BACKGROUND:

Interferon alpha is the only agent approved for the postoperative adjuvant treatment of high-risk cutaneous melanoma. However, the survival advantage associated with this treatment is unclear, especially in terms of overall survival. Thus, adjuvant interferon is not universally considered a gold standard treatment by all oncologists.

OBJECTIVES:

To assess the disease-free survival and overall survival effects of interferon alpha as adjuvant treatment for people with high-risk cutaneous melanoma.

SEARCH METHODS:

We searched the following databases up to August 2012: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2012, issue 8), MEDLINE (from 2005), EMBASE (from 2010), AMED (from 1985), and LILACS (from 1982). We also searched trials databases in 2011, and proceedings of the ASCO annual meeting from 2000 to 2011. We checked the reference lists of selected articles for further references to relevant trials.

SELECTION CRITERIA:

We included only randomised controlled trials (RCTs) comparing interferon alpha to observation (or any other treatment) for the postoperative (adjuvant) treatment of patients with high-risk skin melanoma, that is, people with regional lymph node metastasis (American Joint Committee on Cancer (AJCC) TNM (tumour, lymph node, metastasis) stage III) undergoing radical lymph node dissection, or people without nodal disease but with primary tumour thickness greater than 1 mm (AJCC TNM stage II).

DATA COLLECTION AND ANALYSIS:

Two authors extracted data, and a third author independently verified the extracted data. The main outcome measure was the hazard ratio (HR), which is the ratio of the risk of the event occurring in the treatment arm (adjuvant interferon) compared to the control arm (no adjuvant interferon). The survival data were either entered directly into Review Manager (RevMan) or extrapolated from Kaplan-Meier plots and then entered into RevMan. Based on the presence of between-study heterogeneity, we applied a fixed-effect or random-effects model for calculating the pooled estimates of treatment efficacy.

MAIN RESULTS:

Eighteen RCTs enrolling a total of 10,499 participants were eligible for the review. The results from 17 of 18 of these RCTs, published between 1995 and 2011, were suitable for meta-analysis and allowed us to quantify the therapeutic efficacy of interferon in terms of disease-free survival (17 trials) and overall survival (15 trials). Adjuvant interferon was associated with significantly improved disease-free survival (HR (hazard ratio) = 0.83; 95% CI (confidence interval) 0.78 to 0.87, P value < 0.00001) and overall survival (HR = 0.91; 95% CI 0.85 to 0.97; P value = 0.003). We detected no significant between-study heterogeneity (disease-free survival: I² statistic = 16%, Q-test P value = 0.27; overall survival: I² statistic = 6%; Q-test P value = 0.38).
Considering that the 5-year overall survival rate for TNM stage II–III cutaneous melanoma is 60%, the number needed to treat (NNT) is 35 participants (95% CI = 21 to 108 participants) in order to prevent 1 death. The results of subgroup analysis failed to answer the question of whether some treatment features (i.e. dosage, duration) might have an impact on interferon efficacy or whether some participant subgroups (i.e. with or without lymph node positivity) might benefit differently from interferon adjuvant treatment.
Grade 3 and 4 toxicity was observed in a minority of participants: In some trials, no-one had fever or fatigue of Grade 3 severity, but in other trials, up to 8% had fever and up to 23% had fatigue of Grade 3 severity. Less than 1% of participants had fever and fatigue of Grade 4 severity. Although it impaired quality of life, toxicity disappeared after treatment discontinuation.

AUTHORS' CONCLUSIONS:

The results of this meta-analysis support the therapeutic efficacy of adjuvant interferon alpha for the treatment of people with high-risk (AJCC TNM stage II-III) cutaneous melanoma in terms of both disease-free survival and, though to a lower extent, overall survival. Interferon is also valid as a reference treatment in RCTs investigating new therapeutic agents for the adjuvant treatment of this participant population. Further investigation is required to select people who are most likely to benefit from this treatment.

Epidemiological studies suggest a relationship between suntanning habits and high risk of melanoma. A literature review was carried out for the period between 1977 and 1998 using Medline and Embase (Excerpta Medica) databases. The analysis showed that intentional sun exposure is highly prevalent among youths, despite their awareness of the risks involved in excessive exposure to ultraviolet radiation and their knowledge on skin protection measures. Intentional exposure is a habit fostered by certain beliefs and attitudes towards suntanning and stimulated by peer pressure and aesthetic referents. The most common tanning practices involve a high risk of developing melanoma. It was concluded that the most effective means to prevent melanoma is mass media dissemination of the concept that having a tanned skin is not healthy -- since it implies the skin being damaged by solar ultraviolet radiation -- and education campaigns for effectively changing people's behaviors and their motivations.

A variety of estimates of the value and impact of physician skin examinations (PSEs) in screening for melanoma have been published. Although current melanoma screening guidelines vary, new evidence supports improved melanoma outcomes associated with PSEs. In this systematic review, we evaluated 5 observational studies of the impact of PSEs on melanoma thickness at diagnosis and melanoma mortality rates. Although definitive evidence from randomized controlled trials supporting improved health outcomes associated with PSEs is lacking, these well-designed observational studies have found PSEs to be correlated with thinner melanomas at diagnosis and reduced melanoma mortality rates.

Unknown melanoma occurs as metastasis to skin, nodes or viscera, without a detectable cutaneous primary tumour. We reviewed our database of 4881 melanoma patients, diagnosed and followed up prospectively for a 33-year period. We identified 93 cases of metastatic melanoma without evidence of primary; however, five of these patients had a history of a previous excision of a presumed benign lesion without histological examination and were excluded from analyses. At diagnosis, metastases were cutaneous in 35.3% of cases, nodal in 43.2% and visceral in 17% of cases; in 4.5% of patients, both skin and nodes were involved. In all cases, clinical inspection and staging procedures performed at diagnosis of metastatic disease failed to identify a primary melanoma. In 11 cases (11.8%), extensively regressed pigmented lesions (without evidence of melanoma cells at the histological examination) were documented; moreover, we identified in our series five patients with unknown primary affected by vitiligo. The 5-year and 10-year overall survival rates were 49.6 and 41.4%, respectively, with a median of 4.9 years. The 5-year and 10-year time to progression rates were 39.4 and 32.3%, respectively, with a median of 2.3 years. Survival was longer in females and showed significant differences among patients with skin, lymph node or visceral involvement at diagnosis. In melanoma patients, unknown primary represents a not so rare event, with an uncertain origin. We confirmed the relatively good prognosis of unknown primary melanoma patients, a fact that has to be taken into consideration for their management.

OBJECTIVE:

To systematically review psycho-educational interventions developed for melanoma survivors.

METHODS:

Electronic databases Medline, PsycINFO, Embase, and CINAHL were systematically searched using key words and subject headings for articles describing educational or psychological interventions designed specifically for people affected by melanoma.

RESULTS:

Twenty-seven articles, generated by 16 unique interventions, were included for detailed review. Overall, educational interventions showed increased patient satisfaction with clinical care and information provision, as well as increased frequency of skin self-examination, although accuracy and thoroughness of skin examination were seldom reported. Participation in psychological interventions was associated with decreases in anxiety, health-related distress, and melanoma recurrence rates, as well as positive changes in coping with illness. Programs, when implemented as part of routine clinical care, were found to be cost-effective.

CONCLUSIONS:

Interventions in this field vary widely, limiting the identification of 'active ingredients' for psychological or behavioral change. Future intervention studies should ensure sufficient information is provided to support program replication and comprehensive assessment of program outcomes. Copyright © 2012 John Wiley & Sons, Ltd.

BACKGROUND:

External ear melanoma accounts for only 1% of all cutaneous melanomas, and data on its optimal management and prognosis are limited.

AIM:

We aim to review the literature on external ear melanoma to guide surgeons in the treatment of this uncommon and peculiar pathology.

MATERIALS AND METHODS:

A systematic review of English language studies on ear melanoma published from 1993 to 2013 was performed using the PubMed electronic database. Data on epidemiology, oncological treatment (tumor resection and regional lymph nodes management), and reconstruction were extrapolated from selected papers.

RESULTS:

The total number of patients was 858 (30 studies). The helix was the most common location (57%); superficial spreading melanoma was the most common histopathological subtype (41%). The mean Breslow thickness was 2.01 mm, with 88% of stage I-II patients. Sentinel lymph node biopsy was performed in 45% of patients, with 8% of positive nodes. Available data on its prognosis are fragmentary and contrasting, but the Breslow thickness appears to be the main prognostic factor. There is a tendency towards reduced resection margins and preservation of the underlying perichondrium and cartilage. Local flaps are the most popular reconstructive option.

CONCLUSION:

To the best of our knowledge, this systematic review presents the largest data series on external ear melanoma. There is no general agreement on its surgical management, but a favorable prognosis seems to justify the tendency towards conservative treatments.

RECORD STATUS:

None

CITATION:

Pichon Riviere A., Augustovski F., Garcia Marti S., Glujovsky D., Lopez A., Bardach A., Aruj P., Galante J.. Dermatoscopa Digital en el diagnostico de melanoma . Digital dermoscopy in the diagnosis of melanoma . Buenos Aires: Institute for Clinical Effectiveness and Health Policy (IECS). Informe de Respuesta Rapida No195. 2010

Lifetime risk for malignant melanoma has increased from 1 in 1500 in the United States in 1930 to 1 in 75 projected for the year 2000. Because the tumor's thickness at excision is the primary prognostic determinant, early detection through the history and physical examination can play an important role in the patient's clinical course. Two checklists have been developed as diagnostic aids, the ABCD (A indicates asymmetry; B, border irregularity; C, irregular color; and D, diameter >6 mm) and the revised 7-point checklists. These checklists should be interpreted with some discretion, but 2 studies have found the sensitivity for the ABCD checklist to be 92% (95% confidence interval [CI], 82%-96%) and 100% (95% CI, 54%-100%); 1 study found the specificity to be 98% (95% CI, 95%-99%). The revised 7-point checklist has been reported to have a sensitivity of 79% (95% CI, 70%-85%) to 100% (95% CI, 94%-100%) and specificity of 30% (95% CI, 21%-39%) to 37% (95% CI, 28%-46%). Physicians' global assessments for detecting the presence or absence of melanoma are estimated to have a specificity of 96% to 99%, while sensitivity ranges widely from 50% to 97%. Nondermatologists' examinations appear to be less sensitive than examinations performed by dermatologists.

Melanoma incidence is increasing rapidly worldwide among white-skinned populations. Earlier diagnosis is the principal factor that can improve prognosis. Defining high-risk populations using risk prediction models may help targeted screening and early detection approaches. In this systematic review, we searched Medline, EMBASE, and the Cochrane Library for primary research studies reporting or validating models to predict risk of developing cutaneous melanoma. A total of 4,141 articles were identified from the literature search and six through citation searching. Twenty-five risk models were included. Between them, the models considered 144 possible risk factors, including 18 measures of number of nevi and 26 of sun/UV exposure. Those most frequently included in final risk models were number of nevi, presence of freckles, history of sunburn, hair color, and skin color. Despite the different factors included and different cutoff values for sensitivity and specificity, almost all models yielded sensitivities and specificities that fit along a summary ROC with area under the ROC (AUROC) of 0.755, suggesting that most models had similar discrimination. Only two models have been validated in separate populations and both also showed good discrimination with AUROC values of 0.79 (0.70-0.86) and 0.70 (0.64-0.77). Further research should focus on validating existing models rather than developing new ones.

OBJECTIVE:

To assess data on survival, recurrence and histological factors in positive and negative sentinel lymph nodes in thin melanoma cases.

METHODS:

A systematic review was conducted on observational studies in four databases (Cochrane Library, Medline, Embase and Lilacs). Positive and negative micrometastases in sentinel lymph node biopsy were compared regarding the clinical outcomes - death and recurrence - and six histological factors - vertical growth phase, Breslow thickness, Clark level, ulceration, regression and mitosis rate.

RESULTS:

Positive sentinel lymph node is statistically associated with greater risk of death in six studies (OR: 7.2; 95%CI [2.37-21.83]; I2 0%) and also to recurrence in three studies (OR: 30.7; 95%CI [12.58-74.92]; I2 36%). Comparing positive and negative groups, the histological factors predicting positive sentinel nodes and poor prognosis were: mitosis rate ≥ 5/mm2 (OR: 16.29; 95%CI [3.64-72.84]; I2 40%); VGP (OR: 2.93; 95%CI [1.08-7.93]; I2 59%); Breslow thickness ≥ 0.75mm (OR: 2.23; 95%CI [1.29-3.86]; I2 0%); and Clark level IV-V (OR: 1.61; 95%CI [1.06-2.44]; I234%).

CONCLUSIONS:

The statistically significant results associated with the presence of micrometastases in thin melanomas were Breslow thickness ≥ 0.75 mm, Clark level IV-V and mitoses ≥ 5/mm2, absence of regression. This histological factor of ulceration was associated, but not statistically significant.