Comparative analysis of diagnostic performance, feasibility and cost of different test-methods for thyroid nodules with indeterminate cytology

Since it is impossible to recognize malignancy at fine needle aspiration (FNA) cytology in indeterminate thyroid nodules, surgery is recommended for all of them. However, cancer rate at final histology is < 30%. Many different test-methods have been proposed to increase diagnostic accuracy in such lesions, including Galectin-3-ICC (GAL-3-ICC), BRAF mutation analysis (BRAF), Gene Expression Classifier (GEC) alone and GEC+BRAF, mutation/fusion (M/F) panel, alone, M/F panel+miRNA GEC, and M/F panel by next generation sequencing (NGS), FDG-PET/CT, MIBI-Scan and TSHR mRNA blood assay. We performed systematic reviews and meta-analyses to compare their features, feasibility, diagnostic performance and cost. GEC, GEC+BRAF, M/F panel+miRNA GEC and M/F panel by NGS were the best in ruling-out malignancy (sensitivity = 90%, 89%, 89% and 90% respectively). BRAF and M/F panel alone and by NGS were the best in ruling-in malignancy (specificity = 100%, 93% and 93%). The M/F by NGS showed the highest accuracy (92%) and BRAF the highest diagnostic odds ratio (DOR) (247). GAL-3-ICC performed well as rule-out (sensitivity = 83%) and rule-in test (specificity = 85%), with good accuracy (84%) and high DOR (27) and is one of the cheapest (113 USD) and easiest one to be performed in different clinical settings. In conclusion, the more accurate molecular-based test-methods are still expensive and restricted to few, highly specialized and centralized laboratories. GAL-3-ICC, although limited by some false negatives, represents the most suitable screening test-method to be applied on a large-scale basis in the diagnostic algorithm of indeterminate thyroid lesions

Estimating cancer incidence using a Bayesian back-calculation approach

We propose a Bayesian hierarchical model for the calculation of incidence counts from mortality data by a convolution equation that expresses mortality through its relationship with incidence and the survival probability density. The basic idea is to use mortality data together with an estimate of the survival distribution from cancer incidence to cancer mortality to reconstruct the numbers of individuals who constitute previously incident cases that give rise to the observed pattern of cancer mortality. This model is novel because it takes into account the uncertainty from the survival distribution; thus, a Bayesian-mixture cure model for survival is introduced. Furthermore, projections are obtained starting from a Bayesian age-period-cohort model. The main advantage of the proposed approach is its consideration of the three components of the model: the convolution equation, the survival mixture cure model and the age-period-cohort projection within a directed acyclic graph model. Furthermore, the estimation are obtained through the Gibbs sampler. We applied the model to cases of women with stomach cancer using six age classes [15–45], [45–55], [55–65], [65–75], [75–85] and [85–95] and validated it by using data from the Tuscany Cancer Registry. The model proposed and the program implemented are convenient because they allow different cancer disease to be analysed because the survival time is modelled by flexible distributions that are able to describe different trends

Worldwide Trends in Survival From Common Childhood Brain Tumors: A Systematic Review.

PURPOSE: The histology of brain tumors determines treatment and predicts outcome. Population-based survival reflects the effectiveness of a health care system in managing cancer. No systematic review of worldwide variation and time trends in survival from brain tumors in children is currently available. PATIENTS AND METHODS: We considered longitudinal, observational studies comprising children diagnosed with intracranial astrocytic or embryonal tumors. We searched six electronic databases from database inception to September 30, 2018, using complex search strategies. The outcome measure was 5-year survival, estimated through a time-to-event analysis. This study is registered with PROSPERO, number CRD42018111981. RESULTS: Among 5,244 studies, we identified 47 eligible articles that provided 228 survival estimates. Only five studies were entirely or partially conducted in low-income or middle-income countries. Five-year survival from embryonal tumors increased from 37% in 1980 to approximately 60% in 2009. Although survival for medulloblastoma improved substantially (from 29% to 73% during 1959-2009), survival for primitive neuroectodermal tumors wavered over time (1973-2009) and between countries. Five-year survival from astrocytoma changed very little over the 27 years between 1982 and 2009 (from 78% to 89%). Interpretation of the literature was made difficult by the heterogeneity of study designs. CONCLUSION: Survival has improved for embryonal tumors, but little change has been observed for astrocytic tumors. We found a striking gap in knowledge about survival from childhood brain tumor subtypes in middle-income and low-income countries, where half of these tumors are diagnosed. Larger studies are needed, including in under-represented countries and based on standardized data collection, to provide up-to-date survival estimates

[A comparative analysis between regional mesothelioma registries and cancer registries: results of the ReNaM-AIRTUM project].

OBJECTIVES: to assess the agreement on row data and incidence rates between regional mesothelioma registries (CORs) and population cancer registries (CRs) in Italy, and to contribute in harmonizing the procedures used in identifying the date of incidence and the morphology of mesothelioma cases. SETTING E PARTICIPANTS: the mesothelioma cases registered by 19 CRs and by 9 out of 19 CORs were included in the study. Some CORs were not able to participate in the study, because there were no active CRs in their areas. MAIN OUTCOME MEASURES: agreement on cases defined as mesotheliomas by the two types of registries; Cohen's k was used for the evaluation of the agreement on morphology on specific mesothelioma (ICD-O-3 90513-90533) and mesothelioma not otherwise specified (NOS) (ICD-O-3 90503); instead, Odds Ratio was calculated to evaluate the direction of the discrepancy. Difference among incidence rates were calculated using data collected by the two types of registries. It was also made a comparison between dates of incidence. RESULTS: the comparison among the registered data by the two different types of registry showed a high concordance (>80%), especially in the areas where there is a continuous exchange of data. Only in a few areas a lower concordance was observed. The agreement between specific and non-specific morphology showed a fairly wide range and lower values than the calculation of the positive agreement. CORs used the specific morphology (ICD-O-3 90503-90533) with higher frequency compared to CRs. The CRs incidence standardized rates are higher when only cases defined as «certain » by ReNaM are considered; on the opposite the CORs rates are higher when all cases defined as «certain, probable and possible» are considered. CONCLUSIONS: the study permitted to compare and bring out the different procedures used in identifying the date of incidence of cases and morphology definition. This represents a first step of a cooperative discussion process among the involved registries: the working group hope it will end with the implementation of shared guidelines

[Italian Cancer Figures - Report 2013. Multiple tumours]

Abstract OBJECTIVES: This collaborative study, based on data collected by the network of Italian association of cancer registries (AIRTUM), provides updated estimates on the incidence risk of multiple primary cancer (MP). The objective is to highlight and quantify the bidirectional associations between different oncological diseases. The quantification of the excess or decreased risk of further cancers in cancer patients, in comparison with the general population, may contribute to understand the aetiology of cancer and to address clinical follow-up. MATERIAL AND METHODS: Data herein presented were provided by AIRTUM population-based cancer registries, which cover nowadays 48% of the Italian population. This monograph utilizes the AIRTUM database December 2012), considering all malignant cancer cases diagnosed between 1976 and 2010. All cases are coded according to ICD-O-3. Non-melanoma skin cancer cases, cases based on death certificate only, cases based on autopsy only, and cases with follow-up time equal to zero were excluded. To define multiple primaries, IARC-IACR rules were adopted (http://www.iacr.com.fr/MPrules_july2004.pdf). Data were subjected to standard quality control procedures (described in the AIRTUM data management protocol) and specific quality control checks defined for the present study. A cohort of cancer patients was followed over time from first cancer diagnosis until the date of second cancer diagnosis, death, or the end of follow-up, to evaluate whether the number of observed second cancer cases was greater than expected. Person years at risk (PY) were computed by first cancer site, geographic area (North, Centre, South and Islands), attained age, and attained calendar-year group. All second cancers diagnosed in the cohort's patients were included in the observed numbers of cases. The expected number of cancer cases was computed multiplying the accumulated PY by the expected rates, calculated from the AIRTUM database stratified by cancer site, geographic area, age, and calendar-year group. The Standardized Incidence Ratio (SIR) was calculated as the ratio of observed to expected cancer cases. The Excess Absolute Risk (EAR) beyond the expected amount were calculated subtracting the expected number of subsequent cancers from the observed number of cancer cases; the difference was then divided by the PY and the number of cancer cases in excess (or deficit) was expressed per 1,000 PY. Confidence intervals were stated at 95%. The two months (60 days) after first cancer diagnosis were defined as "synchronicity period", and in the main analysis observed and expected cases during this period were excluded. It was estimated the excess risk in the period after first diagnosis ( 65 0 months), excluding the synchronicity period ( 65 2 months), and during the following periods: 2-11, 12-59, 60-119 and 120 months after diagnosis. First-cancer-site-and-gender-specific sheets are presented, reporting both SIRs and EARs. RESULTS: For 5,979,338 person-years a cohort of 1,635,060 cancer patients (880,361 males and 754,699 females) diagnosed between 1976 and 2010 was followed. The mean follow-up length was 14 years. Overall, 85,399 metachronous (latency 652 months) cancers were observed, while 77,813 were expected during the study period: SIR: 1.10 (95%CI 1.09-1.10), EAR: 1.32 x 1,000 person-years (95%CI 1.19 - 1.46). The SIR was 1.08 (95%CI 1.08-1.09) for men (54,518 observed and 50,260 expected) and 1.12 (95%CI 1.11-1.13) for women (30,881/27,553), and the EAR 1.61 (95%CI 1.37-1.84) and 1.08 x 1,000 person-years (95%CI 0.93-1.24), respectively.Moreover, during the first two months after first cancer diagnosis (synchronous period) 14,807 cancers were observed while 3,536 were expected (SIR: 4.16; 95%CI 4.09-4.22); the SIR was 4.08 (95%CI 4.00-4.16) for men and 4.32 (95%CI 4.20-4.45) for women.The mean age of patients at first cancer diagnosis was 67.0 years among males and 65.8 among females.The risk of MP was related to age being higher for younger patients and lower for older ones. In relation to the time of first cancer diagnosis, the SIR was very high at the beginning and then decreased, although remaining constantly over 1, and then rose over time. No strong differences were evident across the different incidence periods, which all showed an increased MP risk.Women had higher SIRs than expected for 18 cancer sites, men for 12. The statistically significantly SIRs lower than 1 were 2 and 8, respectively. Increased overall MP risk was observed for patients of both sexes with a first primary in the oral cavity (SIR men: 1.93; SIR women: 1.48), pharynx (SIR men: 2.13; SIR women: 1.99), larynx (SIR men: 1.57; SIR women: 1.79), oesophagus (SIR men: 1.45; SIR women: 1.41), lung (SIR men: 1.09; SIR women: 1.13), kidney (SIR men: 1.14; SIR women: 1.15), urinary bladder (SIR men: 1.29; SIR women: 1.22), thyroid (SIR: 1.22 in both sexes), Hodgkin lymphoma (SIR men: 1.59; SIR women: 1.94), and non-Hodgkin lymphoma (SIR men: 1.13; SIR women: 1.12), and for the heterogeneous group "other sites" (SIR men: 1.09; SIR women: 1.07). Moreover, men had a higher MP risk if the first cancer was in the testis (SIR: 1.24), while the same was true for women with gallbladder (SIR: 1.21), skin melanoma (SIR: 1.17), bone (SIR: 1.41), breast (SIR: 1.12), cervix uteri (SIR: 1.23) and corpus uteri (SIR: 1.23), and ovarian cancer (SIR: 1.18). On the contrary, a first liver or pancreas cancer were associated with a decreased MP risk in both sexes (liver SIR: 0.86 and 0.81 for men and women, respectively; pancreas SIR: 0.70 and 0.78 for men and women, respectively), as were those of colon (SIR: 0.93), rectum (SIR: 0.83), gallbladder (SIR: 0.80), prostate (SIR: 0.93), mesothelioma (SIR: 0.65), and central nervous system (SIR: 0.82) among men. Among the cancers for which the EAR is statistically significant, those with higher Excess Absolute Risk of MP were those of the oral cavity (EAR: 16.0 x 1,000 person-years in men and 5.4 in women), pharynx (17.6 and 9.1), larynx (11.4 and 8.8), and oesophagus (8.5 and 4.8). DISCUSSION: This descriptive study provides quantitative information on the risk of developing a second cancer in an Italian population-based cohort of approximately 1.65 million cancer patients, compared to the risk of the general population. During the follow-up time (on average 14 years) cancer patients had an MP risk that was 10% higher in comparison to the general population and an Excess Absolute Risk of 1.32 x 1,000 person-years. Study of MPs and their risk measures are dependent on methods used in the calculation. The definition of MP is not univocal and using different rules can greatly change the number of cancers in a patient with MPs. However, the AIRTUM cancer registries adopt the same recommendations for MP definition. This monograph was therefore made possible by the shared rules and standards used by AIRTUM registries. The cancer site-specific sheets, which represent the core of the monograph, can be useful to highlight and quantify the bidirectional associations among different diseases and therefore provide indications for clinical follow-up. Lifestyle changes in more healthful directions can have a positive effect in the cancer patient population and should always be recommended. PMID: 24259384 [PubMed - in process