Carlo Zocchetti - Academia.edu (original) (raw)
Papers by Carlo Zocchetti
American journal of …, Jan 1, 1989
In 1976, an accidental explosion in a plant near Seveso, Italy, caused the contamination of a pop... more In 1976, an accidental explosion in a plant near Seveso, Italy, caused the contamination of a populated area by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The area was subdivided into three zones (A, B, and R) having decreasing mean levels of TCDD soil contamination. This study examines the mortality between 1976 and 1986 among the subjects, aged 20-74 years, who were resident in the area since the accident (n = 556 in zone A, n = 3,920 in zone B, n = 26,227 in zone R). Subjects' exposure was classified by residence. A referent cohort of 167,391 subjects who lived in the immediate surroundings was concurrently examined. Vital status ascertainment was successful for over 99% of the subjects. Increased mortality from cardiovascular causes was found; incident-related stressors were considered more relevant to increased mortality than was TCDD exposure. Mortality from several cancers was elevated. The increases in biliary cancer (females), brain cancer, and lymphatic and hemopoietic neoplasms (particularly leukemia in males) did not appear to result from chance, confounding, or information/comparison bias. However, no definite patterns related to exposure classification were apparent. Merely suggestive increases in soft tissue tumors and melanoma were also noted. Liver and breast cancer mortality tended to be below expectations. Interpretation is hampered by the short observation period, small number of deaths from certain causes, and poor exposure definition. Further research is in progress.
Journal of evaluation in clinical practice, Jan 20, 2015
Assuring the best standards of care - in a sustainable way - in chronic diseases as breast cancer... more Assuring the best standards of care - in a sustainable way - in chronic diseases as breast cancer is nowadays an important challenge for any health system. The aim of this study was to present the methodology used to define a set of quality indicators, computable from administrative data for the pathway of care of breast cancer, and its application at a population level. The cohort of 2007-2009 incident cases of breast cancer was identified through a network of six cancer registers in Northern Italy. Cases of sarcoma and lymphoma, patients with multiple primary cancers and those metastatic at diagnosis were excluded; 9614 women were retained for the analysis. For each indicator, the sub-cohort of women eligible for the diagnostic/therapeutic procedures was identified and calculations were performed through record linkage between the cohort and sources of health information. Data on potential available confounders or prognostic factors were also collected. For a few indicators, such ...
Giornale italiano di medicina del lavoro ed ergonomia
The 1976 dioxin accident in Seveso, Italy, represented a major environmental health problem for t... more The 1976 dioxin accident in Seveso, Italy, represented a major environmental health problem for the population of the surrounding territory and a challenge for the entire regional area and the health and scientific institutions. The role of occupational health and of epidemiology in the incident investigation and management is discussed. Of major relevance was the consideration of all the different component factors of the interested environment, from chemical pollution to cultural attitudes and psycho-social stressors. Scientific research was helpful in elucidating the incompletely known toxic effects of dioxin and the complex mechanism of cancer induction by this widespread pollutant of our industrialized environments. The experience gained in Seveso was also useful in prompting national and international legislation concerning major industrial accidents, and the lessons learned contributed to the content of this legislation. Preparedness to these events requires mapping of the po...
La Medicina del lavoro
This paper examines the history of an occupational disease which has now disappeared: acroosteoly... more This paper examines the history of an occupational disease which has now disappeared: acroosteolysis of manual tank cleaners in the production of polyvinyl chloride (PVC), which is a rare disease characterized by destructive alterations of the distal phalanges of the hands. All the available literature on this disease was examined. The history of acroosteolysis was studied within the general framework of the history of the discovery of adverse health effects of exposure to vinyl chloride, and this history was studied up to the end of the 1960's. The disease was observed for the first time in mid-1963 in Belgium (Jemeppe) in a chemical plant operated by Solvay, and affected two workers whose job was the manual cleaning of vessels used for the polymerization of vinyl chloride; similar cases occurred in almost all PVC production plants all over the world, but not in the plants where the main activity was the production of vinyl chloride monomer (VCM). Little more than one hundred c...
IARC scientific publications
Metabolic susceptibility genes are important determinants of individual susceptibility to the eff... more Metabolic susceptibility genes are important determinants of individual susceptibility to the effects of environmental carcinogens. These genes follow the form of 'type 2' gene-environment interaction, whereby the polymorphic genetic risk factor functions only in the presence of an environmental exposure. Two different effects of carcinogen dose have been observed for these genes. Sometimes, increasing dose leads to a decreasing interaction, so that cases with the genetic risk factor have lower exposures than those cases without it. Other examples of a direct dose effect, whereby increasing exposure leads to increased interaction, have also been described. We propose a model based on multiple logistic regression to assess the nature of the dose effect in this type of gene-environment interaction. This model allows for distinction between these two dose effects, and other effects such as protective or non-interactive effects of environmental and genetic risk factors.
Epidemiologia e prevenzione
Epidemiologia e prevenzione
Epidemiologia e prevenzione
to present a set of indicators developed from six Local Health Authorities of the Lombardy Region... more to present a set of indicators developed from six Local Health Authorities of the Lombardy Region to monitor the diagnostic and therapeutic pathway of breast cancer patients, applied to 2007-2009 incident cases. retrospective cohort study. all subjects with primary breast cancer, incident in the period 2007-2009, and collected by cancer registries of Milano 1, Bergamo, Cremona, Milano, Milano 2 and Monza-Brianza (5,320,272 inhabitants) were included. through the use of combined current health databases (health registry, hospitalizations, outpatient, pharmaceutical prescription and specific database for anticancer drugs), for each incident case 34 different indicators have been developed to measure the appropriateness of the procedures provided for diagnosis, treatment (surgical and medical) and follow-up. For each indicator, we analyzed the relationship with age, stage, deprivation index, type of treatment, volume of the specific procedure of the hospital where primary surgery was p...
The oncologist, 2014
The evidence supporting the use of trastuzumab (T) in a metastatic setting comes from studies tha... more The evidence supporting the use of trastuzumab (T) in a metastatic setting comes from studies that included (almost) only patients who never received prior T. We investigated the effectiveness of T as first-line therapy for metastatic breast cancer (mBC) in women previously treated with T in the adjuvant setting. By using record linkage of five administrative health care databases of Lombardy, Italy, we identified 2,046 women treated with T for early breast cancer (eBC) in 2006-2009, 96 of whom developed a metastasis and were retreated with T in first-line treatment for mBC (treatment group). We compared the overall survival (OS) of these women with that of 197 women treated with T in first-line treatment for mBC, who were treated with therapies other than T for early disease (control group). We computed Kaplan-Meier 2-year OS and used a proportional hazard model to estimate the multivariate hazard ratio (HR) of death in the intervention group compared with the control group, adjust...
The Breast, 2014
Trastuzumab-based regimens for the adjuvant treatment of HER2-positive early breast cancer signif... more Trastuzumab-based regimens for the adjuvant treatment of HER2-positive early breast cancer significantly prolonged overall survival (OS) and disease free survival (DFS) in large randomized trials, with sustained benefits at four-year follow-up. We assessed long-term survival estimates and predictors in a large cohort of Italian women with early breast cancer treated with trastuzumab in clinical practice. Through a record linkage between five regional healthcare databases, we identified women treated with trastuzumab for early breast cancer in Lombardy (2006-2009). DFS and OS were estimated using the Kaplan-Meier method, and independent predictors were assessed using proportional hazard models. 2046 women received trastuzumab in early breast cancer adjuvant setting. Overall, the proportion of patients surviving free of disease was 93.9% at one year, 85.8% at 2 years, 79.4% at 3 years, and 75.0% at 4 years. OS estimates were 98.7%, 95.4%, 91.5% and 89.4% at 1, 2, 3 and 4 years, respectively. Significant independent predictors of worse survival outcomes were age <40 or ≥70 years compared to age 40-69 years, positive nodal status, radical breast surgery, combination therapy with paclitaxel, having at least one comorbidity (i.e. diabetes, cardiovascular disease), and a trastuzumab-based regimen lasting less than six months. Long term survival rates of women treated with trastuzumab for early breast cancer in clinical practice were consistent with estimates from clinical trials testing the drug in the adjuvant setting.
Science of The Total Environment, 1988
Ferro-chromium production is based on the use of chromium oxide (III) and it is generally accepte... more Ferro-chromium production is based on the use of chromium oxide (III) and it is generally accepted that chromium in this form is not able to cross biological barriers. However, the data on the toxic and carcinogenic effects of hexavalent chromium in man are now firmly~ established. Some studies have questioned these data, calling for a clarification as to whether exposure to trivalent chromium can also produce human effects, perhaps with different latency time.
Scandinavian Journal of Work, Environment & Health, 1992
JH, SIMONATO L, TEPPO L, WESTERHOLM P, WINTER P, ZOCCHETTI C. Lung cancer mortality among workers... more JH, SIMONATO L, TEPPO L, WESTERHOLM P, WINTER P, ZOCCHETTI C. Lung cancer mortality among workers in the European production of man-made mineral fibers -a Poisson regression analysis. Scand J Work Environ Health 1992;18:279-86. One hundred and eighty-one lung cancer deaths among workers during 301 085 person-years in European man-made mineral fiber production between 1930-1955 and 1982were analyzed according to Poisson regression models including age, calendar period, country, and exposure variables. Time since first employment wasthe variable most strongly associated with lung cancer risk in both the rock-slag wool and glass wool subcohorts. Workers in the early technological phase were at higher risk than those in other categories, particularly in rock-slag wool production . No clear trend with duration of employment was suggested. No major changes occurred in the interpretat ion of the results when workers with less than one year of employment or less than 20 years since first exposure were excluded. The original results, based on analyses for standardized mortality ratios, were confirmed, and workers with a short duration of employment or a short time since first employment did not need to be excluded from the analysis.
Occupational and Environmental Medicine, 1997
In occupational epidemiology, the need to consider the age factor properly influences the choice ... more In occupational epidemiology, the need to consider the age factor properly influences the choice of study design and analytical techniques. In most studies, age is viewed as a potential confounder. Age is strongly associated with end points of interest in occupational epidemiology (diseases, physiological characteristics, doses of xenobiotics, etc), but to measure age as a
International Journal of Epidemiology, 1997
International Journal of Epidemiology, 1993
An industrial accident in Seveso, Italy, in 1976, caused contamination of the residential communi... more An industrial accident in Seveso, Italy, in 1976, caused contamination of the residential community with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We investigated cancer occurrence in the first post-accident decade (1977-1986) among nearly 20,000 subjects aged 0-19 years. People who left the area were actively followed with a 99% follow-up rate. For reported cancer cases confirmation was obtained through consultation with original medical records. Two ovarian cancers were observed versus none expected. A suggestive increase was seen for Hodgkin's lymphoma (relative risk [RR] = 2.0; 95% confidence interval [CI] = 0.5-7.6). Myeloid leukaemia showed a clear, but not statistically significant increase (RR = 2.7; 95% CI = 0.7-11.4). The most prominent result concerned thyroid cancer, not just for the magnitude of the increase (two cases, RR = 4.6; 95% CI = 0.6-32.7), but also for its consistency with experimental findings and previous observations in humans. Any conclusive interpretation would be premature because of the short time since initial exposure, ecological definition of exposure status, and limited number of events.
International Archives of Occupational and Environmental Health, 1989
The mortality experience of 1595 male workers employed in one of the largest Italian refineries i... more The mortality experience of 1595 male workers employed in one of the largest Italian refineries in the period from 1949-1982 was examined From the comparison with national and local death rates, increases in mortality owing to lung and kidney cancers, brain tumors, and leukemias emerged No definite trends according to duration of exposure and years since first exposure were apparent The increases regarding cancer of the lung, kidney and brain appeared to be associated with the early period of operations Analysis by exposure category suggested an association of the increased mortality from leukemias with working in production (observed = 2 ; expected = 0 61) Kidney cancer mortality was elevated among maintenance workers (obs = 2 ; exp = 0 18) Small numbers prevented firmer conclusions Workers in the moving department had a significantly increased mortality from all cancers (obs = 22 ; exp = 11 7), and lung cancer (obs = 11 ; exp = 3 6) Confounding by smoking could be excluded as sufficient explanation of the three-fold increase in lung cancer deaths. It was in moving that highest airborne levels of polynuclear aromatic hydrocarbons had been discovered in an independent environmental investigation.
International Archives of Occupational and Environmental Health, 1979
Chelatable lead (Pb U-EDTA) is the best indicator of lead concentration at the critical organ lev... more Chelatable lead (Pb U-EDTA) is the best indicator of lead concentration at the critical organ level (indicator of dose) However, since this test is not easily applicable for the biological monitoring of lead-exposed subjects, the current practice is to determine lead in blood (Pb B) and/or in urine (Pb U). But these tests are indicators of exposure and not of dose To analyze the reliability of Pb B and Pb U in estimating lead dose, the relationships between Pb U-EDTA and Pb B and between Pb U-EDTA and Pb U were studied in two groups of male lead workers: 48 currently exposed and 45 with past exposure to lead. In currently exposed workers the correlation between Pb U-EDTA and Pb B and between Pb U-EDTA and Pb U was very close (r = 0 85, r = 0 74, respectively); in past exposed workers the correlation with Pb U-EDTA was decidedly lower for Pb B (r = 0 54) and not significant for Pb U (r = 0 29) In both cases the relationship between the variables was linear In the previously exposed men, Pb B displayed lower values than those found in currently exposed men.
International Archives of Occupational and Environmental Health, 1985
Cadmium in blood (CdB), cadmium in urine (CdU) and beta 2-microglobulins (beta 2MU) were determin... more Cadmium in blood (CdB), cadmium in urine (CdU) and beta 2-microglobulins (beta 2MU) were determined in 83 male workers exposed to cadmium fumes. CdU was measured both on 24-h urine samples and on spot samples. The behaviour of the biological indicators of cadmium was assessed in relation to degree of current exposure, length of exposure and cumulative exposure (computed as concentration of cadmium at the workplace multiplied by duration of exposure). CdB values were significantly higher in the subgroups of subjects with higher current cadmium exposure and in the subgroups of subjects with greater cumulative exposure, but the test levels were not influenced by duration of exposure. CdU levels were significantly higher in the subgroup of subjects with greater cumulative exposure, but were less influenced by current exposure or duration of exposure. Considering the entire population, a rather close correlation (r = 0.69) was observed between CdB and CdU. When the population was divided according to level of current exposure, a close relationship was observed between the two indicators in all subgroups; nevertheless, for identical CdU values, the CdB values were higher in the subjects with heavier current exposure. Even if in all Cd workers the beta 2MU levels were in the range of reference values, the highest beta 2MU levels were found in the subjects with CdU greater than 10 micrograms/l. The data confirm that CdU is prevalently influenced by the body burden of metal, but they also suggest that the CdB levels are not influenced solely by the intensity of current exposure but also depend to a considerable degree on the body burden.
INDUSTRIAL HEALTH, 2003
The early effects of 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) exposure in the population inv... more The early effects of 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) exposure in the population involved in the Seveso, Italy, incident in 1976, have been examined in numerous studies. Chloracne was the only effect linked with sufficient certainty to dioxin exposure. The possible longterm consequences were investigated with mortality and cancer incidence studies. Mortality and morbidity findings during the 20-year period following the accident showed increased risk from lymphoemopoietic neoplasm, digestive system cancer (rectum in males, and biliary tract among females, in particular) and respiratory system cancer (lung, among males). In the incidence analyses, also thyroid gland and pleura cancer appeared suggestively increased. Soft tissue sarcomas showed an increase in the largest, yet least exposed, exposure sub-cohort. Several hypotheses associating non-cancer effects with dioxin exposure were corroborated by findings in the Seveso population: this was the case with cardiovascular effects (possibly linked to both chemical exposure and stressful disaster experience), endocrine effects (diabetes among females) and reproductive effects: exposure of men to TCDD was linked to a lowered male/female sex ratio in their offspring. The results of many Seveso studies point to possible gender effects, in accordance with animal models. Notwithstanding the acknowledged study limitations (lack of individual exposure markers, short latency, and small population size for certain cancer types), results of previous experimental and epidemiological studies, along with mechanistic knowledge on dioxin toxicity, support the hypotheses that the observed excesses might be associated with dioxin exposure. The mortality and cancer incidence follow-up of the Seveso cohort are continuing.
Epidemiology, 1997
Dioxin (2,3,7,8-tetrachlorodibenzo-para-dioxin, or TCDD) is a powerful carcinogen in experimental... more Dioxin (2,3,7,8-tetrachlorodibenzo-para-dioxin, or TCDD) is a powerful carcinogen in experimental animals, whereas the evidence in humans is limited. We examined cancer mortality from 1976 to 1991 among residents of Seveso, Italy, which was highly contaminated after an industrial accident. The area was divided into zones with decreasing exposure to dioxin (A = highest, B = lower, R = lowest). The population of a surrounding noncontaminated area was used as a reference group. Zone A was small (11,516 person-years); in that zone, we saw a moderate increase in mortality from digestive cancer among women [relative risk (RR) = 1.5; 95% confidence interval (CI) = 0.5-3.5]. In zone B, we also saw excesses at digestive sites (83,610 person-years), 10 years after the accident. Women had an increased mortality from stomach cancer (RR = 2.4; 95% CI = 0.8-5.7), and men had increased mortality from rectal cancer (RR = 6.2; 95% CI = 1.7-15.9). Hematologic neoplasms were increased. The highest risks were seen in zone B for leukemia in men (RR = 3.1; 95% CI = 1.3-6.4), multiple myeloma in women (RR = 6.6; 95% CI = 1.8-16.8), and Hodgkin's disease in both genders (RR = 3.3; 95% CI = 0.4-11.9 in men; and RR = 6.5; 95% CI = 0.7-23.5 in women). Soft tissue sarcoma was elevated only among zone R males (256,408 person-years; RR = 2.1; 95% CI = 0.6-5.4). We found no increase for all-cancer mortality or major specific sites (for example, respiratory among males, breast among females). The specific excesses that we observed were not explained by bias or confounding, and their association with dioxin exposure is plausible. The follow-up is continuing.
American journal of …, Jan 1, 1989
In 1976, an accidental explosion in a plant near Seveso, Italy, caused the contamination of a pop... more In 1976, an accidental explosion in a plant near Seveso, Italy, caused the contamination of a populated area by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The area was subdivided into three zones (A, B, and R) having decreasing mean levels of TCDD soil contamination. This study examines the mortality between 1976 and 1986 among the subjects, aged 20-74 years, who were resident in the area since the accident (n = 556 in zone A, n = 3,920 in zone B, n = 26,227 in zone R). Subjects' exposure was classified by residence. A referent cohort of 167,391 subjects who lived in the immediate surroundings was concurrently examined. Vital status ascertainment was successful for over 99% of the subjects. Increased mortality from cardiovascular causes was found; incident-related stressors were considered more relevant to increased mortality than was TCDD exposure. Mortality from several cancers was elevated. The increases in biliary cancer (females), brain cancer, and lymphatic and hemopoietic neoplasms (particularly leukemia in males) did not appear to result from chance, confounding, or information/comparison bias. However, no definite patterns related to exposure classification were apparent. Merely suggestive increases in soft tissue tumors and melanoma were also noted. Liver and breast cancer mortality tended to be below expectations. Interpretation is hampered by the short observation period, small number of deaths from certain causes, and poor exposure definition. Further research is in progress.
Journal of evaluation in clinical practice, Jan 20, 2015
Assuring the best standards of care - in a sustainable way - in chronic diseases as breast cancer... more Assuring the best standards of care - in a sustainable way - in chronic diseases as breast cancer is nowadays an important challenge for any health system. The aim of this study was to present the methodology used to define a set of quality indicators, computable from administrative data for the pathway of care of breast cancer, and its application at a population level. The cohort of 2007-2009 incident cases of breast cancer was identified through a network of six cancer registers in Northern Italy. Cases of sarcoma and lymphoma, patients with multiple primary cancers and those metastatic at diagnosis were excluded; 9614 women were retained for the analysis. For each indicator, the sub-cohort of women eligible for the diagnostic/therapeutic procedures was identified and calculations were performed through record linkage between the cohort and sources of health information. Data on potential available confounders or prognostic factors were also collected. For a few indicators, such ...
Giornale italiano di medicina del lavoro ed ergonomia
The 1976 dioxin accident in Seveso, Italy, represented a major environmental health problem for t... more The 1976 dioxin accident in Seveso, Italy, represented a major environmental health problem for the population of the surrounding territory and a challenge for the entire regional area and the health and scientific institutions. The role of occupational health and of epidemiology in the incident investigation and management is discussed. Of major relevance was the consideration of all the different component factors of the interested environment, from chemical pollution to cultural attitudes and psycho-social stressors. Scientific research was helpful in elucidating the incompletely known toxic effects of dioxin and the complex mechanism of cancer induction by this widespread pollutant of our industrialized environments. The experience gained in Seveso was also useful in prompting national and international legislation concerning major industrial accidents, and the lessons learned contributed to the content of this legislation. Preparedness to these events requires mapping of the po...
La Medicina del lavoro
This paper examines the history of an occupational disease which has now disappeared: acroosteoly... more This paper examines the history of an occupational disease which has now disappeared: acroosteolysis of manual tank cleaners in the production of polyvinyl chloride (PVC), which is a rare disease characterized by destructive alterations of the distal phalanges of the hands. All the available literature on this disease was examined. The history of acroosteolysis was studied within the general framework of the history of the discovery of adverse health effects of exposure to vinyl chloride, and this history was studied up to the end of the 1960's. The disease was observed for the first time in mid-1963 in Belgium (Jemeppe) in a chemical plant operated by Solvay, and affected two workers whose job was the manual cleaning of vessels used for the polymerization of vinyl chloride; similar cases occurred in almost all PVC production plants all over the world, but not in the plants where the main activity was the production of vinyl chloride monomer (VCM). Little more than one hundred c...
IARC scientific publications
Metabolic susceptibility genes are important determinants of individual susceptibility to the eff... more Metabolic susceptibility genes are important determinants of individual susceptibility to the effects of environmental carcinogens. These genes follow the form of 'type 2' gene-environment interaction, whereby the polymorphic genetic risk factor functions only in the presence of an environmental exposure. Two different effects of carcinogen dose have been observed for these genes. Sometimes, increasing dose leads to a decreasing interaction, so that cases with the genetic risk factor have lower exposures than those cases without it. Other examples of a direct dose effect, whereby increasing exposure leads to increased interaction, have also been described. We propose a model based on multiple logistic regression to assess the nature of the dose effect in this type of gene-environment interaction. This model allows for distinction between these two dose effects, and other effects such as protective or non-interactive effects of environmental and genetic risk factors.
Epidemiologia e prevenzione
Epidemiologia e prevenzione
Epidemiologia e prevenzione
to present a set of indicators developed from six Local Health Authorities of the Lombardy Region... more to present a set of indicators developed from six Local Health Authorities of the Lombardy Region to monitor the diagnostic and therapeutic pathway of breast cancer patients, applied to 2007-2009 incident cases. retrospective cohort study. all subjects with primary breast cancer, incident in the period 2007-2009, and collected by cancer registries of Milano 1, Bergamo, Cremona, Milano, Milano 2 and Monza-Brianza (5,320,272 inhabitants) were included. through the use of combined current health databases (health registry, hospitalizations, outpatient, pharmaceutical prescription and specific database for anticancer drugs), for each incident case 34 different indicators have been developed to measure the appropriateness of the procedures provided for diagnosis, treatment (surgical and medical) and follow-up. For each indicator, we analyzed the relationship with age, stage, deprivation index, type of treatment, volume of the specific procedure of the hospital where primary surgery was p...
The oncologist, 2014
The evidence supporting the use of trastuzumab (T) in a metastatic setting comes from studies tha... more The evidence supporting the use of trastuzumab (T) in a metastatic setting comes from studies that included (almost) only patients who never received prior T. We investigated the effectiveness of T as first-line therapy for metastatic breast cancer (mBC) in women previously treated with T in the adjuvant setting. By using record linkage of five administrative health care databases of Lombardy, Italy, we identified 2,046 women treated with T for early breast cancer (eBC) in 2006-2009, 96 of whom developed a metastasis and were retreated with T in first-line treatment for mBC (treatment group). We compared the overall survival (OS) of these women with that of 197 women treated with T in first-line treatment for mBC, who were treated with therapies other than T for early disease (control group). We computed Kaplan-Meier 2-year OS and used a proportional hazard model to estimate the multivariate hazard ratio (HR) of death in the intervention group compared with the control group, adjust...
The Breast, 2014
Trastuzumab-based regimens for the adjuvant treatment of HER2-positive early breast cancer signif... more Trastuzumab-based regimens for the adjuvant treatment of HER2-positive early breast cancer significantly prolonged overall survival (OS) and disease free survival (DFS) in large randomized trials, with sustained benefits at four-year follow-up. We assessed long-term survival estimates and predictors in a large cohort of Italian women with early breast cancer treated with trastuzumab in clinical practice. Through a record linkage between five regional healthcare databases, we identified women treated with trastuzumab for early breast cancer in Lombardy (2006-2009). DFS and OS were estimated using the Kaplan-Meier method, and independent predictors were assessed using proportional hazard models. 2046 women received trastuzumab in early breast cancer adjuvant setting. Overall, the proportion of patients surviving free of disease was 93.9% at one year, 85.8% at 2 years, 79.4% at 3 years, and 75.0% at 4 years. OS estimates were 98.7%, 95.4%, 91.5% and 89.4% at 1, 2, 3 and 4 years, respectively. Significant independent predictors of worse survival outcomes were age <40 or ≥70 years compared to age 40-69 years, positive nodal status, radical breast surgery, combination therapy with paclitaxel, having at least one comorbidity (i.e. diabetes, cardiovascular disease), and a trastuzumab-based regimen lasting less than six months. Long term survival rates of women treated with trastuzumab for early breast cancer in clinical practice were consistent with estimates from clinical trials testing the drug in the adjuvant setting.
Science of The Total Environment, 1988
Ferro-chromium production is based on the use of chromium oxide (III) and it is generally accepte... more Ferro-chromium production is based on the use of chromium oxide (III) and it is generally accepted that chromium in this form is not able to cross biological barriers. However, the data on the toxic and carcinogenic effects of hexavalent chromium in man are now firmly~ established. Some studies have questioned these data, calling for a clarification as to whether exposure to trivalent chromium can also produce human effects, perhaps with different latency time.
Scandinavian Journal of Work, Environment & Health, 1992
JH, SIMONATO L, TEPPO L, WESTERHOLM P, WINTER P, ZOCCHETTI C. Lung cancer mortality among workers... more JH, SIMONATO L, TEPPO L, WESTERHOLM P, WINTER P, ZOCCHETTI C. Lung cancer mortality among workers in the European production of man-made mineral fibers -a Poisson regression analysis. Scand J Work Environ Health 1992;18:279-86. One hundred and eighty-one lung cancer deaths among workers during 301 085 person-years in European man-made mineral fiber production between 1930-1955 and 1982were analyzed according to Poisson regression models including age, calendar period, country, and exposure variables. Time since first employment wasthe variable most strongly associated with lung cancer risk in both the rock-slag wool and glass wool subcohorts. Workers in the early technological phase were at higher risk than those in other categories, particularly in rock-slag wool production . No clear trend with duration of employment was suggested. No major changes occurred in the interpretat ion of the results when workers with less than one year of employment or less than 20 years since first exposure were excluded. The original results, based on analyses for standardized mortality ratios, were confirmed, and workers with a short duration of employment or a short time since first employment did not need to be excluded from the analysis.
Occupational and Environmental Medicine, 1997
In occupational epidemiology, the need to consider the age factor properly influences the choice ... more In occupational epidemiology, the need to consider the age factor properly influences the choice of study design and analytical techniques. In most studies, age is viewed as a potential confounder. Age is strongly associated with end points of interest in occupational epidemiology (diseases, physiological characteristics, doses of xenobiotics, etc), but to measure age as a
International Journal of Epidemiology, 1997
International Journal of Epidemiology, 1993
An industrial accident in Seveso, Italy, in 1976, caused contamination of the residential communi... more An industrial accident in Seveso, Italy, in 1976, caused contamination of the residential community with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We investigated cancer occurrence in the first post-accident decade (1977-1986) among nearly 20,000 subjects aged 0-19 years. People who left the area were actively followed with a 99% follow-up rate. For reported cancer cases confirmation was obtained through consultation with original medical records. Two ovarian cancers were observed versus none expected. A suggestive increase was seen for Hodgkin's lymphoma (relative risk [RR] = 2.0; 95% confidence interval [CI] = 0.5-7.6). Myeloid leukaemia showed a clear, but not statistically significant increase (RR = 2.7; 95% CI = 0.7-11.4). The most prominent result concerned thyroid cancer, not just for the magnitude of the increase (two cases, RR = 4.6; 95% CI = 0.6-32.7), but also for its consistency with experimental findings and previous observations in humans. Any conclusive interpretation would be premature because of the short time since initial exposure, ecological definition of exposure status, and limited number of events.
International Archives of Occupational and Environmental Health, 1989
The mortality experience of 1595 male workers employed in one of the largest Italian refineries i... more The mortality experience of 1595 male workers employed in one of the largest Italian refineries in the period from 1949-1982 was examined From the comparison with national and local death rates, increases in mortality owing to lung and kidney cancers, brain tumors, and leukemias emerged No definite trends according to duration of exposure and years since first exposure were apparent The increases regarding cancer of the lung, kidney and brain appeared to be associated with the early period of operations Analysis by exposure category suggested an association of the increased mortality from leukemias with working in production (observed = 2 ; expected = 0 61) Kidney cancer mortality was elevated among maintenance workers (obs = 2 ; exp = 0 18) Small numbers prevented firmer conclusions Workers in the moving department had a significantly increased mortality from all cancers (obs = 22 ; exp = 11 7), and lung cancer (obs = 11 ; exp = 3 6) Confounding by smoking could be excluded as sufficient explanation of the three-fold increase in lung cancer deaths. It was in moving that highest airborne levels of polynuclear aromatic hydrocarbons had been discovered in an independent environmental investigation.
International Archives of Occupational and Environmental Health, 1979
Chelatable lead (Pb U-EDTA) is the best indicator of lead concentration at the critical organ lev... more Chelatable lead (Pb U-EDTA) is the best indicator of lead concentration at the critical organ level (indicator of dose) However, since this test is not easily applicable for the biological monitoring of lead-exposed subjects, the current practice is to determine lead in blood (Pb B) and/or in urine (Pb U). But these tests are indicators of exposure and not of dose To analyze the reliability of Pb B and Pb U in estimating lead dose, the relationships between Pb U-EDTA and Pb B and between Pb U-EDTA and Pb U were studied in two groups of male lead workers: 48 currently exposed and 45 with past exposure to lead. In currently exposed workers the correlation between Pb U-EDTA and Pb B and between Pb U-EDTA and Pb U was very close (r = 0 85, r = 0 74, respectively); in past exposed workers the correlation with Pb U-EDTA was decidedly lower for Pb B (r = 0 54) and not significant for Pb U (r = 0 29) In both cases the relationship between the variables was linear In the previously exposed men, Pb B displayed lower values than those found in currently exposed men.
International Archives of Occupational and Environmental Health, 1985
Cadmium in blood (CdB), cadmium in urine (CdU) and beta 2-microglobulins (beta 2MU) were determin... more Cadmium in blood (CdB), cadmium in urine (CdU) and beta 2-microglobulins (beta 2MU) were determined in 83 male workers exposed to cadmium fumes. CdU was measured both on 24-h urine samples and on spot samples. The behaviour of the biological indicators of cadmium was assessed in relation to degree of current exposure, length of exposure and cumulative exposure (computed as concentration of cadmium at the workplace multiplied by duration of exposure). CdB values were significantly higher in the subgroups of subjects with higher current cadmium exposure and in the subgroups of subjects with greater cumulative exposure, but the test levels were not influenced by duration of exposure. CdU levels were significantly higher in the subgroup of subjects with greater cumulative exposure, but were less influenced by current exposure or duration of exposure. Considering the entire population, a rather close correlation (r = 0.69) was observed between CdB and CdU. When the population was divided according to level of current exposure, a close relationship was observed between the two indicators in all subgroups; nevertheless, for identical CdU values, the CdB values were higher in the subjects with heavier current exposure. Even if in all Cd workers the beta 2MU levels were in the range of reference values, the highest beta 2MU levels were found in the subjects with CdU greater than 10 micrograms/l. The data confirm that CdU is prevalently influenced by the body burden of metal, but they also suggest that the CdB levels are not influenced solely by the intensity of current exposure but also depend to a considerable degree on the body burden.
INDUSTRIAL HEALTH, 2003
The early effects of 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) exposure in the population inv... more The early effects of 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) exposure in the population involved in the Seveso, Italy, incident in 1976, have been examined in numerous studies. Chloracne was the only effect linked with sufficient certainty to dioxin exposure. The possible longterm consequences were investigated with mortality and cancer incidence studies. Mortality and morbidity findings during the 20-year period following the accident showed increased risk from lymphoemopoietic neoplasm, digestive system cancer (rectum in males, and biliary tract among females, in particular) and respiratory system cancer (lung, among males). In the incidence analyses, also thyroid gland and pleura cancer appeared suggestively increased. Soft tissue sarcomas showed an increase in the largest, yet least exposed, exposure sub-cohort. Several hypotheses associating non-cancer effects with dioxin exposure were corroborated by findings in the Seveso population: this was the case with cardiovascular effects (possibly linked to both chemical exposure and stressful disaster experience), endocrine effects (diabetes among females) and reproductive effects: exposure of men to TCDD was linked to a lowered male/female sex ratio in their offspring. The results of many Seveso studies point to possible gender effects, in accordance with animal models. Notwithstanding the acknowledged study limitations (lack of individual exposure markers, short latency, and small population size for certain cancer types), results of previous experimental and epidemiological studies, along with mechanistic knowledge on dioxin toxicity, support the hypotheses that the observed excesses might be associated with dioxin exposure. The mortality and cancer incidence follow-up of the Seveso cohort are continuing.
Epidemiology, 1997
Dioxin (2,3,7,8-tetrachlorodibenzo-para-dioxin, or TCDD) is a powerful carcinogen in experimental... more Dioxin (2,3,7,8-tetrachlorodibenzo-para-dioxin, or TCDD) is a powerful carcinogen in experimental animals, whereas the evidence in humans is limited. We examined cancer mortality from 1976 to 1991 among residents of Seveso, Italy, which was highly contaminated after an industrial accident. The area was divided into zones with decreasing exposure to dioxin (A = highest, B = lower, R = lowest). The population of a surrounding noncontaminated area was used as a reference group. Zone A was small (11,516 person-years); in that zone, we saw a moderate increase in mortality from digestive cancer among women [relative risk (RR) = 1.5; 95% confidence interval (CI) = 0.5-3.5]. In zone B, we also saw excesses at digestive sites (83,610 person-years), 10 years after the accident. Women had an increased mortality from stomach cancer (RR = 2.4; 95% CI = 0.8-5.7), and men had increased mortality from rectal cancer (RR = 6.2; 95% CI = 1.7-15.9). Hematologic neoplasms were increased. The highest risks were seen in zone B for leukemia in men (RR = 3.1; 95% CI = 1.3-6.4), multiple myeloma in women (RR = 6.6; 95% CI = 1.8-16.8), and Hodgkin's disease in both genders (RR = 3.3; 95% CI = 0.4-11.9 in men; and RR = 6.5; 95% CI = 0.7-23.5 in women). Soft tissue sarcoma was elevated only among zone R males (256,408 person-years; RR = 2.1; 95% CI = 0.6-5.4). We found no increase for all-cancer mortality or major specific sites (for example, respiratory among males, breast among females). The specific excesses that we observed were not explained by bias or confounding, and their association with dioxin exposure is plausible. The follow-up is continuing.