Trends in cancer survival in the Nordic countries 1990-2016 : the NORDCAN survival studies

Background Differences in cancer survival between the Nordic countries have previously been reported. The aim of this study was to examine whether these differences in outcome remain, based on updated information from five national cancer registers. Materials and methods The data used for the analysis was from the NORDCAN database focusing on nine common cancers diagnosed 1990-2016 in Denmark, Finland, Iceland, Norway and Sweden with maximum follow-up through 2017. Relative survival (RS) was estimated at 1 and 5 years using flexible parametric RS models, and percentage point differences between the earliest and latest years available were calculated. Results A consistent improvement in both 1- and 5-year RS was found for most studied sites across all countries. Previously observed differences between the countries have been attenuated. The improvements were particularly pronounced in Denmark that now has cancer survival similar to the other Nordic countries. Conclusion The reasons for the observed improvements in cancer survival are likely multifactorial, including earlier diagnosis, improved treatment options, implementation of national cancer plans, uniform national cancer care guidelines and standardized patient pathways. The previous survival disadvantage in Denmark is no longer present for most sites. Continuous monitoring of cancer survival is of importance to assess the impact of changes in policies and the effectiveness of health care systems.Peer reviewe

Age-specific survival trends and life-years lost in women with breast cancer 1990-2016 : the NORDCAN survival studies

BackgroundA recent overview of cancer survival trends 1990-2016 in the Nordic countries reported continued improvements in age-standardized breast cancer survival among women. The aim was to estimate age-specific survival trends over calendar time, including life-years lost, to evaluate if improvements have benefited patients across all ages in the Nordic countries.MethodsData on breast cancers diagnosed 1990-2016 in Denmark, Finland, Iceland, Norway, and Sweden were obtained from the NORDCAN database. Age-standardized and age-specific relative survival (RS) was estimated using flexible parametric models, as was reference-adjusted crude probabilities of death and life-years lost.ResultsAge-standardized period estimates of 5-year RS in women diagnosed with breast cancer ranged from 87% to 90% and 10-year RS from 74% to 85%. Ten-year RS increased with 15-18 percentage points from 1990 to 2016, except in Sweden (+9 percentage points) which had the highest survival in 1990. The largest improvements were observed in Denmark, where a previous survival disadvantage diminished. Most recent 5-year crude probabilities of cancer death ranged from 9% (Finland, Sweden) to 12% (Denmark, Iceland), and life-years lost from 3.3 years (Finland) to 4.6 years (Denmark). Although survival improvements were consistent across different ages, women aged >= 70 years had the lowest RS in all countries. Period estimates of 5-year RS were 94-95% in age 55 years and 84-89% in age 75 years, while 10-year RS were 88-91% in age 55 years and 69-84% in age 75 years. Women aged 40 years lost on average 11.0-13.8 years, while women lost 3.8-6.0 years if aged 55 and 1.9-3.5 years if aged 75 years.ConclusionsSurvival for Nordic women with breast cancer improved from 1990 to 2016 in all age groups, albeit with larger country variation among older women where survival was also lower. Women over 70 years of age have not had the same survival improvement as women of younger age.Peer reviewe

Infection-related hospitalizations in breast cancer patients: risk and impact on prognosis

OBJECTIVES: Infections are a common cause of hospitalization in breast cancer patients. We studied the risk, clinical characteristics and outcomes of infection-related hospitalizations in this patient population. METHODS: A Swedish registry-based study including 8338 breast cancer patients diagnosed between 2001 and 2008, followed prospectively for infection-related hospitalizations until 2010. Standardized incidence ratios (SIRs) were calculated using background rates from the general female population. Associations with clinical characteristics and mortality were analyzed using flexible parametric survival models. RESULTS: In total, 720 patients experienced an infection-related hospitalization during a median follow-up of 4.9 years. Infection rates were highest within the first year of diagnosis (SIR = 5.61, 95% CI; 4.98-6.32), and site-specific risks were most pronounced for sepsis (SIR = 3.14, 95% CI; 2.66-3.71) and skin infections (SIR = 2.80, 95% CI; 2.24-3.50). Older age at diagnosis, comorbidities, markers of tumor aggressiveness, chemotherapy and axillary node dissection were independent predictors of infectious disease risk. Infection-related hospitalizations were also independently associated with overall and breast cancer-specific death. CONCLUSIONS: A significant number of breast cancer patients are hospitalized with an infection following diagnosis, which in turn predicts poor prognosis. The risk profile of infection-related hospitalizations is multifactorial, including patient, tumor and treatment-related factors.Swedish Research CouncilFORTEAccepte

Chemotherapy, genetic susceptibility, and risk of venous thromboembolism in breast cancer patients

Purpose: Venous thromboembolism (VTE) is highly heritable and a serious complication of cancer and its treatment. We examined the individual and joint effects of chemotherapy and genetic susceptibility on VTE risk in patients with breast cancer. Experimental design: A Swedish population-based study including 4,261 women diagnosed with primary invasive breast cancer between 2001 and 2008 in Stockholm, followed until 2012. Risk stratification by chemotherapy and genetic susceptibility [a polygenic risk score (PRS), including nine established VTE loci] was assessed using Kaplan-Meier and flexible parametric survival analyses, adjusting for patient, tumor, and treatment characteristics. Results: In total, 276 patients experienced a VTE event during a median follow-up of 7.6 years. Patients receiving chemotherapy [HR (95% CI) = 1.98; 1.40-2.80] and patients in the highest 5% of the PRS [HR (95% CI) = 1.90; 1.24-2.91] were at increased risk of developing VTE. Chemotherapy and PRS acted independently on VTE risk and the 1-year cumulative incidence in patients carrying both risk factors was 9.5% compared with 1.3% in patients not having these risk factors (P < 0.001). Stratified analyses by age showed that the risk-increasing effect of PRS was stronger in older patients (P interaction = 0.04), resulting in an excess risk among genetically susceptible patients receiving chemotherapy aged ≥ 60 years (1-year cumulative incidence = 25.0%). Conclusions: Risk stratification by chemotherapy and genetic susceptibility identifies patients with breast cancer at high VTE risk, who could potentially benefit from thromboprophylaxis. Our results further suggest that genetic testing is more informative in older patients with breast cancer.Swedish Research Council (20142271)Swedish Cancer Society (CAN 2013/469)Swedish Research Council for Health Working Life & Welfare (Forte) (2013-0474)PublishedAccepte

Resolution of the type material of the Asian elephant, Elephas maximus Linnaeus, 1758 (Proboscidea, Elephantidae)

The understanding of Earth’s biodiversity depends critically on the accurate identification and nomenclature of species. Many species were described centuries ago, and in a surprising number of cases their nomenclature or type material remain unclear or inconsistent. A prime example is provided by Elephas maximus, one of the most iconic and well-known mammalian species, described and named by Linnaeus (1758) and today designating the Asian elephant. We used morphological, ancient DNA (aDNA), and high-throughput ancient proteomic analyses to demonstrate that a widely discussed syntype specimen of E. maximus, a complete foetus preserved in ethanol, is actually an African elephant, genus Loxodonta. We further discovered that an additional E. maximus syntype, mentioned in a description by John Ray (1693) cited by Linnaeus, has been preserved as an almost complete skeleton at the Natural History Museum of the University of Florence. Having confirmed its identity as an Asian elephant through both morphological and ancient DNA analyses, we designate this specimen as the lectotype of E. maximus

Buffering of Segmental and Chromosomal Aneuploidies in Drosophila melanogaster

Chromosomal instability, which involves the deletion and duplication of chromosomes or chromosome parts, is a common feature of cancers, and deficiency screens are commonly used to detect genes involved in various biological pathways. However, despite their importance, the effects of deficiencies, duplications, and chromosome losses on the regulation of whole chromosomes and large chromosome domains are largely unknown. Therefore, to explore these effects, we examined expression patterns of genes in several Drosophila deficiency hemizygotes and a duplication hemizygote using microarrays. The results indicate that genes expressed in deficiency hemizygotes are significantly buffered, and that the buffering effect is general rather than being mainly mediated by feedback regulation of individual genes. In addition, differentially expressed genes in haploid condition appear to be generally more strongly buffered than ubiquitously expressed genes in haploid condition, but, among genes present in triploid condition, ubiquitously expressed genes are generally more strongly buffered than differentially expressed genes. Furthermore, we show that the 4th chromosome is compensated in response to dose differences. Our results suggest general mechanisms have evolved that stimulate or repress gene expression of aneuploid regions as appropriate, and on the 4th chromosome of Drosophila this compensation is mediated by Painting of Fourth (POF)

Gynecologic cancers in pregnancy: guidelines based on a third international consensus meeting

We aimed to provide comprehensive protocols and promote effective management of pregnant women with gynecological cancers. New insights and more experience have been gained since the previous guidelines were published in 2014. Members of the International Network on Cancer, Infertility and Pregnancy (INCIP), in collaboration with other international experts, reviewed existing literature on their respective areas of expertise. Summaries were subsequently merged into a manuscript that served as a basis for discussion during the consensus meeting. Treatment of gynecological cancers during pregnancy is attainable if management is achieved by collaboration of a multidisciplinary team of health care providers. This allows further optimization of maternal treatment, while considering fetal development and providing psychological support and long-term follow-up of the infants. Nonionizing imaging procedures are preferred diagnostic procedures, but limited ionizing imaging methods can be allowed if indispensable for treatment plans. In contrast to other cancers, standard surgery for gynecological cancers often needs to be adapted according to cancer type and gestational age. Most standard regimens of chemotherapy can be administered after 14 weeks gestational age but are not recommended beyond 35 weeks. C-section is recommended for most cervical and vulvar cancers, whereas vaginal delivery is allowed in most ovarian cancers. Breast-feeding should be avoided with ongoing chemotherapeutic, endocrine or targeted treatment. More studies that focus on the long-term toxic effects of gynecologic cancer treatments are needed to provide a full understanding of their fetal impact. In particular, data on targeted therapies that are becoming standard of care in certain gynecological malignancies is still limited. Furthermore, more studies aimed at the definition of the exact prognosis of patients after antenatal cancer treatment are warranted. Participation in existing registries (www.cancerinpregnancy.org) and the creation of national tumor boards with multidisciplinary teams of care providers (supplementary Box S1, available at Annals of Oncology online) is encouraged

Protein C Inhibitor—A Novel Antimicrobial Agent

Protein C inhibitor (PCI) is a heparin-binding serine proteinase inhibitor belonging to the family of serpin proteins. Here we describe that PCI exerts broad antimicrobial activity against bacterial pathogens. This ability is mediated by the interaction of PCI with lipid membranes, which subsequently leads to their permeabilization. As shown by negative staining electron microscopy, treatment of Escherichia coli or Streptococcus pyogenes bacteria with PCI triggers membrane disruption followed by the efflux of bacterial cytosolic contents and bacterial killing. The antimicrobial activity of PCI is located to the heparin-binding site of the protein and a peptide spanning this region was found to mimic the antimicrobial activity of PCI, without causing lysis or membrane destruction of eukaryotic cells. Finally, we show that platelets can assemble PCI on their surface upon activation. As platelets are recruited to the site of a bacterial infection, these results may explain our finding that PCI levels are increased in tissue biopsies from patients suffering from necrotizing fasciitis caused by S. pyogenes. Taken together, our data describe a new function for PCI in innate immunity