Cure indicators and prevalence by stage at diagnosis for breast and colorectal cancer patients: A population-based study in Italy.

People alive many years after breast (BC) or colorectal cancer (CRC) diagnoses are increasing. This paper aimed to estimate the indicators of cancer cure and complete prevalence for Italian patients with BC and CRC by stage and age. A total of 31 Italian Cancer Registries (47% of the population) data until 2017 were included. Mixture cure models allowed estimation of net survival (NS); cure fraction (CF); time to cure (TTC, 5-year conditional NS >95%); cure prevalence (who will not die of cancer); and already cured (prevalent patients living longer than TTC). 2.6% of all Italian women (806,410) were alive in 2018 after BC and 88% will not die of BC. For those diagnosed in 2010, CF was 73%, 99% when diagnosed at stage I, 81% at stage II, and 36% at stages III-IV. For all stages combined, TTC was >10 years under 45 and over 65 years and for women with advanced stages, but ≤1 year for all BC patients at stage I. The proportion of already cured prevalent BC women was 75% (94% at stage I). Prevalent CRC cases were 422,407 (0.7% of the Italian population), 90% will not die of CRC. For CRC patients, CF was 56%, 92% at stage I, 71% at stage II, and 35% at stages III-IV. TTC was ≤10 years for all age groups and stages. Already cured were 59% of all prevalent CRC patients (93% at stage I). Cancer cure indicators by stage may contribute to appropriate follow-up in the years after diagnosis, thus avoiding patients' discrimination.

Indicators of cure for women living after uterine and ovarian cancers: a population-based study.

This study aims to estimate long-term survival, cancer prevalence, and several cure indicators for Italian women with gynaecological cancers. Thirty-one cancer registries, representing 47% of the Italian female population, were included. Mixture cure models were used to estimate Net Survival (NS), Cure Fraction, Time To Cure (5-year conditional NS>95%), Cure Prevalence (women who will not die of cancer), and Already Cured (living longer than Time to Cure). In 2018, 0.4% (121,704) of Italian women were alive after corpus uteri cancer, 0.2% (52,551) after cervical, and 0.2% (52,153) after ovarian cancer. More than 90% of patients with uterine cancers and 83% with ovarian cancer will not die from their neoplasm (Cure Prevalence). Women with gynaecological cancers have a residual excess risk of death <5% after 5 years since diagnosis. The Cure Fraction was 69% for corpus uteri, 32% for ovarian, and 58% for cervical cancer patients. Time To Cure was ≤10 years for women with gynaecological cancers aged <55 years. 74% of patients with cervical cancer, 63% with corpus uteri cancer, and 55% with ovarian cancer were Already Cured. These results will contribute to improving follow-up programs for women with gynaecological cancers and supporting efforts against discrimination of already cured ones.

Ubiquitin protease Ubp8 is necessary for S. cerevisiae respiration.

Healthy mitochondria are required in cell metabolism and deregulation of underlying mechanisms is often involved in human diseases and neurological disorders. Post-translational modifications of mitochondrial proteins regulate their function and activity, accordingly, impairment of ubiquitin proteasome system affects mitochondria homeostasis and organelle dynamics. In the present study we have investigated the role of the ubiquitin protease Ubp8 in S. cerevisiae respiration. We show that Ubp8 is necessary for respiration and its expression is upregulated in glycerol respiratory medium. In addition, we show that the respiratory defects in absence of Ubp8 are efficiently rescued by disruption of the E3 Ub-ligase Psh1, suggesting their epistatic link. Interestingly, we found also that Ubp8 is localized into mitochondria as single protein independently of SAGA complex assembly, thus suggesting an independent function from the nuclear one. We also show evidences on the importance of HAT Gcn5 in sustaining Ubp8 expression and affecting the amount of protein in mitochondria. Collectively, our results have investigated the role of Ubp8 in respiratory metabolism and highlight the role of ubiquitin related pathways in the mitochondrial functions of S. cerevisiae.

Mitochondrial diseases: Yeast as a model for the study of suppressors.

Mitochondrial (mt) tRNA gene mutations are an important cause of human morbidity and are associated with different syndromes. We have previously shown that the mitochondrial protein synthesis elongation factor EF-Tu and isolated sequences from the carboxy-terminal domain of yeast and human mt leucyl-tRNA synthetases (LeuRS), have a wide range of suppression capability among different yeast mt tRNA mutants having defective respiratory phenotype. Here we show that the rescuing capability can be restricted to a specific sequence of six amino acids from the carboxy-terminal domain of mt LeuRS. On the other hand by overexpressing a mutated version of mt EF-Tu in a yeast strain deleted for the endogenous nuclear gene we identified the specific region involved in suppression. Results support the possibility that a small peptide could correct defects associated with many mt tRNA mutations, suggesting a novel therapy for mitochondrial diseases treatment. The involvement of the mt EF-Tu in cellular heat stress response has also been suggested.

Characteristics of people living in Italy after a cancer diagnosis in 2010 and projections to 2020.

BACKGROUND: Estimates of cancer prevalence are widely based on limited duration, often including patients living after a cancer diagnosis made in the previous 5 years and less frequently on complete prevalence (i.e., including all patients regardless of the time elapsed since diagnosis). This study aims to provide estimates of complete cancer prevalence in Italy by sex, age, and time since diagnosis for all cancers combined, and for selected cancer types. Projections were made up to 2020, overall and by time since diagnosis. METHODS: Data were from 27 Italian population-based cancer registries, covering 32% of the Italian population, able to provide at least 7 years of registration as of December 2009 and follow-up of vital status as of December 2013. The data were used to compute the limited-duration prevalence, in order to estimate the complete prevalence by means of the COMPREV software. RESULTS: In 2010, 2,637,975 persons were estimated to live in Italy after a cancer diagnosis, 1.2 million men and 1.4 million women, or 4.6% of the Italian population. A quarter of male prevalent cases had prostate cancer (n = 305,044), while 42% of prevalent women had breast cancer (n = 604,841). More than 1.5 million people (2.7% of Italians) were alive since 5 or more years after diagnosis and 20% since ≥15 years. It is projected that, in 2020 in Italy, there will be 3.6 million prevalent cancer cases (+ 37% vs 2010). The largest 10-year increases are foreseen for prostate (+ 85%) and for thyroid cancers (+ 79%), and for long-term survivors diagnosed since 20 or more years (+ 45%). Among the population aged ≥75 years, 22% will have had a previous cancer diagnosis. CONCLUSIONS: The number of persons living after a cancer diagnosis is estimated to rise of approximately 3% per year in Italy. The availability of detailed estimates and projections of the complete prevalence are intended to help the implementation of guidelines aimed to enhance the long-term follow-up of cancer survivors and to contribute their rehabilitation needs.

SAGA complex and Gcn5 are necessary for respiration in budding yeast.

In budding yeast, growth through fermentation and/or respiration is dependent on the type of carbon source present in the medium. SAGA complex is the main acetylation complex and is required, together with Rtg factors, for nucleus-mitochondria communication and transcriptional activation of specific nuclear genes. Even though acetylation is necessary for mitochondria activity and respiratory pathways the direct role of histone acetyltransferases and SAGA complex has never been investigated directly. In this study we demonstrate, for the first time, that Gcn5 and SAGA are needed for respiratory metabolism and oxygen consumption. According to a central role for acetylation in respiration we find that the Gcn5 inhibitor CPTH2 had higher efficacy on cells grown in glycerol containing media. We also demonstrated that the opposing activities of Gcn5 and Hda1 modify selectively H3-AcK18 and are essential for respiration. Taken together our results suggest a novel paradigm coupling acetyltransferase activity to respiratory metabolism. Correspondingly we propose the selective utilization of KAT inhibitor CPTH2, combined to the modulation of the respiratory metabolism of the cell, as a promising novel tool of intervention in cancer cells.

An estimate of the number of people in Italy living after a childhood cancer.

Cancers diagnosed in children below the age of 15 years represent 1.2% of all cancer cases, and survival after a childhood cancer has greatly improved over the past 40 years in all high income countries. This study aims to estimate the number of people living in Italy after a childhood cancer for all cancers combined and for a selection of cancer types. We computed 15-year prevalence using data from 15 Italian population-based cancer registries (covering 19% of Italian population) and estimated complete prevalence for Italy by using the CHILDPREV method, implemented in the COMPREV software. A total of 44,135 persons were alive at January 1st, 2010 after a cancer diagnosed during childhood. This number corresponds to a proportion of 73 per 100,000 Italians and to about 2% of all prevalent cases. Among them, 54% were males and 64% had survived after being diagnosed before 1995, the start of the observation period. A quarter of all childhood prevalent cases were diagnosed with brain and central nervous system tumors, a quarter with acute lymphoid leukemia, and 7% with Hodgkin lymphoma. Nearly a quarter of prevalent patients were aged 40 years and older. Information about the number of people living after a childhood cancer in Italy by cancer type and their specific health care needs may be helpful to health-care planners and clinicians in the development of guidelines aimed to reduce the burden of late effect of treatments during childhood.

Novel mutation in mitochondrial Elongation Factor EF-Tu associated to dysplastic leukoencephalopathy and defective mitochondrial DNA translation.

The mitochondrial Elongation Factor Tu (EF-Tu), encoded by the TUFM gene, is a highly conserved GTPase, which is part of the mitochondrial protein translation machinery. In its activated form it delivers the aminoacyl-tRNAs to the A site of the mitochondrial ribosome. We report here on a baby girl with severe infantile macrocystic leukodystrophy with micropolygyria and a combined defect of complexes I and IV in muscle biopsy, caused by a novel mutation identified in TUFM. Using human mutant cells and the yeast model, we demonstrate the pathological role of the novel variant. Moreover, results of a molecular modeling study suggest that the mutant is inactive in mitochondrial polypeptide chain elongation, probably as a consequence of its reduced ability to bind mitochondrial aa-tRNAs. Four patients have so far been described with mutations in TUFM, and, following the first description of the disease in a single patient, we describe similar clinical and neuroradiological features in an additional patient.

Mortality in Italian veterans deployed in Bosnia-Herzegovina and Kosovo.

BACKGROUND AND AIMS: The possible increase of cancer risk in military personnel deployed in Balkans during and after the 1992-1999 wars, mainly related to the depleted uranium, was addressed by several studies on European veterans of those war theatres. This article reports on the results of the mortality study on the Italian cohort of Bosnia and Kosovo veterans (Balkan cohort). METHODS: Mortality rates for the Balkan cohort (71 144 persons) were compared with those of the Italian general population as well as to those of a comparable and unselected control cohort of not deployed military personnel (114 269 persons). Ascertainment of vital status during the period 1995-2008 of all the persons in the two cohorts has been carried out through deterministic record linkage with the national death records database, from information provided by the respective Armed Force General Staff, and through the civil registry offices of the veterans' residence or birth municipalities. RESULTS: The Balkan cohort experienced a mortality rates lower than both the general population (SMR = 0.56; 95% CI 0.51-0.62) and the control group (SMR = 0.88; 95% CI 0.79-0.97). Cancer mortality in the deployed cohort group was half of that from the general population mortality rates (SMR = 0.50; 95% CI 0.40-0.62) and slightly lower if compared with the control group cancer mortality rates (SMR = 0.95; 95% CI 0.77-1.18). CONCLUSION: Balkan veteran cohort did not show any increase in general mortality or in cancer mortality.

The yeast model suggests the use of short peptides derived from mt LeuRS for the therapy of diseases due to mutations in several mt tRNAs.

We have previously established a yeast model of mitochondrial (mt) diseases. We showed that defective respiratory phenotypes due to point-mutations in mt tRNA(Leu(UUR)), tRNA(Ile) and tRNA(Val) could be relieved by overexpression of both cognate and non-cognate nuclearly encoded mt aminoacyl-tRNA synthetases (aaRS) LeuRS, IleRS and ValRS. More recently, we showed that the isolated carboxy-terminal domain (Cterm) of yeast mt LeuRS, and even short peptides derived from the human Cterm, have the same suppressing abilities as the whole enzymes. In this work, we extend these results by investigating the activity of a number of mt aaRS from either class I or II towards a panel of mt tRNAs. The Cterm of both human and yeast mt LeuRS has the same spectrum of activity as mt aaRS belonging to class I and subclass a, which is the most extensive among the whole enzymes. Yeast Cterm is demonstrated to be endowed with mt targeting activity. Importantly, peptide fragments ß30_31 and ß32_33, derived from the human Cterm, have even higher efficiency as well as wider spectrum of activity, thus opening new avenues for therapeutic intervention. Bind-shifting experiments show that the ß30_31 peptide directly interacts with human mt tRNA(Leu(UUR)) and tRNA(Ile), suggesting that the rescuing activity of isolated peptide fragments is mediated by a chaperone-like mechanism. Wide-range suppression appears to be idiosyncratic of LeuRS and its fragments, since it is not shared by Cterminal regions derived from human mt IleRS or ValRS, which are expected to have very different structures and interactions with tRNAs.

Cancer survival in Europe 1999-2007 by country and age: results of EUROCARE--5-a population-based study.

BACKGROUND: Cancer survival is a key measure of the effectiveness of health-care systems. EUROCARE-the largest cooperative study of population-based cancer survival in Europe-has shown persistent differences between countries for cancer survival, although in general, cancer survival is improving. Major changes in cancer diagnosis, treatment, and rehabilitation occurred in the early 2000s. EUROCARE-5 assesses their effect on cancer survival in 29 European countries. METHODS: In this retrospective observational study, we analysed data from 107 cancer registries for more than 10 million patients with cancer diagnosed up to 2007 and followed up to 2008. Uniform quality control procedures were applied to all datasets. For patients diagnosed 2000-07, we calculated 5-year relative survival for 46 cancers weighted by age and country. We also calculated country-specific and age-specific survival for ten common cancers, together with survival differences between time periods (for 1999-2001, 2002-04, and 2005-07). FINDINGS: 5-year relative survival generally increased steadily over time for all European regions. The largest increases from 1999-2001 to 2005-07 were for prostate cancer (73.4% [95% CI 72.9-73.9] vs 81.7% [81.3-82.1]), non-Hodgkin lymphoma (53.8% [53.3-54.4] vs 60.4% [60.0-60.9]), and rectal cancer (52.1% [51.6-52.6] vs 57.6% [57.1-58.1]). Survival in eastern Europe was generally low and below the European mean, particularly for cancers with good or intermediate prognosis. Survival was highest for northern, central, and southern Europe. Survival in the UK and Ireland was intermediate for rectal cancer, breast cancer, prostate cancer, skin melanoma, and non-Hodgkin lymphoma, but low for kidney, stomach, ovarian, colon, and lung cancers. Survival for lung cancer in the UK and Ireland was much lower than for other regions for all periods, although results for lung cancer in some regions (central and eastern Europe) might be affected by overestimation. Survival usually decreased with age, although to different degrees depending on region and cancer type. INTERPRETATION: The major advances in cancer management that occurred up to 2007 seem to have resulted in improved survival in Europe. Likely explanations of differences in survival between countries include: differences in stage at diagnosis and accessibility to good care, different diagnostic intensity and screening approaches, and differences in cancer biology. Variations in socioeconomic, lifestyle, and general health between populations might also have a role. Further studies are needed to fully interpret these findings and how to remedy disparities. FUNDING: Italian Ministry of Health, European Commission, Compagnia di San Paolo Foundation, Cariplo Foundation.

Isoleucyl-tRNA synthetase levels modulate the penetrance of a homoplasmic m.4277T>C mitochondrial tRNA(Ile) mutation causing hypertrophic cardiomyopathy.

The genetic and epigenetic factors underlying the variable penetrance of homoplasmic mitochondrial DNA mutations are poorly understood. We investigated a 16-year-old patient with hypertrophic cardiomyopathy harboring a homoplasmic m.4277T>C mutation in the mt-tRNA(Ile) (MTTI) gene. Skeletal muscle showed multiple respiratory chain enzyme abnormalities and a decreased steady-state level of the mutated mt-tRNA(Ile). Transmitochondrial cybrids grown on galactose medium demonstrated a functional effect of this mutation on cell viability, confirming pathogenicity. These findings were reproduced in transmitochondrial cybrids, harboring a previously described homoplasmic m.4300A>G MTTI mutation. The pathogenic role of the m.4277T>C mutation may be ascribed to misfolding of the mt-tRNA molecule, as demonstrated by the altered electrophoretic migration of the mutated mt-tRNA. Indeed, structure and sequence analyses suggest that thymidine at position 4277 of mt-tRNA(Ile) is involved in a conserved tertiary interaction with thymidine at position 4306. Interestingly, the mutation showed variable penetrance within family members, with skeletal muscle from the patient's clinically unaffected mother demonstrating normal muscle respiratory chain activities and steady-state levels of mt-tRNA(Ile), while homoplasmic for the m.4277T>C mutation. Analysis of mitochondrial isoleucyl-tRNA synthetase revealed significantly higher expression levels in skeletal muscle and fibroblasts of the unaffected mother when compared with the proband, while the transient over-expression of the IARS2 gene in patient transmitochondrial cybrids improved cell viability. This is the first observation that constitutively high levels of aminoacyl-tRNA synthetases (aaRSs) in human tissues prevent the phenotypic expression of a homoplasmic mt-tRNA point mutation. These findings extend previous observations on aaRSs therapeutic effects in yeast and human.

Structural and functional role of bases 32 and 33 in the anticodon loop of yeast mitochondrial tRNAIle.

Previous work has demonstrated the usefulness of the yeast model to investigate the molecular mechanisms underlying defects due to base substitutions in mitochondrial tRNA genes, and to identify suppressing molecules endowed with potential clinical relevance. The present paper extends these investigations to two human equivalent yeast mutations located at positions 32 and 33 in the anticodon loop of tRNA(Ile). Notwithstanding the proximity of the two T>C base substitutions, the effects of these mutations have been found to be quite different in yeast, as they are in human. The T32C substitution has a very severe effect in yeast, consisting in a complete inhibition of growth on nonfermentable substrates. Conversely, respiratory defects caused by the T33C mutation could only be observed in a defined genetic context. Analyses of available sequences and selected tRNA three-dimensional structures were performed to provide explanations for the different behavior of these adjacent mutations. Examination of the effects of previously identified suppressors demonstrated that overexpression of the TUF1 gene did not rescue the defective phenotypes determined by either mutation, possibly as a consequence of the lack of interactions between EF-Tu and the tRNA anticodon arm in known structures. On the contrary, both the cognate IleRS and the noncognate LeuRS and ValRS are endowed with suppressing activities toward both mutations. This allows us to extend to the tRNA(Ile) mutants the cross-suppression activity of aminoacyl-tRNA synthetases previously demonstrated for tRNA(Leu) and tRNA(Val) mutants.

Cost profiles of colorectal cancer patients in Italy based on individual patterns of care.

BACKGROUND: Due to changes in cancer-related risk factors, improvements in diagnostic procedures and treatments, and the aging of the population, in most developed countries cancer accounts for an increasing proportion of health care expenditures. The analysis of cancer-related costs is a topic of several economic and epidemiological studies and represents a research area of great interest to public health planners and policy makers. In Italy studies are limited either to some specific types of expenditures or to specific groups of cancer patients. Aim of the paper is to estimate the distribution of cancer survivors and associated health care expenditures according to a disease pathway which identifies three clinically relevant phases: initial (one year following diagnosis), continuing (between initial and final) and final (one year before death). METHODS: The methodology proposed is based on the reconstruction of patterns of care at individual level by combining different data sources, surveillance data and administrative data, in areas covered by cancer registration. RESULTS: A total colorectal cancer-related expenditure of 77.8 million Euros for 18012 patients (corresponding to about 4300 Euros per capita) is estimated in 2006 in two Italian areas located in Tuscany and Veneto regions, respectively. Cost of care varies according to the care pathway: 11% of patients were in the initial phase, and consumed 34% of total expenditure; patients in the final (6%) and in the continuing (83%) phase consumed 23% and 43% of the budget, respectively. There is an association between patterns of care/costs and patients characteristics such as stage and age at diagnosis. CONCLUSIONS: This paper represents the first attempt to attribute health care expenditures in Italy to specific phases of disease, according to varying treatment approaches, surveillance strategies and management of relapses, palliative care. The association between stage at diagnosis, profile of therapies and costs supports the idea that primary prevention and early detection play an important role in a public health perspective. Results from this pilot study encourage the use of such analyses in a public health perspective, to increase understanding of patient outcomes and economic consequences of differences in policies related to cancer screening, treatment, and programs of care.

Projecting cancer prevalence by phase of care: a methodological approach for health service planning.

Background: In most developed countries, the number of cancer survivors is expected to increase in the coming decades because of rising incidence and survival rates and an aging population. These patients are heterogeneous in terms of health service demands: from recently diagnosed patients requiring first-course therapy to patients with extensive care needs and severe disabilities to long-term survivors who only need minimal care. Therefore, in terms of providing healthcare planners and policymakers with useful indicators for addressing policies according to health service demands, it is worth supplying updated measures of prevalence for groups of patients based on the level of care they require. The aim of this paper is to illustrate a new method for estimating short-term projections of cancer prevalence by phase of care that applies to areas covered by cancer registration. Methods: The proposed method combines linear regression models to project limited duration prevalence derived from cancer registry data and a session of the freely available software COMPREV to estimate the projected complete prevalence into three distinct clinically relevant phases of care: initial, continuing, and final. The method is illustrated and validated using data from the Veneto region in Italy for breast, colorectal, and lung cancers. Results: Prevalence is expected to increase in 2015-2026 for all considered cancer sites and sexes, with average annual variations spanning from 2.6% for women with lung cancer to 0.5% for men with colorectal cancer. The only exception is lung cancer prevalence in men, which shows an average annual decrease of 1.9%. The majority of patients are in the continuing phase of care, followed by the initial and final phases, except for lung cancer, where the final phase of care prevails over the initial one. Discussion: The paper proposes a method for estimating (short-term) future cancer healthcare needs that is based on user-friendly and freely available software and linear regression models. Validation results confirm the applicability of our method to the most frequent cancer types, provided that cancer registry data with at least 15 years of registration are available. Evidence from this method is addressed to policymakers for planning future cancer care, thus improving the cancer survivorship experience for patients and caregivers.

Trends in radioactive iodine treatment after total thyroidectomy in Italy, 2001-2018.

Objective: A decrease in the use of radioactive iodine (RAI) treatment for thyroid cancer has been described in the last decade in the US following subsequent updates of the American Thyroid Association guidelines. By contrast, population-based data from European countries are lacking. The study aims to assess the frequency and long-term trends in the use of RAI in Italy. Methods: From the Italian national hospital discharge database, the proportion of RAI treatment after total thyroidectomy with thyroid cancer diagnosis has been assessed by sex and age class during 2001-2018. Results: Throughout the whole study period, RAI was performed after 58% of 149,419 total thyroidectomies. The use of RAI was higher for men and younger patients; it peaked in 2007 (64% in women and 68% in men) and declined thereafter (2018: 46% in women and 53% in men), with a similar pattern observed across all ages and areas. Conclusion: National data show that in Italy trends in RAI treatment paraleled those observed in the US. Further monitoring of the use of RAI is warranted in Italy, as elsewhere, to assess the impact of international guidelines on real-life clinical management of thyroid cancer.

Cancer treatment data available in European cancer registries: Where are we and where are we going?

Population-based cancer registries are responsible for collecting incidence and survival data on all reportable neoplasms within a defined geographical area. During the last decades, the role of cancer registries has evolved beyond monitoring epidemiological indicators, as they are expanding their activities to studies on cancer aetiology, prevention, and quality of care. This expansion relies also on the collection of additional clinical data, such as stage at diagnosis and cancer treatment. While the collection of data on stage, according to international reference classification, is consolidated almost everywhere, data collection on treatment is still very heterogeneous in Europe. This article combines data from a literature review and conference proceedings together with data from 125 European cancer registries contributing to the 2015 ENCR-JRC data call to provide an overview of the status of using and reporting treatment data in population-based cancer registries. The literature review shows that there is an increase in published data on cancer treatment by population-based cancer registries over the years. In addition, the review indicates that treatment data are most often collected for breast cancer, the most frequent cancer in women in Europe, followed by colorectal, prostate and lung cancers, which are also more common. Treatment data are increasingly being reported by cancer registries, though further improvements are required to ensure their complete and harmonised collection. Sufficient financial and human resources are needed to collect and analyse treatment data. Clear registration guidelines are to be made available to increase the availability of real-world treatment data in a harmonised way across Europe.

Cancer and Pregnancy: Estimates in Italy from Record-Linkage Procedures between Cancer Registries and the Hospital Discharge Database.

The aim of this study is to describe the frequency and trend of pregnancy-associated cancer (PAC) in Italy, an increasingly relevant phenomenon due to postponing age at childbirth. To this purpose, a population-based retrospective longitudinal study design based on cohorts of women aged 15-49 diagnosed with cancer and concomitant pregnancy is proposed. The study uses 19 population-based Cancer Registries, covering about 22% of Italy, and linked at an individual level with Hospital Discharge Records. A total of 2,861,437 pregnancies and 3559 PAC are identified from 74,165 women of the cohort with a rate of 1.24 PAC per 1000 pregnancies. The most frequent cancer site is breast (24.3%), followed by thyroid (23.9%) and melanoma (14.3%). The most frequent outcome is delivery (53.1%), followed by voluntary termination of pregnancy and spontaneous abortion (both 12.0%). The trend of PAC increased from 2003 to 2015, especially when the outcome is delivery, thus confirming a new attitude of clinicians to manage cancer throughout pregnancy. This represents the first attempt in Italy to describe PAC from Cancer Registries data; the methodology is applicable to other areas with the same data availability. Evidence from this study is addressed to clinicians for improving clinical management of women with PAC.

Complete prevalence and indicators of cancer cure: enhanced methods and validation in Italian population-based cancer registries.

Objectives: To describe the procedures to derive complete prevalence and several indicators of cancer cure from population-based cancer registries. Materials and methods: Cancer registry data (47% of the Italian population) were used to calculate limited duration prevalence for 62 cancer types by sex and registry. The incidence and survival models, needed to calculate the completeness index (R) and complete prevalence, were evaluated by likelihood ratio tests and by visual comparison. A sensitivity analysis was conducted to explore the effect on the complete prevalence of using different R indexes. Mixture cure models were used to estimate net survival (NS); life expectancy of fatal (LEF) cases; cure fraction (CF); time to cure (TTC); cure prevalence, prevalent patients who were not at risk of dying as a result of cancer; and already cured patients, those living longer than TTC at a specific point in time. CF was also compared with long-term NS since, for patients diagnosed after a certain age, CF (representing asymptotical values of NS) is reached far beyond the patient's life expectancy. Results: For the most frequent cancer types, the Weibull survival model stratified by sex and age showed a very good fit with observed survival. For men diagnosed with any cancer type at age 65-74 years, CF was 41%, while the NS was 49% until age 100 and 50% until age 90. In women, similar differences emerged for patients with any cancer type or with breast cancer. Among patients alive in 2018 with colorectal cancer at age 55-64 years, 48% were already cured (had reached their specific TTC), while the cure prevalence (lifelong probability to be cured from cancer) was 89%. Cure prevalence became 97.5% (2.5% will die because of their neoplasm) for patients alive >5 years after diagnosis. Conclusions: This study represents an addition to the current knowledge on the topic providing a detailed description of available indicators of prevalence and cancer cure, highlighting the links among them, and illustrating their interpretation. Indicators may be relevant for patients and clinical practice; they are unambiguously defined, measurable, and reproducible in different countries where population-based cancer registries are active.