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Real-world clinical outcomes of anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC) patients vary. This study aimed to investigate the treatment and clinical outcomes of all ALK+ NSCLC patients in Denmark in the period 2011–2018, regardless of disease stage. A national pathology database with complete coverage was used to identify ALK+ NSCLC patients diagnosed between 2011 and 2018. Clinical data were obtained through retrospective chart reviews. Overall survival (OS) and duration of treatment (DOT) were analyzed using Kaplan-Meier methodologies. A total of 209 ALK+ NSCLC patients were included. The cohort had a slight overrepresentation of female patients (56.5%) with a mean age of 61.6 years. Most patients were adenocarcinoma cases (97%) and presented with an ECOG performance status of 0–1 (79%). Stage IIIb–IVb patients comprised 70% of the cohort. The use of ALK-tyrosine kinase inhibitors (TKIs) as first-line treatment increased over time, with the 1st generation ALK-TKI crizotinib being the predominant treatment in the 1st line. In 1st line treatment, 2nd generation ALK-TKIs had a median DOT more than twice the median DOT of crizotinib (25.1 and 9.1 months, respectively). The median OS for the entire cohort was 44.0 months. Patients with stage I–IIIA disease had a median OS that had not been reached, while those with stage IIIb–IVb disease had a median OS of 31.8 months. Patients with stage IIIb–IVb disease receiving an ALK-TKI as 1st line treatment had a median OS of 42.5 months with immature follow-up. Brain metastases at diagnosis or choice of 1st line treatment did not statistically significantly impact OS. This study gives insights into the treatment and outcome of ALK+ NSCLC patients in Denmark and provides a real-world confirmation of the superior disease control provided by 2nd generation ALK-TKIs as compared to the 1st generation ALK-TKI crizotinib. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the impact of adjuvant chemotherapy on long-term survival in unselected patients with high-risk stage II colon cancer including an analysis of each high-risk feature. Data from the Danish Colorectal Cancer Group, the National Patient Registry and the Danish Pathology Registry from 2014 to 2018 were merged. Patients surviving > 90 days were included. High-risk features were defined as emergency presentation, including self-expanding metal stents (SEMS)/loop-ostomy as a bridge to resection, grade B or C anastomotic leakage, pT4 tumors, lymph node yield < 12 or signet cell carcinoma. Eligibility criteria for chemotherapy were age < 75 years, proficient MMR gene expression, and performance status ≤ 2. The primary outcome was 5-year overall survival. Secondary outcomes included the proportion of eligible patients allocated for adjuvant chemotherapy and the time to first administration. In total 939 of 3937 patients with stage II colon cancer had high-risk features, of whom 408 were eligible for chemotherapy. 201 (49.3%) patients received adjuvant chemotherapy, with a median time to first administration of 35 days after surgery. The crude 5-year overall survival was 84.9% in patients receiving adjuvant chemotherapy compared with 66.3% in patients not receiving chemotherapy, p < 0.001. This association corresponded to an absolute risk difference of 14%. 5-year overall survival was significantly higher in patients with high-risk stage II colon cancer treated with adjuvant chemotherapy compared with no chemotherapy. Adjuvant treatment was given to less than half of the patients who were eligible for it. [ABSTRACT FROM AUTHOR]

The article focuses on the diagnosis of locally recurrent head and neck squamous cell carcinoma (LRC) in Nordic Head and Neck Cancer (HNC) centers and the feasibility of using the Odense-Birmingham definition for uniform diagnosis. Topics discussed include the variation in clinical practice for classifying LRC versus second primary carcinoma (SPC) and the impact of introducing the Odense-Birmingham definition on diagnostic decisions among HNC specialists.

Convincing results from randomized controlled trials (RCTs) have led to increasing use of immune checkpoint inhibitors (ICI) as part of standard therapies in real-world (RW) scenarios. However, RW patients differ clinically from RCT populations and might have reduced long-term survival. Currently, only sparse data on 3-5-year survival rate for RW patients with advanced non-small cell lung cancer (NSCLC) treated with ICI exist. A multicenter study was performed including 729 patients with advanced NSCLC receiving monotherapy with ICI (retrospective data (n = 566) and prospective data (n = 163)). Detailed baseline clinical characteristics, programmed death-ligand 1 (PD-L1) tumor proportion score (TPS), and baseline haematological count were registered. Kaplan–Meier estimates and log-rank test were used for survival analyses, Cox regression for determination of prognostic factors. Median time of follow-up (FU) was 48.7 months (IQR 37.2–54.3). Median overall survival (OS) in first line treatment was 20.4 months (IQR 8.5–45.0) compared to 11.4 months (IQR 4.6–27.1) in ≥2nd line (HR 1.48, 95% CI 1.25–1.75). Estimated probability of OS was 30% at 3 years, 23% at 4 years, and 13% at 5 years in first line compared to 17, 13, and 11% in ≥2nd line, respectively. For those with performance status (PS) 2, the 2-year OS rate was 32% (95% CI 0.22–0.43) compared to 5% (95% CI 0.01–0.15) in patients with PD-L1 ≥ 50% versus <50%, respectively. Compared to RCTs, long-term OS and PFS rates are lower in real-world patients treated with ICI in first line but much improved compared to historic rates on chemotherapy. A promising flattening of both the OS and progression free survival curves illustrates that also a subset of real-world patients obtain long-term remission. Patients with PS 2 and PD-L1 ≥ 50% may obtain clinically meaningful 2-year PFS and OS rates. [ABSTRACT FROM AUTHOR]

Background and purpose Hip fractures are associated with high mortality, but the cause of this is still not entirely clear. We investigated the effect of surgical delay, weekends, holidays, and time of day admission on mortality in hip fracture patients. Patients and methods Using data from the Danish National Indicator Project, we identified 38,020 patients admitted from 2003 to 2010. Logistic regression analysis was used to study the association between sex, age, weekend or holiday admission, night-time admission, time to surgery, and ASA score on the one hand and mortality on the other. Results The risk of death in hospital increased with surgical delay (odds ratio (OR) = 1.3 per 24 h of delay), ASA score (OR (per point added) = 2.3), sex (OR for men 2.2), and age (OR (per 5 years) = 1.4). The mortality rate for patients admitted during weekends or public holidays, or at night, was similar to that found for those admitted during working days. Interpretation Minimizing surgical delay is the most important factor in reducing mortality in hip fracture patients. [ABSTRACT FROM AUTHOR]

Background and purpose -- The risk of dislocation after primary total hip arthroplasty (THA) is affected by several factors, which increases the possibility of substantial differences among hospitals. We compared cumulative incidences of dislocation between regions and hospitals after primary THA surgery in osteoarthritis (OA) patients. Patients and methods -- From the Danish Hip Arthroplasty Register, we included 31,105 THAs performed from 2010 to 2014 with 2 years' follow-up. Dislocations treated by closed reduction were identified in the Danish National Patient Register combined with patient file review. The results are presented as 2-year cumulative incidence on national, regional, and hospital level as proportions with 95% confidence intervals (CI) and as adjusted odds ratios (OR) analyzed by multiple logistic regression. Results -- 1,861 dislocations in 1,079 THAs were identi- fied from 59 orthopedic departments. The 2-year cumulative incidence ranged from 2.2% to 4.3% between the 5 regions in Denmark. Hospital variation was 0--12%. For hospitals with a 5-year volume of more than 100 procedures, the incidence was 0.9--7.4%. Using the highest volume hospital as the reference, ORs for dislocation for the remaining hospitals were between 0.3 (CI 0.1--0.6) and 2.7 (1.9--4.0) after adjusting for age, sex, head size, and fixation method. Low-volume hospitals showed a higher dislocation risk than high-volume units with an adjusted OR of 1.2 (1.1--1.4). Interpretation -- We found substantial variation in the incidence of dislocation between hospitals within Denmark, which can be explained by a combination of patient-, component-, and surgery-related factors. There is a need for continuous monitoring of THA dislocation on regional and hospital levels to reduce overall and local dislocation risk for future patients. [ABSTRACT FROM AUTHOR]

The Danish Shoulder Arthroplasty Registry (DSR) was established in 2004. Data are reported electronically by the surgeons. Patient-reported outcome is collected 10-14 months postoperatively using the Western Ontario osteoarthritis of the shoulder index (WOOS). 2,137 primary shoulder arthroplasties (70% women) were reported to the registry between January 2006 and December 2008. Mean age at surgery was 69 years (SD 12). The most common indications were a displaced proximal humeral fracture (54%) or osteoarthritis (30%). 61% were stemmed hemiarthroplasties, 28% resurfacing hemiarthroplasties, 8% reverse shoulder arthroplasties, and 3% total arthroplasties. Median WOOS was 59% (IQR: 37-82). 5% had been revised by the end of June 2010. The most frequent indications for revision were dislocation or glenoid attrition. [ABSTRACT FROM AUTHOR]

The article discusses a study highlighting long-term bowel dysfunction after right-sided hemicolectomy for cancer. Topics discussed include functional outcome following treatment for colorectal cancer, bowel dysfunction that is very common after rectal resection, and ways in which inflammatory bowel disease and polyposis, colon resections may be associated with a wide range of bowel problems.

Background and purpose -- Telemedicine could allow patients to be discharged more quickly after surgery and contribute to improve fast-track procedures without compromising quality, patient safety, functionality, anxiety, or other patient-perceived parameters. We investigated whether using telemedicine support (TMS) would permit hospital discharge after 1 day without loss of self-assessed quality of life, loss of functionality, increased anxiety, increased rates of re-admission, or increased rates of complications after hip replacement. Patients and methods -- We performed a randomized controlled trial involving 72 Danish patients in 1 region who were referred for elective fast-track total hip replacement between August 2009 and March 2011 (654 were screened for eligibility). Half of the patients received a telemedicine solution connected to their TV. The patients were followed until 1 year after surgery. Results -- Length of stay was reduced from 2.1 days (95% CI: 2.0-2.3) to 1.1 day (CI: 0.9-1.4; p < 0.001) with the TMS intervention. Health-related quality of life increased in both groups, but there were no statistically signifi cant differences between groups. There were also no statistically signifi cant differences between groups regarding timed up-and-go test and Oxford hip score at 3-month follow-up. At 12-month follow-up, the rates of complications and re-admissions were similar between the groups, but the number of postoperative hospital contacts was lower in the TMS group. Interpretation -- Length of postoperative stay was shortened in patients with the TMS solution, without compromising patientperceived or clinical parameters in patients undergoing elective fast-track surgery. These results indicate that telemedicine can be of value in fast-track treatment of patients undergoing total hip replacement. [ABSTRACT FROM AUTHOR]

Background and purpose -- Recent evidence has questioned the effect of arthroscopic knee surgery for middle-aged and older patients with degenerative meniscal tears with or without concomitant radiographic knee osteoarthritis (OA). We investigated the prevalence of early or more established knee OA and patients' characteristics in a cohort of patients undergoing arthroscopic surgery for a meniscal tear. Patients and methods -- 641 patients assigned for arthroscopy on suspicion of meniscus tear were consecutively recruited from February 2013 through January 2015. Of these, 620 patients (mean age 49 (18-77) years, 57% men) with full datasets available were included in the present study. Prior to surgery, patients completed questionnaires regarding onset of symptoms, duration of symptoms, and mechanical symptoms along with the knee injury and osteoarthritis outcome score (KOOS). At arthroscopy, the operating surgeon recorded information about meniscal pathology and cartilage damage. Early or more established knee OA was defined as the combination of self-reported frequent knee pain, cartilage damage, and the presence of degenerative meniscal tissue. Results -- 43% of patients (269 of 620) had early or more established knee OA. Of these, a large proportion had severe cartilage lesions with almost half having a severe cartilage lesion in at least 1 knee compartment. Interpretation -- Based on a definition including frequent knee pain, cartilage damage, and degenerative meniscal tissue, early or more established knee OA was present in 43% of patients undergoing knee arthroscopy for meniscal tear. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented on prognostic value of hypoxia-regulated gene expression in gasatroesophageal cancer.

Background. The Danish Cancer Registry (DCR) is the oldest nationwide population-based cancer registry in the Nordic countries. At the time of the study the DCR recorded date of diagnosis, tumor stage and initial treatment. The validity of the clinical information reported to the DCR has never been analyzed. Material and methods. Patients diagnosed with prostate cancer from 1 May to 31 December 1997 and living in eight Danish counties were identified through the DCR. Clinical data was retrieved from hospital records where date of diagnosis, stage at diagnosis and treatment received were registered. Results.The mean age at diagnosis was 74.6 years (s.d. 8.6 years). Diagnosis was verified histologically for 87% of cases. Overall 95% of the patients had a difference less than three months between the reported date of diagnosis and the date found in hospital records. Correction of dates of diagnosis had no impact on survival. Hospital records identified 86 patients with T1-2 disease without distant metastases (M0), but only 56 of these patients (65%) were reported to the DCR as having localized disease. According to hospital records a total of 242 patients were confirmed having distant metastases (M1) at diagnosis but only 139 of these cases (57%) were reported to the DCR as such. Considerable “over reporting” of curative treatment was observed. Conclusion.The DCR has been shown to be reliable in terms of new cases being reported. For the majority of cases there were insignificant differences concerning the date of diagnosis. However, the DCR information on stage and treatment was found to be inaccurate. Since 2004 the DCR registration process, including staging according to the TNM classification, has been carried out electronically from several registers. Future comparison between cohorts of different time intervals or international comparison should be interpreted with caution when clinical information is included. [ABSTRACT FROM PUBLISHER]

Background.In epidemiological studies, Hodgkin lymphomas (HL) in children younger than 15 years and HL in adolescents and younger adults age 15–35 years has traditionally been studied separately, under the assumption that HL at age 0–14 constitute a homogeneous entity. However, the continued validity of this research practice in affluent settings may be questioned. Specifically, the boundary at age 15 years may not be epidemiologically justified, and therefore also questionable clinically. We therefore updated and further characterised recent HL incidence patterns among Nordic children. Material and methods.We obtained HL incidence data in children aged 0–14 years for the period 1978–2010 from the five nationwide Nordic cancer registries. The data were analysed by log-linear and/or a mixture of Poisson regression models. Results.The analyses showed statistically significantly decreasing and increasing HL incidence rates in children younger and older than eight years, respectively during the study period. Statistical modelling suggested that cases in children age 0–6 years constituted a disease entity of its own, whereas cases in older children were more likely to belong to the younger adult HL entity. Conclusion.Diverging incidence trends and statistical modelling suggest that HL in children age 0–14 years cannot be assumed to constitute a homogeneous disease entity in affluent settings. [ABSTRACT FROM PUBLISHER]

Background.Epidemiological studies that have investigated the association between coffee, tea and caffeine consumption and ovarian cancer risk have produced conflicting results. Furthermore, only few studies have examined the role of coffee and tea consumption separately for borderline ovarian tumors. By use of data from a large Danish population-based case-control study, we examined the risk of ovarian tumors associated with coffee, tea, and caffeine consumption with a particular focus on characterizing risks by tumor behavior and histology. Material and methods. From 1995 through 1999, we included 267 women with ovarian cancer, 115 women with borderline ovarian tumors and 911 randomly selected control women. All women completed a beverage frequency questionnaire with detailed information on coffee and tea consumption. Analyses were performed using multiple logistic regression models. Results. Both coffee (OR = 0.90; 95% CI 0.84–0.97 per cup/day) and total caffeine consumption from coffee and tea combined (OR = 0.93; 95% CI 0.88–0.98 per 100 mg/day) decreased the risk of ovarian cancer. These associations were significant only for the serous and “other” subtypes of ovarian cancer. No relation between tea consumption and ovarian cancer risk was observed. The risk estimates for borderline ovarian tumors resembled those observed for ovarian cancer, but did not reach statistical significance. Conclusions.Our results indicate that coffee consumption and total caffeine consumption from coffee and tea combined is associated with a modest decreased risk of ovarian cancer. However, more biological studies are needed to identify bioactive chemical compounds in coffee that potentially could affect ovarian cancer development. [ABSTRACT FROM AUTHOR]

Background.To examine the variations of risk-estimates of radiation-induced hypothyroidism (HT) from our previously developed normal tissue complication probability (NTCP) model in patients with head and neck squamous cell carcinoma (HNSCC) in relation to variability of delineation of the thyroid gland. Patients and methods.In a previous study for development of an NTCP model for HT, the thyroid gland was delineated in 246 treatment plans of patients with HNSCC. Fifty of these plans were randomly chosen for re-delineation for a study of the intra- and inter-observer variability of thyroid volume, Dmeanand estimated risk of HT. Bland-Altman plots were used for assessment of the systematic (mean) and random [standard deviation (SD)] variability of the three parameters, and a method for displaying the spatial variation in delineation differences was developed. Results.Intra-observer variability resulted in a mean difference in thyroid volume and Dmeanof 0.4 cm3(SD ± 1.6) and -0.5 Gy (SD ± 1.0), respectively, and 0.3 cm3(SD ± 1.8) and 0.0 Gy (SD ± 1.3) for inter-observer variability. The corresponding mean differences of NTCP values for radiation-induced HT due to intra- and inter-observer variations were insignificantly small, -0.4% (SD ± 6.0) and -0.7% (SD ± 4.8), respectively, but as the SDs show, for some patients the difference in estimated NTCP was large. Conclusion.For the entire study population, the variation in predicted risk of radiation-induced HT in head and neck cancer was small and our NTCP model was robust against observer variations in delineation of the thyroid gland. However, for the individual patient, there may be large differences in estimated risk which calls for precise delineation of the thyroid gland to obtain correct dose and NTCP estimates for optimized treatment planning in the individual patient. [ABSTRACT FROM AUTHOR]

Background. Factors differently distributed among social groups like obesity, metabolic syndrome, diabetes, smoking, and alcohol intake predict survival after breast cancer diagnosis and therefore might mediate part of the observed social inequality in survival. Material and methods. We conducted a cohort study among 1250 postmenopausal breast cancer patients identified among 29 875 women in the Danish Diet, Cancer and Health Study. Participants completed questionnaires and anthropometric measurements were made at enrollment. Information on survival, socioeconomic position, and comorbidity was obtained by linkage to national Danish registries. Clinical information was obtained from the nationwide Danish Breast Cancer Database. Selected information was obtained from hospital records at time of diagnosis. All analyses were based on Cox proportional hazard models, using death from all causes as outcome. Results. Median follow-up was 9.6 years [interquartile range (IQR), 2.2-17.0 years]. The hazard ratio (HR) for death from all causes increased with lower education (p for trend, 0.01). Adjustment for disease-related prognostic factors, comorbidity and metabolic indicators measured as BMI, waist circumference and diabetes, and smoking and alcohol affected but did not explain the social gradient. Conclusion. The findings indicate that these factors explain some but not all the social inequality in survival after breast cancer and that improvement of lifestyle to some extent would improve survival among women with low socioeconomic position. [ABSTRACT FROM AUTHOR]

Objective. Little is known about the development of psychological wellbeing over time among women who have been treated for breast cancer. The aim of this study was to identify distinct patterns of distress, anxiety, and depression in such women. Methods. We invited 426 consecutive women with newly diagnosed primary breast cancer to participate in this study, and 323 (76%) provided information on distress ('distress thermometer') and on symptoms of anxiety and depression ('hospital anxiety and depression scale'). Semiparametric group-based mixture modeling was used to identify distinct trajectories of distress, anxiety, and depressive symptoms assessed the week before surgery and four and eight months later. Logistic regression analysis was used to evaluate the characteristics of women in the distinct groups. Results. Although no sub-group of women with chronic severe anxiety or depressive symptoms was found, we did identify a sub-group of 8% of the women who experienced continuously severe distress. Young age, having a partner, shorter education, and receiving chemotherapy but not radiotherapy might characterize women whose psychological symptoms remain strong eight months after diagnosis. Conclusion. By looking beyond the mean, we found that 8% of the women experienced chronic severe distress; no sub-groups with chronic severe anxiety or depression were identified. Several socio-demographic and treatment factors characterized the women whose distress level remained severe eight months after diagnosis. The results suggest that support could be focused on relatively small groups of patients most in need. [ABSTRACT FROM AUTHOR]

Background. To address social inequality in survival after lung cancer, it is important to consider how socioeconomic position (SEP) influences prognosis. We investigated whether SEP influenced receipt of first-line treatment and whether socioeconomic differences in survival could be explained by differences in stage, treatment and comorbidity. Material and methods. In the Danish Lung Cancer Register, we identified 13 045 patients with lung cancer diagnosed in 2004-2010, with information on stage, histology, performance status and first-line treatment. We obtained age, gender, vital status, comorbid conditions and socioeconomic information (education, income and cohabitation status) from nationwide population-based registers. Associations between SEP and receipt of first-line treatment were analysed in multivariate logistic regression models and those with overall mortality in Cox regression models with stepwise inclusion of possible mediators. Results. For both low- and high-stage lung cancer, adjusted ORs for first-line treatment were reduced in patients with short education and low income, although the OR for education did not reach statistical significance in men with high-stage disease. Patients with high-stage disease who lived alone were less likely to receive first-line treatment. The socioeconomic difference in overall survival was partly explained by differences in stage, treatment and comorbidity, although some differences remained after adjustment. Among patients with high-stage disease, the hazard ratio (HR) for death of those with low income was 1.12 (95% CI 1.05-1.19) in comparison with those with high income. Among patients with low-stage disease, those who lived alone had a 14% higher risk for dying (95% CI 1.05-1.25) than those who lived with a partner. The differences in risk for death by SEP were greatest in the first six months after diagnosis. Conclusion. Socioeconomic differences in survival after lung cancer are partly explained by social inequality in stage, first-line treatment and comorbidity. Efforts should be made to improve early diagnosis and adherence to first-line treatment recommendations among disadvantaged lung cancer patients. [ABSTRACT FROM AUTHOR]

Background. Many cancer patients who are smokers when starting cancer therapy continue smoking despite evidence of tobacco smoking as a risk factor for poor treatment response and secondary primary cancers. Small samples and inconsistent results in previous studies warrant further research to identify predictors of being a continuous smoker during and after radiotherapy. Material and methods. In the clinical database of the Danish Head and Neck Cancer Group (DAHANCA), we identified 1455 patients diagnosed with laryngeal cancer between 2000 and 2010, who were all smokers at date of diagnosis and treated with primary radiotherapy. Information on the socio-economic characteristics of the study cohort was obtained from Statistics Denmark the year prior to diagnosis. Logistic regression analyses were applied. Results. In the cohort of laryngeal cancer patients smoking before starting radiotherapy, 50% still smoked one year after radiotherapy similar to the percentage of smokers during treatment. Being younger than 60 years (OR 1.39, 95% CI 1.00-1.91), commenced smoking before the age of 15 (OR 1.77, 95% CI 1.32-2.38), having a poor WHO Performance status (OR 3.09, 95% CI 1.71-5.61), low income (OR 2.21, 95% CI 1.23-3.98) and living alone (OR 1.56, 95% CI 1.13-2.14) were associated with increased risk of continuous smoking during treatment. Similar findings were found two months and one year after radiotherapy, however, no association with living alone (OR 1.08, 95% CI 0.73-1.59) at the one-year follow-up. Tumor stage and the average number of cigarettes smoked per day before radiotherapy were not associated with being a continuous smoker. Conclusion. Younger patients, who had an early smoking initiation, a poor performance status, low income and lived alone, were most likely to continue smoking. Continuous smoking was not related to the extent of disease. [ABSTRACT FROM AUTHOR]

Background. Anxiety and depressive symptoms are common among cancer survivors. Studies of a possible association with social position have had divergent results. We examined these associations, social position being measured by education, in Danish cancer survivors approximately two years after diagnosis. Material and methods. People aged over 18, living in Denmark and registered for a first cancer in the Danish National Patient Registry between 1 May and 31 August 2010 were contacted; 4346 returned a questionnaire shortly after diagnosis, and 2568 were followed up in 2012. Age, sex and cancer site were derived from the registry; all other information was self-reported, with that on education from the 2010 questionnaire and responses to the Hospital Anxiety and Depression Scale from the 2012 questionnaire. General linear models were used, with adjustment for demographic factors, cancer-specific factors, and comorbidity. Results. The study population consisted of 1667 people (response rate, 51%). The mean symptom scores were 4.34 (SD 3.77) for anxiety and 2.94 (SD 3.25) for depression. People with medium and higher education had slightly higher anxiety symptom scores (mean differencemedium = 0.41, 95% CI 20.07; 0.88, mean differencehigher = 0.19, 95% CI 20.27; 0.65). Depressive symptom scores were slightly elevated for people with medium education and reduced for those with higher education (mean differencemedium = 0.34, 95% CI 20.07; 0.75, mean differencehigher = 20,11, 95% CI 20.50; 0.29). Female sex, smoking-related cancers and chemotherapy were significantly associated with higher scores for both anxiety and depressive symptoms, but somatic comorbidity and mental disorders at the time of treatment were most strongly, significantly associated with elevated anxiety and depressive symptom scores. Conclusion. No overall significant differences in anxiety or depressive symptom scores were found with length of education. Previous mental disorders and somatic comorbidity are the strongest indicators of higher levels of anxiety and depressive symptoms. [ABSTRACT FROM AUTHOR]

Background. Women with breast cancer experience different symptoms related to surgical or adjuvant therapy. Previous findings and theoretical models of mind-body interactions suggest that psychological wellbeing, i.e. levels of distress, influence the subjective evaluation of symptoms, which influences or determines functioning. The eight-week mindfulness-based stress reduction (MBSR) program significantly reduced anxiety and depression in breast cancer patients in a randomized controlled trial (NCT00990977). In this study we tested the effect of MBSR on the burden of breast cancer related somatic symptoms, distress, mindfulness and spiritual wellbeing and evaluated possible effect modification by adjuvant therapy and baseline levels of, distress, mindfulness and spiritual wellbeing. Material and methods. A population-based sample of 336 women Danish women operated for breast cancer stages I-III were randomized to MBSR or usual care and were followed up for somatic symptoms, distress, mindfulness skills and spiritual wellbeing post-intervention and after six and 12 months. Effect was tested by general linear regression models post-intervention, and after six and 12 months follow-up and by mixed effects models for repeated measures of continuous outcomes. Effect size (Cohen's d) was calculated to explore clinical significance of effects among intervention group. Finally, modification of effect of MBSR on burden of somatic symptoms after 12 months' follow-up by adjuvant therapy and baseline levels of, distress, mindfulness and spiritual wellbeing were estimated. Results. General linear regression showed a significant effect of MBSR on the burden of somatic symptoms post-intervention and after 6 months' follow-up. After 12 months' follow-up, no significant effect of MBSR on the burden of somatic symptoms was found in mixed effect models. A statistically significant effect of MBSR on distress was found at all time-points and in the mixed effect models. Significant effects on mindfulness were seen after six and 12 months and no significant effect was observed for spiritual wellbeing. No significant modification of MBSR effect on somatic symptom burden was identified. Conclusion. This first report from a randomized clinical trial on the long-term effect of MBSR finds an effect on somatic symptom burden related to breast cancer after six but not 12 months follow-up providing support for MBSR in this patient group. [ABSTRACT FROM AUTHOR]

Background. In 2002, the Danish Cancer Society opened a rehabilitation centre in which cancer patients were offered a free, six-day, multidimensional residential course. Our previous studies of the effects of this course at one and six months of follow-up showed no positive effect on distress. We investigated long-term effects at 12 months of follow-up and whether subgroups with fewer psychosocial resources received more benefit from the intervention than patients with better resources. Material and methods. In two Danish counties, 507 patients with breast, prostate, colon or rectum cancer diagnosed within the past two years who had completed primary treatment were randomised to a six-day, multidimensional residential rehabilitation course or to standard care. Of these, 208 patients received the allocated intervention and 244 received the allocated control condition and were included in the analyses. Patients in both groups completed questionnaires at baseline and at one, six and 12 months of follow-up, including the 'Profile of Mood States short form', the 'General Self-efficacy' scale and a question on emotional support. At 12 months of follow-up, 179 participants in the intervention group and 195 in the control group provided data. Results. No effect of the intervention was found on distress at 12 months of follow-up, even in subgroups with fewer psychosocial resources at baseline, i.e. greater baseline distress, poorer self-efficacy and less emotional support. Conclusion. Multidimensional rehabilitation programmes may not be effective in the treatment of distress. During the past few decades, studies of psychotherapy or psycho-education in cancer patients have shown small to moderate effects. More focused rehabilitation programmes may be more effective. [ABSTRACT FROM AUTHOR]

Background. Socioeconomic differences in survival after head and neck squamous cell carcinoma (HNSCC) are among the greatest for any malignancy. To improve our understanding of the mechanisms by which socioeconomic position influences HNSCC survival, we investigated the association between socioeconomic position and advanced stage HNSCC at diagnosis. Material and methods. Men and women with HNSCC diagnosed between 1992 and 2008 were identified in the Danish Head and Neck Cancer Group (DAHANCA) database, which contains detailed information on all cases of HNSCC treated in Denmark. Individual information on the following four socioeconomic indicators: highest attained educational level, cohabitation status, disposable income and degree of urbanisation were obtained from Statistics Denmark. For the 9683 cases on which there was full information, we estimated odds ratios (ORs) for a diagnosis of advanced stage (TNM III-IV) HNSCC in multivariate logistic regression models by site (glottic, non-glottic larynx, oropharynx, hypopharynx and oral cancer), with adjustment for age, gender, period of diagnosis, education, income, cohabitation status, degree of urbanisation and comorbidity in accordance with a causal diagram. Results. For all HNSCC sites, the ORs for advanced stage at diagnosis were increased for patients with low income and for men living alone. For glottic and oral cancers, the ORs for advanced stage HNSCC increased systematically by decreasing length of education. Increased ORs were found for hypopharynx cancer patients living in rural areas or provincial cities. Having one or more comorbid conditions was associated with an increased OR for advanced stage oral cancer but with a decreased OR for oropharynx cancer. Conclusion. In this nationwide population-based study, socioeconomic differences in stage at diagnosis were found for all HNSCC subsites. Focus on the high risk for advanced stage HNSCC among vulnerable patients may be beneficial during referral and diagnosis in order to improve HNSCC outcomes. [ABSTRACT FROM AUTHOR]

Purpose. Before, during and after autologous hematopoietic stem cell transplantation (HD-ASCT) patients suffer from significant loss of physical function, and experience multiple complications during and after hospitalization. Studies regarding safety and feasibility of physical exercise interventions for patients undergoing treatment with HD-ASCT are missing. Methods. Forty patients referred to HD-ASCT treatment, suffering from multiple myeloma, lymphoma or amyloidosis aged 23-70 years were enrolled in a prospective longitudinal study. The study consisted of a home-based exercise program for use in the ambulatory setting and supervised exercise sessions Monday to Friday for 30-40 minutes during admission. Safety of the exercise program and physical tests were assessed by using a weekly questionnaire and report of inadvertent incidences. Adherence to the home-based exercise program was reported by using a patient diary, weekly questionnaire and count of daily attendance in supervised sessions during hospital stay. Data collection was scheduled shortly after diagnosis, admission, discharge and eight weeks after discharge. Success criteria were: no severe adverse events in relation to exercise program and assessments; performance of three days of physical exercises during ambulatory period and hospital stay and 150 minutes of weekly physical activity. Results. Of the 25 patients who completed the exercise program during the ambulatory period prior to HD-ASCT a mean weekly attendance to home exercises of 5.3 (± 2.8) days and a median weekly physical activity of 240 (± 153.8) minutes was found. During hospital stay the median attendance was 9 (± 3.9) days of 10 (± 6.9) possible. Two months after discharge the patients reported a median weekly physical activity of 360 (2745.5) minutes. No severe adverse events in relation to the exercise program or assessments were reported. Conclusion. Based on the enrolled number of patients the physical exercise intervention for patients undergoing HD-ASCT seems promising regarding feasibility and safety. [ABSTRACT FROM AUTHOR]

Purpose. To test the hypothesis that head and neck cancer (HNC) patients are in need of specialized follow-up (FU). This was done by an evaluation of the FU activities in a cohort of patients followed longitudinally for five years with focus on optimal duration and interval of post-therapeutic follow-up. Methods. The study evaluated a cohort consisting of 197 consecutive patients with HNC treated at Aarhus University Hospital from 1 January to 31 December 2009. The inclusion criteria was that patients should be deemed free of disease two months after completed primary curative intended treatment or after primary curative salvage. It left 141 patients available for analysis. Data were collected through a medical chart review and from the Danish Head and Neck Cancer Group (DAHANCA) database. Parameters recorded were: regular or extraordinary visit, alarm symptoms, late morbidity and the consequences of these. Results. The 141 patients underwent 1408 FU visits. Only 15 of the 141 patients had no tumor problems or morbidity issues raised at any FU visit. Suspicion of recurrent disease was observed at 207 of the 1408 FU visits, involving 97 patients and resulted in a total of 370 diagnostic procedures; 170 (82%) visits with suspicion of recurrence occurred within 3½ years after end of treatment. A recurrence was verified in 30 patients. Additionally four new primary head and neck cancer was diagnosed during follow-up. There were 1150 visits (82%) involving 135 patients in which late treatment-related morbidity was recorded. Actions taken related to morbidity happened in 71 patients, but no new problems appeared after three years. Conclusion. The study document the need of specialized FU, as 86% of all HNC survivors have tumor or severe morbidity issues during FU. The data suggest that 3½-year FU after ended therapy may be sufficient for the majority of patients. [ABSTRACT FROM AUTHOR]

Background. The simultaneous presence of cancer and other medical conditions (comorbidity) is frequent. Cigarette smoking is the major risk factor for as well head and neck cancer (HNC) and lung cancer (LC) as chronic obstructive pulmonary disease (COPD). COPD is the most common comorbidity in LC patients, and presence of COPD worsens the prognosis of HNC and LC. COPD is under-diagnosed and under-treated in the Danish population. The aims of this study were to determine the prevalence of COPD in a HNC and LC population, and to determine the need and feasibility of a randomized controlled phase II trial comparing usual care with optimized medical treatment of COPD in cancer patients. Material and methods. All patients with HNC or LC referred for oncologic treatment in a university hospital during a 10-month period were invited to attend a pulmonary clinic for evaluation of lung function. Patients who were found to have concomitant COPD were randomized to intervention or usual care. Primary endpoints were prevalence of COPD among the referred patients with either LC or HNC, and further whether the patients that were diagnosed with COPD already received treatment in accordance with Danish COPD guidelines. Secondary outcome was feasibility, i.e. the proportion of eligible patients that accepted follow-up in the pulmonary clinic for 24 weeks in addition to oncological treatment. The design of the randomized trail is described in detail. Results. In total 130 patients of whom 65% had LC and 35% HNC have been screened during the first seven months of this ongoing trial. Sixty-eight percent of LC patients and 22% of HNC patients had COPD. All but one of 68 eligible patients accepted randomization. Nearly one third (31%) of the LC and HNC patients with COPD were diagnosed prior to study entry, and of these, only 33% were receiving correct treatment according to current guidelines. Conclusion. For patients with LC, and to a lesser extend HNC, there is a need for improved diagnosis and treatment of concomitant COPD. Furthermore, patients found it acceptable to be scheduled for a 24-week follow-up in a pulmonary clinic along with their oncological treatment. [ABSTRACT FROM AUTHOR]

Objectives. In Denmark, most healthcare services, including cancer treatment and rehabilitation, are offered free of charge by referral from a treating physician; thus, social equality should be expected. In a population-based cohort study of registry-based data, we examined the association between socioeconomic position, measured as educational level, and referral to rehabilitation services among cancer patients. Material and methods. Through the Danish Cancer Registry, we identified all people resident in the Municipality of Copenhagen with cancer diagnosed in 2007-2012. Information on all rehabilitation referrals was retrieved from the Municipal Centre for Cancer Rehabilitation for 2009-2012. Information on demographic and socioeconomic characteristics was obtained from national Danish registers. The Cox proportional hazards model was used to investigate associations between educational level and referral to rehabilitation with adjustment for sex, age, diagnosis, disposable income, cohabitation status and number of children living at home at the time of diagnosis. Results. A primary cancer was diagnosed in 13 840 people, of whom 2148 (16%) were referred to rehabilitation services during follow-up. In the fully adjusted model, we found education to be a predictor of referral, with a hazard ratio of 1.33 (95% CI 1.19-1.49) for patients with long education and a hazard ratio of 1.15 (95% CI 1.03-1.29) for patients with medium education as compared with patients with short education. Conclusions. Our findings suggest that, even after differences in demographics and cancer characteristics are accounted for, referral to rehabilitation services is not equally distributed by social group. Higher educational level is associated with a higher probability of referral to rehabilitation services. [ABSTRACT FROM AUTHOR]

The article discusses a research concerning the effectiveness of stereotactic body radiation therapy (SBRT) or alternatively stereotactic ablative radiotherapy (SABR) in lung treatments. It highlights the number of potential dosimetric benefits of flattening filter free (FFF) beams as compared to the conventional filter flattened beams (FF). It also emphasizes the effect of FFF beams on plan quality, delivery time and delivery accuracy for treatment of lung SBRT.

Background. Clinical trials indicate that the benefit of adding concurrent chemotherapy to radiotherapy of locally advanced non-small cell lung cancer (NSCLC) for fit elderly is similar to the benefit for younger patients. However, since elderly patients are under-represented in most trials, the results might be due to selection bias, thus reports from a cohort of consecutively treated patients are warranted. The current single institution study reports on the influence of age on survival of locally advanced NSCLC patients treated with radiotherapy combined with or without concurrent chemotherapy. Material and methods. Altogether, 478 patients completed radical radiotherapy in doses of 60-66 Gy/30-33 fractions from 1995 to June 2012; 137 of the patients had concurrent chemotherapy. The data was analyzed in age groups < 60, 60-69, and ≥ 70 years. Results. In the analyses of overall and lung cancer specific survival the hazard ratio was related to the use of concurrent chemotherapy was 0.49 (95% CI 0.29; 0.82), 0.68 (95% CI 0.48; 0.98) and 1.01 (95% CI 0.67; 1.51) for the age groups < 60, 60-69, and ≥ 70, respectively. Conclusion. Use of concurrent chemotherapy to radiotherapy of locally advanced NSCLC was associated with a survival benefit in patient younger than 70 years which was not the case for patients older than 70 years, indicating the need to be careful when selecting elderly patients for concurrent chemo-radiation. [ABSTRACT FROM AUTHOR]

Background. As carriers of filaggrin gene ( FLG) mutations may have a compromised cervical mucosal barrier against human papillomavirus infection, our primary objective was to study their risk of cervical cancer. Methods. We genotyped 586 cervical cancer patients for the two most common FLG mutations, R501X and 2282del4, using blood from the Copenhagen Hospital Biobank, Denmark. Controls (n = 8050) were genotyped in previous population-based studies. Information on cervical cancer, mortality and emigration were obtained from national registers. Odds ratios (OR) were estimated by logistic regression with adjustment for age at blood sampling, and weighted by the genotype-specific inverse probability of death between diagnosis and sampling. Hazard ratios (HR) were estimated by Cox regression with time since diagnosis as underlying time, and with adjustment for age at diagnosis and stratification by cancer stage. Results. The primary results showed that FLG mutations were not associated with the risk of cervical cancer (6.3% of cases and 7.7% of controls were carriers; OR adjusted 0.81, 95% CI 0.57-1.14; OR adjusted+ weighted 0.96, 95% CI 0.58-1.57). Among cases, FLG mutations increased mortality due to cervical cancer (HR 4.55, 95% CI 1.70-12.2), however, the association was reduced after stratification by cancer stage (HR 2.53, 95% CI 0.84-7.59). Conclusion. Carriage of FLG mutations was not associated with the risk of cervical cancer. [ABSTRACT FROM AUTHOR]

Background and purpose - Postoperative joint stiffness following total knee arthroplasty (TKA) may compromise the outcome and necessitate manipulation. Previous studies have not been in a fast-track setting with optimized pain treatment, early mobilization, and short length of stay (LOS), which may have influenced the prevalence of joint stiffness and subsequent manipulation. We investigated the prevalence of manipulation following fast-track TKA and identified patients at risk of needing manipulation. Patients and methods - 3,145 consecutive unselected elective primary unilateral TKA patients operated in 6 departments with well-defined fast-track settings were included in the study. Demographic data, prevalence, type and timing of manipulation, and preoperative and postoperative ROM were recorded prospectively, ensuring complete 1-year follow-up. Results - 70 manipulations were performed within 1 year (2.2%) at a mean of 4 months after index surgery. Younger age and not using walking aids preoperatively were associated with a higher risk of manipulation. LOS ≤ 4 days (as opposed to a longer LOS) was not associated with an increased risk of manipulation. Interpretation - The prevalence of manipulation was lower or comparable to that in most published studies following more conventional pathways. Inherent patient demographics were identified as risk factors for manipulation whereas LOS ≤ 4 days was not. Thus, fast-track TKA does not result in increased risk of manipulation-despite a shorter LOS. Optimized pain treatment and early mobilization may contribute to these favorable results that support the use of fast-track. [ABSTRACT FROM AUTHOR]

Background. Long-term Hodgkin lymphoma (HL) survivors have an increased risk of late cardiac morbidity and secondary lung cancer after chemotherapy and mediastinal radiotherapy. In this prospective study we investigate whether radiotherapy with deep inspiration breath-hold (DIBH) can reduce radiation doses to the lungs, heart, and cardiac structures without compromising the target dose. Patients and methods. Twenty-two patients (14 female, 8 male), median age 30 years (18-65 years), with supra-diaphragmatic HL were enrolled and had a thoracic PET/CT with DIBH in addition to staging FDG-PET/CT in free breathing (FB) and a planning CT in both FB and DIBH. For each patient an involved-node radiotherapy plan was done for both DIBH and FB, and the doses to the lungs, heart, and female breasts were recorded prospectively. Mean doses to the heart valves and coronary arteries were recorded retrospectively. Patients were treated with the technique yielding the lowest doses to normal structures. Results. Nineteen patients were treated with DIBH and three with FB. DIBH reduced the mean estimated lung dose by 2.0 Gy (median: 8.5 Gy vs. 7.2 Gy) (p < 0.01) and the mean heart dose by 1.4 Gy (6.0 Gy vs. 3.9 Gy) (p < 0.01) compared to FB. The lung and heart V20Gy were reduced with a median of 5.3% and 6.3%. Mean doses to the female breasts were equal with FB and DIBH. Conclusion. DIBH can significantly decrease the estimated mean doses to the heart and lungs without lowering the dose to the target in radiotherapy for patients with mediastinal HL. [ABSTRACT FROM AUTHOR]

Background. Stereotactic radiation therapy (SRT) of brain metastases is used with good effect around the world, but no consensus exists regarding which prognostic factors that are related to favourable or unfavourable prognosis after the treatment. A better definition of these factors will ensure a more precise application of the treatment. Material and methods. A consecutive cohort of the 198 patients treated for brain metastases with SRT without concurrent whole-brain radiation therapy at our department from 2001 to 2012 was retrospectively analysed. Results. Median survival was seven months and median time to clinical cerebral progression was eight months. The multivariate analysis revealed age ≥ 65 years, Performance Status ≥ 2, extracranial metastases and size of metastasis > 20 mm as independent prognostic factors related to shorter survival. No factors were independently related to clinical cerebral progression. Conclusion. We identified four prognostic factors related to survival after SRT for brain metastases. The grouping of patients by these factors is useful to determine the level of treatment. We discourage the delivery of SRT to patients with 3-4 unfavourable prognostic factors because of the very short median survival of two months. [ABSTRACT FROM AUTHOR]

Background. Trabectedin was in Europe approved for treatment of metastatic soft tissue sarcoma (STS) in 2007 based on results of a phase II study with relatively few patients. The purpose of this nationwide retrospective study was to assess efficacy and safety of using trabectedin in the entire unselected cohort of patients with metastatic sarcoma and to test known, as well as new prognostic factors that may affect overall survival (OS). Patients and methods. Between January 2008 and April 2013, 117 patients were treated with trabectedin for metastatic sarcoma in the three specialized sarcoma centers in Denmark. Known prognostic factors such as age, gender and performance status, the histopathology as well as other new factors such as response to previous chemotherapy and hyponatremia were tested. Results. Median age was 59 years. Lipo- and leiomysosarcomas (L-sarcomas) represented 43% of the cases and 18% had hyponatremia before the start of trabectedin. The median number of previous lines of chemotherapy was two (range 0-6) and the median number of chemotherapy cycles given before trabectedin was nine (range 0-85). The median number of trabectedin cycles was three (range 1-17). The median OS for the whole cohort was seven months. Poor performance status, non-L-sarcomas, and hyponatremia were statistically significant adverse prognostic factors with median survival of: 4, 5, and 2 months compared to 9, 12 and 13 months, respectively. Moreover, having achieved clinical benefit [complete response (CR), partial response (PR) or stable disease (SD)] from previous chemotherapy was a favorable prognostic factor for response to trabectedin. In multivariate analysis hyponatremia was the only independent significant poor prognostic factor affecting OS. Conclusions. This retrospective study confirmed the previously published safety and efficacy of trabectedin in patients with metastatic sarcoma and showed hyponatremia to be a strong independent statistically significant poor prognostic factor. [ABSTRACT FROM AUTHOR]

Background. Treatment of high-grade osteosarcoma remains a major challenge in orthopedic oncology as no major breakthrough in overall survival has occurred in the past 20 years. Due to the rarity of the disease, comparing the results of a single institution to best standard practice needs the establishment of clinical databases. The aim of this study was to report the cumulative 30-years' experience of a single institution and to assess the incidence, survival and prognostic factors of high-grade osteosarcoma using a recently validated, hospital-based database, representing all citizens living in western Denmark, the Aarhus Sarcoma Registry. Material and methods. Between 1979 and 2008, 169 patients were treated at the Sarcoma Centre of Aarhus University Hospital for high-grade osteosarcoma. The incidence was calculated as a WHO age-standardized incidence per million per year. The endpoint was overall survival, analyzed by the Kaplan-Meier method and log-rank. Possible prognostic factors were analyzed by the uni- and multivariate Cox proportional hazard method. Results. The incidence of high-grade osteosarcoma in western Denmark from 1979 to 2008 was 2.7/million inhabitants/year. The five-year overall survival was 42% (95% CI 34; 49) for the whole cohort of patients with high-grade osteosarcoma and 54% (95% CI 43; 64) for patients with localized disease treated with wide excision and chemotherapy. For patients treated with curative intent, no soft tissue extension, treatment with sufficient surgical margin and standard chemotherapy, as well as a high degree of necrosis after chemotherapy were all independent prognostic factors for overall survival. Conclusion. The data from this hospital-based, validated database confirms the relevance of the known prognostic factors of high-grade osteosarcoma and emphasizes the importance of adequate surgical margins and chemotherapy. [ABSTRACT FROM AUTHOR]

Background. Breast cancer is characterized by great molecular heterogeneity demonstrated, e.g. by the intrinsic subtypes. Administration of post-mastectomy radiotherapy (PMRT) does, however, not reflect this heterogeneity. A gene profile (DBCG-RT profile) has recently been developed and validated, and has shown prognostic impact in terms of loco-regional failure and predictive impact for PMRT. Reports have also shown predictive value in terms of benefit of PMRT from intrinsic subtypes and derived approximations. The aim of this study was to examine: 1) the agreement between various methods for determining the intrinsic subtypes; and 2) the relationship between the prognostic and predictive impact of the DBCG-RT profile and the intrinsic subtypes. Material and methods. Intrinsic subtypes and the DBCG-RT profile was determined from microarray analysis based on fresh frozen tissue from 191 patients included in the Danish Breast Cancer Cooperative Group (DBCG) 82bc trial. Corresponding formalin-fixed, paraffin-embedded tissue was available from 146 of these patients and from another 890 DBCG82bc patients. Estrogen receptor, progesterone receptor, HER2, CK5/6, Ki-67 and EGFR were combined into immunohistochemical approximations of the intrinsic subtypes. Endpoint considered was loco-regional recurrence (LRR). Results. The DBCG-RT profile identified a group of patients with low risk of LRR and no additional benefit from PMRT among all subtypes. Combining six immunohistochemical markers identified a subgroup of triple negative patients with high risk of LRR and significant benefit from PMRT. Agreement in the different assignments of tumors to the subtypes was suboptimal, and the clinical outcome and predicted benefit from PMRT varied according to the method used for assignment. Conclusion. The prognostic and predictive information obtained from the DBCG-RT profile cannot be substituted by any approximation of the tumors intrinsic subtype. The predictive value of the intrinsic subtypes in terms of PMRT was influenced by the method used for assignment to the intrinsic subtypes. [ABSTRACT FROM AUTHOR]

Background. The aim of this study was to evaluate two fully automatic segmentation methods in comparison with manual delineations for their use in delineating the heart on planning computed tomography (CT) used in radiotherapy for breast cancer. Material and methods. Automatic delineation of heart in 15 breast cancer patients was performed by two different automatic delineation systems. Analysis of accuracy and precision of the differences between manual and automatic delineations were evaluated on volume, mean dose, maximum dose and spatial distance differences. Two sets of manual delineations were used in the evaluation: 1) a set prior to common delineation guidelines; and 2) a second set repeated with a common set of guidelines. Results. Systematic differences between automatic and manual delineations were small for volume as well as dose. The uncertainty of the difference in volume was smaller than or similar to the inter-observer variation in manual delineations. For dose, the uncertainty was similar to manual delineations performed without common guidelines but slightly higher than the variation in manual delineations with common guidelines. Spatial differences between average manual and automatic delineations were largest at the base of the heart, where also large variations are observed in the manual delineations. Both algorithms could be improved slightly at the apex of the heart where the variation of automatic delineation was larger than for the manual delineations. Conclusion. Automatic delineation is an equal alternative to manual delineation when compared to the inter-observer variation. The reduction in precision of measured dose was small compared to other uncertainties affecting the estimated heart dose and would for most applications be outweighed by the benefits of fully automated delineations. [ABSTRACT FROM AUTHOR]

Background. Comorbidity is an important prognostic factor for survival in other cancers, but the importance in soft tissue sarcoma has not yet been clarified. The aims of this study were to examine the prevalence of comorbidity in soft tissue sarcoma patients, and estimate the impact of comorbidity on overall and disease-specific mortality. Material and methods. Overall, 1210 adult patients with soft tissue sarcoma in the extremities or trunk wall were identified through the Aarhus Sarcoma Registry, a validated population-based database. Information on comorbidity was obtained through the National Patient Registry, and a Charlson's Comorbidity score was calculated for each patient. The prevalence of comorbidity was assessed overall, as well as according to age and year of diagnosis. Overall and disease-specific mortality rates according to level of comorbidity were computed. The prognostic value of comorbidity was estimated using crude and adjusted Cox proportional hazard models. Results. The overall prevalence of comorbidity was 25%. The prevalence increased with increasing age, and patients with comorbidity had a larger proportion of adverse prognostic factors when compared to patients without comorbidity. The five-year disease-specific mortality was 26% (95% CI 24-29) for patients without comorbidity, compared to 33% (95% CI 24-42), 41% (95% CI 32-50), and 44% (95% CI 33-55) for patients with mild, moderate, and severe comorbidity, respectively. After adjusting for age, sex, stage, tumor size, depth, grade, surgical margin, radiotherapy, and chemotherapy, comorbidity was independently associated with an increased overall and disease-specific mortality. Conclusion. Patients with comorbidity had significantly increased overall and disease-specific mortality compared to patients without comorbidity, even when adjusting for important prognostic factors including age. [ABSTRACT FROM AUTHOR]

Background. Eosinophilia may represent an early paraclinical sign of malignant disease and a host anti-tumor effect. The association between eosinophilia and the development of solid tumors has never before been examined in an epidemiological setting. The aim of the present study was to investigate eosinophilia in routine blood samples as a potential biomarker of solid tumor development in a prospective design. Material and methods. From the Copenhagen Primary Care Differential Count ( CopDiff) Database, we identified 356 196 individuals with at least one differential cell count (DIFF) encompassing the eosinophil count during 2000-2007. From these, one DIFF was randomly chosen and categorized according to no (< 0.5 × 109/l), mild (≥ 0.5-1.0 × 109/l) or severe (≥ 1.0 × 109/l) eosinophilia. From the Danish Civil Registration System and the Danish Cancer Registry we ascertained all-cause death and solid tumors within the first three years following the DIFF. Using multivariable logistic regression, odds ratios (OR) were calculated and adjusted for previous eosinophilia, sex, age, year, month, C-reactive protein, previous cancer and Charlson's Comorbidity Index. Results. The risk of bladder cancer was increased with mild eosinophilia [OR 1.93 (CI 1.29-2.89), p = 0.0013]. No associations with eosinophilia were observed for the remaining solid cancers. Conclusion. We demonstrate that eosinophilia in routine blood samples associates with an increased risk of bladder cancer. Our data emphasize that additional preclinical studies are needed in order to shed further light on the role of eosinophils in carcinogenesis, where it is still unknown whether the cells contribute to tumor immune surveillance or neoplastic evolution. [ABSTRACT FROM AUTHOR]

Background and purpose - Obesity is a risk factor for osteoarthritis in the lower limb, yet the cardiovascular risks associated with obesity in hip or knee replacement surgery are unknown. We examined associations between body mass index (BMI) and the risk of a major adverse cardiovascular event (MACE: ischemic stroke, acute myocardial infarction, or cardiovascular death) or the risk of all-cause mortality in a nationwide Danish cohort of patients who underwent primary hip or knee replacement surgery. Methods - Using Danish nationwide registries, we identified 34,744 patients aged ≥ 20 years who underwent elective primary hip or knee replacement surgery between 2005 and 2011. We used multivariable Cox regression models to calculate the 30-day risks of MACE and mortality associated with 5 BMI groups (underweight (BMI < 18.5 kg/m2), normal weight (18.5-24 kg/m2), overweight (25-29 kg/m2), obese 1 (30-34 kg/m2), and obese 2 (≥ 35 kg/m2)). Results - In total, 232 patients (0.7%) had a MACE and 111 (0.3%) died. Compared with overweight, adjusted hazard ratios (HRs) were 1.2 (95% CI: 0.4-3.3), 1.3 (0.95-1.8), 1.6 (1.1-2.2), and 1.0 (0.6-1.9) for underweight, normal weight, obese 1, and obese 2 regarding MACE. Regarding mortality, the corresponding HRs were 7.0 (2.8-15), 2.0 (1.2-3.2), 1.5 (0.9-2.7), and 1.9 (0.9-4.2). Cubic splines suggested a significant U-shaped relationship between BMI and risks with nadir around 27-28. Interpretation - In an unselected cohort of patients undergoing elective primary hip or knee replacement surgery, U-shaped risks of perioperative MACE and mortality were found in relation to BMI. Patients within the extreme ranges of BMI may warrant further attention. [ABSTRACT FROM AUTHOR]

Background - The mechanism of failure of metal-on-metal (MoM) total hip arthroplasty (THA) has been related to a high rate of metal wear debris, which is partly generated from the head-trunnion interface. However, it is not known whether implant fixation is affected by metal wear debris. Patients and methods - 49 cases of MoM THA in 41 patients (10 women) with a mean age of 52 (28-68) years were followed with stereoradiographs after surgery and at 1, 2, and 5 years to analyze implant migration by radiostereometric analysis (RSA). Patients also participated in a 5- to 7-year follow-up with measurement of serum metal ions, questionnaires (Oxford hip score (OHS) and Harris hip score (HHS)), and measurement of cup and stem positions and systemic bone mineral density. Results - At 1-2 years, mean total translation (TT) was 0.04 mm (95% CI: -0.07 to 0.14; p = 0.5) for the stems; at 2-5 years, mean TT was 0.13 mm (95% CI: -0.25 to -0.01; p = 0.03), but within the precision limit of the method. For the cups, there was no statistically significant TT or total rotation (TR) at 1-2 and 2-5 years. At 2-5 years, we found 4 cups and 5 stems with TT migrations exceeding the precision limit of the method. There was an association between cup migration and total OHS < 40 (4 patients, 4 hips; p = 0.04), but there were no statistically significant associations between cup or stem migration and T-scores < -1 (n = 10), cup and stem positions, or elevated serum metal ion levels (> 7µg/L (4 patients, 6 hips)). Interpretation - Most cups and stems were well-fixed at 1-5 years. However, at 2-5 years, 4 cups and 5 stems had TT migrations above the precision limits, but these patients had serum metal ion levels similar to those of patients without measurable migrations, and they were pain-free. Patients with serum metal ion levels > 7 µg/L had migrations similar to those in patients with serum metal ion levels < 7 µg/L. Metal wear debris does not appear to influence the fixation of hip components in large-head MoM articulations at medium-term follow-up. [ABSTRACT FROM AUTHOR]

Background and purpose. Aiming for minimal toxicity after radical prostate cancer (PC) radiotherapy (RT), magnetic resonance imaging (MRI) target delineation could be a possible benefit knowing that clinical target volumes (CTV) are up to 30% smaller, when CTV delineation on MRI is compared to standard computed tomography (CT). This study compares long-term toxicity using CT or MRI delineation before PC RT. Material and methods. Urinary and rectal toxicity assessments 36 months after image-guided RT (78 Gy) using CTC-AE scores in two groups of PC patients. Peak symptom score values were registered. One group of patients (n = 72) had standard CT target delineation and gold markers as fiducials. Another group of patients (n = 73) had MRI target delineation and a nickel-titanium stent as fiducial. Results. At 36 months no difference in overall survival (92% in both groups, p = 0.29) or in PSA-relapse free survival was found between the groups (MRI = 89% and CT = 94%, p = 0.67). A significantly smaller CTV was found in the MRI group (p = 0.02). Urinary retention and frequency were significantly reduced in the MRI group (p = 0.03 in the matter of both). The overall urinary and rectal toxicity did not differ between the two groups. Conclusion. MRI delineation leads to a significantly reduced CTV. Significantly lower urinary frequency and urinary retention toxicity scores were observed following MRI delineation. The study did not find significant differences in overall urinary or rectal toxicity between the two groups. PSA-relapse survival did not differ between the two groups at 36 months. [ABSTRACT FROM AUTHOR]

Background and purpose - Previous studies of soft tissue sarcoma (STS) have identified a number of possible prognostic factors; however, the majority of these include highly selected populations, with unclear validation of data and insufficient statistical methods. We identified prognostic factors in a validated, population- based 30-year series of STS treated at a single institution, using an advanced statistical approach. Patients and methods - Between 1979 and 2008, 922 adult patients from western Denmark were treated at the Aarhus Sarcoma Center for non-metastatic STS in the extremities or trunk. The endpoints were local recurrence (LR) and disease-specific mortality (DSM). Prognostic factors were analyzed using a proportional hazard model, including continuous variables as cubic splines. Directed acyclic graphs were used to depict the causal structure. Results - The 5-year LR was 16% and the 5-year DSM was 24%. Important prognostic factors for both LR and DSM were age, duration of symptoms, tumor size, grade, margin, and radiotherapy, while anatomical location (upper, lower extremity, trunk) was prognostic for DSM. Interpretation - In this population-based series of adult, non-metastatic STS, we included directed acyclic graphs, cubic splines, and a competing risk model in order to minimize bias, and demonstrated that these statistical methods are feasible. Using these statistical methods on a large, validated dataset, we excluded depth as a prognostic factor and established that age, duration of symptoms, size, grade, margin, and radiotherapy were important prognostic factors for both local recurrence and disease-specific mortality. [ABSTRACT FROM AUTHOR]

Zoledronic acid (Zol) is frequently used for the treatment of bone disease in patients with multiple myeloma and breast cancer with metastasis to bone. Therefore, there is also an interest in finding the optimal dosing regimen to optimize effects, minimize side effects and reduce costs. In our phase II clinical trial we investigated the effect of Zol treatment on the serum levels of the bone markers collagen type 1 cross-linked C-telopeptide (CTX) and bone specific alkaline phosphatase (bALP) as well as on creatinine clearance (kidney function) in response to dosing and duration of treatment for each individual patient. Methods. We enrolled 30 multiple myeloma (MM) and 30 breast cancer (BC) patients whereof 10 of each had never received bisphosphonate and 20 had received at least six prior Zol treatments. Results. We found that Zol treatment strongly reduced CTX (Spearman's correlation, rs = −0.59, p = 0.0007) and bALP (Spearman's correlation, rs = −0.51, p = 0.0042) in MM patients while only CTX (Spearman's correlation, rs = −0.42, p = 0.024) was significantly affected in BC patients. Multiple linear regression analyses done on the entire cohort showed that the average time between each dose of Zol had the strongest impact on CTX (p < 0.001) and bALP (p = 0.011) levels while the total accumulated number of Zol infusions had a less pronounced effect on CTX levels (p = 0.015). In contrast, multiple linear regression analysis showed that the total number of Zol infusions had a strong negative impact on kidney function (p = 0.014) while the average time between each dose of Zol had no significant impact. Conclusion. Thus, if MM and BC patients are not treated regularly every month with Zol bone turnover is not fully suppressed, while prolonged treatment with zoledronic acid compromises kidney function. We believe that these data significantly contribute to the knowledge needed to find the optimal Zol treatment schedule. [ABSTRACT FROM AUTHOR]

Background. Osteonecrosis (ON) is a potential sequel in patients treated for malignancies. The goal of this population-based register study was to determine the incidence of ON requiring total joint arthroplasty (TJA) in patients treated for solid tumors in childhood, adolescence, or early adulthood. Material and methods. Patients diagnosed with a solid tumor before the age of 31 years were identified from the Finnish and Danish Cancer Registries. Patients with non-melanoma skin cancers and bone and connective tissue cancers were excluded. The data were combined with data from the National Hospital Discharge Registers and the Finnish Arthroplasty Registry. Data on the orthopedic procedures performed and the diagnosis codes given before the age of 40 years were retrieved. Results. Twenty-five of 18 542 (0.13%) patients had undergone TJA. The overall 20-year cumulative incidence of ON requiring TJA was 1% in patients treated for kidney cancer, followed by 0.5% in patients with breast cancer and 0.2% in patients with testicular cancer. Conclusion. Severe ON requiring TJA is a rare sequel in children and young adults treated for solid tumors. It was observed most commonly in patients treated for renal, breast, or testicular cancer. [ABSTRACT FROM AUTHOR]

Purpose - We used patient-reported outcome and risk of revision to compare hemiarthroplasty (HA) with total shoulder arthroplasty (TSA) and stemmed hemiarthroplasty (SHA) with resurfacing hemiarthroplasty (RHA) in patients with glenohumeral osteoarthritis. Patients and methods - We included all patients reported to the Danish Shoulder Arthroplasty Registry (DSR) between January 2006 and December 2010. 1,209 arthroplasties in 1,109 patients were eligible. Western Ontario Osteoarthritis of the Shoulder index (WOOS) was used to evaluate patient-reported outcome 1 year postoperatively. For simplicity of presentation, the raw scores were converted to a percentage of the maximum score. Revision rates were calculated by checking reported revisions to the DSR until December 2011. WOOS and risk of revision were adjusted for age, sex, previous surgery, and type of osteoarthritis. Results - There were 113 TSAs and 1096 HAs (837 RHAs and 259 SHAs). Patients treated with TSA generally had a better WOOS, exceeding the predefined minimal clinically important difference, at 1 year (mean difference 10, p < 0.001). RHA had a better WOOS than SHA (mean difference 5, p = 0.02), but the difference did not exceed the minimal clinically important difference. There were no statistically significant differences in revision rate or in adjusted risk of revision between any of the groups. Interpretation - Our results are in accordance with the results from other national shoulder registries and the results published in systematic reviews favoring TSA in the treatment of glenohumeral osteoarthritis. Nonetheless, this registry study had certain limitations and the results should be interpreted carefully. [ABSTRACT FROM AUTHOR]

Background. The Danish attitude for diagnosis and treatment of early localized prostate cancer (PCa) has historically been conservative. Denmark introduced radical prostatectomy (RP) as the last of the Nordic countries in 1995. However, a rapid increment in the Danish incidence of PCa is indicative of a shift in attitude with increasing opportunistic PSA testing. This had led to an increasing number of RPs being performed in Denmark. The objective of this study was to analyze changes in preoperative characteristics over time for the complete cohort of 6489 men who underwent RP between 1995 and 2011. Our hypothesis was that an increasing amount of men undergo RP for lower risk PCa. Material and methods. All patients operated from 1995 to 2011 were identified via patient files and registries. Changes over time in age at surgery, preoperative PSA, clinical T-category, biopsy Gleason score (GS), and D'Amico classification are described. Tests for statistically significant changes were performed. Results. Median age increased from 61.4 to 64.8 years (p < 0.0001) during the 16-year period. Median PSA declined from 11.5 to 7.9 ng/ml (p < 0.0001). Distribution of biopsy GS changed significantly, especially after 2005. Biopsy GS = 7 was found in 20.2% of the patients in 2005 compared to 57.1% in 2011. The proportion of T1 disease increased from 32% to 56%. Significant changes in percentage of patients according to the D'Amico classification were found. After 2005 the proportion of intermediate-risk patients increased significantly. The proportion of patients age 70 or above increased from 2% to 13% in the period studies. Conclusion. Significant preoperative stage- and Gleason grade migration was found in this complete Danish nationwide cohort of patients undergoing RP during the past 16 years. This effect is most likely attributed to an increasing use of PSA as marker for early prostate cancer diagnosis in Denmark and new international guidelines for Gleason grading and scoring. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) is associated with poor survival even though patients are treated with curatively intended radiotherapy. Survival is affected negatively by lack of loco-regional tumour control, but survival is also influenced by comorbidity caused by age and smoking, and occurrence of distant metastasis. It is challenging to evaluate loco-regional control after definitive radiotherapy for NSCLC since it is difficult to distinguish between radiation-induced damage to the lung tissue and tumour progression/recurrence. In addition it may be useful to distinguish between intrapulmonary failure and mediastinal failure to be able to optimize radiotherapy in order to improve loco-regional control even though it is not easy to discriminate between the two sites of failure. Material and methods. This study is a retrospective analysis of 331 NSCLC patients treated with definitive radiotherapy from 2002 to 2011. The patients were treated consecutively at the Department of Oncology, Odense University Hospital, Denmark with at least 60 Gy. All patients were followed in a planned follow-up schedule and no patients were lost for follow-up. Results. At the time of the analysis 93 patients had loco-regional failure only. Of these patients, 68 had intrapulmonary failure only, one patient had failure in mediastinum only, and 24 patients had intrapulmonary failure as well as mediastinal failure. Of the patients which had lung failure only, 78% had mediastinal involvement at treatment start. The only covariate with significant impact on developing intrapulmonary failure only was gross tumour volume. Median survival for the total group of 331 patients was 19 months. The median survival for patients with intrapulmonary failure only was 19 months, and it was 20 months for the patients with mediastinal relapse. Conclusion. We conclude that focus should be on increasing doses to intrapulmonary tumour volume, when dose escalation is applied to improve local tumour control in NSCLC patients treated with definitive radiotherapy, since most recurrences are located here. [ABSTRACT FROM AUTHOR]

Background. There is limited knowledge regarding progressive resistance training during adjuvant chemotherapy and the risk of developing breast cancer-related lymphedema (BCRL). Furthermore, no studies have investigated the safety of resistance training with heavy loads (> 80% 1 repetition maximum) in this population. 'Body and Cancer' is a six-week, nine-hour weekly, supervised, multimodal exercise intervention utilizing progressive resistance training with heavy loads for cancer patients undergoing chemotherapy. The purpose of the present study was to estimate the prevalence of BCRL in former participants, and identify associations between progressive resistance training with heavy loads, and the development of BCRL. Material and methods. This was a descriptive study. Population: Women treated for breast cancer (n = 149), who had participated in the 'Body and Cancer' exercise intervention between 1 January 2010 and 31 December 2011 participated in a structured telephone interview. The average follow-up time was 14 months (range 4-26). A clinical diagnosis of BCRL reported by the participant was the primary outcome. Results. A total of 27.5% reported that they had been diagnosed with BCRL by a clinician. This was true for 44.4% with axillary node dissection. No statistically significant association between strength gains during the exercise intervention, and the development of BCRL was observed, nor was self-reported participation in progressive resistance training with heavy loads up to three months post-intervention. Conclusion. The prevalence of BCRL among former 'Body and Cancer' participants at follow-up was 27.5%. There appears to be no association between performing heavy resistance training during adjuvant treatment (chemotherapy/radiotherapy), and the development of BCRL. However randomized controlled trials should be performed to confirm this observation. [ABSTRACT FROM AUTHOR]

Background and purpose - The increased use of patient-reported outcomes (PROs) in orthopedics requires data on estimated minimal clinically important improvements (MCIIs) and patient-acceptable symptom states (PASSs). We wanted to find cut-points corresponding to minimal clinically important PRO change score and the acceptable postoperative PRO score, by estimating MCII and PASS 1 year after total hip arthroplasty (THA) for the Hip Dysfunction and Osteoarthritis Outcome Score (HOOS) and the EQ-5D. Patients and methods - THA patients from 16 different departments received 2 PROs and additional questions preoperatively and 1 year postoperatively. The PROs included were the HOOS subscales pain (HOOS Pain), physical function short form (HOOS-PS), and hip-related quality of life (HOOS QoL), and the EQ-5D. MCII and PASS were estimated using multiple anchor-based approaches. Results - Of 1,837 patients available, 1,335 answered the preoperative PROs, and 1,288 of them answered the 1-year follow-up. The MCIIs and PASSs were estimated to be: 24 and 91 (HOOS Pain), 23 and 88 (HOOS-PS), 17 and 83 (HOOS QoL), 0.31 and 0.92 (EQ-5D Index), and 23 and 85 (EQ-VAS), respectively. MCIIs corresponded to a 38-55% improvement from mean baseline PRO score and PASSs corresponded to absolute follow-up scores of 57-91% of the maximum score in THA patients 1 year after surgery. Interpretation - This study improves the interpretability of PRO scores. The different estimation approaches presented may serve as a guide for future MCII and PASS estimations in other contexts. The cutoff points may serve as reference values in registry settings. [ABSTRACT FROM AUTHOR]