ITALIAN CANCER FIGURES - REPORT 2015: The burden of rare cancers in Italy = I TUMORI IN ITALIA - RAPPORTO 2015: I tumori rari in Italia

OBJECTIVES: This collaborative study, based on data collected by the network of Italian Cancer Registries (AIRTUM), describes the burden of rare cancers in Italy. Estimated number of new rare cancer cases yearly diagnosed (incidence), proportion of patients alive after diagnosis (survival), and estimated number of people still alive after a new cancer diagnosis (prevalence) are provided for about 200 different cancer entities. MATERIALS AND METHODS: Data herein presented were provided by AIRTUM population- based cancer registries (CRs), covering nowadays 52% of the Italian population. This monograph uses the AIRTUM database (January 2015), which includes all malignant cancer cases diagnosed between 1976 and 2010. All cases are coded according to the International Classification of Diseases for Oncology (ICD-O-3). Data underwent standard quality checks (described in the AIRTUM data management protocol) and were checked against rare-cancer specific quality indicators proposed and published by RARECARE and HAEMACARE (www.rarecarenet.eu; www.haemacare.eu). The definition and list of rare cancers proposed by the RARECAREnet "Information Network on Rare Cancers" project were adopted: rare cancers are entities (defined as a combination of topographical and morphological codes of the ICD-O-3) having an incidence rate of less than 6 per 100,000 per year in the European population. This monograph presents 198 rare cancers grouped in 14 major groups. Crude incidence rates were estimated as the number of all new cancers occurring in 2000-2010 divided by the overall population at risk, for males and females (also for gender-specific tumours).The proportion of rare cancers out of the total cancers (rare and common) by site was also calculated. Incidence rates by sex and age are reported. The expected number of new cases in 2015 in Italy was estimated assuming the incidence in Italy to be the same as in the AIRTUM area. One- and 5-year relative survival estimates of cases aged 0-99 years diagnosed between 2000 and 2008 in the AIRTUM database, and followed up to 31 December 2009, were calculated using complete cohort survival analysis. To estimate the observed prevalence in Italy, incidence and follow-up data from 11 CRs for the period 1992-2006 were used, with a prevalence index date of 1 January 2007. Observed prevalence in the general population was disentangled by time prior to the reference date (≤2 years, 2-5 years, ≤15 years). To calculate the complete prevalence proportion at 1 January 2007 in Italy, the 15-year observed prevalence was corrected by the completeness index, in order to account for those cancer survivors diagnosed before the cancer registry activity started. The completeness index by cancer and age was obtained by means of statistical regression models, using incidence and survival data available in the European RARECAREnet data. RESULTS: In total, 339,403 tumours were included in the incidence analysis. The annual incidence rate (IR) of all 198 rare cancers in the period 2000-2010 was 147 per 100,000 per year, corresponding to about 89,000 new diagnoses in Italy each year, accounting for 25% of all cancer. Five cancers, rare at European level, were not rare in Italy because their IR was higher than 6 per 100,000; these tumours were: diffuse large B-cell lymphoma and squamous cell carcinoma of larynx (whose IRs in Italy were 7 per 100,000), multiple myeloma (IR: 8 per 100,000), hepatocellular carcinoma (IR: 9 per 100,000) and carcinoma of thyroid gland (IR: 14 per 100,000). Among the remaining 193 rare cancers, more than two thirds (No. 139) had an annual IR <0.5 per 100,000, accounting for about 7,100 new cancers cases; for 25 cancer types, the IR ranged between 0.5 and 1 per 100,000, accounting for about 10,000 new diagnoses; while for 29 cancer types the IR was between 1 and 6 per 100,000, accounting for about 41,000 new cancer cases. Among all rare cancers diagnosed in Italy, 7% were rare haematological diseases (IR: 41 per 100,000), 18% were solid rare cancers. Among the latter, the rare epithelial tumours of the digestive system were the most common (23%, IR: 26 per 100,000), followed by epithelial tumours of head and neck (17%, IR: 19) and rare cancers of the female genital system (17%, IR: 17), endocrine tumours (13% including thyroid carcinomas and less than 1% with an IR of 0.4 excluding thyroid carcinomas), sarcomas (8%, IR: 9 per 100,000), central nervous system tumours and rare epithelial tumours of the thoracic cavity (5%with an IR equal to 6 and 5 per 100,000, respectively). The remaining (rare male genital tumours, IR: 4 per 100,000; tumours of eye, IR: 0.7 per 100,000; neuroendocrine tumours, IR: 4 per 100,000; embryonal tumours, IR: 0.4 per 100,000; rare skin tumours and malignant melanoma of mucosae, IR: 0.8 per 100,000) each constituted <4% of all solid rare cancers. Patients with rare cancers were on average younger than those with common cancers. Essentially, all childhood cancers were rare, while after age 40 years, the common cancers (breast, prostate, colon, rectum, and lung) became increasingly more frequent. For 254,821 rare cancers diagnosed in 2000-2008, 5-year RS was on average 55%, lower than the corresponding figures for patients with common cancers (68%). RS was lower for rare cancers than for common cancers at 1 year and continued to diverge up to 3 years, while the gap remained constant from 3 to 5 years after diagnosis. For rare and common cancers, survival decreased with increasing age. Five-year RS was similar and high for both rare and common cancers up to 54 years; it decreased with age, especially after 54 years, with the elderly (75+ years) having a 37% and 20% lower survival than those aged 55-64 years for rare and common cancers, respectively. We estimated that about 900,000 people were alive in Italy with a previous diagnosis of a rare cancer in 2010 (prevalence). The highest prevalence was observed for rare haematological diseases (278 per 100,000) and rare tumours of the female genital system (265 per 100,000). Very low prevalence (<10 prt 100,000) was observed for rare epithelial skin cancers, for rare epithelial tumours of the digestive system and rare epithelial tumours of the thoracic cavity. COMMENTS: One in four cancers cases diagnosed in Italy is a rare cancer, in agreement with estimates of 24% calculated in Europe overall. In Italy, the group of all rare cancers combined, include 5 cancer types with an IR>6 per 100,000 in Italy, in particular thyroid cancer (IR: 14 per 100,000).The exclusion of thyroid carcinoma from rare cancers reduces the proportion of them in Italy in 2010 to 22%. Differences in incidence across population can be due to the different distribution of risk factors (whether environmental, lifestyle, occupational, or genetic), heterogeneous diagnostic intensity activity, as well as different diagnostic capacity; moreover heterogeneity in accuracy of registration may determine some minor differences in the account of rare cancers. Rare cancers had worse prognosis than common cancers at 1, 3, and 5 years from diagnosis. Differences between rare and common cancers were small 1 year after diagnosis, but survival for rare cancers declined more markedly thereafter, consistent with the idea that treatments for rare cancers are less effective than those for common cancers. However, differences in stage at diagnosis could not be excluded, as 1- and 3-year RS for rare cancers was lower than the corresponding figures for common cancers. Moreover, rare cancers include many cancer entities with a bad prognosis (5-year RS <50%): cancer of head and neck, oesophagus, small intestine, ovary, brain, biliary tract, liver, pleura, multiple myeloma, acute myeloid and lymphatic leukaemia; in contrast, most common cancer cases are breast, prostate, and colorectal cancers, which have a good prognosis. The high prevalence observed for rare haematological diseases and rare tumours of the female genital system is due to their high incidence (the majority of haematological diseases are rare and gynaecological cancers added up to fairly high incidence rates) and relatively good prognosis. The low prevalence of rare epithelial tumours of the digestive system was due to the low survival rates of the majority of tumours included in this group (oesophagus, stomach, small intestine, pancreas, and liver), regardless of the high incidence rate of rare epithelial cancers of these sites. This AIRTUM study confirms that rare cancers are a major public health problem in Italy and provides quantitative estimations, for the first time in Italy, to a problem long known to exist. This monograph provides detailed epidemiologic indicators for almost 200 rare cancers, the majority of which (72%) are very rare (IR<0.5 per 100,000). These data are of major interest for different stakeholders. Health care planners can find useful information herein to properly plan and think of how to reorganise health care services. Researchers now have numbers to design clinical trials considering alternative study designs and statistical approaches. Population-based cancer registries with good quality data are the best source of information to describe the rare cancer burden in a population

I TUMORI IN ITALIA - RAPPORTO 2013: Tumori multipli = ITALIAN CANCER FIGURES - REPORT 2013: Multiple tumours

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 (≥ 0 months), excluding the synchronicity period (≥ 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 ≥2 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

Italian cancer figures, report 2013: Multiple tumours

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 (≥ 0 months), excluding the synchronicity period (≥ 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 ≥2 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