Papers by Giovanni Corrao
Cancers, 2020
A randomized clinical trial showed that trastuzumab, added to traditional chemotherapy, significa... more A randomized clinical trial showed that trastuzumab, added to traditional chemotherapy, significantly improved overall survival in human epidermal growth factor receptor 2 (HER2)-overexpressing metastatic gastric cancer patients. This population-based study aimed at evaluating both the clinical and economic impact of trastuzumab in a real-world setting. By using the healthcare utilization databases of Lombardy, Italy, a cohort of patients newly diagnosed with metastatic gastric cancer during the period 2011–2016 was selected. Among these, patients initially treated with either trastuzumab-based chemotherapy or standard chemotherapy alone were followed up until death, migration in other regions or June 2018. Overall survival and average cumulative costs were estimated and compared between the two treatment arms. Among the 1198 metastatic gastric cancer patients who started therapy within six months after metastasis detection, 87 were initially treated with trastuzumab-based chemother...
British Journal of Cancer, 2001
Although alcohol is not known to be carcinogenic in animal experimentation, there is strong epide... more Although alcohol is not known to be carcinogenic in animal experimentation, there is strong epidemiological evidence that alcoholic beverages increase the risk of cancers of the oral cavity and pharynx, oesophagus and larynx. The risks are essentially due to total ethanol intake, and tend to increase with the amount of ethanol drunk, but it is still unclear whether there is any threshold below which no effect is evident (IARC, 1988; Doll et al, 1999). Alcohol drinking has been associated with primary liver cancer, although this relation is difficult to investigate in epidemiological studies, since most alcohol-related liver cancers follow a cirrhosis, which leads to a reduction of alcohol drinking (Aricò et al, 1994; La Vecchia et al, 1998). Alcohol drinking has also been linked to cancers of the large bowel in both sexes and of the female breast. Although these associations are still open to discussion, these are the 2 most common neoplasms in developed countries after lung cancer, and therefore even a moderate excess risk may have important public health implications. The association between alcohol drinking and several other neoplasms, including ovary, endometrium and bladder, is still controversial (IARC, 1988; Doll et al, 1999). To evaluate the effect of alcohol on cancer risk, a more accurate quantification of its effects on various neoplasms is required. With this major focus, we therefore updated in the present paper a comprehensive meta-analysis of published case-control and cohort studies investigating the possible relation between alcohol intake and the risk of several neoplasm (Corrao et al, 1999). We also addressed the issue of the potential modifying effect of tobacco on alcohol-related cancerogenesis at various cancer sites. METHODS The statistical methods used for this meta-analysis are described in detail elsewhere (Corrao et al, 1999, 2000). Articles included were found through a search of the literature published from 1966 to 2000. The search was based on several bibliographic databases (MEDLINE, Current Contents, EMBASE, CAB Abstracts and Core Biomedical Collection), supplemented by checking all references in the selected articles. Completeness was verified by a hand-search on the most relevant journals of epidemiology and medicine, and by comparing our search with that of general reviews and meta-analyses published on this issue (IARC,
Respiration; international review of thoracic diseases
Pleural mesothelioma (PM) is a rare, highly lethal tumor. A definite consensus on its management ... more Pleural mesothelioma (PM) is a rare, highly lethal tumor. A definite consensus on its management has yet to be established. To assess management, overall survival (OS), and their predictors in a cohort of patients from Lombardy, the largest Italian region (about 10 million inhabitants). Through a record linkage between Lombardy health care administrative databases, we identified patients diagnosed with PM in 2006-2011 without history of cancer, evaluating their management. OS from PM diagnosis was estimated using the Kaplan-Meier method. Predictors of OS and of treatment were assessed using Cox regression models with time-dependent covariates when appropriate. Out of 1,326 patients, 754 (56.9%) received treatment for PM: 205 (15.5%) underwent surgery, and 696 (52.5%) used chemotherapy. Surgery was spread across several hospitals, and most patients diagnosed in nonspecialized centers (70%) underwent surgery in the same centers. Age at diagnosis was a strong inverse determinant of sur...
Cancers, 2020
A randomized clinical trial showed that trastuzumab, added to traditional chemotherapy, significa... more A randomized clinical trial showed that trastuzumab, added to traditional chemotherapy, significantly improved overall survival in human epidermal growth factor receptor 2 (HER2)-overexpressing metastatic gastric cancer patients. This population-based study aimed at evaluating both the clinical and economic impact of trastuzumab in a real-world setting. By using the healthcare utilization databases of Lombardy, Italy, a cohort of patients newly diagnosed with metastatic gastric cancer during the period 2011–2016 was selected. Among these, patients initially treated with either trastuzumab-based chemotherapy or standard chemotherapy alone were followed up until death, migration in other regions or June 2018. Overall survival and average cumulative costs were estimated and compared between the two treatment arms. Among the 1198 metastatic gastric cancer patients who started therapy within six months after metastasis detection, 87 were initially treated with trastuzumab-based chemother...
British Journal of Cancer, 2001
Although alcohol is not known to be carcinogenic in animal experimentation, there is strong epide... more Although alcohol is not known to be carcinogenic in animal experimentation, there is strong epidemiological evidence that alcoholic beverages increase the risk of cancers of the oral cavity and pharynx, oesophagus and larynx. The risks are essentially due to total ethanol intake, and tend to increase with the amount of ethanol drunk, but it is still unclear whether there is any threshold below which no effect is evident (IARC, 1988; Doll et al, 1999). Alcohol drinking has been associated with primary liver cancer, although this relation is difficult to investigate in epidemiological studies, since most alcohol-related liver cancers follow a cirrhosis, which leads to a reduction of alcohol drinking (Aricò et al, 1994; La Vecchia et al, 1998). Alcohol drinking has also been linked to cancers of the large bowel in both sexes and of the female breast. Although these associations are still open to discussion, these are the 2 most common neoplasms in developed countries after lung cancer, and therefore even a moderate excess risk may have important public health implications. The association between alcohol drinking and several other neoplasms, including ovary, endometrium and bladder, is still controversial (IARC, 1988; Doll et al, 1999). To evaluate the effect of alcohol on cancer risk, a more accurate quantification of its effects on various neoplasms is required. With this major focus, we therefore updated in the present paper a comprehensive meta-analysis of published case-control and cohort studies investigating the possible relation between alcohol intake and the risk of several neoplasm (Corrao et al, 1999). We also addressed the issue of the potential modifying effect of tobacco on alcohol-related cancerogenesis at various cancer sites. METHODS The statistical methods used for this meta-analysis are described in detail elsewhere (Corrao et al, 1999, 2000). Articles included were found through a search of the literature published from 1966 to 2000. The search was based on several bibliographic databases (MEDLINE, Current Contents, EMBASE, CAB Abstracts and Core Biomedical Collection), supplemented by checking all references in the selected articles. Completeness was verified by a hand-search on the most relevant journals of epidemiology and medicine, and by comparing our search with that of general reviews and meta-analyses published on this issue (IARC,
Respiration; international review of thoracic diseases
Pleural mesothelioma (PM) is a rare, highly lethal tumor. A definite consensus on its management ... more Pleural mesothelioma (PM) is a rare, highly lethal tumor. A definite consensus on its management has yet to be established. To assess management, overall survival (OS), and their predictors in a cohort of patients from Lombardy, the largest Italian region (about 10 million inhabitants). Through a record linkage between Lombardy health care administrative databases, we identified patients diagnosed with PM in 2006-2011 without history of cancer, evaluating their management. OS from PM diagnosis was estimated using the Kaplan-Meier method. Predictors of OS and of treatment were assessed using Cox regression models with time-dependent covariates when appropriate. Out of 1,326 patients, 754 (56.9%) received treatment for PM: 205 (15.5%) underwent surgery, and 696 (52.5%) used chemotherapy. Surgery was spread across several hospitals, and most patients diagnosed in nonspecialized centers (70%) underwent surgery in the same centers. Age at diagnosis was a strong inverse determinant of sur...
Epidemiology, biostatistics, and public health, Aug 29, 2013
Record linkage - i.e. the use and linkage of electronic, mainly administrative databases - has be... more Record linkage - i.e. the use and linkage of electronic, mainly administrative databases - has been utilized in epidemiologic research for over three decades now, starting from the system implemented in a few US health maintenance organizations (HMO, i.e. the Kaiser Permanente network), a few Nordic countries systems, or the UK general practice research database (UK GPRD, now clinical practice research datalink, CPRD) [1, 2]...
Journal of Thoracic Oncology, 2016
Introduction: The National Lung Screening Trial has achieved a 7% reduction in total mortality wi... more Introduction: The National Lung Screening Trial has achieved a 7% reduction in total mortality with low-dose computed tomography (LDCT) screening as compared with in the chest radiography arm. Other randomized trials are under way, comparing LDCT screening with no intervention. None of these studies was designed to investigate the impact of smoking habits on screening outcome. In the present study, we tested the effect of stopping smoking on the overall mortality of participants undergoing repeated LDCT screening for many years. Methods: Between 2000 and 2010, 3381 smokers aged 50 years or older were enrolled in two LDCT screening programs. On the basis of the last follow-up information, subjects were divided into two groups: current smokers throughout the screening period and former smokers. Results: With a median follow-up time of 9.7 years and a total of 32,857 person-years (PYs) of follow-up, a total of 151 deaths were observed in the group of 1797 current smokers (17,846 PYs) versus 109 among 1584 former smokers (15,011 PYs), corresponding to mortality rates of 8.46 and 7.26 for every 1000 PYs, respectively. Compared with current smokers, former smokers had an adjusted mortality hazard ratio of 0.61 (95% confidence interval: 0.44-0.83), with a 39% reduction in mortality. A similar reduction in mortality was observed in the subset of 712 late quitters, with a hazard ratio of 0.65 (95% confidence interval: 0.44-0.96). Conclusions: Stopping smoking significantly reduces the overall mortality of smokers enrolled in LDCT screening programs. The beneficial effect of stopping smoking on total mortality appears to be threefold to fivefold greater than the one achieved by earlier detection in the National Lung Screening Trial.
Epidemiology Biostatistics and Public Health, Jul 31, 2013
Background: major clinical outcomes of anticancer drugs may differ between clinical trials and cl... more Background: major clinical outcomes of anticancer drugs may differ between clinical trials and clinical practice. Administrative databases provide long-term information on safety and effectiveness of these drugs in large unselected populations and in selected subgroups of patients. In addition, these data provide complementary information on topics where evidence from randomized clinical trials is unavailable. Methods: this project will investigate 17 new targeted high cost drugs in Lombardy oncology practice between 2006 and 2010 using data from electronic healthcare databases. Specific objectives are: 1) to estimate the incidence of serious adverse events in clinical practice and their predictors; 2) to estimate survival and progression free survival and their predictors; 3) to compare major clinical outcomes according to different regimen of therapy. We will build a database by record linkage of several regional health service sources: the File F registry (in which the administration of the 17 drugs is recorded), the Regional hospital discharge forms (SDO ) database, the drug prescription database, the outpatients' services database, and the Registry Office database. Subjects resident in Lombardy who received at least one prescription of these drugs from 2006 to 2010 will be considered. Complications warranting hospitalization will be derived from the patients' SDO s after the first drug administration. Vital status will be obtained from the Registry Office database. Results: we will provide estimates of the incidence of serious adverse events of novel anticancer therapies, and of overall and disease free survival in clinical practice, overall and in selected subgroups. Conclusions: these data will contribute to a better effectiveness evaluation, particularly in patients under-represented in clinical trials.
European journal of cancer (Oxford, England : 1990), Jan 26, 2015
The evidence on efficacy and safety of trastuzumab in metastatic breast cancers (MBC) mainly deri... more The evidence on efficacy and safety of trastuzumab in metastatic breast cancers (MBC) mainly derives from randomized clinical trials. We assessed short- and long-term overall survival (OS) and cardiotoxicity in a large cohort of women with MBC treated with trastuzumab in clinical settings. Using healthcare administrative data of Lombardy (10 millions inhabitants), we identified a cohort of women receiving trastuzumab for MBC between 2006 and 2009. The cumulative risk of severe cardiac events and the OS from the first trastuzumab administration were estimated using the Kaplan-Meier method. Their predictors were assessed using Cox regression models. We found 681 trastuzumab MBC users. Thirty two (4.7%) women experienced severe cardiac adverse events. The cumulative risk increased sharply, reaching a value of 2.4% and 4.3% during the first and second year; thereafter it increased of about 1% per year. Age was a strong predictor of cardiotoxicity. The OS was 81.8%, 64.0%, 50.2%, 41.1% a...
Pharmacoepidemiology and drug safety, Jan 27, 2015
Insulin and other antidiabetic drugs may modulate hepatocellular carcinoma (HCC) risk in diabetic... more Insulin and other antidiabetic drugs may modulate hepatocellular carcinoma (HCC) risk in diabetics. We have analyzed the role of various antidiabetic drugs on HCC in a nested case-control study using the healthcare utilization databases of the Lombardy Region in Italy. This included 190 diabetic subjects with a hospital discharge reporting a diagnosis of malignant HCC and 3772 diabetic control subjects matched to each case on sex, age, date at cohort entry, and duration of follow-up. Increased risks of HCC were found for use of insulin (odds ratio [OR] = 3.73, 95% confidence interval [CI] 2.52-5.51), sulfonylureas (OR = 1.39, 95%CI 0.98-1.99), and repaglinide (OR = 2.12, 95%CI 1.38-3.26), while a reduced risk was found for use of metformin (OR = 0.57, 95%CI 0.41-0.79). The risk of HCC increased with increasing duration of insulin use (OR = 2.52 for <1 year, 5.41 for 1-2 years, and 6.01 for ≥2 years; p for trend < 0.001), while no clear pattern with duration was observed for su...
Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism, 2001
Alcohol consumption has been linked to an increased risk for various types of cancer. A combined ... more Alcohol consumption has been linked to an increased risk for various types of cancer. A combined analysis of more than 200 studies assessing the link between alcohol and various types of cancer (i.e., a meta-analysis) sought to investigate this association in more detail. This meta-analysis found that alcohol most strongly increased the risks for cancers of the oral cavity, pharynx, esophagus, and larynx. Statistically significant increases in risk also existed for cancers of the stomach, colon, rectum, liver, female breast, and ovaries. Several mechanisms have been postulated through which alcohol may contribute to an increased risk of cancer. Concurrent tobacco use, which is common among drinkers, enhances alcohol's effects on the risk for cancers of the upper digestive and respiratory tract. The analysis did not identify a threshold level of alcohol consumption below which no increased risk for cancer was evident.
Cancer Medicine, 2015
In order to quantify the association between use of statins and the risk of all hematological mal... more In order to quantify the association between use of statins and the risk of all hematological malignancies and of subtypes, we performed a meta-analysis of observational studies. We achieved a MEDLINE/EMBASE comprehensive search for studies published up to August 2014 investigating the association between use of statins and the risk of hematological malignancies, including Hodgkin-and non-Hodgkin lymphoma, leukemia, and myeloma. Fixed-and random-effect models were fitted to estimate the summary relative risk (RR) based on adjusted study-specific results. Between-study heterogeneity was assessed using the Q and I 2 statistics and the sources of heterogeneity were investigated using Deeks' test. Moreover, an influence analysis was performed. Finally, publication bias was evaluated using funnel plot and Egger's regression asymmetry test. Fourteen studies (10 case-control and four cohort studies) contributed to the analysis. Statin use, compared to nonuse of statins, was negatively associated with all hematological malignancies taken together (summary RR 0.86; 95% CI: 0.77-0.96), with leukemia (0.83; 0.74-0.92), and non-Hodgkin lymphoma (0.81; 0.68 to 0.96), but it was not related to the risk of myeloma (0.89; 0.53-1.51). Long-term users of statins showed a statistically significant reduction in the risk of all hematological malignancies taken together (0.78; 0.71-0.87). Statistically significant betweenstudies heterogeneity was observed for all outcome except for leukemia. Heterogeneity was caused by differences confounding-adjustment level of the included studies only for Myeloma. No significant evidence of publication bias was found.
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...
Diabetes Research and Clinical Practice, 2015
To assess the association between use of incretin-based drugs for diabetes mellitus and the occur... more To assess the association between use of incretin-based drugs for diabetes mellitus and the occurrence of acute pancreatitis. A population-based, nested case-control study was performed within a cohort of 166,591 patients from the Lombardy region (Italy) aged 40 years or older who were newly treated with oral antihyperglycaemic agents between 2004 and 2007. Cases were 666 patients who experienced acute pancreatitis from April 1, 2008 until December 31, 2012. For each case patient, up to 20 controls were randomly selected from the cohort and matched on gender, age at cohort entry, and date of index prescription. Conditional logistic regression was used to model the risk of acute pancreatitis associated with use of incretin-based drugs within 30 days before hospitalization, after adjustment for several risk factors, including the use of other antihyperglycaemic agents. Sensitivity analyses were performed in order to account for possible sources of systematic uncertainty. Use of incretin-based drugs within 30 days was reported by 17 (2.6%) cases of acute pancreatitis versus 193 (1.5%) controls. The corresponding multivariate odds ratio was 1.75 (95% confidence interval, 1.02 to 2.99). Slightly lower and no significant excess risks were observed by shortening (15 days) and increasing (60 and 90 days) the time-window at risk. This study supports a possible increased risk of acute pancreatitis in relation to use of incretin-baseddrugs reported in a few previous studies. However, given the potential for bias and the inconsistency with other studies, additional investigations are needed to clarify the safety of incretin-based-drugs.
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 (2006e2009). DFS and OS were estimated using the KaplaneMeier 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 40e69 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.
Epidemiology, biostatistics, and public health, Aug 29, 2013
Record linkage - i.e. the use and linkage of electronic, mainly administrative databases - has be... more Record linkage - i.e. the use and linkage of electronic, mainly administrative databases - has been utilized in epidemiologic research for over three decades now, starting from the system implemented in a few US health maintenance organizations (HMO, i.e. the Kaiser Permanente network), a few Nordic countries systems, or the UK general practice research database (UK GPRD, now clinical practice research datalink, CPRD) [1, 2]...
Journal of Thoracic Oncology, 2016
Introduction: The National Lung Screening Trial has achieved a 7% reduction in total mortality wi... more Introduction: The National Lung Screening Trial has achieved a 7% reduction in total mortality with low-dose computed tomography (LDCT) screening as compared with in the chest radiography arm. Other randomized trials are under way, comparing LDCT screening with no intervention. None of these studies was designed to investigate the impact of smoking habits on screening outcome. In the present study, we tested the effect of stopping smoking on the overall mortality of participants undergoing repeated LDCT screening for many years. Methods: Between 2000 and 2010, 3381 smokers aged 50 years or older were enrolled in two LDCT screening programs. On the basis of the last follow-up information, subjects were divided into two groups: current smokers throughout the screening period and former smokers. Results: With a median follow-up time of 9.7 years and a total of 32,857 person-years (PYs) of follow-up, a total of 151 deaths were observed in the group of 1797 current smokers (17,846 PYs) versus 109 among 1584 former smokers (15,011 PYs), corresponding to mortality rates of 8.46 and 7.26 for every 1000 PYs, respectively. Compared with current smokers, former smokers had an adjusted mortality hazard ratio of 0.61 (95% confidence interval: 0.44-0.83), with a 39% reduction in mortality. A similar reduction in mortality was observed in the subset of 712 late quitters, with a hazard ratio of 0.65 (95% confidence interval: 0.44-0.96). Conclusions: Stopping smoking significantly reduces the overall mortality of smokers enrolled in LDCT screening programs. The beneficial effect of stopping smoking on total mortality appears to be threefold to fivefold greater than the one achieved by earlier detection in the National Lung Screening Trial.
The Oncologist, 2013
Learning Objectives Evaluate the risk of cancer as well as cardiovascular and renal disease in th... more Learning Objectives Evaluate the risk of cancer as well as cardiovascular and renal disease in the use of oral antidiabetics. Define and adequately quantify the effect of TZD on the risk of bladder cancer, other selected cancers, and all neoplasms. Objective. To clarify and quantify the effect of thiazolidinediones (TZDs; e.g., pioglitazone, rosiglitazone) on the risk of bladder cancer, other selected cancers, and overall cancer in patients with type 2 diabetes, we performed a systematic review and meta-analysis of observational studies. Methods. A PubMed/MEDLINE search was conducted for studies published in English up to June 30, 2012. Random-effect models were fitted to estimate summary relative risks (RR). Results. Seventeen studies satisfying inclusion criteria (3 case-control studies and 14 cohort studies) were considered. Use of TZDs was not associated to the risk of cancer overall (summary RR: 0.96; 95% confidence interval [CI]: 0.91–1.01). A modest excess risk of bladder can...
Epidemiology Biostatistics and Public Health, Jul 31, 2013
Background: major clinical outcomes of anticancer drugs may differ between clinical trials and cl... more Background: major clinical outcomes of anticancer drugs may differ between clinical trials and clinical practice. Administrative databases provide long-term information on safety and effectiveness of these drugs in large unselected populations and in selected subgroups of patients. In addition, these data provide complementary information on topics where evidence from randomized clinical trials is unavailable. Methods: this project will investigate 17 new targeted high cost drugs in Lombardy oncology practice between 2006 and 2010 using data from electronic healthcare databases. Specific objectives are: 1) to estimate the incidence of serious adverse events in clinical practice and their predictors; 2) to estimate survival and progression free survival and their predictors; 3) to compare major clinical outcomes according to different regimen of therapy. We will build a database by record linkage of several regional health service sources: the File F registry (in which the administration of the 17 drugs is recorded), the Regional hospital discharge forms (SDO ) database, the drug prescription database, the outpatients' services database, and the Registry Office database. Subjects resident in Lombardy who received at least one prescription of these drugs from 2006 to 2010 will be considered. Complications warranting hospitalization will be derived from the patients' SDO s after the first drug administration. Vital status will be obtained from the Registry Office database. Results: we will provide estimates of the incidence of serious adverse events of novel anticancer therapies, and of overall and disease free survival in clinical practice, overall and in selected subgroups. Conclusions: these data will contribute to a better effectiveness evaluation, particularly in patients under-represented in clinical trials.
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Papers by Giovanni Corrao