Patterns of care for European colorectal cancer patients diagnosed 1996-1998: a EUROCARE high resolution study.

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 < or =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.

Survival for ethmoid sinus adenocarcinoma in European populations.

BACKGROUND: Adenocarcinoma of the ethmoid sinus is rare. EUROCARE data provide a good opportunity to study the survival of this rare disease in a population of continental size. PATIENTS AND METHODS: A total of 204 cases, age 15 to 99 years, diagnosed with primary ethmoid sinus adenocarcinoma between 1983 and 1994, were analyzed. The data were contributed by 22 population-based cancer registries from the nine countries participating in EUROCARE. Relative survival by sex, age, period of diagnosis, region and stage, and adjusted relative excess risk (RER) of death, were estimated. RESULTS: Survival was 83%, 58% and 46%, 1, 3 and 5 years, respectively after diagnosis. Five-year survival was best (60%) in patients of 55-64 years and worst (33%) in the oldest age group (> or =65 years). Five-year survival differ between European population: in Norway (55%, 95% confidence interval 26.4-80.9) and western Europe that includes populations from Eindhoven, Saarland, Geneva, Italy and France (56%, 95%CI 41.3-68.9) was higher than in the UK (41%, 95% CI 30.8-51.8) and eastern Europe which includes Slovakia and Slovenia, (22%, 95% CI 3.5-54.4). Five-year survival did not improve over time. Due to the rarity of the disease, all the survival differences did not reach the statistical significance. CONCLUSIONS: Since no survival improvement with time was evident from this study, efforts should be made to improve early diagnosis. GPs and ENT specialists should be alerted to the disease and encouraged to take occupational histories in people with persistent nasal symptoms, which may lead to a reasonable suspicion of malignancy. Monitoring of exposed workers may also improve early diagnosis. Patients with suspected ethmoid cancer should be referred immediately a specialized diagnosis and treatment centre.

Prostate cancer treatment in Europe at the end of 1990s.

BACKGROUND: There is wide variation in prostate cancer incidence and survival across Europe. In many countries incidence is rising sharply in relation to the introduction of prostate-specific antigen assay, and there is concern that patients may not be treated appropriately. We therefore aimed to characterize treatment for prostate cancer across Europe. METHODS: We performed a high resolution population-based study, collecting information on the treatment of 3 486 prostate cancer cases diagnosed in 1995-1999 in 11 cancer registries from six European countries. RESULTS: Overall, about one in three patients received radical treatment (prostatectomy 23% or radiotherapy 14%); about 60% of younger patients (<70 years) received radical treatment, while a similar proportion of older patients (> or =70 years) received palliation (transurethral prostatectomy or hormone treatment only). A considerable proportion (61%) of patients with apparently high-risk disease were treated radically within a year of diagnosis, with large variation between regions: >70% in Calvados, Haut-Rhin, Tarn and Eindhoven and <50% in Slovakia and Cracow. Overall 34% of patients with apparently low-risk disease received radical treatment, varying from 17% and 22% in Bas-Rhin and Granada, to 52% and 56% in Calvados and Eindhoven. CONCLUSIONS: Our data indicate wide variation in the treatment for prostate cancer even among patients with apparently similar disease, and further suggest a non-negligible proportion may be receiving inappropriate radical treatment for apparently low-risk disease. Current guidelines indicate active surveillance should become the main means of managing low-risk disease.

Human papillomavirus in HNSCC: a European epidemiologic perspective.

The aim of this study was to assess incidence and survival of human papillomavirus-related and unrelated head and neck squamous cell carcinoma sites from 15 European population-based cancer registries. This analysis was performed on 29,265 adult (aged approximately 15 years) cancer patients diagnosed in the period from 1988 to 2002. The human papillomavirus-unrelated cancer sites had an age-standardized incidence higher than the human papillomavirus-related cancer cases (3.8 versus 2.5/100,000 year). Incidence rates of head and neck squamous cell carcinomas increased more for human papillomavirus-related than unrelated cancer sites. Three-year survival rates improved more in human papillomavirus-related than unrelated cancer sites, and women had better rates of survival than men.

The tumor-targeting immunocytokine F16-IL2 in combination with doxorubicin: dose escalation in patients with advanced solid tumors and expansion into patients with metastatic breast cancer.

A phase Ib/II trial was performed to evaluate safety, tolerability, recommended dose (RD) and efficacy of F16-IL2, a recombinant antibody-cytokine fusion protein, in combination with doxorubicin in patients with solid tumors (phase Ib) and metastatic breast cancer (phase II). Six patient cohorts with progressive solid tumors (n = 19) received escalating doses of F16-IL2 [5-25 Million International Units (MIU) of IL2 equivalent dose] in combination with escalating doses of doxorubicin (0-25 mg/m(2)) on day 1, 8 and 15 every 4 weeks. Subsequently, patients with metastatic breast cancer (n = 10) received the drug combination at the RD. Clinical data and laboratory findings were analyzed for safety, tolerability, and activity. F16-IL2 could be administered up to 25 MIU, in combination with the RD of doxorubicin (25 mg/m(2)). No human anti-fusion protein antibodies (HAFA) response was detected. Pharmacokinetics of F16-IL2 was dose-dependent over the tested range, with half-lives of ca. 13 and ca. 8 hours for cohorts dosed at lower and higher levels, respectively. Toxicities were controllable and reversible, with no combination treatment-related death. After 8 weeks, 57% and 67% disease control rates were observed for Phase I and II, respectively (decreasing to 43% and 33% after 12 weeks), considering 14 and 9 patients evaluable for efficacy. One patient experienced a long lasting partial response (45 weeks), still on-going at exit of study. F16-IL2 can be safely and repeatedly administered at the RD of 25 MIU in combination with 25 mg/m(2) doxorubicin; its safety and activity are currently being investigated in combination with other chemotherapeutics, in order to establish optimal therapy settings.

Estimates of cancer burden in Campania.

AIMS AND BACKGROUND: In Campania two cancer registries have been operating since 1996, covering part of the province of Naples and the province of Salerno, and amounting to 29% of the regional population. The aim of this paper is to provide estimates of the incidence, mortality and prevalence of seven major cancers for the entire Campania region. METHODS: The estimates 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. Survival was modeled on the basis of published data from the Italian cancer registries. RESULTS: In 2012 the most frequent cancers were colorectal, breast and lung cancer with 3,969, 3,675 and 3,629 new diagnosed cases, respectively. The cancers with increasing incidence trends were breast cancer, lung cancer and skin melanoma in women, and colorectal cancer and skin melanoma in men. By contrast, the incidence rates of uterine cervix cancer and stomach cancer were decreasing. In men the lung and prostate cancer incidence rates increased, reaching a peak in different periods, and then decreased and stabilized, respectively. Prevalence was increasing for all considered cancers with the exception of cervical cancer. The highest values in 2012 were estimated for breast and colorectal cancer (34,000 and 22,000 prevalent cases, respectively). In the final period under study there was a decline in mortality for all cancers except female lung cancer. The highest crude mortality rates in 2012 were estimated for lung cancer in men and breast cancer in women: 80 and 31 per 100,000, respectively. CONCLUSION: This paper provides a description of the burden of the major cancers in Campania until 2015. The estimates highlight the need to reinforce organized screening, especially for breast and colorectal cancer, and to support evidence-based prevention campaigns against female smoking. All these aspects require continuous and updated monitoring of the main epidemiological indicators in the Campania population.

Estimates of cancer burden in Sicily.

AIMS AND BACKGROUND: Estimates are complementary epidemiological measures which allow to present data on cancer burden, especially in geographical areas where measurements of cancer occurrence are not supported by exhaustive statistics on incidence, mortality and survival. The aim of this paper is to provide cancer incidence, mortality and prevalence estimates and projections for the major cancers in the period 1970-2015 for the entire region of Sicily. METHODS: The estimates were computed 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 the regional cancer survival. RESULTS: In 2012 the most common cancers were breast cancer in women, colorectal cancer in both sexes, and prostate cancer in men, with about 4,000, 3,500 and 3,000 estimated new cases, respectively. The highest crude mortality rates were estimated for lung cancer in men (63.6 per 100,000) and breast cancer in women (30.8 per 100,000) and the lowest for skin melanoma (both sexes) and cancer of the cervix uteri. For colorectal, lung and stomach cancer and skin melanoma, all the indicators were higher in men than women. The prevalence figures in women were more than 9 times the incidence figures for breast cancer and more than 10 times the incidence figures for skin melanoma. The prevalence was twice the incidence for lung cancer in both sexes. The prevalence increased for all the considered cancers except cervical cancer. CONCLUSION: According to our analyses in Sicily we expect about 14,000 new diagnoses and 5,500 deaths for the major cancer types in a year, while about 92,000 persons with a diagnosis of the considered cancers were alive in 2012. We expect an increase in cancer survival and contemporary aging of the population: both expectations will inflate the cancer prevalence, causing more demand for oncology facilities.

Cancer estimates up to 2015 in Friuli Venezia Giulia.

AIMS AND BACKGROUND: This analysis intended to estimate the incidence, mortality and prevalence time trends for the major cancer sites up to 2015 in the Friuli Venezia Giulia region, northeastern Italy, where a population-based cancer registry has been covering the whole area since 1995. METHODS: The MIAMOD method, a statistical back-calculation approach, was applied to estimate incidence, mortality and prevalence figures, in the period 1970-2015, using mortality data from the Italian National Institute of Statistics and relative survival data from Italian cancer registries. RESULTS: We estimated that the cancer sites with the highest incidence rates in the forthcoming years will be breast in women (with an age-standardized incidence rate of 130 per 100,000 in 2015), prostate in men (97 per 100,000) and colon-rectum in both sexes (85 and 42 per 100,000 in men and women, respectively). The incidence rates for lung cancer will continue to decrease only in men (down to 43 per 100,000 in 2015). Although the decline in the mortality rates of lung, breast and colorectal cancers is likely to persist, these tumors will remain the big killers in the near future. The number of people living in Friuli Venezia Giulia after a cancer diagnosis is expected to continue to rise in particular for breast cancer (with a crude prevalence of 3,000 per 100,000 women in 2015), prostate cancer (1,700 per 100,000 men) and colorectal cancer (1,100 and 800 per 100,000 in men and women, respectively). CONCLUSION: These estimates confirmed the epidemiological patterns in time trends of major cancer sites recorded in Friuli Venezia Giulia. They highlighted in particular the increasing number of people living after a cancer diagnosis as a result of population aging, earlier diagnosis and better prognosis, which warrants adequate public health policies.

Multiple tumours in survival estimates.

In international comparisons of cancer registry based survival it is common practice to restrict the analysis to first primary tumours and exclude multiple cancers. The probability of correctly detecting subsequent cancers depends on the registry's running time, which results in different proportions of excluded patients and may lead to biased comparisons. We evaluated the impact on the age-standardised relative survival estimates of also including multiple primary tumours. Data from 2,919,023 malignant cancers from 69 European cancer registries participating in the EUROCARE-4 collaborative study were used. A total of 183,683 multiple primary tumours were found, with an overall proportion of 6.3% over all the considered cancers, ranging from 0.4% (Naples, Italy) to 12.9% (Iceland). The proportion of multiple tumours varied greatly by type of tumour, being higher for those with high incidence and long survival (breast, prostate and colon-rectum). Five-year relative survival was lower when including patients with multiple cancers. For all cancers combined the average difference was -0.4 percentage points in women and -0.7 percentage points in men, and was greater for older registries. Inclusion of multiple tumours led to lower survival in 44 out of 45 cancer sites analysed, with the greatest differences found for larynx (-1.9%), oropharynx (-1.5%), and penis (-1.3%). Including multiple primary tumours in survival estimates for international comparison is advisable because it reduces the bias due to different observation periods, age, registration quality and completeness of registration. The general effect of inclusion is to reduce survival estimates by a variable amount depending on the proportion of multiple primaries and cancer site.

Knowledge, practice and faith on Total Quality Management principles among workers in the Health Care System: evidence from an Italian investigation.

BACKGROUND: The implementation of Total Quality Management (TQM) principles in the sanitary field, in order to be effective, requires a radical change in management practice as well as the organizational culture and its philosophy. The need to monitor such a transformation emerges too. OBJECTIVES: This study surveys how well TQM principles are known and understood by health care professionals from the employees' point of view and the factors affecting it. RESEARCH DESIGN AND SUBJECTS: The Health Care System in Trieste was surveyed. MEASURES: The Total Quality Test was used, a novel and quick instrument aimed at routine assessment of the penetration and interiorization of TQM principles within the health care structure. RESULTS: Direct exposure to public, job role and time spent working within the same structure have been proved related to the penetration of TQM principles, whereas previous formative intervention did not prove to be associated with the penetration of TQM principles. CONCLUSIONS: The implementation of a quick and simple instrument to monitor the TQM implementation highlighted several critical areas for intervention.

The cure of cancer: a European perspective.

Cancer survival analyses based on cancer registry data do not provide direct information on the main aim of cancer treatment, the cure of the patient. In fact, classic survival indicators do not distinguish between patients who are cured, and patients who will die of their disease and in whom prolongation of survival is the main objective of treatment. In this study, we applied parametric cure models to the cancer incidence and follow-up data provided by 49 EUROCARE-4 (European Cancer Registry-based study, fourth edition) cancer registries, with the aims of providing additional insights into the survival of European cancer patients diagnosed from 1988 to 1999, and of investigating between-population differences. Between-country estimates the proportion of cured patients varied from about 4-13% for lung cancer, from 9% to 30% for stomach cancer, from 25% to 49% for colon and rectum cancer, and from 55% to 73% for breast cancer. For all cancers combined, estimates varied between 21% and 47% in men, and 38% and 59% in women and were influenced by the distribution of cases by cancer site. Countries with high proportions of cured and long fatal case survival times for all cancers combined were characterised by generally favourable case mix. For the European pool of cases both the proportion of cured and the survival time of fatal cases were associated with age, and increased from the early to the latest diagnosis period. The increases over time in the proportions of Europeans estimated cured of lung, stomach and colon and rectum cancers are noteworthy and suggest genuine progress in cancer control. The proportion of cured of all cancers combined is a useful general indicator of cancer control as it reflects progress in diagnosis and treatment, as well as success in the prevention of rapidly fatal cancers.

Survival of European children and young adults with cancer diagnosed 1995-2002.

This study analyses survival in 40,392 children (age 0-14 years) and 30,187 adolescents/young adults (age 15-24 years) diagnosed with cancer between 1995 and 2002. The cases were from 83 European population-based cancer registries in 23 countries participating in EUROCARE-4. Five-year survival in countries and in regional groupings of countries was compared for all cancers combined and for major cancers. Survival for 15 rare cancers in children was also analysed. Five-year survival for all cancers combined was 81% in children and 87% in adolescents/young adults. Between-country survival differences narrowed for both children and adolescents/young adults. Relative risk of death reduced significantly, by 8% in children and by 13% in adolescents/young adults, from 1995-1999 to 2000-2002. Survival improved significantly over time for acute lymphoid leukaemia and primitive neuroectodermal tumours in children and for non-Hodgkin lymphoma in adolescents/young adults. Cancer survival in patients <25 years is poorly documented in Eastern European countries. Complete cancer registration should be a priority for these countries as an essential part of a policy for effective cancer control in Europe.

Proper modeling strategies selection for the assessment of post-infarction costs.

BACKGROUND: The evaluation of the economic impact of ischemic disease has gained increasing interest. Such field of investigation is suffering however of the heterogeneity of methods used in evaluating costs, limiting the comparison of study results. OBJECTIVE: The aim of the study is to show how estimates of 1-year costs of treatment of patients with uncomplicated acute myocardial infarction can vary significantly in relation to the statistical method adopted in the analysis. RESEARCH DESIGN AND METHODS: The study analyses post-IMA costs as a function of demographic and clinical covariates, by applying the following statistical survival models: the parametric survival model assuming Weibull distribution, the Cox proportional hazard (PH) model and the Aalen additive regression for modelling costs. The Aalen approach is robust both for the non-proportionality in hazard and for departures from normality. In addition it is able to easily model the effect of covariates on the extreme costs. This cost analysis is based on data collected in the two COSTAMI trials (N=487). RESULTS: There is agreement in all models with the effects of the considered covariates (age, sex, duration of disease and presence of other pathologies). There is a clear tendency of both the Aalen and the Cox model to provide a lower mean cost estimate than the other model, but with the additional feature for the Aalen model to be able to cope with all the other models in furnishing unbiased estimates with the advantage of a greater flexibility in representing the covariates' effect on the cost process. CONCLUSIONS: An appropriate choice of the model is crucial in avoiding mis-interpretation of cost determinants of IMA patients. For our data set the Aalen model proved itself to be a realistic and informative way to characterize the effect of covariates on costs.