BACKGROUND: The optimal surgical excision margins are uncertain for patients with thick (>2 mm) localised cutaneous melanomas. In our previous report of this multicentre, randomised controlled trial, with a median follow-up of 6·7 years, we showed that a narrow excision margin (2 cm vs 4 cm) did not affect melanoma-specific nor overall survival. Here, we present extended follow-up of this cohort.
METHODS: In this open-label, multicentre randomised controlled trial, we recruited patients from 53 hospitals in Sweden, Denmark, Estonia, and Norway. We enrolled clinically staged patients aged 75 years or younger diagnosed with localised cutaneous melanoma thicker than 2 mm, and with primary site on the trunk or upper or lower extremities. Patients were randomly allocated (1:1) to treatment either with a 2-cm or a 4-cm excision margin. A physician enrolled the patients after histological confirmation of a cutaneous melanoma thicker than 2 mm. Some patients were enrolled by a physician acting as responsible for clinical care and as a trial investigator (follow-up, data collection, and manuscript writing). In other cases physicians not involved in running the trial enrolled patients. Randomisation was done by telephone call to a randomisation office, by sealed envelope, or by computer generated lists using permuted blocks. Patients were stratified according to geographical region. No part of the trial was masked. The primary outcome in this extended follow-up study was overall survival and the co-primary outcome was melanoma-specific survival. All analyses were done on an intention-to-treat basis. The study is registered with ClinicalTrials.gov, number NCT03638492.
FINDINGS: Between Jan 22, 1992, and May 19, 2004, 936 clinically staged patients were recruited and randomly assigned to a 4-cm excision margin (n=465) or a 2-cm excision margin (n=471). At a median overall follow-up of 19·6 years (235 months, IQR 200-260), 621 deaths were reported-304 (49%) in the 2-cm group and 317 (51%) in the 4-cm group (unadjusted HR 0·98, 95% CI 0·83-1·14; p=0·75). 397 deaths were attributed to cutaneous melanoma-192 (48%) in the 2-cm excision margin group and 205 (52%) in the 4-cm excision margin group (unadjusted HR 0·95, 95% CI 0·78-1·16, p=0·61).
INTERPRETATION: A 2-cm excision margin was safe for patients with thick (>2 mm) localised cutaneous melanoma at a follow-up of median 19·6 years. These findings support the use of 2-cm excision margins in current clinical practice.
FUNDING: The Swedish Cancer Society, Stockholm Cancer Society, the Swedish Society for Medical Research, Radiumhemmet Research funds, Stockholm County Council, Wallström funds.

BACKGROUND/AIM: This study aimed to identify the prognostic factors and outcomes of osteosarcoma (OS) located in proximal versus distal extremity long bones.
PATIENTS AND METHODS: A nationwide cohort comprising all Norwegian high-grade OSs in extremity long bones between 1982 and 2009 was investigated.
RESULTS: The univariate analysis results identified no significant differences in survival between patients with OS in proximal long bones (101 cases) as a group in comparison to patients with OS in the distal part of these bones (120 cases). However, proximal femur and primary metastasis were both independent adverse prognostic factors for sarcoma-specific survival in multivariate analyses, while elevated LDH and secondary OS were inferior prognostic factors for event-free survival. Adequate surgery and chemotherapy had a positive impact on survival.
CONCLUSION: OS of the proximal femur had an unfavorable outcome in comparison to OS in other anatomical locations in extremity long bones.

OBJECTIVES: We aimed to compare pain experienced during screening mammography, using three different compression paddles: a fixed paddle standardizing pressure (study paddle), a flexible, and a fixed paddle.
MATERIAL AND METHODS: Using a numeric rating scale (NRS), ranged 0-10, we collected information on pain experienced during mammography from a questionnaire completed by 4,675 women screened in Stavanger, May-November 2017, as a part of BreastScreen Norway. The questionnaire also provided information on factors possibly associated with pain. Data on compression force, pressure and breast characteristics were extracted from the DICOM-header, and a breast density software. T-tests were used to compare mean values of the parameters between the types of compression paddles. Linear regression was used to determine the association of a score of ≥7 versus <7 on NRS for experienced pain by compression paddle, adjusting for pressure, breast characteristics and associated factors.
RESULTS: The mean of experienced pain did not differ for the study and flexible paddle (2.5 on NRS), and was lower for the study paddle compared to the fixed paddle (2.4 versus 2.6 on NRS, p < 0.05). Pain in shoulder(s) and/or neck prior to mammography was associated with 33% (RR 1.33, 95%CI 1.07-1.65) higher risk of a score of ≥7 versus <7 for experienced pain.
CONCLUSION: The majority of women reported low scores of experienced pain during mammography, independent of compression paddle used. Further research on image quality is needed to fully understand which paddles should be preferred in a screening setting.

OBJECTIVE: To evaluate the significance of patients' ability to recognise symptoms that signify recurrence.
METHODS: A retrospective analysis was conducted in Norway of demographic, clinical and follow-up data for patients with laryngeal carcinoma considered free of disease following treatment. The study included clinical data from 732 patients with glottic tumours and 249 patients with supraglottic tumours who were considered cured of disease. Data on the site, time and type of recurrence (symptomatic or asymptomatic) were retrieved.
RESULTS: Recurrence was observed in 127 patients with glottic tumours and 71 with supraglottic tumours. A total of 103 glottic recurrences and 53 supraglottic recurrences were symptomatic. For patients with glottic carcinoma, recurrence detection through symptoms was associated with a favourable post-salvage survival rate compared with asymptomatic recurrences (p = 0.003).
CONCLUSION: A patient's ability to self-detect 'red flag' symptoms and self-initiate visits represents a previously ignored prognostic factor, and may rationalise follow up and improve survival.

BACKGROUND & AIMS: Bariatric surgery might reduce overall mortality from obesity. We investigated whether the survival times of patients who have had bariatric surgery are similar to those of the general population and are longer than of obese individuals who did not receive surgery.
METHODS: We performed a population-based cohort study of persons with a diagnosis of obesity listed in nationwide registries from Nordic countries from 1980 through 2012. Bariatric surgery was analyzed in relation to all-cause mortality and the obesity-related morbidities cardiovascular disease, diabetes, cancer, and suicide. Poisson models provided standardized mortality ratios (SMRs) with 95% confidence intervals (CIs). Multivariable Cox regression provided hazard ratios (HRs) for mortality in participants who did and did not have surgery.
RESULTS: Among 505,258 participants, 49,977 had bariatric surgery. Overall all-cause SMR was increased after surgery (1.94; 95% CI, 1.83-2.05) and increased with longer follow-up, to 2.28 (95% CI, 2.07-2.51) at ≥15 years after surgery. SMRs were increased for cardiovascular disease (2.39; 95% CI, 2.17-2.63), diabetes (3.67; 95% CI, 2.85-4.72), and suicide (2.39; 95% CI, 1.96-2.92) but not for cancer (1.05; 95% CI, 0.95-1.17); SMRs increased with time. In obese participants who did not have surgery, all-cause SMR was 2.15 (95% CI, 2.11-2.20), which remained stable during follow-up. Compared with obese participants who did not have surgery, patients who had bariatric surgery had decreased overall mortality from all causes (HR, 0.63; 95% CI, 0.60-0.66), cardiovascular disease (HR, 0.57; 95% CI, 0.52-0.63), and diabetes (HR, 0.38; 95% CI, 0.29-0.49) but increased mortality from suicide (HR, 1.68; 95% CI, 1.32-2.14). Cancer mortality was decreased overall (HR, 0.84; 95% CI, 0.76-0.93) but increased at ≥15 years of follow-up (HR, 1.20; 95% CI, 1.02-1.42).
CONCLUSIONS: In a study of persons with a diagnosis of obesity listed in nationwide registries of Nordic countries, we found that obese patients who have bariatric surgery have longer survival times than obese individuals who did not have bariatric surgery, but their mortality is higher than that of the general population and increases with time. Obesity-related morbidities could account for these findings.

INTRODUCTION: Increased focus on quality indicators and the use of clinical registries for breast cancer for real world studies have shown higher compliance to recommended therapy and better survival. In 2010, the European Society of Breast Cancer Specialist (EUSOMA) proposed quality indicators (QI) covering diagnosis, treatment and follow-up. To become a EUSOMA certified Breast Cancer Unit, 14 specified quality indicators, in addition to other requirements, need to be met. To evaluate the compliance and results of recommended treatment in breast cancer care in Norway and to improve the quality of epidemiological data, the Cancer Registry of Norway (CRN) in cooperation with the Norwegian Breast Cancer Group (NBCG) developed the Norwegian Breast Cancer Registry (NBCR). The objective of this study is to assess the feasibility of using the NBCR for estimating the EUSOMA QI individually for all hospitals diagnosing and treating breast cancer in Norway.
METHODS: To provide researchers with high quality cancer data as well as for the purpose of national cancer statistics, the CRN employs a cancer registry system to 1) longitudinal capture data from all patients from all medical entities that diagnose and/or treat cancer patients (e.g., pathology, radiology and clinical departments) in Norway; 2) curate data, i.e. validate the correctness of collected data, and assemble the validated cancer data as cancer cases; 3) provide data for analytics and presentation. Estimates for 10 EUSOMA QI were calculated at national and hospital level. To compare hospitals, a summary score of QIs was defined for each hospital.
RESULTS: All hospitals currently treating breast cancer patients have the technical ability to submit data to the NBCR for estimation of QIs defined by EUSOMA. Data from pathology and surgery are of high quality. However, data from oncological and radiological departments are incomplete, but improving. This currently hinders three QIs from being calculated. QI on benign to malign diagnosis needs to be calculated at the individual Breast Centre. Over time the adherence to guidelines have improved and the hospital variation for the respective QI have decreased. Two hospitals met all minimum standard on ten QIs in year 2016 and one hospital did not meet one minimum standard, but met all other targets.
CONCLUSION: The NBCR has since 2012 published annual reports on breast cancer care and for the year 2016 measured 10 of 14 QI defined by EUSOMA. Increased compliance of recommended treatment in Norway has been observed during the years the registry has been active.

BACKGROUND: Norway has one of the highest incidences of melanoma in the world. It has been suggested that the majority of all skin cancers could be prevented by changes related to sun-tanning behaviour. This study explores the sun-tanning behaviour of the Norwegian population using a modified Health Belief Model (HBM). Increased knowledge about beliefs, attitudes and sun-tanning behaviour can provide information which may be useful for future sun protection interventions.
METHODS: In 2017, 1004 members of the Norwegian population completed cross-sectional online surveys. People who seek the sun for tanning purposes was the eligibility criterion for this study, reducing the study population to 569. With the aid of the constructs from the HBM, predictive factors explaining sun-tanning behaviour were determined using multivariate linear regression adjusted for demographics (gender, age, education and income). Furthermore, the predictor variables, empowerment and benefits of tanning, were added to the model.
RESULTS: Five of the constructs in the modified HBM showed significant correlation with sun-tanning behaviour using bivariate analysis. The strongest correlation was perceived barriers of sun protection (0.42), with the next strongest being the benefits of tanning (0.30). The modified model explained 31% of the variation in sun-tanning behaviour using multivariate analysis. Significant predictors from the HBM to sun-tanning behaviour were perceived barriers to sun protection (Beta = 0.36, p < 0.001) and the severity of melanoma (Beta = - 0.20, p < 0.001). In addition, empowerment (Beta = 0.05, p = 0.05) and the benefits of tanning (Beta = 0.28, p < 0.001) proved to be variables with significant effect on sun-tanning behaviour. The demographic factors age, education and income were also associated with sun-tanning behaviour (p < 0.05).
CONCLUSION: Based on the results of this study, several factors in the modified HBM had a significant impact on Norwegians' sun-tanning behaviour. The results indicate that future sun protection interventions should focus on reducing barriers in relation to sun protection behaviour, as well as emphasizing the severity of adverse tanning behaviour and melanoma. Efforts to alter the perceptions of the beneficial factors of tanning behaviour can also be appropriate in health promotion campaigns and interventions. Finally, implementing empowerment strategies could have a positive effect on promoting healthy sun-tanning behaviour.

BACKGROUND: Oropharyngeal squamous cell carcinoma (OPSCC) positive for human papillomavirus (HPV) increases wolrd wide.
AIMS/OBJECTIVES: The objective for this study has been to evaluate tumor phenotypes and tumor host responses with respect to five-year disease-specific survival (DSS) in HPV(+) and HPV(-) patients.
MATERIAL AND METHODS: Two hundred patients with OPSCC have been treated between 1992 and 2010. Histopathology slides from these patients have been morphologically evaluated in formalin-fixed, paraffin-embedded (FFPE) stained with hematoxylin-eosin (HE). From HE-stained sections tumor phenotype (keratinization, fraction of mature cancer cells and pattern of invasion) and tumor host responses (inflammation and stromal desmoplasia) were evaluated with respect to five years DSS.
RESULTS: High tumor inflammatory response and low stromal desmoplasia had an independent effect predicting better five-year DSS among all patients and when analyzed separately in the HPV(-) and HPV(+) cohort of patients using a Cox regression survival analysis that also included standard clinical prognostic variables among OPSCC patients.
CONCLUSION: Tumor host responses, inflammation and stromal desmoplasia may become part of routine work-up in OPSCC patients due to prognostic value.
SIGNIFICANCE: We present a method, accessible in most clinical locations and would give important additional information about prognosis in OPSCC patients.

PURPOSE: The diversity in long-term changes in health-related quality of life (HRQoL) among breast cancer (BC) survivors is poorly understood. The aim of this study was to identify clusters of trajectories (subgroups of patients with similar patterns of changes) of selected HRQoL domains over a 1-year period after radiotherapy (RT) in BC patients.
METHODS: The group consisted of 250 BC patients referred for postoperative RT. Global quality of life (QoL), functions, and cancer-specific symptoms were assessed using the European Organisation for Research and Treatment of Cancer (EORTC) core Quality of Life Questionnaire (QLQ-C30) before starting RT, at completion of RT and 3, 6, and 12 months after RT. A hierarchical cluster analysis was used to identify possible trajectories of HRQoL domains.
RESULTS: Three distinct types of clusters of trajectories were identified for all outcome variables: Type 1 clusters encompassing the rather time-stable high-global QoL cluster, high-functioning clusters, and low-symptom clusters (44-98% of patients), Type 2 clusters with medium levels of HRQoL domains (8-49%), Type 3 clusters encompassing low-global QoL, low-functioning, and high-symptoms clusters (2-51%).
CONCLUSIONS: Our results demonstrated a noticeable heterogeneity of changes in HRQoL domains after BC treatment. The findings support the importance of an accurate patient-reported HRQoL assessment as a routine element of BC survivors' care. The pre-RT assessment of HRQoL alone allows to predict the course of HRQoL changes over the 1-year period after RT and the risk of "falling into" low functioning clusters.

BACKGROUND: Local treatment for cervical intraepithelial neoplasia (CIN) by Loop Electrosurgical Excision Procedure (LEEP) has been correlated with reproductive morbidity, while the cervicovaginal microbiota is also known to affect the risk of preterm delivery. CIN and treatment by LEEP might change the cervical microbiota. The main aim of this study was to describe the cervical microbiota before and after LEEP and assess its associaton with cone depth and HPV persistence. Further, we aimed to compare the microbiota to references with normal cervical cytology.
METHODS: Between 2005 and 2007, we prospectively identified 89 women planned for LEEP in a Norwegian hospital and recruited 100 references with a normal cervical cytology. Endocervical swabs were collected prior to treatment and at six (n = 77) and 12 months (n = 72) post LEEP for bacterial culture and PCR, and post LEEP for DNA testing for human papillomavirus (HPV). We compared the cervical microbiota composition before and after treatment and between women planned for LEEP vs references.
RESULTS: There was a reduction in the number of non-Lactobacillus bacterial species six and 12 months after LEEP compared to before treatment and a tendency towards a concomitant increase in Lactobacillus. No association between the detection of cervical bacteria, HPV persistence or cone depth was found. Women planned for LEEP carried significantly more Bacteroides spp., Gardnerella vaginalis, Mycoplasma hominis and Ureaplasma parvum as well as a greater number of bacterial species than the references.
CONCLUSIONS: Local excisional treatment appears to alter the cervical microbiota towards a less diverse microbiota. Women with CIN have a more diverse cervical microbiota compared to women with normal cervical cytology.

PURPOSE: Person-centred care (PCC) is a well-acknowledged goal throughout the western world both within the health care services sector and for the patients themselves. To be able to create a future health care system that includes improved PCC, we need more in-depth knowledge of what matters to patients, how "what matters" might change over time, and tentative descriptions of commonalities across patients' perspectives. The aim of this study is to contribute to this knowledge base.
METHODS: We conducted a qualitative interview series over one year with nine Norwegian patients who were recently diagnosed with rectal cancer tumor-node-metastasis stage I-III.
RESULTS: We found that: (1) patients have an initial focus on "biological goals" and conventional treatment; (2) pathways are unique and dynamic; (3) family and friends affected patient pathways positively with respect to meaningfulness and quality of life, but for some participants also negatively because there were heavy burdens of caretaking; (4) receiving help in the health care system depended on the patients' navigation skills; (5) pluralism in health-seeking behaviour was important in all patient pathways.
CONCLUSION: Long lasting illness may be a dynamic and complex journey. These results represent some features of a pathway with cancer and are important because they contribute with knowledge about what matters most seen from the cancer patients' point of view.

BACKGROUND: Knowledge of chondrosarcoma (CS) of bone to date is based on institutional reports and registry publications with limits in reporting, detail and quality of data.
METHOD: We have performed a retrospective search of CS of bone in the National Cancer Registry in Norway from 1990-2013, cross checked against local tumor databases with further quality control and supplementation of all data from clinical files. The time period is defined by the routine use of axial imaging in clinical practice. A total of 311 cases are included. We performed 108 pathological reviews and 223 radiological reviews. The manuscript was prepared according to the STROBE checklist for strengthening of observational studies. We performed uni-/multivariate cox analyses to define independent prognostic variables from the main cohort of central CS of bone.
RESULTS: The incidence of CS of bone in Norway is 2.85/million/yr. for both sexes overall, rising to 3.45/million/yr. in the last 5-year period. There is an increase in the most common central CS subtype, stronger for women than for men. Central CS had, in general 10-15% local recurrence rates, all evident by 5 years while metastasis rate increases with location and grade. Exceptions are extremity grade 1 CS which displayed no metastatic events and axial grade-3 disease with high rates (50%) of both local and metastatic relapse. Peripheral CS had limited metastatic potential (2%), but rates of local relapse (13%) continue to appear towards 10 years of follow up. Malignancy grade 3 independently predicts rate of metastasis and presence of soft tissue component predicts local recurrence, metastasis and survival.
CONCLUSION: Rates of local recurrence, metastasis and disease specific survival follow clear patterns depending on subtype, location and grade allowing better tailoring of follow-up regimes. Malignancy grade 3 and the presence of a soft tissue component independently predict behavior for central CS of bone.

INTRODUCTION: Based on the National Lung Cancer Screening Trial (NLST), guidelines on screening programs for lung cancer have recommended low-dose computed tomography (LDCT). De Torres et al made a score for COPD patients (COPD-LUCSS) to improve their selection criteria.
OBJECTIVE: To examine and compare the discriminating value of both scores in a community-based cohort of COPD patients.
METHODS: Four hundred and twenty-two ever-smokers with COPD from the GenKOLS study in Bergen were merged with the Cancer Registry of Norway. We divided the patients into groups of high and low risk according to the COPD-LUCSS and the NLST criteria. Cox regression and logistic regression were used to analyse the associations between the scores and lung cancer. We used Harrell's C and area under the curve (AUC) to estimate discriminating values and to compare the models.
RESULTS: Hazard ratio for the high risk vs the low risk in the COPD-LUCSS was 3.0 (1.4-6.5 95% CI), P < 0.01. Hazard ratio for the NLST criteria was 2.2 (95% CI 1.1-4.5), P < 0.05. Harrell's C was 0.63 for the COPD-LUCSS and 0.59 for the NLST selection criteria. AUC was 0.61 for COPD-LUCSS and 0.59 for NLST criteria. Comparing tests showed no differences (P = 0.76).
CONCLUSION: Although the COPD-LUCSS and the NLST criteria were associated with increased risk of lung cancer, the AUC and Harrell's C values showed that these models have poor discriminating abilities in our cohort of COPD patients. The COPD-LUCSS was not significantly better than the NLST criteria.

BACKGROUND: Fully automated assessment of mammographic density (MD), a biomarker of breast cancer risk, is being increasingly performed in screening settings. However, data on body mass index (BMI), a confounder of the MD-risk association, are not routinely collected at screening. We investigated whether the amount of fat in the breast, as captured by the amount of mammographic non-dense tissue seen on the mammographic image, can be used as a proxy for BMI when data on the latter are unavailable.
METHODS: Data from a UK case control study (numbers of cases/controls: 414/685) and a Norwegian cohort study (numbers of cases/non-cases: 657/61059), both with volumetric MD measurements (dense volume (DV), non-dense volume (NDV) and percent density (%MD)) from screening-age women, were analysed. BMI (self-reported) and NDV were taken as measures of adiposity. Correlations between BMI and NDV, %MD and DV were examined after log-transformation and adjustment for age, menopausal status and parity. Logistic regression models were fitted to the UK study, and Cox regression models to the Norwegian study, to assess associations between MD and breast cancer risk, expressed as odds/hazard ratios per adjusted standard deviation (OPERA). Adjustments were first made for standard risk factors except BMI (minimally adjusted models) and then also for BMI or NDV. OPERA pooled relative risks (RRs) were estimated by fixed-effect models, and between-study heterogeneity was assessed by the I
RESULTS: BMI was positively correlated with NDV (adjusted r = 0.74 in the UK study and r = 0.72 in the Norwegian study) and with DV (r = 0.33 and r = 0.25, respectively). Both %MD and DV were positively associated with breast cancer risk in minimally adjusted models (pooled OPERA RR (95% confidence interval): 1.34 (1.25, 1.43) and 1.46 (1.36, 1.56), respectively; I
CONCLUSIONS: When volumetric MD-breast cancer risk associations are investigated, NDV can be used as a measure of adiposity when BMI data are unavailable.

BACKGROUND: Despite the high prevalence of insomnia in patients with advanced cancer, there are no randomized controlled trials on pharmacological interventions for insomnia in this group of patients. A variety of pharmacological agents is recommended to manage sleep disturbance for insomnia in the general population, but their efficacy and safety in adults with advanced cancer are not established. Thus, there is a need to evaluate the effectiveness of medications for insomnia in order to improve the evidence in patients with advanced cancer. One of the most used sleep medications at present in patients with cancer is zopiclone.
METHODS: This is a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial. A total of 100 patients with metastatic cancer who report insomnia will be randomly allocated to zopiclone or placebo. The treatment duration with zopiclone/placebo is 6 consecutive nights. The primary endpoint is patient-reported sleep quality during the final study night (night 6) assessed on a numerical rating scale of 0-10, where 0 = Best sleep and 10 = Worst possible sleep. Secondary endpoints include the mean patient-reported total sleep time and sleep onset latency during the final study night (night 6).
DISCUSSION: Results from this study on treatment of insomnia in advanced cancer will contribute to clinical decision-making and improve the treatment of sleep disturbance in this patient cohort.
TRIAL REGISTRATION: ClinicalTrials.gov, NCT02807922 . Registered on 21 June 2016.

AIMS AND OBJECTIVES: This study aims to describe surgically treated lung cancer patients' experiences of coming home after discharge from hospital to expand the knowledge about their supportive care needs.
BACKGROUND: Existing research reports that patients suffer from a high symptom burden after lung cancer surgery. Such burden has negative impacts on their physical, emotional and social wellbeing. Few studies have explored the surgically treated patients' supportive care needs after being discharged from hospital.
DESIGN: This study used a qualitative descriptive design, following the EQUATOR guidelines (COREQ).
METHODS: The information about 14 patients' experiences was collected from semi-structured interviews. The interviews were conducted in their homes within three weeks after their discharge from hospital. The data were analysed using qualitative content analysis.
RESULTS: The main theme of the study, "Longing to get back on track with their lives", consisted of four categories: "Burdened with problems related to postoperative symptoms and treatment", "Struggling for the needed support", "A pendulum between being in need of support and being independent", and "Striving to adapt to a new way of life". The participants experienced many problems related to postoperative symptoms and treatment. Information and support from healthcare professionals were deficient. Life was characterised by striving to be independent and adapting to a new lifestyle.
CONCLUSIONS: The findings demonstrate the supportive care needs of surgically treated lung cancer patients. Nurses and other healthcare professionals could offer more individualised support during the first few weeks after the patients' discharge by including them and their caregivers in the discharge planning.
RELEVANCE TO CLINICAL PRACTICE: Knowledge of patients' perspectives and experiences of everyday life at home after lung cancer surgery can provide hospital nurses with a better understanding of what is important for such patients beyond hospitalisation. This knowledge should be included in discharge planning.

OBJECTIVE: To describe study design and procedures for a prospective randomized trial investigating whether radical prostatectomy (RP) ± radiation improves cause-specific survival in comparison with primary radiation treatment (RT) and androgen deprivation treatment (ADT) in patients with locally advanced prostate cancer (LAPC).
MATERIALS AND METHODS: SPCG-15 is a prospective, multi-centre, open randomized phase III trial. Patients are randomized to either standard (RT + ADT) or experimental (RP with extended pelvic lymph-node dissection and with addition of adjuvant or salvage RT and/or ADT if deemed necessary) treatment. Each centre follows guidelines regarding the timing and dosing of postoperative RT and adjuvant treatment such as ADT The primary endpoint is cause-specific survival. Secondary endpoints include metastasis-free and overall survival, quality-of-life, functional outcomes and health-services requirements. Each subject will be followed up for a minimum of 10 years.
RESULTS: Twenty-three centres in Denmark, Finland, Norway and Sweden, well established in performing RP and RT for prostate cancer participated. Each country's sites were coordinated by national coordinating investigators and sub-investigators for urology and oncology. Almost 400 men have been randomized of the stipulated 1200, with an increasing rate of accrual.
CONCLUSIONS: The SPCG-15 trial aims to compare the two curatively intended techniques supplying new knowledge to support future decisions in treatment strategies for patients with LAPC The Scandinavian healthcare context is well suited for performing multi-centre long-term prospective randomized clinical trials. Similar care protocols and a history of entirely tax-funded healthcare facilitate joint trials.

BAKGRUNN: I Norge fødes nå om lag 2 500 barn årlig etter fertilitetsbehandling. Hvorvidt behandlingen er forbundet med økt kreftrisiko, er fremdeles usikkert.
KUNNSKAPSGRUNNLAG: Oversikten inkluderer kohortstudier om kreftrisiko hos kvinner behandlet med fertilitetsbehandling og barn unnfanget etter slik behandling. Et systematisk søk etter artikler ble gjort i EMBASE og Medline for perioden 2006-17.
RESULTATER: Resultatene viser ingen generell økning i kreft hos kvinner som har fått fertilitetsbehandling. Hos barn antyder resultatene en tendens til økt risiko for hematologisk kreft, men ingen generell økt kreftrisiko.
FORTOLKNING: Det er ingen entydige funn av forhøyet risiko for kreft hos kvinner som har gjennomgått fertilitetsbehandling, eller hos barn unnfanget etter slik behandling. Oppfølgingstiden er foreløpig kort, og det er behov for store befolkningsbaserte kohortstudier med lengre oppfølgingsperioder.

Chronic pain due to surgery, radiotherapy, or chemotherapy is prevalent in long-term cancer survivors. Chronic pain due to successful cancer treatment should be treated as chronic nonmalignant pain, primarily with nonpharmacological strategies. Based on complete national data from the Cancer Registry of Norway and the Norwegian prescription database, the aim of this study was to compare the use of nonopioid analgesics, opioids, and benzodiazepines 10 years after cancer diagnosis in long-term cancer survivors and the age- and sex-adjusted general population. The 1-year periodic prevalence of use was higher in long-term cancer survivors in all the studied drug classes: opioids (143.5 vs 129.6/1000), paracetamol (88.3 vs 80.7/1000), nonsteroidal anti-inflammatory drugs (229.1 vs 221.7), gabapentinoids (13.4 vs 10.0/1000), benzodiazepines (88.3 vs 77.9/1000), and benzodiazepine-like hypnotics (118.1 vs 97.4/1000). The prevalence of persistent and high-dose opioid use (>365 defined daily doses [DDDs] and >730 DDDs, respectively, during 365 days, and prescriptions all quarters of the year) was also higher in the cancer survivors than in the general population (6.5 vs 4.8/1000 for persistent use and 2.7 vs 1.3/1000 for high-dose use). Less than 10% of persistent and high-dose users received only long-acting opioid formulations. Furthermore, most long-term cancer survivors with persistent or high-dose opioid use were also high-dose users (>100 DDDs/year) of either benzodiazepines or benzodiazepine-like hypnotics. It is an issue of concern that most of those using opioids did not adhere to guidelines regarding opioid formulation and comedication with other drugs with addictive properties.

BACKGROUND: Improved outcome after liver resections have been reported in several series, but outcomes from national cohorts are scarce. Our aim was to evaluate nationwide practice and short-term outcomes after liver surgery in a universal healthcare system.
METHODS: A complete 5-year cohort of all liver resections from the Norwegian Patient Registry (NPR). Short-term outcomes were aggregated length of stay (a-LoS), reoperation and 90-day mortality.
RESULTS: Of 2118 liver resections, 605 (28.6%) were major, median age was 65 years and 1184 (55%) were male. Most common indication was metastatic disease (n = 1554; 73.4%) and primary malignancy (n = 328; 15.3%). Laparoscopy was performed in 513 (33.9%) of minor and 37 (6.1%) of major liver resections and increased over time to 39.1% of minor resections in 2016. Median a-LoS was 12 days for major resections, 8 days for open minor and 3 days for laparoscopic minor resections. Reoperation was reported for 159 (7.4%) and 90-day mortality for 44 (2.1%). Primary malignancy, male gender, elderly patients and major resections were associated with poorer outcome.
CONCLUSIONS: In a national cohort, laparoscopy is used for a substantial proportion of minor resections and was associated with reduced a-LoS. Risk factors for reoperation and mortality were male gender, increased age and major resection for primary malignancy.

PURPOSE: Breast cancer risk associated with pregnancy characteristics may be mediated by maternal hormones or angiogenic factors.
METHODS: We conducted a prospective breast cancer case-control study among women in the Avon Longitudinal Study of Parents and Children (ALSPAC) and Norwegian Mother and Child Cohort Study (MoBa) related to maternal pregnancy prolactin (n = 254 cases and 374 controls), placental growth factor (PlGF, n = 252 and 371), soluble fms-like tyrosine kinase-1 (sFlt-1, n = 118 and 240) and steroid hormone concentrations (ALSPAC only, n = 173 and 171). Odds ratios (OR) and 95% confidence intervals (CI) for a 1 SD change in analytes were estimated using unconditional logistic regression with matching factors (cohort, mother's birth year, serum/plasma, blood collection timing) and gestational age.
RESULTS: Breast cancer ORs (95% CI) were 0.85 (0.51-1.43) for estradiol, 0.86 (0.67-1.09) for testosterone, 0.89 (0.71-1.13) for androstenedione, 0.97 (0.71-1.34) for hCG, 0.93 (0.75, 1.15) for prolactin, 1.00 (0.78-1.27) for PlGF and 1.91 (1.00-3.65 ALSPAC) and 0.94 (0.73-1.21 MoBa) for sFlt-1, and were similar adjusting for potential confounders. Results were similar by blood collection timing, parity, age at first birth or diagnosis, and time between pregnancy and diagnosis.
CONCLUSION: These data do not provide strong evidence of associations between maternal hormones or angiogenic factors with subsequent maternal breast cancer risk.

INTRODUCTION: Colorectal cancer (CRC) remains the second most common cancer in women worldwide. Physical activity (PA) has been associated with reduced risk of CRC; however, this has been demonstrated more consistently in men, while results of studies in women have been largely equivocal. We aimed to further examine the relationship between PA patterns and the risk of CRC in women, using repeated measurements.
METHODS: We followed participants of the Norwegian Women and Cancer (NOWAC) Study - a nationally representative cohort. Baseline information was available for 79,184 women, and we used this information in addition to follow-up information collected 6-8 years later, for repeated measurement analysis. At enrollment, participants were cancer-free and aged 30-70 years, with a median age of 51 years. We used Cox proportional hazards regression to compute hazard ratios (HRs) and 95% confidence intervals (CIs).
RESULTS: During an average of 14.6 years of follow-up and 1.16 million person-years, 885 cases of colon and 426 cases of rectal cancer were identified through linkage to the Norwegian Cancer Registry (median age at diagnosis: 65 years). We found no association between PA level and the risk of colon cancer in baseline or repeated measurements analyses when comparing women with PA level 1-2 to those with PA level 5-6 (reference) (baseline: HR = 0.90, 95% CI 0.66-1.23, p-trend = 0.76; repeated measurements: HR = 0.78, 95% CI 0.55-1.10, p-trend = 0.27). Results were the same when comparing PA level 9-10 to the reference level (baseline: HR = 0.80, 95% CI 0.56-1.12, p-trend = 0.76; repeated measurements: HR = 0.82, 95% CI 0.58-1.16, p-trend = 0.27). Similarly, we found no association between PA levels and the risk of rectal cancer.
CONCLUSIONS: Women may need to look beyond PA in order to reduce their risk of CRC.

BAKGRUNN: Befolkningssammensetningen i Norge har endret seg, og innvandrere utgjør nå nær 14 % av befolkningen. Vi vet ikke hvordan dette påvirker kreftbildet. I denne studien presenterer vi forekomst av kreft for den norskfødte delen av befolkningen for å kunne få et bilde på hvordan forekomsten har endret seg, sett bort fra effekten av innvandring.
MATERIALE OG METODE: Data fra Kreftregisteret og populasjonsdata fra Statistisk sentralbyrå ble benyttet for å beregne aldersstandardiserte insidensrater av kreft i Norge i perioden 1990-2016.
RESULTATER: Studiepopulasjonen besto av 6 703 675 personer, hvorav 82,3 % ble definert som norskfødte. Ratene for alle kreftformer samlet hos norskfødte og totalbefolkningen fulgte hverandre mer eller mindre jevnt. I siste femårsperiode (2012-16) var ratene for den norskfødte delen av befolkningen 2 % høyere enn de nasjonale ratene, og føflekk- og livmorhalskreft hadde den største prosentvise forskjellen med 6-8 % høyere rater. Raten for leverkreft var 3-4 % lavere for norskfødte sammenlignet med totalbefolkningen.
FORTOLKNING: De nasjonale ratene har så langt gitt et godt bilde på kreftutviklingen i den norskfødte delen av befolkningen. Siden forskjellen mellom ratene økte mot slutten av tidsperioden, kan fødeland være en viktig faktor å ta hensyn til i presentasjonen av kreftforekomst.

OBJECTIVES: Treatment on organized stroke units (SUs) improves survival after stroke, and stroke mortality has decreased worldwide in recent decades; however, little is known of survival trends among SU patients specifically. This study investigates changes in survival and characteristics of older stroke patients receiving SU treatment.
MATERIALS & METHODS: We compared 3-year all-cause mortality and baseline characteristics in two cohorts of stroke patients aged ≥60 consecutively admitted to the same comprehensive SU in 1994 (n = 271) and 2012 (n = 546).
RESULTS: Three-year survival was 53.9% in 1994 and 56.0% in 2012, and adjusted hazard ratio (HR) was 0.99 (95% CI: 0.77-1.28). Adjusted 30-day case fatality was slightly higher in 2012, 18.9% versus 16.2%, HR 1.68 (95% CI: 1.14-2.47). There were no significant between-cohort differences in survival beyond 30 days. Patients in 2012 were older (mean age: 78.8 vs. 76.7 years) and more often admitted from nursing homes. There were higher rates of atrial fibrillation (33.7% vs. 21.4%) and malignancy (19.2% vs. 8.9%), and prescription of antiplatelets (46.9% vs. 26.2%) and warfarin (16.3% vs. 5.5%) at admission. Stroke severity was significantly milder in 2012, proportion with mild stroke 66.1% versus 44.3%.
CONCLUSIONS: Three-year survival in older Norwegian stroke patients treated on an SU remained stable despite improved treatment in the last decades. Differences in background characteristics may explain this lack of difference; patients in 2012 were older, more often living in supported care, and had higher prestroke comorbidity; however, their strokes were milder and risk factors more often treated.

BACKGROUND: Noncommunicable diseases represents long term medical conditions, which often puts the patients under enormous demands when following treatment, exposing them to experiencing treatment burden. The Patient Experience with Treatment and Self-Management (PETS) questionnaire was developed as a patient-reported measure to identify treatment burden of chronic illness, using modern measurement theory and tested in a variety of settings. Developed in English, this set of measures had not been previously translated into Norwegian. The objective of this study was to develop a Norwegian version of the PETS and to pretest the translated measures through a cognitive debriefing methodology.
METHODS: A rigorous translation approach was applied, guided by Functional Assessment of Chronic Illness Therapy methodology. Bilingual teams from Norway and the United States reviewed the translation to develop a provisional version, which was evaluated for test content validity with cognitive interviews by probing 12 native Norwegian patients with noncommunicable diseases. The interviews applied both concurrent and retrospective verbal probing techniques, guided by a question route. Audio-recorded interviews were transcribed verbatim and analysed using systematic text condensation.
RESULTS: Assessment of translatability identified the need for cultural adaptation on several core words, balanced with the need to keep close to the original literal meaning. Seven patients with colorectal cancer and five patients with heart failure participated in cognitive testing of the Norwegian version of the PETS. The analytical process of the cognitive interviews identified two emergent main themes, 'comprehension and readability' and 'relevance of the PETS', with seven corresponding subthemes. Most items, response options and instructions were well understood by the patients. Revisions were made concerning cultural relevance.
CONCLUSIONS: PETS items were semantically equivalent to the original. The patients with colorectal cancer and heart failure were able to comprehend the PETS and found it to express their experience with treatment burden in chronic illness. Future work will focus on psychometric construct validation and reliability testing of the PETS.

BACKGROUND: Both conventional health care providers and complementary therapists treat cancer patients. To provide effective treatment, both types of providers should to be familiar with their own as well as alternative types of treatment. Our aim was to compare how conventional health care providers (oncology doctors, oncology nurses, family physicians) and complementary therapists (acupuncturists, reflexologists, massage therapists) seek information about conventional and complementary cancer treatments.
METHOD: This analysis was conducted on the basis of feedback from 466 participants. We used self-administered questionnaires in a cross-sectional study.
RESULTS: The majority of the medical doctors (96%) searched for evidence-based information regarding conventional cancer treatments. They gathered this information mostly from guidelines, which is considered best practice and is expected from Norwegian health personnel. Eighty-one percent of the nurses gather this information from evidence based resources such as UpToDate. Colleagues were asked for information by 58% of the medical doctors and 64% of the nurses. Moreover, 50% of the medical doctors and 57% of the nurses searched for evidence-based information about complementary cancer modalities. The acupuncturists gathered evidence-based information for both conventional (79%) and complementary (77%) modalities, followed by the reflexologists (54 and 54%, respectively) and massage therapists (54 and 52%, respectively). Nearly half of the acupuncturist (49%) asked a colleague for information.
CONCLUSION: To provide safe cancer care, it is important that advice about complementary modalities is based on current and evidence-based evaluations. The majority of the medical doctors and nurses in this study sought information according to evidence-based medicine regarding conventional cancer treatments, and about half of them gathered evidence-based information about complementary cancer modalities. This was also true for the complementary therapists as they gathered information about complementary and conventional treatments from evidence-based evaluations. This demonstrates that since the term evidence-based medicine was first introduced in 1991, the approach has grown extensively and both conventional and complementary providers use this approach to seek information.

BACKGROUND: Anal squamous cell carcinoma (ASCC) is a rare, human papilloma virus-associated cancer. The purpose was to investigate the population-based incidence rates, age and gender distribution, and survival of ASCC.
MATERIALS AND METHODS: All primary ASCC in 1987 to 2016 were identified in the Cancer Registry of Norway (N = 1548), with information on age, gender, stage, county of residence, radiotherapy, and survival.
RESULTS: Median age was 66 years; 71% were females. World age-standardized incidence rates increased (1987-2016) from 0.79 (95% confidence interval [CI], 0.69-0.90) to 1.10 (95% CI, 1.00-1.22) per 100,000 person-years in females and, from 0.34 (95% CI, 0.28-0.42) to 0.47 (95% CI, 0.40-0.54) in males. Estimated annual percentage change was 1.7 (95% CI, 0.9-2.6) for females and 1.3 (95% CI, -0.1 to 2.7) for males. Incidence rates increased with age; the relative risk was higher in major cities. Five-year net survival increased from 63.4% to 72.7% (1987-2016), but for age ≥ 70 years remained ∼57%. Net survival was dependant on stage, age, and gender. Five-year net survival (1997-2016) was 76.4% after curative radiotherapy, and 18.0% after palliative radiotherapy.
CONCLUSION: ASCC incidence rates increased from 1987 to 2016, and survival improved for patients < 70 years. Five-year net survival was 76% after curative radiotherapy in Norway.

Age and tumor subtype are prognostic factors for breast cancer survival, but it is unclear which matters the most. We used population-based data to address this question. We identified 21,384 women diagnosed with breast cancer at ages 20-89 between 2005 and 2015 in the Cancer Registry of Norway. Subtype was defined using estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor 2 (HER2) status as luminal A-like (ER+PR+HER2-), luminal B-like HER2-negative (ER+PR-HER2-), luminal B-like HER2-positive (ER+PR+/-HER2+), HER2-positive (ER-PR-HER2+) and triple-negative (TNBC) (ER-PR-HER2-). Cox regression estimated hazard ratios (HR) for breast cancer-specific 7-year survival by age and subtype, while adjusting for year, grade, TNM stage and treatment. Young women more often had HER2-positive and TNBC tumors, while elderly women (70-89) more often had luminal A-like tumors. Compared to age 50-59, young women had doubled breast cancer-specific mortality rate (HR = 2.26, 95% CI 1.81-2.82), while elderly had two to five times higher mortality rate (70-79: HR = 2.25, 1.87-2.71; 80-89: HR = 5.19, 4.21-6.41). After adjustments, the association was non-significant among young women but remained high among elderly. Young age was associated with increased breast cancer-specific mortality among luminal A-like subtype, while old age was associated with increased mortality in all subtypes. Age and subtype were strong independent prognostic factors. The elderly always did worse, also after adjustment for subtype. Tumor-associated factors (subtype, grade and stage) largely explained the higher breast cancer-specific mortality among young. Future studies should address why luminal A-like subtype is associated with a higher mortality rate in young women.

BACKGROUND: Sedentary behavior is thought to pose different risks to those attributable to physical inactivity. However, few studies have examined the association between physical activity and sitting time with cancer incidence within the same population.
METHODS: We followed 38,154 healthy Norwegian adults in the Nord-Trøndelag Health Study (HUNT) for cancer incidence from 1995-97 to 2014. Cox proportional hazards regression was used to estimate risk of site-specific and total cancer incidence by baseline sitting time and physical activity.
RESULTS: During the 16-years follow-up, 4,196 (11%) persons were diagnosed with cancer. We found no evidence that people who had prolonged sitting per day or had low levels of physical activity had an increased risk of total cancer incidence, compared to those who had low sitting time and were physically active. In the multivariate model, sitting ≥8 h/day was associated with 22% (95% CI, 1.05-1.42) higher risk of prostate cancer compared to sitting <8 h/day. Further, men with low physical activity (≤8.3 MET-h/week) had 31% (95% CI, 1.00-1.70) increased risk of colorectal cancer (CRC) and 45% (95% CI, 1.01-2.09) increased risk of lung cancer compared to participants with a high physical activity (>16.6 MET-h/week). The joint effects of physical activity and sitting time the indicated that prolonged sitting time increased the risk of CRC independent of physical activity in men.
CONCLUSIONS: Our findings suggest that prolonged sitting and low physical activity are positively associated with colorectal-, prostate- and lung cancer among men. Sitting time and physical activity were not associated with cancer incidence among women. The findings emphasizing the importance of reducing sitting time and increasing physical activity.

Chronic fatigue is a common phenomenon in inflammatory and autoimmune conditions, in cancer, and in neurodegenerative diseases. Although pain and psychological factors influence fatigue, there is an increasing understanding that there is a genetic basis, and that activation of the innate immune system is an essential generator of fatigue. Mast cells are important actors in innate immunity and serve specialized defense responses against parasites and other pathogens. They are also major effector cells in allergic reactions. Primary disorders causing constitutively hyperactivity of mast cells are called mastocytosis and are frequently due to a gain-of-function mutation of the KIT gene encoding the transmembrane tyrosine kinase receptor. It is a clinical experience that patients with mast cell disorders suffer from fatigue, but there is a lack of scientific literature on the phenomenon. We performed a controlled study of fatigue in mastocytosis patients and document a 54% prevalence of clinical significant fatigue.