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Taste and smell alterations have been recognized as common symptoms in relation to various cancers. However, previous research suggests that patients do not receive sufficient support in managing taste and smell alterations. Therefore, the objective of this study is to investigate how persons with experience from lung cancer-related taste and smell alterations reason about resources and strategies offered and used to manage these symptoms. Data from semi-structured individual interviews with 13 women and four men were analyzed with qualitative content analysis. We used Kleinman's now classic medical anthropological model of local health care systems, consisting of the personal, professional, and folk sector, to interpret and understand how people respond to sickness experiences in their daily lives. By presenting the findings using this model, we demonstrate that most strategies for dealing with taste and smell alterations were undertaken in the personal sector, i.e. in participants' daily lives, on an individual level and in interaction with family, social networks and communities. Taste and smell alterations implied two overarching challenges: 1) adjusting to no longer being able to trust information provided by one's own senses of taste and/or smell, and 2) coming to terms with taste and smell alterations as a part of having lung cancer. Health care professionals' involvement was described as limited, but appeared to fulfil most participants' expectations. However, through provision of normalizing information, practical advice, and to some extent, emotional support, health care professionals had potential to influence strategies and resources used for dealing with taste and smell alterations. With this study, we further the understanding of how people deal with lung cancer-related taste and smell alterations and discuss the role of health care professionals for this process.

Little is known about cutaneous malignant melanoma (CMM) among immigrants in Europe. We aimed to investigate clinical characteristics and disease-specific survival among first- and second-generation immigrants in Sweden. This nationwide population-based study included 27,235 patients from the Swedish Melanoma Register diagnosed with primary invasive CMM, 1990-2007. Data were linked to nationwide, population-based registers followed up through 2013. Logistic regression and Cox regression models were used to determine the association between immigrant status, stage and CMM prognosis, respectively. After adjustments for confounders, first generation immigrants from Southern Europe were associated with significantly more advanced stages of disease compared to Swedish-born patients [Stage II vs. I: Odds ratio (OR) = 2.37, 95% CI = 1.61-3.50. Stage III-IV vs I: OR = 2.40, 95% CI = 1.08-5.37]. The ORs of stage II-IV versus stage I disease were increased among men (OR = 1.9; 95% CI = 1.1-3.3; p = 0.020), and women (OR = 4.8; 95% CI = 2.6-9.1; p < 0.001) in a subgroup of immigrants from former Yugoslavia compared to Swedish-born patients. The CMM-specific survival was significantly decreased among women from former Yugoslavia versus Swedish-born women [hazard ratio (HR)=2.2; 95% CI = 1.1-4.2; p = 0.043]. After additional adjustments including stage, the survival difference was no longer significant. No survival difference between the second generation immigrant group and Swedish-born patients were observed. In conclusion, a worse CMM-specific survival in women from former Yugoslavia was associated with more advanced stages of CMM at diagnosis. Secondary prevention efforts focusing on specific groups may be needed to further improve the CMM prognosis., (© 2016 UICC.)

Purpose: Taste and smell alterations (TSAs) are common symptoms in patients with cancer that may interfere with nutritional intake and quality of life. In this study, we explore and describe how characteristics of self-reported TSAs change in individuals with lung cancer over time using a multiple case study approach to present longitudinal data from individuals., Methods: Patients under investigation for lung cancer were recruited from one university hospital in Sweden. The 52 patients providing data eligible for the analyses presented here were those treated for primary lung cancer with three measurement time-points, of which one was prior to treatment and two after treatment start. Four self-report instruments were used for data collection. These included the Taste and Smell Survey, used to characterize TSAs for each individual at the three time-points and instruments measuring nutritional status, symptom burden and well-being. Three patient cases are described in detail to illustrate variation in individual experiences of TSAs., Results: The characteristics of the TSAs experienced changed over time for many of the individuals in this study, including those undergoing surgery or stereotactic radiotherapy. The case descriptions show how the individual experiences of TSAs and the impact on daily life of these symptoms not only depend on TSA characteristics, but may be influenced by contextual factors, e.g. other symptoms and life situation., Conclusions: Our results suggest that healthcare professionals need to consider the variation in characteristics of TSAs among and within patients over time, and be attentive to individual experiences of TSAs., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Germline CDKN2A mutations are found in 5-20% of melanoma families. Numerous studies have shown that carriers of CDKN2A mutations have increased risks of non-melanoma cancers, but so far there have been no studies investigating cancer risks in CDKN2A wild type (wt) melanoma families. In this prospective cohort study, index melanoma cases (n = 224) and their first-degree relatives (n = 944) were identified from 154 confirmed CDKN2A wt melanoma families. Cancer diagnoses in family members and matched controls were obtained from the Swedish Cancer Registry. Relative risks (RR), odds ratios (OR) and two-sided 95% confidence intervals (95% CI) were calculated. In index cases and first-degree relatives, the prospective RR for melanoma was 56.9 (95% CI 31.4-102.1) and 7.0 (95% CI 4.2-11.4), respectively, and for squamous cell skin cancers 9.1 (95% CI 6.0-13.7) and 3.4 (95% CI 2.2-5.2), respectively. In neither group, elevated risks were seen for non-skin cancers. In a subgroup analysis, CDKN2A wt melanoma families with young (<40 years) melanoma cases were found to have increased risk of non-skin cancers (RR 1.5, 95% CI 1.0-1.5). Further, MC1R gene variants were increased in familial melanoma cases compared to controls (OR 2.4, 95% CI 1.6-3.4). Our findings suggest that in the majority of CDKN2A wt melanoma families, a segregation of variants in low-risk melanoma genes such as MC1R causes increased skin cancer susceptibility, rather than mutations in high-risk cancer predisposing genes, such mutations are more probable to be found in melanoma families with young melanoma cases. This study further supports an implication of CDKN2A mutation screening as a clinical test that determines counseling and follows up routines of melanoma families., (© 2015 UICC.)

Background: Both patient survival and the proportion of patients diagnosed with thin cutaneous malignant melanoma (CMM) have been steadily rising in Sweden as in most Western countries, although the rate of improvement in survival appears to have declined in Sweden at the end of the last millennium., Objectives: To analyse the most recent trends in the distribution of tumour thickness (T category) as well as CMM-specific survival in Swedish patients diagnosed during 1997-2011., Methods: This nationwide population-based study included 30,590 patients registered in the Swedish Melanoma Register (SMR) and diagnosed with a first primary invasive CMM during 1997-2011. The patients were followed through 2012 in the national Cause of Death Register., Results: Logistic and Cox regression analyses adjusting for age at diagnosis, tumour site and healthcare region were carried out. The odds ratio for being diagnosed with thicker tumours was significantly reduced (P < 0·001) and the CMM-specific survival significantly improved in men diagnosed during 2007-2011 compared with men diagnosed during 1997-2001 (hazard ratio = 0·81; 95% confidence interval 0·72-0·91; P < 0·001), while the corresponding differences for women were not significant. Women were diagnosed with significantly thicker tumours during 2002-2006 and a tendency towards decreased survival was observed compared with those diagnosed earlier (during 1997-2001) and later (during 2007-2011)., Conclusions: In Sweden, the CMMs of men are detected earlier over time and this seems to be followed by an improved CMM-specific survival for men. Women are still diagnosed with considerably thinner tumours and they experience a better survival than men., (© 2014 British Association of Dermatologists.)

Background: The prognostic impact of several histopathological prognostic features in cutaneous malignant melanoma (CMM) remains controversial., Objectives: To assess the independent prognostic value of mitotic rate, regression, tumour-infiltrating lymphocytes (TILs) and growth phase in primary stage I and II CMMs., Methods: Clinicohistopathological data were obtained from the Stockholm-Gotland registry for 4237 patients diagnosed with an incident primary stage I or II CMM followed up to December 2011. The risk of CMM-specific death was evaluated by a Cox regression model., Results: A mitotic rate of 1-10 mitoses per mm(2) [hazard ratio (HR) 1·69, 95% confidence interval (CI) 1·16-2·45] and > 10 mitoses per mm(2) (HR 2·27, 95% CI 1·46-3·52) were significant; TILs and regression were not. A more detailed analysis of data assessed between 1989 and 1995 confirmed significantly increased HRs for the presence vs. absence of mitoses (HR1-5/mm² 2·25, 95% CI 1·36-3·76; HR6-10/mm² 2·34, 95% CI 1·23-4·44; HR> 10/mm² 2·64, 95% CI 1·39-4·99). Other prognosticators were increasing T-stage vs. T1, presence of ulceration and presence of vertical growth phase (VGP). In T1 CMMs, an increasing tumour thickness vs. < 0·7 mm (HR0·7-0·8 mm 2·24, 95% CI 1·24-4·04; HR>0·8 mm  2·92, 95% CI 1·57-5·43) and presence of ulceration were significantly associated with higher HRs; mitotic rate, TILs, regression and growth phase were not., Conclusions: Determinants of increased risk of CMM death in stage I and II CMMs were increasing T-stage, presence of ulceration, presence of mitoses and VGP. This was not found for TILs or regression., (© 2014 British Association of Dermatologists.)

Unlabelled: This study of patients under investigation for lung cancer (LC) aims to: 1) examine the prevalence of self-reported taste and smell alterations (TSAs) and their relationships with demographic and clinical characteristics; and 2) explore nutritional importance of TSAs by examining their associations with patient-reported weight loss, symptoms interfering with food intake, and changes in food intake., Methods: Patients were recruited consecutively during investigation for LC from one university hospital in Sweden. Patient-reported information on TSAs, demographics, six-month weight history, symptoms interfering with food intake, and changes in food intake was obtained. Relationships between TSAs and other variables were examined using two-tailed significance tests. In addition, putative explanatory factors for weight loss were explored in those patients diagnosed with LC, since a relationship between TSAs and weight loss was found in this group., Results: The final sample consisted of 215 patients, of which 117 were diagnosed with primary LC within four months of study inclusion and 98 did not receive a cancer diagnosis. The 38% prevalence of TSAs was identical in both groups, and were generally reported as mild and not interfering with food intake. However, a statistically significant relationship between TSAs and weight loss was found among patients with LC, with a median weight change of - 5.5% and a higher frequency of weight loss ≥ 10%. Patients with LC and weight loss ≥ 10%, had higher frequency of reporting TSAs, of decreased food intake and of ≥ 1 symptom interfering with food intake compared with those with less weight loss., Conclusion: TSAs, although relatively mild, were present in 38% of patients with and without LC. Relationships between TSAs and weight loss were found among patients with LC, but not fully explained by decreased food intake. This highlights the complexity of cancer-related weight loss.

Purpose: To investigate the association between cohabitation status, clinical stage at diagnosis, and disease-specific survival in cutaneous malignant melanoma (CMM)., Methods: This nationwide population-based study included 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 registers followed up through 2012., Results: After adjustment for age at diagnosis, level of education, living area, period of diagnosis, and tumor site, the odds ratios (ORs) of higher stage at diagnosis were significantly increased among men living alone versus men living with a partner (stage II v stage I: OR, 1.42; 95% CI, 1.29 to 1.57; stage III or IV v stage I: OR, 1.43; 95% CI, 1.14 to 1.79). The OR for stage II versus stage I disease was also increased among women living alone (OR, 1.15; 95% CI, 1.04 to 1.28). After adjustments for the factors listed earlier, the CMM-specific survival was significantly decreased among men living alone (hazard ratio [HR] for death, 1.48; 95% CI, 1.33 to 1.65; P < .001). After additional adjustments for all potential and established prognostic factors, CMM-specific survival among men living alone versus men living with a partner remained significantly decreased (HR, 1.31; 95% CI, 1.18 to 1.46; P < .001), suggesting a residual adverse effect on survival not accounted for by these parameters., Conclusion: In all age groups among men, living alone is significantly associated with reduced CMM-specific survival, partially attributed to a more advanced stage at diagnosis. This emphasizes the need for improved prevention and early detection strategies for this group.

Objectives: A large proportion of patients with cutaneous malignant melanoma (CMM) do not experience excess mortality due to their disease. This group of patients is referred to as the cure proportion. Few studies have examined the possibility of cure for CMM. The aim of this study was to estimate the cure proportion of patients with CMM in a Swedish population., Methods: We undertook a population-based study of 5850 CMM patients in two Swedish health care regions during 1996-2005. We used flexible parametric cure models to estimate cure proportions and median survival times (MSTs) of uncured by stage, sex, age and anatomical site., Results: Disease stage at diagnosis was the most important factor for the probability of cure, with a cure proportion of approximately 1.0 for stage IA. While the probability of cure decreased with older age, the influence of age was smaller on the MST of uncured. Differences in prognosis between males and females were mainly attributed to differences in cure as opposed to differences in MST of uncured., Conclusions: This population-based study showed approximately 100% cure among stage IA disease. Almost 50% of patients had stage IA disease and the high cure proportion for this large patient group is reassuring., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Clinical management of primary cutaneous melanomas is based on histopathological staging of the tumour. The aim of this study was to investigate, in a non-selected population in clinical practice, the agreement rate between general pathologists and pathologists experienced in melanoma in terms of the evaluation of histopathological prognostic parameters in cutaneous malignant melanomas, and to what extent the putative variability affected clinical management. A total of 234 cases of invasive cutaneous malignant melanoma were included in the study from the Stockholm-Gotland Healthcare Region in Sweden. Overall interobserver variability between a general pathologist and an expert review was 68.8-84.8%. Approximately 15.5% of melanomas ≤1 mm were re-classified either as melanoma in situ or melanomas >1 mm after review. In conclusion, review by a pathologist experienced in melanoma resulted in a change in recommendations about surgical excision margins and/or sentinel node biopsy in subgroups of T1 melanomas.

Background: Survival and prognostic factors for thin melanomas have been studied relatively little in population-based settings. This patient group accounts for the majority of melanomas diagnosed in western countries today, and better prognostic information is needed., Objectives: The aim of this study was to use established prognostic factors such as ulceration, tumour thickness and Clark's level of invasion for risk stratification of T1 cutaneous melanoma., Methods: From 1990 to 2008, the Swedish Melanoma Register included 97% of all melanomas diagnosed in Sweden. Altogether, 13,026 patients with T1 melanomas in clinical stage I were used for estimating melanoma-specific 10- and 15-year mortality rates. The Cox regression model was used for further survival analysis on 11,165 patients with complete data., Results: Ulceration, tumour thickness and Clark's level of invasion all showed significant, independent, long-term prognostic information. By combining these factors the patients could be subdivided into three risk groups: a low-risk group (67·9% of T1 cases) with a 10-year melanoma-specific mortality rate of 1·5% (1·2-1·9%); an intermediate-risk group (28·6% of T1 cases) with a 10-year mortality rate of 6·1% (5·0-7·3%); and a high-risk group (3·5% of T1 cases) with a 10-year mortality rate of 15·6% (11·2-21·4%). The high- and intermediate-risk groups accounted for 66% of melanoma deaths within T1., Conclusions: Using a population-based melanoma register, and combining ulceration, tumour thickness and Clark's level of invasion, three distinct prognostic subgroups were identified., (© 2012 The Authors. BJD © 2012 British Association of Dermatologists.)

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., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

In a prospective randomised Scandinavian trial, patients with localised invasive cutaneous melanoma of the trunk or extremities with tumours more than 2 mm thick were randomly assigned to excision with narrow (2 cm) or wide (4 cm) margins after primary surgery. The aims of the present study were to find out if there were any differences in health-related quality of life (QoL) and emotional distress between patients in the two arms over time. Patients were assessed at four time points: before randomisation, and at 3, 9, and 15 months after inclusion, using the EORTC QLQ-C30, the Hospital Anxiety and Depression Scale and the Impact of Event Scale. A study-specific questionnaire was used to assess patient-reported problems related to the scar. A total of 144 patients were included; 70 randomised to narrow excision and 74 to wide excision margins. The response rate was >85% at all assessment points. No differences between the two arms were found for health-related QoL or emotional distress. Emotional functioning, insomnia, anxiety, intrusion, and avoidance improved over time (p

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.

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.

We have previously demonstrated the use of pyrosequencing to investigate NRAS [neuroblastoma RAS viral (v-ras) oncogene homolog] mutations in melanoma biopsies. Here, we expanded the analysis to include BRAF (V-raf murine sarcoma viral oncogene homolog B1), another member of the Ras-Raf-mitogen-activated protein kinase (MAPK) signalling pathway, and analysed a total of 294 melanoma tumours from 219 patients. Mutations in BRAF exons 11 and 15 were identified in 156 (53%) tumours and NRAS exon 2 mutations in 86 (29%) tumours. Overall, mutations in NRAS or BRAF were found in 242 of 294 tumours (82%) and were found to be mutually exclusive in all but two cases (0.7%). Multiple metastases were analysed in 57 of the cases and mutations were identical in all except three, indicating that BRAF and NRAS mutations occur before metastasis. Association with preexisting nevi was significantly higher in BRAF mutated tumours (P=0.014). In addition, tumours with BRAF mutations showed a significantly more frequent moderate to pronounced infiltration of lymphocytes (P=0.013). NRAS mutations were associated with a significantly higher Clark level of invasion (P=0.022) than BRAF mutations. Age at diagnosis was significantly higher in tumours with NRAS mutations than in those with BRAF mutations (P=0.019). NRAS and BRAF mutations, however, did not influence the overall survival from time of diagnosis (P=0.7). In conclusion, the separate genotypes were associated with differences in several key clinical and pathological parameters, indicating differences in the biology of melanoma tumours with different proto-oncogene mutations.

Temozolomide is a rapidly absorbed chemotherapeutic agent, achieving significant central nervous system penetration. Previous clinical trials suggested that temozolomide in sequence with low-dose recombinant human interleukin-2 might be an efficacious and relatively non-toxic chemo-immunotherapeutic treatment, which may synergistically eliminate tumours. The primary objective was to determine the safety and tolerance of temozolomide administered orally 200 mg/m days 1-5, in sequential combination with subcutaneous injections of 4.5x10 IU recombinant human interleukin-2 on days 8-11, 15-18 and 22-25 in patients with measurable, progressive metastatic malignant melanoma without radiological signs of central nervous system metastases. The secondary objectives were to determine tumour response and time to progression. Twenty-seven patients were included, of which four were non-evaluable for response. Twenty-three patients tolerated the regimen with side effects below grade 3 according to the World Health Organization (WHO) scale. Three patients suspended the treatment because of WHO grade 3 side effects already during the first 3 days of the first course of temozolomide. Seven patients showed no tumour progression during the first four treatment cycles. Two patients had complete responses, three partial responses and two stable disease at the end of the four cycles defined by the protocol and they continued the treatment until signs of relapse or a maximum of 21 courses. Five of these patients are still alive. Thrombocytopenia was significantly more pronounced in patients with objective response and stable disease than in non-responders to therapy. The median time to progression for all patients was 3.1 months and for responding and stable disease patients was 15 months. Five of 23 treated patients (22%) developed brain metastases during follow-up. Temozolomide in combination with recombinant human interleukin-2 is a well-tolerated regimen for outpatient treatment and the bio-chemotherapy combination induced durable clinical responses. Thrombocytopenia might be a positive predictive factor for response to therapy.

The effectiveness of a short-duration presentation of the educational material 'You and Your Skin' was tested on 184 adolescents (age 13-15) at the Year 7 and 8 levels. A non-equivalent control group design was used with pre-testing and post-testing 3 months after the intervention. The intervention increased the students' knowledge of known risks factors for skin cancers. However, the students' attitudes to abstaining from sunbathing and tanning was not significantly affected. The effect of the intervention on the stage of change was primarily a progression from the precontemplation stage to the contemplation stage regarding avoiding the mid-day sun. We conclude that a brief presentation of the educational kit 'You and Your Skin' can be used to increase knowledge, but there is a need for a more extensive intervention effort to affect students' readiness to change their behavior and attitude towards sunbathing and tanning. Therefore, it is important to emphasize the necessity of using the educational kit as a multi-lesson programme with its several group exercises.

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.

Purpose: To evaluate whether S-100B protein in serum is an independent prognostic marker in malignant melanoma., Materials and Methods: S-100B protein in serum was analyzed in 1,007 consecutive patients with histologically verified cutaneous malignant melanoma. At the time of blood sampling, 876 patients were in clinical stage I, 35 were in stage II, and 96 were in stage III. The serum concentrations of S-100B protein were measured by a luminescence immunoassay (LIA)., Results: The mean serum concentration of S-100B protein was significantly related to clinical stage, with the lowest level in stage I and the highest in stage III. In a multivariate analysis, S-100B protein levels in serum showed the strongest prognostic impact of the factors analyzed with respect to disease-specific survival in clinical stages II to III, followed by clinical stage. Serum S-100B protein was not a significant independent prognostic factor in clinical stage I, where tumor thickness showed the strongest relation to melanoma-specific survival, followed by ulceration and satellites., Conclusion: This investigation contains the largest material of patients so far analyzed with the new LIA assay of S-100B protein in serum and confirms that S-100B protein in serum is correlated with clinical stage and is an independent prognostic marker in clinical stages II and III.

Unlabelled: 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., Study Design: Patient material collected prospectively for an 18-year period in a Swedish cancer registry underwent statistical analyses to establish the most reliable prognostic factors and the influence of surgical treatment on the survival of patients with CMM of the head and neck., Methods: Data originated from the CMM database of the Stockholm-Gotland area of Sweden. Tumor thickness or invasiveness (Breslow or Clark's levels), extent of surgical margin, sex, histogenetic type, anatomic site, and ulceration were compared statistically for 469 patients., Results: Male patients with head and neck CMM had a 68% 10-year survival rate; the 10-year survival rate for female patients was 87%. The corresponding figures for CMM at other sites were 83% and 90%, respectively. Tumor thickness (or Clark level of invasion) was the only statistically significant prognostic factor in a multivariate analysis (P < .001). The surgical resection margin seemed to be of no importance to outcome., Conclusions: Long-term survival after treatment for CMM of the head and neck is better than reported in most earlier publications, presumably because our evaluation used population-based materials, an important factor in accurate reporting of this kind. Tumor thickness is the main prognostic factor in estimating outcome.

Background: The rise in melanoma-related mortality in Sweden has been less pronounced than the increase in incidence. Interventional activities aimed at early detection may have contributed to this discrepancy., Methods: Individuals with malignant melanoma as the underlying cause of death between 1970 and 1996 (n = 7177) formed the basis of this study. Annual age-standardized mortality rates were calculated using the direct method of standardization with the Swedish population of 1970 as reference. Temporal trends in the standardized rates were evaluated using a log-linear model. The effects of age, period, and cohort on the mortality trends were estimated using a Poisson regression model., Results: Since the mid-1980s, melanoma-related mortality in Sweden has leveled off, with no further increase during the last 10-15 years. The contribution to the mortality from noncutaneous melanoma was proportionally stable (20-25%) during the studied period. In females, a significant decrease in mortality from cutaneous melanoma was shown for the period of 1987-1996 with an estimated annual decrease of -2.3% (95% confidence interval: -4.3 to -0.3). This trend appeared to be more pronounced in the Stockholm-Gotland region. The observed trends were best explained with the age-period model in both genders., Conclusions: Melanoma-related mortality in Sweden has leveled off since the mid-1980s. During the period 1987-1996, a statistically significant downward trend was observed for females. This trend coincides with increased preventional activities., (Copyright 2000 American Cancer Society.)

Recent reports have suggested that elevated chromosomal aberration yields following X-ray irradiation of skin fibroblasts and peripheral lymphocytes in the G2 phase of the cell cycle are characteristic of affected members of cancer-prone families. These studies propose that the phenomenon is a consequence of impaired caffeine- and arabinofuranosylcytosine (ara-C)-sensitive DNA repair and might be a useful indicator of genetic susceptibility to cancer. We have tested G2 chromosomal X-ray sensitivity in peripheral blood lymphocytes from members of kindreds with hereditary cutaneous malignant melanoma (HCMM) combined with the dysplastic nevus syndrome (DNS), disorders in which susceptibility to skin cancer is inherited in an autosomal dominant pattern. In the assay lymphocytes from patients with HCMM/DNS exhibited responses indistinguishable from normal healthy controls. Furthermore, the radiation-induced aberration yields were potentiated to the same strong extent by post-treatments with caffeine, or a combination of ara-C and hydroxyurea, both in lymphocytes from individuals with HCMM/DNS and lymphocytes from healthy controls. Thus, lymphocytes of affected patients with HCMM/DNS do not have an increased sensitivity to X-ray irradiation in the G2 phase of the cell cycle., (Copyright 1999 Elsevier Science B.V.)

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.

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, Clark's 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.

Tumour thickness is the most important prognostic factor in malignant melanoma. To reduce the melanoma-related mortality, factors related to the presentation of thick melanoma have to be identified. Three samples of melanoma patients (n=694) were studied for this purpose. Histogenetic type was the only factor which differentiated between 'thin' (< or = 0.8 mm) and 'thick' (> 2.0 mm) lesions. During a 10-year period only 3% of the nodular lesions were 'thin' at diagnosis. Differences in knowledge about melanoma or the location of the lesion (either 'easy' or 'difficult' for the patient to observe) did not explain differences in tumour thickness. The most common tumour site irrespective of histogenetic type and gender was 'back of the trunk'. 'Increase in diameter' and 'bleeding' were the symptoms most frequently reported by patients with 'thick' melanoma. 'Thick' lesions were diagnosed in older age groups and in men to a greater extent. Considering these results, melanoma prevention should also be targeted to older age groups and attention should be paid to symptoms such as 'increase in diameter' even in the absence of other characteristic symptoms of melanoma. An increased proportion of nodular melanoma diagnosed as 'thin' lesions can be interpreted as a step forward in secondary prevention.

Stereological estimation of nuclear volume was performed in a case control study of 72 malignant melanomas, thickness < or = 0.8 mm and Clark's level II-III. However, stereological measurements could be performed in only 57 thin melanomas due to too sparse cellularity. Thus, 21 thin metastasizing melanomas were individually compared with 33 thin non-metastasizing melanomas after individual matching of cases with one or two randomly chosen controls for site of primary tumour, tumour thickness, level of invasion, tumour regression and follow-up. Conditional logistic regression analysis showed no significant differences in nuclear volume between metastasizing and non-metastasizing thin malignant melanomas.

The objectives of this population-based study were to assess putative prognostic factors for central nervous system (CNS) metastases among patients with cutaneous malignant melanoma, to assess the cumulative risk of CNS metastases in different subsets of patients with recurrent disease, and to describe patient outcome. At a median follow-up of 11 years, 201/2516 patients with melanoma had developed CNS metastases, corresponding to a cumulative risk at 5 years of 7%. In 41 of these 201 patients the CNS metastases were recorded as the first site of recurrence. In a Cox's multivariate model, primary tumor thickness and ulceration in stage I patients were independent risk factors. The cumulative rates of incidence of CNS metastases 5 years after local or regional recurrence as first event were 5 and 42%, respectively. These results may help to form an individually based risk assessment, which might be of value for melanoma patients in certain occupations.

Background: The definition of local recurrence of cutaneous malignant melanoma varies. The outcomes of patients with a local recurrence reported in the literature also vary, but the appearance of a local recurrence has generally been considered a negative prognostic sign. Few studies have been population-based thus far., Methods: During the period 1976-1997, 3706 patients with cutaneous malignant melanoma (including 575 patients with melanoma in situ) were registered in a population-based regional cancer registry. Local recurrence was defined as a recurrence within the scar or transplant with no signs of regional or distant spread of the disease. Prognostic factors were investigated using univariate and multivariate analytic techniques. The prognostic importance of a local recurrence in terms of survival was analyzed using the Cox proportional hazards regression model, with local recurrence as a time-dependent covariate., Results: Local recurrence as a first event was rare (occurring in 48 of 3706 patients, or 1.3%). Twenty-eight percent (11 of 39) of the patients with local recurrence of invasive primary melanoma developed distant metastases and subsequently died. Only ulceration had prognostic significance in univariate analysis. A Cox analysis, with melanoma death as the endpoint and local recurrence as a time-dependent covariate, demonstrated a relative risk of 1.3 associated with local recurrence; however, this was not statistically significant (confidence interval, 0.7-2.3)., Conclusions: In this population-based study, local recurrence was a rare event. The outcomes after diagnosis were relatively favorable. The results did not indicate a major detrimental effect on survival from the local recurrence per se.

Background: Approximately 10% of human cutaneous melanomas occur in families in which several members are affected. The familial predisposition to this disease is often associated with dysplastic nevus syndrome, a condition in which afflicted family members have multiple dysplastic nevi (atypical moles). The chromosome region 9p21 and markers on chromosomes 1p and 6p have been linked to melanoma susceptibility. The tumor suppressor genes CDKN2A and CDKN2B have been mapped to the 9p21 region, and genetic analyses have revealed the presence of germline CDKN2A alterations in melanoma families. The reported frequencies of such alterations, however, vary among these families., Purpose: The present investigation was carried out to determine the frequencies of CDKN2A and CDKN2B germline gene mutations among members in a population-based cohort of Swedish melanoma families (i.e., melanoma kindreds)., Methods: DNA was prepared from blood samples obtained from 181 individuals belonging to 100 melanoma kindreds. The polymerase chain reaction (PCR) technique, followed by single-strand conformation polymorphism (SSCP) and nucleotide sequence analyses, were used to identify the types and frequencies of mutations in exons 1, 1beta, 2, and 3 of the CDKN2A gene and in exons 1 and 2 of the CDKN2B gene., Results: CDKN2A gene aberrations were independently identified by both SSCP and nucleotide-sequence analyses. Nucleotide-sequence analysis identified a single point mutation leading to a substitution of leucine for proline in codon 48 of exon 1 in a family with a history of melanoma and several other cancers. A second abnormality, leading to an insertion of an extra arginine residue at codon number 113 of exon 2, was seen in four separate families. The CDKN2A exon-3 coding region had the wild-type sequence in all samples. No germline mutations were found in the alternative exon 1beta of the CDKN2A gene or in exons 1 and 2 of the CDKN2B gene., Conclusions: The present investigation demonstrates that CDKN2A germline gene mutations were observed in 7.8% of the 64 Swedish melanoma kindreds that each included at least two first-degree relatives with melanoma and dysplastic nevus syndrome. No CDKN2A exon 1beta or CDKN2B mutations were identified. The critical genes responsible for the inheritance of a susceptibility to develop melanoma among family members in this population have yet to be identified.

Using a randomized design, the effects of an information programme for melanoma patients were studied. The programme consisted of a group meeting and a brochure. The present study reports on the six-month follow-up of the effects of the programme. A total of 128 patients participated in the programme, 55 before and 73 after the first medical control visit. Questionnaires regarding knowledge about melanoma, psychological and psychosomatic variables were completed at the first medical control visit and six months later by mail. A questionnaire concerning patients attitudes to the programme was included after six months. Knowledge about melanoma increased and a majority of patients were satisfied with the information brochure, the group meeting and the group leader, but 40% considered that too few participants attended in their group meeting. No effects on psychological or psychosomatic variables were found. Men and women participated to the same extent.

Objectives: To study two different procedures for inviting subjects to screening for malignant melanoma, and to study the role of specially trained nurses as primary examiners., Methods: The study was carried out in Stockholm county and comprised 5000 randomly selected men and women aged 40 to 60, of whom 2,500 were invited with a personal invitation letter and with a set time of appointment and 2,500 were sent a questionnaire and instructions for self examination of the skin. To test the nurses' competence, a survey was made, comparing the judgments of skin examination between nurses and doctors., Results: 1654 (66%) of those invited for a skin examination took part. 1507 (60%) replied in the questionnaire group, of whom 1024 (41%) requested and attended a subsequent skin examination. Of the subjects attending from both groups, the nurses judged 9% v 11% as having skin lesions suggesting malignant melanoma, whereas the two doctors referred 4% v 3% of the subjects for surgical biopsy. Two malignant melanomas were detected, both of them in the questionnaire group. In the study of nurses' screening competence, both nurses and doctors equally judged one case out of 19 as having a lesion suspicious for malignant melanoma., Conclusions: When the questionnaire method was used the results were achieved with one third fewer skin examinations, but it is difficult to conclude whether one of the procedures is better than the other. The results also indicate that nurses can be trained to be the primary examiners in a melanoma screening programme.

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.