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Background CEA, CYFRA21-1 and NSE are tumor markers used for monitoring the response to chemotherapy in advanced adenocarcinoma, squamous cell carcinoma and small-cell lung cancer, respectively. Their role in cancer immunotherapy needs to be elucidated. Methods Patients with advanced non-small cell lung cancer (NSCLC) were treated with nivolumab 3 mg/kg every 2 weeks within the Italian Nivolumab Expanded Access Program. Blood samples were collected at baseline, at each cycle up to cycle 5 and then every two cycles until patient’s withdrawn from the study. All patients underwent a CT-scan after every 4 cycles of treatment and responses were classified according to RECIST 1.1. The biomarkers serum levels were measured with a chemiluminescent microparticle immunoassay for CEA and with an immuno radiometric assay for CYFRA21-1 and NSE. The markers values at baseline and after 4 cycles were used to analyze the relationship between their variation over baseline and the tumor response, evaluated as disease control rate (DCR: CR + PR + SD), and survival (PFS and OS). Results A total of 70 patients were evaluable for the analysis. Overall, a disease control was obtained in 24 patients (35.8%, 4 PR + 20 SD). After 4 cycles of nivolumab a CEA or CYFRA21-1 reduction ≥ 20% over the baseline was significantly associated with DCR (CEA, p = 0.021; CYFRA21-1, p < 0.001), PFS (CEA, p = 0.028; CYFRA21-1, p < 0.001) and OS (CEA, p = 0.026; CYFRA21-1, p = 0.019). Multivariate analysis confirmed the ability of CYFRA21-1 reduction ≥ 20% to predict DCR (p = 0.002) and PFS (p < 0.001). Conclusion The reduction in serum level of CYFRA21-1 or CEA might be a reliable biomarker to predict immunotherapy efficacy in NSCLC patients. NSE was not significant for monitoring the efficacy of nivolumab.

Background/Objectives: Only a few papers have treated of the relationship between Barrett’s esophagus (BE) or erosive esophagitis (E) and coffee or tea intake. We evaluated the role of these beverages in BE and E occurrence. Subjects/Methods: Patients with BE (339), E (462) and controls (619) were recruited. Data on coffee and tea and other individual characteristics were collected using a structured questionnaire. Results: BE risk was higher in former coffee drinkers, irrespective of levels of exposure (cup per day; ⩽1: OR=3.76, 95% CI 1.33–10.6; >1: OR=3.79, 95% CI 1.31–11.0; test for linear trend (TLT) P =0.006) and was higher with duration (>30 years: OR=4.18, 95% CI 1.43–12.3; TLT P =0.004) and for late quitters, respectively (⩽3 years from cessation: OR=5.95, 95% CI 2.19–16.2; TLT P <0.001). The risk of BE was also higher in subjects who started drinking coffee later (age >18 years: OR=6.10, 95% CI 2.15–17.3). No association was found in current drinkers, but for an increased risk of E in light drinkers (<1 cup per day OR =1.85, 95% CI 1.00–3.43). A discernible risk reduction of E (about 20%, not significant) and BE (about 30%, P <0.05) was observed in tea drinkers. Conclusions: Our data were suggestive of a reduced risk of BE and E with tea intake. An adverse effect of coffee was found among BE patients who had stopped drinking coffee. Coffee or tea intakes could be indicative of other lifestyle habits with protective or adverse impact on esophageal mucosa.

ObjectiveThe impact of a screening programme on colorectal cancer (CRC) incidence in its target population depends on several variables, including coverage with invitations, participation rate, positivity rate of the screening test, compliance with an invitation to second-level assessment and endoscopists’ sensitivity. We propose a synthetic indicator that may account for all the variables influencing the potential impact of a screening programme on CRC incidence.DesignWe defined the ‘rate of advanced adenoma on the target population’ (AA-TAP) as the rate of patients who received a diagnosis of advanced adenoma within a screening programme, divided by the programme target population. We computed the AA-TAP for the CRC Italian screening programmes (biennial faecal immunochemical test, target population 50–69 year olds) using the data of the Italian National Survey from 2003 to 2016, overall and by region, and assessed the association between AA-TAP and CRC incidence fitting a linear regression between the trend of regional CRC incidence rates in 50–74 year old subjects and the cumulative AA-TAP.ResultsIn 2016, the AA-TAP at a national level was 105×100 000, whereas significant differences were observed between the northern and central regions (respectively 126 and 149×100 000) and the South and Islands (36×100 000). The cumulative AA-TAP from 2004 to 2012 was significantly correlated with the difference between CRC incidence rates in 2013–2014 and those in 2003–2004 (p=0.009).ConclusionThe AA-TAP summarises into a single indicator the potential impact of a screening programme in reducing CRC incidence rates.

Only a few papers have treated of the relationship between Barrett%apos;s esophagus (BE) or erosive esophagitis (E) and coffee or tea intake. We evaluated the role of these beverages in BE and E occurrence. BE risk was higher in former coffee drinkers, irrespective of levels of exposure (cup per day; [precedes/equal to]1: OR=3.76, 95% CI 1.33-10.6; [greater than] 1: OR=3.79, 95% CI 1.31-11.0; test for linear trend (TLT) P=0.006) and was higher with duration ( [greater than] 30 years: OR=4.18, 95% CI 1.43-12.3; TLT P=0.004) and for late quitters, respectively ([precedes/equal to]3 years from cessation: OR=5.95, 95% CI 2.19-16.2; TLT P [less than] 0.001). The risk of BE was also higher in subjects who started drinking coffee later (age [greater than] 18 years: OR=6.10, 95% CI 2.15-17.3). No association was found in current drinkers, but for an increased risk of E in light drinkers ( [less than] 1 cup per day OR =1.85, 95% CI 1.00-3.43). Our data were suggestive of a reduced risk of BE and E with tea intake. An adverse effect of coffee was found among BE patients who had stopped drinking coffee. Coffee or tea intakes could be indicative of other lifestyle habits with protective or adverse impact on esophageal mucosa.

PurposeWith better access to early diagnosis and appropriate treatment, cervical cancer (CC) burden decreased in several European countries. In Eastern European (EE) countries, which accessed European Union in 2004, CC survival was worse than in the rest of Europe. The present study investigates CC survival differences across five European regions, considering stage at diagnosis (local, regional and metastatic), morphology (mainly squamous versus glandular tumours) and patients’ age.MethodsWe analysed 101,714 CC women diagnosed in 2000–2007 and followed-up to December 2008. Age-standardised 5-year relative survival (RS) and the excess risks of cancer death in the 5 years after diagnosis were computed.ResultsEE women were older and less commonly diagnosed with glandular tumours. Proportions of local stage cancers were similar across Europe, while morphology- and stage-specific RS (especially for non-metastatic disease) were lower in Eastern Europe. Adjusting for age and morphology, excess risk of local stage CC death for EE patients remained higher than that for other European women.ConclusionStage, age and morphology alone do not explain worse survival in Eastern Europe: less effective care may play a role, probably partly due to fewer or inadequate resources being allocated to health care in this area, compared to the rest of Europe.

The main objective of the SUDCAN study was to compare, for 15 cancer sites, the trends in net survival and excess mortality rates from cancer 5 years after diagnosis between six European Latin countries (Belgium, France, Italy, Portugal, Spain and Switzerland). The data were extracted from the EUROCARE-5 database. The study period ranged from 6 (Portugal, 2000–2005) to 18 years (Switzerland, 1989–2007). Trend analyses were carried out separately for each country and cancer site; the number of cases ranged from 1500 to 104 000 cases. We developed an original flexible excess rate modelling strategy that accounts for the continuous effects of age, year of diagnosis, time since diagnosis and their interactions. Nineteen models were constructed; they differed in the modelling of the effect of the year of diagnosis in terms of linearity, proportionality and interaction with age. The final model was chosen according to the Akaike Information Criterion. The fit was assessed graphically by comparing model estimates versus nonparametric (Pohar-Perme) net survival estimates. Out of the 90 analyses carried out, the effect of the year of diagnosis on the excess mortality rate depended on age in 61 and was nonproportional in 64; it was nonlinear in 27 out of the 75 analyses where this effect was considered. The model fit was overall satisfactory. We analysed successfully 15 cancer sites in six countries. The refined methodology proved necessary for detailed trend analyses. It is hoped that three-dimensional parametric modelling will be used more widely in net survival trend studies as it has major advantages over stratified analyses.

Esophageal cancer represents a major clinical challenge because of its poor prognosis. The aim of the SUDCAN collaborative study was to compare the net survival from esophageal cancer between six European Latin countries (Belgium, France, Italy, Portugal, Spain, and Switzerland) and report the trends in net survival and the dynamics of excess mortality rates (EMRs) up to 5 years after diagnosis. The data were extracted from the EUROCARE-5 database. First, net survival was studied over the period 2000–2004 using the Pohar-Perme estimator. For trend analyses, the study period was specific to each country. The results were reported from 1992 to 2004 in France, Italy, Spain, and Switzerland and from 2000 to 2004 in Belgium and Portugal. These trend analyses were carried out using a flexible excess rate modeling strategy. There were some differences between countries in age-standardized net survival (2000–2004). The 5-year net survival ranged between 9 (Spain) and 21% (Belgium). The small increase in net survival from 1992 and 2004 was mostly observed at ages 55 and 65, but was less marked at age 75. There was a slight decrease in EMR between 1992 and 2004 until ~ 24 months after diagnosis. Beyond this period, the decrease in the EMR was moderate and the same in all countries irrespective of the year of diagnosis. Some improvement in the 5-year net survival was observed in all countries limited to the 24 months after diagnosis. However, survival differences between countries persisted. Further improvement is expected from innovative treatments.

The aim of the SUDCAN collaborative study was to compare the net survival from 15 cancers diagnosed in 2000–2004 in six European Latin countries and provide trends in net survival and dynamics of excess mortality rates up to 5 years after diagnosis from 1992 to 2004 in France, Italy, Spain, and Switzerland, and from 2000 to 2004 in Belgium and Portugal. This paper presents a detailed description of the data analyzed and quality indicators. Incident cases from Belgium, France, Italy, Portugal, Spain, and Switzerland were retrieved from 56 general or specialized population-based cancer registries that participated in the EUROCARE-5 database. Fifteen cancer sites were analyzed. The data were checked according to the EUROCARE protocol. The percentages of excluded cases, cases based on death-certificate only, cases lost to follow-up at 5 years after diagnosis, and the proportions of microscopically verified cases were evaluated across countries and cancer sites. Data exclusions for major flaws were negligible. Cases based on death-certificate only were quite rare, except for some poor-prognosis cancers in some countries. The site-specific proportions of microscopically verified cases were generally high, but slightly lower in Italy than elsewhere. The percentage of cases lost to follow-up at 5 years after diagnosis was generally low. The net survival analyses in 2000–2004 included 873 314 tumors, whereas trend analyses included 1 426 004 tumors. The quality of the data analyzed was generally good. In fact, the analyzed data have been already checked and accepted for EUROCARE-5. However, slight differences in quality indexes, for some cancers, should be kept in mind in the interpretation of survival comparisons across countries.

Pancreatic cancer represents a real clinical challenge. The aim of the SUDCAN collaborative study was to compare the net survival from pancreatic cancer between six European Latin countries (Belgium, France, Italy, Portugal, Spain and Switzerland) and provide trends in net survival and dynamics of excess mortality rates up to 5 years after diagnosis. The data were extracted from the EUROCARE-5 database. First, net survival was studied over the period 2000–2004 using the Pohar-Perme estimator. For trend analyses, the study period was specific to each country. Results were reported from 1992 to 2004 in France, Italy, Spain and Switzerland and from 2000 to 2004 in Belgium and Portugal. These analyses were carried out using a flexible excess rate modelling strategy. There were little differences between countries in age-standardized net survivals (2000–2004). The 5-year net survival was poor (range: 6–10%). The changes in net survival from 1992 to 2004 were mostly related to early survival and patients aged 60 years. A slight decrease in the excess mortality rate between 1992 and 2004 was observed, limited to the 18 months after diagnosis. This study confirmed that, despite some improvement, survival from pancreatic cancer is still poor throughout European Latin countries. The major improvements in clinical imaging did not result in improvements in prognosis. Development of truly innovative treatments is highly needed to improve prognosis.