CD8+CD103+PD1+TIM3+ T cells in glioblastoma microenvironment correlate with prognosis.

Glioblastoma, isocitrate dehydrogenase-wildtype (GB), is the most common and aggressive primary brain malignancy with poor outcome. Immune checkpoint inhibitors (ICIs) have been tested in GB and, despite disappointing results, the identification of a small subgroup of responders underlies the need to improve our understanding of the tumour microenvironment (TME) immunity. This study aimed to determine whether the expression of selected immune checkpoints on tissue-resident memory T cells (Trm) may predict patient outcome. We conducted a single cohort observational study. Tumour samples were collected from 45 patients with histologically confirmed GB (WHO grade 4) and processed to obtain single-cell suspensions. Patients were assessed for the correlation of Trm phenotype with overall survival (OS) or progression-free survival (PFS) using multiparametric flow cytometry and uni/multivariate analyses. Levels of Trm expressing programmed cell death protein 1 (PD1) and T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) were found to be linked to clinical outcome. Low frequency of Trm expressing PD1 or TIM3 or both markers defined subgroups as independent positive prognostic factors for patient survival. On multivariate analysis, low CD8+CD103+PD1+TIM3+ Trm and Karnofsky performance status (KPS) ≥70 were confirmed to be the most predictive independent factors associated with longer OS (hazard ratios-HR [95%CI]: 0.14 [0.04-0.52] p < 0.001, 0.39 [0.16-0.96] p = 0.04, respectively). The CD8+CD103+ Trm subgroups were also age-related predictors for survival in GB.

Impact of COVID-19 Diagnosis on Mortality in Patients with Ischemic Stroke Admitted during the 2020 Pandemic in Italy.

AIMS: The impact of the COVID-19 pandemic on the event rate of patients with ischemic stroke has been poorly investigated. We sought to evaluate the impact of the COVID-19 infection on mortality in patients with ischemic stroke admitted during the 2020 pandemic in Italy. METHODS: We analyzed a nationwide, comprehensive, and universal administrative database of patients who were admitted for ischemic stroke during and after the national lockdown for the COVID-19 infection in 2020, and the equivalent periods over the previous 5 years in Italy. The 2020 observed hospitalization and mortality rates of stroke patients with and without COVID-19 infection were compared with the expected rates, in accordance with the trend of the previous 5 years. RESULTS: During the period of observation, 300,890 hospitalizations for ischemic stroke occurred in Italy. In 2020, 41,302 stroke patients (1102 with concomitant COVID-19 infection) were admitted at 771 centers. The rate of admissions for ischemic stroke during the 2020 pandemic was markedly reduced compared with previous years (percentage change vs. 2015: -23.5). Based on the 5 year trend, the 2020 expected 30 day and 1 year mortality rates were 9.8% and 23.9%, respectively, and the observed incidence of death rates were 12.2% and 26.7%, respectively (both p < 0.001). After multiple corrections, higher rates of mortality were observed among patients admitted for stroke with a concomitant COVID-19 diagnosis. CONCLUSIONS: During the COVID-19 pandemic in 2020 in Italy, the rate of hospitalizations for ischemic stroke was dramatically reduced, although both the 30 day and 1 year mortality rates increased compared with the previous 5 year trend.

A direct method for the identification of patterns of care using administrative databases: the case of breast cancer.

OBJECTIVES: To identify and provide lists of procedures and drugs related to diagnosis and treatment of breast cancer. These lists can be used for the estimation of the cost of illness. METHODS: The method consists of identifying lists of procedures/interventions/drugs related to the tumour of interest, drawn by a panel of expert clinicians and oncologists on the basis of clinical guidelines and current practice. The lists are applied to data referring to breast cancer female patients, collected by population-based Cancer Registries and linked at individual level with information on health care treatments. A comparison with lists obtained via the matched control method is implemented. RESULTS: The distribution of administered procedures and drug prescriptions is coherent with the patient clinical pathway: surgery is the main cause of hospitalization in the first year since diagnosis, diagnostic and monitoring interventions are more frequent in the following years (recurrences detection), and at end-of-life (palliative care). Most outpatient services are due to diagnosis and monitoring, one third of services in the first year since diagnosis is radiotherapy and chemotherapy. Drugs prescribed to patients and sold in pharmacy include hormonal drugs as first course treatment and analgesics as palliative care. CONCLUSIONS: This direct method represents a valid alternative to the matched control method in describing patterns of care and costs related to the entire disease pathway. It is particularly suitable in case of cancer sites with complex patterns of care, such as breast cancer. The lists of codes developed here are based on international classification systems and can be easily applicable to other countries.

The Economic Impact of Rectal Cancer: A Population-Based Study in Italy

Costs of cancer care are increasing worldwide, and sustainability of cancer burden is critical. In this study, the economic impact of rectal cancer on the Italian healthcare system, measured as public healthcare expenditure related to investigation and treatment of rectal cancer patients is estimated. A cross-sectional cohort of 9358 rectal cancer patients is linked, on an individual basis, to claims associated to rectal cancer diagnosis and treatments. Costs refer mainly to years 2010-2011 and are estimated by phase of care, as healthcare needs vary along the care pathway: diagnostic procedures are mainly provided in the first year, surveillance procedures are addressed to chronically ill patients, and end-of-life procedures are given in the terminal status. Clinical approaches and corresponding costs are specific by cancer type and vary by phase of care, stage at diagnosis, and age. Surgery is undertaken by the great majority of patients. Thus, hospitalization is the main cost driver. The evidence produced can be used to improve planning and allocation of healthcare resources. In particular, early diagnosis of rectal cancer is a gain in healthcare budget. Policies raising spreading of and adherence to screening plans, above all when addressed to people living in Southern Italy, should be strongly encouraged.

Cancer cure for 32 cancer types: results from the EUROCARE-5 study.

BACKGROUND: Few studies have estimated the probability of being cured for cancer patients. This study aims to estimate population-based indicators of cancer cure in Europe by type, sex, age and period. METHODS: 7.2 million cancer patients (42 population-based cancer registries in 17 European countries) diagnosed at ages 15-74 years in 1990-2007 with follow-up to 2008 were selected from the EUROCARE-5 dataset. Mixture-cure models were used to estimate: (i) life expectancy of fatal cases (LEF); (ii) cure fraction (CF) as proportion of patients with same death rates as the general population; (iii) time to cure (TTC) as time to reach 5-year conditional relative survival (CRS) >95%. RESULTS: LEF ranged from 10 years for chronic lymphocytic leukaemia patients to <6 months for those with liver, pancreas, brain, gallbladder and lung cancers. It was 7.7 years for patients with prostate cancer at age 65-74 years and >5 years for women with breast cancer. The CF was 94% for testis, 87% for thyroid cancer in women and 70% in men, 86% for skin melanoma in women and 76% in men, 66% for breast, 63% for prostate and <10% for liver, lung and pancreatic cancers. TTC was <5 years for testis and thyroid cancer patients diagnosed below age 55 years, and <10 years for stomach, colorectal, corpus uteri and melanoma patients of all ages. For breast and prostate cancers, a small excess (CRS < 95%) remained for at least 15 years. CONCLUSIONS: Estimates from this analysis should help to reduce unneeded medicalization and costs. They represent an opportunity to improve patients' quality of life.

Patterns of care and cost profiles of women with breast cancer in Italy: EPICOST study based on real world data.

OBJECTIVES: To estimate total direct health care costs associated to diagnosis and treatment of women with breast cancer in Italy, and to investigate their distribution by service type according to the disease pathway and patient characteristics. METHODS: Data on patients provided by population-based Cancer Registries are linked at individual level with data on health-care services and corresponding claims from administrative databases. A combination of cross-sectional approach and a threephase of care decomposition model with initial, continuing and final phases-of-care defined according to time occurred since diagnosis and disease outcome is adopted. Direct estimation of cancer-related costs is obtained. RESULTS: Study cohort included 49,272 patients, 15.2% were in the initial phase absorbing 42% of resources, 79.7% in the continuing phase absorbing 44% of resources and 5.1% in the final phase absorbing 14% of resources. Hospitalization was the most important cost driver, accounting for over 55% of the total costs. CONCLUSIONS: This paper represents the first attempt in Italy to estimate the economic burden of cancer at population level taking into account the entire disease pathway and using multiple current health care databases. The evidence produced by the study can be used to better plan resources allocation. The model proposed is replicable to countries with individual health care information on services and claims.

Prognosis and cure of long-term cancer survivors: A population-based estimation.

BACKGROUND: Increasing evidence of cure for some neoplasms has emerged in recent years. The study aimed to estimate population-based indicators of cancer cure. METHODS: Information on more than half a million cancer patients aged 15-74 years collected by population-based Italian cancer registries and mixture cure models were used to estimate the life expectancy of fatal tumors (LEFT), proportions of patients with similar death rates of the general population (cure fraction), and time to reach 5-year conditional relative survival (CRS) >90% or 95% (time to cure). RESULTS: Between 1990 and 2000, the median LEFT increased >1 year for breast (from 8.1 to 9.4 years) and prostate cancers (from 5.2 to 7.4 years). Median LEFT in 1990 was >5 years for testicular cancers (5.8) and Hodgkin lymphoma (6.3) below 45 years of age. In both sexes, it was ≤0.5 years for pancreatic cancers and NHL in 1990 and in 2000. The cure fraction showed a 10% increase between 1990 and 2000. It was 95% for thyroid cancer in women, 94% for testis, 75% for prostate, 67% for breast cancers, and <20% for liver, lung, and pancreatic cancers. Time to 5-year CRS >95% was <10 years for testis, thyroid, colon cancers, and melanoma. For breast and prostate cancers, the 5-year CRS >90% was reached in <10 years but a small excess remained for >15 years. CONCLUSIONS: The study findings confirmed that several cancer types are curable. Became aware of the possibility of cancer cure has relevant clinical and social impacts.

Quality analysis of population-based information on cancer stage at diagnosis across Europe, with presentation of stage-specific cancer survival estimates: A EUROCARE-5 study.

BACKGROUND: Cancer registries (CRs) are fundamental for estimating cancer burden, evaluating screening and monitoring health service performance. Stage at diagnosis-an essential information item collected by CRs-has been made available, for the first time, by CRs participating in EUROCARE-5. We analysed the quality of this information and estimated stage-specific survival across Europe for CRs with good data quality. DATA AND METHODS: Sixty-two CRs sent stage (as TNM, condensed TNM or extent of disease) for 15 cancers diagnosed in 2000-2007. We assessed the quality, partly by comparing stage according to the three systems. We also developed procedures to reconstruct stage (categories: local, regional, metastatic and unknown) using information from all three systems, thus minimising the amount of missing information. RESULTS: Moderate-to-excellent stage concordance was found for practically all 24 CRs, for which it was possible to compare at least two staging systems. However, since stage was often incorrectly assigned, and information on the presence/absence of metastases was often lacking, data on only 7/15 cancers from 34/62 CRs (15 countries) were of sufficient quality for further analysis. Cases diagnosed ≥70 years had more advanced (or lacking) stage- and worse stage-specific survival than those <70 years. CONCLUSIONS: Many European CRs collect and record reasonably accurate stage information. Others have difficulties. Both the completeness of primary data and the accuracy of stage coding need to be improved in order for CRs to fulfil their expanding roles in cancer control. We propose our stage reconstruction/checking procedures as a means of fully exploiting the stage information provided by EUROCARE CRs. More advanced (or lacking) stage at diagnosis plus poorer stage-specific survival in the elderly are worrying.

Italian cancer figures--Report 2015: The burden of rare cancers in Italy.

OBJECTIVES: This collaborative study, based on data collected by the network of Italian Cancer Registries (AIRTUM), describes the burden of rare cancers in Italy. Estimated number of new rare cancer cases yearly diagnosed (incidence), proportion of patients alive after diagnosis (survival), and estimated number of people still alive after a new cancer diagnosis (prevalence) are provided for about 200 different cancer entities. MATERIALS AND METHODS: Data herein presented were provided by AIRTUM population- based cancer registries (CRs), covering nowadays 52% of the Italian population. This monograph uses the AIRTUM database (January 2015), which includes all malignant cancer cases diagnosed between 1976 and 2010. All cases are coded according to the International Classification of Diseases for Oncology (ICD-O-3). Data underwent standard quality checks (described in the AIRTUM data management protocol) and were checked against rare-cancer specific quality indicators proposed and published by RARECARE and HAEMACARE (www.rarecarenet.eu; www.haemacare.eu). The definition and list of rare cancers proposed by the RARECAREnet "Information Network on Rare Cancers" project were adopted: rare cancers are entities (defined as a combination of topographical and morphological codes of the ICD-O-3) having an incidence rate of less than 6 per 100,000 per year in the European population. This monograph presents 198 rare cancers grouped in 14 major groups. Crude incidence rates were estimated as the number of all new cancers occurring in 2000-2010 divided by the overall population at risk, for males and females (also for gender-specific tumours).The proportion of rare cancers out of the total cancers (rare and common) by site was also calculated. Incidence rates by sex and age are reported. The expected number of new cases in 2015 in Italy was estimated assuming the incidence in Italy to be the same as in the AIRTUM area. One- and 5-year relative survival estimates of cases aged 0-99 years diagnosed between 2000 and 2008 in the AIRTUM database, and followed up to 31 December 2009, were calculated using complete cohort survival analysis. To estimate the observed prevalence in Italy, incidence and follow-up data from 11 CRs for the period 1992-2006 were used, with a prevalence index date of 1 January 2007. Observed prevalence in the general population was disentangled by time prior to the reference date (≤2 years, 2-5 years, ≤15 years). To calculate the complete prevalence proportion at 1 January 2007 in Italy, the 15-year observed prevalence was corrected by the completeness index, in order to account for those cancer survivors diagnosed before the cancer registry activity started. The completeness index by cancer and age was obtained by means of statistical regression models, using incidence and survival data available in the European RARECAREnet data. RESULTS: In total, 339,403 tumours were included in the incidence analysis. The annual incidence rate (IR) of all 198 rare cancers in the period 2000-2010 was 147 per 100,000 per year, corresponding to about 89,000 new diagnoses in Italy each year, accounting for 25% of all cancer. Five cancers, rare at European level, were not rare in Italy because their IR was higher than 6 per 100,000; these tumours were: diffuse large B-cell lymphoma and squamous cell carcinoma of larynx (whose IRs in Italy were 7 per 100,000), multiple myeloma (IR: 8 per 100,000), hepatocellular carcinoma (IR: 9 per 100,000) and carcinoma of thyroid gland (IR: 14 per 100,000). Among the remaining 193 rare cancers, more than two thirds (No. 139) had an annual IR <0.5 per 100,000, accounting for about 7,100 new cancers cases; for 25 cancer types, the IR ranged between 0.5 and 1 per 100,000, accounting for about 10,000 new diagnoses; while for 29 cancer types the IR was between 1 and 6 per 100,000, accounting for about 41,000 new cancer cases. Among all rare cancers diagnosed in Italy, 7% were rare haematological diseases (IR: 41 per 100,000), 18% were solid rare cancers. Among the latter, the rare epithelial tumours of the digestive system were the most common (23%, IR: 26 per 100,000), followed by epithelial tumours of head and neck (17%, IR: 19) and rare cancers of the female genital system (17%, IR: 17), endocrine tumours (13% including thyroid carcinomas and less than 1% with an IR of 0.4 excluding thyroid carcinomas), sarcomas (8%, IR: 9 per 100,000), central nervous system tumours and rare epithelial tumours of the thoracic cavity (5%with an IR equal to 6 and 5 per 100,000, respectively). The remaining (rare male genital tumours, IR: 4 per 100,000; tumours of eye, IR: 0.7 per 100,000; neuroendocrine tumours, IR: 4 per 100,000; embryonal tumours, IR: 0.4 per 100,000; rare skin tumours and malignant melanoma of mucosae, IR: 0.8 per 100,000) each constituted <4% of all solid rare cancers. Patients with rare cancers were on average younger than those with common cancers. Essentially, all childhood cancers were rare, while after age 40 years, the common cancers (breast, prostate, colon, rectum, and lung) became increasingly more frequent. For 254,821 rare cancers diagnosed in 2000-2008, 5-year RS was on average 55%, lower than the corresponding figures for patients with common cancers (68%). RS was lower for rare cancers than for common cancers at 1 year and continued to diverge up to 3 years, while the gap remained constant from 3 to 5 years after diagnosis. For rare and common cancers, survival decreased with increasing age. Five-year RS was similar and high for both rare and common cancers up to 54 years; it decreased with age, especially after 54 years, with the elderly (75+ years) having a 37% and 20% lower survival than those aged 55-64 years for rare and common cancers, respectively. We estimated that about 900,000 people were alive in Italy with a previous diagnosis of a rare cancer in 2010 (prevalence). The highest prevalence was observed for rare haematological diseases (278 per 100,000) and rare tumours of the female genital system (265 per 100,000). Very low prevalence (<10 prt 100,000) was observed for rare epithelial skin cancers, for rare epithelial tumours of the digestive system and rare epithelial tumours of the thoracic cavity. COMMENTS: One in four cancers cases diagnosed in Italy is a rare cancer, in agreement with estimates of 24% calculated in Europe overall. In Italy, the group of all rare cancers combined, include 5 cancer types with an IR>6 per 100,000 in Italy, in particular thyroid cancer (IR: 14 per 100,000).The exclusion of thyroid carcinoma from rare cancers reduces the proportion of them in Italy in 2010 to 22%. Differences in incidence across population can be due to the different distribution of risk factors (whether environmental, lifestyle, occupational, or genetic), heterogeneous diagnostic intensity activity, as well as different diagnostic capacity; moreover heterogeneity in accuracy of registration may determine some minor differences in the account of rare cancers. Rare cancers had worse prognosis than common cancers at 1, 3, and 5 years from diagnosis. Differences between rare and common cancers were small 1 year after diagnosis, but survival for rare cancers declined more markedly thereafter, consistent with the idea that treatments for rare cancers are less effective than those for common cancers. However, differences in stage at diagnosis could not be excluded, as 1- and 3-year RS for rare cancers was lower than the corresponding figures for common cancers. Moreover, rare cancers include many cancer entities with a bad prognosis (5-year RS <50%): cancer of head and neck, oesophagus, small intestine, ovary, brain, biliary tract, liver, pleura, multiple myeloma, acute myeloid and lymphatic leukaemia; in contrast, most common cancer cases are breast, prostate, and colorectal cancers, which have a good prognosis. The high prevalence observed for rare haematological diseases and rare tumours of the female genital system is due to their high incidence (the majority of haematological diseases are rare and gynaecological cancers added up to fairly high incidence rates) and relatively good prognosis. The low prevalence of rare epithelial tumours of the digestive system was due to the low survival rates of the majority of tumours included in this group (oesophagus, stomach, small intestine, pancreas, and liver), regardless of the high incidence rate of rare epithelial cancers of these sites. This AIRTUM study confirms that rare cancers are a major public health problem in Italy and provides quantitative estimations, for the first time in Italy, to a problem long known to exist. This monograph provides detailed epidemiologic indicators for almost 200 rare cancers, the majority of which (72%) are very rare (IR<0.5 per 100,000). These data are of major interest for different stakeholders. Health care planners can find useful information herein to properly plan and think of how to reorganise health care services. Researchers now have numbers to design clinical trials considering alternative study designs and statistical approaches. Population-based cancer registries with good quality data are the best source of information to describe the rare cancer burden in a population.

Survival of male genital cancers (prostate, testis and penis) in Europe 1999-2007: Results from the EUROCARE-5 study.

BACKGROUND: We provide updated estimates of survival and survival trends of male genital tumours (prostate, testicular and penis cancers), in Europe and across European areas. METHODS: The complete approach was used to obtain relative survival estimates for patients diagnosed in 2000-2007, and followed up through 2008 in 29 countries. Data came from 87 cancer registries (CRs) for prostate tumours and from 86 CRs for testis and penis tumours. Relative survival time trends in 1999-2007 were estimated by the period approach. Data came from 49 CRs in 25 countries. RESULTS: We analysed 1,021,275 male genital cancer cases. Five-year relative survival was high and decreased with increasing age for all tumours considered. We found limited variation in survival between European regions with Eastern Europe countries having lower survival than the others. Survival for penile cancer patients did not improve from 1999 to 2007. Survival for testicular cancer patients remained stable at high levels since 1999. Survival for prostate cancer patients increased over time. CONCLUSIONS: Treatment standardisation and centralisation for very rare diseases such as penile cancers or advanced testicular tumours should be supported. The high survival of testicular cancer makes long-term monitoring of testicular cancer survivors necessary and CRs can be an important resource. Prostate cancer patients' survival must be interpreted considering incidence and mortality data. The follow-up of the European Randomised Study of Screening for Prostate Cancer should continue to clarify the impact of screening on prostate cancer mortality together with population based studies including information on stage and treatments.

Survival of adults with primary malignant brain tumours in Europe; Results of the EUROCARE-5 study.

BACKGROUND: Primary malignant brain tumours are rare but represent a serious health burden due to their poor survival. This manuscript describes the survival of malignant brain tumours in adults diagnosed 2000-2007 in Europe. METHODS: For this study we analysed patients archived in 86 European population-based cancer registries, followed up to 31st December 2008. Only primary malignant neuroepithelial brain tumours (with pathological confirmation) and primary malignant unspecified brain tumours without pathological confirmation were included. We estimated 1-year and 5-year relative survival (RS) weighted by age group and country. We also estimated country-specific and age-specific survival, together with survival differences between time periods (for 1999-2001, 2002-2004 and 2005-2007). RESULTS: Glioblastoma represents 49% of all brain tumours, followed by other/unspecified astrocytoma (18%), oligodendroglioma/oligoastrocytoma (9%), ependymoma (1.5%) and embryonal tumours (1%). Five-year RS was 20% for all tumours combined, but ranged from 58% for ependymoma to only 6% for glioblastoma and sharply decreased with increasing age. Differences between countries were relatively small, but generally RS in Ireland/United Kingdom (UK) and Eastern Europe was below the average. An increase in 1-year RS (up to 10-12%) was noted over time, being largest in Central and Northern Europe in patients between 45 and 74years of age. CONCLUSIONS: Despite an increase in 1-year RS in most European regions, the survival of primary malignant brain tumours is still poor. Disparities between countries were evident, being even larger at the end of the study period than at the beginning, suggesting differences in availability of the latest treatment modalities.

Childhood cancer survival in Europe 1999-2007: results of EUROCARE-5--a population-based study.

BACKGROUND: Survival and cure rates for childhood cancers in Europe have greatly improved over the past 40 years and are mostly good, although not in all European countries. The EUROCARE-5 survival study estimates survival of children diagnosed with cancer between 2000 and 2007, assesses whether survival differences among European countries have changed, and investigates changes from 1999 to 2007. METHODS: We analysed survival data for 157,499 children (age 0-14 years) diagnosed between Jan 1, 1978 and Dec 31, 2007. They came from 74 population-based cancer registries in 29 countries. We calculated observed, country-weighted 1-year, 3-year, and 5-year survival for major cancers and all cancers combined. For comparison between countries, we used the corrected group prognosis method to provide survival probabilities adjusted for multiple confounders (sex, age, period of diagnosis, and, for all cancers combined without CNS cancers, casemix). Age-adjusted survival differences by area and calendar period were calculated with period analysis and were given for all cancers combined and the major cancers. FINDINGS: We analysed 59,579 cases. For all cancers combined for children diagnosed in 2000-07, 1-year survival was 90.6% (95% CI 90.2-90.9), 3-year survival was 81.0 % (95% CI 80.5-81.4), and 5-year survival was 77.9% (95% CI 77.4-78.3). For all cancers combined, 5-year survival rose from 76.1% (74.4-77.7) for 1999-2001, to 79.1% (77.3-80.7) for 2005-07 (hazard ratio 0.973, 95% CI 0.965-0.982, p<0.0001). The greatest improvements were in eastern Europe, where 5-year survival rose from 65.2% (95% CI 63.1-67.3) in 1999-2001, to 70.2% (67.9-72.3) in 2005-07. Europe-wide average yearly change in mortality (hazard ratio) was 0.939 (95% CI 0.919-0.960) for acute lymphoid leukaemia, 0.959 (0.933-0.986) for acute myeloid leukaemia, and 0.940 (0.897-0.984) for non-Hodgkin lymphoma. Mortality for all of Europe did not change significantly for Hodgkin's lymphoma, Burkitt's lymphoma, CNS tumours, neuroblastoma, Wilms' tumour, Ewing's sarcoma, osteosarcoma, and rhabdomyosarcoma. Disparities for 5-year survival persisted between countries and regions, ranging from 70% to 82% (for 2005-07). INTERPRETATION: Several reasons might explain persisting inequalities. The lack of health-care resources is probably most important, especially in some eastern European countries with limited drug supply, lack of specialised centres with multidisciplinary teams, delayed diagnosis and treatment, poor management of treatment, and drug toxicity. In the short term, cross-border care and collaborative programmes could help to narrow the survival gaps in Europe. FUNDING: Italian Ministry of Health, European Commission, Compagnia di San Paolo Foundation.

Estimates of cancer burden in Umbria.

AIMS AND BACKGROUND: Model-based estimates and projections of epidemiological indicators related to cancer are important tools to support public health policies and planning. The aim of the present study is to produce projections of cancer incidence, mortality and prevalence for the Umbria region (900,000 inhabitants) in central Italy. METHODS: The estimations were obtained by applying the MIAMOD method, a statistical back-calculation approach to derive incidence and prevalence figures starting from mortality and relative survival data. Published data from the Italian cancer registries were modeled in order to estimate regional cancer survival. Estimated incidence rates were validated with observed incidence rates obtained from the Umbria regional cancer registry. RESULTS: The most frequent cancer sites estimated were colon-rectum, prostate and breast in women, with 970, 615 and 729 new diagnoses, respectively, in 2012. The incidence rates were increasing for female lung cancer, male colorectal cancer, and melanoma. By contrast, the rates have been declining for cervix and stomach cancer. For lung cancer and prostate cancer in men and colorectal cancer in women the rates increased, reaching a peak in different periods, and then decreased. The incidence rates of breast cancer rose, reaching a plateau in the mid 2010s. Favorable mortality trends were predicted for all cancers except skin melanoma and lung cancer in women. The prevalence of cancer was increasing with the only exception of cervical cancer in women and lung cancer in men in the most recent estimation period. CONCLUSION: The scenario found for cancer incidence and prevalence was largely influenced by screening activities, so that increasing or stable incidence rates may reflect active preventive efforts. Aging, screening, and more complex and costly treatments pose a problem of sustainability and selection of interventions to the regional oncology system. Evaluation of effectiveness of intervention and cost-benefit analyses will be important to ensure cancer control in the future.

Estimates of cancer burden in Marche.

AIMS AND BACKGROUND: The aim of this paper is to provide estimates of the incidence, mortality and prevalence of seven major cancers in the Marche region for the period 1970-2015. METHODS: The MIAMOD method, a statistical back-calculation approach, was applied to derive incidence and prevalence figures from mortality and relative survival data. Published data from the Italian cancer registries were used as the basis for survival modeling. RESULTS: Colorectal, breast and prostate cancer were the most frequent cancers in 2012, with 1,563, 1,215 and 1,191 estimated incident cases, and leading to 539, 224 and 228 deaths, respectively. Age-standardized rates were estimated to decrease for stomach and cervical cancer and to increase for skin melanoma and female lung cancer. In men, the lung cancer incidence rates reached their maximum level during the late 1980s and decreased thereafter. The colorectal cancer trend showed an initially increasing pattern, followed by a decrease in the last decade, both for men and women. The estimated incidence rates of prostate cancer presented a very steep rise in the period 1985-2002 and then remained stable at the high levels reached in 2003. The largest increases in prevalence were for breast, colorectal and prostate cancer, for which 17,098, 11,844 and 9,269 cases were estimated, respectively, in 2012. CONCLUSION. This paper provides a description of the burden of the major cancers in the Marche region until 2015. The estimates were fairly consistent with previously published data by the Macerata province cancer registry. The MIAMOD method provides a picture of the impressive increase in the prevalence of breast cancer and prostate cancer over the period studied, thereby allowing to foresee an increasing demand for cancer care services as one of the major challenges for the regional health care system.

Rare neuroendocrine tumours: results of the surveillance of rare cancers in Europe project.

Because of the low incidence, and limited opportunities for large patient volume experiences, there are very few relevant studies of neuroendocrine tumours (NETs). A large population-based database (including cancer patients diagnosed from 1978 to 2002 and registered in 76 population-based cancer registries [CRs]), provided by the project 'surveillance of rare cancers in Europe' (RARECARE) is used to describe the basic indicators of incidence, prevalence and survival of NETs, giving a unique overview on the burden of NETs in Europe. NETs at all cancer sites, excluding lung, were analysed in this study. In total over 20,000 incident cases of NETs were analysed and a data quality check upon specific NETs was performed. The overall incidence rate for NETs was 25/1,000,000 and was highest in patients aged 65 years and older with well differentiated endocrine carcinomas (non-functioning pancreatic and gastrointestinal) (40 per 1,000,000). We estimated that slightly more than 100,000 people were diagnosed with NETs and still alive in EU27 at the beginning of 2008. Overall, NETs had a 5 year relative survival of 50%; survival was low (12%) for poorly differentiated endocrine carcinoma, and relatively high (64%) for well differentiated carcinoma (not functioning of the pancreas and digestive organs). Within NETs, endocrine carcinoma of thyroid gland had the best 5-year relative survival (82%). Because of the complexity and number of the different disciplines involved with NETs (as they arise in many organs), a multidisciplinary approach delivered in highly qualified reference centres and an international network between those centres is recommended.

Rare thoracic cancers, including peritoneum mesothelioma.

Rare thoracic cancers include those of the trachea, thymus and mesothelioma (including peritoneum mesothelioma). The aim of this study was to describe the incidence, prevalence and survival of rare thoracic tumours using a large database, which includes cancer patients diagnosed from 1978 to 2002, registered in 89 population-based cancer registries (CRs) and followed-up to 31st December 2003. Over 17,688 cases of rare thoracic cancers were selected based on the list of the RACECARE project. Mesothelioma was the most common tumour (19 per million per year) followed by epithelial tumours of the trachea and thymus (1.3 and 1.7, respectively). The age standardised incidence rates of epithelial tumours of the trachea was double in Eastern and Southern Europe versus the other European regions: 2 per million per year. Epithelial tumours of the thymus had the lowest incidence in Northern and Eastern Europe and UK and Ireland(1) and somewhat higher incidence in Central and Southern Europe.(2) Highest incidence in mesothelioma was seen in UK and Ireland(23) and lowest in Eastern Europe.(4) Patients with tumours of the thymus had the best prognosis (1-year survival 85%, 66% at 5 years). Five year survival was lowest for the mesothelioma 5% compared to 14% of patients with tumours of the trachea. Mesothelioma was the most prevalent rare cancer (12,000 cases), followed by thymus (7000) and trachea (1400). Cancer Registry (CR) data play an important role in revealing the burden of rare thoracic cancers and monitoring the effect of regulations on asbestos use and smoking related policies.

Rare cancers are not so rare: the rare cancer burden in Europe.

PURPOSE: Epidemiologic information on rare cancers is scarce. The project Surveillance of Rare Cancers in Europe (RARECARE) provides estimates of the incidence, prevalence and survival of rare cancers in Europe based on a new and comprehensive list of these diseases. MATERIALS AND METHODS: RARECARE analysed population-based cancer registry (CR) data on European patients diagnosed from 1988 to 2002, with vital status information available up to 31st December 2003 (latest date for which most CRs had verified data). The mean population covered was about 162,000,000. Cancer incidence and survival rates for 1995-2002 and prevalence at 1st January 2003 were estimated. RESULTS: Based on the RARECARE definition (incidence <6/100,000/year), the estimated annual incidence rate of all rare cancers in Europe was about 108 per 100,000, corresponding to 541,000 new diagnoses annually or 22% of all cancer diagnoses. Five-year relative survival was on average worse for rare cancers (47%) than common cancers (65%). About 4,300,000 patients are living today in the European Union with a diagnosis of a rare cancer, 24% of the total cancer prevalence. CONCLUSION: Our estimates of the rare cancer burden in Europe provide the first indication of the size of the public health problem due to these diseases and constitute a useful base for further research. Centres of excellence for rare cancers or groups of rare cancers could provide the necessary organisational structure and critical mass for carrying out clinical trials and developing alternative approaches to clinical experimentation for these cancers.

Future lung cancer incidence in Poland and Finland based on forecasts on hypothetical changes in smoking habits.

OBJECTIVE: the aim is to estimate the future lung cancer incidence in Poland and Finland based on forecasts on hypothetical changes in smoking habits. MATERIAL AND METHODS: data on population, lung cancer and smoking prevalence come from known sources. The simulation model utilized for forecasting was based on smoothing the smoking habit - specific risk ratios estimated for males and females in Europe. RESULTS: depending on the analyzed scenario in 2030 in Poland mortality rates among men would range from 8 to 125/10(5) and among women from 7 to 47/10(5); in Finland among men 5 to 60/10(5) and among women 4 to 22/10(5). CONCLUSIONS: the results obtained clearly indicate that cutting down on the number of smokers translates directly into a considerable reduction of the lung cancer incidence rate.

Breast cancer survivors in the United States: geographic variability and time trends, 2005-2015.

BACKGROUND: : Breast cancer continues to place a significant burden on the healthcare system. Regional prevalence measures are instrumental in the development of cancer control policies. Very few population-based cancer registries are able to provided local, long-term incidence and follow-up information that permits the direct calculation of prevalence. Model-based prevalence estimates are an alternative when this information is lacking or incomplete. The current work represents a comprehensive collection of female breast cancer prevalence from 2005 to 2015 in the United States and the District of Columbia (DC). METHODS: : Breast cancer prevalence estimates were derived from state-specific cancer mortality and survival data using a statistical package called the Mortality-Incidence Analysis Model or MIAMOD. Cancer survival models were derived from the Surveillance, Epidemiology, and End Results Program data and were adjusted to represent state-specific survival. Comparisons with reported incidence for 39 states and DC had validated estimates. RESULTS: : By the year 2010, 2.9 million breast cancer survivors are predicted in the US, equaling 1.85% of the female population. Large variability in prevalent percentages was reported between states, ranging from 1.4% to 2.4% in 2010. Geographic variability was reduced when calculating age-standardized prevalence proportions or cancer survivors by disease duration, including 0 to 2 years and 2 to 5 years. The residual variability in age-adjusted prevalence was explained primarily by the state-specific, age-adjusted breast cancer incidence rates. State-specific breast cancer survivors are expected to increase from 16% to 51% in the decennium from 2005 to 2015 and by 31% at the national level. CONCLUSIONS: : To the authors' knowledge, the current study is the first to provide systematic estimations of breast cancer prevalence in all US states through 2015. The estimated levels and time trends were consistent with the available population-based data on breast cancer incidence, prevalence, and population aging. Cancer 2009. (c) 2009 American Cancer Society.

The cancer survival gap between elderly and middle-aged patients in Europe is widening.

The present study is aimed to compare survival and prognostic changes over time between elderly (70-84 years) and middle-aged cancer patients (55-69 years). We considered seven cancer sites (stomach, colon, breast, cervix and corpus uteri, ovary and prostate) and all cancers combined (but excluding prostate and non-melanoma skin cancers). Five-year relative survival was estimated for cohorts of patients diagnosed in 1988-1999 in a pool of 51 European populations covered by cancer registries. Furthermore, we applied the period-analysis method to more recent incidence data from 32 cancer registries to provide 1- and 5-year relative survival estimates for the period of follow-up 2000-2002. A significant survival improvement was observed from 1988 to 1999 for all cancers combined and for every cancer site, except cervical cancer. However, survival increased at a slower rate in the elderly, so that the gap between younger and older patients widened, particularly for prostate cancer in men and for all considered cancers except cervical cancer in women. For breast and prostate cancers, the increasing gap was likely attributable to a larger use of, respectively, mammographic screening and PSA test in middle-aged with respect to the elderly. In the period analysis of the most recent data, relative survival was much higher in middle-aged patients than in the elderly. The differences were higher for breast and gynaecological cancers, and for prostate cancer. Most of this age gap was due to a very large difference in survival after the 1st year following the diagnosis. Differences were much smaller for conditional 5-year relative survival among patients who had already survived the first year. The increase of survival in elderly men is encouraging but the lesser improvement in women and, in particular, the widening gap for breast cancer suggest that many barriers still delay access to care and that enhanced prevention and clinical management remain major issues.