Project description:Studies of survival in hematological malignancies (HMs) have generally shown an improvement over time, although most of these studies are limited by a short follow-up period. Using the NORDCAN database with data from Denmark, Finland, Norway and Sweden, we follow periodic increases in relative survival in seven HMs through half a century up to 2015-2019. Five-year survival improved in all seven HMs, reaching 90% for Hodgkin lymphoma (HL), myeloproliferative neoplasias and chronic lymphocytic leukemia (CLL), 60% for multiple myeloma (MM) and chronic myeloid leukemias (CMLs), 50% for the myelodysplastic syndromes and 30% for acute myeloid leukemia (AML). Improvements in survival over 50 years ranged from 20% to more than 50% units across the different HMs. The likely reasons for such progress include earlier diagnoses, improved risk stratification and advances in treatment. We observed differing temporal trends in improvements in survival. The gradual increases observed in HL, CLL and AML highlight the impact of optimization of existing therapies and improvements in diagnostics and risk stratification, whereas the rapid increases observed in the CMLs and MM highlight the impact of novel therapies. Recent therapeutic advances may further improve survival in HMs where survival remains low such as in AML.
Project description:BackgroundDuring the 1970s the Nordic countries liberalized their abortion laws.ObjectiveWe assessed epidemiological trends for induced abortion on all Nordic countries, considered legal similarities and diversities, effects of new medical innovations and changes in practical and legal provisions during the subsequent years.MethodsNew legislation strengthened surveillance of induced abortion in all countries and mandated hospitals that performed abortions to report to national abortion registers. Published data from the Nordic abortion registers were considered and new comparative analyses done. The data cover complete national populations.Results and conclusionsAfter an increase in abortion rates during the first years following liberalization, the general abortion rates stabilized and even decreased in all Nordic countries, especially for women under 25 years. From the mid-1980s higher awareness about pregnancy termination led women to present at an earlier gestational age, which was accelerated by the introduction of medical abortion some years later. Most terminations (80-86%) are now done before the 9th gestational week in all countries, primarily by medical rather than surgical means. Introduction of routine ultrasound screening in pregnancy during the late 1980s, increased the number of 2nd trimester abortions on fetal anomaly indications without an overall increase in the proportion of 2nd relative to 1st trimester abortions. Further refinement of ultrasound screening and non-invasive prenatal diagnostic methods led to a slight increase in the proportion of early 2nd trimester abortions after the year 2000. Country-specific differences in abortion rates have remained stable over the 50 years of liberalized abortion laws.
Project description:BACKGROUND: Nordic countries' data offer a unique possibility to evaluate the long-term benefit of cervical cancer screening in a context of increasing risk of human papillomavirus infection. METHODS: Ad hoc-refined age-period-cohort models were applied to the last 50-year incidence data from Denmark, Finland, Norway and Sweden to project expected cervical cancer cases in a no-screening scenario. RESULTS: In the absence of screening, projected incidence rates for 2006-2010 in Nordic countries would have been between 3 and 5 times higher than observed rates. Over 60,000 cases or between 41 and 49% of the expected cases of cervical cancer may have been prevented by the introduction of screening in the late 1960s and early 1970s. CONCLUSIONS: Our study suggests that screening programmes might have prevented a HPV-driven epidemic of cervical cancer in Nordic countries. According to extrapolations from cohort effects, cervical cancer incidence rates in the Nordic countries would have been otherwise comparable to the highest incidence rates currently detected in low-income countries.
Project description:BackgroundSurvival in breast cancer (BC) has developed favorably but late recurrences are still a problem.MethodsWe model survival data from the NORDCAN database and analyze 1-, 5-, and 10-year relative survival and 5/1- and 10/5-year conditional survival in BC from Denmark (DK), Finland (FI), Norway (NO), and Sweden (SE) between 1971 and 2020. Conditional survival measures survival in those who had survived year 1 to reach year 5 (5/1), or in those who had survived year 5 to reach year 10 (10/5).ResultsAlmost all survival metrics were best for SE but survival in all countries improved in the course of time approaching the SE levels which were 98.3% for 1-year, 92.3% for 5-year, and 87.8% for 10-year survival. Conditional 10/5-year survival, covering 5 years, was better than 5/1-year survival, covering 4 years. A contributing factor is most likely the high rate of recurrence in period 2-5 years. The difference was observed for all countries but for DK 10/5-year survival approached 1-year survival and for NO and SE 10/5-year survival was only barely better than 5/1-year survival. The explanation to this was the excellent 10/5-year survival in DK compared to SE and particularly to NO. Literature search suggested that the reason for the relatively low 10/5-year survival in NO might be stagnant survival development in old patients.ConclusionsWe assume that late mortality is critically limiting survival in BC and either interference with the late metastatic process or effective treatment will be key to future improvements in BC survival.
Project description:Background & aimsLiver cancer (LC) and pancreatic cancer (PC) are often diagnosed at an advanced stage resulting in high mortality. High-quality survival data are rarely available for trend analyses over a long period.MethodsThe Danish, Finnish, Norwegian, and Swedish cancer data were accessed at the NORDCAN database. We analysed relative 1- and 5-year survival trends in LC and PC between years 1970 and 2019.ResultsRelative 1-year survival in LC for Nordic men and women was about 10% in the period between 1970 and 1974, and it increased moderately by year 2000 and steeply thereafter, eventually reaching 40-50%. The patterns in 5-year survival were similar, but after the year 2000, survival in Norway and Sweden increased steeply to 23%, whereas survival in Denmark and Finland lagged behind, reaching 10% to 15%. The patterns for PC also showed rapid improvement after the year 2000, with 1-year survival reaching 30% to 40% and 5-year survival reaching 10% for Finland and 15% for Norway and Sweden. Survival was best for patients diagnosed before age 50 years, and it was worst for older patients. For both cancers the difference between 1- and 5-year survival increased with time.ConclusionsSurvival in LC and PC improved first modestly and then steeply over the 50-year period covered. The increase in 5-year survival was less than that of 1-year survival. The survival gains were most likely the result of earlier diagnosis, improved treatment, and better organised supportive care. The challenges are to keep up these positive trends, to extend survival benefits past Year 1, and to obtain similar results in elderly patients. Primary prevention through avoidance of risk factors would reduce case numbers.Lay summaryLiver and pancreatic cancers are among the most lethal of all cancers. In 50 years, survival in these cancers has slowly improved, and in the past 20 years, the development has been increasingly favourable. Widespread adoption of healthy lifestyles will be key to reducing the risk of these cancers.
Project description:Proteolysis targeting chimeras (PROTACs) are heterobifunctional small molecules that uses the proteasome ubiquitin system to target proteins of interest and promote their degradation with remarkable selectivity. Importantly, unlike conventional small molecule inhibitors, PROTACs have proven highly effective in targeting undruggable proteins and those bearing mutations. Because of these considerations, PROTACs have increasingly become an emerging technology for the development of novel targeted anticancer therapeutics. Interestingly, many PROTACs have demonstrated a great potency and specificity in degrading several oncogenic drivers. Many of these, following extensive preclinical evaluation, have reached advanced stages of clinical testing in various cancers including hematologic malignancies. In this review, we provide a comprehensive summary of the recent advances in the development of PROTACs as therapeutic strategies in diverse hematological malignancies. A particular attention has been given to clinically relevant PROTACs and those targeting oncogenic mutants that drive resistance to therapies. We also discus limitations, and various considerations to optimize the design for effective PROTACs.
Project description:BackgroundGastric cancer (GC) and esophageal cancer (EC) are among the most fatal cancers and improving survival in them is a major clinical challenge. Nordic cancer data were recently released up to year 2019. These data are relevant for long-term survival analysis as they originate from high-quality national cancer registries from countries with practically free access to health care, thus documenting 'real-world' experience for entire populations.Patients/methodsData were obtained for Danish (DK), Finnish (FI), Norwegian (NO), and Swedish (SE) patients from the NORDCAN database from years 1970 through 2019. Relative 1- and 5-year survival were analyzed, and additionally the difference between 1- and 5-year survival was calculated as a measure of trends between years 1 and 5 after diagnosis.ResultsRelative 1-year survival for Nordic men and women in GC was 30% in period 1970-74 and it increased close to 60%. Early 5-year survival ranged between 10 and 15% and the last figures were over 30% for all women and NO men while survival for other men remain below 30%. Survival in EC was below that in GC, and it reached over 50% for 1-year survival only for NO patients; 5-year survival reached over 20% only for NO women. For both cancers, the difference between 1- and 5-year survival increased with time. Survival was worst among old patients.ConclusionGC and EC survival improved over the 50-year period but the increase in 5-year survival was entirely explained by gains in 1-year survival, which improved at an accelerated pace in EC. The likely reasons for improvements are changes in diagnosis, treatment, and care. The challenges are to push survival past year 1 with attention to old patients. These cancers have a potential for primary prevention through the avoidance of risk factors.
Project description:Kidney and bladder cancers share etiology and relatively good recent survival, but long-term studies are rare. We analyzed survival for these cancers in Denmark, Finland, Norway (NO), and Sweden (SE) over a 50-year period (1971-2020). Relative 1- and 5-year survival data were obtained from the NORDCAN database, and we additionally calculated conditional 5/1-year survival. In 2016-2020, 5-year survivals for male kidney (79.0%) and bladder (81.6%) cancers were best in SE. For female kidney cancer, NO survival reached 80.0%, and for bladder cancer, SE survival reached 76.1%. The magnitude of 5-year survival improvements during the 50-year period in kidney cancer was over 40% units; for bladder cancer, the improvement was over 20% units. Survival in bladder cancer was worse for women than for men, particularly in year 1. In both cancers, deaths in the first year were approximately as many as in the subsequent 4 years. We could document an impressive development for kidney cancer with tripled male and doubled female 5-year survival in 50 years. Additionally, for bladder cancer, a steady improvement was recorded. The current challenges are to curb early mortality and target treatment to reduce long-term mortality.
Project description:Survival in female breast cancers has generally improved but the relative contribution of early detection or treatment in this positive development is not known. Our aim was to assess the possible role of national mammography screening programs in survival improvement. Such screening has been offered to women, usually at 50-69 years of age, in Finland and Sweden since the 1980s and in Denmark and Norway since the 1990s. Participation rates have been high, ranging from 60% to 90%. We analyzed incidence and mortality changes and relative 5- and 10-year survival trends in breast cancer as novel measures in these countries using the NORDCAN database. Survival trends were compared in age groups of women who were screened to those who were not screened. We observed a relative survival advantage in 5-year and 10-year survival in the screened age groups after the period of national mammography screening was in place and this was consistent in each country. Timing and age-specific targeting of the improvements suggest that mammography may have contributed to the survival benefits. However, as we had no individual data on women who used the service, more detailed studies are needed to confirm the suggested survival advantage, particularly concerning mortality in stage-specific breast cancer.
Project description:Background: Survival studies in intestinal cancers have generally shown favorable development, but few studies have been able to pinpoint the timing of the changes in survival over an extended period. Here, we compared the relative survival rates for colon, rectal and small intestinal cancers from Denmark (DK), Finland (FI), Norway (NO) and Sweden (SE). Design: Relative 1-, 5- and 5/1-year conditional survival data were obtained from the NORDCAN database for the years 1971-2020. Results: The 50-year survival patterns were country-specific. For colon and rectal cancers, the slopes of survival curves bended upwards for DK, were almost linear for NO and bended downwards for FI and SE; 5-year survival was the highest in DK. Survival in small intestinal cancer was initially below colon and rectal cancers but in FI and NO it caught up toward the end of the follow-up. Conclusions: Relative survival in intestinal cancers has developed well in the Nordic countries, and DK is an example of a country which in 20 years was able to achieve excellent survival rates in colon and rectal cancers. In the other countries, the increase in survival curves for colon and rectal cancer has slowed down, which may be a challenge posed by metastatic cancers.