Danish Cancer Registry Research Articles

Colorectal cancer screening participation among citizens not recommended to be screened: a cohort study

BackgroundGuidelines on colorectal cancer (CRC) screening recommend screening of average-risk adults only. In addition, screening of individuals with active inflammatory bowel disease (IBD) might result in too many false-positive cases. However, the organisers of CRC screening programmes are often uninformed of whom to exclude due to an elevated CRC risk or active IBD. It is therefore unknown how often high-risk individuals (i.e. individuals with a previous diagnosis of CRC or polyps associated with hereditary CRC syndromes and certain patient groups with a diagnosis of inflammatory bowel disease (IBD) or multiple polyps) and individuals with active IBD participate in CRC screening following invitation.Materials and methodsWe used data from the first two years of the Danish CRC screening programme (2014–2015). Information on invitations, participations and FIT test results were obtained from the national screening database, while information on previous CRC, hereditary CRC syndromes, IBD or multiple polyps diagnoses were obtained from the Danish Cancer Registry and the Danish Patient Register. Screening participation rates and FIT-positive rates were calculated and compared for high-risk invitees, invitees having IBD and an average risk group of remaining invitees not diagnosed with colorectal polyps in 10 years preceding the invitation.ResultsWhen invited to CRC screening, 28–48% of high-risk residents (N: 29; 316; 5584) and 55% of residents with IBD (N: 2217; 6927) chose to participate. The participation rate was significantly higher (67%) among residents without previous colorectal disease, i.e. the average risk group (N = 585,624). In this average group 6.7% of the participants had a positive FIT test. The proportion of positive FIT results was higher among all disease groups (7.7–14.8%), though not statistically significant for participants with prior CRC diagnosis and participants with high-risk IBD.ConclusionWhen high-risk residents and residents with IBD receive an invitation to CRC screening, many participate despite being recommended not to. The screening program was not intended for these groups and further research is needed as several of these groups have a higher rate of positive screening result than the average risk population.

Diagnostic Age, Age at Death and Stage Migration in Men Dying with or from Prostate Cancer in Denmark.

The impact of changes in diagnostic activity and treatment options on prostate cancer epidemiology remains a subject of debate. Newly published long-term survival outcomes may not represent contemporary patients and new perspectives are in demand. All men dying in Denmark with prostate cancer diagnosis during a 10-year period were analyzed to address the stage migration of and time lived with prostate cancer diagnosis. All male deaths in Denmark between 2007 and 2016 (n = 261,657) were obtained and crosslinked with The Danish Prostate Cancer Registry (DaPCaR) and the Danish Cancer Registry. Correlation in diagnostic age and stage (localized, locally advanced, metastatic), age at death and cause of death were investigated by Kruskal-Wallis test and linear regression in 15,692 men diagnosed with prostate cancer. Prostate cancer mortality remained stable during the study period. Among the men who died of prostate cancer, 65% had locally advanced or metastatic disease at diagnosis. Age at diagnosis declined in men diagnosed with localized disease and remained constant in men with locally advanced or metastatic disease. Age at death increased in all men. Despite increased efforts to detect prostate cancer early, two-thirds of men who die from prostate cancer still have advanced prostate cancer at the time of diagnosis. Our data show increased life-expectancy in men diagnosed with prostate cancer, however, this benefit must be weighed against increased time of living with the disease and overdiagnosis. The intensified treatment of elderly men and men with advanced disease may be the key to lower prostate cancer mortality.

Increased use of diagnostic CT imaging increases the detection of stage IA lung cancer: pathways and patient characteristics

BackgroundAt Silkeborg Regional Hospital, Denmark, the number of stage IA lung cancer increased after implementation of increased use of CT investigations and a corresponding reduction in chest X-ray. The aim of the present study was to understand the changes in referral pathways, patient characteristics and imaging procedures behind the observed increase in early-stage lung cancer.MethodsThe referral and imaging pathways for all patients diagnosed with lung cancer in 2013–2018 were described based on manually curated information from the electronic health care systems and staging information from the Danish Lung Cancer Registry. We compared the clinical characteristics of patients diagnosed in 2013–2015 and in 2016–2018 after implementation of a change in the use of low dose CT scan (LDCT). For patients diagnosed in 2016–2018, stage IA lung cancer were compared to higher stages using univariable logistic regression analysis.ResultsFive hundred and forty-seven patients were diagnosed with lung cancer in 2013–2018. Stage IA constituted 13.8% (34/247) in 2013–2015, and 28.3% (85/300) in 2016–2018. Stage IA patients in 2016–2018 were characterised by more comorbidity, fewer packyears and tended to be older than patients with higher stages. In 2016–2018, the largest proportion of stage IA patients (55%) came from within-hospital referrals. The majority of these lung cancers were detected due to imaging procedures with other indications than suspicion of lung cancer.The proportion of stage IA increased from 12% (12/99) to 36% (47/129) (p < 0.001) for hospital referrals and from 17% (22/129) to 23% (38/165) for GP referrals (p = 0.21). The imaging procedures contributing to the increase in stage IA was contrast enhanced CT (22%¸11/51), LDCT (35%; 18/51) and X-ray followed by LDCT (25%; 13/51).ConclusionThe increased access to LDCT for patients referred from general practice and the increased hospital requested CT activity resulted in an increase in the number of stage IA lung cancers. Incidental findings on imaging performed for diagnostic purposes unrelated to suspicion of lung cancer contributed a large proportion of the increase.

Base of tongue/tonsillar and laryngeal cancer in Denmark 1994–2018: Temporal trends in incidence according to education and age

ObjectivesBase-of-tongue (BOT)/tonsillar cancer incidence is rising, primarily due to human papillomavirus; meanwhile, rates of the mainly smoking-associated laryngeal cancer is declining. Little is known about whether these trends are seen in all socioeconomic levels and age-groups. We describe incidence trends of BOT/tonsillar and laryngeal cancer in Denmark 1994–2018 by educational level and age. MethodsBOT/tonsillar and laryngeal cancer cases diagnosed 1994–2018 were identified from the Danish Cancer Registry. We obtained individual-level educational information from nationwide registries. We estimated age-standardized incidence rates of BOT/tonsillar and laryngeal cancer according to sex, education and age. Temporal incidence trends were evaluated by the average annual percentage change (AAPC) with corresponding 95% confidence intervals (CIs) using linear and Poisson regression models for age-standardized incidence rates. ResultsWe identified 4245 individuals with BOT/tonsillar cancer and 6123 with laryngeal cancer. BOT/tonsillar cancer incidence increased among men with short (AAPC:3.4, 95% CI 2.1;4.6) and long (AAPC:5.1, 95% CI 3.2;7.1) education, and all age-groups, while decreased from 2012 among men with medium education (AAPC:-4.3, 95 %CI −7.6;-1.0). Laryngeal cancer incidence decreased from 2007 in men with medium (AAPC:-4.7, 95% CI −6.7;-2.7) and long (AAPC:-2.4, 95% CI −3.4;-1.4) education, and all age-groups, whereas increased in men with short education (AAPC:1.0, 95% CI 0.2;1.8). Similar trends were seen among women. ConclusionsOver the last 25 years, BOT/tonsillar cancer incidence in Denmark has generally increased in all age-groups and educational levels. In contrast, social inequality was seen in laryngeal cancer trends as incidence decreased in individuals with medium and long education, while incidence increased in individuals with short education.

Residential road traffic and railway noise and risk of childhood cancer: A nationwide register-based case-control study in Denmark

BackgroundThe aetiology of most childhood cancers remains poorly understood. We conducted a nationwide register-based case-control study to assess the association between residential road traffic and railway noise exposure and risk of childhood cancers. MethodsWe identified all cases of first cancers diagnosed in children aged 0–19 years in 1985–2013 from the Danish Cancer Registry (N = 3962) and sampled four individually matched (by sex and date of birth) controls per case (N = 14,790) using the Central Population Register. We estimated time-weighted exposure averages of residential road traffic and railway noise at the most (Lden max) and least (Lden min) exposed façades from birth to index-date (for additional analysis: in utero period) based on the individual address history for the respective time windows. We fitted conditional logistic regression models to estimate odds ratios (OR) and their 95% confidence intervals (CI). ResultsORs varied by noise estimate and cancer type, with generally wide CIs mostly including 1.00. We found a tendency of higher ORs with increasing railway and road traffic noise for Hodgkin lymphoma (ORs for railway and road Lden min were 1.63 (95% CI 1.00; 2.66) and 1.14 (95% CI 0.87; 1.48) per 10 dB), as well as a tendency of higher ORs with increasing railway noise for non-Hodgkin lymphoma. For embryonal CNS tumours and astrocytoma and other glioma we observed also some weak suggestions of a positive association. Analysing exposure to traffic noise in utero revealed similar patterns to those of the main analyses. ConclusionsThis nationwide study with minimal risk of bias suggests no strong associations between traffic noise and risk of most childhood cancers. We found however some suggestive evidence for a positive association with Hodgkin lymphoma, non-Hodgkin lymphoma and some CNS tumours. Further research is warranted to confirm these associations in other populations and elucidate the underlying biological mechanisms.

Effects of early maternal cancer and fertility treatment on the risk of adverse birth outcomes

SummaryBackgroundEarly maternal cancer and fertility treatment each increase the risk for adverse birth outcomes, but the joint effect of these outcomes has not yet been reported. Thus, the aim was to assess the individual and joint effect of maternal cancer and fertility treatment on the risk for adverse birth outcomes.MethodsThis population-based cohort study included 5487 live-born singletons identified in the Danish Medical Birth Register (1994–2016) of mothers with previous cancer (<40 years) recorded in the Danish Cancer Registry (1955–2014). We randomly selected 80,262 live-born singletons of mothers with no cancer <40 years matched to mothers with cancer by birth year and month. We calculated odds ratios (ORs) for preterm birth, low birth weight (LBW) (<2500 g) and small for gestational age (SGA), mean differences in birth weight in grams, and additional cases of preterm birth (gestational age<259 days) per 100,000 person-years. Multiplicative and additive interaction of maternal cancer and fertility treatment was compared with outcomes of children conceived naturally to mothers with no maternal cancer (reference group).FindingsAmong 84,332 live-born singletons, increased ORs for preterm birth were observed among children born to mothers with previous cancer (1·48, 95% confidence interval [CI] 1·33–1.65) or after fertility treatment (1·43, 95% 1·28–1–61), with 22 additional cases of preterm birth among both group of children (95% CI 15–29; 95% CI 14–30). In the joint analyses, the OR for SGA for children born after fertility treatment to mothers with previous cancer was similar to that of the reference group (OR 1·02, 95% CI 0·72–1·44, P for interaction=0·52). Children with both exposures had increased ORs for LBW (1·86, 95% CI 1·17–2·96, P for interaction=0·06) and preterm birth (2·31, 955 CI 1·66–3·20, P for interaction = 0·56), with 61 additional cases of preterm birth (95% CI 27–95, P for interaction=0.26) over that of children in the reference group. The mean birth weight was also lower in children born to mothers with both exposures (-140 g, 95% CI -215; -65) (P for interaction=0.06) but decreased to -22 g (95% CI -76; 31) after adjustment for GA.InterpretationAlthough we did not find any statistically significant additive interaction between maternal cancer and fertility treatment, children born after fertility treatment of mothers with previous cancer were at increased risk for adverse birth outcomes. Thus, pregnant women with both exposures need close follow-up during pregnancy.FundingThe Danish Cancer Society and the Danish Childhood Cancer Foundation.

The impact of subdivisions of microscopically positive (R1) margins on patterns of relapse in stage III colorectal cancer - A retrospective cohort study.

Microscopically positive (R1) margins are associated with poorer outcomes in patients with colorectal cancer. However, the impact of subdivisions of R1 margins, be they to the primary tumour (R1 tumour) or to lymph node metastases (R1LNM), on patterns of relapse is unknown. Patients treated for stage III colorectal cancer from 01 January 2016 to 31 December 2019 in four specialist centres were identified from the Danish national cancer registry. Patients were stratified into three groups according to margin status (R0 vs. R1 tumour vs. R1LNM). The primary outcomes were local recurrence-free survival (LRFS), distant metastases-free survival (DMFS) and disease-specific survival (DSS). A total of 1,164 patients were included, with R1 margins found in 237 (20.4%). Irrespective of tumour location, R1 tumour and R1LNM margins were independent prognostic factors for systemic relapse (R1 tumour HR 1.84, CI: 1.17-2.88, p= 0.008; R1LNM HR 1.59, CI: 1.12-2.27, p= 0.009) and disease-related death (R1 tumour HR 2.08, CI: 1.12-3.85, p= 0.020; R1LNM HR 1.84, CI: 1.12-3.02, p= 0.016). Whereas R1 tumour margins were associated with poorer 3-year LRFS in both colon and rectum cancer, R1LNM margins only reduced LRFS in patients with rectal cancer. Patterns of relapse differed between R1 subdivisions, with R1 tumour margins more likely to affect multiple anatomical sites, with a predilection for extra-hepatic/pulmonary metastases. Subdivisions of R1 margins have a distinct impact on the oncological outcomes and patterns of disease relapse in patients with stage III colorectal cancer.

Cancer in twin pairs discordant for smoking: The Nordic Twin Study of Cancer.

The discordant twin pair study design is powerful to control for familial confounding. We employed this approach to investigate the associations of smoking with several cancers. The NorTwinCan study combines data from the Danish, Finnish, Norwegian and Swedish twin and cancer registries. Follow‐up started when smoking status was determined and ended at cancer diagnosis confirmed by information in the cancer registry, death or end of follow‐up. We classified the participants as never (n = 59 093), former (n = 21 168) or current (n = 47 314) smokers. We pooled data from twin pairs where one co‐twin was diagnosed with any of the following tobacco‐related cancers: esophagus, kidney, larynx, liver, oral cavity, pancreas, pharynx or urinary bladder, while their co‐twin had none of those. Lung cancer was included in further analysis. We used Cox regression allowing for pair‐specific baseline functions to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). For tobacco‐related cancer sites, we recorded 7379 cases during median 27 years of follow‐up. The analyses based on individual twins showed that former (HR 1.31, 95% CI: 1.17‐1.48) and current (HR 2.14 [1.95‐2.34]) smokers are at increased risk to develop one of cancers listed above, compared to never smokers. Among 109 monozygotic twin pairs discordant for cancer and smoking, the HR was 1.85 (95% CI: 1.15‐2.98) among current smokers and 1.69 (1.00‐2.87) among former smokers when compared to their never smoking co‐twin. Thus, associations of smoking with several cancers were replicated for discordant identical twin pairs. Analyses based on genetically informative data provide evidence consistent with smoking causing multiple cancers.

Medication-Associated Phthalate Exposure and Childhood Cancer Incidence.

Human phthalate exposure is widespread through contact with myriad consumer products. Exposure is particularly high through medications formulated with phthalates. Phthalates disrupt normal endocrine signaling and are associated with reproductive outcomes and incidence of some cancers. We measured associations between gestational and childhood medication-associated phthalate exposures and the incidence of childhood cancers. We identified all live births in Denmark between 1997 and 2017, including both children and birth mothers. Using drug ingredient data merged with the Danish National Prescription Registry, we measured phthalate exposure through filled prescriptions for mothers during pregnancy (gestational exposure) and for children from birth until age 19 years (childhood exposure). Incident childhood cancers were ascertained from the Danish Cancer Registry, and associations were estimated with Cox regression models. Among 1 278 685 children, there were 2027 childhood cancer cases diagnosed over 13.1 million person-years of follow-up. Childhood phthalate exposure was strongly associated with incidence of osteosarcoma (hazard ratio [HR] = 2.78, 95% confidence interval [CI] = 1.63 to 4.75). We also observed a positive association with incidence of lymphoma (HR = 2.07, 95% CI = 1.36 to 3.14), driven by associations with Hodgkin and non-Hodgkin lymphoma but not Burkitt lymphoma. Associations were apparent only for exposure to low-molecular phthalates, which have purportedly greater biological activity. Childhood phthalate exposure was associated with incidence of osteosarcoma and lymphoma before age 19 years. Lingering questions include which specific phthalate(s) are responsible for these associations, by what mechanisms they occur, and to what extent childhood cancer cases could be avoided by reducing or eliminating the phthalate content of medications and other consumer products.

Long-term residential exposure to air pollution and risk of testicular cancer in Denmark: A population-based case-control study.

The incidence rate risk of testicular cancer has increased over the last four decades, and most significant increase has been among Caucasian men in Nordic countries. Second-generation immigrant studies indicate a significant role of environmental exposure in testicular cancer. We conducted a nationwide register-based case-control study, including 6,390 testicular cancer cases registered in the Danish Cancer Registry between 1989 and 2014. Up to four age-matched controls for each case (n=18,997) were randomly selected from Civil Registration System. Ambient air pollution levels were estimated at addresses of cases and controls with a state-of-the-art air pollution modeling system. We mostly found ORs close to 1.00 and with 95% confidence intervals (CI) spanning 1.00. Exposure during the year preceding birth was associated with ORs for NO2 of 0.87 (95%CI: 0.77-0.97) per 10 µg/m3 and for organic carbon of 0.84 (95%CI: 0.72-0.98) per 1 µg/m3. Exposure during the first 10 years of life was associated with ORs for organic carbon of 0.79 (95%CI: 0.67-0.93) per 1 µg/m3, for O3 of 1.20 (95%CI: 1.07-1.34) per 10 µg/m3 and for secondary inorganic aerosols of 1.07 (95%CI: 1.00-1.15) per 1 µg/m3. Early-life exposure to NO2 and OC was associated with lower risk for testicular cancer whereas early-life exposure to O3 and SIA was associated with higher risk. We report both positive and negative associations between ambient air pollutants and risk of testicular, dependent on pollutant, exposure time window and age at diagnosis. This is the first study to investigate such associations.

Inflammation-scores as prognostic markers of overall survival in lung cancer: a register-based study of 6,210 Danish lung cancer patients

BackgroundInflammation-scores based on general inflammation markers are suggested as prognostic markers of overall survival (OS) in lung cancer. However, whether these inflammation-scores improves the prognostication performed by well-established prognostic markers is unsettled. In a large register-based lung cancer patient cohort, nine different inflammation-scores were compared, and their ability to optimize the prognostication of OS was evaluated.MethodsLung cancer patients diagnosed from 2009–2018 in The Central Denmark Region were identified in the Danish Lung Cancer Registry. Pre-treatment inflammation markers were extracted from the clinical laboratory information system. Prognostication of OS was evaluated by Cox proportional hazard models. Comparison of the inflammation-scores and their added value to established prognostic markers were assessed by Akaike's information criteria and Harrel's C-index.ResultsIn total, 5,320 patients with non-small cell lung cancer (NSCLC) and 890 patients with small cell lung cancer (SCLC) were identified. In NSCLC, the Aarhus composite biomarker score (ACBS), including albumin, C-reactive protein, neutrophil count, lymphocyte count and haemoglobin, and the neutrophil-lymphocyte-ratio (NLR) were superior. Furthermore, they improved the prognostication of OS significantly (p <0.0001) (ACBS: HR: 2.24 (95%CI: 1.97–2.54); NLR: HR: 1.58 (95%CI: 1.47 – 1.69)). In SCLC, three scores were equally superior and improved the prognostication of OS p < 0.0001): neutrophil–lymphocyte-ratio (HR:1.62 (95%CI: 1.38–1.90)), modified Glasgow Prognostic Score (mGPS) (HR:1.70 (95%CI: 1.55–1.86) and the Combined NLR and GPS (CNG) (HR:2.10 (95%CI: 1.77–2.49).ConclusionsThe ACBS was the optimal score in NSCLC, whereas neutrophil–lymphocyte-ratio, mGPS and CNG were equally superior in SCLC. Additionally, these inflammation-scores all optimised the prognostication of OS and added value to well-established prognostic markers.

Trends in incidence and survival from anal cancer and incidence of high-grade anal intraepithelial neoplasia in Denmark

ObjectiveThe aim of the current study was to assess temporal trends in incidence of anal squamous cell carcinomas (SCC) and high-grade anal intraepithelial lesions (AIN2/3), and estimate survival from anal cancer and factors related to 5-year mortality in Denmark. MethodsWe analyzed anal SCC and AIN2/3 cases in the period of 1998–2018 from the Danish Cancer Register and the Danish Registry of Pathology, respectively. Overall, period, gender, and histology specific age-standardized incidence rates, average annual percentage change (AAPC), and 5-year relative survival were estimated. Cox proportional hazards models were applied to evaluate the effect on 5-year mortality of period, age, gender, and stage of disease. ResultsAltogether 2580 anal cancers and 871 AIN2/3 were identified. The AIN2/3 incidence increased for women 1998–2007 (AAPC: 3.5% (95% CI −0.7, 8.0)) and then tended to decrease during 2008–2018(AAPC: −5.2% (95% CI −9.6, −0.6)). A similar pattern was observed for men, although at a lower incidence with the decrease starting later (2008–2012) and the trend not reaching statistical significance. The anal SCC incidence increased over the whole study period for both women and men (women AAPC: 4.0% (95% CI 3.2%, 4.9%) and men AAPC: 3.6% (95% CI 2.3%, 4.9%)). The relative survival improved over time (from 61% to 72%). Being older and male was associated with a higher risk of dying within 5 years. ConclusionsThere is a need to focus attention on anal cancer and its precursor lesions, as the cancer incidence continues to increase. Actions could include screening and gender-neutral HPV vaccination.

Updated fraction of cancer attributable to lifestyle and environmental factors in Denmark in 2018

Environmental exposures and avoidable risk factors account for a large proportion of cancer burden. Exposures and lifestyle vary over time and between populations, which calls for updated and population-specific quantification of how various avoidable risk factors influence cancer risk to plan and design rational and targeted prevention initiatives. The study considered 12 risk-factor groups categorized as class I carcinogens by IARC/WCRF. Exposure data was derived from national studies and surveys and were linked to cancer incidence in 2018 based on the nationwide Danish Cancer Registry. In 2018, 23,078 men and 21,196 women were diagnosed with cancer excluding non-melanoma skin cancer, in Denmark. Of these, 14,235 (32.2%) were estimated to be attributable to avoidable class I carcinogens. Tobacco smoking accounted for 14.6% of total cancers, followed by UV-radiation that accounted for 5.8%. Based on exposure data from 2008, one-third of the cancers in Denmark in 2018 are estimated to be caused by class I carcinogens with tobacco use being the main contributor followed by UV-radiation. Our results should be integrated with public health policies to effectively increase awareness and promote strategies to decrease risk factor exposures at population level.

Cancer Incidence and Risk of Multiple Cancers after Environmental Asbestos Exposure in Childhood-A Long-Term Register-Based Cohort Study.

Objectives: To examine the asbestos-associated cancer incidence and the risk of multiple cancers in former school children exposed to environmental asbestos in childhood. Methods: A cohort of 12,111 former school children, born 1940–1970, was established using 7th grade school records from four schools located at a distance of 100–750 m in the prevailing wind direction from a large asbestos-cement plant that operated from 1928 to 1984 in Aalborg, Denmark. Using the unique Danish personal identification number, we linked information on employments, relatives’ employments, date of cancer diagnosis, and type of cancer and vital status to data on cohortees extracted from the Supplementary Pension Fund Register (employment history), the Danish Cancer Registry, and the Danish Civil Registration System. We calculated standardized incidence rates (SIRs) for asbestos-associated cancers, all cancers, and multiple cancers using rates for a gender and five-year frequency-matched reference cohort. Results: The overall incidence of cancer was modestly increased for the school cohort (SIR 1.07, 95% confidence interval (CI) 1.02–1.12) compared with the reference cohort. This excess was driven primarily by a significantly increased SIR for malignant mesothelioma (SIR 8.77, 95% CI 6.38–12.05). Former school children who had combined childhood environmental and subsequent occupational exposure to asbestos had a significantly increased risk of lung cancer. Within this group, those with additional household exposure by a relative had a significantly increased SIR for cancer of the pharynx (SIR 4.24, 95% CI 1.59–11.29). We found no significant difference in the number of subjects diagnosed with multiple cancers between the two cohorts. Conclusions: Our study confirms the strong association between environmental asbestos exposure and malignant mesothelioma and suggests that environmental asbestos exposure in childhood may increase the overall cancer risk later in life.

Pretreatment Albumin-to-Alkaline Phosphatase Ratio Is a Prognostic Marker in Lung Cancer Patients: A Registry-Based Study of 7077 Lung Cancer Patients.

Simple SummarySince the albumin-to-alkaline phosphatase ratio (AAPR) has shown promising prognostic prediction in cancer patients, the prognostic value of the AAPR was evaluated in a large cohort of 7077 lung cancer patients. We combined patient data from the Danish Lung Cancer Registry and the clinical laboratory information system (LABKA) and showed that a low AAPR was independently associated with an inferior median overall survival in non-small cell lung cancer patients and small cell lung cancer patients. Furthermore, data indicated a level-dependent correlation between the AAPR and survival and that the AAPR added additional prognostic value to the already well-established prognostic markers in lung cancer. Therefore, if our findings are validated in the future, the AAPR should be incorporated as a factor in the general prognostication of lung cancer patients.The albumin-to-alkaline phosphatase ratio (AAPR) is a novel promising prognostic marker in cancer patients. However, the evidence for its significance in lung cancer is scarce. Therefore, we assessed the prognostic value of the AAPR in a large cohort of lung cancer patients. Data on lung cancer patients diagnosed from January 2009 to June 2018 were extracted from the Danish Lung Cancer Registry and combined with data on the pretreatment serum AAPR level extracted from the clinical laboratory information system (LABKA). AAPR tertiles were applied as cutoffs. Cox proportional hazard models assessed the prognostic value of the AAPR. In total, 5978 non-small cell lung cancer (NSCLC) patients and 1099 small cell lung cancer (SCLC) patients were included. Decreasing AAPR level was significantly associated with declining median overall survival (OS) in NSCLC patients (medium vs. low AAPR, adjusted HR = 0.73 (95% confidence interval (CI) 0.68–0.79); high vs. low AAPR, adjusted HR = 0.68 (95% CI 0.62–0.73)) and in SCLC patients (medium vs. low AAPR, adjusted HR = 0.62 (95% CI 0.52–0.74); high vs. low, adjusted HR = 0.59 (95% CI 0.50–0.70)). In conclusion, the AAPR was an independent prognostic factor in NSCLC and SCLC patients. The correlation seems to be level dependent, with reducing survival found to be associated with decreasing AAPR level.

The significance of subdivisions of microscopically positive (R1) margins in colorectal cancer: A retrospective study of a national cancer registry.

Microscopically positive (R1) margins are associated with poorer outcomes in patients with colorectal cancer. However, little is known of the differential impact of subdivisions of R1margins, be they to the primary tumour (R1tumour) or to lymph node metastases/tumour deposits (R1LNM). Patients treated for Stage III colorectal cancer from 1 January 2016 to 31 December 2019 were identified from the Danish national cancer registry. Patients were stratified into threegroups according to margin status (R0 vs. R1tumour vs. R1LNM). The primary outcome was overall survival. In all, 4186 patients were included, comprising 3012 patients with colon cancer and 1174 patients with rectal cancer. The R1 resection rates were 16.5% and 18.2% in patients with colon and rectum cancer, respectively. In colon cancers, 3-year overall survival was reduced in patients with R1LNM (65.7%, 95% CI 62.8-68.6) or R1tumour margins (51.8%, 95% CI 47.3-56.3) compared with R0 resections (80.8%, 95% CI 79.9-81.6, P<0.001). A similar impact on survival was seen in rectal cancers (R0, 84.2%, 95% CI 82.9-85.5; R1LNM, 72.2%, 95% CI 67.8-76.6; R1tumour, 56.6%, 95% CI 50.0-63.2, P<0.001). Margin status was independently prognostic of survival in both colon (R1tumour, hazard ratio 2.08, 95% CI 1.50-2.89, P<0.001; R1LNM, hazard ratio 1.48, 95% CI 1.11-1.97, P=0.008) and rectal cancers (R1tumour, hazard ratio 2.35, 95% CI 1.42-3.90, P<0.001; R1LNM, hazard ratio 1.54, 95% CI 0.95-2.48, P=0.077). R1 subdivisions have distinct impacts on survival in Stage III colorectal cancer. Further focused research in these patient subgroups is warranted.

Trends in survival of epithelial ovarian/tubal cancer by histology and socioeconomic status in Denmark 1996–2017

ObjectivesTo examine time trends in ovarian/tubal cancer relative survival, excess mortality, and all-cause mortality for different histological types and levels of socioeconomic position. MethodsWomen with ovarian/tubal cancer diagnosed 1996–2017 were identified in the Danish Cancer Registry (n = 11,755). Age-standardized 5-year relative survival over time was estimated by histology, socioeconomic status, and stage. Furthermore, 5-year excess mortality rate ratios (EMRR) according to calendar time for all categories of histology and socioeconomic status were calculated using a Poisson regression model. Finally, all-cause mortality by histology and socioeconomic status was estimated in multivariate Cox proportional hazards regression models. ResultsStatistically significant improvements in 5-year relative survival occurred for all histological types over time except mucinous tumors (5-year EMRR, localized: 0.92 (95% CI: 0.71–1.16); advanced: 0.96 (95% CI: 0.85–1.08). Increase in relative survival over time and corresponding decrease in excess mortality was observed for all categories of socioeconomic status except for women with localized disease in the lowest income group (5-year EMRR = 0.91 (95% CI:0.76–1.10)). The impact of histology and socioeconomic status on all-cause mortality depended on time since diagnosis. Among the socioeconomic factors, especially low educational level and living alone were associated with increased all-cause mortality, particularly in the first year after diagnosis. ConclusionsOvarian/tubal cancer survival generally increased over time across histological types and socioeconomic factors. However, the lack of improvement for mucinous tumors needs further research. Additionally, the results for women with low income and education shows that continued focus on social equality in survival is necessary.

Pre-Treatment C-Reactive Protein Predicts Survival in Small Cell Lung Cancer Patients

Improved prognostication of small cell lung cancer (SCLC) patients could strengthen the treatment strategy and, thereby, potentially improve the overall survival (OS) of these patients. C-reactive protein (CRP) has been proposed as a prognostic indicator of inferior survival, although so far, only based on data from smaller studies. Data on SCLC patients diagnosed from January 2009 to June 2018 were extracted from the Danish Lung Cancer Registry and the clinical laboratory information system. CRP measurements were divided at the clinical cut-off value of 8 mg/L or 75 nmol/L) and stratified into quartiles. Cox proportional hazards model assessed the prognostic value of the CRP level. C-statistics further evaluated the biomarker’s prognostic value. In total, 923 patients were included. A pre-treatment CRP level above the clinical cut-off significantly correlated to inferior OS (adjusted hazard ratio (HR) = 1.25 (95% confidence interval (CI): 1.08–1.46). When divided into quartiles, a level-dependent correlation was observed with only the highest quartiles significantly associated with OS (3rd quartile: adjusted HR = 1.26 (95% CI: 1.03–1.55) 4th quartile: adjusted HR = 1.44 (95% CI: 1.17–1.77)). Adding CRP level to already well-established prognostic factors improved the prognostication of SCLC patients. In conclusion, high pre-treatment CRP level is an independent prognostic factor in SCLC patients.

Thrombocytopenia Among Patients with Hematologic Malignancies and Solid Tumors: Risk and Prognosis

▪Introduction: Despite the large body of research in cancer and increasing numbers of cancer survivors, knowledge about the risks and prognoses related to thrombocytopenia in the clinical care setting is scarce. Such information is important to understanding the need and potential impact of platelet transfusion and emerging drug therapies for thrombocytopenia. In this study, we examined the risk of thrombocytopenia among patients with incident cancer. Further, we studied the extent to which thrombocytopenia was associated with adverse clinical outcomes.Methods: This population-based cohort study was conducted using data from the Danish Cancer Registry. All patients diagnosed with incident hematologic malignancies and solid tumors (age of ≥18 years) during 2015─2018 were identified. Data were linked with routine laboratory test results from the primary care and hospital settings, as recorded in the Danish Register of Laboratory Results for Research. Based on platelet count levels (x 10 9/L), thrombocytopenia was categorized as grade 0 (any count)<150; grade 1:<100; grade 2:<75; grade 3:<50; and grade 4: <25. We tabulated the prevalence of thrombocytopenia at study inclusion and calculated the cumulative incidence proportion (risk) of thrombocytopenia, accounting for the competing risk of death. Each patient with thrombocytopenia was matched up to 5 cancer patients without thrombocytopenia by age, sex, cancer type, cancer stage, and time from cancer diagnosis and index date. Cox proportional hazards regression analysis was used to compute hazard ratios (HRs) with 95% confidence intervals (CIs) of adverse clinical outcomes, including any bleeding leading to hospitalization, site-specific bleeding leading to hospitalization, transfusion (red blood cell, platelet, or fresh frozen plasma), and death. HRs were adjusted for Charlson Comorbidity Index scores and matching factors by design.Results: The analytic cohort comprised 11,785 patients with hematologic malignancies and 57,600 patients with solid tumors (median age=70 years). Any thrombocytopenia was observed during the 6 months preceding study inclusion among 18% of patients with hematologic malignancies (grades 1-2: 6% and grades 3-4: 5%) and 4% of patients with solid tumors (grades 1-2: 1% and grades 3-4: 0%). The 1-year and 4-year risks of new-onset thrombocytopenia were 30% and 40% for hematologic malignancies and 21% and 28% for solid tumors, respectively (Figure 1). Among patients who initiated chemotherapy following their cancer diagnosis (n=33,165), the 1-year and 4-year risks of thrombocytopenia were 50% and 62% for hematologic malignancies and 39% and 49% for solid tumors, respectively (Figure 2). Patients with grade 4 thrombocytopenia had higher rates of any bleeding leading to hospitalization than patients without thrombocytopenia [hematologic malignancies: HR=2.31 (95% CI: 1.43-3.73) and solid tumors: HR=4.52 (95% CI: 2.00-10.24)], while grades 1-3 thrombocytopenia did not confer a significantly increased rate of hospitalization for bleeding (Table 1). All grades of thrombocytopenia were associated with an increased rate of transfusion [overall for hematologic malignancies: HR=2.06 (95% CI: 1.91-2.23), and overall for solid tumors: HR=2.13 (95% CI: 1.83-2.48)] and with death [overall for hematologic malignancies: HR=2.01 (95% CI: 1.84-2.20), and overall for solid tumors: HR=1.44 (95% CI: 1.39-1.49)]. These associations increased in magnitude with decreasing platelet count levels.Conclusions: The risk of thrombocytopenia was substantial following a diagnosis of incident hematologic malignancy and solid tumors, with higher risks among patients who initiated chemotherapy. While only severe thrombocytopenia was a predictor of any hospitalization for bleeding, all grades of thrombocytopenia were associated with increased rates of transfusion and death. Our findings support the need for regular assessment of platelet count levels to identify cancer patients at risk of serious clinical outcomes. [Display omitted] DisclosuresClouser: Amgen: Current Employment, Other: This work is related to Chemotherapy Induced Thrombocytopenia as a disease state, in this essence it is not directly related to an Amgen product; CIT is an area of scientific interest to Amgen with Romiplostim under development for this potential indicati. Saad: Amgen: Current Employment, Current equity holder in publicly-traded company.

Trends in rectal cancer incidence, relative survival, and mortality in Denmark during 1978-2018.

Rectal cancer is common in developed countries, though incidence varies globally. We assessed time trends in incidence, relative survival and mortality in Denmark. Rectal cancer cases ( N = 50 461) diagnosed in 1978-2018 were identified in the Danish Cancer Registry. We calculated age-standardized incidence rates, overall and according to sex and age. Average annual percentage changes (AAPC) were estimated using Poisson regression. We estimated 5-year relative survival and evaluated the effect of age, calendar year of diagnosis, sex and stage of disease on mortality using the Cox proportional hazards model. The incidence of rectal cancer tended to decrease in all age groups and both sexes during 1978-1997, but increased since 1998, more in men (AAPC = 2.05%; 95% CI,1.80; 2.31) than in women (AAPC = 0.99%; 95% CI,0.68; 1.30). It increased in men until 79 years and in women up to 59 years. Mortality decreased over time when adjusting for age, stage and sex. Overall, men had the highest 5-year mortality after adjusting for age, calendar period and stage. Five-year relative survival improved (1978-2018) for all stages. Initially, the overall 5-year relative survival tended to be better for women, but in recent years, it has been similar in both sexes. Incidence of rectal cancer increased in the last two decades, most markedly in women 59 years and younger. Mortality decreased when adjusting for age and stage. Relative survival improved over time more for men than for women, so in recent years, it has been virtually identical in men and women.