Search

Dear Editor, Only a few studies have investigated health-related quality of life (HR-QoL) in patients with melanoma[[1]] (reviewed in Chernyshov I et al i .[5]). Paper questionnaires were mailed to patients during 2015 if they were registered in the Swedish melanoma register (covering approximately 99% of all individuals with cutaneous melanoma[6]), diagnosed with cutaneous melanoma during 2013-2014, residing in the south eastern or northern region of Sweden and over 18 years of age. As patients with melanomas > 1 mm are more likely to have invasive staging work-ups and worse outcomes, we hypothesized that patients with these thicker melanomas would have worse HR-QoL than those with thinner melanomas. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.)

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.)

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.

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.

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.

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.