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Iceland

Cancer Statistics
Population in 2012: 0.3m
People newly diagnosed with cancer (excluding NMSC) / yr: 1,400
Age-standardised rate, incidence per 100,000 people/yr: 284.4
Risk of getting cancer before age 75:28.7%
People dying from cancer /yr: 500
Data from IARC GlobalCan (2012)
Iceland Cancer Organisations and Resources
Latest Research Publications Related to Iceland

Iceland Cancer Organisations and Resources (8 links)


Latest Research Publications Related to Iceland

Marks JH, Salem JF, Valsdottir EB, et al.
Quality of Life and Functional Outcome After Transanal Abdominal Transanal Proctectomy for Low Rectal Cancer.
Dis Colon Rectum. 2017; 60(3):258-265 [PubMed] Related Publications
BACKGROUND: Transanal abdominal transanal proctectomy is a sphincter-preserving procedure designed to avoid colostomy in patients with cancer in the distal third of the rectum. Oncologic outcomes of this procedure have been established. However, data regarding patient satisfaction and quality of life are scant.
OBJECTIVE: The purpose of this study was to evaluate the quality of life and functional outcomes of patients after transanal abdominal transanal proctectomy.
DESIGN: This is a cross-sectional study.
SETTINGS: The study was conducted at a tertiary referral colorectal center.
PATIENTS: Patients who underwent transanal abdominal transanal proctectomy were included and surveyed using the Fecal Incontinence Quality of Life Scale, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30, the Quality of Life Questionnaire CR38 module, and a questionnaire designed by the authors to assess satisfaction with quality of life.
MAIN OUTCOME MEASURES: Quality of life, functional outcomes, and patient satisfaction were measured and compared by age, tumor level, and stage of the disease.
RESULTS: A total of 133 surveys were mailed, and 90 patients responded and were included in the study. Patient quality of life was not significantly different after surgery. Patients with more proximal tumors had better lifestyle, physical, and emotional scores. Older patients performed better on multiple levels, including coping, emotional, body image, future perspective, and digestive. Stage of disease had no impact on quality of life. Compared with reference values, patients who underwent transanal abdominal transanal proctectomy performed better on most of the components. All of patients preferred transanal abdominal transanal proctectomy over having a stoma based on their current anal sphincter function, and >97% of patients preferred transanal abdominal transanal proctectomy based on their current quality of life, sexual function, and level of activities.
LIMITATIONS: This study is limited by the lack of a comparison group and a potential selection bias.
CONCLUSIONS: Satisfaction with quality of life and functional outcomes is high after transanal abdominal transanal proctectomy. Older patients and those with more proximal tumors performed better. This patient population clearly preferred a sphincter-preserving option for treatment of their rectal cancer.

Lindqvist EK, Landgren O, Lund SH, et al.
History of autoimmune disease is associated with impaired survival in multiple myeloma and monoclonal gammopathy of undetermined significance: a population-based study.
Ann Hematol. 2017; 96(2):261-269 [PubMed] Free Access to Full Article Related Publications
Multiple myeloma (MM) is a plasma cell disorder preceded by monoclonal gammopathy of undetermined significance (MGUS). Incidence of MM and MGUS is higher among patients with autoimmune disease. The aim of this study was to determine whether a history of autoimmunity has an impact on survival in MM and MGUS. Using high-quality national Swedish registries, we identified 8367 patients with MM, 18,768 patients with MGUS, and 110,251 matched control subjects, and obtained information on previous autoimmune disease in patients and controls. Cox regression was used to calculate hazard ratios (HRs) for overall survival with 95 % confidence intervals (CIs). In patients with MM and a prior autoimmune disease, the risk of death was significantly increased, HR = 1.2 (95 % CI 1.2-1.3) compared to MM patients with no history of autoimmunity. In MGUS patients, a prior autoimmune disease was associated with a significantly 1.4-fold elevated risk of death (95 % CI 1.3-1.4). When analyzing different types of autoimmune diseases, a history of ulcerative colitis had a stronger impact on survival in MM than in controls. Our findings that a history of autoimmune disease has a negative impact on survival in MM and MGUS could be due to shared underlying common genetic factors, or that patients with a history of autoimmunity develop more severe cases of MM and MGUS, or cumulative comorbidity in the individual. Our results suggest that more attention should be paid to comorbidity as a prognostic factor in MGUS and MM, and underlines the need for studies aimed at tailoring therapy according to comorbidity.

Derogar M, Dahlstrand H, Carlsson S, et al.
Preparedness for side effects and bother in symptomatic men after radical prostatectomy in a prospective, non-randomized trial, LAPPRO.
Acta Oncol. 2016; 55(12):1467-1476 [PubMed] Related Publications
BACKGROUND: Many clinicians believe that preparedness before surgery for possible post-surgery side effects reduces the level of bother experienced from urinary incontinence and decreased sexual health after surgery. There are no published studies evaluating this belief. Therefore, we aimed to study the level of preparedness before radical prostatectomy and the level of bother experienced from urinary incontinence and decreased sexual health after surgery.
MATERIAL AND METHODS: We prospectively collected data from a non-selected group of men undergoing radical prostatectomy in 14 centers between 2008 and 2011. Before surgery, we asked about preparedness for surgery-induced urinary problems and decreased sexual health. One year after surgery, we asked about bother caused by urinary incontinence and erectile dysfunction. As a measure of the association between preparedness and bothersomeness we modeled odds ratios (ORs) by means of logistic regression.
RESULTS: Altogether 1372 men had urinary incontinence one year after surgery as well as had no urinary leakage or a small urinary dribble before surgery. Among these men, low preparedness was associated with bother resulting from urinary incontinence [OR 2.84; 95% confidence interval (CI) 1.59-5.10]. In a separate analysis of 1657 men we found a strong association between preparedness for decreased sexual health and experiencing bother from erectile dysfunction (OR 5.92; 95% CI 3.32-10.55).
CONCLUSION: In this large-sized prospective trial, we found that preparedness before surgery for urinary problems or sexual side effects decreases bother from urinary incontinence and erectile dysfunction one year after surgery.

Angenete E, Angerås U, Börjesson M, et al.
Physical activity before radical prostatectomy reduces sick leave after surgery - results from a prospective, non-randomized controlled clinical trial (LAPPRO).
BMC Urol. 2016; 16(1):50 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Studies have reported that early physical rehabilitation after surgical procedures is associated with improved outcome measured as shorter hospital stay and enhanced recovery. The aim of this study was to explore the relationship between the preoperative physical activity level and subsequent postoperative complications, sick-leave and hospital stay after radical prostatectomy for prostate cancer in the setting of the LAPPRO trial (LAParoscopic Prostatectomy Robot Open).
METHODS: LAPPRO is a prospective controlled trial, comparing robot-assisted laparoscopic and open surgery for localized prostate cancer between 2008 and 2011. 1569 patients aged 64 or less with an occupation were included in this sub-study. The Gleason score was <7 in 52 % of the patients. Demographics and the level of self-assessed preoperative physical activity, length of hospital stay, complications, quality of life, recovery and sick-leave were extracted from clinical record forms and questionnaires. Multivariable logistic regression, with log-link and logit-link functions, was used to adjust for potential confounding variables.
RESULTS: The patients were divided into four groups based on their level of activity. As the group with lowest engagement of physical activity was found to be significantly different in base line characteristics from the other groups they were excluded from further analysis. Among patients that were physically active preoperativelly (n = 1467) there was no significant difference between the physical activity-groups regarding hospital stay, recovery or complications. However, in the group with the highest self-assessed level of physical activity, 5-7 times per week, 13 % required no sick leave, compared to 6.3 % in the group with a physical activity level of 1-2 times per week only (p < 0.0001).
CONCLUSIONS: In our study of med operated with radical prostatectomy, a high level of physical activity preoperatively was associated with reduced need for sick leave after radical prostatectomy compared to men with lower physical activity.
TRIAL REGISTRATION: The trial is registered at the ISCRTN register. ISRCTN06393679 .

Sormunen J, Talibov M, Martinsen JI, et al.
Perceived physical strain at work and incidence of colorectal cancer: A nested case-control study.
Cancer Epidemiol. 2016; 43:100-4 [PubMed] Related Publications
The evidence for a relationship between colon cancer incidence and physical activity is not fully convincing, and the association between physical activity and rectal cancer is also unclear. We studied the association between perceived physical workload (PPWL) at work and colorectal cancer, stratified by subsite, in a nested case-control setting in the Nordic Occupational Cancer (NOCCA) data from Finland, Iceland, Norway and Sweden. Five population controls were selected for each cancer patient. PPWL showed a bigger protective effect on colon cancer for males (odds ratio [OR] 0.74 in the highest PPWL decile as compared with the lowest PPWL category, 95% confidence interval [95% CI]: 0.72-0.77) than for females (OR 0.87, 95% CI: 0.81-0.95), with a significant trend for different levels of PPWL for both males and females. In males, the OR of cancer in the descending colon for the highest PPWL decile of males was 0.61 (95% CI: 0.54-0.69). For females the protective effect was most notable in the transversal part of the colon (OR 0.83, 95% CI: 0.67-1.03). The OR for rectal cancer in the highest PPWL decile for males was 0.87 (95% CI: 0.85-0.90) and for females 0.93 (95% CI: 0.83-1.04). Inclusion of further agents in multivariate analyses did not alter the ORs for PPWL. The incidence of colon cancer and, to a lesser extent, rectal cancer is lowest in professions with the highest PPWL. The association is clearer in males than in females. The biggest protective effect appears to be in the descending colon in males.

Morganella S, Alexandrov LB, Glodzik D, et al.
The topography of mutational processes in breast cancer genomes.
Nat Commun. 2016; 7:11383 [PubMed] Free Access to Full Article Related Publications
Somatic mutations in human cancers show unevenness in genomic distribution that correlate with aspects of genome structure and function. These mutations are, however, generated by multiple mutational processes operating through the cellular lineage between the fertilized egg and the cancer cell, each composed of specific DNA damage and repair components and leaving its own characteristic mutational signature on the genome. Using somatic mutation catalogues from 560 breast cancer whole-genome sequences, here we show that each of 12 base substitution, 2 insertion/deletion (indel) and 6 rearrangement mutational signatures present in breast tissue, exhibit distinct relationships with genomic features relating to transcription, DNA replication and chromatin organization. This signature-based approach permits visualization of the genomic distribution of mutational processes associated with APOBEC enzymes, mismatch repair deficiency and homologous recombinational repair deficiency, as well as mutational processes of unknown aetiology. Furthermore, it highlights mechanistic insights including a putative replication-dependent mechanism of APOBEC-related mutagenesis.

Nik-Zainal S, Davies H, Staaf J, et al.
Landscape of somatic mutations in 560 breast cancer whole-genome sequences.
Nature. 2016; 534(7605):47-54 [PubMed] Free Access to Full Article Related Publications
We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, another with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.

Lu D, Andersson TM, Fall K, et al.
Clinical Diagnosis of Mental Disorders Immediately Before and After Cancer Diagnosis: A Nationwide Matched Cohort Study in Sweden.
JAMA Oncol. 2016; 2(9):1188-96 [PubMed] Related Publications
IMPORTANCE: Psychiatric comorbidities are common among patients with cancer. However, whether or not there is increased risk of mental disorders during the diagnostic workup leading to a cancer diagnosis was unknown.
OBJECTIVE: To examine the relative risks of depression, anxiety, substance abuse, somatoform/conversion disorder, and stress reaction/adjustment disorder during the periods before and after cancer diagnosis compared with individuals without cancer.
DESIGN, SETTING, AND PARTICIPANTS: Nationwide matched cohort study from January 1, 2001, to December 31, 2010, in a Swedish population and health registers.
MAIN OUTCOMES AND MEASURES: We estimated the time-varying hazard ratios (HRs) of the first clinical diagnosis of the studied mental disorders from 2 years before cancer diagnosis, through the time of diagnosis, and until 10 years after diagnosis, adjusting for age, sex, calendar period, and educational level. To assess milder mental conditions and symptoms, we further assessed the use of related psychiatric medications for patients with cancer diagnosed during 2008-2009.
RESULTS: The study included 304 118 patients with cancer and 3 041 174 cancer-free individuals who were randomly selected from the Swedish population and individually matched to the patients with cancer on year of birth and sex. The median age at diagnosis for the patients with cancer was 69 years, and 46.9% of the patients were female. The relative rate for all studied mental disorders started to increase from 10 months before cancer diagnosis (HR, 1.1; 95% CI, 1.1-1.2), peaked during the first week after diagnosis (HR, 6.7; 95% CI, 6.1-7.4), and decreased rapidly thereafter but remained elevated 10 years after diagnosis (HR, 1.1; 95% CI, 1.1-1.2). The rate elevation was clear for all main cancers except nonmelanoma skin cancer and was stronger for cancers of poorer prognosis. Compared with cancer-free individuals, increased use of psychiatric medications was noted from 1 month before cancer diagnosis and peaked around 3 months after diagnosis among patients with cancer.
CONCLUSIONS AND RELEVANCE: Patients diagnosed as having cancer had increased risks of several common mental disorders from the year before diagnosis. These findings support the existing guidelines of integrating psychological management into cancer care and further call for extended vigilance for multiple mental disorders starting from the time of the cancer diagnostic workup.

Kjellander C, Björkholm M, Källman O, et al.
Bloodstream infections in patients with chronic lymphocytic leukemia: a longitudinal single-center study.
Ann Hematol. 2016; 95(6):871-9 [PubMed] Related Publications
Infectious complications in chronic lymphocytic leukemia (CLL) represent a major cause of morbidity and mortality. The aim of the study was to investigate temporal trends in bloodstream infections (BSIs) among patients with CLL. Individuals with blood cultures were linked to Swedish Cancer Registry and divided into three time periods (1988-1993, 1994-1999, and 2000-2006) according to year of CLL diagnosis. CLL patients (n = 275) with 1092 blood culture episodes were identified and linked to the nationwide Cause of Death Registry and Swedish Patient Registry (to retrieve information on splenectomies). The most common causes of BSI among CLL patients were Escherichia coli (11/43, 15/78, and 9/33), Streptococcus pneumoniae (7/43, 13/78, and 6/33), Pseudomonas aeruginosa (2/43, 8/78, and 3/33), Staphylococcus aureus (1/43, 6/78, and 6/33), and Viridans streptococci (5/43, 6/78, and 2/33). Coagulase-negative staphylococci was the most frequent microorganism found in blood cultures (22/70, 23/106, and 5/41, respectively) but is a frequent contaminant. Based on the largest study to date on BSI in CLL patients, we found a stable proportion of Gram-positive to Gram-negative bacteria and no temporal change of distribution was observed for BSIs 1988-2006.

Oskarsdottir GN, Bjornsson J, Jonsson S, et al.
Primary adenocarcinoma of the lung--histological subtypes and outcome after surgery, using the IASLC/ATS/ERS classification of lung adenocarcinoma.
APMIS. 2016; 124(5):384-92 [PubMed] Related Publications
Adenocarcinoma is the most common histological type of lung carcinoma. Recently the histologic classification of adenocarcinomas in the lung was modified to better reflect biologic properties and prognosis. We reviewed the histology of all primary lung adenocarcinomas operated on in Iceland during a 20-year period and assessed the impact of histology on survival. This nationwide study included 285 patients (mean age 67 years, 57% female), who underwent resection in Iceland from 1991 to 2010. Tumors were reclassified according to the current IASLC/ATS/ERS classification system. Overall survival was estimated by the Kaplan-Meier method and Cox regression analysis used to evaluate prognostic factors of overall mortality. Acinar predominant adenocarcinoma was the most common histological subtype (46%) followed by solid-predominant (SPA) with mucin production comprised (23%). Non-invasive carcinomas were rare. A difference in survival between the histological adenocarcinoma subtypes was not seen (p = 0.32) and multivariate analysis showed that advanced stage and age predicted worse outcome, but histologic subtyping of adenocarcinoma did not. In this nation-wide study there was not a statistical difference in survival according to adenocarcinoma subtypes and the histological subtype did not predict mortality. Preinvasive and minimally invasive adenocarcinomas were rare.

Dunning AM, Michailidou K, Kuchenbaecker KB, et al.
Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.
Nat Genet. 2016; 48(4):374-86 [PubMed] Free Access to Full Article Related Publications
We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.

Holm K, Staaf J, Lauss M, et al.
An integrated genomics analysis of epigenetic subtypes in human breast tumors links DNA methylation patterns to chromatin states in normal mammary cells.
Breast Cancer Res. 2016; 18(1):27 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Aberrant DNA methylation is frequently observed in breast cancer. However, the relationship between methylation patterns and the heterogeneity of breast cancer has not been comprehensively characterized.
METHODS: Whole-genome DNA methylation analysis using Illumina Infinium HumanMethylation450 BeadChip arrays was performed on 188 human breast tumors. Unsupervised bootstrap consensus clustering was performed to identify DNA methylation epigenetic subgroups (epitypes). The Cancer Genome Atlas data, including methylation profiles of 669 human breast tumors, was used for validation. The identified epitypes were characterized by integration with publicly available genome-wide data, including gene expression levels, DNA copy numbers, whole-exome sequencing data, and chromatin states.
RESULTS: We identified seven breast cancer epitypes. One epitype was distinctly associated with basal-like tumors and with BRCA1 mutations, one epitype contained a subset of ERBB2-amplified tumors characterized by multiple additional amplifications and the most complex genomes, and one epitype displayed a methylation profile similar to normal epithelial cells. Luminal tumors were stratified into the remaining four epitypes, with differences in promoter hypermethylation, global hypomethylation, proliferative rates, and genomic instability. Specific hyper- and hypomethylation across the basal-like epitype was rare. However, we observed that the candidate genomic instability drivers BRCA1 and HORMAD1 displayed aberrant methylation linked to gene expression levels in some basal-like tumors. Hypomethylation in luminal tumors was associated with DNA repeats and subtelomeric regions. We observed two dominant patterns of aberrant methylation in breast cancer. One pattern, constitutively methylated in both basal-like and luminal breast cancer, was linked to genes with promoters in a Polycomb-repressed state in normal epithelial cells and displayed no correlation with gene expression levels. The second pattern correlated with gene expression levels and was associated with methylation in luminal tumors and genes with active promoters in normal epithelial cells.
CONCLUSIONS: Our results suggest that hypermethylation patterns across basal-like breast cancer may have limited influence on tumor progression and instead reflect the repressed chromatin state of the tissue of origin. On the contrary, hypermethylation patterns specific to luminal breast cancer influence gene expression, may contribute to tumor progression, and may present an actionable epigenetic alteration in a subset of luminal breast cancers.

Silvestri V, Barrowdale D, Mulligan AM, et al.
Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2.
Breast Cancer Res. 2016; 18(1):15 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs).
METHODS: We characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database.
RESULTS: Among BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 × 10(-5)) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor-positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15-21.80] and progesterone receptor-positive (OR 5.04; 95 % CI 3.17-8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 × 10(-12)).
CONCLUSIONS: On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management.

Einarsson EJ, Patel M, Petersen H, et al.
Oculomotor Deficits after Chemotherapy in Childhood.
PLoS One. 2016; 11(1):e0147703 [PubMed] Free Access to Full Article Related Publications
Advances in the diagnosis and treatment of pediatric malignancies have substantially increased the number of childhood cancer survivors. However, reports suggest that some of the chemotherapy agents used for treatment can cross the blood brain barrier which may lead to a host of neurological symptoms including oculomotor dysfunction. Whether chemotherapy at young age causes oculomotor dysfunction later in life is unknown. Oculomotor performance was assessed with traditional and novel methods in 23 adults (mean age 25.3 years, treatment age 10.2 years) treated with chemotherapy for a solid malignant tumor not affecting the central nervous system. Their results were compared to those from 25 healthy, age-matched controls (mean age 25.1 years). Correlation analysis was performed between the subjective symptoms reported by the chemotherapy treated subjects (CTS) and oculomotor performance. In CTS, the temporal control of the smooth pursuit velocity (velocity accuracy) was markedly poorer (p<0.001) and the saccades had disproportionally shorter amplitude than normal for the associated saccade peak velocity (main sequence) (p = 0.004), whereas smooth pursuit and saccade onset times were shorter (p = 0.004) in CTS compared with controls. The CTS treated before 12 years of age manifested more severe oculomotor deficits. CTS frequently reported subjective symptoms of visual disturbances (70%), unsteadiness, light-headedness and that things around them were spinning or moving (87%). Several subjective symptoms were significantly related to deficits in oculomotor performance. To conclude, chemotherapy in childhood or adolescence can result in severe oculomotor dysfunctions in adulthood. The revealed oculomotor dysfunctions were significantly related to the subjects' self-perception of visual disturbances, dizziness, light-headedness and sensing unsteadiness. Assessments of oculomotor function may, thus, offer an objective method to track and rate the level of neurological complications following chemotherapy.

Vélez R, Turesson I, Landgren O, et al.
Incidence of multiple myeloma in Great Britain, Sweden, and Malmö, Sweden: the impact of differences in case ascertainment on observed incidence trends.
BMJ Open. 2016; 6(1):e009584 [PubMed] Free Access to Full Article Related Publications
OBJECTIVES: The increased incidence of multiple myeloma (MM) across China and East Asia stimulated us to examine the current rates in Great Britain, where rates increased dramatically in the second half of the 20th century. However, rates have been stable and high during this period in Malmö, Sweden, where there is a keen interest in MM. We thus assessed recent changes in MM incidence in Great Britain, Sweden overall, and Malmö, Sweden, and examined how these changes might explain recent reports of increased MM incidence across Asia.
DESIGN: Estimation of MM incidence for Great Britain, Sweden overall, and Malmö, Sweden.
POPULATIONS: MM incidence data for Great Britain (1975-2009) were obtained from Cancer Research UK and for Sweden (1970-2009) from the Swedish Cancer Registry. MM incidence data from Malmö, Sweden, were available from 1950 to 2012.
MAIN OUTCOME MEASURES: Age-specific incidence of MM in Great Britain, Sweden overall, and Malmö, Sweden.
RESULTS: MM incidence in Great Britain, Sweden overall, and Malmö increased progressively with age, even among the oldest group. The MM age-adjusted incidence (European standard population) increased by 69% from 1975-1979 to 2005-2009 in Great Britain, from 3.2/100,000 to 5.4/100,000. The largest increases occurred among those 70-79 years of age, for whom rates increased from 17.9/100,000 to 33.6/100,000; reflecting an increase of 69%. During this same period, the age-adjusted incidence (European stand population) in Sweden overall remained stable, at approximately 4.7/100,000.
CONCLUSIONS: MM age-specific incidence is now similar in Great Britain, Sweden overall, and Malmö. We believe this is a result of improvements in case ascertainment in Great Britain, particularly among the elderly. Similar changes can be predicted to occur across Asia as improved access to healthcare contributes to better diagnosis of MM.

Thorgeirsson T, Jordahl KM, Flavin R, et al.
Intracellular location of BRCA2 protein expression and prostate cancer progression in the Swedish Watchful Waiting Cohort.
Carcinogenesis. 2016; 37(3):262-8 [PubMed] Related Publications
Prostate cancer patients with inherited BRCA2 mutations have a survival disadvantage. However, it is unknown whether progression is associated with BRCA2 protein expression in diagnostic prostate cancer tissue, among men without inherited mutations. We conducted a nested case-control study within the Swedish Watchful Waiting cohort. The case group included all 71 patients who died from prostate cancer within 5 years from diagnosis and controls were all patients (n = 165) who lived at least 7 years after diagnosis. Tissue microarrays were stained using antibodies for C- and N-terminal domains of the BRCA2 protein. Location (nuclear, cytoplasmic and membranous) and magnitude (intensity and percentage) of expression were assessed. Logistic regression models produced odds ratios (OR) and 95% confidence intervals (CI) adjusted for age, year of diagnosis and Gleason score. Positive BRCA2 staining at the cell membrane was associated with reduced risk of death within 5 years (N-terminal: OR = 0.47, 95% CI = 0.21-1.04, P = 0.06; C-terminal: OR = 0.41, 95% CI = 0.18-0.91, P = 0.03) and low Gleason scores (P = 0.006). Positive cytoplasmic C-terminal staining was associated with higher Gleason scores and increased lethality (OR = 3.61, 95% CI = 1.61-8.07, P = 0.002). BRCA2 protein expression at the cell membrane and lack of C-terminal expression in the cytoplasm were associated with a reduced risk of rapidly fatal prostate cancer. BRCA2 protein expression in prostate cancer tissue may have independent prognostic value. The potential biological significance of BRCA2 expression at the cell membrane warrants further investigation.

Jinga V, Csiki IE, Manolescu A, et al.
Replication study of 34 common SNPs associated with prostate cancer in the Romanian population.
J Cell Mol Med. 2016; 20(4):594-600 [PubMed] Free Access to Full Article Related Publications
Prostate cancer is the third-most common form of cancer in men in Romania. The Romanian unscreened population represents a good sample to study common genetic risk variants. However, a comprehensive analysis has not been conducted yet. Here, we report our replication efforts in a Romanian population of 979 cases and 1027 controls, for potential association of 34 literature-reported single nucleotide polymorphisms (SNPs) with prostate cancer. We also examined whether any SNP was differentially associated with tumour grade or stage at diagnosis, with disease aggressiveness, and with the levels of PSA (prostate specific antigen). In the allelic analysis, we replicated the previously reported risk for 19 loci on 4q24, 6q25.3, 7p15.2, 8q24.21, 10q11.23, 10q26.13, 11p15.5, 11q13.2, 11q13.3. Statistically significant associations were replicated for other six SNPs only with a particular disease phenotype: low-grade tumour and low PSA levels (rs1512268), high PSA levels (rs401681 and rs11649743), less aggressive cancers (rs1465618, rs721048, rs17021918). The strongest association of our tested SNP's with PSA in controls was for rs2735839, with 29% increase for each copy of the major allele G, consistent with previous results. Our results suggest that rs4962416, previously associated only with prostate cancer, is also associated with PSA levels, with 12% increase for each copy of the minor allele C. The study enabled the replication of the effect for the majority of previously reported genetic variants in a set of clinically relevant prostate cancers. This is the first replication study on these loci, known to associate with prostate cancer, in a Romanian population.

Mucci LA, Hjelmborg JB, Harris JR, et al.
Familial Risk and Heritability of Cancer Among Twins in Nordic Countries.
JAMA. 2016; 315(1):68-76 [PubMed] Related Publications
IMPORTANCE: Estimates of familial cancer risk from population-based studies are essential components of cancer risk prediction.
OBJECTIVE: To estimate familial risk and heritability of cancer types in a large twin cohort.
DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 80,309 monozygotic and 123,382 same-sex dizygotic twin individuals (N = 203,691) within the population-based registers of Denmark, Finland, Norway, and Sweden. Twins were followed up a median of 32 years between 1943 and 2010. There were 50,990 individuals who died of any cause, and 3804 who emigrated and were lost to follow-up.
EXPOSURES: Shared environmental and heritable risk factors among pairs of twins.
MAIN OUTCOMES AND MEASURES: The main outcome was incident cancer. Time-to-event analyses were used to estimate familial risk (risk of cancer in an individual given a twin's development of cancer) and heritability (proportion of variance in cancer risk due to interindividual genetic differences) with follow-up via cancer registries. Statistical models adjusted for age and follow-up time, and accounted for censoring and competing risk of death.
RESULTS: A total of 27,156 incident cancers were diagnosed in 23,980 individuals, translating to a cumulative incidence of 32%. Cancer was diagnosed in both twins among 1383 monozygotic (2766 individuals) and 1933 dizygotic (2866 individuals) pairs. Of these, 38% of monozygotic and 26% of dizygotic pairs were diagnosed with the same cancer type. There was an excess cancer risk in twins whose co-twin was diagnosed with cancer, with estimated cumulative risks that were an absolute 5% (95% CI, 4%-6%) higher in dizygotic (37%; 95% CI, 36%-38%) and an absolute 14% (95% CI, 12%-16%) higher in monozygotic twins (46%; 95% CI, 44%-48%) whose twin also developed cancer compared with the cumulative risk in the overall cohort (32%). For most cancer types, there were significant familial risks and the cumulative risks were higher in monozygotic than dizygotic twins. Heritability of cancer overall was 33% (95% CI, 30%-37%). Significant heritability was observed for the cancer types of skin melanoma (58%; 95% CI, 43%-73%), prostate (57%; 95% CI, 51%-63%), nonmelanoma skin (43%; 95% CI, 26%-59%), ovary (39%; 95% CI, 23%-55%), kidney (38%; 95% CI, 21%-55%), breast (31%; 95% CI, 11%-51%), and corpus uteri (27%; 95% CI, 11%-43%).
CONCLUSIONS AND RELEVANCE: In this long-term follow-up study among Nordic twins, there was significant excess familial risk for cancer overall and for specific types of cancer, including prostate, melanoma, breast, ovary, and uterus. This information about hereditary risks of cancers may be helpful in patient education and cancer risk counseling.

Stacey SN, Kehr B, Gudmundsson J, et al.
Insertion of an SVA-E retrotransposon into the CASP8 gene is associated with protection against prostate cancer.
Hum Mol Genet. 2016; 25(5):1008-18 [PubMed] Free Access to Full Article Related Publications
Transcriptional and splicing anomalies have been observed in intron 8 of the CASP8 gene (encoding procaspase-8) in association with cutaneous basal-cell carcinoma (BCC) and linked to a germline SNP rs700635. Here, we show that the rs700635[C] allele, which is associated with increased risk of BCC and breast cancer, is protective against prostate cancer [odds ratio (OR) = 0.91, P = 1.0 × 10(-6)]. rs700635[C] is also associated with failures to correctly splice out CASP8 intron 8 in breast and prostate tumours and in corresponding normal tissues. Investigation of rs700635[C] carriers revealed that they have a human-specific short interspersed element-variable number of tandem repeat-Alu (SINE-VNTR-Alu), subfamily-E retrotransposon (SVA-E) inserted into CASP8 intron 8. The SVA-E shows evidence of prior activity, because it has transduced some CASP8 sequences during subsequent retrotransposition events. Whole-genome sequence (WGS) data were used to tag the SVA-E with a surrogate SNP rs1035142[T] (r(2) = 0.999), which showed associations with both the splicing anomalies (P = 6.5 × 10(-32)) and with protection against prostate cancer (OR = 0.91, P = 3.8 × 10(-7)).

Figueroa JD, Middlebrooks CD, Banday AR, et al.
Identification of a novel susceptibility locus at 13q34 and refinement of the 20p12.2 region as a multi-signal locus associated with bladder cancer risk in individuals of European ancestry.
Hum Mol Genet. 2016; 25(6):1203-14 [PubMed] Article available free on PMC after 15/03/2017 Related Publications
Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P < 1 × 10(-6)), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P = 2.19 × 10(-11)) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 × 10(-10)). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5551 bladder cancer cases and 10 242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast, we detected two signals in the 20p12.2 region-the first signal is marked by rs6104690, and the second signal is marked by two moderately correlated SNPs (r(2) = 0.53), rs6108803 and the previously reported rs62185668. The second 20p12.2 signal is more strongly associated with the risk of muscle-invasive (T2-T4 stage) compared with non-muscle-invasive (Ta, T1 stage) bladder cancer (case-case P ≤ 0.02 for both rs62185668 and rs6108803). Functional analyses are needed to explore the biological mechanisms underlying these novel genetic associations with risk for bladder cancer.

Tulstrup M, Larsen HB, Castor A, et al.
Parents' and Adolescents' Preferences for Intensified or Reduced Treatment in Randomized Lymphoblastic Leukemia Trials.
Pediatr Blood Cancer. 2016; 63(5):865-71 [PubMed] Related Publications
BACKGROUND: When offered participation in clinical trials, families of children with cancer face a delicate balance between cure and toxicity. Since parents and children may perceive this balance differently, this paper explores whether adolescent patients have different enrollment patterns compared to younger children in trials with different toxicity profiles.
PROCEDURE: Age-dependent participation rates in three consecutive, randomized childhood leukemia trials conducted by the Nordic Society of Paediatric Haematology and Oncology were evaluated. The ALL2000 dexamethasone/vincristine (Dx/VCR) trial tested treatment intensifications to improve cure, and the back-to-back ALL2008 6-mercaptopurine (6MP) and ALL2008 PEG-asparaginase (ASP) trials tested treatment intensifications (6MP) and toxicity reduction without compromising survival (ASP). Patient randomization and toxicity data were prospectively registered by the treating physicians.
RESULTS: Parents of young children favored treatment intensifications (Dx/VCR: 12% refusal; 6MP: 14%; ASP: 21%), whereas parents of adolescents favored treatment reductions (Dx/VCR: 52% refusal; 6MP: 30%; ASP: 8%). Adolescents were more likely to refuse intensification trials than young children (adjusted ORs 6.3; P < 0.01 [Dx/VCR] and 2.1; P = 0.04 [6MP]). Adolescents were less likely to refuse the ASP trial, with varying effect size depending on the length of the preceding consolidation treatment (adjusted OR for median consolidation length 0.15; P = 0.01). Younger children participated more frequently in only 6MP than in only ASP (14% vs. 5%), and adolescents vice versa (2% vs. 17%; P = 0.001).
CONCLUSIONS: Parents' and adolescents' divergent inclinations toward intensified or reduced therapy emphasize the necessity of actively involving adolescents in the informed consent process, which should also address motives for trial participation.

Tuckuviene R, Ranta S, Albertsen BK, et al.
Prospective study of thromboembolism in 1038 children with acute lymphoblastic leukemia: a Nordic Society of Pediatric Hematology and Oncology (NOPHO) study.
J Thromb Haemost. 2016; 14(3):485-94 [PubMed] Related Publications
UNLABELLED: ESSENTIALS: Children with acute lymphoblastic leukemia (ALL) are at risk of thromboembolism (TE). This is a prospective evaluation of the incidence, risk factors and outcomes of TE in 1038 children with ALL. TE occurred in 6.1% of children, with the highest incidence (20.5%) among those aged 15-17 years. A TE-associated case fatality of 6.4% indicates that TE is a severe complication of ALL treatment.

Markt SC, Flynn-Evans EE, Valdimarsdottir UA, et al.
Sleep Duration and Disruption and Prostate Cancer Risk: a 23-Year Prospective Study.
Cancer Epidemiol Biomarkers Prev. 2016; 25(2):302-8 [PubMed] Article available free on PMC after 15/03/2017 Related Publications
BACKGROUND: Sleep deficiency is a major public health problem. There are limited human data on whether sleep duration or disruption are risk factors for prostate cancer.
METHODS: We prospectively followed 32,141 men in the Health Professionals Follow-Up Study who reported their typical sleep duration in 1987, 2000, and 2008. We identified 4,261 incident prostate cancer cases, including 563 lethal cases through 2010. Sleep disruption was assessed in 2004 among 19,639 men, with 930 prostate cancer cases (50 lethal) identified from 2004 to 2010. Cox proportional hazards models were used to evaluate the association between sleep insufficiency and risk of overall and lethal prostate cancer.
RESULTS: In 1987, 2% of men reported sleeping ≤5 hours per night. We found no association between habitual sleep duration or change in sleep duration with the risk of advanced or lethal prostate cancer. We also found no association between waking up during the night, difficulty falling asleep, or waking up too early, and risk of prostate cancer. In 2004, 6% of men reported never feeling rested when they woke up; these men had an increased risk of developing lethal prostate cancer compared with those who reported always feeling rested when they woke up (RR, 3.05; 95% CI, 1.15-8.10).
CONCLUSIONS: We found no consistent association between self-reported sleep duration or sleep disruption and any of our prostate cancer outcomes.
IMPACT: We did not find support for a consistent association between self-reported sleep and risk of advanced or lethal prostate cancer in this large cohort of men.

Weibull CE, Eloranta S, Smedby KE, et al.
Pregnancy and the Risk of Relapse in Patients Diagnosed With Hodgkin Lymphoma.
J Clin Oncol. 2016; 34(4):337-44 [PubMed] Related Publications
PURPOSE: Many patients and clinicians are worried that pregnancy after the diagnosis of Hodgkin lymphoma (HL) may increase the risk of relapse despite a lack of empirical evidence to support such concerns. We investigated if an association exists between pregnancy and relapse in women with a diagnosis of HL.
MATERIALS AND METHODS: Using Swedish healthcare registers combined with medical records, we included 449 women who received a diagnosis of HL between 1992 and 2009 and who were age 18 to 40 years at diagnosis. Follow-up started 6 months after diagnosis, when the patients' condition was assumed to be in remission. Pregnancy-associated relapse was defined as a relapse during pregnancy or within 5 years after delivery. Hazard ratios (HRs) with 95% CIs were estimated by using the Cox proportional hazards model.
RESULTS: Among the 449 women, 144 (32%) became pregnant during follow-up. Overall, 47 relapses were recorded, of which one was a pregnancy-associated relapse. The adjusted HR for the comparison of the pregnancy-associated relapse rate to the non-pregnancy-associated relapse rate was 0.29 (95% CI, 0.04 to 2.18). The expected number of relapses in women with a recent pregnancy, given that they would experience the same relapse rate as that of women without a recent pregnancy, was 3.76; the observed-to-expected ratio was 0.27 (95% exact CI, 0.01 to 1.51).
CONCLUSION: We found no evidence that a pregnancy after diagnosis increases the relapse rate among women whose HL is in remission. Survivors of HL need to consider a range of factors when deciding about future reproduction. However, given the results of this study, the risk of pregnancy-associated relapse does not need to be considered.

Lu D, Sundström K, Sparén P, et al.
Bereavement Is Associated with an Increased Risk of HPV Infection and Cervical Cancer: An Epidemiological Study in Sweden.
Cancer Res. 2016; 76(3):643-51 [PubMed] Article available free on PMC after 15/03/2017 Related Publications
Grief over the loss of a family member may cause physical and mental illness, but an association between bereavement and cancer risk has not been established. Based on the Swedish National Cervical Screening Register (1969-2011) including 14,011,269 smears from 2,466,107 women, we conducted two nested case-control studies to examine the associations of bereavement (i.e., loss of a family member due to death) with abnormal cytology (390,310 first abnormal and 1,951,319 normal smears) and in situ/invasive cervical cancer (75,128 case and 375,640 control women), both individually matched on year of birth and screening adherence. Among 1,696 of the control women, we further investigated bereavement in association with human papillomavirus (HPV) infection, both HPV16 and other HPV types. Bereavement was consistently associated with a 4% to 9% increased risk for first abnormal cytology, in situ and invasive cervical cancer (all P < 0.02). The associations became stronger when multiple losses, loss of child, sibling or spouse, and loss due to unnatural cause were analyzed separately (P for trend or difference < 0.0001), and for women with high screening adherence (P for difference < 0.05). Among 1,696 women who had not developed cervical cancer, we further investigated the link between bereavement and HPV infection. Bereavement was associated with a 62% increased risk of HPV16 infection, high viral load, and recurrent infection, and was also more strongly associated with HPV infections designated as high-risk compared with low-risk determinants of cervical carcinogenesis. Collectively, our findings demonstrate that bereavement is associated with an increased risk of developing cervical cancer. Further, they suggest that this association may be attributed to stress-induced oncogenic HPV infections.

Thomsen H, Filho MI, Woltmann A, et al.
Inbreeding and homozygosity in breast cancer survival.
Sci Rep. 2015; 5:16467 [PubMed] Article available free on PMC after 15/03/2017 Related Publications
Genome-wide association studies (GWASs) help to understand the effects of single nucleotide polymorphisms (SNPs) on breast cancer (BC) progression and survival. We performed multiple analyses on data from a previously conducted GWAS for the influence of individual SNPs, runs of homozygosity (ROHs) and inbreeding on BC survival. (I.) The association of individual SNPs indicated no differences in the proportions of homozygous individuals among short-time survivors (STSs) and long-time survivors (LTSs). (II.) The analysis revealed differences among the populations for the number of ROHs per person and the total and average length of ROHs per person and among LTSs and STSs for the number of ROHs per person. (III.) Common ROHs at particular genomic positions were nominally more frequent among LTSs than in STSs. Common ROHs showed significant evidence for natural selection (iHS, Tajima's D, Fay-Wu's H). Most regions could be linked to genes related to BC progression or treatment. (IV.) Results were supported by a higher level of inbreeding among LTSs. Our results showed that an increased level of homozygosity may result in a preference of individuals during BC treatment. Although common ROHs were short, variants within ROHs might favor survival of BC and may function in a recessive manner.

Möller S, Mucci LA, Harris JR, et al.
The Heritability of Breast Cancer among Women in the Nordic Twin Study of Cancer.
Cancer Epidemiol Biomarkers Prev. 2016; 25(1):145-50 [PubMed] Related Publications
BACKGROUND: Family history is an established risk factor for breast cancer. Although some important genetic factors have been identified, the extent to which familial risk can be attributed to genetic factors versus common environment remains unclear.
METHODS: We estimated the familial concordance and heritability of breast cancer among 21,054 monozygotic and 30,939 dizygotic female twin pairs from the Nordic Twin Study of Cancer, the largest twin study of cancer in the world. We accounted for left-censoring, right-censoring, as well as the competing risk of death.
RESULTS: From 1943 through 2010, 3,933 twins were diagnosed with breast cancer. The cumulative lifetime incidence of breast cancer taking competing risk of death into account was 8.1% for both zygosities, although the cumulative risk for twins whose co-twins had breast cancer was 28% among monozygotic and 20% among dizygotic twins. The heritability of liability to breast cancer was 31% [95% confidence interval (CI), 10%-51%] and the common environmental component was 16% (95% CI, 10%-32%). For premenopausal breast cancer these estimates were 27% and 12%, respectively, and for postmenopausal breast cancer 22% and 16%, respectively. The relative contributions of genetic and environmental factors were constant between ages 50 and 96. Our results are compatible with the Peto-Mack hypothesis.
CONCLUSION: Our findings indicate that familial factors explain almost half of the variation in liability to develop breast cancer, and results were similar for pre- and postmenopausal breast cancer
IMPACT: We estimate heritability of breast cancer, taking until now ignored sources of bias into account.

Thorsteinsdottir UA, Thorsteinsdottir M, Lambert IH
Protolichesterinic Acid, Isolated from the Lichen Cetraria islandica, Reduces LRRC8A Expression and Volume-Sensitive Release of Organic Osmolytes in Human Lung Epithelial Cancer Cells.
Phytother Res. 2016; 30(1):97-104 [PubMed] Related Publications
We have tested the effect of protolichesterinic acid (PA) on the activity of the volume-sensitive release pathway for the organic osmolyte taurine (VSOAC) and the expression of the leucine-rich-repeat-channel 8A (LRRC8A) protein, which constitutes an essential VSOAC component. Exposing human lung cancer cells (A549) to PA (20 µg/mL, 24 h) reduces LRRC8A protein expression by 25% and taurine release following osmotic cell swelling (320 → 200 mOsm) by 60%. C75 (20 µg/mL, 24 h), a γ-lactone with a C8 carbon fatty acid chain, reduces VSOAC activity by 30%, i.e. less than PA. Stearic acid (20 µg/mL, 24 h) has no effect on VSOAC. Hence, length of PA's fatty acid chain adds to γ-lactone's inhibitory action. 5-Lipoxygenase (5-LO) activity is essential for swelling-induced activation of VSOAC. PA has no effect on cellular concentration of leukotrienes (5-HETE/LTB4 ) under hypotonic conditions, excluding that PA mediated inhibition of VSOAC involves 5-LO inhibition. A549 cells exposed to the chemotherapeutic drug cisplatin (10 μM, 24 h) reveal signs of apoptosis, i.e. 25% reduction in cell viability as well as 1.3-, 1.5- and 3.3-fold increase in the expression of LRRC8A, Bax (regulator of apoptosis) and p21 (regulator of cell cycle progression), respectively. PA reduces cell viability by 30% but has no effect on p21/Bax expression. This excludes PA as a pro-apoptotic drug in A549 cells.

Grimsrud TK, Skaug HK, Larsen IK
Lung cancer – changes in incidence by gender, age and county of residence 1984-2013.
Tidsskr Nor Laegeforen. 2015; 135(20):1844-9 [PubMed] Related Publications
BACKGROUND: The Cancer Registry of Norway has reported a decline in age-standardised lung cancer rates for men and an unconfirmed levelling-off in the rate for women. This study describes the development in trends according to gender and age, nationwide as well as by county.
MATERIAL AND METHOD: Data on lung cancer from the Cancer Registry of Norway and the NORDCAN website are presented as age-specific and age-standardised rates by gender and place of residence, with a main emphasis on the period 1984-2013.
RESULTS: Out of 62,937 Norwegian lung cancer patients (1984-2013), altogether 63% were men. Nationally there was a decline in the rate for middle-aged men (50-69 years), but only a levelling-off in the oldest age group (≥ 70 years). For women, the rates increased in both age groups, most markedly in the oldest one. The rates for older men in the Agder, Vestfold and Finnmark counties have remained above the national average for a prolonged period, and there are only modest signs of a decline among the middle-aged. Oslo is a clear exception, with a clear and sustained decline among men in both age groups. Vest-Agder county had the highest rate for women during the last five-year period, while the rates in Oslo are now at the national average. The national rates for middle-aged women and middle-aged men are converging, intersecting each other in Akershus county.
INTERPRETATION: The large differences between genders, age groups, counties and nations in terms of trends in lung cancer indicate that through preventive efforts, we might have achieved much more in a shorter time.

Schulman C, Cornel E, Matveev V, et al.
Intermittent Versus Continuous Androgen Deprivation Therapy in Patients with Relapsing or Locally Advanced Prostate Cancer: A Phase 3b Randomised Study (ICELAND).
Eur Urol. 2016; 69(4):720-7 [PubMed] Related Publications
BACKGROUND: Intermittent androgen deprivation (IAD) has received increasing attention; however, the current literature is still limited, especially in nonmetastatic prostate cancer (PCa), and the relative efficacy and safety benefits of IAD versus continuous androgen deprivation (CAD) remain unclear.
OBJECTIVE: To add to the knowledge base regarding efficacy and potential benefits, including reduced side effects and improved quality of life (QoL), of IAD versus CAD in patients with nonmetastatic relapsing or locally advanced PCa.
DESIGN, SETTING, AND PARTICIPANTS: A 42-mo phase 3b open-label randomised study in 933 patients from 20 European countries.
INTERVENTION: Following a 6-mo induction with leuprorelin acetate (Eligard) 22.5mg 3-mo depot, patients were randomised to CAD or IAD with leuprorelin for 36 mo.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point was time to prostate-specific antigen (PSA) progression while receiving luteinising hormone-releasing hormone agonist, defined as three consecutive increasing PSA values ≥ 4 ng/ml ≥ 2 wk apart. Secondary end points included PSA progression-free survival (PFS), overall survival (OS), testosterone levels, performance status, and QoL.
RESULTS AND LIMITATIONS: A total of 933 patients entered the induction phase; 701 were randomised. The median number of injections administered after randomisation was 12 (range: 1-12) for the CAD group and 3 (range: 1-10) for the IAD group. There were no statistically significant or clinically relevant differences between the groups for time to PSA progression, PSA PFS, OS, mean PSA levels over time, or QoL. A similar number of adverse events was observed in each group; the most common were hot flushes and hypertension. Study limitations include the open-label design and absence of formal testosterone recovery assessment.
CONCLUSIONS: IAD and CAD demonstrated similar efficacy, tolerability, and QoL in men with nonmetastatic PCa. The principal benefit of IAD compared with CAD is a potential cost reduction with comparable OS rates. There are no apparent QoL benefits.
PATIENT SUMMARY: This randomised trial showed that both intermittent and continuous hormone therapy had similar efficacy, tolerability, and quality-of-life profiles in patients with relapsing M0 or locally advanced prostate cancer. Intermittent therapy may be a valid option for selected patients.
TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00378690.

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