Cardiovascular Risk After Adjuvant Trastuzumab in Early Breast Cancer: An Italian Population-Based Cohort Study.

BACKGROUND: Although trastuzumab (T) represents the standard of care for the adjuvant treatment of HER2-positive early-stage breast cancer, contrasting results are available about the cardiac toxicity associated to its use. We conducted a multiregional population-based cohort investigation aimed to assess both the short- and long-term cardiovascular (CV) outcomes in women with early breast cancer treated with T-based or standard adjuvant chemotherapy (CT). MATERIALS AND METHODS: We used health care use databases of six Italian regions, overall accounting for 42% of the Italian population. The study cohort was made by all women surgically treated for breast cancer who started a first-line adjuvant T-based or CT treatment. Patients treated with T were 1:2 matched to those treated with CT based on date of treatment start, age, and presence of CV risk factors. Short- and long-term CV outcomes (heart failure and cardiomyopathy) were measured, respectively, after 1 year and at the end of follow-up. RESULTS: Among 28,599 women who met the inclusion criteria, 6,208 T users were matched to 12,416 CT users. After a mean follow-up of 5.88 years, short- and long-term cumulative CV risk were 0.8% and 2.6% in patients treated with T and 0.2% and 2.8% in those treated with CT, respectively. Adjusted hazard ratios were 4.6 (95% confidence interval [CI], 2.6-8.0) for short-term and 1.2 (95% CI, 0.9-1.6) for long-term CV risk. DISCUSSION: In our large real-world investigation, T-associated cardiotoxicity was limited to the treatment period. The addition of T to adjuvant CT did not result in long-term worsening of CV events. IMPLICATIONS FOR PRACTICE: Adjuvant trastuzumab-based chemotherapy represents the backbone therapy in patients with HER2-positive early breast cancer. Although well tolerated, cardiovascular events can manifest during or after therapy because of treatment-related toxicities. In this wide multicenter and unselected cohort, long-term symptomatic cardiotoxicity was low and limited to the treatment period. The findings suggest that developing tools that would be adequately able to predict cardiac toxicity at an early stage remains an important area in which additional research efforts are needed.

Endocrine treatment and incidence of relapse in women with oestrogen receptor-positive breast cancer in Europe: a population-based study.

PURPOSE: Endocrine therapy (ET) is the mainstream adjuvant treatment for ER-positive breast cancer (BC). We analysed 9293 ER-positive BC patients diagnosed in nine European countries in 2009-2013 to investigate how comorbidities at diagnosis, age, stage and subtype affected ET use over time, and relapse. METHODS: Adjusted odds ratios (ORs) and 95% confidence intervals (95%CIs) of receiving ET were estimated according to Charlson comorbidity, age, stage and subtype using logistic regression. The 2-year cumulative incidence and adjusted sub-hazard ratios (SHRs) of relapse were estimated using competing risk analysis, with all-cause death as the competing event. The z-test was used to assess differences in the proportion of patients receiving ET in 1996-1998 and 2009-2013. RESULTS: Ninety percent of the patients started adjuvant ET, range 96% (Belgium, Estonia, Slovenia, Spain)-75% (Switzerland). ORs of starting ET were lower for women aged > 75 years, with severe comorbidities, or luminal B HER2-positive cancer. The factors independently increasing the risk of relapse were: not receiving ET (SHR 2.26, 95%CI 1.02-5.03); severe comorbidity (SHR 1.94, 95%CI 1.06-3.55); luminal B, either HER2 negative (SHR 3.06, 95%CI 1.61-5.79) or positive (SHR 3.10, 95%CI 1.36-7.07); stage II (SHR 3.20, 95%CI 1.56-6.57) or stage III (SHR 7.41, 95%CI 3.48-15.73). ET use increased significantly but differently across countries from 51-85% in 1996-1998 to 86-96% in 2009-2013. CONCLUSIONS: ER-positive BC patients in Europe are increasingly prescribed ET but between-country disparities persist. Older women and women with severe comorbidity less frequently receive ET. ET omission and severe comorbidity independently predict early disease relapse.

Reasons for low cervical cancer survival in new accession European Union countries: a EUROCARE-5 study.

PURPOSE: With better access to early diagnosis and appropriate treatment, cervical cancer (CC) burden decreased in several European countries. In Eastern European (EE) countries, which accessed European Union in 2004, CC survival was worse than in the rest of Europe. The present study investigates CC survival differences across five European regions, considering stage at diagnosis (local, regional and metastatic), morphology (mainly squamous versus glandular tumours) and patients' age. METHODS: We analysed 101,714 CC women diagnosed in 2000-2007 and followed-up to December 2008. Age-standardised 5-year relative survival (RS) and the excess risks of cancer death in the 5 years after diagnosis were computed. RESULTS: EE women were older and less commonly diagnosed with glandular tumours. Proportions of local stage cancers were similar across Europe, while morphology- and stage-specific RS (especially for non-metastatic disease) were lower in Eastern Europe. Adjusting for age and morphology, excess risk of local stage CC death for EE patients remained higher than that for other European women. CONCLUSION: Stage, age and morphology alone do not explain worse survival in Eastern Europe: less effective care may play a role, probably partly due to fewer or inadequate resources being allocated to health care in this area, compared to the rest of Europe.

Resection of pancreatic cancer in Europe and USA: an international large-scale study highlighting large variations.

OBJECTIVE: Resection can potentially cure resectable pancreatic cancer (PaC) and significantly prolong survival in some patients. This large-scale international study aimed to investigate variations in resection for PaC in Europe and USA and determinants for its utilisation. DESIGN: Data from six European population-based cancer registries and the US Surveillance, Epidemiology, and End Results Program database during 2003-2016 were analysed. Age-standardised resection rates for overall and stage I-II PaCs were computed. Associations between resection and demographic and clinical parameters were assessed using multivariable logistic regression models. RESULTS: A total of 153 698 records were analysed. In population-based registries in 2012-2014, resection rates ranged from 13.2% (Estonia) to 21.2% (Slovenia) overall and from 34.8% (Norway) to 68.7% (Denmark) for stage I-II tumours, with great international variations. During 2003-2014, resection rates only increased in USA, the Netherlands and Denmark. Resection was significantly less frequently performed with more advanced tumour stage (ORs for stage III and IV versus stage I-II tumours: 0.05-0.18 and 0.01-0.06 across countries) and increasing age (ORs for patients 70-79 and ≥80 versus those <60 years: 0.37-0.63 and 0.03-0.16 across countries). Patients with advanced-stage tumours (stage III-IV: 63.8%-81.2%) and at older ages (≥70 years: 52.6%-59.5%) receiving less frequently resection comprised the majority of diagnosed cases. Patient performance status, tumour location and size were also associated with resection application. CONCLUSION: Rates of PaC resection remain low in Europe and USA with great international variations. Further studies are warranted to explore reasons for these variations.

Comorbidities, age and period of diagnosis influence treatment and outcomes in early breast cancer.

Survival for breast cancer (BC) is lower in eastern than northern/central Europe, and in older than younger women. We analysed how comorbidities at diagnosis affected whether selected standard treatments (STs) were given, across Europe and over time, also assessing consequences for survival/relapse. We analysed 7581 stage I/IIA cases diagnosed in 9 European countries in 2009-2013, and 4 STs: surgery; breast-conserving surgery plus radiotherapy (BCS + RT); reconstruction after mastectomy; and prompt treatment (≤6 weeks after diagnosis). Covariate-adjusted models estimated odds of receiving STs and risks of death/relapse, according to comorbidities. Pearson's R assessed correlations between odds and risks. The z-test assessed the significance of time-trends. Most women received surgery: 72% BCS; 24% mastectomy. Mastectomied patients were older with more comorbidities than BCS patients (p < 0.001). Women given breast reconstruction (25% of mastectomies) were younger with fewer comorbidities than those without reconstruction (p < 0.001). Women treated promptly (45%) were younger than those treated later (p = 0.001), and more often without comorbidities (p < 0.001). Receiving surgery/BCS + RT correlated strongly (R = -0.9), but prompt treatment weakly (R = -0.01/-0.02), with reduced death/relapse risks. The proportion receiving BCS + RT increased significantly (p < 0.001) with time in most countries. This appears to be the first analysis of the influence of comorbidities on receiving STs, and of consequences for outcomes. Increase in BCS + RT with time is encouraging. Although women without comorbidities usually received STs, elderly patients often received non-standard less prompt treatments, irrespective of comorbidities, with increased risk of mortality/relapse. All women, particularly the elderly, should receive ST wherever possible to maximise the benefits of modern evidence-based treatments.

Disparities in the management of cutaneous malignant melanoma. A population-based high-resolution study.

Population-based cancer registry data from three Spanish areas were used to assess the patterns of care and adherence to guidelines for cutaneous malignant melanoma. We included 934 cases diagnosed in 2009-2013. Completeness of the pathology reports, imaging for detecting distant metastasis and the use of sentinel lymph node biopsy (SLNB) were analysed. The proportion of pathology reports that mentioned the essential pathological features required for T staging was 93%, ranging across geographic areas from 81% to 98% (p < 0.001). The percentage of low-risk patients who underwent no imaging studies, as proposed by guidelines, or only chest imaging ranged among areas from 0.6% to 84% (p < 0.001). Of the patients with clinically node-negative melanoma >1 mm thick and no distant metastases, 68% underwent SLNB, varying by area from 61% to 78% (p = 0.017). This study revealed wide geographic variation in different aspects of melanoma care. The use of a standardised structured pathology report could strengthen the completeness of reporting. Improvement strategies should also include efforts to reduce overuse of imaging in low-risk patients and to increase the adherence to guidelines recommendations on the use of SLNB.

Association of adiposity, dysmetabolisms, and inflammation with aggressive breast cancer subtypes: a cross-sectional study.

Obesity and metabolic syndrome are risk and prognostic factors for breast cancer (BC) and are associated with chronic inflammation. We investigated the association between distinct BC subtypes and markers of adiposity, dysmetabolisms, and inflammation. We analyzed 1779 patients with primary invasive BC treated at a single institution, for whom anthropometric and clinical-pathological data were archived. BC subtypes were classified by immunohistochemical staining of ER, PR, HER2, and Ki67, and their relations with the study markers were assessed by multinomial logistic regression. Adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated taking luminal A as reference. All subtypes more aggressive than luminal A were significantly more frequent in younger (<45 years) than older women. Before menopause, luminal B HER2-negative tumors were positively associated with large waist (OR 2.55, 95 % CI 1.53-4.24) and insulin resistance (OR 1.90, 95 % CI 1.05-3.41); luminal B HER2-positive tumors with large waist (OR 2.11, 95 % CI 1.03-4.35) and triple-negative tumors with overweight (OR 3.04, 95 % CI 1.43-6.43) and high C-reactive protein (p trend = 0.026). In postmenopausal women aged <65, luminal B HER2-negative (OR 1.94, 95 % CI 1.16-3.24) and luminal B HER2-positive tumors (OR 2.48, 95 % CI 1.16-5.27) were positively related with metabolic syndrome. Dysmetabolisms and inflammation may be related to different BC subtypes. Before menopause, triple-negative cancers were related to obesity and chronic inflammation, and aggressive luminal subtypes to abdominal adiposity. After menopause, in women aged <65 these latter subtypes were related to metabolic syndrome. Control of adiposity and dysmetabolism can reduce the risk of aggressive BC subtypes, improving the prognosis.

Sternal Gland Scent-Marking Signals Sex, Age, Rank, and Group Identity in Captive Mandrills.

Mandrills are one of the few Old World primates to show scent-marking. We combined ethological and chemical approaches to improve our understanding of this behavior in 3 zoo-managed groups. We observed the olfactory behavior performed by adults and adolescents (N = 39) for 775h. We investigated the volatile components of sternal scent-marks using gas chromatography-mass spectrometry and compared volatile profiles with traits of the signaler. Males marked more than females and within each sex the frequency of scent-marking was related to age and dominance status, but alpha males scent-marked most frequently and particularly in specific areas at the enclosure boundaries. We identified a total of 77 volatile components of sternal gland secretion, including compounds functioning as male sex pheromones in other mammals, in scent-marks spontaneously released on filter paper by 27 male and 18 female mandrills. We confirmed our previous findings that chemical profiles contain information including sex, male age and rank, and we also found that odor may encode information about group membership in mandrills. Our results support the hypotheses that scent-marking signals the status of the dominant male as well as playing territorial functions but also suggest that it is part of sociosexual communication.

Survival for haematological malignancies in Europe between 1997 and 2008 by region and age: results of EUROCARE-5, a population-based study.

BACKGROUND: More effective treatments have become available for haematological malignancies from the early 2000s, but few large-scale population-based studies have investigated their effect on survival. Using EUROCARE data, and HAEMACARE morphological groupings, we aimed to estimate time trends in population-based survival for 11 lymphoid and myeloid malignancies in 20 European countries, by region and age. METHODS: In this retrospective observational study, we included patients (aged 15 years and older) diagnosed with haematological malignancies, diagnosed up to Dec 31, 2007, and followed up to Dec 31, 2008. We used data from the 30 cancer registries (across 20 countries) that provided continuous incidence and good quality data from 1992 to 2007. We used a hybrid approach to estimate age-standardised and age-specific 5-year relative survival, for each malignancy, overall and for five regions (UK, and northern, central, southern, and eastern Europe), and four 3-year periods (1997-99, 2000-02, 2003-05, 2006-08). For each malignancy, we also estimated the relative excess risk of death during the 5 years after diagnosis, by period, age, and region. FINDINGS: We analysed 560 444 cases. From 1997-99 to 2006-08 survival increased for most malignancies: the largest increases were for diffuse large B-cell lymphoma (42·0% [95% CI 40·7-43·4] to 55·4% [54·6-56·2], p<0·0001), follicular lymphoma (58·9% [57·3-60·6] to 74·3% [72·9-75·5], p<0·0001), chronic myeloid leukaemia (32·3% [30·6-33·9] to 54·4% [52·5-56·2], p<0·0001), and acute promyelocytic leukaemia (50·1% [43·7-56·2] to 61·9% [57·0-66·4], p=0·0038, estimate not age-standardised). Other survival increases were seen for Hodgkin's lymphoma (75·1% [74·1-76·0] to 79·3% [78·4-80·1], p<0·0001), chronic lymphocytic leukaemia/small lymphocytic lymphoma (66·1% [65·1-67·1] to 69·0% [68·1-69·8], p<0·0001), multiple myeloma/plasmacytoma (29·8% [29·0-30·6] to 39·6% [38·8-40·3], p<0·0001), precursor lymphoblastic leukaemia/lymphoma (29·8% [27·7-32·0] to 41·1% [39·0-43·1], p<0·0001), acute myeloid leukaemia (excluding acute promyelocytic leukaemia, 12·6% [11·9-13·3] to 14·8% [14·2-15·4], p<0·0001), and other myeloproliferative neoplasms (excluding chronic myeloid leukaemia, 70·3% [68·7-71·8] to 74·9% [73·8-75·9], p<0·0001). Survival increased slightly in southern Europe, more in the UK, and conspicuously in northern, central, and eastern Europe. However, eastern European survival was lower than that for other regions. Survival decreased with advancing age, and increased with time only slightly in patients aged 75 years or older, although a 10% increase in survival occurred in elderly patients with follicular lymphoma, diffuse large B-cell lymphoma, and chronic myeloid leukaemia. INTERPRETATION: These trends are encouraging. Widespread use of new and more effective treatment probably explains much of the increased survival. However, the persistent differences in survival across Europe suggest variations in the quality of care and availability of the new treatments. High-resolution studies that collect data about stage at diagnosis and treatments for representative samples of cases could provide further evidence of treatment effectiveness and explain geographic variations in survival. FUNDING: Compagnia di San Paolo, Fondazione Cariplo, European Commission, and Italian Ministry of Health.

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.

Disease presentation, treatment and survival for Italian colorectal cancer patients: a EUROCARE high resolution study.

We analysed presentation, treatment and survival in a representative population-based sample of 3753 Italian colorectal cancer cases, diagnosed 2003-05: 70% were >65 years, 44% stage I-II, 27% stage IV and 92% received surgery. Chemotherapy was given to 58% of stage III colon cases, radiotherapy to 25% of rectal cases. Four percent of surgical cases underwent endoscopic polypectomy, and in 57% ≥11 lymph nodes were examined. Five-year relative survival was good (60%), independent of sex and site. Adherence to treatment guidelines was satisfactory, but wider use of faecal blood testing and colonoscopy will anticipate stage at diagnosis and likely improve survival.

Predictions of survival up to 10 years after diagnosis for European women with breast cancer in 2000-2002.

Few studies have addressed longer-term survival for breast cancer in European women. We have made predictions of 10-year survival for European women diagnosed with breast cancer in 2000-2002. Data for 114,312 adult women (15-99 years) diagnosed with a first primary malignant cancer of the breast during 2000-2002 were collected in the EUROCARE-4 study from 24 population-based cancer registries in 14 European countries. We estimated relative survival at 1, 5, and 10 years after diagnosis for women who were alive at some point during 2000-2002, using the period approach. We also estimated 10-year survival conditional on survival to 1 and 5 years after diagnosis. Ten-year survival exceeded 70% in most regions, but was only 54% in Eastern Europe, with the highest value in Northern Europe (about 75%). Ten-year survival conditional on survival for 1 year was 2-6% higher than 10-year survival in all European regions, and geographic differences were smaller. Ten-year survival for women who survived at least 5 years was 88% overall, with the lowest figure in Eastern Europe (79%) and the highest in the UK (91%). Women aged 50-69 years had higher overall survival than older and younger women (79%). Six cancer registries had adequate information on stage at diagnosis; in these jurisdictions, 10-year survival was 89% for local, 62% for regional and 10% for metastatic disease. Data on stage are not collected routinely or consistently, yet these data are essential for meaningful comparison of population-based survival, which provides vital information for improving breast cancer control.

A method for differentiating cancer prevalence according to health status, exemplified using a population-based sample of Italian colorectal cancer cases.

UNLABELLED: Cancer prevalence is the proportion of a population diagnosed with cancer. We present a method for differentiating prevalence into the proportions expected to survive without relapse, die of cancer within a year, and die of cancer within 10 years or survive with relapse at the end of the 10th year. MATERIAL AND METHODS: The method was applied to samples of colorectal cancer cases, randomly extracted from four Italian cancer registries (CRs). The CRs collected data on treatments, local relapses, distant relapses, and causes of death: 1) over the entire follow-up to 31 December 2007 for 601 cases diagnosed in 2002 (cohort approach); 2) over a single year (2007) for five cohorts of cases defined by year of diagnosis (from 1997 to 2001), alive at 1 January 2007 (total 298 cases). The cohorts were combined into a fictitious cohort with 10 years survival experience. For each year j after diagnosis the health status of cases alive at the beginning of j was estimated at the end of the 10th year. From these estimates the 10-year colorectal cancer prevalence was differentiated. RESULTS: We estimated: 74.7% alive without relapse or not undergoing treatment at the end of 10 years; 8.1% had died of colorectal cancer within a year; 11.4% had died of colorectal cancer 1-10 years after diagnosis or had relapsed or were undergoing treatment at the end of the 10th year; and 5.8% had died of other causes. CONCLUSIONS: We have introduced a new method for estimating the healthcare and rehabilitation demands of cancer survivors based on CR data plus treatment and relapse data specifically collected for samples of cases archived by CRs.

Pancreatic cancer survival trends in the US from 2001 to 2014: a CONCORD-3 study.

BACKGROUND: Survival from pancreatic cancer is low worldwide. In the US, the 5-year relative survival has been slightly higher for women, whites and younger patients than for their counterparts, and differences in age and stage at diagnosis [Corrections added Nov 16, 2022, after first online publication: a new affiliation is added to Maja Niksic] may contribute to this pattern. We aimed to examine trends in survival by race, stage, age and sex for adults (15-99 years) diagnosed with pancreatic cancer in the US. METHODS: This population-based study included 399,427 adults registered with pancreatic cancer in 41 US state cancer registries during 2001-2014, with follow-up to December 31, 2014. We estimated age-specific and age-standardized net survival at 1 and 5 years. RESULTS: Overall, 12.3% of patients were blacks, and 84.2% were whites. About 9.5% of patients were diagnosed with localized disease, but 50.5% were diagnosed at an advanced stage; slightly more among blacks, mainly among men. No substantial changes were seen over time (2001-2003, 2004-2008, 2009-2014). In general, 1-year net survival was higher in whites than in blacks (26.1% vs. 22.1% during 2001-2003, 35.1% vs. 31.4% during 2009-2014). This difference was particularly evident among patients with localized disease (49.6% in whites vs. 44.6% in blacks during 2001-2003, 60.1% vs. 55.3% during 2009-2014). The survival gap between blacks and whites with localized disease was persistent at 5 years after diagnosis, and it widened over time (from 24.0% vs. 21.3% during 2001-2003 to 39.7% vs. 31.0% during 2009-2014). The survival gap was wider among men than among women. CONCLUSIONS: Gaps in 1- and 5-year survival between blacks and whites were persistent throughout 2001-2014, especially for patients diagnosed with a localized tumor, for which surgery is currently the only treatment modality with the potential for cure.

Survival of European patients with central nervous system tumors.

We present estimates of population-based 5-year relative survival for adult Europeans diagnosed with central nervous system tumors, by morphology (14 categories based on cell lineage and malignancy grade), sex, age at diagnosis and region (UK and Ireland, Northern, Central, Eastern and Southern Europe) for the most recent period with available data (2000-2002). Sources were 39 EUROCARE cancer registries with continuous data from 1996 to 2002. Survival time trends (1988 to 2002) were estimated from 24 cancer registries with continuous data from 1988. Overall 5-year relative survival was 85.0% for benign, 19.9% for malignant tumors. Benign tumor survival ranged from 90.6% (Northern Europe) to 77.4% (UK and Ireland); for malignant tumors the range was 25.1% (Northern Europe) to 15.6% (UK and Ireland). Survival decreased with age at diagnosis and was slightly better for women (malignant tumors only). For glial tumors, survival varied from 83.5% (ependymoma and choroid plexus) to 2.7% (glioblastoma); and for non-glioma tumors from 96.5% (neurinoma) to 44.9% (primitive neuroectoderm tumor/medulloblastoma). Survival differences between regions narrowed after adjustment for morphology and age, and were mainly attributable to differences in morphology mix; however UK and Ireland and Eastern Europe patients still had 40% and 30% higher excess risk of death, respectively, than Northern Europe patients (reference). Survival for benign tumors increased from 69.3% (1988-1990) to 77.1% (2000-2002); but survival for malignant tumors did not improve indicating no useful advances in treatment over the 14-year study period, notwithstanding major improvement in the diagnosis and treatment of other solid cancers.

Survival for ovarian cancer in Europe: the across-country variation did not shrink in the past decade.

BACKGROUND: Survival for ovarian cancer is the poorest of all gynaecological cancer sites. Our aim was to present the most up-to-date survival estimate for ovarian cancer by age and morphology and to answer the question whether survival for ovarian cancer improved in Europe during the 1990s. MATERIAL AND METHODS: This analysis was performed with data from the EUROCARE database. We considered all adult women diagnosed with ovarian cancer between 1995 and 2002 and life status followed up until the end of 2003. A total of 97 691 cases were contributed by 72 European cancer registries in 24 countries. We estimated the most up-to-date relative survival for a mean of 23 661 patients followed up in 2000-2003 using the period hybrid approach and described the relative survival trends from the beginning of 1990s. RESULTS AND CONCLUSION: Overall, the European age-standardised one-year, five-year and five-year conditional on surviving one-year relative survival were 67.2% (95% CI 66.6-67.8), 36.1% (95% CI 35.4-36.8) and 53.7% (95% CI 52.8-54.7), respectively. Five-year relative survival was 58.6% (95% CI 57.4-59.8), 37.1% (95% CI 36.1-38.1) and 20.5% (95% CI 19.1-21.9) in women aged 15-54, 55-74 and 75-99 years, respectively. The age-standardised five-year relative survival was 38.1% (95% CI 36.9-39.3) for serous tumours and 51.9% (95% CI 49.0-54.9) for mucinous cancers and the crude five-year relative survival was 85.6% (95% CI 81.2-90.0) for germ cell cancers. Overall, the age-standardised five-year relative survival increased from 32.4% (95% CI 31.7-33.2) in 1991-1993 to 36.3% (95% CI 35.5-37.0) in 2000-2003. There is a need to better understand the reasons for the wide variation in survival of ovarian cancer in Europe. Actions aiming to harmonise the protocols for therapy should contribute to narrowing the wide gap in survival and research on screening and early detection of ovarian cancer should be enforced.

Clear Improvement in Real-World Chronic Myeloid Leukemia Survival: A Comparison With Randomized Controlled Trials.

Tyrosine kinase inhibitors (TKIs) have been improving the prognosis of patients with chronic myeloid leukemia (CML), but there are still large differences in survival among European countries. This raises questions on the added value of results from population-based studies, which use real-world data, compared to results of randomized controlled trials (RCTs) involving patients with CML. There are also questions about the extent of the findings on RCTs effectiveness for patients in the general population. We compare survival data extracted from our previous systematic review and meta-analysis of CML RCTs with the latest updated population-based survival data of EUROCARE-6, the widest collaborative study on cancer survival in Europe. The EUROCARE-6 CML survival estimated in patients (15-64 years) diagnosed in 2000-2006 vs. 2007-2013 revealed that the prognostic improvement highlighted by RCTs was confirmed in real-world settings, too. The study shows, evaluating for the first time all European regions, that the optimal outcome figures obtained in controlled settings for CML are also achievable (and indeed achieved) in real-world settings with prompt introduction of TKIs in daily clinical practice. However, some differences still persist, particularly in Eastern European countries, where overall survival values are lower than elsewhere, probably due to a delayed introduction of TKIs. Our results suggest an insufficient adoption of adequate protocols in daily clinical practice in those countries where CML survival values remain lower in real life than the values obtained in RCTs. New high-resolution population-based studies may help to identify failures in the clinical pathways followed there.

Association of Sentinel Node Biopsy and Pathological Report Completeness with Survival Benefit for Cutaneous Melanoma and Factors Influencing Their Different Uses in European Populations.

Objectives: Standard care for cutaneous melanoma includes an accurate pathology report (PR) and sentinel lymph node biopsy (SLNB) for staging clinically node-negative >1 mm melanomas. We aimed to investigate the frequency of these indicators across European countries, also assessing consequences for survival. Methods: We analyzed 4245 melanoma cases diagnosed in six European countries in 2009−2013. Multivariable logistic regression was used to estimate the Odds Ratio (OR) of receiving complete PR with eight items or SLNB and model-based survival to estimate the five-year relative excess risks of death (RER). Results: Overall, 12% patients received a complete PR (range 2.3%, Estonia­20.1%, Italy); SLNB was performed for 68.8% of those with cN0cM0 stage (range 54.4%, Spain­81.7%, Portugal). The adjusted OR of receiving a complete PR was lower than the mean in Estonia (OR 0.11 (0.06−0.18)) and higher in Italy (OR 6.39 (4.90−8.34)) and Portugal (OR 1.39 (1.02−1.89)); it was higher for patients operated on in specialized than general hospitals (OR 1.42 (1.08−1.42)). In the multivariate models adjusted for age, sex, country and clinical-pathological characteristics, the RER resulted in being higher than the reference for patients not receiving a complete PR with eight items (RER 1.72 (1.08−2.72)), or for those not undergoing SLNB (RER 1.76 (1.26−2.47)) Patients with non-metastatic node-negative thickness >1 mm melanoma who did not undergo SLNB had a higher risk of death (RER (RER 1.69 (1.02−2.80)) than those who did. Conclusions: Accurate pathology profiling and SLNB carried survival benefit. Narrowing down between-countries differences in adhesion to guidelines might achieve better outcomes.

Worldwide trends in population-based survival for children, adolescents, and young adults diagnosed with leukaemia, by subtype, during 2000-14 (CONCORD-3): analysis of individual data from 258 cancer registries in 61 countries.

BACKGROUND: Leukaemias comprise a heterogenous group of haematological malignancies. In CONCORD-3, we analysed data for children (aged 0-14 years) and adults (aged 15-99 years) diagnosed with a haematological malignancy during 2000-14 in 61 countries. Here, we aimed to examine worldwide trends in survival from leukaemia, by age and morphology, in young patients (aged 0-24 years). METHODS: We analysed data from 258 population-based cancer registries in 61 countries participating in CONCORD-3 that submitted data on patients diagnosed with leukaemia. We grouped patients by age as children (0-14 years), adolescents (15-19 years), and young adults (20-24 years). We categorised leukaemia subtypes according to the International Classification of Childhood Cancer (ICCC-3), updated with International Classification of Diseases for Oncology, third edition (ICD-O-3) codes. We estimated 5-year net survival by age and morphology, with 95% CIs, using the non-parametric Pohar-Perme estimator. To control for background mortality, we used life tables by country or region, single year of age, single calendar year and sex, and, where possible, by race or ethnicity. All-age survival estimates were standardised to the marginal distribution of young people with leukaemia included in the analysis. FINDINGS: 164 563 young people were included in this analysis: 121 328 (73·7%) children, 22 963 (14·0%) adolescents, and 20 272 (12·3%) young adults. In 2010-14, the most common subtypes were lymphoid leukaemia (28 205 [68·2%] patients) and acute myeloid leukaemia (7863 [19·0%] patients). Age-standardised 5-year net survival in children, adolescents, and young adults for all leukaemias combined during 2010-14 varied widely, ranging from 46% in Mexico to more than 85% in Canada, Cyprus, Belgium, Denmark, Finland, and Australia. Individuals with lymphoid leukaemia had better age-standardised survival (from 43% in Ecuador to ≥80% in parts of Europe, North America, Oceania, and Asia) than those with acute myeloid leukaemia (from 32% in Peru to ≥70% in most high-income countries in Europe, North America, and Oceania). Throughout 2000-14, survival from all leukaemias combined remained consistently higher for children than adolescents and young adults, and minimal improvement was seen for adolescents and young adults in most countries. INTERPRETATION: This study offers the first worldwide picture of population-based survival from leukaemia in children, adolescents, and young adults. Adolescents and young adults diagnosed with leukaemia continue to have lower survival than children. Trends in survival from leukaemia for adolescents and young adults are important indicators of the quality of cancer management in this age group. FUNDING: Children with Cancer UK, the Institut National du Cancer, La Ligue Contre le Cancer, Centers for Disease Control and Prevention, Swiss Re, Swiss Cancer Research foundation, Swiss Cancer League, Rossy Family Foundation, US National Cancer Institute, and the American Cancer Society.

Olfactory signals and fertility in olive baboons.

Female primates signal impending ovulation with a suite of sexual signals. Studies of these signals have focussed on visual, and to a lesser extent, acoustic signals, neglecting olfactory signals. We aimed to investigate the information content of female olfactory signals in captive olive baboons (Papio anubis) and relate these to the female fertile period. We studied eight adult females living in four groups at the CNRS Station de Primatologie, Rousset-sur-Arc, France. We used vaginal cytology to detect ovulation. We investigated the volatile component of odour signals using solid-phase microextraction and gas chromatography-mass spectrometry. We found a total of 74 volatile compounds, of which we tentatively identified 25, including several ketones, alcohols, aldehydes, terpenes, volatile fatty acids and hydrocarbons that have been identified in odour profiles of other primates. Our results show that vaginal odour intensity differs with sexual cycle stage suggesting that odour might play a role in signalling female baboon fertility. We found differences in vaginal odour between females living in all-female and in mixed sex groups but we could not distinguish the effects of group composition, female age and identity. This study of olfactory signalling improves our understanding of how female primates advertise their sexual receptivity.