specimen. J Am Acad Dermatol. 2004;53(3):469-474.
9. Dhingra N, Gajdasty A, Neal JW, Mukherjee AN, Lane CM. Confident complete excision of lid-margin BCCs using a marginal strip: An alternative to Mohs’ surgery. Brit J Ophthalmol. 2007;91(6):794-796.
10. Minton TJ. Contemporary Mohs surgery applications. Curr Opin Otolaryngol Head Neck Surg. 2008;16(4):376-380.
11. Mosterd K, Krekels GA, Nieman FH, et al. Surgical excision versus Mohs’ micrographic surgery for primary and recurrent basal-cell carcinoma of the face: A prospective randomised controlled trial with 5-years’ follow-up. Lancet Oncol. 2008;9(12):1149-1156.
12. Weiss MA. Analytic variables; diagnostic accuracy. In: Nakhleh RE, Fitzgibbons PL, eds. Quality Management in Anatomic Pathology. Northfield, IL: College of American Pathologists; 2005:50-76.
New law will speed sunscreen ingredient approval
President Obama has signed into law a bill that requires speedier review of sunscreen ingredients.
The Sunscreen Innovation Act garnered support from Democrats and Republicans in the House and Senate, and from manufacturers and dermatologists as well. The House and Senate reconciled their two proposals – S. 2141 and H.R. 4250 – in mid-November, and the final bill was signed by the president on Nov. 26.
The law sets strict timetables for Food and Drug Administration action. The bill was prompted by a huge backlog of ingredients that have been awaiting review at the agency.
According to the PASS Coalition, the last new over-the-counter sunscreen ingredient was approved in the 1990s. Manufacturers have sought approval for eight new ingredients since 2002, but none has been acted on, according to PASS, an advocacy group made up of manufacturers, physicians, and organizations including the American Cancer Society Cancer Action Network, the American College of Mohs Surgery, and the Melanoma International Foundation.
The approval by Congress of the new law “signals the urgent public health need to make more effective products available to consumers, as skin cancer rates continue to rise at an alarming pace,” American Academy of Dermatology President Brett M. Coldiron said in a statement issued in mid-November. “The AADA looks forward to working closely with the FDA to implement the new law, and will be providing comments on its implementation,” said Dr. Coldiron.
Rep. Ed Whitfield (R-Ky.), a coauthor of the original House bill, said that it had been too long since the approval of a new sunscreen ingredient. “With the president’s signature, Americans will finally be able to begin purchasing products that take advantage of improved research,” said Rep. Whitfield, in a statement.
President Obama has signed into law a bill that requires speedier review of sunscreen ingredients.
The Sunscreen Innovation Act garnered support from Democrats and Republicans in the House and Senate, and from manufacturers and dermatologists as well. The House and Senate reconciled their two proposals – S. 2141 and H.R. 4250 – in mid-November, and the final bill was signed by the president on Nov. 26.
The law sets strict timetables for Food and Drug Administration action. The bill was prompted by a huge backlog of ingredients that have been awaiting review at the agency.
According to the PASS Coalition, the last new over-the-counter sunscreen ingredient was approved in the 1990s. Manufacturers have sought approval for eight new ingredients since 2002, but none has been acted on, according to PASS, an advocacy group made up of manufacturers, physicians, and organizations including the American Cancer Society Cancer Action Network, the American College of Mohs Surgery, and the Melanoma International Foundation.
The approval by Congress of the new law “signals the urgent public health need to make more effective products available to consumers, as skin cancer rates continue to rise at an alarming pace,” American Academy of Dermatology President Brett M. Coldiron said in a statement issued in mid-November. “The AADA looks forward to working closely with the FDA to implement the new law, and will be providing comments on its implementation,” said Dr. Coldiron.
Rep. Ed Whitfield (R-Ky.), a coauthor of the original House bill, said that it had been too long since the approval of a new sunscreen ingredient. “With the president’s signature, Americans will finally be able to begin purchasing products that take advantage of improved research,” said Rep. Whitfield, in a statement.
President Obama has signed into law a bill that requires speedier review of sunscreen ingredients.
The Sunscreen Innovation Act garnered support from Democrats and Republicans in the House and Senate, and from manufacturers and dermatologists as well. The House and Senate reconciled their two proposals – S. 2141 and H.R. 4250 – in mid-November, and the final bill was signed by the president on Nov. 26.
The law sets strict timetables for Food and Drug Administration action. The bill was prompted by a huge backlog of ingredients that have been awaiting review at the agency.
According to the PASS Coalition, the last new over-the-counter sunscreen ingredient was approved in the 1990s. Manufacturers have sought approval for eight new ingredients since 2002, but none has been acted on, according to PASS, an advocacy group made up of manufacturers, physicians, and organizations including the American Cancer Society Cancer Action Network, the American College of Mohs Surgery, and the Melanoma International Foundation.
The approval by Congress of the new law “signals the urgent public health need to make more effective products available to consumers, as skin cancer rates continue to rise at an alarming pace,” American Academy of Dermatology President Brett M. Coldiron said in a statement issued in mid-November. “The AADA looks forward to working closely with the FDA to implement the new law, and will be providing comments on its implementation,” said Dr. Coldiron.
Rep. Ed Whitfield (R-Ky.), a coauthor of the original House bill, said that it had been too long since the approval of a new sunscreen ingredient. “With the president’s signature, Americans will finally be able to begin purchasing products that take advantage of improved research,” said Rep. Whitfield, in a statement.
Biopsy can underestimate diversity, aggressiveness of basal cell carcinomas
SAN DIEGO – Histology of basal cell carcinomas removed by Mohs micrographic surgery showed that presurgical biopsies had not revealed all tumor subtypes in 64% of cases, and had underestimated the aggressiveness of the tumors 24% of the time, according to data from a large, multicenter, retrospective study.
“Unfortunately, while cheap and cost-effective, biopsies are a subsample of the full malignancy,” said Dr. Murad Alam, professor of dermatology, otolaryngology, and surgery at Northwestern University in Chicago. “Skin biopsy of basal cell carcinoma [BCC] may fail to detect all BCC subtypes, and as such may underestimate the aggressiveness of an individual BCC tumor.”
Basal cell carcinoma is the most common skin cancer worldwide, and can broadly be grouped into aggressive and indolent types, Dr. Alam said at the annual meeting of the American Society for Dermatologic Surgery. But tumors often show mixed histology, and cancer treatment needs to target the most aggressive subtype present in the tumor, he added. Results of past studies suggested that biopsies of BCCs could miss tumor subtypes, but the current research is the first large, multicenter study to confirm these findings, he and his associates said.
For the study, the investigators compared biopsy reports and microscopic slides of Mohs micrographic surgery (MMS) specimens from 871 consecutive cases of BCC treated at three hospitals in Illinois from 2013 to 2014. Patients first underwent biopsies, followed by complete excision of their tumors during MMS. Almost 59% of patients were male, and tumors were most commonly removed from the nose or cheek. In all, 78% of biopsies were obtained by the shave technique, but punch and excisional biopsies also were performed, the researchers noted.
Using standard definitions of BCC subtypes, the investigators compared levels of concordance between biopsy and MMS histology findings, Dr. Alam said. They also grouped tumor specimens as high risk (that is, infiltrative, morpheic, micronodular, basosquamous) or low risk (superficial or nodular), and determined whether tumor biopsy and MMS histology yielded the same or discordant risk assessments, he added.
Biopsies identified only 18% of tumors as being of mixed histology, compared with 57% of MMS specimens, said Dr. Alam. Biopsy results matched MMS histologies in only 31% of cases, while in 64% of cases, the MMS specimen yielded more tumor subtypes than the biopsy specimen. The researchers noted that biopsy yielded more subtypes than did MMS in 4% of cases, and that MMS and biopsy subtypes were fully discordant in only four cases.
Dr. Alam and his associates declared no external funding sources or conflicts of interest.
SAN DIEGO – Histology of basal cell carcinomas removed by Mohs micrographic surgery showed that presurgical biopsies had not revealed all tumor subtypes in 64% of cases, and had underestimated the aggressiveness of the tumors 24% of the time, according to data from a large, multicenter, retrospective study.
“Unfortunately, while cheap and cost-effective, biopsies are a subsample of the full malignancy,” said Dr. Murad Alam, professor of dermatology, otolaryngology, and surgery at Northwestern University in Chicago. “Skin biopsy of basal cell carcinoma [BCC] may fail to detect all BCC subtypes, and as such may underestimate the aggressiveness of an individual BCC tumor.”
Basal cell carcinoma is the most common skin cancer worldwide, and can broadly be grouped into aggressive and indolent types, Dr. Alam said at the annual meeting of the American Society for Dermatologic Surgery. But tumors often show mixed histology, and cancer treatment needs to target the most aggressive subtype present in the tumor, he added. Results of past studies suggested that biopsies of BCCs could miss tumor subtypes, but the current research is the first large, multicenter study to confirm these findings, he and his associates said.
For the study, the investigators compared biopsy reports and microscopic slides of Mohs micrographic surgery (MMS) specimens from 871 consecutive cases of BCC treated at three hospitals in Illinois from 2013 to 2014. Patients first underwent biopsies, followed by complete excision of their tumors during MMS. Almost 59% of patients were male, and tumors were most commonly removed from the nose or cheek. In all, 78% of biopsies were obtained by the shave technique, but punch and excisional biopsies also were performed, the researchers noted.
Using standard definitions of BCC subtypes, the investigators compared levels of concordance between biopsy and MMS histology findings, Dr. Alam said. They also grouped tumor specimens as high risk (that is, infiltrative, morpheic, micronodular, basosquamous) or low risk (superficial or nodular), and determined whether tumor biopsy and MMS histology yielded the same or discordant risk assessments, he added.
Biopsies identified only 18% of tumors as being of mixed histology, compared with 57% of MMS specimens, said Dr. Alam. Biopsy results matched MMS histologies in only 31% of cases, while in 64% of cases, the MMS specimen yielded more tumor subtypes than the biopsy specimen. The researchers noted that biopsy yielded more subtypes than did MMS in 4% of cases, and that MMS and biopsy subtypes were fully discordant in only four cases.
Dr. Alam and his associates declared no external funding sources or conflicts of interest.
SAN DIEGO – Histology of basal cell carcinomas removed by Mohs micrographic surgery showed that presurgical biopsies had not revealed all tumor subtypes in 64% of cases, and had underestimated the aggressiveness of the tumors 24% of the time, according to data from a large, multicenter, retrospective study.
“Unfortunately, while cheap and cost-effective, biopsies are a subsample of the full malignancy,” said Dr. Murad Alam, professor of dermatology, otolaryngology, and surgery at Northwestern University in Chicago. “Skin biopsy of basal cell carcinoma [BCC] may fail to detect all BCC subtypes, and as such may underestimate the aggressiveness of an individual BCC tumor.”
Basal cell carcinoma is the most common skin cancer worldwide, and can broadly be grouped into aggressive and indolent types, Dr. Alam said at the annual meeting of the American Society for Dermatologic Surgery. But tumors often show mixed histology, and cancer treatment needs to target the most aggressive subtype present in the tumor, he added. Results of past studies suggested that biopsies of BCCs could miss tumor subtypes, but the current research is the first large, multicenter study to confirm these findings, he and his associates said.
For the study, the investigators compared biopsy reports and microscopic slides of Mohs micrographic surgery (MMS) specimens from 871 consecutive cases of BCC treated at three hospitals in Illinois from 2013 to 2014. Patients first underwent biopsies, followed by complete excision of their tumors during MMS. Almost 59% of patients were male, and tumors were most commonly removed from the nose or cheek. In all, 78% of biopsies were obtained by the shave technique, but punch and excisional biopsies also were performed, the researchers noted.
Using standard definitions of BCC subtypes, the investigators compared levels of concordance between biopsy and MMS histology findings, Dr. Alam said. They also grouped tumor specimens as high risk (that is, infiltrative, morpheic, micronodular, basosquamous) or low risk (superficial or nodular), and determined whether tumor biopsy and MMS histology yielded the same or discordant risk assessments, he added.
Biopsies identified only 18% of tumors as being of mixed histology, compared with 57% of MMS specimens, said Dr. Alam. Biopsy results matched MMS histologies in only 31% of cases, while in 64% of cases, the MMS specimen yielded more tumor subtypes than the biopsy specimen. The researchers noted that biopsy yielded more subtypes than did MMS in 4% of cases, and that MMS and biopsy subtypes were fully discordant in only four cases.
Dr. Alam and his associates declared no external funding sources or conflicts of interest.
Key clinical point: Definitive excision by Mohs micrographic surgery reveals more information about basal cell carcinoma subtypes and tumor behavior than does biopsy.
Major finding: Compared with Mohs specimens, biopsy underestimated the diversity of tumor subtypes in 64% of cases, and underestimated tumor aggressiveness in 24% of cases.
Data source: Multicenter retrospective study of 871 basal cell carcinomas that were biopsied and then removed by Mohs micrographic surgery.
Disclosures: The investigators declared no external funding sources or conflicts of interest.
Vismodegib offers promise for basal cell carcinoma, with caveats
SAN DIEGO – Patients treated with vismodegib for locally advanced or metastatic basal cell carcinoma went a median of 15 months before their disease progressed or they stopped treatment because of side effects, according to a 30-month update of the pivotal ERIVANCE basal cell carcinoma study.
Median progression-free survival on the first-in-class oral hedgehog-pathway inhibitor was 9 months, reported Dr. Seaver Soon at the annual meeting of the American Society for Dermatologic Surgery.
Data from two other trials of vismodegib resemble results from ERIVANCE, added Dr. Soon, a dermatologist in private practice in La Jolla, Calif. An expanded access study (J. Am. Acad. Dermatol 2014;70:60-9) of 119 patients with advanced basal cell carcinoma (BCC) reported comparable objective response rates (46.4% for patients with locally advanced BCC and 30.8% for patients with metastatic disease), and an interim analysis of data from the STEVIE trial had findings that were “very similar” to ERIVANCE, he said.
Thus far, vismodegib “offers a hope in treating otherwise difficult to manage, unresectable basal cell carcinoma tumors,” said Dr. Iren Kossintseva, a dermatologist in Vancouver, B.C. But the drug “may not be as tissue sparing as promised, she added. In a patient with chronic lymphocytic leukemia who had a large BCC on his lower eyelid and cheek, 7.5 months of vismodegib reduced the exophyticity and erosiveness of the tumor, but “likely did not substantially reduce the overall extent of necessary reconstruction,” she reported.
Vismodegib can cause potentially severe side effects. All seven patients who Dr. Kossintseva treated with 150 mg vismodegib per day during 2013-2014 developed “notable” adverse effects – including polycyclic rash, sensory and motor problems within the tumor area, bilateral edema of the lower limbs, congestive heart failure, and renal failure that has been slow to improve after stopping vismodegib, she said. “These are unique patients, and it’s often an uphill battle with these patients,” she added.
Tumors also can exhibit primary and secondary resistance to vismodegib, Dr. Soon noted. Studies have shown primary resistance characterized by tumor progression after as little as 2 months of treatment (Mol. Oncol. 2014; S1574-7891:00216-6) while secondary (or acquired) resistance occurs after an initial response to treatment and is linked to a mutation that interferes with drug binding, he said. Acquired resistance typically occurs when patients have been on vismodegib for about a year, Dr. Soon added. “Concurrent treatment with an alternative smoothened inhibitor, such as itraconazole, and downstream target inhibitors may overcome resistance,” he said. Dr. Kossintseva declared no conflicts of interest. Dr. Soon reported receiving honoraria and research grants from Genentech, the maker of vismodegib.
SAN DIEGO – Patients treated with vismodegib for locally advanced or metastatic basal cell carcinoma went a median of 15 months before their disease progressed or they stopped treatment because of side effects, according to a 30-month update of the pivotal ERIVANCE basal cell carcinoma study.
Median progression-free survival on the first-in-class oral hedgehog-pathway inhibitor was 9 months, reported Dr. Seaver Soon at the annual meeting of the American Society for Dermatologic Surgery.
Data from two other trials of vismodegib resemble results from ERIVANCE, added Dr. Soon, a dermatologist in private practice in La Jolla, Calif. An expanded access study (J. Am. Acad. Dermatol 2014;70:60-9) of 119 patients with advanced basal cell carcinoma (BCC) reported comparable objective response rates (46.4% for patients with locally advanced BCC and 30.8% for patients with metastatic disease), and an interim analysis of data from the STEVIE trial had findings that were “very similar” to ERIVANCE, he said.
Thus far, vismodegib “offers a hope in treating otherwise difficult to manage, unresectable basal cell carcinoma tumors,” said Dr. Iren Kossintseva, a dermatologist in Vancouver, B.C. But the drug “may not be as tissue sparing as promised, she added. In a patient with chronic lymphocytic leukemia who had a large BCC on his lower eyelid and cheek, 7.5 months of vismodegib reduced the exophyticity and erosiveness of the tumor, but “likely did not substantially reduce the overall extent of necessary reconstruction,” she reported.
Vismodegib can cause potentially severe side effects. All seven patients who Dr. Kossintseva treated with 150 mg vismodegib per day during 2013-2014 developed “notable” adverse effects – including polycyclic rash, sensory and motor problems within the tumor area, bilateral edema of the lower limbs, congestive heart failure, and renal failure that has been slow to improve after stopping vismodegib, she said. “These are unique patients, and it’s often an uphill battle with these patients,” she added.
Tumors also can exhibit primary and secondary resistance to vismodegib, Dr. Soon noted. Studies have shown primary resistance characterized by tumor progression after as little as 2 months of treatment (Mol. Oncol. 2014; S1574-7891:00216-6) while secondary (or acquired) resistance occurs after an initial response to treatment and is linked to a mutation that interferes with drug binding, he said. Acquired resistance typically occurs when patients have been on vismodegib for about a year, Dr. Soon added. “Concurrent treatment with an alternative smoothened inhibitor, such as itraconazole, and downstream target inhibitors may overcome resistance,” he said. Dr. Kossintseva declared no conflicts of interest. Dr. Soon reported receiving honoraria and research grants from Genentech, the maker of vismodegib.
SAN DIEGO – Patients treated with vismodegib for locally advanced or metastatic basal cell carcinoma went a median of 15 months before their disease progressed or they stopped treatment because of side effects, according to a 30-month update of the pivotal ERIVANCE basal cell carcinoma study.
Median progression-free survival on the first-in-class oral hedgehog-pathway inhibitor was 9 months, reported Dr. Seaver Soon at the annual meeting of the American Society for Dermatologic Surgery.
Data from two other trials of vismodegib resemble results from ERIVANCE, added Dr. Soon, a dermatologist in private practice in La Jolla, Calif. An expanded access study (J. Am. Acad. Dermatol 2014;70:60-9) of 119 patients with advanced basal cell carcinoma (BCC) reported comparable objective response rates (46.4% for patients with locally advanced BCC and 30.8% for patients with metastatic disease), and an interim analysis of data from the STEVIE trial had findings that were “very similar” to ERIVANCE, he said.
Thus far, vismodegib “offers a hope in treating otherwise difficult to manage, unresectable basal cell carcinoma tumors,” said Dr. Iren Kossintseva, a dermatologist in Vancouver, B.C. But the drug “may not be as tissue sparing as promised, she added. In a patient with chronic lymphocytic leukemia who had a large BCC on his lower eyelid and cheek, 7.5 months of vismodegib reduced the exophyticity and erosiveness of the tumor, but “likely did not substantially reduce the overall extent of necessary reconstruction,” she reported.
Vismodegib can cause potentially severe side effects. All seven patients who Dr. Kossintseva treated with 150 mg vismodegib per day during 2013-2014 developed “notable” adverse effects – including polycyclic rash, sensory and motor problems within the tumor area, bilateral edema of the lower limbs, congestive heart failure, and renal failure that has been slow to improve after stopping vismodegib, she said. “These are unique patients, and it’s often an uphill battle with these patients,” she added.
Tumors also can exhibit primary and secondary resistance to vismodegib, Dr. Soon noted. Studies have shown primary resistance characterized by tumor progression after as little as 2 months of treatment (Mol. Oncol. 2014; S1574-7891:00216-6) while secondary (or acquired) resistance occurs after an initial response to treatment and is linked to a mutation that interferes with drug binding, he said. Acquired resistance typically occurs when patients have been on vismodegib for about a year, Dr. Soon added. “Concurrent treatment with an alternative smoothened inhibitor, such as itraconazole, and downstream target inhibitors may overcome resistance,” he said. Dr. Kossintseva declared no conflicts of interest. Dr. Soon reported receiving honoraria and research grants from Genentech, the maker of vismodegib.
Dabrafenib and trametinib combo boosts melanoma survival
The combination of dabrafenib and trametinib achieves significant improvements in overall survival and progression-free survival in patients with untreated metastatic melanoma compared with treatment with vemurafenib alone, new data suggest.
An open-label randomized phase III trial showed the combination of BRAF inhibitor dabrafenib with MEK inhibitor trametinib in patients with BRAF V600E or V600K mutant melanoma resulted in a significant reduction in death rates at 12 months compared with monotherapy with BRAF inhibitor vemurafenib (HR 0.69, 95% CI 0.53-0.89, P = .005).
Researchers observed a median progression-free survival rate of 11.4 months in the combination arm, compared with 7.3 months in the monotherapy arm (HR 0.56, 95% CI 0.46-0.69, P < .001), according to data presented at the 2014 International Congress for the Society for Melanoma Research.
The most common adverse event was fever, experienced by 53% of patients in the combination arm and 21% of patients in the monotherapy arm; however, there were more grade 3 and 4 adverse events noted among patients treated with vemurafenib alone.
Pyrexia was the most common reason for dose interruption or reduction in the dabrafenib-plus-trametinib group, while rash was the same for the vemurafenib group.
The study, which presented data from a preplanned interim analysis of 704 patients and 222 events, showed an overall response rate of 64% for the combination of dabrafenib and trametinib, and 51% among those treated with vemurafenib alone.
In a paper published simultaneously online Nov. 16 in the New England Journal of Medicine, researchers said that combining a BRAF inhibitor with a MEK inhibitor could address some of the limitations of monotherapy by delaying the development of resistance and reducing the incidence of BRAF inhibitor–induced skin tumors (N. Engl. J. Med. 2014 Nov. 16 [doi: 10.1056/NEJMoa1412690]).
“Together with the previously reported phase II and phase III trials of dabrafenib plus trametinib, as compared with dabrafenib monotherapy, these data provide clear evidence for the benefit of this combination therapy over BRAF monotherapy in prolonging survival,” wrote Dr. Caroline Robert of Institut Gustave Roussy, Paris, and her colleagues.
The researchers noted that more patients in the vemurafenib monotherapy arm received further anticancer therapy than in the combination arm (43% vs. 20%).
The study was supported by GlaxoSmithKline. Some authors declared grants, travel expenses, and personal fees from pharmaceutical companies including GlaxoSmithKline, and several were employees of the company.
The combination of dabrafenib and trametinib achieves significant improvements in overall survival and progression-free survival in patients with untreated metastatic melanoma compared with treatment with vemurafenib alone, new data suggest.
An open-label randomized phase III trial showed the combination of BRAF inhibitor dabrafenib with MEK inhibitor trametinib in patients with BRAF V600E or V600K mutant melanoma resulted in a significant reduction in death rates at 12 months compared with monotherapy with BRAF inhibitor vemurafenib (HR 0.69, 95% CI 0.53-0.89, P = .005).
Researchers observed a median progression-free survival rate of 11.4 months in the combination arm, compared with 7.3 months in the monotherapy arm (HR 0.56, 95% CI 0.46-0.69, P < .001), according to data presented at the 2014 International Congress for the Society for Melanoma Research.
The most common adverse event was fever, experienced by 53% of patients in the combination arm and 21% of patients in the monotherapy arm; however, there were more grade 3 and 4 adverse events noted among patients treated with vemurafenib alone.
Pyrexia was the most common reason for dose interruption or reduction in the dabrafenib-plus-trametinib group, while rash was the same for the vemurafenib group.
The study, which presented data from a preplanned interim analysis of 704 patients and 222 events, showed an overall response rate of 64% for the combination of dabrafenib and trametinib, and 51% among those treated with vemurafenib alone.
In a paper published simultaneously online Nov. 16 in the New England Journal of Medicine, researchers said that combining a BRAF inhibitor with a MEK inhibitor could address some of the limitations of monotherapy by delaying the development of resistance and reducing the incidence of BRAF inhibitor–induced skin tumors (N. Engl. J. Med. 2014 Nov. 16 [doi: 10.1056/NEJMoa1412690]).
“Together with the previously reported phase II and phase III trials of dabrafenib plus trametinib, as compared with dabrafenib monotherapy, these data provide clear evidence for the benefit of this combination therapy over BRAF monotherapy in prolonging survival,” wrote Dr. Caroline Robert of Institut Gustave Roussy, Paris, and her colleagues.
The researchers noted that more patients in the vemurafenib monotherapy arm received further anticancer therapy than in the combination arm (43% vs. 20%).
The study was supported by GlaxoSmithKline. Some authors declared grants, travel expenses, and personal fees from pharmaceutical companies including GlaxoSmithKline, and several were employees of the company.
The combination of dabrafenib and trametinib achieves significant improvements in overall survival and progression-free survival in patients with untreated metastatic melanoma compared with treatment with vemurafenib alone, new data suggest.
An open-label randomized phase III trial showed the combination of BRAF inhibitor dabrafenib with MEK inhibitor trametinib in patients with BRAF V600E or V600K mutant melanoma resulted in a significant reduction in death rates at 12 months compared with monotherapy with BRAF inhibitor vemurafenib (HR 0.69, 95% CI 0.53-0.89, P = .005).
Researchers observed a median progression-free survival rate of 11.4 months in the combination arm, compared with 7.3 months in the monotherapy arm (HR 0.56, 95% CI 0.46-0.69, P < .001), according to data presented at the 2014 International Congress for the Society for Melanoma Research.
The most common adverse event was fever, experienced by 53% of patients in the combination arm and 21% of patients in the monotherapy arm; however, there were more grade 3 and 4 adverse events noted among patients treated with vemurafenib alone.
Pyrexia was the most common reason for dose interruption or reduction in the dabrafenib-plus-trametinib group, while rash was the same for the vemurafenib group.
The study, which presented data from a preplanned interim analysis of 704 patients and 222 events, showed an overall response rate of 64% for the combination of dabrafenib and trametinib, and 51% among those treated with vemurafenib alone.
In a paper published simultaneously online Nov. 16 in the New England Journal of Medicine, researchers said that combining a BRAF inhibitor with a MEK inhibitor could address some of the limitations of monotherapy by delaying the development of resistance and reducing the incidence of BRAF inhibitor–induced skin tumors (N. Engl. J. Med. 2014 Nov. 16 [doi: 10.1056/NEJMoa1412690]).
“Together with the previously reported phase II and phase III trials of dabrafenib plus trametinib, as compared with dabrafenib monotherapy, these data provide clear evidence for the benefit of this combination therapy over BRAF monotherapy in prolonging survival,” wrote Dr. Caroline Robert of Institut Gustave Roussy, Paris, and her colleagues.
The researchers noted that more patients in the vemurafenib monotherapy arm received further anticancer therapy than in the combination arm (43% vs. 20%).
The study was supported by GlaxoSmithKline. Some authors declared grants, travel expenses, and personal fees from pharmaceutical companies including GlaxoSmithKline, and several were employees of the company.
FROM THE SMR INTERNATIONAL CONGRESS
Key clinical point: The combination of dabrafenib and trametinib boosts overall survival and progression-free survival compared with vemurafenib alone in metastatic BRAF V600E or V600K mutant melanoma.
Major finding: Dabrafenib plus trametinib achieved a 31% reduction in mortality at 12 months compared with vemurafenib.
Data source: Preplanned interim analysis from an open-label randomized phase III trial of 704 patients with untreated, metastatic melanoma.
Disclosures: Several of the researchers disclosed ties with GlaxoSmithKline, which funded the study.
Nivolumab bests dacarbazine for melanoma survival
Nivolumab achieves significant improvements in overall survival and progression-free survival compared with conventional chemotherapy in untreated patients with advanced melanoma, regardless of PD-L1 status, according to data presented at the International Congress for the Society for Melanoma Research.
Data from a randomized, double-blind, placebo-controlled phase III trial showed patients treated with nivolumab – a PD-1 immune checkpoint inhibitor – showed there was a 58% lower incidence of death at 1 year among patients treated with nivolumab compared with those treated with dacarbazine (72.9% vs. 42.1% HR 0.42, 95% CI 0.25-0.73, P < .001).
Median progression-free survival was 5.1 months in the nivolumab arm compared with 2.2 months in the dacarbazine group (HR for death or disease progression: 0.43, 95% CI 0.34-0.56, P < .001). The results were published simultaneously online Nov. 16 in the New England Journal of Medicine.
Researchers randomly assigned 418 previously untreated patients with BRAF mutation-negative advanced melanoma to nivolumab plus placebo, and dacarbazine plus placebo, finding an objective response rate of 40% in patients receiving nivolumab compared with 13.9% in the dacarbazine group.
While PD-L1-positive patients treated with nivolumab showed a greater median response rate compared with PD-L1-negative or indeterminate patients (52.7% vs. 33.1%), both still achieved greater response than either subgroup treated with dacarbazine (N. Engl. J. Med. 2014 Nov. 16 [doi:10.1056/NEJMoa1412082]).
The overall incidence of treatment-related adverse events was similar in the two study arms, although there was a higher incidence of treatment-related grade 3 and 4 adverse events, such as gastrointestinal and hematologic events, in the dacarbazine group.
“It has generally been accepted that immunotherapy is associated with long-term responses in a subset of patients, whereas targeted therapies, such as BRAF inhibitors, are associated with high response rates and a rapid effect, but the responses are often short-lived,” wrote Dr. Caroline Robert of Institut Gustave Roussy, Paris, and her colleagues.
“The present study shows nivolumab is associated with a high response rate, a rapid median time to response (2.1 months, which is similar to the time to response for dacarbazine), and a durable response (the median duration of response was not reached but the duration of follow-up was short),” the investigators said.
The study was supported by Bristol Myers-Squibb. Some authors declared grants, travel expenses, and personal fees from pharmaceutical companies including Bristol Myers-Squibb, and several were employees of the company.
Nivolumab achieves significant improvements in overall survival and progression-free survival compared with conventional chemotherapy in untreated patients with advanced melanoma, regardless of PD-L1 status, according to data presented at the International Congress for the Society for Melanoma Research.
Data from a randomized, double-blind, placebo-controlled phase III trial showed patients treated with nivolumab – a PD-1 immune checkpoint inhibitor – showed there was a 58% lower incidence of death at 1 year among patients treated with nivolumab compared with those treated with dacarbazine (72.9% vs. 42.1% HR 0.42, 95% CI 0.25-0.73, P < .001).
Median progression-free survival was 5.1 months in the nivolumab arm compared with 2.2 months in the dacarbazine group (HR for death or disease progression: 0.43, 95% CI 0.34-0.56, P < .001). The results were published simultaneously online Nov. 16 in the New England Journal of Medicine.
Researchers randomly assigned 418 previously untreated patients with BRAF mutation-negative advanced melanoma to nivolumab plus placebo, and dacarbazine plus placebo, finding an objective response rate of 40% in patients receiving nivolumab compared with 13.9% in the dacarbazine group.
While PD-L1-positive patients treated with nivolumab showed a greater median response rate compared with PD-L1-negative or indeterminate patients (52.7% vs. 33.1%), both still achieved greater response than either subgroup treated with dacarbazine (N. Engl. J. Med. 2014 Nov. 16 [doi:10.1056/NEJMoa1412082]).
The overall incidence of treatment-related adverse events was similar in the two study arms, although there was a higher incidence of treatment-related grade 3 and 4 adverse events, such as gastrointestinal and hematologic events, in the dacarbazine group.
“It has generally been accepted that immunotherapy is associated with long-term responses in a subset of patients, whereas targeted therapies, such as BRAF inhibitors, are associated with high response rates and a rapid effect, but the responses are often short-lived,” wrote Dr. Caroline Robert of Institut Gustave Roussy, Paris, and her colleagues.
“The present study shows nivolumab is associated with a high response rate, a rapid median time to response (2.1 months, which is similar to the time to response for dacarbazine), and a durable response (the median duration of response was not reached but the duration of follow-up was short),” the investigators said.
The study was supported by Bristol Myers-Squibb. Some authors declared grants, travel expenses, and personal fees from pharmaceutical companies including Bristol Myers-Squibb, and several were employees of the company.
Nivolumab achieves significant improvements in overall survival and progression-free survival compared with conventional chemotherapy in untreated patients with advanced melanoma, regardless of PD-L1 status, according to data presented at the International Congress for the Society for Melanoma Research.
Data from a randomized, double-blind, placebo-controlled phase III trial showed patients treated with nivolumab – a PD-1 immune checkpoint inhibitor – showed there was a 58% lower incidence of death at 1 year among patients treated with nivolumab compared with those treated with dacarbazine (72.9% vs. 42.1% HR 0.42, 95% CI 0.25-0.73, P < .001).
Median progression-free survival was 5.1 months in the nivolumab arm compared with 2.2 months in the dacarbazine group (HR for death or disease progression: 0.43, 95% CI 0.34-0.56, P < .001). The results were published simultaneously online Nov. 16 in the New England Journal of Medicine.
Researchers randomly assigned 418 previously untreated patients with BRAF mutation-negative advanced melanoma to nivolumab plus placebo, and dacarbazine plus placebo, finding an objective response rate of 40% in patients receiving nivolumab compared with 13.9% in the dacarbazine group.
While PD-L1-positive patients treated with nivolumab showed a greater median response rate compared with PD-L1-negative or indeterminate patients (52.7% vs. 33.1%), both still achieved greater response than either subgroup treated with dacarbazine (N. Engl. J. Med. 2014 Nov. 16 [doi:10.1056/NEJMoa1412082]).
The overall incidence of treatment-related adverse events was similar in the two study arms, although there was a higher incidence of treatment-related grade 3 and 4 adverse events, such as gastrointestinal and hematologic events, in the dacarbazine group.
“It has generally been accepted that immunotherapy is associated with long-term responses in a subset of patients, whereas targeted therapies, such as BRAF inhibitors, are associated with high response rates and a rapid effect, but the responses are often short-lived,” wrote Dr. Caroline Robert of Institut Gustave Roussy, Paris, and her colleagues.
“The present study shows nivolumab is associated with a high response rate, a rapid median time to response (2.1 months, which is similar to the time to response for dacarbazine), and a durable response (the median duration of response was not reached but the duration of follow-up was short),” the investigators said.
The study was supported by Bristol Myers-Squibb. Some authors declared grants, travel expenses, and personal fees from pharmaceutical companies including Bristol Myers-Squibb, and several were employees of the company.
FROM THE SMR INTERNATIONAL CONGRESS
Key clinical point: Nivolumab achieves significant improvements in overall survival and progression-free survival compared with dacarbazine in untreated patients with advanced melanoma.
Major finding: Nivolumab was associated with a 58% lower incidence of death at 1 year compared with dacarbazine
Data source: Randomized, double-blind, placebo-controlled phase III trial of 418 previously-untreated patients with advanced melanoma.
Disclosures: Several of the researchers disclosed ties with Bristol-Myers Squibb, which funded the study.
Skin cancer treatment costs skyrocket over past decade
The average annual cost for skin cancer treatment more than doubled from 2002 to 2011, a report from the Centers for Disease Control and Prevention found.
From 2002 to 2006, the average annual skin cancer treatment cost was $3.6 billion, while for 2007-2011, the average annual cost was $8.1 billion, an increase of about 126%. The cost of nonmelanoma skin cancers increased 74%, from $2.7 billion to $4.8 billion, but the average annual cost for melanoma cancers increased about 280%, from $864 million to $3.3 billion, according to the CDC (Am. J. Prev. Med. 2014 Nov. 9 [doi:10.1016/j.amepre.2014.08.036]).
From 2002 to 2006, the average annual number of adults treated for skin cancer was 3.4 million, which increased to an average annual number of 4.9 million for 2007-2011. The average annual cost per person for all skin cancers increased by 57%, from $1,044 for 2002-2006 to $1,643 for 2007-2011, while the average cost for melanomas more than doubled from $2,320 to $4,780. The increase in annual cost for nonmelanoma skin cancers was more modest; only a 25% increase, from $882 to $1,105, was noted between the two time periods, the CDC reported.
The average annual cost for all cancer treatment rose from $67.3 billion for 2002-2006 to $87.8 billion for 2007-2011, an increase of $20.5 billion. While skin cancer treatment costs represented only 5% of all treatment costs in 2002-2006, the increase in skin cancer costs was 22% of the total increase, so from 2007 to 2011, skin cancer represented 9% of all treatment costs, according to data from the Medical Expenditure Panel Survey.
The average annual cost for skin cancer treatment more than doubled from 2002 to 2011, a report from the Centers for Disease Control and Prevention found.
From 2002 to 2006, the average annual skin cancer treatment cost was $3.6 billion, while for 2007-2011, the average annual cost was $8.1 billion, an increase of about 126%. The cost of nonmelanoma skin cancers increased 74%, from $2.7 billion to $4.8 billion, but the average annual cost for melanoma cancers increased about 280%, from $864 million to $3.3 billion, according to the CDC (Am. J. Prev. Med. 2014 Nov. 9 [doi:10.1016/j.amepre.2014.08.036]).
From 2002 to 2006, the average annual number of adults treated for skin cancer was 3.4 million, which increased to an average annual number of 4.9 million for 2007-2011. The average annual cost per person for all skin cancers increased by 57%, from $1,044 for 2002-2006 to $1,643 for 2007-2011, while the average cost for melanomas more than doubled from $2,320 to $4,780. The increase in annual cost for nonmelanoma skin cancers was more modest; only a 25% increase, from $882 to $1,105, was noted between the two time periods, the CDC reported.
The average annual cost for all cancer treatment rose from $67.3 billion for 2002-2006 to $87.8 billion for 2007-2011, an increase of $20.5 billion. While skin cancer treatment costs represented only 5% of all treatment costs in 2002-2006, the increase in skin cancer costs was 22% of the total increase, so from 2007 to 2011, skin cancer represented 9% of all treatment costs, according to data from the Medical Expenditure Panel Survey.
The average annual cost for skin cancer treatment more than doubled from 2002 to 2011, a report from the Centers for Disease Control and Prevention found.
From 2002 to 2006, the average annual skin cancer treatment cost was $3.6 billion, while for 2007-2011, the average annual cost was $8.1 billion, an increase of about 126%. The cost of nonmelanoma skin cancers increased 74%, from $2.7 billion to $4.8 billion, but the average annual cost for melanoma cancers increased about 280%, from $864 million to $3.3 billion, according to the CDC (Am. J. Prev. Med. 2014 Nov. 9 [doi:10.1016/j.amepre.2014.08.036]).
From 2002 to 2006, the average annual number of adults treated for skin cancer was 3.4 million, which increased to an average annual number of 4.9 million for 2007-2011. The average annual cost per person for all skin cancers increased by 57%, from $1,044 for 2002-2006 to $1,643 for 2007-2011, while the average cost for melanomas more than doubled from $2,320 to $4,780. The increase in annual cost for nonmelanoma skin cancers was more modest; only a 25% increase, from $882 to $1,105, was noted between the two time periods, the CDC reported.
The average annual cost for all cancer treatment rose from $67.3 billion for 2002-2006 to $87.8 billion for 2007-2011, an increase of $20.5 billion. While skin cancer treatment costs represented only 5% of all treatment costs in 2002-2006, the increase in skin cancer costs was 22% of the total increase, so from 2007 to 2011, skin cancer represented 9% of all treatment costs, according to data from the Medical Expenditure Panel Survey.
FROM THE AMERICAN JOURNAL OF PREVENTIVE MEDICINE
Health-Related Quality of Life in Skin Cancer Patients
As the most common form of cancer in the United States,1 dermatologists often focus on treating the physical aspects of skin cancer, but it is equally important to consider the consequences that this disease has on a patient’s quality of life (QOL). Health is a dynamic process, encompassing one’s physical, emotional, and psychosocial well-being. There are a number of ways to measure health outcomes including mortality, morbidity, health status, and QOL. In recent years, health-related QOL (HRQOL) outcomes in dermatology have become increasingly important to clinical practice and may become factors in quality measurement or reimbursement.
Understanding a patient’s HRQOL allows health care providers to better evaluate the burden of disease and disability associated with skin cancer and its treatment. Clinical severity is not always able to capture the extent to which a disease affects one’s life.2 Furthermore, physician estimation of disease severity is not always consistent with patient-reported outcomes.3 As such, clinical questionnaires may be invaluable tools capable of objectively reporting a patient’s perception of improvement in health, which may affect how a dermatologist approaches treatment, discussion, and maintenance.
Nonmelanoma Skin Cancer
Most nonmelanoma skin cancer (NMSC) occurs in readily visible areas, namely the head and neck. Surgical treatment minimizes recurrence and complication rates. Nonmelanoma skin cancer has a low mortality and a high cure rate if diagnosed early; therefore, it may be difficult to assess treatment efficacy on cure rates alone. The amalgamation of anxiety associated with the diagnosis, aesthetic and functional concerns regarding treatment, and long-term consequences including fear of future skin cancer may have a lasting effect on an individual’s psychosocial relationships and underscores the need for QOL studies.
Most generic QOL and dermatology-specific QOL instruments fail to accurately detect the concerns of patients with NMSC.4-6 Generic QOL measures used for skin cancer patients report scores of patients that were similar to population norms,4 suggesting that these tools may fail to appropriately assess unique QOL concerns among individuals with skin cancer. Furthermore, dermatology-specific instruments have been reported to be insensitive to specific appearance-related concerns of patients with NMSC, likely because skin cancer patients made up a small percentage of the initial population in their design.4,7 Nevertheless, dermatology-specific instruments may be suitable depending on the objectives of the study.8
Recently, skin cancer–specific QOL instruments have been developed to fill the paucity of appropriate tools for this population. These questionnaires include the Facial Skin Cancer Index, Skin Cancer Index, and the Skin Cancer Quality of Life Impact Tool.7 The Skin Cancer Index is a 15-item questionnaire validated in patients undergoing Mohs micrographic surgery and has been used to assess behavior modification and risk perceptions in NMSC patients. Importantly, it does ask the patient if he/she is worried about scarring. The Facial Skin Cancer Index and the Skin Cancer Quality of Life Impact Tool do not take into account detailed aesthetic concerns regarding facial disfigurement and scarring or expectations of reconstruction.7 It may be prudent to assess these areas with supplemental scales.
Melanoma
Melanoma, the third most common skin cancer, is highly aggressive and can affect young and middle-aged patients. Because the mortality associated with later-stage melanoma is greater, the QOL impact of melanoma differs from NMSC. There are also 3 distinct periods of melanoma HRQOL impact: diagnosis, treatment, and follow-up. Approximately 30% of patients diagnosed with melanoma report high levels of psychological distress.9 The psychosocial effects of a melanoma diagnosis are longitudinal, as there is a high survival rate in early disease but also an increased future risk for melanoma, affecting future behaviors and overall QOL. The diagnosis of melanoma also affects family members due to the increased risk among first-degree relatives. After removal of deeper melanoma, the patient remains at risk for disease progression, which can have a profound impact on his/her social and professional activities and overall lifestyle. There may be a role for longitudinal QOL assessments to monitor changes over time and direct ongoing therapy.
The proportion of patients with melanoma who report high levels of impairment in QOL is comparable to that seen in other malignancies.10 Generic QOL instruments have found that melanoma patients have medium to high levels of distress and substantial improvement in HRQOL has been achieved with cognitive-behavioral intervention.11 Quality-of-life studies also have shown levels of distress are highest at initial diagnosis and immediately following treatment.12 In a randomized surgical trial, patients with a larger excision margin had poorer mental and physical function scores on assessment.13 Skin-specific QOL instruments have been used in studies of patients with melanoma and found that postmelanoma surveillance did not impact QOL. Also, women experienced greater improvements in QOL over time after reporting lower scores immediately postsurgery.13
The FACT-melanoma (Functional Assessment of Cancer Therapy) is a melanoma-specific HRQOL assessment that has been used in patients undergoing clinical trials. It has been shown to distinguish between early and advanced-stage (stages III or IV) HRQOL issues.14 Patients with early-stage melanoma are more concerned with cosmetic outcome, and those with later-stage melanoma are more concerned with morbidity and mortality associated with treatment.
Comment
Choosing the best QOL instrument depends on the specific objectives of the study. Although generic QOL questionnaires have performed poorly in studies of specific skin diseases and even dermatology-specific tools have shown limited responsiveness in skin cancer, a combination of tools may be an effective approach. However, dermatologists must be cautious when administering these valuable tools to ensure that they do not become a burdensome task for the patient.15 Although no single skin cancer–specific QOL tool is perfect, it is likely that the current questionnaires still allow for aid with appropriate patient management and comparison of treatments.16
It behooves clinicians to recognize and appreciate the value of QOL instruments as an important adjunct to treatment. These tools have shown QOL to be an independent predictor of survival among many types of cancer patients, including melanoma.10 Currently, the psychological and emotional needs of skin cancer patients often go overlooked and undetected by conventional methods. Within one’s own practice, introducing QOL assessments can improve patient self-awareness and physician awareness of matters that may have a greater impact on patient health. On a larger scale, introducing patient-reported outcome measures can affect resource allocation by identifying patient populations that may be most impacted and can give a comprehensive method for physicians to gauge treatment efficacy, leading to improved outcomes.
1. Robinson JK. Sun exposure, sun protection, and vitamin D. JAMA. 2005;294:1541-1543.
2. Motley RJ, Finlay AY. Practical use of a disability index in the routine management of acne. Clin Exp Dermatol. 1992;17:1-3.
3. Chren MM, Lasek RJ, Quinn LM, et al. Skindex, a quality-of-life measure for patients with skin disease: reliability, validity, and responsiveness. J Invest Dermatol. 1996;107:707-713.
4. Gibbons EC, Comabella CI, Fitzpatrick R. A structured review of patient-reported outcome measures for patients with skin cancer, 2013. Br J Dermatol. 2013;168:1176-1186.
5. Burdon-Jones D, Thomas P, Baker R. Quality of life issues in nonmetastatic skin cancer. Br J Dermatol. 2010;162:147-151.
6. Lear W, Akeroyd JD, Mittmann N, et al. Measurement of utility in nonmelanoma skin cancer. J Cutan Med Surg. 2008;12:102-106.
7. Bates AS, Davis CR, Takwale A, et al. Patient-reported outcome measures in nonmelanoma skin cancer of the face: a systematic review. Br J Dermatol. 2013;168:1187-1194.
8. Lee EH, Klassen AF, Nehal KS, et al. A systematic review of patient-reported outcome instruments of nonmelanoma skin cancer in the dermatologic population. J Am Acad Dermatol. 2013;69:e59-e67.
9. Kasparian NA. Psychological stress and melanoma: are we meeting our patients’ psychological needs? Clin Dermatol. 2013;31:41-46.
10. Cormier JN, Cromwell KD, Ross MI. Health-related quality of life in patients with melanoma: overview of instruments and outcomes. Dermatol Clin. 2012;30:245-254.
11. Trask PC, Paterson AG, Griffith KA, et al. Cognitive-behavioral intervention for distress in patients with melanoma: comparison with standard medical care and impact on quality of life. Cancer. 2003;98:854-864.
12. Boyle DA. Psychological adjustment to the melanoma experience. Semin Oncol Nurs. 2003;191:70-77.
13. Newton-Bishop JA, Nolan C, Turner F, et al. A quality-of-life study in high-risk (thickness > = or 2 mm) cutaneous melanoma patients in a randomized trial of 1-cm versus 3-cm surgical excision margins. J Investig Dermatol Symp Proc. 2004;9:152-159.
14. Winstanley JB, Saw R, Boyle F, et al. The FACT-Melanoma quality-of-life instrument: comparison of a five-point and four-point response scale using the Rasch measurement model. Melanoma Res. 2013;23:61-69.
15. Swartz RJ, Baum GP, Askew RL, et al. Reducing patient burden to the FACT-Melanoma quality-of-life questionnaire. Melanoma Res. 2012;22:158-163.
16. Black N. Patient-reported outcome measures in skin cancer. Br J Dermatol. 2013;168:1151.
As the most common form of cancer in the United States,1 dermatologists often focus on treating the physical aspects of skin cancer, but it is equally important to consider the consequences that this disease has on a patient’s quality of life (QOL). Health is a dynamic process, encompassing one’s physical, emotional, and psychosocial well-being. There are a number of ways to measure health outcomes including mortality, morbidity, health status, and QOL. In recent years, health-related QOL (HRQOL) outcomes in dermatology have become increasingly important to clinical practice and may become factors in quality measurement or reimbursement.
Understanding a patient’s HRQOL allows health care providers to better evaluate the burden of disease and disability associated with skin cancer and its treatment. Clinical severity is not always able to capture the extent to which a disease affects one’s life.2 Furthermore, physician estimation of disease severity is not always consistent with patient-reported outcomes.3 As such, clinical questionnaires may be invaluable tools capable of objectively reporting a patient’s perception of improvement in health, which may affect how a dermatologist approaches treatment, discussion, and maintenance.
Nonmelanoma Skin Cancer
Most nonmelanoma skin cancer (NMSC) occurs in readily visible areas, namely the head and neck. Surgical treatment minimizes recurrence and complication rates. Nonmelanoma skin cancer has a low mortality and a high cure rate if diagnosed early; therefore, it may be difficult to assess treatment efficacy on cure rates alone. The amalgamation of anxiety associated with the diagnosis, aesthetic and functional concerns regarding treatment, and long-term consequences including fear of future skin cancer may have a lasting effect on an individual’s psychosocial relationships and underscores the need for QOL studies.
Most generic QOL and dermatology-specific QOL instruments fail to accurately detect the concerns of patients with NMSC.4-6 Generic QOL measures used for skin cancer patients report scores of patients that were similar to population norms,4 suggesting that these tools may fail to appropriately assess unique QOL concerns among individuals with skin cancer. Furthermore, dermatology-specific instruments have been reported to be insensitive to specific appearance-related concerns of patients with NMSC, likely because skin cancer patients made up a small percentage of the initial population in their design.4,7 Nevertheless, dermatology-specific instruments may be suitable depending on the objectives of the study.8
Recently, skin cancer–specific QOL instruments have been developed to fill the paucity of appropriate tools for this population. These questionnaires include the Facial Skin Cancer Index, Skin Cancer Index, and the Skin Cancer Quality of Life Impact Tool.7 The Skin Cancer Index is a 15-item questionnaire validated in patients undergoing Mohs micrographic surgery and has been used to assess behavior modification and risk perceptions in NMSC patients. Importantly, it does ask the patient if he/she is worried about scarring. The Facial Skin Cancer Index and the Skin Cancer Quality of Life Impact Tool do not take into account detailed aesthetic concerns regarding facial disfigurement and scarring or expectations of reconstruction.7 It may be prudent to assess these areas with supplemental scales.
Melanoma
Melanoma, the third most common skin cancer, is highly aggressive and can affect young and middle-aged patients. Because the mortality associated with later-stage melanoma is greater, the QOL impact of melanoma differs from NMSC. There are also 3 distinct periods of melanoma HRQOL impact: diagnosis, treatment, and follow-up. Approximately 30% of patients diagnosed with melanoma report high levels of psychological distress.9 The psychosocial effects of a melanoma diagnosis are longitudinal, as there is a high survival rate in early disease but also an increased future risk for melanoma, affecting future behaviors and overall QOL. The diagnosis of melanoma also affects family members due to the increased risk among first-degree relatives. After removal of deeper melanoma, the patient remains at risk for disease progression, which can have a profound impact on his/her social and professional activities and overall lifestyle. There may be a role for longitudinal QOL assessments to monitor changes over time and direct ongoing therapy.
The proportion of patients with melanoma who report high levels of impairment in QOL is comparable to that seen in other malignancies.10 Generic QOL instruments have found that melanoma patients have medium to high levels of distress and substantial improvement in HRQOL has been achieved with cognitive-behavioral intervention.11 Quality-of-life studies also have shown levels of distress are highest at initial diagnosis and immediately following treatment.12 In a randomized surgical trial, patients with a larger excision margin had poorer mental and physical function scores on assessment.13 Skin-specific QOL instruments have been used in studies of patients with melanoma and found that postmelanoma surveillance did not impact QOL. Also, women experienced greater improvements in QOL over time after reporting lower scores immediately postsurgery.13
The FACT-melanoma (Functional Assessment of Cancer Therapy) is a melanoma-specific HRQOL assessment that has been used in patients undergoing clinical trials. It has been shown to distinguish between early and advanced-stage (stages III or IV) HRQOL issues.14 Patients with early-stage melanoma are more concerned with cosmetic outcome, and those with later-stage melanoma are more concerned with morbidity and mortality associated with treatment.
Comment
Choosing the best QOL instrument depends on the specific objectives of the study. Although generic QOL questionnaires have performed poorly in studies of specific skin diseases and even dermatology-specific tools have shown limited responsiveness in skin cancer, a combination of tools may be an effective approach. However, dermatologists must be cautious when administering these valuable tools to ensure that they do not become a burdensome task for the patient.15 Although no single skin cancer–specific QOL tool is perfect, it is likely that the current questionnaires still allow for aid with appropriate patient management and comparison of treatments.16
It behooves clinicians to recognize and appreciate the value of QOL instruments as an important adjunct to treatment. These tools have shown QOL to be an independent predictor of survival among many types of cancer patients, including melanoma.10 Currently, the psychological and emotional needs of skin cancer patients often go overlooked and undetected by conventional methods. Within one’s own practice, introducing QOL assessments can improve patient self-awareness and physician awareness of matters that may have a greater impact on patient health. On a larger scale, introducing patient-reported outcome measures can affect resource allocation by identifying patient populations that may be most impacted and can give a comprehensive method for physicians to gauge treatment efficacy, leading to improved outcomes.
As the most common form of cancer in the United States,1 dermatologists often focus on treating the physical aspects of skin cancer, but it is equally important to consider the consequences that this disease has on a patient’s quality of life (QOL). Health is a dynamic process, encompassing one’s physical, emotional, and psychosocial well-being. There are a number of ways to measure health outcomes including mortality, morbidity, health status, and QOL. In recent years, health-related QOL (HRQOL) outcomes in dermatology have become increasingly important to clinical practice and may become factors in quality measurement or reimbursement.
Understanding a patient’s HRQOL allows health care providers to better evaluate the burden of disease and disability associated with skin cancer and its treatment. Clinical severity is not always able to capture the extent to which a disease affects one’s life.2 Furthermore, physician estimation of disease severity is not always consistent with patient-reported outcomes.3 As such, clinical questionnaires may be invaluable tools capable of objectively reporting a patient’s perception of improvement in health, which may affect how a dermatologist approaches treatment, discussion, and maintenance.
Nonmelanoma Skin Cancer
Most nonmelanoma skin cancer (NMSC) occurs in readily visible areas, namely the head and neck. Surgical treatment minimizes recurrence and complication rates. Nonmelanoma skin cancer has a low mortality and a high cure rate if diagnosed early; therefore, it may be difficult to assess treatment efficacy on cure rates alone. The amalgamation of anxiety associated with the diagnosis, aesthetic and functional concerns regarding treatment, and long-term consequences including fear of future skin cancer may have a lasting effect on an individual’s psychosocial relationships and underscores the need for QOL studies.
Most generic QOL and dermatology-specific QOL instruments fail to accurately detect the concerns of patients with NMSC.4-6 Generic QOL measures used for skin cancer patients report scores of patients that were similar to population norms,4 suggesting that these tools may fail to appropriately assess unique QOL concerns among individuals with skin cancer. Furthermore, dermatology-specific instruments have been reported to be insensitive to specific appearance-related concerns of patients with NMSC, likely because skin cancer patients made up a small percentage of the initial population in their design.4,7 Nevertheless, dermatology-specific instruments may be suitable depending on the objectives of the study.8
Recently, skin cancer–specific QOL instruments have been developed to fill the paucity of appropriate tools for this population. These questionnaires include the Facial Skin Cancer Index, Skin Cancer Index, and the Skin Cancer Quality of Life Impact Tool.7 The Skin Cancer Index is a 15-item questionnaire validated in patients undergoing Mohs micrographic surgery and has been used to assess behavior modification and risk perceptions in NMSC patients. Importantly, it does ask the patient if he/she is worried about scarring. The Facial Skin Cancer Index and the Skin Cancer Quality of Life Impact Tool do not take into account detailed aesthetic concerns regarding facial disfigurement and scarring or expectations of reconstruction.7 It may be prudent to assess these areas with supplemental scales.
Melanoma
Melanoma, the third most common skin cancer, is highly aggressive and can affect young and middle-aged patients. Because the mortality associated with later-stage melanoma is greater, the QOL impact of melanoma differs from NMSC. There are also 3 distinct periods of melanoma HRQOL impact: diagnosis, treatment, and follow-up. Approximately 30% of patients diagnosed with melanoma report high levels of psychological distress.9 The psychosocial effects of a melanoma diagnosis are longitudinal, as there is a high survival rate in early disease but also an increased future risk for melanoma, affecting future behaviors and overall QOL. The diagnosis of melanoma also affects family members due to the increased risk among first-degree relatives. After removal of deeper melanoma, the patient remains at risk for disease progression, which can have a profound impact on his/her social and professional activities and overall lifestyle. There may be a role for longitudinal QOL assessments to monitor changes over time and direct ongoing therapy.
The proportion of patients with melanoma who report high levels of impairment in QOL is comparable to that seen in other malignancies.10 Generic QOL instruments have found that melanoma patients have medium to high levels of distress and substantial improvement in HRQOL has been achieved with cognitive-behavioral intervention.11 Quality-of-life studies also have shown levels of distress are highest at initial diagnosis and immediately following treatment.12 In a randomized surgical trial, patients with a larger excision margin had poorer mental and physical function scores on assessment.13 Skin-specific QOL instruments have been used in studies of patients with melanoma and found that postmelanoma surveillance did not impact QOL. Also, women experienced greater improvements in QOL over time after reporting lower scores immediately postsurgery.13
The FACT-melanoma (Functional Assessment of Cancer Therapy) is a melanoma-specific HRQOL assessment that has been used in patients undergoing clinical trials. It has been shown to distinguish between early and advanced-stage (stages III or IV) HRQOL issues.14 Patients with early-stage melanoma are more concerned with cosmetic outcome, and those with later-stage melanoma are more concerned with morbidity and mortality associated with treatment.
Comment
Choosing the best QOL instrument depends on the specific objectives of the study. Although generic QOL questionnaires have performed poorly in studies of specific skin diseases and even dermatology-specific tools have shown limited responsiveness in skin cancer, a combination of tools may be an effective approach. However, dermatologists must be cautious when administering these valuable tools to ensure that they do not become a burdensome task for the patient.15 Although no single skin cancer–specific QOL tool is perfect, it is likely that the current questionnaires still allow for aid with appropriate patient management and comparison of treatments.16
It behooves clinicians to recognize and appreciate the value of QOL instruments as an important adjunct to treatment. These tools have shown QOL to be an independent predictor of survival among many types of cancer patients, including melanoma.10 Currently, the psychological and emotional needs of skin cancer patients often go overlooked and undetected by conventional methods. Within one’s own practice, introducing QOL assessments can improve patient self-awareness and physician awareness of matters that may have a greater impact on patient health. On a larger scale, introducing patient-reported outcome measures can affect resource allocation by identifying patient populations that may be most impacted and can give a comprehensive method for physicians to gauge treatment efficacy, leading to improved outcomes.
1. Robinson JK. Sun exposure, sun protection, and vitamin D. JAMA. 2005;294:1541-1543.
2. Motley RJ, Finlay AY. Practical use of a disability index in the routine management of acne. Clin Exp Dermatol. 1992;17:1-3.
3. Chren MM, Lasek RJ, Quinn LM, et al. Skindex, a quality-of-life measure for patients with skin disease: reliability, validity, and responsiveness. J Invest Dermatol. 1996;107:707-713.
4. Gibbons EC, Comabella CI, Fitzpatrick R. A structured review of patient-reported outcome measures for patients with skin cancer, 2013. Br J Dermatol. 2013;168:1176-1186.
5. Burdon-Jones D, Thomas P, Baker R. Quality of life issues in nonmetastatic skin cancer. Br J Dermatol. 2010;162:147-151.
6. Lear W, Akeroyd JD, Mittmann N, et al. Measurement of utility in nonmelanoma skin cancer. J Cutan Med Surg. 2008;12:102-106.
7. Bates AS, Davis CR, Takwale A, et al. Patient-reported outcome measures in nonmelanoma skin cancer of the face: a systematic review. Br J Dermatol. 2013;168:1187-1194.
8. Lee EH, Klassen AF, Nehal KS, et al. A systematic review of patient-reported outcome instruments of nonmelanoma skin cancer in the dermatologic population. J Am Acad Dermatol. 2013;69:e59-e67.
9. Kasparian NA. Psychological stress and melanoma: are we meeting our patients’ psychological needs? Clin Dermatol. 2013;31:41-46.
10. Cormier JN, Cromwell KD, Ross MI. Health-related quality of life in patients with melanoma: overview of instruments and outcomes. Dermatol Clin. 2012;30:245-254.
11. Trask PC, Paterson AG, Griffith KA, et al. Cognitive-behavioral intervention for distress in patients with melanoma: comparison with standard medical care and impact on quality of life. Cancer. 2003;98:854-864.
12. Boyle DA. Psychological adjustment to the melanoma experience. Semin Oncol Nurs. 2003;191:70-77.
13. Newton-Bishop JA, Nolan C, Turner F, et al. A quality-of-life study in high-risk (thickness > = or 2 mm) cutaneous melanoma patients in a randomized trial of 1-cm versus 3-cm surgical excision margins. J Investig Dermatol Symp Proc. 2004;9:152-159.
14. Winstanley JB, Saw R, Boyle F, et al. The FACT-Melanoma quality-of-life instrument: comparison of a five-point and four-point response scale using the Rasch measurement model. Melanoma Res. 2013;23:61-69.
15. Swartz RJ, Baum GP, Askew RL, et al. Reducing patient burden to the FACT-Melanoma quality-of-life questionnaire. Melanoma Res. 2012;22:158-163.
16. Black N. Patient-reported outcome measures in skin cancer. Br J Dermatol. 2013;168:1151.
1. Robinson JK. Sun exposure, sun protection, and vitamin D. JAMA. 2005;294:1541-1543.
2. Motley RJ, Finlay AY. Practical use of a disability index in the routine management of acne. Clin Exp Dermatol. 1992;17:1-3.
3. Chren MM, Lasek RJ, Quinn LM, et al. Skindex, a quality-of-life measure for patients with skin disease: reliability, validity, and responsiveness. J Invest Dermatol. 1996;107:707-713.
4. Gibbons EC, Comabella CI, Fitzpatrick R. A structured review of patient-reported outcome measures for patients with skin cancer, 2013. Br J Dermatol. 2013;168:1176-1186.
5. Burdon-Jones D, Thomas P, Baker R. Quality of life issues in nonmetastatic skin cancer. Br J Dermatol. 2010;162:147-151.
6. Lear W, Akeroyd JD, Mittmann N, et al. Measurement of utility in nonmelanoma skin cancer. J Cutan Med Surg. 2008;12:102-106.
7. Bates AS, Davis CR, Takwale A, et al. Patient-reported outcome measures in nonmelanoma skin cancer of the face: a systematic review. Br J Dermatol. 2013;168:1187-1194.
8. Lee EH, Klassen AF, Nehal KS, et al. A systematic review of patient-reported outcome instruments of nonmelanoma skin cancer in the dermatologic population. J Am Acad Dermatol. 2013;69:e59-e67.
9. Kasparian NA. Psychological stress and melanoma: are we meeting our patients’ psychological needs? Clin Dermatol. 2013;31:41-46.
10. Cormier JN, Cromwell KD, Ross MI. Health-related quality of life in patients with melanoma: overview of instruments and outcomes. Dermatol Clin. 2012;30:245-254.
11. Trask PC, Paterson AG, Griffith KA, et al. Cognitive-behavioral intervention for distress in patients with melanoma: comparison with standard medical care and impact on quality of life. Cancer. 2003;98:854-864.
12. Boyle DA. Psychological adjustment to the melanoma experience. Semin Oncol Nurs. 2003;191:70-77.
13. Newton-Bishop JA, Nolan C, Turner F, et al. A quality-of-life study in high-risk (thickness > = or 2 mm) cutaneous melanoma patients in a randomized trial of 1-cm versus 3-cm surgical excision margins. J Investig Dermatol Symp Proc. 2004;9:152-159.
14. Winstanley JB, Saw R, Boyle F, et al. The FACT-Melanoma quality-of-life instrument: comparison of a five-point and four-point response scale using the Rasch measurement model. Melanoma Res. 2013;23:61-69.
15. Swartz RJ, Baum GP, Askew RL, et al. Reducing patient burden to the FACT-Melanoma quality-of-life questionnaire. Melanoma Res. 2012;22:158-163.
16. Black N. Patient-reported outcome measures in skin cancer. Br J Dermatol. 2013;168:1151.
Risk Factors for Malignant Melanoma and Preventive Methods
Cutaneous melanoma is a malignant tumor of the skin that develops from melanin-producing pigment cells known as melanocytes. The development of melanoma is a multifactorial process. External factors, genetic predisposition, or both may cause damage to DNA in melanoma cells. Genetic mutations may occur de novo or can be transferred from generation to generation. The most important environmental risk factor is UV radiation, both natural and artificial. Other risk factors include skin type, ethnicity, number of melanocytic nevi, number and severity of sunburns, frequency and duration of UV exposure, geographic location, and level of awareness about malignant melanoma (MM) and its risk factors.1
Melanoma accounts for only 1% to 2% of all tumors but is known for its rapidly increasing incidence.2 White individuals who reside in sunny areas of North America, northern Europe, Australia, and New Zealand seem to be at the highest risk for developing melanoma.3 The global incidence of MM from 2004 to 2008 was 20.8 individuals per 100,000 people.4 In Central Europe, 10 to 12 individuals per 100,000 people were diagnosed with melanoma, and 50 to 60 individuals per 100,000 people were diagnosed in Australia. In 2011, the lifetime risk of being diagnosed with melanoma was 1% in Central Europe and 4% in Australia.2 The incidence of melanoma is lower in populations with darker skin types (ie, Africans, Asians). In some parts of the world, the overall incidence and/or severity of melanoma has been declining over the last few decades, possibly reflecting improved public awareness.5
Cutaneous MM is an aggressive skin cancer that has fatal consequences if diagnosed late. Chances of survival, however, increase dramatically when melanoma is detected early. Collecting and analyzing data about a certain disease leads to a better understanding of the condition and encourages the development of prevention strategies. Epidemiologic research helps to improve patient care by measuring the occurrence of an event and by investigating the relationship between the occurrence of an event and associated factors; in doing so, epidemiologic research directly enables a better understanding of the disease and promotes effective preventive and therapeutic approaches.6
Although risk factors for melanoma are well established, current epidemiologic research shows that information on UV exposure and its association with this disease in many parts of the world, including Central Europe, is lacking. The aim of this study was to investigate behavioral and sociodemographic factors associated with the development of MM in the Czech Republic and Germany.
Materials and Methods
This hospital-based, case-control study was conducted in the largest dermatology departments in the Czech Republic (Clinic of Dermatology and Venereology, Third Faculty of Medicine, Charles University, Prague) and Germany (Department of Dermatology and Allergology, Ludwig Maximilian University, Munich). Data from the Czech Republic and Germany were not evaluated separately. These 2 countries were chosen as a representative sample population from Central Europe.
Study Population
The study population included 207 patients (103 men; 104 women) aged 31 to 94 years who were consecutively diagnosed with MM (cases). Patients with acral lentiginous melanoma were excluded from the study due to the generally accepted theory that the condition is not linked to UV exposure. Melanoma diagnosis was based on histopathologic examination. The study population also included 235 randomly selected controls (110 men; 125 women) from the same 2 study centers who had been hospitalized due to other dermatologic diagnoses with no history of any skin cancer. Among patients asked to take part in the study, the participation rates were 83% among cases and 62% among controls.
Assessment
Various sociodemographic factors and factors related to UV exposure were assessed via administration of a structured questionnaire that was completed by all 442 patients.
Four statistical models concerning variables were constructed. The basic model, which was part of all subsequent models, included age, sex, education, and history of skin tumors. Variables included in the biological model were eye color (light vs dark) and Fitzpatrick skin type (I–V). Variables included in the lifestyle model were the use of sunscreen (never and rarely; often; always; always and repetitively), sun exposure during work (yes/no), and seaside vacation (never, rarely, regularly, more than once per year). The variable in the exposure model was the number of sunburns during childhood and adolescence (none, 1–5 times, 6–10 times, ≥11 times).
Sociodemographic characteristics (sex, age, education) and prior incidence of skin tumor were included in each model. Although there were no statistically significant differences in the incidence of melanoma associated with sex and age, those variables were kept in the models to control the impact of other variables by sex and age.
Other variables were added into the model one by one, and the likelihood ratio was tested step-by-step. Only the variables that improved the model fit were kept in the final model. Impact of variables on dependent variables also was tested; variables with no significant impact on dependent variables were left out of the model.
Statistical Analysis
The association between risk factors and MM was assessed using multivariate logistic regression. In total, 4 models were included in the results, which were presented as odds ratios (ORs) and 95% confidence intervals (CIs). A significance level of α=.05 was chosen. The statistical program Stata 11 was used for all analyses.
Results
Descriptive data on the 442 patients surveyed are shown in Table 1. The results of the logistic regression in all studied models are shown in Table 2.
Basic Model
There was no difference in the proportion of men and women in the melanoma and control groups. We observed that more patients in the melanoma group had a university degree than patients in the control group. Patients in the melanoma group with a history of MM showed 4.2 times higher risk for developing another melanoma.
Biological Model
Eye color and Fitzpatrick skin type were the focus of the biological model. The odds of being diagnosed with melanoma were 2.5 times greater in respondents with a light eye color (ie, blue, green, gray) than in respondents with a dark eye color (ie, brown, black). Respondents with Fitzpatrick skin types I and II had a significantly higher association with melanoma (OR, 4.25 and 6.98; 95% CI, 2.13-8.51 and 3.78-12.88) than Fitzpatrick skin type III (OR, 1.0)(P<.001 for both). Respondents with darker skin types (IV and V) also were present in our study population. The numbers were low, and the CI was too wide; nevertheless, the results were statistically significant (P<.001).
Lifestyle Model
The lifestyle model included patients’ use of sunscreen and level of sun exposure at work and on vacation. Respondents who did not use sunscreen were 12 times more likely to develop melanoma than those who always used it (95% CI, 5.56-27.14); however, individuals who used sunscreen always and repetitively (ie, more than once during 1 period of sun exposure) had a higher likelihood of melanoma compared to those who always used it. The incidence of melanoma was lower in respondents who regularly spent their vacations by the sea than those who did not vacation in seaside regions. Respondents who worked in direct sunlight were approximately 2 times more likely to present with melanoma than individuals who did not work outside.
Exposure Model
The number of sunburns sustained during childhood and adolescence was assessed in the exposure model. Respondents with a history of 1 to 5 sunburns during childhood and adolescence did not show a statistically significant increase in the incidence of melanoma diagnosis; however, those with a history of 6 or more sunburns during these periods showed a significant increase in the odds of developing melanoma (OR, 4.95 and 25.52; 95% CI, 2.29-10.71 and 12.16-53.54)(P<.001 for both).
Comment
In this study, we concentrated on UV exposure and various sociodemographic factors that were possibly connected to a higher risk for developing melanoma. We observed that the majority of patients in the melanoma group had achieved a higher level of education than the control group. Most of the melanoma group patients had light-colored eyes and spent more time in direct sunlight at work. Although seaside vacations did not correlate with a higher occurrence of melanoma, it was noted that the melanoma patients used sunscreen much less often than the control group. Major differences among respondents in the melanoma group versus the control group were seen in the reported number of sunburns sustained in childhood and adolescence. More sunburns during these periods seemed to play the most important role in the risk for melanoma. Some of the patient responses to the questionnaire may be biased, as respondents answered the questions by themselves.
Because risk factors for and preventive methods against melanoma are well established, one would assume that general knowledge regarding melanoma is adequate. On the contrary, it has been shown that knowledge about melanoma is insufficient, even among professionals and individuals with higher levels of education. In a study based on a questionnaire administered to plastic surgeons, only 37.5% (27/72) of respondents correctly identified the duration of action of sunscreen to be 3 to 4 hours.7 Approximately half of the respondents (37/72) did not know that geographical conditions such as altitude and latitude as well as shade can alter sunscreen efficacy and also were not aware of the protective action of clothing. These results are alarming and indicate that even medical professionals, who should play a main role in improving the health knowledge of the general population, have an unsatisfactory level of education in prevention of melanoma. Another important part of better education of specialists treating skin disorders is good knowledge of dermatoscopy. In fact, the Annual Skin Cancer Conference 2011 in Australia emphasized the importance of dermatoscopy in primary and secondary prevention of skin cancer.8 Teaching dermatoscopy should be part of melanoma campaigns for professionals.
Our basic model demonstrated that a higher level of education was connected to a higher occurrence of MM, which may seem surprising, considering that most diseases, along with their incidence, prevalence, and mortality, usually are associated with lower levels of education or lower socioeconomic status. A similar trend also was reported in prior studies, with higher socioeconomic groups showing higher incidences of cutaneous melanoma; colon cancer; brain cancer in men; and breast and ovarian cancer in women. Additionally, patients with higher socioeconomic status have been shown to have a survival advantage.9 Individuals with higher socioeconomic status can afford to travel more often for vacation and are more frequently exposed to direct sun. Individuals with higher levels of education also are generally more aware of the importance of disease prevention and therefore go for preventive checkups more often. The detection of melanoma in this socioeconomic group should be higher.
Our biological model demonstrated that respondents with lighter eyes had melanoma almost 3 times more often than individuals with darker eyes. Fitzpatrick skin types I and II also were significantly associated with the development of melanoma (P<.001). These findings are generally confirmed in the literature. In a study of the incidence of melanoma in Spain, statistically significant risk factors included blonde or red hair (P=.002), multiple melanocytic nevi (P=.002), Fitzpatrick skin types I and II (P=.002), and a history of actinic keratosis (P=.021) or nonmelanoma skin cancer (P=.002).10 A group in Italy also has investigated the main risk factors for melanoma. This study suggested dividing patients into high-risk subgroups to help minimize exposure to UV radiation and diagnose melanoma in its early stage.11
The results from our study confirmed the importance of concentrating melanoma prevention campaign efforts on high-risk patients. Dividing these patients into subgroups (eg, individuals who play outdoor sports, individuals with occupations associated with UV exposure, individuals who use indoor tanning beds, individuals with a family history of melanoma) may be helpful. A case-control study on sun-seeking behavior in the Czech Republic showed that the most alarming risk factors were all-day sun exposure during adolescence, frequent holidays spent in the mountains, and inadequate use of sunscreen in adulthood.12 We investigated the effects of sunscreen use on the incidence of melanoma in our lifestyle model and discovered that it decreased the risk for melanoma. Respondents who used it always had a much lower risk for developing melanoma than those who never or rarely applied it. Individuals who used sunscreen always and repetitively (ie, more than once per period of sun exposure) did not show a lower risk than those who used it once per period of sun exposure. This finding could mean that patients who are known to get sunburns or who feel a certain discomfort on direct exposure to the sun tend to use sunscreen always and repetitively.
It is important to note that some investigators disagree with the importance of some generally accepted means of prevention, such as the effect of sunscreen products. Due to insufficient evidence, the role of sunscreen use in reducing the risk for skin cancer, especially cutaneous MM, is controversial.13 Although we could prove there is a considerable difference in the incidence of melanoma in patients who claimed to use sunscreen always versus those who never use it, we agree that more evidence on this topic is needed. Furthermore, it has been reported that risk for melanoma has increased with rising intermittent sun exposure and indoor tanning bed use.14,15
Respondents who regularly traveled to seaside regions showed a surprisingly lower incidence of melanoma than respondents who did not spend their vacations in seaside locations. It is possible that individuals who choose not to spend their vacations at the seaside are more prone to sunburns and therefore do not prefer to spend their free time in direct sunlight. Another possible explanation is that individuals who regularly travel to seaside regions actively try to protect themselves from sunlight and sunburns. A higher incidence of melanoma also was observed in respondents who reported sun exposure during work.
In our exposure model, we demonstrated that a history of sunburns is the strongest risk factor for melanoma. Frequent sunburns during childhood and adolescence were strongly associated with the development of MM. This association has been supported in a systematic review on sun exposure during childhood and associated risks.16
Conclusion
To improve patient knowledge about melanoma prevention, we suggest directing targeted campaigns that address high-risk population groups, such as individuals with red hair and/or light eyes, people with an occupation associated with frequent UV exposure, and individuals with higher levels of education. With regard to younger populations, parents as well as physicians and teachers should be aware that frequent sunburns during childhood and adolescence and use of tanning beds are 2 main risk factors for MM.
1. IARC monographs on the evaluation of carcinogenic risks to humans. solar and ultraviolet radiation. IARC Monogr Eval Carcinog Risks Hum. 1992;55:1-316.
2. Kunte C, Geimer T, Baumert J, et al. Analysis of predictive factors for the outcome of complete lymph node dissection in melanoma patients with metastatic sentinel lymph nodes. J Am Acad Dermatol. 2011;64:655-662.
3. Parkin D, Bray F, Ferlay J, et al. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74-108.
4. SEER Stat Fact Sheets: melanoma of the skin. Bethesda, MD: National Cancer Institute; 2013. http://seer.cancer.gov/statfacts/html/melan.html#incidence-mortality. Accessed October 25, 2014.
5. Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893-2917.
6. Nijsten T, Stern RS. How epidemiology has contributed to a better understanding of skin disease [published online ahead of print December 8, 2011]. J Invest Dermatol. 2012;132(3, pt 2):994-1002.
7. Magdum A, Leonforte F, McNaughton E, et al. Sun protection–do we know enough [published online ahead of print February 8, 2012]? J Plast Reconstr Aesthet Surg. 2012;65:1384-1389.
8. Zalaudek I, Whiteman D, Rosendahl C, et al. Update on melanoma and non-melanoma skin cancer. Annual Skin Cancer Conference 2011, Hamilton Island, Australia, 2011. Expert Rev Anticancer Ther. 2011;11:1829-1832.
9. Mackenbach JP. Health inequalities: Europe in profile. http://ec.europa.eu/health/ph_determinants/socio_economics/documents/ev_060302_rd06_en.pdf. Published February 2006. Accessed October 25, 2014.
10. Ballester I, Oliver V, Bañuls J, et al. Multicenter case-control study of risk factors for cutaneous melanoma in Valencia, Spain [published online ahead of print May 22, 2012]. Actas Dermosifiliogr. 2012;103:790-797.
11. Jaimes N, Marghoob AA. An update on risk factors, prognosis and management of melanoma patients. G Ital Dermatol Venereol. 2012;147:1-19.
12. Vranova J, Arenbergerova M, Arenberger P, et al. Incidence of cutaneous malignant melanoma in the Czech Republic: the risks of sun exposure for adolescents. Neoplasma. 2012;59:316-325.
13. Planta MB. Sunscreen and melanoma: is our prevention message correct? J Am Board Fam Med. 2011;24:735-739.
14. Veierød MB, Adami HO, Lund E, et al. Sun and solarium exposure and melanoma risk: effects of age, pigmentary characteristics, and nevi. Cancer Epidemiol Biomarkers Prev. 2010;19:111-120.
15. Doré JF, Chignol MC. Tanning salons and skin cancer [published online ahead of print August 15, 2011]. Photochem Photobiol Sci. 2012;11:30-37.
16. Whiteman DC, Whiteman CA, Green AC. Childhood sun exposure as a risk factor for melanoma: a systematic review of epidemiologic studies. Cancer Causes Control. 2001;12:69-82.
Cutaneous melanoma is a malignant tumor of the skin that develops from melanin-producing pigment cells known as melanocytes. The development of melanoma is a multifactorial process. External factors, genetic predisposition, or both may cause damage to DNA in melanoma cells. Genetic mutations may occur de novo or can be transferred from generation to generation. The most important environmental risk factor is UV radiation, both natural and artificial. Other risk factors include skin type, ethnicity, number of melanocytic nevi, number and severity of sunburns, frequency and duration of UV exposure, geographic location, and level of awareness about malignant melanoma (MM) and its risk factors.1
Melanoma accounts for only 1% to 2% of all tumors but is known for its rapidly increasing incidence.2 White individuals who reside in sunny areas of North America, northern Europe, Australia, and New Zealand seem to be at the highest risk for developing melanoma.3 The global incidence of MM from 2004 to 2008 was 20.8 individuals per 100,000 people.4 In Central Europe, 10 to 12 individuals per 100,000 people were diagnosed with melanoma, and 50 to 60 individuals per 100,000 people were diagnosed in Australia. In 2011, the lifetime risk of being diagnosed with melanoma was 1% in Central Europe and 4% in Australia.2 The incidence of melanoma is lower in populations with darker skin types (ie, Africans, Asians). In some parts of the world, the overall incidence and/or severity of melanoma has been declining over the last few decades, possibly reflecting improved public awareness.5
Cutaneous MM is an aggressive skin cancer that has fatal consequences if diagnosed late. Chances of survival, however, increase dramatically when melanoma is detected early. Collecting and analyzing data about a certain disease leads to a better understanding of the condition and encourages the development of prevention strategies. Epidemiologic research helps to improve patient care by measuring the occurrence of an event and by investigating the relationship between the occurrence of an event and associated factors; in doing so, epidemiologic research directly enables a better understanding of the disease and promotes effective preventive and therapeutic approaches.6
Although risk factors for melanoma are well established, current epidemiologic research shows that information on UV exposure and its association with this disease in many parts of the world, including Central Europe, is lacking. The aim of this study was to investigate behavioral and sociodemographic factors associated with the development of MM in the Czech Republic and Germany.
Materials and Methods
This hospital-based, case-control study was conducted in the largest dermatology departments in the Czech Republic (Clinic of Dermatology and Venereology, Third Faculty of Medicine, Charles University, Prague) and Germany (Department of Dermatology and Allergology, Ludwig Maximilian University, Munich). Data from the Czech Republic and Germany were not evaluated separately. These 2 countries were chosen as a representative sample population from Central Europe.
Study Population
The study population included 207 patients (103 men; 104 women) aged 31 to 94 years who were consecutively diagnosed with MM (cases). Patients with acral lentiginous melanoma were excluded from the study due to the generally accepted theory that the condition is not linked to UV exposure. Melanoma diagnosis was based on histopathologic examination. The study population also included 235 randomly selected controls (110 men; 125 women) from the same 2 study centers who had been hospitalized due to other dermatologic diagnoses with no history of any skin cancer. Among patients asked to take part in the study, the participation rates were 83% among cases and 62% among controls.
Assessment
Various sociodemographic factors and factors related to UV exposure were assessed via administration of a structured questionnaire that was completed by all 442 patients.
Four statistical models concerning variables were constructed. The basic model, which was part of all subsequent models, included age, sex, education, and history of skin tumors. Variables included in the biological model were eye color (light vs dark) and Fitzpatrick skin type (I–V). Variables included in the lifestyle model were the use of sunscreen (never and rarely; often; always; always and repetitively), sun exposure during work (yes/no), and seaside vacation (never, rarely, regularly, more than once per year). The variable in the exposure model was the number of sunburns during childhood and adolescence (none, 1–5 times, 6–10 times, ≥11 times).
Sociodemographic characteristics (sex, age, education) and prior incidence of skin tumor were included in each model. Although there were no statistically significant differences in the incidence of melanoma associated with sex and age, those variables were kept in the models to control the impact of other variables by sex and age.
Other variables were added into the model one by one, and the likelihood ratio was tested step-by-step. Only the variables that improved the model fit were kept in the final model. Impact of variables on dependent variables also was tested; variables with no significant impact on dependent variables were left out of the model.
Statistical Analysis
The association between risk factors and MM was assessed using multivariate logistic regression. In total, 4 models were included in the results, which were presented as odds ratios (ORs) and 95% confidence intervals (CIs). A significance level of α=.05 was chosen. The statistical program Stata 11 was used for all analyses.
Results
Descriptive data on the 442 patients surveyed are shown in Table 1. The results of the logistic regression in all studied models are shown in Table 2.
Basic Model
There was no difference in the proportion of men and women in the melanoma and control groups. We observed that more patients in the melanoma group had a university degree than patients in the control group. Patients in the melanoma group with a history of MM showed 4.2 times higher risk for developing another melanoma.
Biological Model
Eye color and Fitzpatrick skin type were the focus of the biological model. The odds of being diagnosed with melanoma were 2.5 times greater in respondents with a light eye color (ie, blue, green, gray) than in respondents with a dark eye color (ie, brown, black). Respondents with Fitzpatrick skin types I and II had a significantly higher association with melanoma (OR, 4.25 and 6.98; 95% CI, 2.13-8.51 and 3.78-12.88) than Fitzpatrick skin type III (OR, 1.0)(P<.001 for both). Respondents with darker skin types (IV and V) also were present in our study population. The numbers were low, and the CI was too wide; nevertheless, the results were statistically significant (P<.001).
Lifestyle Model
The lifestyle model included patients’ use of sunscreen and level of sun exposure at work and on vacation. Respondents who did not use sunscreen were 12 times more likely to develop melanoma than those who always used it (95% CI, 5.56-27.14); however, individuals who used sunscreen always and repetitively (ie, more than once during 1 period of sun exposure) had a higher likelihood of melanoma compared to those who always used it. The incidence of melanoma was lower in respondents who regularly spent their vacations by the sea than those who did not vacation in seaside regions. Respondents who worked in direct sunlight were approximately 2 times more likely to present with melanoma than individuals who did not work outside.
Exposure Model
The number of sunburns sustained during childhood and adolescence was assessed in the exposure model. Respondents with a history of 1 to 5 sunburns during childhood and adolescence did not show a statistically significant increase in the incidence of melanoma diagnosis; however, those with a history of 6 or more sunburns during these periods showed a significant increase in the odds of developing melanoma (OR, 4.95 and 25.52; 95% CI, 2.29-10.71 and 12.16-53.54)(P<.001 for both).
Comment
In this study, we concentrated on UV exposure and various sociodemographic factors that were possibly connected to a higher risk for developing melanoma. We observed that the majority of patients in the melanoma group had achieved a higher level of education than the control group. Most of the melanoma group patients had light-colored eyes and spent more time in direct sunlight at work. Although seaside vacations did not correlate with a higher occurrence of melanoma, it was noted that the melanoma patients used sunscreen much less often than the control group. Major differences among respondents in the melanoma group versus the control group were seen in the reported number of sunburns sustained in childhood and adolescence. More sunburns during these periods seemed to play the most important role in the risk for melanoma. Some of the patient responses to the questionnaire may be biased, as respondents answered the questions by themselves.
Because risk factors for and preventive methods against melanoma are well established, one would assume that general knowledge regarding melanoma is adequate. On the contrary, it has been shown that knowledge about melanoma is insufficient, even among professionals and individuals with higher levels of education. In a study based on a questionnaire administered to plastic surgeons, only 37.5% (27/72) of respondents correctly identified the duration of action of sunscreen to be 3 to 4 hours.7 Approximately half of the respondents (37/72) did not know that geographical conditions such as altitude and latitude as well as shade can alter sunscreen efficacy and also were not aware of the protective action of clothing. These results are alarming and indicate that even medical professionals, who should play a main role in improving the health knowledge of the general population, have an unsatisfactory level of education in prevention of melanoma. Another important part of better education of specialists treating skin disorders is good knowledge of dermatoscopy. In fact, the Annual Skin Cancer Conference 2011 in Australia emphasized the importance of dermatoscopy in primary and secondary prevention of skin cancer.8 Teaching dermatoscopy should be part of melanoma campaigns for professionals.
Our basic model demonstrated that a higher level of education was connected to a higher occurrence of MM, which may seem surprising, considering that most diseases, along with their incidence, prevalence, and mortality, usually are associated with lower levels of education or lower socioeconomic status. A similar trend also was reported in prior studies, with higher socioeconomic groups showing higher incidences of cutaneous melanoma; colon cancer; brain cancer in men; and breast and ovarian cancer in women. Additionally, patients with higher socioeconomic status have been shown to have a survival advantage.9 Individuals with higher socioeconomic status can afford to travel more often for vacation and are more frequently exposed to direct sun. Individuals with higher levels of education also are generally more aware of the importance of disease prevention and therefore go for preventive checkups more often. The detection of melanoma in this socioeconomic group should be higher.
Our biological model demonstrated that respondents with lighter eyes had melanoma almost 3 times more often than individuals with darker eyes. Fitzpatrick skin types I and II also were significantly associated with the development of melanoma (P<.001). These findings are generally confirmed in the literature. In a study of the incidence of melanoma in Spain, statistically significant risk factors included blonde or red hair (P=.002), multiple melanocytic nevi (P=.002), Fitzpatrick skin types I and II (P=.002), and a history of actinic keratosis (P=.021) or nonmelanoma skin cancer (P=.002).10 A group in Italy also has investigated the main risk factors for melanoma. This study suggested dividing patients into high-risk subgroups to help minimize exposure to UV radiation and diagnose melanoma in its early stage.11
The results from our study confirmed the importance of concentrating melanoma prevention campaign efforts on high-risk patients. Dividing these patients into subgroups (eg, individuals who play outdoor sports, individuals with occupations associated with UV exposure, individuals who use indoor tanning beds, individuals with a family history of melanoma) may be helpful. A case-control study on sun-seeking behavior in the Czech Republic showed that the most alarming risk factors were all-day sun exposure during adolescence, frequent holidays spent in the mountains, and inadequate use of sunscreen in adulthood.12 We investigated the effects of sunscreen use on the incidence of melanoma in our lifestyle model and discovered that it decreased the risk for melanoma. Respondents who used it always had a much lower risk for developing melanoma than those who never or rarely applied it. Individuals who used sunscreen always and repetitively (ie, more than once per period of sun exposure) did not show a lower risk than those who used it once per period of sun exposure. This finding could mean that patients who are known to get sunburns or who feel a certain discomfort on direct exposure to the sun tend to use sunscreen always and repetitively.
It is important to note that some investigators disagree with the importance of some generally accepted means of prevention, such as the effect of sunscreen products. Due to insufficient evidence, the role of sunscreen use in reducing the risk for skin cancer, especially cutaneous MM, is controversial.13 Although we could prove there is a considerable difference in the incidence of melanoma in patients who claimed to use sunscreen always versus those who never use it, we agree that more evidence on this topic is needed. Furthermore, it has been reported that risk for melanoma has increased with rising intermittent sun exposure and indoor tanning bed use.14,15
Respondents who regularly traveled to seaside regions showed a surprisingly lower incidence of melanoma than respondents who did not spend their vacations in seaside locations. It is possible that individuals who choose not to spend their vacations at the seaside are more prone to sunburns and therefore do not prefer to spend their free time in direct sunlight. Another possible explanation is that individuals who regularly travel to seaside regions actively try to protect themselves from sunlight and sunburns. A higher incidence of melanoma also was observed in respondents who reported sun exposure during work.
In our exposure model, we demonstrated that a history of sunburns is the strongest risk factor for melanoma. Frequent sunburns during childhood and adolescence were strongly associated with the development of MM. This association has been supported in a systematic review on sun exposure during childhood and associated risks.16
Conclusion
To improve patient knowledge about melanoma prevention, we suggest directing targeted campaigns that address high-risk population groups, such as individuals with red hair and/or light eyes, people with an occupation associated with frequent UV exposure, and individuals with higher levels of education. With regard to younger populations, parents as well as physicians and teachers should be aware that frequent sunburns during childhood and adolescence and use of tanning beds are 2 main risk factors for MM.
Cutaneous melanoma is a malignant tumor of the skin that develops from melanin-producing pigment cells known as melanocytes. The development of melanoma is a multifactorial process. External factors, genetic predisposition, or both may cause damage to DNA in melanoma cells. Genetic mutations may occur de novo or can be transferred from generation to generation. The most important environmental risk factor is UV radiation, both natural and artificial. Other risk factors include skin type, ethnicity, number of melanocytic nevi, number and severity of sunburns, frequency and duration of UV exposure, geographic location, and level of awareness about malignant melanoma (MM) and its risk factors.1
Melanoma accounts for only 1% to 2% of all tumors but is known for its rapidly increasing incidence.2 White individuals who reside in sunny areas of North America, northern Europe, Australia, and New Zealand seem to be at the highest risk for developing melanoma.3 The global incidence of MM from 2004 to 2008 was 20.8 individuals per 100,000 people.4 In Central Europe, 10 to 12 individuals per 100,000 people were diagnosed with melanoma, and 50 to 60 individuals per 100,000 people were diagnosed in Australia. In 2011, the lifetime risk of being diagnosed with melanoma was 1% in Central Europe and 4% in Australia.2 The incidence of melanoma is lower in populations with darker skin types (ie, Africans, Asians). In some parts of the world, the overall incidence and/or severity of melanoma has been declining over the last few decades, possibly reflecting improved public awareness.5
Cutaneous MM is an aggressive skin cancer that has fatal consequences if diagnosed late. Chances of survival, however, increase dramatically when melanoma is detected early. Collecting and analyzing data about a certain disease leads to a better understanding of the condition and encourages the development of prevention strategies. Epidemiologic research helps to improve patient care by measuring the occurrence of an event and by investigating the relationship between the occurrence of an event and associated factors; in doing so, epidemiologic research directly enables a better understanding of the disease and promotes effective preventive and therapeutic approaches.6
Although risk factors for melanoma are well established, current epidemiologic research shows that information on UV exposure and its association with this disease in many parts of the world, including Central Europe, is lacking. The aim of this study was to investigate behavioral and sociodemographic factors associated with the development of MM in the Czech Republic and Germany.
Materials and Methods
This hospital-based, case-control study was conducted in the largest dermatology departments in the Czech Republic (Clinic of Dermatology and Venereology, Third Faculty of Medicine, Charles University, Prague) and Germany (Department of Dermatology and Allergology, Ludwig Maximilian University, Munich). Data from the Czech Republic and Germany were not evaluated separately. These 2 countries were chosen as a representative sample population from Central Europe.
Study Population
The study population included 207 patients (103 men; 104 women) aged 31 to 94 years who were consecutively diagnosed with MM (cases). Patients with acral lentiginous melanoma were excluded from the study due to the generally accepted theory that the condition is not linked to UV exposure. Melanoma diagnosis was based on histopathologic examination. The study population also included 235 randomly selected controls (110 men; 125 women) from the same 2 study centers who had been hospitalized due to other dermatologic diagnoses with no history of any skin cancer. Among patients asked to take part in the study, the participation rates were 83% among cases and 62% among controls.
Assessment
Various sociodemographic factors and factors related to UV exposure were assessed via administration of a structured questionnaire that was completed by all 442 patients.
Four statistical models concerning variables were constructed. The basic model, which was part of all subsequent models, included age, sex, education, and history of skin tumors. Variables included in the biological model were eye color (light vs dark) and Fitzpatrick skin type (I–V). Variables included in the lifestyle model were the use of sunscreen (never and rarely; often; always; always and repetitively), sun exposure during work (yes/no), and seaside vacation (never, rarely, regularly, more than once per year). The variable in the exposure model was the number of sunburns during childhood and adolescence (none, 1–5 times, 6–10 times, ≥11 times).
Sociodemographic characteristics (sex, age, education) and prior incidence of skin tumor were included in each model. Although there were no statistically significant differences in the incidence of melanoma associated with sex and age, those variables were kept in the models to control the impact of other variables by sex and age.
Other variables were added into the model one by one, and the likelihood ratio was tested step-by-step. Only the variables that improved the model fit were kept in the final model. Impact of variables on dependent variables also was tested; variables with no significant impact on dependent variables were left out of the model.
Statistical Analysis
The association between risk factors and MM was assessed using multivariate logistic regression. In total, 4 models were included in the results, which were presented as odds ratios (ORs) and 95% confidence intervals (CIs). A significance level of α=.05 was chosen. The statistical program Stata 11 was used for all analyses.
Results
Descriptive data on the 442 patients surveyed are shown in Table 1. The results of the logistic regression in all studied models are shown in Table 2.
Basic Model
There was no difference in the proportion of men and women in the melanoma and control groups. We observed that more patients in the melanoma group had a university degree than patients in the control group. Patients in the melanoma group with a history of MM showed 4.2 times higher risk for developing another melanoma.
Biological Model
Eye color and Fitzpatrick skin type were the focus of the biological model. The odds of being diagnosed with melanoma were 2.5 times greater in respondents with a light eye color (ie, blue, green, gray) than in respondents with a dark eye color (ie, brown, black). Respondents with Fitzpatrick skin types I and II had a significantly higher association with melanoma (OR, 4.25 and 6.98; 95% CI, 2.13-8.51 and 3.78-12.88) than Fitzpatrick skin type III (OR, 1.0)(P<.001 for both). Respondents with darker skin types (IV and V) also were present in our study population. The numbers were low, and the CI was too wide; nevertheless, the results were statistically significant (P<.001).
Lifestyle Model
The lifestyle model included patients’ use of sunscreen and level of sun exposure at work and on vacation. Respondents who did not use sunscreen were 12 times more likely to develop melanoma than those who always used it (95% CI, 5.56-27.14); however, individuals who used sunscreen always and repetitively (ie, more than once during 1 period of sun exposure) had a higher likelihood of melanoma compared to those who always used it. The incidence of melanoma was lower in respondents who regularly spent their vacations by the sea than those who did not vacation in seaside regions. Respondents who worked in direct sunlight were approximately 2 times more likely to present with melanoma than individuals who did not work outside.
Exposure Model
The number of sunburns sustained during childhood and adolescence was assessed in the exposure model. Respondents with a history of 1 to 5 sunburns during childhood and adolescence did not show a statistically significant increase in the incidence of melanoma diagnosis; however, those with a history of 6 or more sunburns during these periods showed a significant increase in the odds of developing melanoma (OR, 4.95 and 25.52; 95% CI, 2.29-10.71 and 12.16-53.54)(P<.001 for both).
Comment
In this study, we concentrated on UV exposure and various sociodemographic factors that were possibly connected to a higher risk for developing melanoma. We observed that the majority of patients in the melanoma group had achieved a higher level of education than the control group. Most of the melanoma group patients had light-colored eyes and spent more time in direct sunlight at work. Although seaside vacations did not correlate with a higher occurrence of melanoma, it was noted that the melanoma patients used sunscreen much less often than the control group. Major differences among respondents in the melanoma group versus the control group were seen in the reported number of sunburns sustained in childhood and adolescence. More sunburns during these periods seemed to play the most important role in the risk for melanoma. Some of the patient responses to the questionnaire may be biased, as respondents answered the questions by themselves.
Because risk factors for and preventive methods against melanoma are well established, one would assume that general knowledge regarding melanoma is adequate. On the contrary, it has been shown that knowledge about melanoma is insufficient, even among professionals and individuals with higher levels of education. In a study based on a questionnaire administered to plastic surgeons, only 37.5% (27/72) of respondents correctly identified the duration of action of sunscreen to be 3 to 4 hours.7 Approximately half of the respondents (37/72) did not know that geographical conditions such as altitude and latitude as well as shade can alter sunscreen efficacy and also were not aware of the protective action of clothing. These results are alarming and indicate that even medical professionals, who should play a main role in improving the health knowledge of the general population, have an unsatisfactory level of education in prevention of melanoma. Another important part of better education of specialists treating skin disorders is good knowledge of dermatoscopy. In fact, the Annual Skin Cancer Conference 2011 in Australia emphasized the importance of dermatoscopy in primary and secondary prevention of skin cancer.8 Teaching dermatoscopy should be part of melanoma campaigns for professionals.
Our basic model demonstrated that a higher level of education was connected to a higher occurrence of MM, which may seem surprising, considering that most diseases, along with their incidence, prevalence, and mortality, usually are associated with lower levels of education or lower socioeconomic status. A similar trend also was reported in prior studies, with higher socioeconomic groups showing higher incidences of cutaneous melanoma; colon cancer; brain cancer in men; and breast and ovarian cancer in women. Additionally, patients with higher socioeconomic status have been shown to have a survival advantage.9 Individuals with higher socioeconomic status can afford to travel more often for vacation and are more frequently exposed to direct sun. Individuals with higher levels of education also are generally more aware of the importance of disease prevention and therefore go for preventive checkups more often. The detection of melanoma in this socioeconomic group should be higher.
Our biological model demonstrated that respondents with lighter eyes had melanoma almost 3 times more often than individuals with darker eyes. Fitzpatrick skin types I and II also were significantly associated with the development of melanoma (P<.001). These findings are generally confirmed in the literature. In a study of the incidence of melanoma in Spain, statistically significant risk factors included blonde or red hair (P=.002), multiple melanocytic nevi (P=.002), Fitzpatrick skin types I and II (P=.002), and a history of actinic keratosis (P=.021) or nonmelanoma skin cancer (P=.002).10 A group in Italy also has investigated the main risk factors for melanoma. This study suggested dividing patients into high-risk subgroups to help minimize exposure to UV radiation and diagnose melanoma in its early stage.11
The results from our study confirmed the importance of concentrating melanoma prevention campaign efforts on high-risk patients. Dividing these patients into subgroups (eg, individuals who play outdoor sports, individuals with occupations associated with UV exposure, individuals who use indoor tanning beds, individuals with a family history of melanoma) may be helpful. A case-control study on sun-seeking behavior in the Czech Republic showed that the most alarming risk factors were all-day sun exposure during adolescence, frequent holidays spent in the mountains, and inadequate use of sunscreen in adulthood.12 We investigated the effects of sunscreen use on the incidence of melanoma in our lifestyle model and discovered that it decreased the risk for melanoma. Respondents who used it always had a much lower risk for developing melanoma than those who never or rarely applied it. Individuals who used sunscreen always and repetitively (ie, more than once per period of sun exposure) did not show a lower risk than those who used it once per period of sun exposure. This finding could mean that patients who are known to get sunburns or who feel a certain discomfort on direct exposure to the sun tend to use sunscreen always and repetitively.
It is important to note that some investigators disagree with the importance of some generally accepted means of prevention, such as the effect of sunscreen products. Due to insufficient evidence, the role of sunscreen use in reducing the risk for skin cancer, especially cutaneous MM, is controversial.13 Although we could prove there is a considerable difference in the incidence of melanoma in patients who claimed to use sunscreen always versus those who never use it, we agree that more evidence on this topic is needed. Furthermore, it has been reported that risk for melanoma has increased with rising intermittent sun exposure and indoor tanning bed use.14,15
Respondents who regularly traveled to seaside regions showed a surprisingly lower incidence of melanoma than respondents who did not spend their vacations in seaside locations. It is possible that individuals who choose not to spend their vacations at the seaside are more prone to sunburns and therefore do not prefer to spend their free time in direct sunlight. Another possible explanation is that individuals who regularly travel to seaside regions actively try to protect themselves from sunlight and sunburns. A higher incidence of melanoma also was observed in respondents who reported sun exposure during work.
In our exposure model, we demonstrated that a history of sunburns is the strongest risk factor for melanoma. Frequent sunburns during childhood and adolescence were strongly associated with the development of MM. This association has been supported in a systematic review on sun exposure during childhood and associated risks.16
Conclusion
To improve patient knowledge about melanoma prevention, we suggest directing targeted campaigns that address high-risk population groups, such as individuals with red hair and/or light eyes, people with an occupation associated with frequent UV exposure, and individuals with higher levels of education. With regard to younger populations, parents as well as physicians and teachers should be aware that frequent sunburns during childhood and adolescence and use of tanning beds are 2 main risk factors for MM.
1. IARC monographs on the evaluation of carcinogenic risks to humans. solar and ultraviolet radiation. IARC Monogr Eval Carcinog Risks Hum. 1992;55:1-316.
2. Kunte C, Geimer T, Baumert J, et al. Analysis of predictive factors for the outcome of complete lymph node dissection in melanoma patients with metastatic sentinel lymph nodes. J Am Acad Dermatol. 2011;64:655-662.
3. Parkin D, Bray F, Ferlay J, et al. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74-108.
4. SEER Stat Fact Sheets: melanoma of the skin. Bethesda, MD: National Cancer Institute; 2013. http://seer.cancer.gov/statfacts/html/melan.html#incidence-mortality. Accessed October 25, 2014.
5. Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893-2917.
6. Nijsten T, Stern RS. How epidemiology has contributed to a better understanding of skin disease [published online ahead of print December 8, 2011]. J Invest Dermatol. 2012;132(3, pt 2):994-1002.
7. Magdum A, Leonforte F, McNaughton E, et al. Sun protection–do we know enough [published online ahead of print February 8, 2012]? J Plast Reconstr Aesthet Surg. 2012;65:1384-1389.
8. Zalaudek I, Whiteman D, Rosendahl C, et al. Update on melanoma and non-melanoma skin cancer. Annual Skin Cancer Conference 2011, Hamilton Island, Australia, 2011. Expert Rev Anticancer Ther. 2011;11:1829-1832.
9. Mackenbach JP. Health inequalities: Europe in profile. http://ec.europa.eu/health/ph_determinants/socio_economics/documents/ev_060302_rd06_en.pdf. Published February 2006. Accessed October 25, 2014.
10. Ballester I, Oliver V, Bañuls J, et al. Multicenter case-control study of risk factors for cutaneous melanoma in Valencia, Spain [published online ahead of print May 22, 2012]. Actas Dermosifiliogr. 2012;103:790-797.
11. Jaimes N, Marghoob AA. An update on risk factors, prognosis and management of melanoma patients. G Ital Dermatol Venereol. 2012;147:1-19.
12. Vranova J, Arenbergerova M, Arenberger P, et al. Incidence of cutaneous malignant melanoma in the Czech Republic: the risks of sun exposure for adolescents. Neoplasma. 2012;59:316-325.
13. Planta MB. Sunscreen and melanoma: is our prevention message correct? J Am Board Fam Med. 2011;24:735-739.
14. Veierød MB, Adami HO, Lund E, et al. Sun and solarium exposure and melanoma risk: effects of age, pigmentary characteristics, and nevi. Cancer Epidemiol Biomarkers Prev. 2010;19:111-120.
15. Doré JF, Chignol MC. Tanning salons and skin cancer [published online ahead of print August 15, 2011]. Photochem Photobiol Sci. 2012;11:30-37.
16. Whiteman DC, Whiteman CA, Green AC. Childhood sun exposure as a risk factor for melanoma: a systematic review of epidemiologic studies. Cancer Causes Control. 2001;12:69-82.
1. IARC monographs on the evaluation of carcinogenic risks to humans. solar and ultraviolet radiation. IARC Monogr Eval Carcinog Risks Hum. 1992;55:1-316.
2. Kunte C, Geimer T, Baumert J, et al. Analysis of predictive factors for the outcome of complete lymph node dissection in melanoma patients with metastatic sentinel lymph nodes. J Am Acad Dermatol. 2011;64:655-662.
3. Parkin D, Bray F, Ferlay J, et al. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74-108.
4. SEER Stat Fact Sheets: melanoma of the skin. Bethesda, MD: National Cancer Institute; 2013. http://seer.cancer.gov/statfacts/html/melan.html#incidence-mortality. Accessed October 25, 2014.
5. Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893-2917.
6. Nijsten T, Stern RS. How epidemiology has contributed to a better understanding of skin disease [published online ahead of print December 8, 2011]. J Invest Dermatol. 2012;132(3, pt 2):994-1002.
7. Magdum A, Leonforte F, McNaughton E, et al. Sun protection–do we know enough [published online ahead of print February 8, 2012]? J Plast Reconstr Aesthet Surg. 2012;65:1384-1389.
8. Zalaudek I, Whiteman D, Rosendahl C, et al. Update on melanoma and non-melanoma skin cancer. Annual Skin Cancer Conference 2011, Hamilton Island, Australia, 2011. Expert Rev Anticancer Ther. 2011;11:1829-1832.
9. Mackenbach JP. Health inequalities: Europe in profile. http://ec.europa.eu/health/ph_determinants/socio_economics/documents/ev_060302_rd06_en.pdf. Published February 2006. Accessed October 25, 2014.
10. Ballester I, Oliver V, Bañuls J, et al. Multicenter case-control study of risk factors for cutaneous melanoma in Valencia, Spain [published online ahead of print May 22, 2012]. Actas Dermosifiliogr. 2012;103:790-797.
11. Jaimes N, Marghoob AA. An update on risk factors, prognosis and management of melanoma patients. G Ital Dermatol Venereol. 2012;147:1-19.
12. Vranova J, Arenbergerova M, Arenberger P, et al. Incidence of cutaneous malignant melanoma in the Czech Republic: the risks of sun exposure for adolescents. Neoplasma. 2012;59:316-325.
13. Planta MB. Sunscreen and melanoma: is our prevention message correct? J Am Board Fam Med. 2011;24:735-739.
14. Veierød MB, Adami HO, Lund E, et al. Sun and solarium exposure and melanoma risk: effects of age, pigmentary characteristics, and nevi. Cancer Epidemiol Biomarkers Prev. 2010;19:111-120.
15. Doré JF, Chignol MC. Tanning salons and skin cancer [published online ahead of print August 15, 2011]. Photochem Photobiol Sci. 2012;11:30-37.
16. Whiteman DC, Whiteman CA, Green AC. Childhood sun exposure as a risk factor for melanoma: a systematic review of epidemiologic studies. Cancer Causes Control. 2001;12:69-82.
Practice Points
- Our study revealed the following common risk factors associated with higher melanoma incidence: light eye color (ie, blue, green, gray), Fitzpatrick skin types I and II, frequent sunburns during childhood and adolescence, and higher level of education.
- Prevention campaigns should be implemented to improve awareness of melanoma to reduce exposure to UV radiation among high-risk patient populations.