Have the recent advancements in cancer therapy and survival benefitted patients of all age groups across the Nordic countries? NORDCAN survival analyses 2002-2021.

BACKGROUND: Since the early 2000s, overall and site-specific cancer survival have improved substantially in the Nordic countries. We evaluated whether the improvements have been similar across countries, major cancer types, and age groups. MATERIAL AND METHODS: Using population-based data from the five Nordic cancer registries recorded in the NORDCAN database, we included a cohort of 1,525,854 men and 1,378,470 women diagnosed with cancer (except non-melanoma skin cancer) during 2002-2021, and followed for death until 2021. We estimated 5-year relative survival (RS) in 5-year calendar periods, and percentage points (pp) differences in 5-year RS from 2002-2006 until 2017-2021. Separate analyses were performed for eight cancer sites (i.e. colorectum, pancreas, lung, breast, cervix uteri, kidney, prostate, and melanoma of skin). RESULTS: Five-year RS improved across nearly all cancer sites in all countries (except Iceland), with absolute differences across age groups ranging from 1 to 21 pp (all cancer sites), 2 to 20 pp (colorectum), -1 to 36 pp (pancreas), 2 to 28 pp (lung), 0 to 9 pp (breast), -11 to 26 pp (cervix uteri), 2 to 44 pp (kidney), -2 to 23 pp (prostate) and -3 to 30 pp (skin melanoma). The oldest patients (80-89 years) exhibited lower survival across all countries and sites, although with varying improvements over time. INTERPRETATION: Nordic cancer patients have generally experienced substantial improvements in cancer survival during the last two decades, including major cancer sites and age groups. Although survival has improved over time, older patients remain at a lower cancer survival compared to younger patients.

Survival of patients with basal cell carcinoma, squamous cell carcinoma, and squamous cell carcinoma in situ: A whole population study.

BACKGROUND: Keratinocyte carcinoma (KC) is the commonest type of malignancy in humans; however, the impact of KC on survival is poorly understood. OBJECTIVES: This study characterizes the impact of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and squamous cell carcinoma in situ (SCCis) on the survival of Icelanders. METHODS: This whole population study evaluated relative survival of KC in Iceland by using a cancer registry containing records of all BCC, SCCis, and SCC cases recorded in Iceland between 1981 and 2015. RESULTS: Between 1981 and 2015, 8767 Icelanders were diagnosed with their first localized KC. A total of 6473 individuals with BCC, 1194 with SCCis, and 1100 with invasive SCC, respectively. BCC was not associated with decreased survival except for men diagnosed with BCC between 1981 and 1995 for whom decreased 10-year relative survival was observed (85.3, 95% CI [77.9-92.7]). SCC and SCCis were both associated with a decrease in relative survival for certain population subgroups such as individuals <50 years of age at time of diagnosis. CONCLUSION: Our whole population cohort survival study examining the Icelandic Cancer Registry supports prior studies demonstrating that BCC is not associated with a reduction in relative survival and that SCC and SCCis are associated with comparatively poor relative survival in certain population subgroups.

[Breastfeeding in Iceland: Changes in prevalence and duration over a century].

INTRODUCTION: Worldwide, the health-promoting effects of breastfeeding on children and their mothers are indisputable. The frequency and duration of breastfeeding varies greatly internationally but studies on prevalence and influencing factors of breastfeeding in Iceland are scanty and the published ones deal with small groups. The aim of this research is to describe the epidemiology of breastfeeding duration and its influencing factors in Iceland among a large cohort in a whole population over almost one century. MATERIAL AND METHODS: This is a historical cohort study, using data from The Cancer Detection Clinic Cohort of The Icelandic Cancer Society, collected retrospectively by questionnaires during the years 1964-2008. The data consisted of mothers´ reported information on breastfeeding of their 81,889 children, 36,537 first-borns and 45,352 younger siblings. The frequency and duration of breastfeeding was calculated and the effects of the following exposure variables were assessed: Maternal age, BMI (N=4950, data collected 1979-2008) and smoking (N=32.087, data collected 1995-2008), the child's year of birth and its order in the sibling group. RESULTS: The children were born in the period of 1917-2008. In the late 1970s, the average duration of breastfeeding began to increase, in all age groups of mothers, increasing rapidly from 3 months to 7-8 months. At about the same time, the breastfeeding duration increased depending on the birth order of the children, younger children were breastfed for longer than their older siblings. Women with normal weight (BMI 18.5 to 24.9) breastfed their babies the longest, while obese women breastfed the shortest. Women with any history of smoking reported shorter duration of breastfeeding than women who had never smoked. CONCLUSION: The increase in the average duration of breastfeeding in Iceland a few decades ago is in accordance with the information in the World Health Organization's database from European countries 1975-2000, where the Nordic countries and most Northern European countries promoted breastfeeding at a similar time. High BMI and maternal smoking are important variables when studying breastfeeding and this study indicates their negative association with the duration of breastfeeding.

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

BACKGROUND: A 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. METHODS: Data 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. RESULTS: Age-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. CONCLUSIONS: Survival 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.

[Screening for cancer of the colon and rectum A review on incidence, mortality, cost and benefit].

In this article the incidence and mortality for cancer of the colon and rectum in Iceland is discussed. The two most common screening methods, faecal immunochemical test (FIT) and colonoscopy are compared and an estimate of cost and benefits for the Icelandic society will be made. The incidence of cancer of the colon and rectum has been increasing in Iceland in last decades but mortality has decreased and survival improved. However, more individuals die from cancer of the colon and rectum than from both breast- and cervical cancer added together. It is likely that screening for cancer of the colon and rectum, could prevent at least 6 of the 28 deaths related to those cancers, occurring yearly in Iceland in screening age, given a screening ages of 50-74 years. The extra cost for the Icelandic community due to the implementation of screening for cancer of the colon and rectum will be acceptable due to the lower cost of simpler treatments, lower cancer incidence and reduced mortality.

Cumulative exposure to premenopausal obesity and risk of postmenopausal cancer: A population-based study in Icelandic women.

Obesity, often assessed at one point in time, is an established risk factor of several types of cancer, however, associations with cumulative exposure to obesity across the life course are not well understood. We investigated the relationship between combined measures of duration and intensity of premenopausal overweight and obesity and the incidence of postmenopausal breast, endometrial, and colorectal cancers in Icelandic women. Body mass index (BMI) trajectories between ages 20 and 50 of 88,809 women from the Cancer Detection Clinic Cohort were predicted using growth curve models. Indicators of overweight and obesity duration and intensity were computed and their association with risk of postmenopausal breast, endometrial, and colorectal cancers was examined using multivariate Cox models for subjects followed-up beyond the age of 50 (n = 67,488). During a mean follow-up of 17 years, incident events of 3,016 postmenopausal breast, 410 endometrial and 987 colorectal cancers were ascertained. Each 0.1 kg/m2 per year increase in BMI between ages 20 and 50 was positively associated with risks of postmenopausal breast, endometrium and colorectal cancers with hazard ratios equal to 1.09 (95% Confidence Interval (CI):1.04-1.13), 1.31 (95% CI: 1.18-1.44) and 1.10 (95% CI: 1.00-1.21), respectively. Compared to women who were never obese, cumulative BMI × years of obesity were linearly positively associated with risk of endometrial cancer, whereas the association with breast cancer was initially positive, but leveled off with increasing cumulative BMI × years. Cumulative exposure to obesity may provide additional insights into the etiology of cancer and should be considered in future studies that assess obesity-cancer relationships.

Breast cancer survival in Nordic BRCA2 mutation carriers-unconventional association with oestrogen receptor status.

BACKGROUND: The natural history of breast cancer among BRCA2 carriers has not been clearly established. In a previous study from Iceland, positive ER status was a negative prognostic factor. We sought to identify factors that predicted survival after invasive breast cancer in an expanded cohort of BRCA2 carriers. METHODS: We studied 608 women with invasive breast cancer and a pathogenic BRCA2 mutation (variant) from four Nordic countries. Information on prognostic factors and treatment was retrieved from health records and by analysis of archived tissue specimens. Hazard ratios (HR) were estimated for breast cancer-specific survival using Cox regression. RESULTS: About 77% of cancers were ER-positive, with the highest proportion (83%) in patients under 40 years. ER-positive breast cancers were more likely to be node-positive (59%) than ER-negative cancers (34%) (P < 0.001). The survival analysis included 584 patients. Positive ER status was protective in the first 5 years from diagnosis (multivariate HR = 0.49; 95% CI 0.26-0.93, P = 0.03); thereafter, the effect was adverse (HR = 1.91; 95% CI 1.07-3.39, P = 0.03). The adverse effect of positive ER status was limited to women who did not undergo endocrine treatment (HR = 2.36; 95% CI 1.26-4.44, P = 0.01) and patients with intact ovaries (HR = 1.99; 95% CI 1.11-3.59, P = 0.02). CONCLUSIONS: The adverse effect of a positive ER status in BRCA2 carriers with breast cancer may be contingent on exposure to ovarian hormones.

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.

Why is colon cancer survival improving by time? A nationwide survival analysis spanning 35 years.

There is limited information present to explain temporal improvements in colon cancer survival. This nationwide study investigates the temporal changes in survival over a 35-year period (1970-2004) in Iceland and uses incidence, mortality, surgery rate, stage distribution, lymph node yield, tumor location and histological type to find explanations for these changes. Patients diagnosed with colon cancer in Iceland 1970-2004 were identified (n = 1962). All histopathology was reassessed. Proportions, age-standardized incidence and mortality, relative, cancer-specific and overall survival and conditional survival were calculated. When comparing first and last diagnostic periods (1970-1978 and 1997-2004), 5-year relative survival improved by 12% for men and 9% for women. At the same time surgery rate increased by 12% and the proportion of stage I increased by 9%. Stage-stratified, improved 5-year relative survival was mainly observed in stages II and III and coincided with higher lymph node yields, proportional reduction of stage II cancers and proportional increase of stage III cancers, indicating stage migration between these stages. Improvement in 1-year survival was mainly observed in stages III and IV. Five-year survival improvement for patients living beyond 1 year was minimum to none. There were no changes in histology that coincided with neither increased incidence nor possibly influencing improved survival. Concluding, as a novel finding, 1-year mortality, which previously has been identified as an important variable in explaining international survival differences, is in this study identified as also being important in explaining temporal improvements in colon cancer survival in Iceland.

Estrogen-progestin use and breast cancer characteristics in lean and overweight postmenopausal women.

PURPOSE: Breast cancer associated with estrogen-progestin (EP) therapy may have more favorable characteristics than cancer in never users, but results are conflicting. It is not well known either whether Body Mass Index (BMI) modifies this association. We investigated breast cancer characteristics in EP users for lean (BMI < 25 kg/m2) and overweight women (BMI ≥ 25 kg/m2). METHODS: The Icelandic Cancer Detection Clinic cohort, with information on breast cancer risk factors for 90% of Icelandic women, was linked with the population-based Icelandic Cancer Registry. A total of 781 women with invasive breast cancer diagnosed 51 years or older were matched with 7761 controls from the cohort. Conditional logistic regression was used for estimating adjusted odds ratios (OR) and 95% confidence intervals (CI) according to tumor characteristics, stratified by BMI. Polytomous logistic regression was applied in a case-only analysis for testing whether the risk associated with EP use differed according to tumor characteristics. RESULTS: Ever EP users had a twofold higher risk of breast cancer compared with never users (OR 2.05, 95% CI 1.71-2.45). In lean women, EP use was significantly less likely to be associated with grade 2 or 3 tumors than grade 1 tumors, contrary to overweight women for whom risk was increased irrespective of grade. EP use in overweight women was associated with a higher risk of lobular than ductal cancer (OR 2.75, 95% CI 1.29-5.87). CONCLUSION: Among lean EP users, tumor characteristics were more favorable than among never users. This effect was not observed for overweight women.

Oestrogen receptor status, treatment and breast cancer prognosis in Icelandic BRCA2 mutation carriers.

BACKGROUND: The impact of an inherited BRCA2 mutation on the prognosis of women with breast cancer has not been well documented. We studied the effects of oestrogen receptor (ER) status, other prognostic factors and treatments on survival in a large cohort of BRCA2 mutation carriers. METHODS: We identified 285 breast cancer patients with a 999del5 BRCA2 mutation and matched them with 570 non-carrier patients. Clinical information was abstracted from patient charts and pathology records and supplemented by evaluation of tumour grade and ER status using archived tissue specimens. Univariate and multivariate hazard ratios (HR) were estimated for breast cancer-specific survival using Cox regression. The effects of various therapies were studied in patients treated from 1980 to 2012. RESULTS: Among mutation carriers, positive ER status was associated with higher risk of death than negative ER status (HR=1.94; 95% CI=1.22-3.07, P=0.005). The reverse association was seen for non-carriers (HR=0.71; 95% CI: 0.51-0.97; P=0.03). CONCLUSIONS: Among BRCA2 carriers, ER-positive status is an adverse prognostic factor. BRCA2 carrier status should be known at the time when treatment decisions are made.

Oral contraceptives, hormone replacement therapy and breast cancer risk: a cohort study of 16 928 women 48 years and older.

BACKGROUND: Findings on potential interactive effects of oral contraceptives (OCs) and hormone replacement therapy (HRT) on breast cancer risk have been inconsistent. We aimed to use population-based cohort data to determine whether former use of OCs affects breast cancer risk among HRT users, taking into account regimens of HRT, duration and currency of use. METHODS: The cohort consisted of 16 928 Icelandic women who visited the Icelandic Cancer Detection Clinic in 1979-2006 and provided information on use of OCs and HRT when they were 48 years or older. By record linkage to the Icelandic Cancer Registry, all breast cancer diagnosed during follow-up was identified. Using Cox regression, hazard ratios (HRs) for breast cancer according to hormone use were estimated, adjusting for menstrual and reproductive risk factors. Also, interaction analyses were carried out. RESULTS: Breast cancer risk was significantly increased among ever users of combined estrogen and progestin (EP-HRT) preparations (HR=2.61; 95% CI 2.00-3.41) and not among users of estrogen-only regimens (E-only HRT) (HR=1.13; 95% CI 0.85-1.49). Ever users of both OCs and HRT had higher breast cancer risk than users of only one of the two (HR=2.19; 95% CI 1.67-2.87). After restricting the analysis to EP-HRT and focusing on long-term and current use, there was an indication of a negative interaction with ever OC use (p=0.06); HR=2.87; 95% CI 1.79-4.60 for never OC users and HR=2.24; 95% CI 1.51-3.34 for former OC users. CONCLUSION: After taking HRT regimen, duration and currency of use into account, the results of our population-based cohort study do not support the notion that former OC use increases breast cancer risk among HRT users, on the contrary there was an indication of a slightly lower risk in former OC users, restricted to current, long-term EP-HRT users.

Survival trends for patients diagnosed with cutaneous malignant melanoma in the Nordic countries 1990-2016: The NORDCAN survival studies.

BACKGROUND: The survival in patients diagnosed with cutaneous malignant melanoma (CMM) has improved in the Nordic countries in the last decades. It is of interest to know if these improvements are observed in all ages and for both women and men. METHODS: Patients diagnosed with CMM in the Nordic countries in 1990-2016 were identified in the NORDCAN database. Flexible parametric relative survival models were fitted, except for Iceland where a non-parametric Pohar-Perme approach was used. A range of survival metrics were estimated by sex, both age-standardised and age-specific. RESULTS: The 5-year relative survival improved in all countries, in both women and men and across age. While the improvement was more pronounced in men, women still had a higher survival at the end of the study period. The survival was generally high, with age-standardised estimates of 5-year relative survival towards the end of the study period ranging from 85% in Icelandic men to 95% in Danish women. The age-standardised and reference-adjusted 5-year crude probability of death due to CMM ranged from 5% in Danish and Swedish women to 13% in Icelandic men. CONCLUSION: Although survival following CMM was relatively high in the Nordic countries in 1990, continued improvements in survival were observed throughout the study period in both women and men and across age.

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

OBJECTIVES: The aim of this study was to evaluate if the previously reported improvements in lung cancer survival were consistent across age at diagnosis and by lung cancer subtypes. MATERIALS AND METHODS: Data on lung cancers diagnosed between 1990 and 2016 in Denmark, Finland, Iceland, Norway and Sweden were obtained from the NORDCAN database. Flexible parametric models were used to estimate age-standardized and age-specific relative survival by sex, as well as reference-adjusted crude probabilities of death and life-years lost. Age-standardised survival was also estimated by the three major subtypes; adenocarcincoma, squamous cell and small-cell carcinoma. RESULTS: Both 1- and 5-year relative survival improved continuously in all countries. The pattern of improvement was similar across age groups and by subtype. The largest improvements in survival were seen in Denmark, while improvements were comparatively smaller in Finland. In the most recent period, age-standardised estimates of 5-year relative survival ranged from 13% to 26% and the 5-year crude probability of death due to lung cancer ranged from 73% to 85%. Across all Nordic countries, survival decreased with age, and was lower in men and for small-cell carcinoma. CONCLUSION: Lung cancer survival has improved substantially since 1990, in both women and men and across age. The improvements were seen in all major subtypes. However, lung cancer survival remains poor, with three out of four patients dying from their lung cancer within five years of diagnosis.

Tumour diploidy and survival in breast cancer patients with BRCA2 mutations.

It is not well known to what extent carrying a BRCA2 mutation affects the survival of women with breast cancer and prognostic factors among BRCA2-positive women warrant investigation. Using a record linkage approach we compared the long-term survival in carriers and noncarriers of an inherited BRCA2 founder mutation (999del5), and sought to identify prognostic factors among the BRCA2 mutation-positive subset, including markers of genetic instability (aneuploidy) and mitotic activity (S-phase fraction). We established the genetic status of 2,967 Icelandic breast cancer patients (215 mutation carriers and 2,752 noncarriers) diagnosed from 1955 to 2004, representing 72 % of all cases diagnosed in the country during this period. Tumour ploidy and S-phase fraction were assessed on tumour cells by DNA flow cytometry. Prognostic factors were assessed blindly with respect to mutation status. Univariate and multivariate hazard ratios (HR) were estimated for breast cancer-specific survival by BRCA2 status, using Cox regression. After a median follow-up of 9.5 years, BRCA2 mutation carriers had a higher risk of death from breast cancer than noncarriers (HR 1.64, 95 % CI 1.24-2.16, p < 0.001). The risk increase was restricted to women with diploid tumours (HR 3.03, 95 % CI 1.91-4.79, p < 0.001). Among breast cancer patients with aneuploid tumours, survival of carriers was similar to that of noncarriers (HR 0.76, 95 % CI 0.41-1.41, p = 0.38). Increased tumour size and a positive nodal status predicted worse prognosis in all patients, whereas the highly correlated prognostic factors diploidy, low proliferative activity and a positive estrogen receptor status had reverse effects in mutation carriers and noncarriers. Breast cancer patients who carry the Icelandic founder BRCA2 mutation have inferior long-term survival than noncarriers, but the adverse prognosis is restricted to mutation carriers with diploid, slowly proliferating tumours.

Estrogen receptor-positive breast cancer and adverse outcome in BRCA2 mutation carriers and young non-carrier patients.

Estrogen receptor-positive (ER+) breast cancer generally confers a more favorable prognosis than ER-negative cancer, however, a different picture is emerging for BRCA2 mutation carriers and young patients. We used nationwide data from population-based registries to study prognostic effects in those two groups. Of all 2817 eligible women diagnosed with breast cancer in Iceland during 1980-2004, 85% had been tested for the Icelandic 999del5 BRCA2 (c.771_775delTCAAA) founder pathogenic variant. We compared breast cancer-specific survival, effects of ER status, other clinical parameters, and treatment, between three mutually exclusive groups: BRCA2-carriers, non-carriers diagnosed 40 years or younger, and older non-carriers. Prevalence of the BRCA2 mutation among tested patients <=40 years of age was 21.0%, but it was 5.4% among women diagnosed >40 years of age. For ER+ cancer, breast cancer-specific 15-year survival was 49.7%, 55.2%, and 74.7%, among BRCA2-carriers, young and older non-carriers, respectively, whereas for ER-negative cancer, survival was similar (64.0-69.3%) for all three groups. Neither BRCA2 carriers nor young non-carriers did tumor grade 3 predict worse survival than did tumor grade 1. The adverse outcome for the young cases cannot be explained by BRCA2 mutations, as carriers were excluded from the group. Those two clinically important patient groups need special attention with respect to treatment choices, in particular, if diagnosed with ER+ tumors. It is thus advisable to have knowledge of BRCA2 status when treatment decisions are made. Finally, it is important to understand the biological basis for the specific nature of ER+ tumors in young women and BRCA2 carriers.

Nordcan.R: a new tool for federated analysis and quality assurance of cancer registry data.

Aim of the article: We present our new GDPR-compliant federated analysis programme (nordcan.R), how it is used to compute statistics for the Nordic cancer statistics web platform NORDCAN, and demonstrate that it works also with non-Nordic data. Materials and methods: We chose R and Stata programming languages for writing nordcan.R. Additionally, the internationally used CRG Tools programme by International Agency for Research on Cancer (IARC/WHO) was employed. A formal assessment of (GDPR-compliant) anonymity of all nordcan.R outputs was performed. In order to demonstrate that nordcan.R also works with non-Nordic data, we used data from the Netherlands Cancer Registry. Results: nordcan.R, publicly available on Github, takes as input cancer and general population data and produces tables of statistics. Each NORDCAN participant runs nordcan.R locally and delivers its results to IARC for publication. According to our anonymity assessment the data can be shared with international organizations, including IARC. nordcan.R incidence results on Norwegian and Dutch data are highly similar to those produced by two other independent methods. Conclusion: nordcan.R produces accurate cancer statistics where all personal and sensitive data are kept within each cancer registry. In the age of strict data protection policies, we have shown that international collaboration in cancer registry research and statistics reporting is achievable with the federated analysis approach. Undertakings similar to NORDCAN should consider using nordcan.R.

Were cancer patients worse off than the general population during the COVID-19 pandemic? A population-based study from Norway, Denmark and Iceland during the pre-vaccination era.

Background: In a population-based setting, we investigated the risks of testing positive for SARS-CoV-2 and developing severe COVID-19 outcomes among cancer patients compared with the general population. Methods: In nationwide cohorts, we identified all individuals in Norway, Denmark and Iceland who tested positive for SARS-CoV-2 or had a severe COVID-19 outcome (hospitalisation, intensive care, and death) from March until December 2020, using data from national health registries. We estimated standardised incidence ratios (SIRs) with 95% confidence intervals (CIs) comparing cancer patients with the general population. Findings: During the first wave of the pandemic, cancer patients in Norway and Denmark had higher risks of testing SARS-CoV-2 positive compared to the general population. Throughout 2020, recently treated cancer patients were more likely to test SARS-CoV-2 positive. In Iceland, cancer patients experienced no increased risk of testing positive. The risk of COVID-19-related hospitalisation was higher among cancer patients diagnosed within one year of hospitalisation (Norway: SIR = 2.43, 95% CI 1.89-3.09; Denmark: 2.23, 1.96-2.54) and within five years (Norway: 1.58, 1.35-1.83; Denmark: 1.54, 1.42-1.66). Risks were higher in recently treated cancer patients and in those diagnosed with haematologic malignancies, colorectal or lung cancer. Risks of COVID-19-related intensive care and death were higher among cancer patients. Interpretation: Cancer patients were at increased risk of testing positive for SARS-CoV-2 during the first pandemic wave when testing availability was limited, while relative risks of severe COVID-19 outcomes remained increased in cancer patients throughout 2020. Recent cancer treatment and haematologic malignancy were the strongest risk factors. Funding: Nordic Cancer Union.

Association of symptoms of colon cancer patients with tumor location and TNM tumor stage.

OBJECTIVE: Colon cancer is the second most common cause of cancer death in Iceland and accounts for 8% of malignancies. We related information on symptoms of colon cancer patients with information on tumor location and pTNM-stage. MATERIAL AND METHODS: The study is retrospective and population-based. Information on all patients diagnosed with colon cancer in Iceland in 1995-2004 was obtained. Information on symptoms of patients and blood hemoglobin was collected from patients' files. The pathological parameters were derived from a previously performed study. RESULTS: A total of 768 patients (422 males, 346 females) participated in this study. Median age was 73 years. Nearly 60% had anemia at the time of diagnosis, 53% had visible blood in stools, and 65% had changes in bowel habits. Around 84% had visible blood in stools and/or anemia. Of those with right-sided tumors, 75% had anemia and were more likely to be diagnosed incidentally (40%) than those with left-sided tumors (20%). Left-sided tumors were associated with blood in stools (68% compared to 41%, p < 0.05) and changes in bowel habits (74% compared to 57%, p < 0.05). Multivariate analysis indicated that blood in stools was strongly associated with a lower TNM-stage (OR = 0.75, p < 0.05). Anemia was strongly associated with a higher TNM-stage (OR = 1.84, p < 0.05). CONCLUSION: Right-sided tumors were associated with anemia and incidental diagnosis; left-sided tumors were associated with visible blood in stools and changes in bowel habits. Visible blood in stools was significantly associated with lower TNM-stage, whereas abdominal pain, general and acute symptoms were associated with higher TNM-stage.

Cytogenetic polyclonality of breast carcinomas: association with clinico-pathological characteristics and outcome.

Routinely used prognostic factors fail to predict clinical outcome in a significant proportion of breast cancer patients, implying that they can not detect some important biological characteristics. Chromosomal changes have been described in breast carcinomas for many years but their significance is not clear. We compared chromosomal changes with clinico-pathological characteristics and clinical outcome in 203 breast cancer patients with a follow-up of 9-18 years. Combining data from classical cytogenetics and flow cytometry revealed chromosomal abnormalities in 142 cases (70%). Of these, 51 (35.9%) contained two or more cytogenetically abnormal clones. Polyclonality was significantly associated with poor breast-cancer-specific survival (P = 0.03) within 5 years, independent of tumor size, lymph node metastases, and hormone receptors. Specific changes were similar to those previously described, but a new finding was a significant association between del 3p12p21 and poor survival. Polyclonality was significantly associated with TP53-mutations but not with a germline BRCA2 mutation. Less than one third of the polyclonal samples were identified by flow cytometry alone. Cytogenetic changes were detected in 17 out of 114 samples from non-tumorous tissue (15%), two of them identical with a clone in the corresponding tumor. Several samples contained clearly unrelated clones within the tumor and outside, implying either multifocal origin or early divergence. In conclusion, the common deletion on Chromosome 3p12p21 was associated with poor clinical outcome. Chromosomal polyclonality is common in breast carcinomas and predicts poor survival. Polyclonality was poorly detected by one-sample flow cytometry. Multiple sampling might improve the detection rate.