Patients with cancer who will be cured and projections of complete prevalence in Italy from 2018 to 2030.

BACKGROUND: The number and projections of cancer survivors are necessary to meet the healthcare needs of patients, while data on cure prevalence, that is, the percentage of patients who will not die of cancer by time since diagnosis, are lacking. MATERIALS AND METHODS: Data from Italian cancer registries (duration of registration ranged from 9 to 40 years, with a median of 22 years) covering 47% of the population were used to calculate the limited-duration prevalence, the complete prevalence in 2018, projections to 2030, and cure prevalence, by cancer type, sex, age, and time since diagnosis. RESULTS: A total of 3 347 809 people were alive in Italy in 2018 after a cancer diagnosis, corresponding to 5.6% of the resident population. They will increase by 1.5% per year to 4 012 376 in 2030, corresponding to 6.9% of the resident population, 7.6% of women and ∼22% after age 75 years. In 2030, more than one-half of all prevalent cases (2 million) will have been diagnosed by ≥10 years. Those with breast (1.05 million), prostate (0.56 million), or colorectal cancers (0.47 million) will be 52% of all prevalent patients. Cure prevalence was 86% for all patients alive in 2018 (87% for patients with breast cancer and 99% for patients with thyroid or testicular cancer), increasing with time since diagnosis to 93% for patients alive after 5 years and 96% after 10 years. Among patients who survived at least 5 years, the excess risk of death (1 - cure prevalence) was <5% for patients with most cancer types except for those with cancers of the breast (8.3%), lung (11.1%), kidney (13.2%), and bladder (15.5%). CONCLUSIONS: Study findings encourage the implementation of evidence-based policies aimed at improving long-term clinical follow-up and rehabilitation of people living after cancer diagnosis throughout the course of the disease. Updated estimates of complete prevalence are important to enhance data-driven cancer control planning.

Mediterranean diet and risk of endometrial cancer: a pooled analysis of three Italian case-control studies.

BACKGROUND: Some components of the Mediterranean diet have favourable effects on endometrial cancer, and the Mediterranean diet as a whole has been shown to have a beneficial role on various neoplasms. METHODS: We analysed this issue pooling data from three case-control studies carried out between 1983 and 2006 in various Italian areas and in the Swiss Canton of Vaud. Cases were 1411 women with incident, histologically confirmed endometrial cancer, and controls were 3668 patients in hospital for acute diseases. We measured the adherence to the Mediterranean diet using a Mediterranean Diet Score (MDS), based on the nine dietary components characteristics of this diet, that is, high intake of vegetables, fruits/nuts, cereals, legumes, fish; low intake of dairy products and meat; high monounsaturated to saturated fatty acid ratio; and moderate alcohol intake. We estimated the odds ratios (OR) and the corresponding 95% confidence intervals (CI) for increasing levels of the MDS (varying from 0, no adherence, to 9, maximum adherence) using multiple logistic regression models, adjusted for major confounding factors. RESULTS: The adjusted OR for a 6-9 components of the MDS (high adherence) compared with 0-3 (low adherence) was 0.43 (95% CI 0.34-0.56). The OR for an increment of one component of MDS diet was 0.84 (95% CI 0.80-0.88). The association was consistent in strata of various covariates, although somewhat stronger in older women, in never oral contraceptive users and in hormone-replacement therapy users. CONCLUSIONS: Our study provides evidence for a beneficial role of the Mediterranean diet on endometrial cancer risk, suggesting a favourable effect of a combination of foods rich in antioxidants, fibres, phytochemicals, and unsaturated fatty acids.

Nutrient-based dietary patterns and nasopharyngeal cancer: evidence from an exploratory factor analysis.

BACKGROUND: To our knowledge, no study assessed the association between dietary patterns and nasopharyngeal carcinoma (NPC) in low-incidence areas. METHODS: We examined this association in a hospital-based case-control study carried out in Italy between 1992 and 2008, including 198 incident NPC cases and 594 controls. A posteriori dietary patterns were identified through principal component factor analysis performed on 28 nutrients and minerals derived from a 78-item food-frequency questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional multiple logistic regression models on tertiles of factor scores. RESULTS: We identified five dietary patterns named Animal products, Starch-rich, Vitamins and fibre, Animal unsaturated fatty acids (AUFAs), and Vegetable unsaturated fatty acids (VUFAs). The Animal product (OR=2.62, 95% CI=1.67-4.13, for the highest vs lowest score tertile), Starch-rich (OR=2.05, 95% CI=1.27-3.33), and VUFA (OR=1.90, 95% CI=1.22-2.96) patterns were positively associated with NPC. The AUFA pattern showed a positive association of borderline significance, whereas the Vitamins and fibre pattern was nonsignificantly but inversely associated with NPC. CONCLUSIONS: These findings suggest that diets rich in animal products, starch, and fats are positively related to NPC risk in this low-incidence country.

Long-term survival, prevalence, and cure of cancer: a population-based estimation for 818 902 Italian patients and 26 cancer types.

BACKGROUND: Persons living after a cancer diagnosis represent 4% of the whole population in high-income countries. The aim of the study was to provide estimates of indicators of long-term survival and cure for 26 cancer types, presently lacking. PATIENTS AND METHODS: Data on 818 902 Italian cancer patients diagnosed at age 15-74 years in 1985-2005 were included. Proportions of patients with the same death rates of the general population (cure fractions) and those of prevalent patients who were not at risk of dying as a result of cancer (cure prevalence) were calculated, using validated mixture cure models, by cancer type, sex, and age group. We also estimated complete prevalence, conditional relative survival (CRS), time to reach 5- and 10-year CRS >95%, and proportion of patients living longer than those thresholds. RESULTS: The cure fractions ranged from >90% for patients aged <45 years with thyroid and testis cancers to <10% for liver and pancreatic cancers of all ages. Five- or 10-year CRS >95% were both reached in <10 years by patients with cancers of the stomach, colon-rectum, pancreas, corpus and cervix uteri, brain, and Hodgkin lymphoma. For breast cancer patients, 5- and 10-year CRSs reached >95% after 19 and 25 years, respectively, and in 15 and 18 years for prostate cancer patients. Five-year CRS remained <95% for >25 years after cancer diagnosis in patients with liver and larynx cancers, non-Hodgkin lymphoma, myeloma, and leukaemia. Overall, the cure prevalence was 67% for men and 77% for women. Therefore, 21% of male and 31% of female patients had already reached 5-year CRS >95%, whereas 18% and 25% had reached 10-year CRS >95%. CONCLUSIONS: A quarter of Italian cancer patients can be considered cured. This observation has a high potential impact on health planning, clinical practice, and patients' perspective.

Fiber intake and pancreatic cancer risk: a case-control study.

BACKGROUND: Scanty and inconsistent studies are available on the relation between dietary fiber intake and pancreatic cancer. A case-control study was carried out in northern Italy to further investigate the role of various types of dietary fibers in the etiology of pancreatic cancer. PATIENTS AND METHODS: Cases were 326 patients with incident pancreatic cancer, excluding neuroendocrine tumors, admitted to major teaching and general hospitals during 1991-2008. Controls were 652 patients admitted for acute, nonneoplastic conditions to the same hospital network of cases. Information was elicited using a validated food frequency questionnaire. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated for intake quintiles of different types of fiber after allowance for total energy intake and other potential confounding factors. RESULTS: Total fiber intake was inversely related to risk of pancreatic cancer (OR=0.4 for highest versus lowest quintile of intake; 95% CI 0.2-0.7). An inverse association emerged between pancreatic cancer and both soluble (OR=0.4; 95% CI 0.2-0.7) and total insoluble fiber (OR=0.5; 95% CI 0.3-0.8), particularly cellulose (OR=0.4; 95% CI 0.3-0.7) and lignin (OR=0.5; 95% CI 0.3-0.9). Fruit fiber intake was inversely associated with pancreatic cancer (OR=0.5; 95% CI 0.3-0.8), whereas grain fiber was not (OR=1.2; 95% CI 0.7-2.0). CONCLUSIONS: This study suggests that selected types of fiber and total fiber are inversely related to pancreatic cancer.

Early and short-term acenocumarine or dalteparin for the prevention of central vein catheter-related thrombosis in cancer patients: a randomized controlled study based on serial venographies.

BACKGROUND: We evaluated efficacy and safety of early and short-term prophylaxis with acenocumarine or dalteparin in the prevention of non-occlusive or occlusive central vein catheter-related thrombosis (CVCrT). PATIENTS AND METHODS: Consecutive cancer patients scheduled for chemotherapy randomly received: acenocumarine 1 mg/day for 3 days before and 8 days after central vein catheter (CVC) insertion; dalteparin 5000 IU 2 h before and daily for 8 days after CVC insertion; no anticoagulant treatment (NT). All patients underwent venography on days 8 and 30, some of them on days 90, 150 and 210 after CVC. RESULTS: A total of 450 patients were randomized, 348 underwent at least two venography. Both acenocumarine and dalteparin reduced venography-detected CVCrT rate [21.9% acenocumarine versus 52.6% NT, odds ratio (OR) 0.3, P < 0.01; 40% dalteparin versus 52.6% NT, OR 0.6, P = 0.05]. Acenocumarine was more effective than dalteparin (OR 0.4, P = 0.01). The rate of occlusive CVCrT was not different in the three groups (0.9% acenocumarine, 3.3% dalteparin, 1.8% NT; P = 0.40). Most CVCrTs (95.6%) were observed on day 8 after CVC insertion and were non-occlusive. CONCLUSIONS: In this study of early and short-term prophylaxis, acenocumarine was more effective than dalteparin on non-occlusive and asymptomatic CVCrT events. The first days following CVC insertion represent the highest risk for CVCrT.

Epidemiological and ethical aspects of multiplex autoantibody testing.

Arrays are one of the technologies able to detect autoantibodies by measuring simultaneously many thousands of markers from a unique biological sample. The main purpose of a diagnostic test is making an early and accurate diagnosis. From a statistical point of view, multiple testing increases the probability of false positive and false negative results. Some correction methods are available to account for this problem for instance family-wise error rate or false discovery rate. From an ethical point of view, the decision to accept or decline a test not requested has to be made autonomously. Some people may seek clarification about tests and implications of their choices. A scarcity of proven measures to reduce mortality has to be considered too. Reasons may also include avoidance of psychological harm or anxiety. Moreover, protection of confidentiality and privacy has to be respected. In conclusion, the fact that testing is optional and that surveillance advice can be offered on the basis of risk alone without a test should be discussed in the consultation. The implication of a positive test result should be discussed to make a decision about the degree to which early treatment of the condition is better than late (or no) treatment.

Pre-storage leucocyte depletion and transfusion reaction rates in cancer patients.

Passenger leucocytes transfused with allogenic blood are responsible for potential adverse effects. The impact of pre-storage leucodepletion (in-line filtration) of all whole blood units on transfusion reaction rate among patients suffering from cancer was retrospectively studied, comparing all reactions following red blood cell (RBC) transfusions during 2 years of pre-storage vs. 2 years of selective (bedside) leucodepletion. During selective leucodepletion, 5165 RBC units - of which 2745 were bedside filtered units- were transfused to 866 patients. Twenty-eight reactions were recorded: 22 (15 in the bedside group) febrile non-haemolytic transfusion reactions (FNHTR) and six allergic reactions (five in the bedside group). The overall percentage of reactions was 0.54 (0.76 for bedside) and 0.42 for FNHTR (0.54 for bedside). During pre-storage leucodepletion, 4116 RBC units were transfused to 841 patients. Eleven reactions were recorded: four FNHTR and seven allergic reactions (urticaria). The percentage of reactions for transfused RBC units was 0.26 (0.09 for FNHTR). Comparison between pre-storage filtration and bedside filtration with regard to FNHTR showed an odds ratio of 2.80 (95% confidence interval = 0.83-14.87) for bedside filtration. The study suggests that, for transfused patients affected by cancer, pre-storage leucodepletion is more effective than selective (bedside) filtration in reducing the incidence of transfusion reactions (FNHTR).

Macronutrients, fatty acids, cholesterol and prostate cancer risk.

BACKGROUND: The role of selected macronutrients, fatty acids and cholesterol in the etiology of prostate cancer was analyzed using data from a case-control study carried out in five Italian areas between 1991 and 2002. PATIENTS AND METHODS: Cases were 1294 men with incident, histologically confirmed prostate cancer, and admitted to the major teaching and general hospitals of study areas. Controls were 1451 men admitted for acute, non-neoplastic conditions to the same hospital network. Information on dietary habits was elicited using a validated food frequency questionnaire including 78 food groups and recipes. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for increasing levels of nutrient intake. RESULTS: A direct association with prostate cancer was found for starch intake (OR = 1.4 in the highest versus the lowest quintile of intake; 95% CI: 1.1-1.8), whereas an inverse association emerged for polyunsaturated fatty acids (OR = 0.8; 95% CI: 0.6-1.0). Among polyunsaturated fatty acids, linolenic acid (OR = 0.7; 95% CI: 0.6-0.9) and linoleic acid (OR = 0.8; 95% CI: 0.6-1.0) were inversely related to prostate cancer. When the six major macronutrients were included in the same model, the adverse effect of high intake of starch and monounsaturated fatty acids was statistically significant together with the protective effect of polyunsaturated fatty acids. Results were consistent in separate strata of age, body mass index and family history of prostate cancer. CONCLUSIONS: Starch and monounsaturated fatty acids were directly associated with prostate cancer risk and polyunsaturated fatty acids were inversely associated.

[Analysis of infectious disease mortality in Italy]. / Analisi della mortalita per malattie infettive in Italia.

Our research aimed to describe infectious disease mortality in Italy between 1969 and 1999, with particular emphasis on sex, age, and geographic differences. Using mortality data provided by the Italian Central Institute for Statistics (ISTAT), we evaluated all codes of the ICD8 and ICD9 classifications to identify each cause of death attributable to infectious agents. Deaths for HIV/AIDS were excluded. Infectious diseases accounted for 1.7% of overall mortality between 1969-1999, and our approach identified 57.5% of all deaths from infections not included in the ICD8 and ICD9 infectious disease codes. Up to 1994, the mortality for all infectious diseases showed a very strong downward trend, with a 6-fold decline. This trend levelled off in 1995-1999, mainly due to increasing deaths due to septicaemias, heart infections and hepatitis. An increasing proportion of deaths due to infectious diseases occurred in the elderly, from 48.1% in 1969-1979 to 77.3% in 1990-1999. Mortality rates were consistently higher in men than in women and showed a substantial geographic heterogeneity. In the newborn, mortality rates declined 10-fold and an inverse north-south geographic gradient persisted during the study period. This exhaustive methodological approach to identifying infectious causes of deaths allows us to better define the burden of infections on mortality and register downward trends similar to those found in other industrialized countries.

Ifosfamide in the adjuvant therapy of soft tissue sarcomas.

Ifosfamide and anthracyclines are the only active agents in advanced soft tissue sarcomas. Doxorubicin was always used in sarcomas, whereas ifosfamide was reintroduced in the clinic after the discovery of mesna which prevents its typical dose-limiting toxicity: hemorrhagic cystitis. In the adjuvant setting, doxorubicin was used alone or in combination in the first-generation trials, whereas its parent compounds epirubicin and ifosfamide were employed in the second-generation adjuvant trials, which started in the early 90s. Other relevant aspects of the second-generation trials are the use of the hematopoietic growth factors and the increase of the dose intensity, the introduction of more restrictive selection criteria and the use of the two most active agents, ifosfamide and anthracyclines. Only the Italian cooperative trial has been concluded, and the results reported and updated. After a median follow-up of 89.6 months (range 56-119), the intention-to-treat analysis still reveals a difference in overall survival which, however, is not statistically significant. However, the 5-year overall survival estimate, which is a reasonable end point for the survival analysis of adjuvant treatment in soft tissue sarcomas, was 66.0 and 46.1% for the treatment and the control groups, respectively (p = 0.04).

Prognostic factors in soft tissue sarcomas: a study of 395 patients.

AIMS: The aim of this study was to report prognostic factors, end-points of local recurrence, distant recurrence, post-metastasis survival, and overall survival in a cohort of patients with soft tissue sarcomas. METHODS: We analysed a database of 395 patients affected by primary soft tissue sarcomas of various primary sites, treated and followed up at the Centro di Riferimento Oncologico, Aviano, Italy from January 1985 to January 1997. RESULTS: Grade, size, stage, surgical margins, distant metastasis, age, sex, performance status, and haemoglobin value were significant for overall survival. Histology, grade, stage, and surgical margins were significant for local recurrence. Grade, size, and stage, were significant for distant recurrence; and surgical margin was significant variable for post-metastasis survival. CONCLUSIONS: Grade, size, and TNM stage (UICC/AJCC) have stronger prognostic significance for overall survival and distant recurrence than for local relapse. Positive surgical margins are the main predictors for local relapse. Age was the most consistent adverse independent prognostic factor for survival.

Combined effect of tobacco and alcohol on laryngeal cancer risk: a case-control study.

OBJECTIVE: To provide information on the effects of alcohol and tobacco on laryngeal cancer and its subsites. METHODS: This was a case-control study conducted between 1992 and 2000 in northern Italy and Switzerland. A total of 527 cases of incident squamous-cell carcinoma of the larynx and 1297 hospital controls frequency-matched with cases on age, sex, and area of residence were included. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using multiple logistic regression. RESULTS: In comparison with never smokers, ORs were 19.8 for current smokers and 7.0 for ex-smokers. The risk increased in relation to the number of cigarettes (OR = 42.9 for > or = 25 cigarettes/day) and for duration of smoking (OR = 37.2 for > or = 40 years). For alcohol, the risk increased in relation to number of drinks (OR = 5.9 for > or = 56 drinks per week). Combined alcohol and tobacco consumption showed a multiplicative (OR = 177) rather than an additive risk. For current smokers and current drinkers the risk was higher for supraglottis (ORs 54.9 and 2.6, respectively) than for glottis (ORs 7.4 and 1.8) and others subsites (ORs 10.9 and 1.9). CONCLUSIONS: Our study shows that both cigarette smoking and alcohol drinking are independent risk factors for laryngeal cancer. Heavy consumption of alcohol and cigarettes determined a multiplicative risk increase, possibly suggesting biological synergy.

Viral load of human herpesvirus 8 in peripheral blood of human immunodeficiency virus-infected patients with Kaposi's sarcoma.

Viral load is an important marker of activity of viral diseases for a number of viruses. We wished to evaluate whether the viral load of human herpesvirus 8 (HHV-8) in peripheral blood was a consistent feature of Kaposi's sarcoma (KS) patients and whether the viral load correlated with human immunodeficiency virus (HIV) RNA levels, CD4 counts, and/or the HHV-8 seroreactivity. Fifty-four consecutive plasma samples from 14 patients with KS were evaluated for HHV-8 viral load by quantitative real-time PCR. Samples were analyzed at the start of highly active antiretroviral therapy (HAART) and at different intervals during treatments. The median HHV-8 DNA load before HAART treatment was 8,998 (ranging from 170 to 40,100) copies/ml and 12,270 (ranging from 40 to 142,575) copies/ml during HAART. There were both increasing and decreasing trends. There was an association between HHV-8 DNA and HIV RNA viral loads (odds ratio [OR] = 5.40; 95% confidence interval [95% CI], 1.54 to 18.98) and between HHV-8 viral load and CD4 cell counts (OR = 7.24; 95% CI, 1.30 to 40.35). High HHV-8 viral load was also correlated with the titers of antibodies to the lytic HHV-8 antigen detected with immunofluorescence (P < 0.01), but not with antibodies to the latent HHV-8 antigen. In conclusion, we found that HHV-8 viremia in KS is associated with HIV viral load, CD4 cell counts, and lytic HHV-8 serological reactivity. HHV-8 viral load monitored by real time PCR might be useful for determination HHV-8 viral load during the follow-up of KS patients.

Micronutrients and ovarian cancer: a case-control study in Italy.

BACKGROUND: The role of selected micronutrients, vitamins and minerals in the aetiology of epithelial ovarian cancer was investigated using data from a case-control study conducted between 1992 and 1999 in five Italian areas. PATIENTS AND METHODS: Cases were 1,031 patients with histologically confirmed incident epithelial ovarian cancer. Controls were 2,411 subjects admitted for acute, non-neoplastic diseases to major hospitals in the same catchment areas. Dietary habits were elicited using a validated food frequency questionnaire including 78 food groups and recipes. Odds ratios (OR) and 95% confidence intervals (95% CI) were computed by quintiles of intake of nutrients. RESULTS: Inverse associations emerged for vitamin E (OR = 0.6; 95% CI: 0.5-0.8), beta-carotene (OR = 0.8; 95% CI: 0.6-1.0), lutein/zeaxanthin (OR = 0.6; 95% CI: 0.5-0.8 for the highest vs. the lowest quintile of intake), and calcium intake (OR = 0.7; 95% CI: 0.6-1.0). When the combined effect of calcium and vitamin E was considered, the OR reached 0.4 (95% CI: 0.3-0.7) for subjects in the highest compared to those in the lowest intake tertile of both micronutrients. Results were consistent across strata of menopausal status, parity and family history of ovarian or breast cancer. CONCLUSIONS: The intake of selected micronutrients, which were positively correlated to a diet rich in vegetables and fruits, was inversely associated with ovarian cancer.

Comparison of cancers of the oral cavity and pharynx worldwide: etiological clues.

We assessed separate and combined sex-specific incidence rates of oral and pharyngeal cancer for 1988-92 and oral/pharyngeal ratios from 49 different cancer registries in five continents. Incidence trends over a period of approximately 30 years were evaluated in 16 long active registries for men and four for women. Cancers of the lip, salivary glands, and nasopharynx were excluded. The incidence of both oral and pharyngeal cancer among men is highest in northern France, southern India, a few areas of central and eastern Europe, and Latin America. Among women, the highest incidence is observed in India. Oral/pharyngeal ratio is everywhere systematically lower in men compared to women. Recent trends for oral cancer are more favourable than those for pharyngeal cancer in developing countries. In developed countries, trends in oral cancer appears to be more closely correlated to changes in alcohol consumption than those of pharyngeal cancer.

Role of macronutrients, vitamins and minerals in the aetiology of squamous-cell carcinoma of the oesophagus.

Between 1992 and 1997 we conducted a case-control study of oesophageal cancer in 3 areas of northern Italy. Cases were 304 patients (29 women), ages 39-77 years (median age 60 years), with a first incident squamous-cell carcinoma (SCC) of the oesophagus. Controls were 743 patients (150 women), ages 35-77 years (median age 60 years), admitted for acute illnesses, unrelated to tobacco and alcohol, to major hospitals of the areas under surveillance. We derived estimates of daily dietary intake of 6 macronutrients, cholesterol, and 20 micronutrients or minerals from a validated food-frequency questionnaire, including 78 food groups and recipes and 15 questions on individual eating patterns. After allowance for age, gender, area of residence, education, body mass index, physical activity, smoking habit, alcohol consumption and energy intake, most micronutrients were inversely associated with oesophageal SCC risk. Highly significant associations emerged for monounsaturated fatty acids [odds ratio (OR) in highest vs. lowest intake quintile = 0.5]; carotene (OR = 0.3); lutein + zeaxanthin (OR = 0.4); vitamin C (OR = 0.4); and niacin (OR = 0.5). Only retinol appeared to be positively related to risk (OR = 1.9). The effect of the above nutrients, expressed as ORs, appeared to be similar in non-smokers and smokers, and non/light drinkers and heavy drinkers.