Impact of Indoor Radon Exposure on Lung Cancer Incidence in Slovenia.

Indoor radon is an important risk factor for lung cancer, as 3-14% of lung cancer cases can be attributed to radon. The aim of our study was to estimate the impact of indoor radon exposure on lung cancer incidence over the last 40 years in Slovenia. We analyzed the distribution of lung cancer incidence across 212 municipalities and 6032 settlements in Slovenia. The standardized incidence ratios were smoothed with the Besag-York-Mollie model and fitted with the integrated nested Laplace approximation. A categorical explanatory variable, the risk of indoor radon exposure with low, moderate and high risk values, was added to the models. We also calculated the population attributable fraction. Between 2.8% and 6.5% of the lung cancer cases in Slovenia were attributable to indoor radon exposure, with values varying by time period. The relative risk of developing lung cancer was significantly higher among the residents of areas with a moderate and high risk of radon exposure. Indoor radon exposure is an important risk factor for lung cancer in Slovenia in areas with high natural radon radiation (especially in the southern and south-eastern parts of the country).

Estimating exposure to extremely low frequency magnetic fields near high-voltage power lines and assessment of possible increased cancer risk among Slovenian children and adolescents.

BACKGROUND: Some previous research showed that average daily exposure to extremely low frequency (ELF) magnetic fields (MF) of more than 0.3 or 0.4 µT could potentially increase risk of childhood leukaemia. MATERIALS AND METHODS: To allow calculations of ELF MF around high voltage (HV) power lines (PL) for the whole Slovenia, a new three-dimensional method including precision terrain elevation data was developed to calculate the long-term average ELF MF. Data on population of Slovenian children and adolescents and on cancer patients with leukaemia's aged 0-19 years, brain tumours at age 0-29, and cancer in general at age 0-14 for a 12-year period 2005-2016 was obtained from the Slovenian Cancer Registry. RESULTS: According to the large-scale calculation for the whole country, only 0.5% of children and adolescents under the age of 19 in Slovenia lived in an area near HV PL with ELF MF density greater than 0.1 µT. The risk of cancer for children and adolescents living in areas with higher ELF MF was not significantly different from the risk of their peers. CONCLUSIONS: The new method enables relatively fast calculation of the value of low-frequency magnetic fields for arbitrary loads of the power distribution network, as the value of each source for arbitrary load is calculated by scaling the value for nominal load, which also enables significantly faster adjustment of calculated estimates in the power distribution network.

Impact of the COVID-19 epidemic on cancer burden and cancer care in Slovenia: a follow-up study.

BACKGROUND: In Slovenia, cancer care services were exempt from government decrees for COVID-19 containment. Nevertheless, cancer control can be impacted also by access to other health services and changes in health-seeking behaviour. In this follow up study, we explored changes in cancer burden and cancer care beyond the first months after the onset of the COVID-19 epidemic. MATERIALS AND METHODS: We analysed routinely collected data for the period January 2019 through July 2022 from three sources: (1) pathohistological and clinical practice cancer notifications from two major cancer centres in Ljubljana and Maribor (source: Slovenian Cancer Registry); (2) referrals issued for oncological services (source: e-referral system); and (3) outpatient appointments and diagnostic imaging performed (source: administrative data of the Institute of Oncology Ljubljana - IOL). Additionally, changes in certain clinical and demographic characteristics in patients diagnosed and treated during the epidemic were analysed using the Hospital-Based Cancer Registry of the IOL (period 2015-2021). RESULTS: After a drop in referrals to follow-up cancer appointments in April 2020, in June-August 2020, there was an increase in referrals, but it did not make-up for the drop in the first wave; the numbers in 2021 and 2022 were even lower than 2020. Referrals to first cancer care appointments and genetic testing and counselling increased in 2021 compared to 2019 and in 2022 increased further by more than a quarter. First and follow-up outpatient appointments and cancer diagnostic imaging at the IOL dropped after the onset of the epidemic in March 2020 but were as high as expected according to 2019 baseline already in 2021. Some deficits remain for follow-up outpatients' appointments in surgical and radiotherapy departments. There were more CT, MRI and PET scans performed during the COVID-19 period than before. New cancer diagnoses dropped in all observed years 2020, 2021 and until July 2022 by 6%, 3% and 8%, respectively, varying substantially by cancer type. The largest drop was seen in the 50-64 age group (almost 14% in 2020 and 16% in 2021), while for patients older than 80 years, the numbers were above expected according to the 2015-2019 average (4% in 2020, 8% in 2021). CONCLUSIONS: Our results show a varying effect of COVID-19 epidemic in Slovenia for different types of cancers and at different stages on the patient care pathway - it is probably a mixture of changes in health-seeking behaviour and systemic changes due to modifications in healthcare organisation on account of COVID-19. A general drop in new cancer cases reflects disruptions in the pre-diagnostic phase and could have profound long-term consequences on cancer burden indicators.

Prognostic factors and outcomes in women with breast cancer in Slovenia in relation to step-wise implementation of organized screening.

INTRODUCTION: The aim of organized breast cancer screening is early detection and reduction in mortality. Organized screening should promote equal access and reduce socio-economic inequalities. In Slovenia, organized breast cancer screening achieved complete coverage in 11-years' time. We explored whether step-wise implementation reflects in prognostic factors (earlier diagnosis and treatment) and survival of breast cancer patients in our population. METHODS: Using population-based cancer registry and screening registry data on breast cancer cases from 2008-2018, we compared stage distribution and mean time to surgical treatment in (A) women who underwent at least one mammography in the organized screening programme, women who received at least one invitation but did not undergo mammography and women who did not receive any screening invitation, and in (B) women who were invited to organized screening and those who were not. We also compared net survival by stage in different groups of women according to their screening programme status. RESULTS: Women who underwent at least one mammography in organized screening had lower disease stage at diagnosis. Time-to-treatment analysis showed mean time to surgery was shortest in women not included in organized screening (all stages = 36.0 days vs. 40.3 days in women included in organized screening). This could be due to quality assurance protocols with an obligatory multidisciplinary approach within the organized screening vs. standard treatment pathways which can vary in different (smaller) hospitals. Higher standard of care in screening is reflected in better survival in women included in organized screening (5-years net survival for regional stage: at least one mammography in the screening programme- 96%; invitation, but no mammography- 87.4%; no invitation or mammography in the screening programme- 82.6%). CONCLUSION: Our study, which is one of the first in central European countries, shows that introduction of organized screening has temporary effects on population cancer burden indicators already during roll-out period, which should therefore be as short as possible.

Overall and stage-specific survival of patients with screen-detected colorectal cancer in European countries: A population-based study in 9 countries.

Background: An increasing proportion of colorectal cancers (CRCs) are detected through screening due to the availability of organised population-based programmes. We aimed to analyse survival probabilities of patients with screen-detected CRC in European countries. Methods: Data from CRC patients were obtained from 16 population-based cancer registries in nine European countries. We included patients with cancer diagnosed from the year organised CRC screening programmes were introduced until the most recent year with available data at the time of analysis, whose ages at diagnosis fell into the age groups targeted by screening. Patients were followed up with regards to vital status until 2016-2020 across the various countries. Overall and CRC-specific survival were analysed by mode of detection and stage at diagnosis for all countries combined and for each country separately using the Kaplan-Meier method. Findings: We included data from 228 134 patients, of whom 134 597 (aged 60-69 years at diagnosis targeted by screening in all countries) were considered in analyses for all countries combined. 22·3% (38 080/134 597) of patients had cancer detected through screening. Most screen-detected cancers were found at stages I-II (65·6% [12 772/19 469 included in stage-specific analyses]), while the majority of non-screen-detected cancers were found at stages III-IV (56·4% [31 882/56 543 included in stage-specific analyses]). Five-year overall and CRC-specific survival rates for patients with screen-detected cancer were 83·4% (95% CI 82·9-83·9) and 89·2% (88·8-89·7), respectively; for patients with non-screen-detected cancer, they were much lower (57·5% [57·2-57·8] and 65·7% [65·4-66·1], respectively). The favourable survival of patients with screen-detected cancer was also seen within each stage - five-year overall survival rates for patients with screen-detected stage I, II, III, and IV cancers were 92.4% (95% CI 91·6-93·1), 87·9% (86·6-89·1), 80·7% (79·3-82·0), and 32·3 (29·4-35·2), respectively. These patterns were also consistently seen for each individual country. Interpretation: Patients with cancer diagnosed at screening have a very favourable prognosis. In the rare case of detection of advanced stage cancer, survival probabilities are still much higher than those commonly reported for all patients regardless of mode of detection. Although these results cannot be taken to quantify screening effects, they provide useful and encouraging information for patients with screen-detected CRC and their physicians. Funding: This study was supported in part by grants from the German Federal Ministry of Education and Research and the German Cancer Aid.

Proportion and stage distribution of screen-detected and non-screen-detected colorectal cancer in nine European countries: an international, population-based study.

BACKGROUND: The effects of recently implemented colorectal cancer screening programmes in Europe on colorectal cancer mortality will take several years to be fully known. We aimed to analyse the characteristics and parameters of screening programmes, proportions of colorectal cancers detected through screening, and stage distribution in screen-detected and non-screen-detected colorectal cancers to provide a timely assessment of the potential effects of screening programmes in several European countries. METHODS: We conducted this population-based study in nine European countries for which data on mode of detection were available (Belgium, Denmark, England, France, Italy, Ireland, the Netherlands, Slovenia, and Spain). Data from 16 population-based cancer registries were included. Patients were included if they were diagnosed with colorectal cancer from the year that organised colorectal cancer screening programmes were implemented in each country until the latest year with available data at the time of analysis, and if their age at diagnosis fell within the age groups targeted by the programmes. Data collected included sex, age at diagnosis, date of diagnosis, topography, morphology, clinical and pathological TNM information based on the edition in place at time of diagnosis, and mode of detection (ie, screen detected or non-screen detected). If stage information was not available, patients were not included in stage-specific analyses. The primary outcome was proportion and stage distribution of screen-detected versus non-screen detected colorectal cancers. FINDINGS: 228 667 colorectal cancer cases were included in the analyses. Proportions of screen-detected cancers varied widely across countries and regions. The highest proportions (40-60%) were found in Slovenia and the Basque Country in Spain, where FIT-based programmes were fully rolled out, and participation rates were higher than 50%. A similar proportion of screen-detected cancers was also found for the Netherlands in 2015, where participation was over 70%, even though the programme had not yet been fully rolled out to all age groups. In most other countries and regions, proportions of screen-detected cancers were below 30%. Compared with non-screen-detected cancers, screen-detected cancers were much more often found in the distal colon (range 34·5-51·1% screen detected vs 26·4-35·7% non-screen detected) and less often in the proximal colon (19·5-29·9% screen detected vs 24·9-32·8% non-screen detected) p≤0·02 for each country, more often at stage I (35·7-52·7% screen detected vs 13·2-24·9% non-screen detected), and less often at stage IV (5·8-12·5% screen detected vs 22·5-31·9% non-screen detected) p<0·0001 for each country. INTERPRETATION: The proportion of colorectal cancer cases detected by screening varied widely between countries. However, in all countries, screen-detected cancers had a more favourable stage distribution than cancers detected otherwise. There is still much need and scope for improving early detection of cancer across all segments of the colorectum, and particularly in the proximal colon and rectum. FUNDING: Deutsche Krebshilfe.

Cancer Patients' Survival According to Socioeconomic Environment in a High-Income Country with Universal Health Coverage.

Despite having an established systematic approach to population survival estimation in Slovenia, the influence of socioeconomic environment on cancer patients' survival has not yet been evaluated. Thus, the main aim of our study was to quantify the potential impact of socioeconomic environment on cancer patients' survival in our population in the 21st century. The net survival was calculated and stratified into quintiles of Slovenian version of the European Deprivation Index for all adult cancer patients diagnosed between 2004 and 2018 using the national cancer registry data. After accounting for basic demographic variables (age and gender), differences in stage at diagnosis, as well as the impact of the cancer treatment improvements over time, we found that cancer patients in Slovenia with lower socioeconomic status experience worse survival and have higher mortality. In particular, the odds of dying from oral, stomach, colorectal, liver, pancreatic, lung, breast, ovarian, corpus uteri, prostate, and bladder cancers, as well as for melanoma, leukemia, and non-Hodgkin lymphoma, are significantly higher in the socioeconomically most deprived group of patients compared to the most affluent group. The inequalities in cancer burden we found could help decision-makers to better understand the magnitude of this problem.

Trends in population-based cancer survival in Slovenia.

BACKGROUND: The aim of our study was to describe the survival of Slovenian cancer patients diagnosed in the last twenty years. An insight is given into the improvement made in different cancer types, population groups and prognostic factors. MATERIALS AND METHODS: The principal data source was the population-based Slovenian Cancer Registry. The survival analysis included patients diagnosed with cancer in twenty years period from 1997 to 2016, which has been divided into four consecutive five-year periods. In addition, the analysis was stratified by cancer type, gender, age and stage. The survival was estimated using net survival calculated by the Pohar-Perme method and the complete approach has been applied. RESULTS: The survival of Slovenian cancer patients has been increasing over time. During the 20 years observed, five-year net survival increased by 11 percentage points. Significantly higher growth was observed in men. Age and stage at diagnosis are still crucial for the survival of cancer patients. Five-year net survival is lowest in those over 75 years of age at diagnosis but has also improved by seven percentage points over the past 20 years. The five-year net survival of patients in the localized stage increased by ten percentage points over the 20 years under observation. Survival of patients in the distant stage has not been improving. In both sexes, survival for melanoma, colorectal and lung cancers have increased significantly over the last 20 years. Progress has also been made in the two most common gender specific cancers: breast cancer in women and prostate cancer in men. Still, the significant progress in prostate cancer is probably mostly due to lead-time bias as during the study period, Slovenia used indiscriminate PSA testing, which probably artificially prolonged survival. CONCLUSIONS: The survival of Slovenian cancer patients has been increasing over time, which gives us a basis and an incentive for future improvements. To monitor the effectiveness of managing the cancer epidemic, the cancer burden needs to be monitored also in the future, using quality data and scientifically justified methodological approaches. In this process a well organised population-based cancer registries should play a key role.

Screening Strategy Modification Based on Personalized Breast Cancer Risk Stratification and its Implementation in the National Guidelines - Pilot Study.

BACKGROUND: One of the most consistent models for estimating personalized breast cancer (BC) risk is the Tyrer-Cuzick algorithm that is incorporated into the International Breast Cancer Intervention Study (IBIS) software. Our main objective was to provide criteria for the classification of the Slovenian population, which has BC incidence below the European average, into risk groups, and to evaluate the integration of the criteria in Slovenian guidelines. Our main focus was on women age <50 with higher BC risk, since no organized BC screening is available for these women. METHODS: Slovenian age-specific BC risks were incorporated into IBIS software and threshold values of risk categories were determined. Risk categories were assigned according to the individual's ten-year risk for women aged 40 and older, and lifetime risk for women between 20 and 39. To test the software, we compared screening strategies with the use vs. no use of IBIS. RESULTS: Of the 197 women included in the study IBIS assigned 75.1% to the BC risk group, and the rest to the moderately increased risk. Without IBIS 80 women were offered mammographic and 33 ultrasound screening. In contrast, 28 instead of 80 would have been offered mammographic screening and there would have been no referrals for ultrasound if IBIS had been used. CONCLUSIONS: The Slovenian IBIS has been developed, tested and suggested for personalized breast cancer risk assessment. The implementation of the software with the consideration of Slovenian risk thresholds enables a more accurate and nationally unified assessment.

Impact of COVID-19 on cancer diagnosis and management in Slovenia - preliminary results.

Background The COVID-19 pandemic has disrupted the provision and use of healthcare services throughout the world. In Slovenia, an epidemic was officially declared between mid-March and mid-May 2020. Although all non-essential health care services were put on hold by government decree, oncological services were listed as an exception. Nevertheless, as cancer control depends also on other health services and additionally major changes in people's behaviour likely occurred, we aimed to analyse whether cancer diagnosis and management were affected during the COVID-19 epidemic in Slovenia. Methods We analysed routine data for the period November 2019 through May 2020 from three sources: (1) from the Slovenian Cancer Registry we analysed data on pathohistological and clinical practice cancer notifications from two major cancer centres in Ljubljana and Maribor; (2) from the e-referral system we analysed data on all referrals in Slovenia issued for oncological services, stratified by type of referral; and (3) from the administrative data of the Institute of Oncology Ljubljana we analysed data on outpatient visits by type as well as on diagnostic imaging performed. Results Compared to the November 2019 - February 2020 average, the decrease in April 2020 was about 43% and 29% for pathohistological and clinical cancer notifications; 33%, 46% and 85% for first, control and genetic counselling referrals; 19% (53%), 43% (72%) and 20% (21%) for first (and control) outpatient visits at the radiotherapy, surgery and medical oncology sectors at the Institute of Oncology Ljubljana, and 48%, 76%, and 42% for X-rays, mammograms and ultrasounds performed at the Institute, respectively. The number of CT and MRI scans performed was not affected. Conclusions Significant drops in first referrals for oncological services, first visits and imaging studies performed at the Institute, as well as cancer notifications in April 2020 point to a possibility of a delayed cancer diagnosis for some patients during the first surge of SARS-CoV-2 cases in Slovenia. The reasons for the delay cannot be ascertained with certainty and could be linked to health-seeking behaviour of the patients, the beliefs and practices of doctors and/ or the health system management during the epidemic. Drops in control referrals and control visits were expected and are most likely due to the Institute of Oncology Ljubljana postponing non-essential follow-ups through May 2020.

Socioeconomic inequalities in cancer incidence in Europe: a comprehensive review of population-based epidemiological studies.

Background Since the end of the previous century, there has not been a comprehensive review of European studies on socioeconomic inequality in cancer incidence. In view of recent advances in data source linkage and analytical methods, we aimed to update the knowledge base on associations between location-specific cancer incidence and individual or area-level measures of socio-economic status (SES) among European adults. Materials and methods We systematically searched three databases (PubMed, Scopus and Web of Science) for articles on cancer incidence and SES. Qualitative synthesis was performed on the 91 included English language studies, published between 2000 and 2019 in Europe, which focused on adults, relied on cancer registry data and reported on relative risk (RR) estimates. Results Adults with low SES have increased risk of head and neck, oesophagogastric, liver and gallbladder, pancreatic, lung, kidney, bladder, penile and cervical cancers (highest RRs for lung, head and neck, stomach and cervix). Conversely, high SES is linked with increased risk of thyroid, breast, prostate and skin cancers. Central nervous system and haematological cancers are not associated with SES. The positive gap in testicular cancer has narrowed, while colorectal cancer shows a varying pattern in different countries. Negative associations are generally stronger for men compared to women. Conclusions In Europe, cancers in almost all common locations are associated with SES and the inequalities can be explained to a varying degree by known life-style related factors, most notably smoking. Independent effects of many individual and area SES measures which capture different aspects of SES can also be observed.

Corrigendum to "Is IVF/ICSI an Independent Risk Factor for Spontaneous Preterm Birth in Singletons? A Population-Based Cohort Study".

[This corrects the article DOI: 10.1155/2018/7124362.].

Is IVF/ICSI [corrected] an Independent Risk Factor for Spontaneous Preterm Birth in Singletons? A Population-Based Cohort Study.

The aim of our study was to explore the risk factors for very preterm (gestation under 32 weeks) and moderate preterm birth (gestation weeks 32-36 6/7) in singleton pregnancies in a national retrospective cohort study. We also wanted to establish whether IVF/ICSI is an independent risk factor for preterm birth after adjusting for already known confounders. We used data for 267 718 singleton births from 2002-2015 from the National Perinatal Information System of Slovenia, containing data on woman, pregnancy, birth, the postpartum period, and the neonate for each mother-infant pair. Mode of conception, maternal age, education, BMI, parity, smoking, history of cervical excision procedure, history of hysteroscopic resection of uterine septum, presence of other congenital uterine malformations, bleeding in pregnancy, preeclampsia or HELLP and maternal heart, and pulmonary or renal illness were included in the analyses. Unadjusted OR for very preterm birth after IVF-ICSI [corrected] was 2.8 and for moderate preterm birth was 1.7. After adjusting for known confounders, the OR was still significantly elevated (1.6 and 1.3, respectively). Risk factors for very preterm birth with OR higher than 2.4 were history of cervical excision procedure, resection of uterine septum, operation or having other congenital uterine malformations, and bleeding in pregnancy. Risk factors for very preterm birth with OR between 1.4 and 2.1 were age >35 years, being underweight or obese, not having professional education, smoking, first birth, preeclampsia/HELLP, and IVF/ICSI. Risk factors for moderate preterm birth with OR higher than 2.4 were history of cold knife conization and other congenital uterine malformations. We found that even after adjustment, IVF/ICSI represents a single risk factor for early and late preterm birth even after adjustment with other risks such as maternal age, smoking, or a history of invasive procedures for either cervical intraepithelial neoplasia or infertility treatment.

Cold-knife conisation and large loop excision of transformation zone significantly increase the risk for spontaneous preterm birth: a population-based cohort study.

OBJECTIVES: Our aim was to explore the association between cold-knife conisation and large loop excision of transformation zone (LLETZ) with spontaneous preterm birth in a large 10-year national sample. We wanted to explore further the association of these procedures with preterm birth according to gestation. STUDY DESIGN: We conducted a population based retrospective cohort study, using data from national Medical Birth Registry. The study population consisted of all women giving birth to singletons in the period 2003-2012 in Slovenia, excluding all induced labors and elective cesarean sections before 37 weeks of gestation (N=192730). We compared the prevalence of spontaneous preterm births (before 28 weeks, before 32 weeks, before 34 weeks and before 37 weeks of gestation) in women with cold-knife conisation or LLETZ compared to women without history of conisation, calculating odds ratios (OR), adjusted for potential confounders. Chi-square test was used for descriptive analysis. Logistic regression analyses were performed to estimate crude odds ratio (OR) and adjusted odds ratio (aOR) and their 95% confidence intervals (95% CI) with two-sided probability (p) values. RESULTS: A total of 8420 (4.4%) women had a preterm birth before 37 weeks of gestation, 2250 (1.2%) before 34 weeks of gestation, 1333 (0.7%) before 32 weeks of gestation and 603 (0.3%) before 28 weeks of gestation. A total of 4580 (2.4%) women had some type of conisation in their medical history: 2083 (1.1%) had cold-knife conisation and 2498 (1.3%) had LLETZ. In women with history of cold-knife conisation, the adjusted OR for preterm birth before 37 weeks of gestation was 3.13 (95% CI; 2.74-3.57) and for preterm birth before 28 weeks of gestation 5.96 (95% CI; 4.3-8.3). In women with history of LLETZ, the adjusted OR was 1.95 (95% CI; 1.68-2.25) and 2.88 (95% CI; 1.87-4.43), respectively. CONCLUSIONS: Women with cervical excision procedure of any kind have significantly increased odds for preterm birth, especially for preterm birth before 28 weeks and before 32 weeks of gestation.