Critical survival periods in prostate cancer in Sweden explored by conditional survival analysis.

BACKROUND: We wanted to characterize conditional survival in prostate cancer (PC) in Sweden around and after 2005 when the vast increase in incidence due to the opportunistic testing for prostate specific antigen (PSA) culminated. We hypothesize that analyzing survival data during that time period may help interpret survival trends. We focus on stage-specific analysis using conditional survival in order to define the periods when deaths most commonly occurred. METHODS: Data on PC patients were obtained from the Swedish cancer registry for analysis of 1-, 2.5- and 5-year relative survival and conditional relative survival between years 2004 and 2018. Tumor-node-metastatic stage classification at diagnosis was used to specify survival. RESULTS: Small improvements were observed in stage- and age-related relative survival duriring the study period. Applying conditional relative survival showed that survival in stage T3 up to 2.5 years was better than survival between years 2.5 and 5. Survival in stage T4 was approximately equal in the first and the subsequent 2.5-year period. For M1, the first 2.5 year survival period was worse than the subsequent one. The proportion of high risk and M1 disease in old patients (80+ years) remained very high and their survival improved only modestly. CONCLUSIONS: The data indicate that M1 metastases kill more patients in the first 2.5 years than between years 2.5 and 5 after diagnosis; T4 deaths are equal in the two periods, and in T3 mortality in the first 2.5-year period is lower than between years 2.5 and 5 after diagnosis. Conditional survival could be applied to explore critical survival periods even past 5 years after diagnoses and to monitor success in novel diagnostic and treatment practices. Improvement of survival in elderly patients may require clinical input.

Survival in oral and pharyngeal cancers is catching up with laryngeal cancer in the NORDIC countries through a half century.

BACKGROUND: Cancers of the head and neck (HN) are heterogeneous tumors with incidence rates varying globally. In Northern Europe oral and oropharyngeal cancers are the most common individual types. Survival for HN varies by individual tumor type but for most of them survival trends are not well known over extended periods of time. METHODS: Data for a retrospective survival study were obtained for Danish, Finnish, Norwegian, and Swedish patients from the NORDCAN database from 1971 to 2020. Relative 1- and 5-year survival rates and 5/1-year conditional survival for years 2-5 were calculated. RESULTS: Both 1- and 5-year survival improved for all HN cancers but only marginally for laryngeal cancer. For the other cancers a 50-year increase in 5-year survival was about 30% units for nasopharyngeal and oropharyngeal cancers, 20% units for oral cancer and somewhat less for hypopharyngeal cancer. CONCLUSIONS: 5-year survival reached about 65% for all HN cancers, except for hypopharyngeal cancer (30%). Human papilloma virus infection is becoming a dominant risk factor for the rapidly increasing oropharyngeal cancer, the prevention of which needs to emphasize oral sex as a route of infection.

Long-term outcomes and cost savings of office fulguration of papillary Ta low-grade bladder cancer.

OBJECTIVES: To assess whether office-based fulguration (OF) under local anaesthesia for small, recurrent, pathological Ta low-grade (LG) non-muscle-invasive bladder cancer (NMIBC) is an effective alternative to transurethral resection of bladder tumour (TURBT), avoiding the costs and risks of procedure, and anesthesia. PATIENTS AND METHODS: Of 521 patients with primary TaLG NMIBC, this retrospective study included 270 patients who underwent OF during follow-up for recurrent, small, papillary LG-appearing tumours at a university centre (University Health Network, University of Toronto, Canada). We assessed the cumulative incidence of cancer-specific mortality (CSM) and disease progression (to MIBC or metastases), as well as possible direct cost savings. RESULTS: In the 270 patients with recurrent TaLG NMIBC treated with OF, the mean (sd) age was 64.9 (13.3) years, 70.8% were men, and 60.3% had single tumours. The mean (sd, range) number of OF procedures per patient was 3.1 (3.2, 1-22). The median (interquartile range) follow-up was 10.1 (5.8-16.2) years. Patients also underwent a mean (sd) of 3.6 (3.0) TURBTs during follow-up in case of numerous or bulkier recurrence. In all, 44.4% of patients never received intravesical therapy. The 10-year incidence of CSM and progression were 0% and 3.1% (95% confidence interval 0.8-5.4%), respectively. Direct cost savings in Ontario were estimated at $6994.14 (Canadian dollars) per patient over the study follow-up. CONCLUSIONS: This study supports that properly selected patients with recurrent, apparent TaLG NMIBC can be safely managed with OF under local anaesthesia with occasional TURBT for larger or numerous recurrent tumours, without compromising long-term oncological outcomes. This approach could generate substantial cost-saving to healthcare systems, is patient-friendly, and could be adopted more widely.

Long-Term Periodic and Conditional Survival Trends in Prostate, Testicular, and Penile Cancers in the Nordic Countries, Marking Timing of Improvements.

Survival studies are important tools for cancer control, but long-term survival data on high-quality cancer registries are lacking for all cancers, including prostate (PC), testicular (TC), and penile cancers. Using generalized additive models and data from the NORDCAN database, we analyzed 1- and 5-year relative survival for these cancers in Denmark (DK), Finland (FI), Norway (NO), and Sweden (SE) over a 50-year period (1971-2020). We additionally estimated conditional 5/1-year survival for patients who survived the 1st year after diagnosis. Survival improved early for TC, and 5-year survival reached 90% between 1985 (SE) and 2000 (FI). Towards the end of the follow-up, the TC patients who had survived the 1st year survived the next 4 years with comparable probability to the background population. For PC, the 90% landmark was reached between 2000 (FI) and after 2010 (DK). For penile cancer, 5-year survival never reached the 90% landmark, and the improvements in survival were modest at best. For TC, early mortality requires attention, whereas late mortality should be tackled for PC. For penile cancer, the relatively high early mortality may suggest delays in diagnosis and would require more public awareness and encouragement of patients to seek medical opinion. In FI, TC and penile cancer patients showed roughly double risk of dying compared to the other Nordic countries, which warrants further study and clinical attention.

Early mortality critically impedes improvements in thyroid cancer survival through a half century.

OBJECTIVES: We analyze survival in thyroid cancer from Denmark (DK), Finland (FI), Norway (NO), and Sweden (SE) over a 50-year period (1971-2020), and additionally consider concomitant changes in incidence and mortality. DESIGN: Population-based survival study. METHODS: Relative 1-, 5/1 (conditional)-, and 5-year survival data were obtained from the NORDCAN database for years 1971-2020. Incidence and mortality rates were also assessed. RESULTS: A novel consistent observation was that 1-year survival was worse than 5/1-year survival but the difference between these decreased with time. Relative 1-year survival in thyroid cancer (mean for the 4 countries) reached 92.7% for men and 95.6% for women; 5-year survival reached 88.0% for men and 93.7% for women. Survival increased most for DK which started at a low level and reached the best survival at the end. Male and female incidence rates for thyroid cancer increased 3- and 4-fold, respectively. In the same time, mortality halved for men and for women, it decreased by 2/3. CONCLUSIONS: We documented worse relative survival in the first year than in the 4 subsequent years, most likely because of rare anaplastic cancer. Overall survival in thyroid cancer patients increased in the Nordic countries in the course of 50 years; 5-year survival was close to 90% for men and close to 95% for women. Even though overdiagnosis may explain some of 5-year survival increase, it is unlikely to influence the substantial increase in 1-year survival. The unmet need is to increase 1-year survival by diagnosing and treating aggressive tumors before metastatic spread.

Steady survival improvements in soft tissue and bone sarcoma in the Nordic countries through 50 years.

PURPOSE: Sarcomas are rare cancers with many subtypes in soft tissues, bone and cartilage. International survival trends in these cancers are not well known. We present 50-year survival trends for soft tissue sarcoma (STS) and bone sarcoma (BS) in Denmark (DK), Finland (FI), Norway (NO) and Sweden (SE). METHODS: Relative 1-, 5/1 conditional- and 5-year survival data were obtained from the NORDCAN database for years 1971-20. We additionally estimated annual changes in survival rates and determined significant break points. RESULTS: In the last period, 2016-20, 5-year survival in STS was best for NO men (74.6%) and FI women (71.1%). For the rarer BS, survival rates for SE men (72.0%) and DK women (71.1%) were best. Survival in BS was lower than that in STS in 1971-75 and the difference remained in 2016-20 for men, but for women the rates were almost equal. Sex- and country-specific differences in survival in STS were small. The 50-year improvement in 5-year survival in STS was highest in NO men, 34.0 % units and FI women, 30.0 % units. The highest improvements in BS were in SE men 26.2 % units and in FI women 29.2 % units. CONCLUSIONS: The steady development in survival over the half century suggests contribution by stepwise improvements in diagnostics, treatment and care. The 10-15% mortality in the first year probably indicates diagnostic delays which could be improved by organizing patient pathways for aggressive rare diseases. Early diagnosis would also reduce metastatic disease and breakthroughs in treatment are a current challenge.

Conditional Survival in Prostate Cancer in the Nordic Countries Elucidates the Timing of Improvements.

BACKGROUND: The incidence of prostate cancer (PC) increased vastly as a result of prostate-specific antigen (PSA) testing. Survival in PC improved in the PSA-testing era, but changes in clinical presentation have hampered the interpretation of the underlying causes. DESIGN: We analyzed survival trends in PC using data from the NORDCAN database for Denmark (DK), Finland (FI), Norway (NO) and Sweden (SE) by analyzing 1-, 5- and 10-year relative survival and conditional relative survival over the course of 50 years (1971-2020). RESULTS: In the pre-PSA era, survival improved in FI and SE and improved marginally in NO but not in DK. PSA testing began toward the end of the 1980s; 5-year survival increased by approximately 30%, and 10-year survival improved even more. Conditional survival from years 6 to 10 (5 years) was better than conditional survival from years 2 to 5 (4 years), but by 2010, this difference disappeared in countries other than DK. Survival in the first year after diagnosis approached 100%; by year 5, it was 95%; and by year 10, it was 90% in the best countries, NO and SE. CONCLUSIONS: In spite of advances in diagnostics and treatment, further attention is required to improve PC survival.

Effective intravenous delivery of adenovirus armed with TNFα and IL-2 improves anti-PD-1 checkpoint blockade in non-small cell lung cancer.

Lung cancer remains among the most difficult-to-treat malignancies and is the leading cause of cancer-related deaths worldwide. The introduction of targeted therapies and checkpoint inhibitors has improved treatment outcomes; however, most patients with advanced-stage non-small cell lung cancer (NSCLC) eventually fail these therapies. Therefore, there is a major unmet clinical need for checkpoint refractory/resistant NSCLC. Here, we tested the combination of aPD-1 and adenovirus armed with TNFα and IL-2 (Ad5-CMV-mTNFα/mIL-2) in an immunocompetent murine NSCLC model. Moreover, although local delivery has been standard for virotherapy, treatment was administered intravenously to facilitate clinical translation and putative routine use. We showed that treatment of tumor-bearing animals with aPD-1 in combination with intravenously injected armed adenovirus significantly decreased cancer growth, even in the presence of neutralizing antibodies. We observed an increased frequency of cytotoxic tumor-infiltrating lymphocytes, including tumor-specific cells. Combination treatment led to a decreased percentage of immunosuppressive tumor-associated macrophages and an improvement in dendritic cell maturation. Moreover, we observed expansion of the tumor-specific memory T cell compartment in secondary lymphoid organs in the group that received aPD-1 with the virus. However, although the non-replicative Ad5-CMV-mTNFα/mIL-2 virus allows high transgene expression in the murine model, it does not fully reflect the clinical outcome in humans. Thus, we complemented our findings using NSCLC ex vivo models fully permissive for the TNFα and IL-2- armed oncolytic adenovirus TILT-123. Overall, our data demonstrate the ability of systemically administered adenovirus armed with TNFα and IL-2 to potentiate the anti-tumor efficacy of aPD-1 and warrant further investigation in clinical trials.

Survival, Incidence, and Mortality Trends in Female Cancers in the Nordic Countries.

Background: Female cancers cover common breast cancers, relatively common endometrial, ovarian, and cervical cancers and rare vulvar cancer. Survival in these cancers is known to be relatively good compared to all cancers but long-term studies for these cancers are rare, and to fill the gap, here, we generate survival data through 50 years. Materials and Methods: We applied generalized additive models to data from the NORDCAN database and analyzed 1- and 5-year relative survival for these cancers in Denmark (DK), Finland (FI), Norway (NO), and Sweden (SE) over half a century (1971-2020). Conditional 5/1-year survival for patients who survived the 1st year after diagnosis and annual survival changes was also estimated. Results: In 2016-20, 5-year survival was best for breast cancer reaching 92.3% (in SE), followed by endometrial cancer at 86.1% (SE) and cervical cancer at 75.6% (NO). Improvement in 5-year survival over the 50 years was the largest for ovarian cancer (20% units), finally reaching 52.9% (SE). For vulvar cancer, the final survival was between 70 and 73%. The best 5-year survival rate in 2016-20 was recorded for SE in breast, endometrial, and ovarian cancers; NO showed the highest rate for cervical and DK for vulvar cancers. DK had the lowest survival for breast and ovarian cancers, and FI, for the other cancers. Conclusions: The overall survival development appeared to consist of continuous improvements, most likely because of novel treatment and imaging techniques as well as overall organization of patient care. The large survival improvement for ovarian cancer was probably achieved by a surgical focus on tumors spread in the peritoneal cavity. For cervical and vulvar cancers, the high early mortality requires attention and could be helped by raising increasing public awareness of early symptoms in these cancers and developing pathways for fast initiation of treatment.

Survival in Kidney and Bladder Cancers in Four Nordic Countries through a Half Century.

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.

Survival in Lung Cancer in the Nordic Countries Through A Half Century.

Objective: Lung cancer is often diagnosed at an advanced stage and survival has been poor, although long-term studies have been rare. We analyzed data on survival in lung cancer from Denmark, Finland, Norway, and Sweden over a 50-year period (1971-2020). Methods: Relative 1- and 5-year survival data were obtained from the NORDCAN database for 1971-2020. We used generalized additive models to estimate survival trends over time and uncertainty of these estimates. We additionally calculated conditional survival from the 1st to 5th year (5/1-year), estimated annual changes in survival rates, and determined significant breaking points. Results: In 2016-2020, 5-year survival rate for lung cancer was best for Norwegian men (26.6%) and women (33.2%). The sex difference was significant and it was found for each country. Survival improved modestly until the year 2000, after which time survival curves increased steeply and kept the linear shape to the end of follow-up, indicating consistent improvement in survival. Survival curves for 1- and 5/1-year survival were almost superimposable, indicating that deaths in the first year were approximately as many as in the subsequent 4 years, thus marking sustained long-term survival. Conclusion: We could document a positive development in lung cancer survival with steep upward trends after the year 2000. Intensions for curative treatment have been increasing and the outcomes have been improving with the help of novel imaging methods. Pathways for facile patient access to treatment have been instituted. Close to 90% of the patients are ever smokers. National anti-smoking acts and alerting people who smoke about early symptoms may be beneficial, as metastatic lung cancer remains difficult to cure.

Survival in melanoma in the nordic countries into the era of targeted and immunological therapies.

OBJECTIVES: Survival in melanoma has been increasing and the most recent interest is to observe the population-level impact of novel targeted therapies and immunotherapy. We analysed survival in melanoma from Denmark (DK), Finland (FI), Norway (NO) and Sweden (SE) over a 50-years period (1971-2020). METHODS: Relative 1-5/1- and 5-year survival data were obtained from the NORDCAN database for the years 1971-2020. We estimated annual changes in survival rates and determined significant breaking points for trends. RESULTS: Survival in melanoma has reached the point where 1-year survival is approaching 100% (men 97.5-98.6%, women 98.4-99.3%, depending on the country) and 5-year survival is 93% for men (91.5-95.2%) and 96% for women (95.3-97.2%). The highest survival figures were for DK. Significant increases in both 1- and 5-year survival were observed in most countries even towards the end of the follow-up (from 2006 to 2010-2011-2015 and further to 2016-2020). CONCLUSIONS: The main increase in melanoma survival took place up to year 1990, which was probably largely achieved through successful population campaigns for sun protection and programmes for early detection of lesions. Survival increased again after year 2000 up to the last period 2016-2020. This late development coincided with the introduction of targeted therapies using BRAF and BRAF/MEK inhibitors, and towards the end of the time period availability of checkpoint inhibitors. The success of melanoma treatment in DK was mostly likely due to the efficient use of modern therapies and to the centralised treatment for metastatic disease.

Survival in gastric and esophageal cancers in the Nordic countries through a half century.

BACKGROUND: Gastric 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/METHODS: Data 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. RESULTS: Relative 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. CONCLUSION: GC 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.

Long-term survival trends in solid cancers in the Nordic countries marking timing of improvements.

Survival studies are an important indicator of the success of cancer control. We analyzed the 5-year relative survival in 23 solid cancers in Denmark, Finland, Norway and Sweden over a 50-year period (1970-2019) at the NORDCAN database accessed from the International Agency for Research on Cancer website. We plotted survival curves in 5-year periods and showed 5-year periodic survival. The survival results were summarized in four groups: (1) cancers with historically good survival (>50% in 1970-1974) which include melanoma and breast, endometrial and thyroid cancers; (2) cancers which constantly improved survival at least 20% units over the 50 year period, including cancers of the stomach, colon, rectum, kidney, brain and ovary; (3) cancer with increase in survival >20% units with changes taking place in a narrow time window, including oral, oropharyngeal, testicular and prostate cancers; (4) the remaining cancers with <20% unit improvement in survival including lung, esophageal, liver, pancreatic, bladder, soft tissue, penile, cervical and vulvar cancers. For cancers in groups 1 and 2, the constant development implied multiple improvements in therapy, diagnosis and patient care. Cancers in group 3 included testicular cancers with known therapeutic improvements but for the others large incidence changes probably implied that cancer stage (prostate) or etiology (oropharynx) changed into a more tractable form. Group 4 cancers included those with dismal survival 50 years ago but a clear tendency upwards. In 17 cancers 5-year survival reached between 50% and 100% while in only six cancers it remained at below 50%.

Long-term survival trends for primary liver and pancreatic cancers in the Nordic countries.

Background & Aims: Liver 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. Methods: The 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. Results: Relative 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. Conclusions: Survival 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 summary: Liver 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.

Local delivery of interleukin 7 with an oncolytic adenovirus activates tumor-infiltrating lymphocytes and causes tumor regression.

Cytokines have proven to be effective for cancer therapy, however whilst low-dose monotherapy with cytokines provides limited therapeutic benefit, high-dose treatment can lead to a number of adverse events. Interleukin 7 has shown promising results in clinical trials, but anti-cancer effect was limited, in part due to a low concentration of the cytokine within the tumor. We hypothesized that arming an oncolytic adenovirus with Interleukin 7, enabling high expression localized to the tumor microenvironment, would overcome systemic delivery issues and improve therapeutic efficacy. We evaluated the effects of Ad5/3-E2F-d24-hIL7 (TILT-517) on tumor growth, immune cell activation and cytokine profiles in the tumor microenvironment using three clinically relevant animal models and ex vivo tumor cultures. Our data showed that local treatment of tumor bearing animals with Ad5/3- E2F-d24-hIL7 significantly decreased cancer growth and increased frequency of tumor-infiltrating cells. Ad5/3-E2F-d24-hIL7 promoted notable upregulation of pro-inflammatory cytokines, and concomitant activation and migration of CD4+ and CD8 + T cells. Interleukin 7 expression within the tumor was positively correlated with increased number of cytotoxic CD4+ cells and IFNg-producing CD4+ and CD8+ cells. These findings offer an approach to overcome the current limitations of conventional IL7 therapy and could therefore be translated to the clinic.

Incidence and survival in laryngeal and lung cancers in Finland and Sweden through a half century.

Global survival studies have shown favorable development in most cancers but few studies have considered laryngeal cancer, particularly over extended periods or in populations for which medical care is essentially free of charge. We analyzed laryngeal and lung cancer incidence and survival in Finland (FI) and Sweden (SE) over a 50-year period (1970-2019) using data and statistical tools from the Nordcan database. Laryngeal cancer reached an incidence maximum in FI men in 1965, which in SE men occurred over 10 years later and peaking at 42% of the FI maximum. The FI incidence halved in 20 years while halving of the SE rate took almost twice as long. At maximum the male rate exceeded the female rate 20 times in FI and 10 times in SE. Incidence rates for lung cancer were approximately 10 times higher than those for laryngeal cancer, and they peaked 5 to 10 years after laryngeal cancer in both countries. The female lung cancer rates increased through the follow-up time but laryngeal cancer rates were relatively stable. Relative 1-year survival data for laryngeal cancer remained at around 85% through 50 years, and 5-year survival lagged constantly around 65%. For lung cancer 1-year survival improved and reached about 50% by 2019. Even 5-year survival improved reaching 20 to 30%, except for FI men. Incidence rates for laryngeal and lung cancers have drastically decreased in FI and SE men parallel to reduced smoking prevalence. In females, rates have clearly increased in lung but not in FI laryngeal cancer. This finding warrants further investigations into possible contributing factors, other than smoking. Survival in laryngeal cancer has not improved compared to the positive development in lung cancer. Historical smoking prevalence was unrelated of survival trends. As long-term survival in these cancers remains discouraging, the most efficient way to fight them is to target the main cause and promote non-smoking.

Long-term incidence in hepatocellular carcinoma and intrahepatic bile duct cancer in Denmark, Finland, Norway and Sweden, role of Thorotrast?

We analyzed long-term incidence trends in liver cancer (including hepatocellular carcinoma and intrahepatic cholangiocarcinoma) with an aim to interpret the changes in terms of known risk factors and hypothesize that historical exposure to Thorotrast, a radiographic contrast medium emitting alpha particles, has changed population rates. The NORDCAN database was used to collect cancer registry data from Denmark (DK), Finland (FI), Norway (NO) and Sweden (SE), which we used from 1953 (DK, FI and NO) and 1960 (SE) through 2019. Thorotrast, which caused a 100-fold risk of liver cancer was used in DK and SE, and probably also in FI between 1930 and 1950, but not in NO. The incidence trend for liver cancer showed a broad maximum at around 1980, most prominent and statistically significant in SE and DK men and women, and in all countries, a steadily increasing trend towards the end of follow-up. Incidence for NO was lower than for the other countries and the rates showed no peaking at around 1980. Birth cohort analysis identified a transient risk which could be dated to a period between 1930 and 1950 in countries other than NO. Considering a lag time between Thorotrast use and liver cancer appearance, the large incidence peak around 1980 in DK and DE was probably contributed by Thorotrast but considering the ecological nature of the findings, the association should be considered cautiously as hypothesis generating. The late increase in liver cancer risk is most likely lifestyle related and largely preventable.

Incidence and survival in oral and pharyngeal cancers in Finland and Sweden through half century.

BACKGROUND: Cancers of the oral cavity and pharynx encompass a heterogeneous group of cancers for which known risk factors include smoking, alcohol consumption and human papilloma virus (HPV) infection but their influence is site-specific with HPV mainly influencing oropharyngeal cancer. Their incidence and survival rates are not well known over extended periods of time. PATIENTS/METHODS: Data were obtained for Finnish (FI) and Swedish (SE) patients from the Nordcan database recently updated through 2019. Age-adjusted incidence trends (FI from 1953, SE from 1960) and relative survival rates for years 1970 through 2019 were calculated. RESULTS: We observed a prominent increase in oral and oropharyngeal cancers in FI and SE men and women but the trend for oral cancer was interrupted for SE men in 1985 and possibly also for FI and SE women in 2015. The trend changes in male and female oral cancer was confirmed in data for Denmark and Norway. Relative survival for these cancers has improved overall but they differed for one cluster of oral, oropharyngeal and nasopharyngeal cancers with 60-70% 5-year survival in the last period and hypopharyngeal cancer with 25% male survival. In all these cancers, survival for old patients was unfavorable. DISCUSSION/CONCLUSION: We hypothesize that reduction in smoking prevalence helped to stop the increase in oral cancer especially in men. As the prevalence of smoking is decreasing, HPV is becoming a dominant risk factor, particularly for the increasing oropharyngeal cancer. Prevention needs to emphasize sexual hygiene and HPV vaccination.