Eva Månsson-Brahme

2-cm versus 4-cm surgical excision margins for primary cutaneous melanoma thicker than 2 mm: a randomised, multicentre trial

BACKGROUND Optimum surgical resection margins for patients with clinical stage IIA-C cutaneous melanoma thicker than 2 mm are controversial. The aim of the study was to test whether survival was different for a wide local excision margin of 2 cm compared with a 4-cm excision margin. METHODS We undertook a randomised controlled trial in nine European centres. Patients with cutaneous melanoma thicker than 2 mm, at clinical stage IIA-C, were allocated to have either a 2-cm or a 4-cm surgical resection margin. Patients were randomised in a 1:1 allocation to one of the two groups and stratified by geographic region. Randomisation was done by sealed envelope or by computer generated lists with permuted blocks. Our primary endpoint was overall survival. The trial was not masked at any stage. Analyses were by intention to treat. Adverse events were not systematically recorded. The study is registered with ClinicalTrials.gov, number NCT01183936. FINDINGS 936 patients were enrolled from Jan 22, 1992, to May 19, 2004; 465 were randomly allocated to treatment with a 2-cm resection margin, and 471 to receive treatment with a 4-cm resection margin. One patient in each group was lost to follow-up but included in the analysis. After a median follow-up of 6·7 years (IQR 4·3-9·5) 181 patients in the 2-cm margin group and 177 in the 4-cm group had died (hazard ratio 1·05, 95% CI 0·85-1·29; p=0.64). 5-year overall survival was 65% (95% CI 60-70) [corrected] in the 2-cm group and 65% (40-70) in the 4-cm group (p=0·69). INTERPRETATION Our findings suggest that a 2-cm resection margin is sufficient and safe for patients with cutaneous melanoma thicker than 2 mm. FUNDING Swedish Cancer Society and Stockholm Cancer Society.

Psychological reactions in patients with malignant melanoma

Psychological and psychosomatic reactions to malignant melanoma were studied, comparing patients with tumour thickness < or = 0.8 mm versus > 0.8 mm and recurrent versus non-recurrent patients. Gender differences were also studied. Consecutive melanoma patients, Stage I (n = 144), were interviewed at their first postsurgery follow-up visit to an oncology clinic and completed questionnaires 7 and 13 months later. The questionnaire contained items regarding interest in nevi, sleeping problems, psychosomatic complaints, and the Hospital Anxiety and Depression Scale. Patients with a more unfavourable prognosis (tumour thickness > 0.8 mm), subjected to regular medical procedures, did not differ from those with a more favourable prognosis (< or = 0.8 mm), except reporting more sleeping problems. Women had considerably higher levels of problems than men. Amongst patients with an unfavourable prognosis, those with recurrence within 2 years showed lower levels of anxiety at the first visit compared with those free from recurrence after 2 years.

Trends in Incidence of Cutaneous Malignant Melanoma in a Swedish Population 1976-1994

The incidence of cutaneous malignant melanoma has been increasing in Sweden for several decades. In the Stockholm-Gotland area educational activities for healthcare professionals were started in the late 1970s and public primary and secondary prevention campaigns were initiated in the mid-1980s. Melanoma incidence trends have been studied in Sweden, with special reference to trends in the Stockholm-Gotland area where these prevention campaigns were first started. During 1976-1994 the average annual increase of age-standardized incidence in the Stockholm-Gotland area was about 5%, the increase being associated mainly with thin tumors and melanoma in situ. During the 1990s, the incidence among males leveled off. In contrast, no such shift in trend was observed among females, or among males or females residing outside the Stockholm-Gotland area. The campaigns may have contributed to a trend towards earlier diagnosis but there is still no clear effect of the primary prevention efforts.

Metastatic Patterns, Clinical Outcome, and Malignant Phenotype in Malignant Cutaneous Melanoma

The objective of this population-based study was to assess metastatic pathways and outcomes vs. selected clinical and histopathologic features of the primary tumor in patients with recurrent cutaneous malignant melanoma. At a median follow-up time of 11 years, 569/2493 patients with recurrence were identified. We demonstrated a 5-year survival rate of 82% and 30% among those with a primary local or regional recurrence, respectively. Patients with primary distant skin, distant lymph node, or pulmonary metastases had a significantly better survival compared with those with CNS, bone, visceral, liver, or multiple sites of first distant metastases. The metastatic pathways were similar with regard to histogenetic type, primary tumor thickness, Clarks level of invasion, and primary tumor ulceration. Different histogenetic types, as assessed by light microscopy, imply different risks of recurrence. However, once the recurrence is manifest, the metastatic pathways are uniform, as well as prognosis, and survival.

Epidemiological Characteristics of Cutaneous Malignant Melanoma of the Head and Neck: A Population-based Study

Since cutaneous malignant melanoma (CMM) and melanoma in situ (MIS) of the head and neck have only partially been differentiated from CMM of other anatomic sites, these lesions are classified in detail in this study. Data from 756 patients derived from the population-based register of the Stockholm-Gotland area were analyzed and the findings showed that the incidence of CMM was 3.4 times higher in the face compared to the skin outside the head-neck area and that lentigo maligna melanoma was 74 times and nodular melanoma 2.3 times more common in the face. Mean age at diagnosis was significantly higher for patients with CMM of the head and neck irrespective of histogenetic type. Tumor site within the head and neck related to age at diagnosis. CMM of the head and neck differs from CMM of other locations. Epidemiological data are in agreement with the hypothesis that UV radiation (chronic or intermittent) may give rise to melanomas with various phenotypic traits.

A Prospective Population‐Based Study of Cutaneous Malignant Melanoma of the Head and Neck

Objectives/Hypothesis For cutaneous malignant melanoma (CMM) of the head and neck, neither prognostic factors in population‐based groups, nor outcome with respect to surgical resection margins is clear. Therefore, we analyzed data in a regional registry to align treatment results for CMM of the head and neck with prognosis and survival times.

Monitoring of Kindreds With Hereditary Predisposition for Cutaneous Melanoma and Dysplastic Nevus Syndrome: Results of a Swedish Preventive Program

PURPOSE To evaluate a program initiated in 1987 by the Swedish Melanoma Study Group aiming to provide preventive surveillance to kindreds with hereditary cutaneous melanoma and dysplastic nevus syndrome. PATIENTS AND METHODS Overall, 2,080 individuals belonging to 280 melanoma families were followed for 14 years between 1987 and 2001 at 12 participating centers. Data were registered in a central database. RESULTS Among 1,912 skin lesions excised during follow-up, 41 melanomas were removed in 32 individuals. Of these, 15 (37%) were in situ melanomas and 26 (63%) invasive melanomas. The median tumor thickness of invasive melanomas was 0.5 mm. Ulceration was absent in 24 of 26 invasive melanomas (92%) and 12 (46%) lacked vertical growth phase. Compared with melanomas in the general Swedish population, the melanomas identified in these kindreds during follow-up had better prognostic characteristics. All melanomas except one were diagnosed in families with two or more first-degree relatives with melanoma. Diagnosis of melanoma occurred in three of eight kindreds with germline CDKN2A mutations, supporting that families with such mutations are at increased risk for melanoma development. Of the 32 individuals who developed melanoma during follow-up, 21 (66%) had had at least one previously diagnosed melanoma. CONCLUSION This study shows that a coordinated program aimed at detecting and offering skin surveillance in kindreds with hereditary cutaneous melanoma results in a low incidence of melanomas during the follow-up period and that the tumors that do arise have favorable prognostic characteristics.

Low level of education is associated with later stage at diagnosis and reduced survival in cutaneous malignant melanoma : a nationwide population-based study in Sweden

BACKGROUND A worse outcome has been reported for cutaneous malignant melanoma (CMM) patients with low socioeconomic status. We have investigated the association between level of education, clinical stage at diagnosis (stage at diagnosis) and CMM-specific survival in Sweden. METHODS We identified 27,235 patients from the Swedish Melanoma Register diagnosed with a primary invasive CMM between 1990 and 2007 and linked data to nationwide, population-based, health and census registers with a follow-up to 2010. RESULTS The odds ratio (OR) of higher disease stage at diagnosis was significantly increased in lower education groups (OR stage II versus I=1.6; 95% confidence interval (CI)=1.5-1.7. OR stage III-IV versus I=2.3; 95% CI=1.8-2.9). The risk of dying of CMM, was significantly increased in patients with low (hazard ratio (HR) low versus high=2.02; 95% CI=1.80-2.26; p<0.0001) and intermediate (HR intermediate versus high=1.35; 95% CI=1.20-1.51; p<0.0001) level of education. After adjustment for age, gender, stage at diagnosis and other known prognostic factors, the HRs remained significant for low versus high (HR=1.13; 95% CI=1.01-1.27; p=0.04) but not for intermediate versus high (HR=1.11; 95% CI=0.99-1.24; p=0.08) education. The HR associated with low level of education was significantly higher among female patients, patients <55 years, patients with truncal tumours and during the first 5 years after diagnosis. CONCLUSION Lower level of education is associated with reduced CMM-specific survival, which may at least partially be attributed to a more advanced stage at diagnosis. These results emphasise the need for improved early detection strategies.

MC1R variation and melanoma risk in the Swedish population in relation to clinical and pathological parameters

The genetic background of cutaneous malignant melanoma (CMM) includes both germ line aberrations in high‐penetrance genes, like CDKN2A, and allelic variation in low‐penetrance genes like the melanocortin‐1 receptor gene, MC1R. Red‐hair colour associated MC1R alleles (RHC) have been associated with red hair, fair skin and risk of CMM. We investigated MC1R and CDKN2A variation in relation to phenotype, clinical factors and CMM risk in the Swedish population. The study cohort consisted of sporadic primary melanoma patients, familial melanoma patients and a control group. An allele‐dose dependent increase in melanoma risk for carriers of variant MC1R alleles (after adjusting for phenotype), with an elevated risk among familial CMM patients, was observed. This elevated risk was found to be significantly associated with an increased frequency of dysplastic nevi (DN) among familial patients compared to sporadic patients. MC1R variation was found to be less frequent among acral lentiginous melanomas (ALM) and dependent on tumour localisation. No association was found between CDKN2A gene variants and general melanoma risk. Two new variants in the POMC gene were identified in red haired individuals without RHC alleles.

Prevalence of primary acquired melanosis and nevi of the conjunctiva and uvea in the dysplastic nevus syndrome. A case-control study.

PURPOSE To investigate whether conjunctival and uveal nevi and primary acquired melanosis are more common in individuals with the dysplastic nevus syndrome than in control subjects derived from the general population. METHODS Power calculations were used to determine the sample size. After invitation, 162 individuals with the dysplastic nevus syndrome and 119 control subjects, matched for sex and age but otherwise randomized from the Stockholm county census file, were entered into the study. All individuals were examined in a masked fashion by the same ophthalmologist, and the presence of conjunctival and uveal melanocytic lesions and the iris color, skin type, and hair color of each individual were recorded. Contingency tables and odds ratios were used for statistical evaluation. RESULTS The proportions of individuals with the dysplastic nevus syndrome featuring primary acquired melanosis of the conjunctiva, or nevi of the iris and choroid were not significantly different from those of control subjects. However, individuals with the dysplastic nevus syndrome appeared to have a more sun-sensitive skin type and a reddish or blond hair color more often than control subjects. CONCLUSION In contrast to previous reports, this study suggests that ocular melanocytic lesions are no more common in individuals with the dysplastic nevus syndrome than in the general population. Therefore, this work does not provide support that periodic ophthalmic surveillance of individuals with the dysplastic nevus syndrome for the purpose of detecting conjunctival or uveal melanomas, or their precursors, is meaningful.