Real Life Clinical Management and Survival in Advanced Cutaneous Melanoma: The Italian Clinical National Melanoma Registry Experience.

BACKGROUND: Cutaneous melanoma (CM) is one of the most aggressive types of skin cancer. Currently, innovative approaches such as target therapies and immunotherapies have been introduced in clinical practice. Data of clinical trials and real life studies that evaluate the outcomes of these therapeutic associations are necessary to establish their clinical utility. The aim of this study is to investigate the types of oncological treatments employed in the real-life clinical management of patients with advanced CM in several Italian centers, which are part of the Clinical National Melanoma Registry (CNMR). METHODS: Melanoma-specific survival and overall survival were calculated. Multivariate Cox regression models were used to estimate the hazard ratios adjusting for confounders and other prognostic factors. RESULTS: The median follow-up time was 36 months (range 1.2-185.1). 787 CM were included in the analysis with completed information about therapies. All types of immunotherapy showed a significant improved survival compared with all other therapies (p=0.001). 75% was the highest reduction of death reached by anti-PD-1 (HR=0.25), globally immunotherapy was significantly associated with improved survival, either for anti-CTLA4 monotherapy or combined with anti-PD-1 (HR=0.47 and 0.26, respectively) and BRAFI+MEKI (HR=0.62). CONCLUSIONS: The nivolumab/pembrolizumab in combination of ipilimumab and the addition of ant-MEK to the BRAFi can be considered the best therapies to improve survival in a real-world-population. The CNMR can complement clinical registries with the intent of improving cancer management and standardizing cancer treatment.

Epidemiology and genetic susceptibility of malignant melanoma in North Sardinia, Italy.

The aim of this report was to study the descriptive and genetic epidemiology of malignant melanoma in North Sardinia, Italy, in the period 1992-2011. Epidemiological data were obtained from the local tumor registry, which is part of the Italian Association for Tumor Registries. Among patients included in the North Sardinia tumor registry, 316 patients first evaluated for familial recurrence of melanoma were submitted to mutation analysis in CDKN2A and CDK4 genes. The overall number of cases registered was 532. The male-to-female ratio was 1 : 1 and the mean age was 56 years for men and 55 years for women. The standardized incidence rates were 4.9/100 000 and 4.4/100 000 and the standardized mortality rates were 1.7/100 000 and 1.3/100 000 for men and women, respectively. The relative 5-year survival was 77% for men and 79% for women. In our series, 24/316 (7.6%) patients had a familial occurrence of melanoma (presence of at least one additional family member affected). Among these, one variant (Gly23Asp), reported previously as a low-frequency disease-causing mutation, was detected by mutational screening in the p16 gene only. With the exception of polymorphisms, none of either the sporadic melanoma patients or healthy controls presented a germline mutation in candidate genes. An increase in incidence and a decrease in mortality rates of malignant melanoma were registered in North Sardinia, from 1992 to 2011, whereas survival was similar to that reported in recent international reports. The high-penetrance melanoma susceptibility genes (CDKN2A and CDK4) are not involved in predisposition to melanoma in North Sardinia.

Prognostic impact of KRAS, NRAS, BRAF, and PIK3CA mutations in primary colorectal carcinomas: a population-based study.

BACKGROUND: Activation of oncogenes downstream the EGFR gene contributes to colorectal tumorigenesis and determines the sensitivity to anti-EGFR treatments. The aim of this study was to evaluate the prognostic value of KRAS, BRAF, NRAS and PIK3CA mutations in a large collection of CRC patients from genetically-homogeneous Sardinian population. METHODS: A total of 1284 Sardinian patients with histologically-proven diagnosis of colorectal carcinoma (CRC) and presenting with metastatic disease were included into the study. Genomic DNA was isolated from formalin-fixed, paraffin-embedded primary tumour tissue samples of CRC patients and screened for mutations in RAS and BRAF genes, using pyrosequencing assays, and in PIK3CA gene, using automated DNA sequencing assays. RESULTS: Overall, mutation rates were 35.6 % for KRAS, 4.1 % for NRAS, and 2.1 % for BRAF. Among available DNA samples, 114/796 (14.3 %) primary CRCs were found to carry a mutation in the PIK3CA gene. In this subset of patients analysed in all four genes, a pathogenetic mutation of at least one gene was discovered in about half (378/796; 47.5 %) of CRC cases. A mutated BRAF gene was found to steadily act as a negative prognostic factor for either time to progression as metastatic disease (from detection of primary CRC to diagnosis of first distant metastasis; p = 0.009) or partial survival (from diagnosis of advanced disease to the time of death or last control; p = 0.006) or overall survival (p < 0.001). No significant impact on prognosis was observed for mutated KRAS, NRAS, and PIK3CA genes or combined RAS mutations (all RAS). CONCLUSIONS: Our study defines both prevalence and prognostic role of main activated oncogenes in a population-based large collection of CRC patients.

Prognostic role of KRAS mutations in Sardinian patients with colorectal carcinoma.

The presence of mutations in the KRAS gene is a predictor of a poor clinical response to EGFR-targeted agents in patients affected by colorectal cancer (CRC), but its significance as a global prognostic factor remains unclear. The aim of the present study was to evaluate the impact of the KRAS mutational status on time to first metastasis (TTM) and overall survival (OS) in a cohort of Sardinian CRC patients. A total of 551 patients with metastatic CRC at the time of enrolment were included. Clinical and pathological features of the disease, including follow-up information, were obtained from medical records and cancer registry data. For mutational analysis formalin-fixed paraffin-embedded tissue samples were processed using a standard protocol. The coding sequence and splice junctions of exons 2 and 3 of the KRAS gene were screened for mutations by direct automated sequencing. Overall, 186 KRAS mutations were detected in 183/551 (33%) patients: 125 (67%) were located in codon 12, 36 (19%) in codon 13, and 18 (10%) in codon 61. The remaining mutations (7; 4%) were detected in uncommonly-affected codons. No significant correlation between KRAS mutations and gender, age, anatomical location and stage of the disease at the time of diagnosis was identified. Furthermore, no prognostic value of KRAS mutations was found considering either TTM or OS. When patients were stratified by KRAS mutational status and gender, males were significantly associated with a longer TTM. The results of the present study indicate that KRAS mutation correlated with a slower metastatic progression in males with CRC from Sardinia, irrespective of the age at diagnosis and the codon of the mutation.

Screening for colorectal cancer in Italy: 2011-2012 survey.

We utilised the IMPATTO study's archives to describe the 2000-2008 colorectal cancer (CRC) incidence rate trends in Italy, once screening programmes based on the faecal immunochemical test were implemented in different areas. Data on CRCs diagnosed in Italy from 2000 to 2008 in subjects aged 40-79 years were collected by 23 cancer registries. Incidence rate trends were evaluated as a whole and by macro-area (North-Centre and South-Islands), presence of a screening programme, sex, ten-year age class, anatomic site, stage at diagnosis, and pattern of diagnosis (screen-detected, non-screen-detected). The annual percent change (APC) of incidence rate trends, with 95% confidence intervals (95%CI), were computed. The study included 46,857 CRCs diagnosed in subjects aged 40-79 years, of which 2,806 were screen-detected. The incidence rates in the North-Centre were higher than in the South and on the Islands. During the study period, screening programmes had been implemented only in the North-Centre and had a significant effect on incidence rates, with an initial sharp increase in incidence, followed by a decrease that started in the 3rd-4th years of screening. These incidence rate trends were exclusively due to modifications in the rates of stage I cases. After screening programmes started, incidence increased in all anatomic sites, particularly in the distal colon. The differential figures introduced by the implementation of screening programmes warrant a continuous surveillance of CRC incidence and mortality trends to monitor the impact of screening at a national level.

Genome-wide association study of susceptibility loci for breast cancer in Sardinian population.

BACKGROUND: Despite progress in identifying genes associated with breast cancer, many more risk loci exist. Genome-wide association analyses in genetically-homogeneous populations, such as that of Sardinia (Italy), could represent an additional approach to detect low penetrance alleles. METHODS: We performed a genome-wide association study comparing 1431 Sardinian patients with non-familial, BRCA1/2-mutation-negative breast cancer to 2171 healthy Sardinian blood donors. DNA was genotyped using GeneChip Human Mapping 500 K Arrays or Genome-Wide Human SNP Arrays 6.0. To increase genomic coverage, genotypes of additional SNPs were imputed using data from HapMap Phase II. After quality control filtering of genotype data, 1367 cases (9 men) and 1658 controls (1156 men) were analyzed on a total of 2,067,645 SNPs. RESULTS: Overall, 33 genomic regions (67 candidate SNPs) were associated with breast cancer risk at the p < 0(-6) level. Twenty of these regions contained defined genes, including one already associated with breast cancer risk: TOX3. With a lower threshold for preliminary significance to p < 10(-5), we identified 11 additional SNPs in FGFR2, a well-established breast cancer-associated gene. Ten candidate SNPs were selected, excluding those already associated with breast cancer, for technical validation as well as replication in 1668 samples from the same population. Only SNP rs345299, located in intron 1 of VAV3, remained suggestively associated (p-value, 1.16 x 10(-5)), but it did not associate with breast cancer risk in pooled data from two large, mixed-population cohorts. CONCLUSIONS: This study indicated the role of TOX3 and FGFR2 as breast cancer susceptibility genes in BRCA1/2-wild-type breast cancer patients from Sardinian population.

Epidemiological and genetic factors underlying melanoma development in Italy.

Among human cancers, melanoma remains one of the malignancies with an ever-growing incidence in white populations. Recent advances in biological and immunological therapeutic approaches as well as increased efforts for secondary prevention are contributing to improve the survival rates. It is likely that a significant fall in mortality rates for melanoma will be achieved by further increase of the early detection through a more accurate selection of the higher-risk individuals (i.e., carriers of predisposing genetic alterations). A similar scenario occurs in Italy. In the present review, we have considered data on incidence, survival and mortality rates of melanoma in Italian population, including evaluation of the main risk factors and genetic mutations underlying disease susceptibility.

ERCC1 polymorphisms as prognostic markers in T4 breast cancer patients treated with platinum-based chemotherapy.

BACKGROUND: Polymorphisms in the excision repair cross-complimentary group 1 (ERCC1) gene have been involved in the prognosis of various cancers. In the present study, we evaluated the prognostic role of the two most common ERCC1 polymorphisms in patients with T4 breast cancer receiving platinum-based chemotherapy. METHODS: A total of 47 patients with T4 breast cancer undergoing treatment with a platinum-based regimen were collected and followed up (median 159 months; range, 42-239 months). ERCC1 C8092A (rs3212986) and T19007C (rs11615) polymorphisms were genotyped, using an automated sequencing approach. The same series was screened for BRCA1/2 mutations by DHPLC analysis and DNA sequencing. RESULTS: Among the tested patients, 16 (34%) and 25 (53%) presented the 8092A (homo-zygosity A/A or heterozygosity A/C) and the 19007C (homozygosity C/C or heterozygosity C/T) genotypes, respectively. The 8092A and 19007C genotypes in ERCC1 were significantly associated with overall survival in T4 breast cancer patients treated with chemotherapy containing platinum (p-values = 0.036 and 0.004, respectively). Univariate and multivariate Cox regression analyses showed that combination of 8092A and 19007C genotypes acts as a significant prognostic factor in women with T4 breast cancer receiving platinum-based chemotherapy (p-values = 0.022 and 0.049, respectively). Two (4.3%) out of 47 cases were found to carry BRCA1/2 mutations; they presented the highest overall survival rates into the series. CONCLUSIONS: The ERCC1 8092A and 19007C genotypes or their combination may predict a favorable prognosis in T4 breast cancer patients undergoing a platinum-based treatment. Further large-scale, prospective studies are needed to validate our findings.

Triple-negative breast cancer frequency and type of BRCA mutation: Clues from Sardinia.

Germline mutations in BRCA1 or BRCA2 genes have been demonstrated to increase the risk of developing breast cancer. Among the prognostic factors currently used in clinical practice, the disease stage and the receptor status play a crucial role in the management of breast carcinoma. Triple-negative breast cancer (TNBC) has been classified as a disease subgroup that is negative for oestrogen, progesterone and HER2 receptor expression, and presents a poor prognosis. The present study investigated the correlation between BRCA1/2 mutations and TNBC status in a large series (n=726) of breast cancer patients from Sardinia. The BRCA mutation screening was performed on genomic DNA from peripheral blood samples by denaturing high-performance liquid chromatography analysis and automated DNA sequencing. Overall, 21/726 (2.9%) patients carried a germline mutation in BRCA1 or BRCA2. The TNBC phenotype was significantly associated with the BRCA1 mutations (P<0.001), whereas no association was found with the BRCA2 mutations (P=0.837). With respect to patient origin within Sardinia, a significant inverse distribution of mutations was found; BRCA1 and BRCA2 mutations represented 86 and 93% of the mutated cases in Southern and Middle-Northern Sardinia, respectively (P<0.001). Patients from the geographical area with BRCA1 mutation prevalence presented a TNBC incidence much higher than that observed in cases from the area with BRCA2 mutation prevalence (12 vs. 4%, respectively; P=0.037). These findings further confirmed that the occurrence of TNBC is significantly associated with the BRCA1 mutation carrier status and that a different 'genetic background' may have a phenotypic impact in the onset of breast cancer.

Epidemiology of malignant pleural mesothelioma in the province of Sassari (Sardinia, Italy). A population-based report.

UNLABELLED: The aim of this population-based study was to analyze and describe the epidemiological characteristics and trends of malignant pleural mesothelioma in the province of Sassari (Sardinia, Italy), in the period 1992-2010. Data were obtained from the local tumor registry which makes part of a wider registry web, coordinated today by the Italian Association for Tumor Registries. The overall number of malignant pleural mesothelioma cases registered was 70. The male-to-female ratio was 4:1 and the mean age 65.1 years for males and 63.4 years for females. The standardized incidence rates were 1.2/100,000 and 0.3/100,000 and the standardized mortality rates 0.6/100,000 and 0.2/100,000 for males and females respectively. A trend to increase in incidence in recent years was evidenced. This trend seems to follow the general national tendency and it depends on a large diffusion of asbestos usage in the past, delayed legislative interventions and probably a cleaning strategy of residual contamination fonts to intensify. The relative 5 years survival was low, suggesting the necessity to further intensify research and cure methods for the treatment of this extremely aggressive disease. KEY WORDS: Asbestos exposure, Mesothelioma, Pleura, Sassari.

Estimates of cancer burden in Sardinia.

AIMS AND BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

High fasting blood glucose and obesity significantly and independently increase risk of breast cancer death in hormone receptor-positive disease.

PURPOSE: We investigated the effect of fasting blood glucose and body mass index (BMI) at diagnosis on risk of breast cancer death for cases diagnosed in five Italian cancer registries in 2003-2005 and followed up to the end of 2008. METHODS: For 1607 Italian women (≥15 years) with information on BMI or blood glucose or diabetes, we analysed the risk of breast cancer death in relation to glucose tertiles (≤84.0, 84.1-94.0, >94.0 mg/dl) plus diabetic and unspecified categories; BMI tertiles (≤23.4, 23.5-27.3, >27.3 kg/m(2), unspecified), stage (T1-3N0M0, T1-3N+M0 plus T4anyNM0, M1, unspecified), oestrogen (ER) and progesterone (PR) status (ER+PR+, ER-PR-, ER and PR unspecified, other), age, chemotherapy and endocrine therapy, using multiple regression models. Separate models for ER+PR+ and ER-PR- cases were also run. RESULTS: Patients often had T1-3N0M0, ER+PR+ cancers and received chemotherapy or endocrine therapy; only 6% were M1 and 17% ER-PR-. Diabetic patients were older and had more often high BMI (>27 kg/m(2)), ER-PR-, M1 cancers than other patients. For ER+PR+ cases, with adjustment for other variables, breast cancer mortality was higher in women with high BMI than those with BMI 23.5-27.3 kg/m(2) (hazard ratio (HR)=2.9, 95% confidence interval (CI) 1.2-6.9). Breast cancer mortality was also higher in women with high (>94 mg/dl) blood glucose compared to those with glucose 84.1-94.0mg/dl (HR=2.6, 95% CI 1.2-5.7). CONCLUSION: Our results provide evidence that in ER+PR+ patients, high blood glucose and high BMI are independently associated with increased risk of breast cancer death. Detection and correction of these factors in such patients may improve prognosis.

Lung cancer epidemiology in North Sardinia, Italy.

BACKGROUND: The aim of this study was to analyze and describe the epidemiological characteristics and trends of lung cancer in North Sardinia, Italy, in the period 1992-2010. METHODS: Data were obtained from the tumor registry of Sassari province which is a part of a wider registry web, coordinated today by the Italian Association for Tumor Registries. RESULTS: The overall number of lung cancer cases registered was 4,325. The male-to-female ratio was 4.6:1 and the mean age 68.1 years for males and 67 years for females. The standardized incidence rates were 73.1/100,000 and 13.5/100,000 and the standardized mortality rates 55.7/100,000 and 9.9/100,000 for males and females, respectively. An increasing trend in incidence of lung cancer in women was evidenced. Conversely, incidence was found to decrease in males. Relative survival at 5 years from diagnosis was low (8.8% for males and 14.9% for females). Furthermore, an increase in mortality rates was observed in both sexes in the period under investigation. CONCLUSIONS: Our data show an increasing trend of lung cancer incidence in women in North Sardinia in the last decades. Conversely, a reduction of incidence rates was observed in males. Furthermore, a slightly increasing trend in mortality rates was observed in both sexes, suggesting the need to enhance smoking control strategies, consider adoption of effective surveillance policies, and improve diagnosis and treatment methods.

Impact of diabetes on overall and cancer-specific mortality in colorectal cancer patients.

PURPOSE: Diabetes is associated with increased risk of developing colorectal cancer (CRC), but its effect on overall and cancer-specific mortality in CRC patients has been little investigated. The aim of this study was to assess the influence of diabetes on overall and cancer-specific mortality in Italian CRC patients. METHODS: Cases of adult (≥15 years) CRC, diagnosed in 2003-2005, most followed-up to the end of 2008, were randomly selected from the Italian Cancer Registries database. Diabetic status, sex, age, tumor stage, subsite, treatment, morphology, and grade were obtained by consultation of patient clinical records. Poisson multivariable regression models, adjusted for potential confounding variables, were used to estimate hazard ratios (HRs) for all-cause and CRC-specific mortality, according to diabetic status. RESULTS: A total of 1,039 CRC cases with known fasting glucose or diabetic status, archived in 7 cancer registries, was analyzed. Compared to non-diabetics, diabetics (specific diagnosis or glucose ≥126 mg/dl) were older and less likely to receive adjuvant therapy. Diabetics were at higher risk of all-cause death [HR 1.41; 95 % confidence interval (CI) 1.18-1.70] and CRC death (HR 1.36; 95 % CI 1.11-1.67), with no differences by sex or subsite. CONCLUSIONS: Diabetes was significantly associated with increased overall and CRC-specific mortality. Our findings indicate that diabetes is a negative prognostic factor for CRC and suggest that in patients with CRC, diabetes prevention and treatments that stabilize the condition and control its complications might reduce mortality. Further studies are required to ascertain the mechanisms linking diabetes to greater mortality in CRC patients.

In vitro activity of the αvß3 integrin antagonist RGDechi-hCit on malignant melanoma cells.

BACKGROUND: In malignant melanoma (MM), overexpression of αvß3 integrin is linked to a more metastatic phenotype. Development of anti-αvß3 agents able to counteract melanoma progression would be helpful for disease treatment. A new selective ligand of αvß3, RGDechi-hCit, has anti-angiogenic properties against endothelial cells in animal angiogenesis models. The aim of this study was to evaluate the in vitro effects of the RGDechi-hCit peptide on MM cell lines. MATERIALS AND METHODS: Cytofluorimetric analysis characterized the cell surface expression of αvß3 integrin on seven MM cell lines: A375, WM266-4, SK-Mel-28, Sbcl2, LB24Dagi, PR-Mel and PNP-Mel. Cell proliferation, adhesion, and migration assays were carried out using the αvß3-antagonist RGDechi-hCit. RESULTS: Proliferation was not significantly inhibited by RGDechi-hCit, although striking morphological changes were detected in MM cell lines highly expressing αvß3. Conversely, assays on fibronectin-coated plates showed a significant RGDechi-hCit dose-dependent inhibitory effect on both adhesion and migration. CONCLUSION: The data demonstrate anti-adhesion and anti-migration, but not antiproliferative, activities of RGDechi-hCit against MM cells.

Epidemiology of thyroid cancer in an area of epidemic thyroid goiter.

The aim of this study was to analyze and describe the epidemiological characteristics and trends of thyroid cancer in the province of Sassari (Sardinia, Italy), an area with epidemic thyroid goiter, in the period 1992-2010. Data were obtained from the local tumor registry which makes part of a wider registry web, coordinated today by the Italian Association for Tumor Registries. An increasing trend in the incidence of thyroid cancer in the province of Sassari was evidenced. This trend seems to follow the general worldwide trend and does not seem to be related to the high incidence of thyroid goiter in the area. The frequencies of the different histological subtypes were similar to those reported in numerous national and international reports. Women are affected earlier than men and, therefore, suffer greater professional, economic, and social impacts. Overall mortality is low and a relative 5-year survival is excellent, especially in comparison to other malignancies.

Prevalence of KRAS, BRAF, and PIK3CA somatic mutations in patients with colorectal carcinoma may vary in the same population: clues from Sardinia.

BACKGROUND: Role of KRAS, BRAF and PIK3CA mutations in pathogenesis of colorectal cancer (CRC) has been recently investigated worldwide. In this population-based study, we evaluated the incidence rates and distribution of such somatic mutations in genetically isolated population from Sardinia. METHODS: From April 2009 to July 2011, formalin-fixed paraffin-embedded tissues (N = 478) were prospectively collected from Sardinian CRC patients at clinics across the entire island. Genomic DNA was isolated from tissue sections and screened for mutations in KRAS, BRAF, and PIK3CA genes by automated DNA sequencing. RESULTS: Overall, KRAS tumour mutation rate was 30% (145/478 positive cases). Distribution of mutation carriers was surprisingly different within the island: 87/204 (43%) in North Sardinia vs. 58/274 (21%) in Middle-South Sardinia (p<0.001). Among 384 CRC cases whose DNA was available, only one (0.3%) patient carried a mutation in BRAF gene; PIK3CA was found mutated in 67 (17%) patients. A significant inverse distribution of PIK3CA mutation rates was observed within Sardinian population: 19/183 (10%) cases from northern vs. 48/201 (24%) cases from central-southern island (p<0.001). This heterogeneity in frequencies of KRAS/PIK3CA somatic mutations is consistent with already-reported discrepancies in distribution of germline mutations for other malignancies within Sardinian population. Preliminary clinical evaluation of 118 KRAS wild-type patients undergoing anti-EGFR-based treatment indicated lack of role for PIK3CA in predicting response to therapy. CONCLUSIONS: Our findings support the hypothesis that differences in patients' origins and related genetic backgrounds may contribute to even determine the incidence rate of somatic mutations in candidate cancer genes.

Regional inequalities in cancer care persist in Italy and can influence survival.

BACKGROUND: Population-based cancer registry studies of care patterns can help elucidate reasons for the marked geographic variation in cancer survival across Italy. The article provides a snapshot of the care delivered to cancer patients in Italy. METHODS: Random samples of adult patients with skin melanoma, breast, colon and non-small cell lung cancers diagnosed in 2003-2005 were selected from 14 Italian cancer registries. Logistic models estimated odds of receiving standard care (conservative surgery plus radiotherapy for early breast cancer; surgery plus chemotherapy for Dukes C colon cancer; surgery for lung cancer; sentinel node biopsy for >1mm melanoma, vs. other treatment) in each registry compared to the entire sample (reference). RESULTS: Stage at diagnosis for breast, colon and melanoma was earlier in north/central than southern registries. Odds of receiving standard care were lower than reference in Sassari (0.68, 95%CI 0.51-0.90) and Napoli (0.48, 95%CI 0.35-0.67) for breast cancer; did not differ across registries for Dukes C colon cancer; were higher in Romagna (3.77, 95%CI 1.67-8.50) and lower in Biella (0.38, 95%CI 0.18-0.82) for lung cancer; and were higher in Reggio Emilia (2.37, 95%CI 1.12-5.02) and lower in Ragusa (0.27, 95%CI 0.14-0.54) for melanoma. CONCLUSIONS: Notwithstanding limitations due to variations in the availability of clinical information and differences in stage distribution between north/central and southern registries, our study shows that important disparities in cancer care persist across Italy. Thus the public health priority of reducing cancer survival disparities will not be achieved in the immediate future.

Differences in stage and treatment of breast cancer across Italy point to inequalities in access to and availability of proper care.

AIMS AND BACKGROUND: Population-based cancer registry studies of patterns of care can help elucidate reasons for differences in breast cancer survival across Italy documented by previous studies. The aims of the present study were to investigate across-country variation in stage at presentation and standard care for breast cancer cases diagnosed in Italy in the early 2000s. METHODS: Samples of adult (≥ 15 years) women with breast cancer diagnosed in 2003-2005 were randomly selected in 9 Italian cancer registries. Logistic regression models were used to estimate the odds of receiving breast-conserving surgery plus radiotherapy (BCS + RT) in each cancer registry, age group, and disease stage category compared with the entire sample (reference); the z test was used to evaluate differences in proportions of stage at diagnosis, employment of chemotherapy in node-positive (N+) disease, and use of endocrine treatment in estrogen-receptor positive (ER+) and negative (ER-) tumors across Italy. RESULTS: Stage at diagnosis was earlier in northern/central registries than in southern areas. Compared with the reference, the odds of receiving BCS + RT was significantly lower in Trapani, Sassari and Naples (southern Italy) after adjusting for age and stage at diagnosis. Among N+ patients, 73% received adjuvant chemotherapy (range, 51% [Biella, northern Italy] to 87% [Ragusa, southern Italy]). Eighty percent of ER+ cancers (range, 50% [Biella, northern Italy] to 97% [Ragusa, southern Italy]) and 18% of ER- cancers (range, 6% [Modena, northern Italy] to 28% [Umbria, central Italy]) were treated with hormonal therapy. CONCLUSIONS: Disparities in stage distributions and conservative surgery in breast cancer persist across Italy. On a positive note, we found lower variations in the use of systemic treatment between Italian regions.

Changes in the incidence of thyroid cancer between 1991 and 2005 in Italy: a geographical analysis.

BACKGROUND: The incidence of thyroid cancer (TC) has been increasing over the last 30 years in several countries, with some of the worldwide highest TC incidence rates (IRs) reported in Italy. The objectives of this study were to evaluate by histological subtypes the geographical heterogeneity of the incidence of TC in Italy and to analyze recent time trends for papillary thyroid carcinoma (PTC) in different cancer registries (CRs). METHODS: The study included cases of TC (<85 years of age) reported to 25 Italian CRs between 1991 and 2005. Age-standardized IRs were computed for all histological subtypes of TC according to CRs. Estimated annual percent change and joinpoint regression analysis were used for analysis of PTC. RESULTS: In women, IRs of PTC ranged between 3.5/100,000 in Latina and 8.5/100,000 in Sassari for the period 1991-1995 (a 2.4-fold difference) and between 7.3/100,000 in Alto Adige and 37.5/100,000 in Ferrara for 2001-2005 (a 5.1-fold difference). In men, IRs ranged between 0.7/100,000 in Latina and 3.4/100,000 in Sassari for the period 1991-1995 (a 4.9-fold difference) and between 2.0/100,000 (Alto Adige, Trento) and 10.6/100,000 in Ferrara for 2001-2005 (a 5.3-fold difference). In both sexes, IRs significantly higher than the pooled estimates emerged for the most recent period in the majority of CRs located within the Po River plain and in Latina, but they were lower in the Alpine belt. For women, CRs reported higher IRs than pool estimates showed, between 1991 to 2005, a significantly more marked annual percent change (+12%) than other CRs (+7%). For men the corresponding estimates were +11% and +8%. CONCLUSIONS: The distribution of PTC does not lend support to a role of environmental radiation exposure due to the Chernobyl fallout, iodine deficiency, or (volcanic) soils. Between 1991 and 2005, wide geographic variations in the incidence of PTC and heterogeneous upward trends emerged, suggesting that the heterogeneity was a relatively recent phenomenon; this appeared to be mainly explained by variations, at a local level, in medical surveillance.