Relative Survival Data Research Articles

Statistical Analysis of Zero-Inflated Nonnegative Continuous Data: A Review

Zero-inflated nonnegative continuous (or semicontinuous) data arise frequently in biomedical, economical, and ecological studies. Examples include substance abuse, medical costs, medical care utilization, biomarkers (e.g., CD4 cell counts, coronary artery calcium scores), single cell gene expression rates, and (relative) abundance of microbiome. Such data are often characterized by the presence of a large portion of zero values and positive continuous values that are skewed to the right and heteroscedastic. Both of these features suggest that no simple parametric distribution may be suitable for modeling such type of outcomes. In this paper, we review statistical methods for analyzing zero-inflated nonnegative outcome data. We will start with the cross-sectional setting, discussing ways to separate zero and positive values and introducing flexible models to characterize right skewness and heteroscedasticity in the positive values. We will then present models of correlated zero-inflated nonnegative continuous data, using random effects to tackle the correlation on repeated measures from the same subject and that across different parts of the model. We will also discuss expansion to related topics, for example, zero-inflated count and survival data, nonlinear covariate effects, and joint models of longitudinal zero-inflated nonnegative continuous data and survival. Finally, we will present applications to three real datasets (i.e., microbiome, medical costs, and alcohol drinking) to illustrate these methods. Example code will be provided to facilitate applications of these methods.

Survival after cardiac resynchronization therapy: results from 50084 implantations.

AimsRandomized controlled trials have shown that cardiac resynchronization therapy (CRT) prolongs survival in patients with heart failure. No studies have explored survival after CRT in relation to individuals in the general population (relative survival, RS). We sought to determine observed and RS after CRT in a nationwide cohort undergoing CRT.Methods and resultsA national administrative database was used to quantify observed mortality for patients undergoing CRT. Relative survival (RS) was quantified using life tables. In 50 084 patients [age 72.1 ± 11.6 years (mean ± standard deviation)] undergoing CRT with (CRT-D) (n = 25 273) or without (CRT-P) defibrillation (n = 24 811) over 8.8 years (median follow-up 2.7 years, interquartile range 1.3–4.8), expected survival decreased with age. Device type, male sex, ischaemic heart disease, diabetes, and chronic kidney disease predicted excess mortality. In multivariate analyses, excess mortality (analogue of RS) was lower after CRT-D than after CRT-P in all patients [adjusted hazard ratio (aHR) 0.80, 95% confidence interval (CI) 0.76–0.84] as well as in subgroups with (aHR 0.79, 95% CI 0.74–0.84) or without (aHR 0.82, 95% CI 0.74–0.91) ischaemic heart disease. A Charlson Comorbidity Index (CCI) ≥3 portended a higher excess mortality (aHR 3.04, 95% CI 2.76–3.34). Relative survival was higher in 2015–2017 than in 2009–2011 (aHR 0.64, 95% CI 0.59–0.69).ConclusionReference RS data after CRT is presented. Sex, ischaemic heart disease, diabetes, chronic kidney disease, and CCI were major determinants of RS after CRT. CRT-D was associated with a higher RS than CRT-P in patients with or without ischaemic heart disease. Relative survival after CRT improved from 2009 to 2017.

Increased survival of patients aged 0-29years with osteosarcoma: A period analysis, 1984-2013.

PurposeOsteosarcoma is the most common primary malignancy of bone, and typically occurs among children and adolescence. This study aims to evaluate treatment outcomes among children, adolescents and young adults with osteosarcoma over the three decades by the changes in the long‐term relative survival.MethodsOsteosarcoma incidence and relative survival data from Surveillance, Epidemiology, and End Results (SEER) registries during 1984‐2013 were analyzed. The survival differences over three decades, age, sex, race, and socioeconomic status (SES) were assessed by comparing Kaplan‐Meier curves.ResultsThe overall incidence of osteosarcoma kept relatively stable with 0.4 per 100 000 in the three decades with the peak incidence occurring in the aged 10‐19 group. The 10‐year relative survival rate (RSR) increased from 57.7% to 61.0% in the three decades, with the greatest increase in the aged 0‐9 group from 48.2% to 65.7%. The 10‐year RSR improved from 54.1% to 61.5% in males, and from 62.4% to 63.0% in females, respectively, in the three decades. Furthermore, survival dramatically improved from 30% to 60% in the high‐poverty group over the three decades.ConclusionThis study demonstrated that the overall incidence of osteosarcoma remained stable, with an improvement in survival in the three decades. The improved survival was greater in males than in females in the three decades. Furthermore, the survival significantly increased in high‐poverty group, which was attributed to increasing improved health care system and patients with low finance can also have access to receiving effective and consistent treatment without distinction.

Prognostic Significance of Mesenchymal–Epithelial Transition in Triple-Negative Breast Cancers

IntroductionThe prognostic value of the mesenchymal–epithelial transition (MET) in triple-negative breast cancers (TNBCs) remains controversial. A meta-analysis of the impact of MET in TNBCs was performed by searching published data. MethodsPubMed and Embase databases were searched for eligible literature. The principal outcome measures were hazard ratios (HRs) for recurrence-free survival or overall survival according to MET expression. Combined HRs were calculated using fixed- or random-effects models according to heterogeneity. ResultsSix studies involving 785 patients met our selection criteria. The meta-analysis results showed that MET overexpression was associated with a 1.29-fold increased risk of recurrence (combined HR 1.29; 95% confidence interval, 1.04-1.60; P = .020) in the TNBCs. Three studies provided the related overall survival data (488 cases). The results showed that MET overexpression was associated with a 1.38-fold increased risk of mortality (HR, 1.38; 95% confidence interval, 1.08-1.76; P = .009). ConclusionMET is an adverse prognostic marker for TNBCs. The results strengthen the rationale for targeted therapy of TNBCs using MET inhibitors in future clinical trials.

Explained variation of excess hazard models.

The availability of longstanding collection of detailed cancer patient information makes multivariable modelling of cancer‐specific hazard of death appealing. We propose to report variation in survival explained by each variable that constitutes these models. We adapted the ranks explained (RE) measure to the relative survival data setting, ie, when competing risks of death are accounted for through life tables from the general population. RE is calculated at each event time. We introduce weights for each death reflecting its probability to be a cancer death. RE varies between −1 and +1 and can be reported at given times in the follow‐up and as a time‐varying measure from diagnosis onward. We present an application for patients diagnosed with colon or lung cancer in England. The RE measure shows reasonable properties and is comparable in both relative and cause‐specific settings. One year after diagnosis, RE for the most complex excess hazard models reaches 0.56, 95% CI: 0.54 to 0.58 (0.58 95% CI: 0.56–0.60) and 0.69, 95% CI: 0.68 to 0.70 (0.67, 95% CI: 0.66–0.69) for lung and colon cancer men (women), respectively. Stage at diagnosis accounts for 12.4% (10.8%) of the overall variation in survival among lung cancer patients whereas it carries 61.8% (53.5%) of the survival variation in colon cancer patients. Variables other than performance status for lung cancer (10%) contribute very little to the overall explained variation. The proportion of the variation in survival explained by key prognostic factors is a crucial information toward understanding the mechanisms underpinning cancer survival. The time‐varying RE provides insights into patterns of influence for strong predictors.

Clinical characters and prognostic factors of young female patients (pts) with metastatic gastric adenocarcinoma (GC).

133 Background: GC is one of the most common cancers worldwide, and has an even higher incidence rate in China. The incidence rate of GC is rising in young pts (≤ 40 years). Previous studies suggested that the percentage of female pts was higher in young pts than that in older pts. The clinical characters and potential prognostic factors have not been well described for young female pts with metastatic GC. Methods: A retrospective chart review was conducted for all GC pts treated at our institution from 1995 to 2012. Pt demographics, clinical characters, treatment related information and survival data were collected. Kaplan-Meier test was used for the survival analysis. Cox regression was conducted for uni- and multi-variate analysis. Results: In total, 1,862 pts with histologically confirmed GC were identified. Among these pts, 11.3% were young pts when first diagnosed. The male to female ratio was 2.76:1 for the whole group and 1:1.02 for young pts. Ninety-eight female pts were ≤ 40 years when diagnosed of metastatic GC. For this group, median age was 35 years (range: 19-40 years). Seventy-one (72.4%) had > 1 metastatic sites, and 85 (86.7%) received palliative chemotherapy. The median overall survival (OS) was 14.9 months (95% confidence interval [CI] 11.8-18.0 months). Seventy-six (77.6%) pts had intact primary tumor when diagnosed of metastatic disease. Compared to 22 pts who relapsed after radical surgery, OS was similar for pts presented with de novo metastatic disease (Hazard Ratio (HR) 1.03, 95% CI: 0.55 to 1.92, P= 0.9). Of these 76 pts, 36 underwent palliative gastric resection, which was associated with improved OS (15.3 vs. 9.0 months; HR 0.37, 95% CI: 0.19 to 0.74, P = 0.003). Forty-six (46.9%) pts had ovarian metastasis, and 20 had oophorectomy. Palliative oophorectomy was associated with significantly improved OS (36.6 vs. 12.4 months, HR 0.34, 95% CI: 0.14 to 0.80, P = 0.013). Conclusions: There was an increased ratio of females in young GC pts. In young female pts with metastatic GC, palliative resection of gastric primary and ovarian metastasis were associated with significantly improved OS, and should be considered in appropriate pts.

Estimates of cancer burden in Puglia.

A regional population-based cancer registry that provides incidence and survival data has become active only recently. Since it is important to know the time trends of basic epidemiological indicators to understand the cancer burden in the region, this paper will provide incidence, prevalence and mortality estimates in the region for seven major cancers for the period 1970-2015. 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. The incidence rates are estimated to be still increasing for female breast cancer, colorectal cancer in men and skin melanoma in both sexes. By contrast, the incidence rates indicate a decreasing trend for cervix uteri cancer and stomach cancer, the latter both in men and women. For these cancers an analogous trend is observed for mortality, confirming the reduction of the risk factors related to these cancer types. The incidence rates for lung cancer and prostate cancer in men were estimated to rise, reach a peak, and then decrease in the last part of the considered period. Prevalence increased for all the considered cancers except cervix cancer. The increase was striking for breast cancer and less pronounced for stomach cancer in both genders. This paper provides a description of the burden of the major cancers until 2015. The results highlight the need to reinforce effective preventive measures to contrast cancers related to an unhealthy lifestyle and to increase the compliance with organized screening programs to reduce the colorectal and breast cancer burden.

Estimates of cancer burden in Lombardy.

Cancer registration in Lombardy covers almost half of the regional population and started in 1976 in the Varese province. The aim of this paper is to provide estimates of the incidence, mortality and prevalence of seven major cancers for the entire Lombardy region in the period 1970-2015. 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. Published data from the Italian cancer registries were modeled in order to estimate the regional cancer survival. In Lombardy, about 9,000 new cases of breast cancer, 8,500 of colorectal cancer, 7,200 of prostate cancer and 6,700 of lung cancer were expected to be diagnosed in the year 2012. Incidence rates are still rising for female breast cancer, skin melanoma in both sexes, and lung cancer in women. By contrast, the rates have been declining for cervix and stomach cancer. For lung cancer in men, prostate cancer and colorectal cancer the rates increased, reaching a peak in different periods, and then decreased. Prevalence increased for all cancers considered except cervix cancer. The rise was less pronounced in stomach cancer due to the impressive reduction of its incidence and was striking for breast and prostate cancer, with 116,000 and 58,900 prevalent cases in 2012. Mortality dropped for all considered cancers with the only exception of lung cancer in women. This up-to-date picture of the cancer risk and burden in Lombardy shows the increasing demand for oncology services as one of the major challenges for the region. However, primary prevention is still the only way to simultaneously reduce incidence, prevalence and mortality rates, thus saving further lives and preserving health resources.

Estimating all cancers incidence with the MIAMOD model: a new method to include multiple tumors.

The MIAMOD method has been widely applied to derive regional and national cancer burden estimates. The method is based on a back-calculation approach using cancer-specific mortality and relative survival to derive expected incident and prevalent cases. Multiple tumors occurring in the same site for the same person (for example colon-colon) can be estimated just once. This has little effect on cancer-specific estimates, whereas it limits all cancers-combined estimates, where only cancer cases, rather than cancer diagnoses, can be accounted for by the method. The aim of this article is to present a specific strategy of application of the MIAMOD method to all cancers sites, which better approximates an estimate of 'cancer diagnoses'. The strategy consists of breaking down the estimation process in separate applications to the most frequent cancer sites and to a 'remainder-site', given by all malignant sites except the previous ones. The separate estimates are then summed up to derive the overall quantities for all cancers combined. Cancer-specific mortality in the years 1985-2004 in the Tuscany cancer registry area (about 1,200,000 inhabitants) and relative survival data in the same area and periods (end of follow-up, 31 December 2006) were used to produce the estimates, which were then tested using observed incidence data in the same area and period. The standard application of the MIAMOD method underestimates all cancer incidence for both sexes. The mean relative difference between observed and expected incident cases is -14.8% for males and -17.2% for females. With the alternative method, the same mean relative difference drops to -8.2% for males and -6.1% for females. The study provides a strategy to reduce a structural limit of the MIAMOD method in estimating the total burden of cancer disease.

Estimates of cancer burden in Lazio.

Since 1983 a population-based cancer registry has been operating in Lazio which provides incidence and survival data and covers the entire Latina province, amounting to 10% of the regional population. The aim of this paper is to provide estimates of the incidence, mortality and prevalence for seven major cancers in the Lazio region for the period 1970-2015. 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. In 2012 the most frequent cancer sites were breast, colon-rectum and prostate with 5,529, 5,315 and 4,759 new diagnosed cases, respectively. The cancers with increasing incidence trends were breast cancer, lung cancer and skin melanoma in women, and prostate cancer, colorectal cancer and melanoma in men. The incidence rates of uterine cervix and stomach cancer decreased. The male lung cancer rates increased, reaching a peak in the late 1980s, and then decreased. Prevalence increased for all the considered cancers except cervix cancer. In 2012 breast, colorectal and prostate cancer had the highest prevalence, with 68,239, 36,617 and 33,934 prevalent cases, respectively. In the final period of the study the mortality declined for all cancers except female lung cancer. In 2012, the highest mortality rates were estimated for lung cancer in both men and women, with 89 and 40 deaths per 100,000, respectively. These estimates give a useful description of the present and future cancer patterns in the Lazio region. Incidence, mortality and prevalence projections provide new information for health resource planning. Furthermore, they point to the need to reinforce the organized screening programs, especially for breast and colorectal cancer.

Estimates of cancer burden in Trentino-Alto Adige.

The Trentino-Alto Adige region is composed of two autonomous provinces (Trento and Bolzano), each with its own cancer registry. The registries' total coverage is 100% of the regional population. The main difference between the two provinces in terms of cancer epidemiology is related to the prostate cancer incidence and survival, with higher values in Bolzano. This paper provides an update until 2015 of the basic epidemiological indicators for seven major cancers for the entire region. The indicators were estimated by means of the MIAMOD method, a statistical back-calculation approach to derive incidence and prevalence figures starting from mortality and relative survival data. Mortality data were provided by ISTAT for the period 1970-2002 while survival was modeled on the basis of published data from the Italian cancer registries. The estimates for 2012 show that breast cancer was the most common cancer in women and prostate cancer was most common in men. Incidence and mortality were decreasing for cervix cancer and stomach cancer in both genders during the whole study period. The lung cancer incidence and mortality were decreasing in men but increasing in women. The colorectal cancer incidence rose in both genders while the mortality was decreasing in women. The incidence of skin melanoma increased in both sexes, while the mortality remained very low. The breast cancer incidence was increasing up to 2015 while the mortality was declining since 1986. The prostate cancer incidence increased up to 2006, thereafter the rates stabilized while mortality started to decrease in the early 2000s. The highest mortality rates were estimated for lung cancer in men and breast cancer in women. Lifestyle plays an important role in cancer trends, as does organized screening for early detection of cervix, breast and colorectal cancer. The provincial data on risk factor distribution and adherence to and coverage of organized screening are satisfactory and their optimization may allow additional benefits in terms of public health.

Estimates of cancer burden in Campania.

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. 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. 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. 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.

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. 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. 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. 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.

Estimates of cancer burden in Marche.

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

Estimates of cancer burden in Veneto.

In Veneto a regional cancer registry has been operating since 1987 which provides incidence and survival data for the region. It currently covers 48% of the regional population. The aim of this paper is to provide estimates of the incidence, mortality and prevalence of the major cancers for the whole Veneto region in the period 1970-2015. 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. In 2012 the most frequent cancer sites were colon-rectum, prostate and breast with 4,677, 3,760 and 3,729 new diagnosed cases, respectively. The incidence rates were estimated to increase constantly for female lung cancer, prostate cancer, colorectal cancer and melanoma, while they were decreasing for cervical cancer and stomach cancer. For male lung cancer and female breast cancer the rates increased, reaching a peak, and then decreased. In the last years of the period of analysis, mortality declined for all cancers: the highest number of deaths (2,390 in both sexes) was estimated for lung cancer in 2012. Prevalence was increasing for all the considered cancer sites with the exception of lung cancer in men, for which the prevalence was estimated to increase until 2007 and then stabilize. By contrast, the cervical cancer decreased during the whole period. In 2012 breast cancer had the highest prevalence, with about 52,000 cases. This paper provides a description of the burden of the major cancers in Veneto until 2015. The estimates highlight the continuing reduction of cancer mortality. This decline can be related to the improvement of clinical treatments and to multidisciplinary treatment approaches. In order for this positive trend to continue, implementation and reinforcement of the screening programs is needed, especially for breast and colorectal cancer.

Estimates of cancer burden in Sardinia.

Cancer registration in Sardinia covers 43% of the population and started in 1992 in the Sassari province. The aim of this paper is to provide estimates of the incidence, mortality and prevalence of seven major cancers for the entire region in the period 1970-2015. 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. Estimates were compared with the available observed data. In 2012 the lowest incidence was estimated for stomach cancer and melanoma among men, with 140 and 74 new cases, respectively, per 100,000. The mortality rates were highest for lung cancer and were very close to the incidence rates (77 and 95 per 100,000, respectively). In women, breast was by far the most frequent cancer site both in terms of incidence (1,512 new cases) and mortality (295 deaths), followed by colon-rectum (493 cases and 201 deaths), lung (205 cases and 167 deaths), melanoma (106 cases and 15 deaths), stomach (82 cases and 61 deaths), and uterine cervix (36 cases and 19 deaths). The highest prevalence was estimated for breast cancer (15,180 cases), followed by colorectal cancer with about 7,300 prevalent cases in both sexes. This paper provides a description of the burden of the major cancers in Sardinia until 2015. The comparisons between the estimated age-standardized incidence rates and those observed in the Sassari registry indicate good agreement. The estimates show a general decrease in cancer mortality, with the exception of female lung cancer. By contrast, the prevalence is steeply increasing for all considered cancers (with the only exception of cancer of the uterine cervix). This points to the need for more strongly supporting evidence-based prevention campaigns focused on contrasting female smoking, unhealthy nutrition and sun exposure.

Cancer estimates up to 2015 in Friuli Venezia Giulia.

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. 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. 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). 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.

Estimates of cancer burden in Umbria.

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

Estimates of cancer burden in Basilicata and Calabria.

Basilicata and Calabria are two neighboring, low income regions of southern peninsular Italy with an overall population of about 2.5 million in 2010. Cancer registration has covered the entire Basilicata population since 2005 and the province of Catanzaro (18.3% of the Calabria population) since 2003. This paper will provide estimates and projections for the period 1970-2015 of the basic epidemiological indicators - incidence, prevalence and mortality - in the Basilicata and Calabria regions for the major cancers (lung, colon and rectum, stomach, skin mela-noma, breast, cervix and prostate). The indicators were estimated by applying the MIAMOD statistical back-calculation method to the 1970-2002 official mortality data, and to the 1985-2002 relative survival data collected by population-based registries of the southern regions of Italy. The incidence rates were estimated to be still rising for breast, prostate and colorectal cancer, and for skin melanoma in men. By contrast, they were estimated to be declining for cervix and stomach cancer. The incidence increased, reaching a peak, and subsequently decreased for lung cancer in men and for skin melanoma in women. The age-standardized mortality rates were estimated to decrease for all considered cancers except prostate cancer in men and lung cancer in women, which presented quite stable mortality rates from the mid 2000s onwards. Except for cervix cancer, prevalence was increasing for all considered cancers, particularly those of the breast and prostate. These data support the need for health policies focused on primary and secondary prevention, which is the main way to reduce the overall impact of cancer and to preserve health care resources, as well as on actions aimed at ensuring equal access to cancer care and at transferring innovation into clinical practice.

Identification of hub miRNA biomarkers for bladder cancer by weighted gene coexpression network analysis.

Bladder cancer (BC) is a common urinary system tumor with high aggressiveness, and it results in relatively high mortality due to a lack of precise and suitable biomarkers. In this study, we applied the weighted gene coexpression network analysis method to miRNA expression data from BC patients, and screened for network modules associated with BC progression. Hub miRNAs were selected, followed by functional enrichment analyses of their target genes for the most closely related module. These hub miRNAs were found to be involved in several functional pathways including pathway in cancer, regulation of actin cytoskeleton, PI3K-Akt signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, Wnt signaling pathway, proteoglycans in cancer, focal adhesion and p53 signaling pathway via regulating target genes. Finally, their prognostic significance was tested using analyses of overall survival. A few novel prognostic miRNAs were identified based on expression profiles and related survival data. In conclusion, several miRNAs that were critical in BC initiation and progression have been identified in this study. These miRNAs, which may contribute to a comprehensive understanding of the pathogenesis of BC, could serve as potential biomarkers for BC prognosis or as new therapeutic targets.