MGMT promoter methylation is associated with temozolomide response and prolonged progression-free survival in disseminated cutaneous melanoma.

To investigate the predictive and prognostic value of O(6) -methylguanine DNA methyltransferase (MGMT) inactivation by analyses of promoter methylation in pretreatment tumor biopsies from patients with cutaneous melanoma treated with dacarbazine (DTIC) or temozolomide (TMZ) were performed. The patient cohorts consisted of Belgian and Swedish disseminated melanoma patients. Patients were subdivided into those receiving single-agent treatment with DTIC/TMZ (cohort S, n = 74) and those treated with combination chemotherapy including DTIC/TMZ (cohort C, n = 79). Median follow-up was 248 and 336 days for cohort S and cohort C, respectively. MGMT promoter methylation was assessed by three methods. The methylation-related transcriptional silencing of MGMT mRNA expression was assessed by real-time RT-PCR. Response to chemotherapy and progression-free survival (PFS) and overall survival were correlated to MGMT promoter methylation status. MGMT promoter methylation was detected in tumor biopsies from 21.5 % of the patients. MGMT mRNA was found to be significantly lower in tumors positive for MGMT promoter methylation compared to tumors without methylation in both treatment cohorts (p < 0.005). DTIC/TMZ therapy response rate was found to be significantly associated with MGMT promoter methylation in cohort S (p = 0.0005), but did not reach significance in cohort C (p = 0.16). Significantly longer PFS was observed among patients with MGMT promoter-methylated tumors (p = 0.002). Multivariate Cox regression analysis identified presence of MGMT promoter methylation as an independent variable associated with longer PFS. Together, this implies that MGMT promoter methylation is associated with response to single-agent DTIC/TMZ and longer PFS in disseminated cutaneous melanoma.

Later stage at diagnosis and worse survival in cutaneous malignant melanoma among men living alone: a nationwide population-based study from Sweden.

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.

Invasive cutaneous malignant melanoma in Sweden, 1990-1999. A prospective, population-based study of survival and prognostic factors.

BACKGROUND: The objective of the current study was to compile prospective, population-based data on cutaneous invasive melanomas in Sweden during the period from 1990 to 1999, to describe and analyze survival data and prognostic factors, and to make comparisons with previously published Swedish and international data. METHODS: Twelve thousand five hundred thirty-three patients, which included 97% of all registered melanomas in Sweden, were included and described. Among these, 9515 patients with clinical Stage I and II melanoma were included in an analysis of survival and in a univariate analysis, and 6191 patients were included in a multivariate analysis of prognostic factors. RESULTS: There was no significant change in melanoma incidence during 1990-1999. Favorable prognostic factors were found, especially in younger and female patients, resulting in a relative 5-year survival rate of 91.5%. In the multivariate analysis, significant factors that had a negative effect on survival were Clark level of invasion, Breslow thickness, ulceration, older patient age, trunk location, greatest tumor dimension, nodular histogenetic type, and male gender. CONCLUSIONS: During the period from 1990 to 1999, the 5-year survival of patients with malignant melanoma in Sweden was better compared with the previously reported rates in published, population-based studies from Sweden, probably as a result of better secondary prevention due to better knowledge and awareness by both patients and the medical profession. The more favorable prognostic factors and the change in melanoma location found in younger patients, compared with earlier reports, may reflect changes in clothing as well as tanning habits; however, a decrease also was found in Clark Level II and thin melanomas for the same patient group. The authors concluded that further improvements can be achieved with better access to health care and with the use of early melanoma detection campaigns.

The Swedish Council on Technology Assessment in Health Care (SBU) systematic overview of radiotherapy for cancer including a prospective survey of radiotherapy practice in Sweden 2001--summary and conclusions.

A systematic assessment of radiotherapy for cancer was conducted by The Swedish Council on Technology Assessment in Health Care (SBU) and published in 1996. The assessment reviewed the scientific literature up to 1993 on the use of radiotherapy in the treatment of solid tumours, and estimated the costs associated with radiotherapy. It also described the current practise of radiotherapy in Sweden 1992 and compared practise with scientific knowledge. The SBU has now conducted a follow-up study on radiotherapy for cancer, including a review of the scientific literature from 1994 and a prospective survey of radiotherapy practise in Sweden 2001. The following conclusions were drawn: The role of radiotherapy as an important form of treatment for cancer with both curative and palliative intent has been further confirmed. The use of radiotherapy in Sweden has increased and is now at the internationally recommended level. Radiotherapy in Sweden is mostly given in accordance with the scientific evidence but may still be underutilized in certain situations. The resources for radiotherapy are being utilized more efficiently. The costs of radiotherapy are still 5% of the total cost of cancer care, while the cost of an individual treatment (fraction) has decreased. The need for radiotherapy capacity will increase. In addition, half of the treatment equipment will have to be replaced in the next few years.

Radiotherapy techniques in current use in Sweden.

A systematic assessment of radiotherapy for cancer was conducted by The Swedish Council on Technology Assessment in Health Care (SBU) in 2001. The assessment included a review of radiotherapy techniques in current use in Sweden. The following conclusions were drawn: Radiotherapy demands adequate knowledge of diagnostic methods, anatomy, cancer biology and of the physical and biological properties of ionizing radiation. Well-functioning teamwork on the part of the oncologist, medical physicist and oncology nurse is important. Radiotherapy has a high degree of technical sophistication, including the use of computers, which necessitates expert technical support. Technical development is rapid, and since the previous report, multileaf collimators and electronic portal imaging have been introduced in the clinical routine. The use of brachytherapy for treatment of non-gynaecological malignancies is rapidly increasing. The need for quality assurance in all steps of the radiotherapy procedure is stressed. A critical review of the literature on intraoperative radiotherapy is also included as an Appendix.

Radiotherapy and cancer care in Sweden.

A systematic assessment of radiotherapy for cancer was conducted by The Swedish Council on Technology Assessment in Health Care (SBU) in 2001. It included an overview of the organisation of radiotherapy and cancer care in Sweden and education of staff. It further included an update of cancer statistics for Sweden and an estimate of the need for radiotherapy resources by the year 2010. The following conclusions were drawn: Compared with a similar assessment in 1992, the number of departments of oncology at the county hospital level has increased by one, and one more department was scheduled to start radiotherapy during 2002. The speciality of oncology in Sweden includes all types of non-surgical cancer treatment, in contrast to the situation in most countries, where radiation oncology and medical oncology are independent specialities. Gynaecologic oncology is a unique speciality for Sweden. The number of new cancer cases increased by 13% between 1990 and 2000, and continues to increase by more than 1.0% per year. The projections of cancer incidence stated in the previous report were checked against observed data for the year 2000 and found to be an underestimation. To maintain the current capacity for radiotherapy in relation to number of new cancer cases by the year 2010, a total of 65 accelerators would be needed.

A prospective survey of radiotherapy practice 2001 in Sweden.

A prospective survey of radiotherapy practice in Sweden was conducted during 12 weeks in the autumn of 2001. All hospitals that provided radiotherapy participated, and all patients who started radiotherapy during the study period were included. The final patient sample comprised 5,105 treatments given to 4,171 patients. The results were compared with those of a similar survey conducted in 1992, and the following conclusions were drawn: A substantial increase in the use of radiotherapy was noted; The estimated proportion of cancer cases receiving radiotherapy (compared to the incident number of cases) had increased from 32% in 1992 to 47%; The proportion of cancer patients receiving radiotherapy was estimated at between 37 and 46%; 54% of treatments were given with curative intent, a small increase since 1992; The difference between regional and county departments for proportion of treatments with curative intent had diminished; Treatments with curative intent used a higher proportion of resources measured in terms of fractions; The proportion of palliative treatment was slightly lower than in 1992, but the absolute number of treatments had increased by more than 20%; No improvement in participation in clinical trials was noted; Treatments given with curative intent were more complex with more fields; Hyperfractionation was used, mainly in treatments of cancers of the head and neck, lung, and bladder; The use of brachytherapy for non-gynaecological malignancies had increased dramatically; Treatment of bone metastases with a single or few fractions was used much more frequently; Dose planning and patient set-up showed a high standard but quality control of dosimetry of given treatment did not fully comply with Swedish and European recommendations; The treatment devices seem to be used more efficiently.

Radiotherapy practices in Sweden compared to the scientific evidence.

A systematic assessment of radiotherapy for cancer was conducted by The Swedish Council on Technology Assessment in Health Care (SBU) in 2001. The assessment included a critical review of the literature on radiotherapy for cancer published in 1994-2001 and a prospective survey of radiotherapy practice in Sweden during 12 weeks in the autumn of 2001. The results of the survey were compared with the evidence derived from the scientific literature, and the following conclusions could be drawn: Radiotherapy is currently given to approximately 47% of new cancer cases This figure is on a par with rates reported from other countries. For most tumour types, curative radiotherapy practices in Sweden are generally supported by the literature. Interstitial brachytherapy has been included in the treatment of non-gynaecological malignancies, and prostate cancer is now the most common indication. Palliative radiotherapy has increased and is today given in a more rational way using single or few fractions However, it still seems to be under-utilized in Sweden. The need for radiotherapy can be expected to increase until the year 2010.