Mammographic density to predict response to neoadjuvant systemic breast cancer therapy.

BACKGROUND: Mammographic density (MD) is a risk factor for breast cancer (BC) development, and recurrence. However, its predictive value has been less studied. Herein, we challenged MD as a biomarker associated with response in patients treated with neoadjuvant therapy (NAT). METHODS: Data on all NAT treated BC patients prospectively collected in the registry of Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy (2009-2019) were identified. Diagnostic mammograms were used to evaluate and score MD as categorized by the Breast Imaging-Reporting and Data System (BI-RADS), which identifies 4 levels of MD in keeping with relative increase of fibro-glandular over fat tissue. Each case was classified according to the following categories a (MD < 25%), b (26-50%), c (51-75%), and d (> 75%). The association between MD and pathological complete response (pCR), i.e., absence of BC cells in surgical specimens, was analyzed in multivariable setting used logistic regression models with adjustment for clinical and pathological variables. RESULTS: A total of 442 patients were analyzed, 120 of which (27.1%) attained a pCR. BI-RADS categories a, b, c, and d accounted for 10.0%, 37.8%, 37.1% and 15.2% of cases. Corresponding pCR were 20.5%, 26.9%, 30.5%, 23.9%, respectively. At multivariable analysis, when compared to cases classified as BI-RADS a, those with denser breast showed an increased likelihood of pCR with odds ratio (OR) of 1.70, 2.79, and 1.47 for b, c and d categories, respectively (p = 0.0996), independently of age, BMI [OR underweight versus (vs) normal = 3.76], clinical nodal and tumor status (OR T1/Tx vs T4 = 3.87), molecular subtype (HER2-positive vs luminal = 10.74; triple-negative vs luminal = 8.19). In subgroup analyses, the association of MD with pCR was remarkable in triple-negative (ORs of b, c and d versus a: 1.85, 2.49 and 1.55, respectively) and HER2-positive BC cases (ORs 2.70, 3.23, and 1.16). CONCLUSION: Patients with dense breast are more likely to attain a pCR at net of other predictive factors. The potential of MD to assist decisions on BC management and as a stratification factor in neoadjuvant clinical trials should be considered.

Older age and comorbidity in breast cancer: is RT alone the new therapeutic frontier?

AIM: To assess the impact of age, comorbidities and endocrine therapy (ET) in older breast cancer (BC) patients treated with hypofractionated radiotherapy (Hypo-RT). METHODS: From June 2009 to December 2017, we enrolled in this study 735 ER-positive BC patients (stage pT1-T2, pNx-1, M0 and age ≥ 65 years) receiving hypo-RT and followed them until September 2019. Baseline comorbidities included in the hypertension-augmented Charlson Comorbidity Index were retrospectively retrieved. Logistic regression model estimated adjusted-odds ratios (ORs) of ET prescription in relation to baseline patient and tumor characteristics. Competing risk analysis estimated 5-year cumulative incidence function (CIF) of ET discontinuation due to side effects (with BC progression or death as competing events), and its effect on locoregional recurrence (LRR) and distant metastasis (DM) (with death as competing event). RESULTS: ET has been prescribed in 89% patients. In multivariable analysis, the odds of ET prescription was significantly reduced in older patients (≥ 80 years, OR 0.08, 95% CI 0.03-0.20) and significantly increased in patients with moderate comorbidity. Patients ≥ 80 years discontinued the prescribed therapy earlier and more frequently than younger (65-69 years) patients (p = 0.060). Five-year CIF of LLR, DM and death from causes other that BC were 1.7%, 2.2% and 7.5%, respectively. Patients who discontinued ET had higher chance of LRR (p = 0.004). ET use did not impact on OS in any of the analyzed groups. CONCLUSIONS: In older patients, ET did not show a benefit in terms of overall survival. Further studies focusing on tailored treatment approaches are warranted to offer the best care in terms of adjuvant treatment to these patients.

Axillary nodal involvement by primary tumor features in early breast cancer: an analysis of 2600 patients.

BACKGROUND: Primary tumor characteristics, which are readily available to all clinicians, may aid in selecting the optimal adjuvant therapy for patients with breast cancer (BC). Herein, we investigated the relationship between tumor size, hormone receptor and HER2 status, Ki67 and age with axillary lymph node metastases (ALNM) in early-BC patients. METHODS: We analyzed data on consecutive 2600 early-BC cases collected in the registry of Fondazione IRCC Istituto Nazionale dei Tumori, Milano, Italy. Correlation between Ki67 and primary tumor size (T-size) was calculated by Spearman's rank correlation coefficient. Association of ALNM with Ki67 and other tumor characteristics was investigated by logistic regression. Adjusted odds ratios (ORs) with 95% confidence intervals (95% CIs) were estimated in all cases, and separately analyzed according to age, T-size and BC subtype. RESULTS: Large tumor size strongly associated to ALNM, with an adjusted odds ratio (OR) for each 5-mm increase of 1.32 (95% CI 1.24-1.41), except for triple-negative BC (TNBC) cases. In tumors =10 mm, without lymphovascular invasion, representing the strongest predictor of ALNM (OR 6.09, 95% CI 4.93-7.53), Ki67 resulted particularly informative, with a fourfold increased odds of ALNM for values > 30%. CONCLUSIONS: These results raise the question whether axillary node status is redundant in cases with exceptionally good features, i.e., small tumors with low Ki67, or in those candidate to adjuvant systemic treatment/radiotherapy anyway including TNBC, and support the incorporation of primary BC tumor characteristics as stratification factors in ongoing trials aiming at de-escalating axillary surgical procedures.

Patient, tumor, and healthcare factors associated with regional variability in lung cancer survival: a Spanish high-resolution population-based study.

PURPOSE: The third most frequently diagnosed cancer in Europe in 2018 was lung cancer; it is also the leading cause of cancer death in Europe. We studied patient and tumor characteristics, and patterns of healthcare provision explaining regional variability in lung cancer survival in southern Spain. METHODS: A population-based cohort study included all 1196 incident first invasive primary lung cancer (C33-C34 according to ICD-10) cases diagnosed between 2010 and 2011 with follow-up until April 2015. Data were drawn from local population-based cancer registries and patients' hospital medical records from all public and private hospitals from two regions in southern Spain. RESULTS: There was evidence of regional differences in lung cancer late diagnosis (58% stage IV in Granada vs. 65% in Huelva, p value < 0.001). Among patients with stage I, only 67% received surgery compared with 0.6% of patients with stage IV. Patients treated with a combination of radiotherapy, chemotherapy, and surgery had a 2-year mortality risk reduction of 94% compared with patients who did not receive any treatment (excess mortality risk 0.06; 95% CI 0.02-0.16). Geographical differences in survival were observed between the two regions: 35% vs. 26% at 1-year since diagnosis. CONCLUSIONS: The observed geographic differences in survival between regions are due in part to the late cancer diagnosis which determines the use of less effective therapeutic options. Results from our study justify the need for promoting lung cancer early detection strategies and the harmonization of the best practice in lung cancer management and treatment.

Cancer survival in adult patients in Spain. Results from nine population-based cancer registries

Introduction. With the aim of providing cancer control indicators, this work presents cancer survival in adult (≥15 years) patients in Spain diagnosed during the period 2000-2007 from Spanish cancer registries participating in the EUROCARE project. Methods. Cancer cases from nine Spanish population-based cancer registries were included and analysed as a whole. All primary malignant neoplasms diagnosed in adult patients were eligible for the analysis. Cancer patients were followed until 31 December 2008. For each type of cancer, 1-, 3- and 5-year observed and relative survival were estimated by sex, age and years from diagnosis. Furthermore, age-standardized 5-year relative survival for the period 2000-2007 has been compared with that of the period 1995-1999. Results. Skin melanoma (84.6 95% CI 83.0-86.2), prostate (84.6% 95% CI 83.6-85.6) and thyroid (84.2% CI 95% 82.0-86.6) cancers showed the highest 5-year relative survival, whereas the worst prognosis was observed in pancreatic (6% 95% CI 5.1-7.0) and oesophageal (9.4% 95% CI 7.9-11.1) cancers. Overall, survival is higher in women (58.0%) than in men (48.9%). The absolute difference in relative survival between 2000-2007 and 1995-1999 was positive for all cancers as a whole (+4.8% in men, +1.6% in women) and for most types of tumours. Survival increased significantly for chronic myeloid leukaemia, non-Hodgkin’s lymphoma and rectum cancer in both sexes, and for acute lymphoid leukaemia, prostate, liver and colon cancers in men and Hodgkin’s lymphoma and breast cancer in women. Survival patterns by age were similar in Europe and Spain. A decline in survival by age was observed in all tumours, being more pronounced for ovarian, corpus uteri, prostate and urinary bladder and less for head and neck and rectum cancers. Conclusion. High variability and differences have been observed in survival among adults in Spain according to the type of cancer diagnosed, from above 84% to below 10%, reflecting high heterogeneity. The differences in prognosis by age, sex and period of diagnosis reveal opportunities for improving cancer care in Spain (AU)

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Cancer survival in adult patients in Spain. Results from nine population-based cancer registries.

INTRODUCTION: With the aim of providing cancer control indicators, this work presents cancer survival in adult (≥15 years) patients in Spain diagnosed during the period 2000-2007 from Spanish cancer registries participating in the EUROCARE project. METHODS: Cancer cases from nine Spanish population-based cancer registries were included and analysed as a whole. All primary malignant neoplasms diagnosed in adult patients were eligible for the analysis. Cancer patients were followed until 31 December 2008. For each type of cancer, 1-, 3- and 5-year observed and relative survival were estimated by sex, age and years from diagnosis. Furthermore, age-standardized 5-year relative survival for the period 2000-2007 has been compared with that of the period 1995-1999. RESULTS: Skin melanoma (84.6 95% CI 83.0-86.2), prostate (84.6% 95% CI 83.6-85.6) and thyroid (84.2% CI 95% 82.0-86.6) cancers showed the highest 5-year relative survival, whereas the worst prognosis was observed in pancreatic (6% 95% CI 5.1-7.0) and oesophageal (9.4% 95% CI 7.9-11.1) cancers. Overall, survival is higher in women (58.0%) than in men (48.9%). The absolute difference in relative survival between 2000-2007 and 1995-1999 was positive for all cancers as a whole (+4.8% in men, +1.6% in women) and for most types of tumours. Survival increased significantly for chronic myeloid leukaemia, non-Hodgkin's lymphoma and rectum cancer in both sexes, and for acute lymphoid leukaemia, prostate, liver and colon cancers in men and Hodgkin's lymphoma and breast cancer in women. Survival patterns by age were similar in Europe and Spain. A decline in survival by age was observed in all tumours, being more pronounced for ovarian, corpus uteri, prostate and urinary bladder and less for head and neck and rectum cancers. CONCLUSION: High variability and differences have been observed in survival among adults in Spain according to the type of cancer diagnosed, from above 84% to below 10%, reflecting high heterogeneity. The differences in prognosis by age, sex and period of diagnosis reveal opportunities for improving cancer care in Spain.

Factors influencing acute and late toxicity in the era of adjuvant hypofractionated breast radiotherapy.

PURPOSE: To evaluate toxicity in breast cancer patients treated with anthracycline and taxane based chemotherapy and whole breast hypofractionated radiotherapy, and to identify the risk factors for toxicity. METHODS AND MATERIALS: 537 early breast cancer patients receiving hypofractionated radiotherapy after conservative surgery were enrolled from April 2009 to December 2014, in an Italian cancer institute. The dose was 42.4 Gy in 16 daily fractions, 2.65 Gy per fraction. The boost to the tumor bed was administered only in grade III breast cancer patients and in patients with close or positive margins. Acute and late toxicity were prospectively assessed during and after radiotherapy according to RTOG scale. The impact of patients clinical characteristics, performed treatments and dose inhomogeneities on the occurrence of an higher level of acute skin toxicity and late fibrosis has been evaluated by univariate and multivariate analysis. RESULTS: The mean age was 74 (range 46-91 yrs). 27% of patients received boost. 22% of cases (n = 119) received also chemotherapy. The median follow-up was 32 months. G1 and G2/G3 acute skin toxicity were 61.3% and 20.5% and G1 and G2/G3 late fibrosis 12.6% and 4.3% respectively. Chemotherapy (p = 0.04), diabetes (p = 0.04) and boost administration (p < 0.01) were found to be statistically significant on the occurrence of late fibrosis, but a multivariate analysis did not show any factors connected. The boost administration (p < 0.01), the breast volume (p = 0.05), dose inhomogeneities (p < 0.01) and boost volume (p = 0.04) were found to be statistically significant as concerns the occurrence of acute skin reaction at the univariate analysis, but only the boost administration (p = 0.02), at multivariate analysis. CONCLUSIONS: The results of our study, according to the large randomized trials, confirmed that hypofractionated whole breast irradiation is safe, and only the boost administration seems to be an important predictor for toxicity. Chemotherapy does not impact on acute and late skin toxicity.

Survival for oesophageal, stomach and small intestine cancers in Europe 1999-2007: Results from EUROCARE-5.

BACKGROUND: European regional variation in cancer survival was reported in the EUROCARE-4 study for patients diagnosed in 1995-1999. Relative survival (RS) estimates are here updated for patients diagnosed with cancer of the oesophagus, stomach and small intestine from 2000 to 2007. Trends in RS from 1999-2001 to 2005-2007 are presented to monitor and discuss improvements in patient survival in Europe. MATERIALS AND METHODS: EUROCARE-5 data from 29 countries (87 cancer registries) were used to investigate 1- and 5-year RS. Using registry-specific life-tables stratified by age, gender and calendar year, age-standardised 'complete analysis' RS estimates by country and region were calculated for Northern, Southern, Eastern and Central Europe, and for Ireland and United Kingdom (UK). Survival trends of patients in periods 1999-2001, 2002-2004 and 2005-2007 were investigated using the 'period' RS approach. We computed the 5-year RS conditional on surviving the first year (5-year conditional survival), as the ratio of age-standardised 5-year RS to 1-year RS. RESULTS: Oesophageal cancer 1- and 5-year RS (40% and 12%, respectively) remained poor in Europe. Patient survival was worst in Eastern (8%), Northern (11%) and Southern Europe (10%). Europe-wide, there was a 3% improvement in oesophageal cancer 5-year survival by 2005-2007, with Ireland and the UK (3%), and Central Europe (4%) showing large improvements. Europe-wide, stomach cancer 5-year RS was 25%. Ireland and UK (17%) and Eastern Europe (19%) had the poorest 5-year patient survival. Southern Europe had the best 5-year survival (30%), though only showing an improvement of 2% by 2005-2007. Small intestine cancer 5-year RS for Europe was 48%, with Central Europe having the best (54%), and Ireland and UK the poorest (37%). Five-year patient survival improvement for Europe was 8% by 2005-2007, with Central, Southern and Eastern Europe showing the greatest increases (⩾9%). CONCLUSIONS: Survival for these cancer sites, particularly oesophageal cancer, remains poor in Europe with wide variation. Further investigation into the wide variation, including analysis by histology and anatomical sub-site, will yield insights to better monitor and explain the improvements in survival observed over time.

Operative mortality after gastric cancer resection and long-term survival differences across Europe.

BACKGROUND: : Little is known at a population level about operative mortality after surgery for gastric cancer and whether differences between countries can explain differences in long-term survival. This study compared operative mortality recorded by ten cancer registries in seven European countries. METHODS: : Non-conditional logistic regression analysis was performed to estimate the independent effect of the studied factors on mortality within 30 days of surgery. A multivariable survival model was employed with and without operative mortality. RESULTS: : The overall operative mortality rate in 1611 patients studied was 8.9 (range 5.2-16) per cent. Country of residence was a significant prognostic factor in the multivariable analysis. The likelihood of operative mortality was lower in Italy, France and the UK than in the Netherlands, Spain, Slovenia and Poland. Age, type of gastrectomy and stage at diagnosis were also significant factors. Cancer site was not found to be significant in the multivariable analysis. The overall 5-year relative survival rate varied between 42.0 per cent (Italy) and 24 per cent (Poland); after excluding operative mortality, the 5-year survival rate was 44.3 and 28 per cent respectively. CONCLUSION: : Within Europe, the substantial differences in operative mortality after gastrectomy only partly explain marked differences in survival after gastric cancer resection.

Prognostic value of morphology and hormone receptor status in breast cancer - a population-based study.

We analysed the 5-year relative survival among 4473 breast cancer cases diagnosed in 1990-1992 from cancer registries in Estonia, France, Italy, Spain, the Netherlands and the UK. Among eight categories based on ICD-O codes (infiltrating ductal carcinoma, lobular plus mixed carcinoma, comedocarcinoma, 'special types', medullary carcinoma, not otherwise specified (NOS) carcinoma, other carcinoma and cancer without microscopic confirmation), the 5-year relative survival ranged from 66% (95% CI 61-71) for NOS carcinoma to 95% (95% CI 90-100) for special types (tubular, apocrine, cribriform, papillary, mucinous and signet ring cell); 27% (95% CI 18-36) for cases without microscopic confirmation. Differences in 5-year relative survival by tumor morphology and hormone receptor status were modelled using a multiple regression approach based on generalised linear models. Morphology and hormone receptor status were confirmed as significant survival predictors in this population-based study, even after adjusting for age and stage at diagnosis.

Thromboprophylaxis for caesarean section--how can uptake and coverage be improved?

The objective of this study was to determine the proportion of patients requiring thromboprophylaxis and evaluate adherence to local protocols on thromboprophylaxis after caesarean section. This was a retrospective audit of 200 consecutive patients undergoing caesarean section between January and March 2002. The study was carried out at two obstetric units in Hull. We evaluated the proportion of patients requiring prophylaxis, appropriate and inappropriate treatment given and those omitted from receiving prophylaxis. Adherence to a risk assessment protocol was also assessed. The majority of women (84.5%) had at least one risk factor for thromboembolism. Use of a checklist did not increase the appropriate use of thromboprophylaxis and did not reduce inappropriate use. The checklist was used appropriately in only 54% of cases. Thromboprophylaxis has not been associated with problems if given after operation, thus the inappropriate administration is probably not a serious mistake. Universal prophylaxis with low molecular weight heparin would prevent at-risk women being missed and should be considered.

European health systems and cancer care.

INTRODUCTION: Data on the survival of all incident cases collected by population-based cancer registries make it possible to evaluate the overall performance of diagnostic and therapeutic actions on cancer in those populations. EUROCARE-3 is the third round of the EUROCARE project, the largest cancer registry population based collaborative study on survival in European cancer patients. The EUROCARE-3 study analysed the survival of cancer patients diagnosed from 1990 to 1994 and followed-up to 1999. Sixty-seven cancer registries of 22 European countries characterised by differing health systems participated in the study. This paper includes essays providing brief overviews of the state and evolution of the health systems of the considered countries and comments on the relation between cancer survival in Europe and some European macro-economic and health system indicators, in the 1990s. OVERVIEW OF THE EUROPEAN HEALTH SYSTEMS: The European health systems underwent a great deal of reorganisation in the last decade; a general tendency being to facilitate expanding involvement of the private sector in health care, a process which occurred mainly in the eastern countries (i.e. the Czech Republic, Estonia, Poland, Slovakia and Slovenia). In contrast, organisational changes in the northern European countries (i.e. Denmark, Iceland, Finland and Sweden) tended to confirm the established public sector systems. Other countries, including the UK and some southern European countries (i.e. England, Scotland, Wales, Malta and Italy) have reduced the public role while the systems remain basically public, at least at present. Our findings clearly suggest that cancer survival (all cancer combined) is related to macro-economic variables such as the gross domestic product (GDP), the total national (public and private) expenditure on health (TNEH) and the total public expenditure on health (TPEH). We found, however, that survival is related to wealth (GDP), but only up to a certain level, after which survival continues to be related to the level of health investment (both TNEH and TPEH). According to the Organisation for Economic Co-operation and Development (OECD), the TNEH increased during the 1990s in all EUROCARE-3 countries, while the ratio of TPEH to TNEH reduced in all countries except Portugal. CONCLUSIONS: Cancer survival depends on the widespread application of effective diagnosis and treatment modalities, but our enquiry suggests that the availability of these depends on macro-economic determinants, including health and public health investment. Analysis of the relationship between health system organisation and cancer outcome is complicated and requires more information than is at present available. To describe cancer and cancer management in Europe, the European Cancer Health Indicator Project (EUROCHIP) has proposed a list of indicators that have to be adopted to evaluate the effects on outcome of proposed health system modifications.

EUROCARE-3: survival of cancer patients diagnosed 1990-94--results and commentary.

EUROCARE-3 analysed the survival of 1815584 adult cancer patients diagnosed from 1990 to 1994 in 22 European countries. The results are reported in tables, one per cancer site, coded according to the International Classification of Diseases (ICD)-9 classification. The main findings of the tables are summarised and commented on in this article. For most solid cancers, wide differences in survival between different European populations were found, as also reported by EUROCARE-1 and EUROCARE-2, despite a remarkable (10%) overall increase in cancer survival from 1985 to 1994. Survival was highest in northern Europe (Sweden, Norway, Finland and Iceland), and fairly good in central-southern Europe (France, Switzerland, Austria and Spain). Survival was particularly low in eastern Europe, low in Denmark and the UK, and fairly low in Portugal and Malta. The mix of tumour stage at diagnosis explains much of the survival differences for cancers of the digestive tract, female reproductive system, breast, thyroid, and also skin melanoma. For tumours of the urinary tract and prostate, the differences were explained mainly by differences in diagnostic criteria and procedures. The case mix by anatomic subsite largely explains differences in survival for head and neck cancers. For oesophagus, pancreas, liver and brain cancer, with poor prognoses, survival differences were limited. Tumours, for which highly effective treatments are available, such as testicular cancer, Hodgkin's lymphoma and some haematological malignancies, had fairly uniform survival across Europe. Survival for all tumours combined (an indicator of the overall cancer care performance of a nation's health system) was better in young than old patients, and better in women than men. The affluence of countries influenced overall cancer survival through the availability of adequate diagnostic and treatment procedures, and screening programmes.

Cancer survival increases in Europe, but international differences remain wide.

The EUROCARE project analysed cancer survival data from 45 population-based cancer registries in 17 European countries, revealing wide international differences in cancer survival. We calculated 5-year relative survival for 1836287 patients diagnosed with one of 13 cancers during the period 1978-1989. The data, from 20 cancer registries in 13 countries, were grouped into four regions: Finland, Sweden, Iceland (Northern Europe); Denmark, England and Scotland (UK and Denmark); France, The Netherlands, Germany, Italy and Switzerland (Western Europe); Estonia and Poland (Eastern Europe), and broken down into four periods (1978-1980, 1981-1983, 1984-1986, 1987-1989). For each cancer, mean European and regional survival was estimated as the weighted mean of 5-year relative survival in each country. Survival increased with time for all tumours, particularly for cancers of testis (12% increase, i.e. from 79.9 to 91.9%), breast, large bowel, skin melanoma (approximately 9-10%), and lymphomas (approximately 7%). For most solid tumours, survival was highest in Northern Europe and lowest in Eastern Europe, and also low in the UK and Denmark. Regional variation was less marked for the lymphomas. Survival improved more in Western than Northern Europe, and the differences between these regions fell for bowel cancer (from 8.0% for those diagnosed in 1978-1980 to 2% for those diagnosed in 1987-1989), breast cancer (from 7.4% to 3.9%), skin melanoma (from 13.4% to 11.0%) and Hodgkin's disease (from 7.2 to 0.6%). For potentially curable malignancies such as Hodgkin's disease, large bowel, breast and testicular cancers, there were substantial increases in survival, suggesting an earlier diagnosis and more effective treatment. The persisting regional differences suggest there are corresponding differences in the availability of diagnostic and therapeutic facilities, and in the effectiveness of healthcare systems.

Differences in stage and therapy for breast cancer across Europe.

We examined variations in stage, diagnostic workup and therapy for breast cancer across Europe. Seventeen cancer registries in six European countries contributed 4,480 cases diagnosed in 1990-91. The clinical records of these cases were examined, and the distribution of stage, diagnostic examinations and therapy were analyzed. Stage was earliest in the French registries, followed by those of Italy and Eindhoven (Netherlands). The proportion of stage I cancers was highest in the French areas with screening in place. Estonia, the English registries and Granada (Spain) had the most advanced stage at diagnosis. Use of liver ultrasonography varied from 84% (Italian registries) to 18% (Granada). Bone scan use varied from 81% (Italian registries) to 15% (Mersey, UK). The highest proportions treated by breast-conserving surgery were in the French (57%) and English registries (63%); the lowest were in Estonia (6%) and Granada (11%). The highest proportions of Halsted mastectomies were in Italy (19%) and Granada (8%). In all countries except England, 90% of operations included axillary lymphadenectomy. Medical treatment only was given to 8% of (mostly advanced) cases overall. Estonia (21%) and the English registries (14%) had the highest proportions of patients given medication only. Chemotherapy was given to low proportions of node-positive cases in the Italian (76%) and English (74%) areas; breast-conserving surgery for stage I tumors varied from 24% in Granada to 84% in England. These wide differences in breast cancer care across Europe in the early 1990s indicate a need for continual monitoring of past treatments to help ensure application of the most effective protocols.

Incidence and prevalence of all cancerous diseases in Italy: trends and implications.

The burden of cancer in ageing populations is causing great concern, particularly in Italy with Europe's fastest growing elderly population. Studying all cancers combined in one group, although of limited medical value, is of great interest from the viewpoints of public health, epidemiology and the economy. Using mortality data and an estimate of cancer patients' survival we have estimated and projected incidence and prevalence in Italy of all cancers combined in one group. Five major phenomena are highlighted in the paper: (1) the decrease in the age-adjusted cancer mortality rates among females and the stable mortality rates among males since 1990; (2) the changing pattern of cancer incidence since 1990, it has started to decrease for females and is stabilising for males; (3) the decrease in cancer incidence among males and females born after 1940; (4) the increase in the proportion of cancer patients that are cured with calendar years of diagnosis; (5) the increase in the total and the healthy life expectancy (i.e. cancer-free) among the Italian population since 1970. The declining and flat trends in age-adjusted cancer incidence and mortality rates since 1990 is the combined effect of survival improvements and cancer risk reduction for younger cohort groups, after 1940. These favourable trends contribute to the increase in healthy life expectation, thus supporting the idea that we live longer and healthier.

Survival for retinoblastoma in Europe.

The survival of 954 cases of retinoblastoma, diagnosed between 1978 and 1989 in 28 populations belonging to 17 European countries and covered by cancer registration, is analysed in this study. Data were collected in the framework of the EUROCARE study following a common protocol and data-check procedures and were analysed centrally by the Kaplan-Meier method and by the Cox regression model. Overall 5-year survival in the European pool was 93% (95% confidence interval (CI): 91--95%), for both sexes. Five-, 10- and 18-year survival for a subset of 235 patients diagnosed in 1978--1981 was 91, 89 and 86%, respectively. Children diagnosed in their first year of age had a slightly higher survival (94%) than those diagnosed subsequently (92%). Survival rates lower than the European average were found in the Eastern European countries, Italy, England and Wales, Scotland, Spain and Denmark. Higher survival was found in the other Nordic countries and in Central European countries. However, none of these differences was statistically significant. There was statistically significant effect related to the period of diagnosis, with a 50% reduction in the relative risk (RR) for children diagnosed in 1986--1989 compared with those diagnosed in 1978-1981.

Understanding variations in survival for colorectal cancer in Europe: a EUROCARE high resolution study.

BACKGROUND: Marked differences in population based survival across Europe were found for colorectal cancers diagnosed in 1985-1989. AIMS: To understand the reasons for these differences in survival in a new analysis of colorectal cancers diagnosed between 1988 and 1991. SUBJECTS: A total of 2720 patients with adenocarcinoma of the large bowel from 11 European cancer registries (CRs). METHODS: We obtained information on stage at diagnosis, diagnostic determinants, and surgical treatment (not routinely collected by CRs) and analysed the data in relation to three year observed survival, calculating relative risks (RRs) of death and adjusting for age, sex, site, stage, and determinants of stage. RESULTS: Three year observed survival rates ranged from 25% (Cracow) to 59% (Modena), and were low in the Thames area (UK) (38%). Survival rates between registries for "resected" patients varied less than those for all patients. When age, sex, and site were considered, RRs ranged from 0.7 (95% confidence intervals (CI) 0.6-0.9) (Modena) to 2.3 (95% CI 1.9-2.9) (Cracow). After further adjustment by stage, between registry RR variation was between 0.8 (95% CI 0.6-0.9) and 1.8 (95% CI 1.5-2.2). Inter-registry RR differences were slightly reduced when the determinants of stage (number of nodes examined and liver imaging) were included in the model. The reduction was marked for the UK registries. CONCLUSIONS: The wide differences across Europe in colorectal cancer survival depend to a large extent on differences in stage at diagnosis. There are wide variations in diagnostic and surgical practices. There was a twofold range in the risk of death from colorectal cancer even after adjustment for surgery and disease stage.