Rapid increases in cervical adenocarcinoma incidence have been observed in Western countries in recent decades. Postulated explanations include an increasing specificity of subtype-the capability to ...diagnose the disease, an inability of cytologic screening to reduce adenocarcinoma, and heterogeneity in cofactors related to persistent human papillomavirus infection. This study examines the possible contribution of these factors in relation with trends observed in Europe. Age-period-cohort models were fitted to cervical adenocarcinoma incidence trends in women ages <75 in 13 European countries. Age-adjusted adenocarcinoma incidence rates increased throughout Europe, the rate of increase ranging from around 0.5% per annum in Denmark, Sweden, and Switzerland to >/=3% in Finland, Slovakia, and Slovenia. The increases first affected generations born in the early 1930s through the mid-1940s, with risk invariably higher in women born in the mid-1960s relative to those born 20 years earlier. The magnitude of this risk ratio varied considerably from around 7 in Slovenia to almost unity in France. Declines in period-specific risk were observed in United Kingdom, Denmark, and Sweden, primarily among women ages >30. Whereas increasing specificity of subtype with time may be responsible for some of the increases in several countries, the changing distribution and prevalence of persistent infection with high-risk human papillomavirus types, alongside an inability to detect cervical adenocarcinoma within screening programs, would accord with the temporal profile observed in Europe. The homogeneity of trends in adenocarcinoma and squamous cell carcinoma in birth cohort is consistent with the notion that they share a similar etiology irrespective of the differential capability of screen detection. Screening may have had at least some impact in reducing cervical adenocarcinoma incidence in several countries during the 1990s.
The role of chemotherapy in the treatment of pancreatic cancer (PaC) has been well‐established, while radiation plays ambiguous roles. This international large‐scale population‐based study aimed to ...investigate the real‐world application of chemotherapy and radiotherapy for resected and unresected PaC in Europe and USA. Population‐based data from multiple European national cancer registries and the US Surveillance, Epidemiology and End Results (SEER)‐18 database during 2003–2014 were analyzed. Temporal trends and geographical variations in the application rates of chemotherapy and radiotherapy were quantified using age standardization. Associations of treatment with demographic and clinical characteristics were assessed using multivariable logistic regression. A total of 141,533 PaC patients were analyzed. From 2003–2005 to 2012–2014, chemotherapy administration rates increased in most countries and more strongly among resected patients, while radiation rates were generally low with a slight decline or no obvious trend. In 2012–2014, 12.5% (Estonia) to 61.7% (Belgium) of resected and 17.1% (Slovenia) to 56.9% (Belgium) of unresected patients received chemotherapy. Radiation was administered in 2.6% (Netherlands) to 32.6% (USA) of resected and 1.0% (USA) to 6.0% (Belgium) of unresected patients. Strong temporal and geographical variations were observed. Patterns and strengths of associations of treatment administration with various demographic and clinical factors differed substantially between resected and unresected cancers and varied greatly across countries. Conclusively, administration of chemotherapy but not radiotherapy for PaC increased during the last decade in Europe and USA. Treatment rates were low and the uptake strongly varied across countries, highlighting the need for standardization in PaC treatment to improve patient care.
What's new?
The use of combination chemotherapy after tumor resection is associated with improved overall survival in pancreatic cancer. Chemotherapy can be further used alongside radiotherapy, though the extent to which this approach is employed for pancreatic cancer is uncertain. In this international population‐based study of pancreas cancer cases diagnosed from 2003–2014, chemotherapy use was found to increase in most countries, most notably for resected pancreatic cancer. Meanwhile, radiotherapy use was low. Associations between treatment and clinicopathologic factors varied according to resection and country. The findings highlight a possible need for treatment standardization to improve care for pancreatic cancer patients.
The prognosis of pancreatic cancer (PaC) strongly varies across different stages and age groups, which has unfortunately not been well recorded in the literature. This international population-based ...study aimed to provide tumor-node-metastasis (TNM) stage- and age-specific survival estimates and trends in resected and overall (resected and unresected) PaC in the early twenty-first century.
Using data from the US Surveillance, Epidemiology, and End Results-18 Program and the national cancer registries of the Netherlands, Belgium, Norway, and Slovenia, short-term and long-term overall survival results stratified by TNM stage and age in resected and overall primary PaC, irrespective of being microscopically confirmed or not, in 2003-2014 were computed using the Kaplan-Meier method. The temporal survival trends over three predefined periods (2003-2005, 2006-2008, and 2009-2011) were further examined using the log-rank test.
In total, data for 125,183 patients were analyzed. Overall, age-stratified 3-year survival was 20-34% (< 60 years), 14-25% (60-69 years), and 9-13% (≥ 70 years) in stages I-II PaC; and 2-5% (< 60 years), 1-2% (60-69 years), and < 1-1% (≥ 70 years) in stages III-IV cancer. Patients who underwent operation had higher 3-year survival in each stage and age group (stages I-II: 23-39% (< 60 years), 16-31% (60-69 years), and 17-30% (≥ 70 years); stages III-IV: 5-19% (< 70 years) and 2-14% (≥ 70 years)). Perioperative survival also decreased with advancing stage and older age (stages I-II: 98-100% (< 60 years), 97-99% (60-69 years), and 94-99% (≥ 70 years); stages III-IV: 94-99% (< 70 years) and 81-96% (≥ 70 years)). Between 2003 and 2005 and 2009-2011, for overall PaC, both short-term and long-term survival improvements were observed in all countries except Belgium; for resected disease, short-term improvements were present only in the USA and Slovenia, but long-term improvements were observed in all countries except Slovenia, with stage-specific variations.
Our large international study provides TNM stage- and age-specific population-based survival in overall and resected PaC that will facilitate clinical counseling. While the survival expectations for patients with resected PaC are substantially higher than the widely available and known dismal survival predictions for overall patients, conclusions on the benefits of resection cannot be made from this observational study. Patients with advanced-stage disease and/or older age should undergo careful risk assessment before treatment. Limited but inspiring improvement in survival is observed.
Pancreatic cancer (PaC) remains extremely lethal worldwide even after resection. PaC resection rates are low, making prognostic studies in resected PaC difficult. This large international ...population-based study aimed at exploring factors associated with survival in patients with resected TNM stage I-II PaC receiving chemotherapy and at developing and internationally validating a survival-predicting model.
Data of stage I-II PaC patients resected and receiving chemotherapy in 2003-2014 were obtained from the national cancer registries of Belgium, the Netherlands, Slovenia, and Norway, and the US Surveillance, Epidemiology, and End Results (SEER)-18 Program. Multivariable Cox proportional hazards models were constructed to investigate the associations of patient and tumor characteristics with overall survival, and analysis was performed in each country respectively without pooling. Prognostic factors remaining after backward selection in SEER-18 were used to build a nomogram, which was subjected to bootstrap internal validation and external validation using the European datasets.
A total of 11,837 resected PaC patients were analyzed, with median survival time of 18-23 months and 3-year survival rates of 21-31%. In the main analysis, patient age, tumor T stage, N stage, and differentiation were associated with survival across most countries, with country-specific association patterns and strengths. However, tumor location was mostly not significantly associated with survival. Resection margin, hospital type, tumor size, positive and harvested lymph node number, lymph node ratio, and comorbidity number were associated with survival in certain countries where the information was available. A median survival time- and 1-, 2-, 3-, and 5-year survival probability-predictive nomogram incorporating the backward-selected variables in the main analysis was established. It fits each European national cohort similarly well. Calibration curves showed very good agreement between nomogram-prediction and actual observation. The concordance index of the nomogram (0.60) was significantly higher than that of the T and N stage-based model (0.56) for predicting survival.
In these large international population-based cohorts, patients with resected PaC receiving chemotherapy have distinct characteristics independently associated with survival, with country-specific patterns and strengths. A robust benchmark population-based survival-predicting model is established and internationally validated. Like previous models predicting survival in resected PaC, our nomogram performs modestly.
The 2003 European Council recommendation urging the Member States to introduce or scale up breast, cervical and colorectal cancer screening through an organized population‐based approach has had a ...remarkable impact. We argue that the recommendation needs to be updated for at least two sets of reasons. First, some of the current clinical guidelines include new tests or protocols that were not available at the time of the Council document. Some have already been adopted by organized screening programs, such as newly defined age ranges for mammography screening, Human Papillomavirus (HPV)‐based cervical cancer screening, fecal immunochemical test (FIT) and sigmoidoscopy for colorectal cancer screening. Second, the outcomes of randomized trials evaluating screening for lung and prostate cancer have been published recently and the balance between harms and benefits needs to be pragmatically assessed. In the European Union, research collaboration and networking to exchange and develop best practices should be regularly supported by the European Commission. Integration between primary and secondary preventive strategies through comprehensive approaches is necessary not only to maximize the reduction in cancer burden but also to control the rising trend of other noncommunicable diseases sharing the same risk factors.
Breast cancer survival is reportedly higher in the US than in Europe. The first worldwide study (CONCORD) found wide international differences in age‐standardized survival. The aim of this study is ...to explain these survival differences. Population‐based data on stage at diagnosis, diagnostic procedures, treatment and follow‐up were collected for about 20,000 women diagnosed with breast cancer aged 15–99 years during 1996–98 in 7 US states and 12 European countries. Age‐standardized net survival and the excess hazard of death up to 5 years after diagnosis were estimated by jurisdiction (registry, country, European region), age and stage with flexible parametric models. Breast cancers were generally less advanced in the US than in Europe. Stage also varied less between US states than between European jurisdictions. Early, node‐negative tumors were more frequent in the US (39%) than in Europe (32%), while locally advanced tumors were twice as frequent in Europe (8%), and metastatic tumors of similar frequency (5–6%). Net survival in Northern, Western and Southern Europe (81–84%) was similar to that in the US (84%), but lower in Eastern Europe (69%). For the first 3 years after diagnosis the mean excess hazard was higher in Eastern Europe than elsewhere: the difference was most marked for women aged 70–99 years, and mainly confined to women with locally advanced or metastatic tumors. Differences in breast cancer survival between Europe and the US in the late 1990s were mainly explained by lower survival in Eastern Europe, where low healthcare expenditure may have constrained the quality of treatment.
What's new?
Most of the diagnostic and therapeutic modalities used for breast cancer more than 10 years ago remain in widespread use today. Understanding the extent to which access to those modalities can explain international differences in cancer survival therefore remains highly relevant. This is the largest population‐based high‐resolution study, with a common protocol, standard quality‐control procedures and central analyses. The modelling approach to estimate net survival is a methodological strength.
The COVID-19 pandemic threatens the impact of cervical cancer screening and global cervical cancer elimination goals. As cervical cancer screening programmes were adjusting to the new situation, we ...evaluated the intensity, quality, and outcomes of cervical cancer screening in Slovenia in the first seven months of the pandemic.
Historical observational study on data from a population-based cervical cancer screening registry. Number of cervical cytopathology (screening and follow-up), histopathology (diagnostic procedures, invasive procedures and number of newly diagnosed CIN2+ cases) and HPV test results from the entire Slovenian women population between January 1st and September 30th 2020 were compared to a three-year average of the years 2017–19.
A two-month screening lock-down between March 12th and May 8th 2020 resulted in an epidemic deficit of screening (-92%), follow-up (-70%), and HPV triage tests (-68%), as well as invasive diagnostic (-47%) and treatment (-15%) of cervical lesions. Time to diagnosis and treatment did not increase; times to laboratory results fluctuated but stayed within standards. Slovenia has entered the second epidemic intending to add as little as possible to the pandemic deficit of screening smears (-23%) and yearly CIN2+ cases (-10%). Women aged 30–39 were most affected, with the highest pandemic deficit of screening smears (-26%) and yearly CIN2+ cases (-19%).
The pandemic has deeply affected all levels of our lives. New vulnerable groups and inequalities have emerged that require recognition and action. To prevent long-term increases in the cervical cancer burden due to the COVID-19 pandemic, it is crucial that organised screening is maintained and monitored in settings where it can be safely and comprehensively provided.
None.
p16/Ki-67 dual immunocytochemical staining (DS) has been proven as a sensitive and specific test for triage of HPV positive women with good reproducibility and accuracy. However, implementation of ...the test into an organized screening program (OSP) is not easy. The aims of this study were to compare the performance and agreement of DS results among three Slovenian cytopathological laboratories involved in the national OSP, and to define cases where staining results can be difficult to interpret.
Cervical smears were obtained for DS from 129 women referred to colposcopy. Smears were evaluated blindly in three laboratories by a cytotechnologist and a cytopathologist after initial training. Results were positive, suspicious, negative or inadequate. Five characteristics of DS staining were recorded. After primary evaluation, an extensive expert-led additional training was undertaken, including a discussion of difficult cases and a practical exam. Smears were re-evaluated and results compared to primary evaluation.
After the additional training, the overall percentage of agreement among the three laboratories increased from 77.5 to 89.9% and kappa increased from 0.70 to 0.86. Sensitivity for CIN2+ increased in two laboratories, to 90.5 and 85.7%, without the loss of specificity (75.8%). In one laboratory, the sensitivity slightly decreased from 90.5 to 88.9%, but the specificity increased from 63.6 to 68.2%. Difficult cases had significantly less DS cells, weak intensity of p16 staining, suboptimal cell morphology and background staining compared to positive cases.
Additional expert-led training and discussion of difficult cases are necessary for accurate interpretation of DS in laboratories involved in OSP. The most difficult cases were those with single stained cells and weak p16 staining. Training protocol for safe implementation of p16/Ki-67 DS in OSP is proposed.
Background:
Monitoring and improving quality of cancer care has become pivotal today. This is especially relevant for head and neck cancers since the disease is complex, it needs multi therapy, ...patients tend to be older, they tend to have comorbidities and limited social support. However, information on quality of care for head and neck cancers is scarce. In the context of the project “Information Network on Rare Cancers” we aimed to identify indicators of quality of care specific for the head and neck cancers management and to measure the quality of care for head and neck cancers in different EU Member States.
Methods:
We defined indicators of quality of care for head and neck cancers based on a multidisciplinary and expert-based consensus process at a European level. To test the proposed indicators, we performed an observational population-based retrospective study in four countries (Ireland, Italy, Netherlands, and Slovenia) in the years 2009–2011.
Results:
The main quality indicators identified are: availability of formalized multidisciplinary team, participation in clinical and translational research; timeliness of care, high quality of surgery and radiotherapy, and of pathological reporting. For head and neck cancers, the quality of care did not reach the optimal standards in most of the countries analyzed. A high proportion of patients was diagnosed at an advanced disease stage, showed delays in starting treatment (especially for radiotherapy), and there was only a very limited use of multi therapy.
Conclusions:
According to the achieved consensus, indicators of quality of care for head and neck cancers have to cover the patient journey (i.e., diagnosis and treatment). Our results, showed suboptimal quality of care across countries and call for solutions for ensuring good quality of care for head and neck cancer patients in all EU countries. One possible option might be to refer head and neck cancer patients to specialized centers or to networks including specialized centers.
Abstract
Objective. To identify disparities in the management of colon and rectal cancer across Europe by assessing population-based information from 12 European cancer registries (CR) participating ...in EUROCARE, together with additional information obtained from individual clinical records. Methods and patients. We considered five indicators: (a) resection with curative intent; (b) post-operative mortality; (c) proportion of stage II/III colon cancer cases given adjuvant chemotherapy; (d) proportion of rectal cancer cases receiving radiotherapy; and (e) proportion of curative intent resections with 12 or more lymph nodes examined. Results. A total of 6 871 colorectal cancer patients, diagnosed between 1996-1998, were examined. Overall 71% of patients received resection with curative intent, range 44-86% by CR; 46% of stage III colon cancer cases (range 24-73% by CR) and 22% of stage II cases (not then recommended) received adjuvant chemotherapy; 12% of rectal cancer cases received adjuvant radiotherapy, range ≤2% in five CRs to >51% in two CRs. For only 29% of curative intent resections were 12 or more lymph nodes examined. Conclusions. This study reveals that, although most patients received surgery with curative intent, disparities in treatment for colorectal cancer across Europe in the late 1990s were unexpectedly large, with many patients not receiving treatments indicated by published clinical trials. Consensus guidelines for CRC management are now becoming available and should be adopted across Europe. It is hoped that dissemination of guidelines will improve the use of scientifically proven treatments for the disease, but this should be monitored by further population-based studies.
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