Search

Background: We previously demonstrated the cumulative poor prognostic role of concomitant medications on the clinical outcome of patients with advanced cancer treated with immune checkpoint inhibitors, creating and validating a drug-based prognostic score to be calculated before immunotherapy initiation in patients with advanced solid tumours. This ‘drug score’ was calculated assigning score 1 for each between proton-pump inhibitor and antibiotic administration until a month before cancer therapy initiation and score 2 in case of corticosteroid intake. The good risk group included patients with score 0, intermediate risk with score 1–2 and poor risk with score 3–4. Methods: Aiming at validating the prognostic and putative predictive ability depending on the anticancer therapy, we performed the present comparative analysis in two cohorts of advanced non–small-cell lung cancer (NSCLC), respectively, receiving first-line pembrolizumab or chemotherapy through a random case-control matching and through a pooled multivariable analysis including the interaction between the computed score and the therapeutic modality (pembrolizumab vs chemotherapy). Results: Nine hundred fifty and 595 patients were included in the pembrolizumab and chemotherapy cohorts, respectively. After the case-control random matching, 589 patients from the pembrolizumab cohort and 589 from the chemotherapy cohort were paired, with no statistically significant differences between the characteristics of the matched subjects. Among the pembrolizumab-treated group, good, intermediate and poor risk evaluable patients achieved an objective response rate (ORR) of 50.0%, 37.7% and 23.4%, respectively, (p < 0.0001), whereas among the chemotherapy-treated group, patients achieved an ORR of 37.0%, 40.0% and 32.4%, respectively (p = 0.4346). The median progression-free survival (PFS) of good, intermediate and poor risk groups was 13.9 months, 6.3 months and 2.8 months, respectively, within the pembrolizumab cohort (p < 0.0001), and 6.2 months, 6.2 months and 4.3 months, respectively, within the chemotherapy cohort (p = 0.0280). Among the pembrolizumab-treated patients, the median overall survival (OS) for good, intermediate and poor risk patients was 31.4 months, 14.5 months and 5.8 months, respectively, (p < 0.0001), whereas among the chemotherapy-treated patients, it was 18.3 months, 16.8 months and 10.6 months, respectively (p = 0.0003). A similar trend was reported considering the two entire populations. At the pooled analysis, the interaction term between the score and the therapeutic modality was statistically significant with respect to ORR (p = 0.0052), PFS (p = 0.0003) and OS (p < 0.0001), confirming the significantly different effect of the score within the two cohorts. Conclusion: Our ‘drug score’ showed a predictive ability with respect to ORR in the immunotherapy cohort only, suggesting it might be a useful tool for identifying patients unlikely to benefit from first-line single-agent pembrolizumab. In addition, the prognostic stratification in terms of PFS and OS was significantly more pronounced among the pembrolizumab-treated patients.

Management of early-stage non-small cell lung cancer (NSCLC) consists in multimodal treatment, including surgery, radiotherapy and chemotherapy. The mainstay of treatment is radical surgery. Definitive radiotherapy using stereotactic techniques can provide adequate local disease control, and is the treatment of choice in medically inoperable patients. Most early-stage patients are at significant risk of disease relapse after local treatment. Adjuvant platinum-based chemotherapy has demonstrated to provide an absolute survival benefit of 5% compared to observation. However, unlike advanced/metastatic disease, little progress has been made in the treatment of early-stage NSCLC over the past decade. In recent years, plenty of research has focused on the optimization of adjuvant and neoadjuvant treatment. Several trials with novel drugs, such as targeted agents and immune-checkpoint inhibitors are currently underway, with preliminary positive results. Customization of treatment on patients’ characteristics before, and major pathological response after therapy, will further improve survival outcomes in this subset of patients.

Liver cancer is the third most common cause of cancer-associated death. Advances in the last decade have provided more options for treating hepatocellular carcinoma. The use of immune checkpoint inhibitors represents a leap forward and broadens the armamentarium for clinicians. In this article, we provide a state-of-the-art review of molecular therapy. We also detail the mechanisms of checkpoint inhibitor therapy, which blocks the interaction of programmed cell death receptor protein with programmed cell death ligand, reducing the immune checkpoint activity on regulatory T cells, thereby inhibiting tumor cell growth.

Introduction Patients with initially inoperable non-metastatic pancreatic cancer (PC) have a poor prognosis, often similar to those with metastatic disease. Neoadjuvant chemotherapy (CT) plus concomitant or sequential radiotherapy (RT) may cause tumor shrinkage and allow for radical surgery. We pooled data of studies in which patients with locally advanced (unresectable) or borderline resectable PC were treated with a course of induction (or consolidation) CT followed or preceded by neoadjuvant CTRT regimen. Materials and methods We searched articles, including phase 2 or 3 studies, published in English from 2010 up to December 2020 in PubMed, SCOPUS, the Cochrane Library, and EMBASE. The primary outcomes were the pooled radical and R0 resection rates, median PFS and OS of included patients (those included in the intent to treat analysis). Results A total of 28 studies were finally considered eligible for inclusion in quantitative analysis for a total of 2446 patients with locally advanced/borderline resectable PC. Overall the pooled rate of resection was 29.7% (95%CI 26.7–32.8%). In patients who completed the CT + CTRT program, the overall resection rate was 31.8% (95% 28.4–35.4%). After exclusion of studies that included resectable PCs, the overall resection rate was 19.9% (95%CI 17.3–22.7%). In studies were all patients had unresectable PC (n = 20 studies), the resection rate was 12.1% (95%CI 10–14.5%). In two studies that enrolled all borderline resectable PCs the resection rate was 59.2% (95%CI 48.9–68.8%). The pooled R0 resection rate was 68.7% (95%CI 64.7–72.3%). The median pooled OS was 15.7 months (95%CI 14–17.2 months) and the median pooled PFS was 10.7 (95%CI 9.3–12.1 months). Conclusions Surgery is a treatment option in about one third of patients with initially inoperable PC, following total neoadjuvant therapy. In unresectable cases the resection rate was 12%. Median OS and PFS rates were comparable with historical data of advanced PCs. Optimal integration and sequence of chemo- and radiotherapy in unresectable PC must still be defined.

Background Patients with cancer are considered at high risk for the novel respiratory illness coronavirus disease 2019 (COVID‐19). General measures to keep COVID‐19–free cancer divisions have been adopted worldwide. The objective of this study was to evaluate the efficacy of triage to identify COVID‐19 among patients with cancer. Methods From March 20 to April 17, 2020, data were collected from patients who were treated or followed at the authors' institution in a prospective clinical trial. The primary endpoint was to estimate the cumulative incidence of COVID‐19–positive patients who were identified using a triage process through the aid of medical and patient questionnaires. Based on a diagnostic algorithm, patients with suspect symptoms underwent an infectious disease specialist's evaluation and a COVID‐19 swab. Serologic tests were proposed for patients who had symptoms or altered laboratory tests that did not fall into the diagnostic algorithm but were suspicious for COVID‐19. Results Overall, 562 patients were enrolled. Six patients (1%) were diagnosed with COVID‐19, of whom 4 (67%) had the disease detected through telehealth triage, and 2 patients (33%) without suspect symptoms at triage had the disease detected later. Seventy‐one patients (13%) had suspect symptoms and/or altered laboratory tests that were not included in the diagnostic algorithm and, of these, 47 patients (73%) underwent testing for severe acute respiratory syndrome coronavirus 2 antibody: 6 (13%) were positive for IgG (n = 5) or for both IgM and IgG (n = 1), and antibody tests were negative in the remaining 41 patients. Conclusions The triage process had a positive effect on the detection of COVID‐19 in patients with cancer. Telehealth triage was helpful in detecting suspect patients and to keep a COVID‐19–free cancer center. The overall incidence of COVID‐19 diagnosis (1%) and antibody positivity (13%) in patients with suspect symptoms was similar to that observed in the general population., The adoption of a structured triage process can be useful for the detection of coronavirus disease 2019 symptoms and signs. Oncology activities can be safely carried out during the pandemic with the aid of a triage process and containment measures.

Background: COVID-19 has shocked the entire planet, leading each State to set ever stricter health regulations, managing pandemic in very short time In the oncology department (hospitalization and DH) there have been effects that have changed the working lifestyle of the health workers (director, doctors, nurses, socio-health assistants and administrative staff within the department) therefore an attempt was made to measure their nature and impact The aspects investigated were stress, anxiety, depression and insomnia Methods: The methods used are the naturalistic observation and the self-report questionnaires: the Dass-21 and the index insomnia The research was very well received by the operators, eager both to make a contribution to the research, and to know their psychological situation, specifically the emotional sphere Results: The questionnaires revealed a discomfort distributed on all health workers, in particular: stress 65% (30% severe and extremely severe, 25% moderate, 10% average);anxiety 45% (25% severe and extremely severe, 5% moderate, 15% average);depression 40% (20% severe and extremely severe, 10% moderate, 10% medium);insomnia 30% (15% severe and 15% moderate) We have chosen to report only the clinically significant and deserving percentages of a psychological support intervention The naturalistic observation confirmed the results obtained in the self-assessment questionnaires: the health staff in the oncology department experienced more stressful situations, anxiety, depression and insomnia especially for those who work in close contact with patients and therefore perceive greater vulnerability to contagion Nevertheless, the data that emerged disconfirm the expectations, it was in fact thought to record higher scores Conclusions: Covid-19 put a strain on the work organization in the oncology department, changing the lifestyle of health workers both in terms of coping and interpersonal interactions Contrary to expectations, there was a good cognitive and emotional management of the emergency, probably due to precise precautions to be adopted (PPE, reduction of the influx of users and social distancing), pre-existing exposure to death and its processing, good resources personal and social in the management of the covid-19 emergency Cases of stress, anxiety and depression will be monitored and taken care of for a clinical psychological intervention

Introduction Metastatic breast cancer (MBC) is a life-threatening disease, and although some data suggest a trend in survival improvement, it has not yet been unequivocally demonstrated. This study aimed to evaluate the overall survival (OS) of MBC patients, assessing its correlation with prognostic factors. Patients and Methods COSMO (Checking Overall Survival in a MBC Observational study) is an Italian longitudinal retrospective multicenter study that enrolled patients with MBC diagnosed between 2000 and 2008. The primary objective was to detect a temporal difference in OS; the secondary objective was to identify prognostic factors as causal factors of the temporal variation in OS. Results A total of 3721 of 3930 patients from 31 centers were distributed in 3 periods: 886 (23.8%), 1302 (35.0%), and 1533 (41.2%) in 2000-2002, 2003-2005, and 2006-2008, respectively. With a median follow-up of 9.3 years, median OS was 2.8 years (95% confidence interval, 2.6-2.9). No difference in OS was found in the 3 cohorts (P for trend = .563). The worst prognosis was observed for patients with triple-negative MBC (OS, 1.5 years) and for those with central nervous system metastases (1.7 years); the best prognosis was observed in those with bone metastases or nonvisceral disease (3.4 and 3.2 years, respectively) and in patients with a disease-free interval, defined as the time between resection of the primary malignancy and diagnosis of MBC, of > 2 years (3 years). Conclusions The COSMO study found improvement in OS between 2000 and 2008. Molecular subtype remained the strongest prognostic factor, and the role of other prognostic factors was confirmed, in particular disease-free interval, site of metastasis, and age.

Anaplastic lymphoma kinase (ALK) inhibitors are potent oral anti-cancer agents acting as tyrosine kinase inhibitors (TKIs), which are approved for the treatment of ALK+ non-small cell lung cancer (NSCLC). Over the last years, several new molecules have been developed and are currently under clinical investigation.In this paper, the authors review the most relevant clinical findings of ALK inhibitors in the treatment of ALK+ NSCLC. The authors discuss differences in the efficacy and treatment-related adverse events (AEs) incidence of distinct ALK inhibitors, molecular mechanisms of acquired resistance, and ongoing clinical studies assessing the use of ALK inhibitors in innovative settings and novel combinations.ALK inhibitors have dramatically improved the prognosis of patients with ALK+ NSCLC and revolutionized therapy options. Nowadays, several molecules are approved for the treatment of ALK+ NSCLC, either in first or further lines of systemic treatment. Several clinical trials are currently ongoing in order to define a potential role of ALK inhibitors in combination with novel anti-cancer agents, as well as monotherapy in neo- and adjuvant settings.

BACKGROUND - Metastatic breast cancer (MBC) is a life-threatening disease. It is important to provide data about real-life MBC patients (pts) to understand the current prognostic factors. The aim of the present observational study, named COSMO (Checking Overall Survival in a MBC Observational study) is to describe the overall survival (OS) in a large cohort of MBC pts, assessing its correlation with specific prognostic factors (demographic, clinic, pathologic and biological). PATIENTS AND METHODS - The COSMO study is a multicenter, retrospective, cohort study, developed throughout the collaboration of 31 Italian oncological centers. Data about pts diagnosed as metastatic from 01/01/2000 to 31/12/2008, were collected. The association between molecular subtypes, metastatic sites, disease free interval (DFI) and OS were assessed. Pts were classified in three subgroups, based on the biological characteristics of their tumor: luminal, HER2-positive (regardless of hormone receptor) and triple negative (TN). Metastatic sites were categorized as visceral versus non-visceral disease, only bone and central nervous system (CNS) metastases. DFI was calculated from diagnosis to first relapse only for M0 pts. RESULTS - Of 3931 MBC pts enrolled in the study, 3720 were evaluable, with a median age of 61 years (interquartile range, IQR, 51-71). 1804 (62,1%) pts had a luminal disease, 691 (23,8%) HER2-positive, 410 (14.1%) TN. Median DFI was 3.2 years (IQR 1.7- 6.0). Regarding metastatic sites, pts with visceral disease were 2332 (63%); 826 (22,2%) pts had bone isolated metastases; in 306 (8,3%) pts, CNS metastases were reported. With a median follow up of 9 years (IQR 5.7-11.0) and 3098 (83.3%) recorded events, we founded a median OS of 2.8 years (95%CI: 2.7-2.9) years. OS was strictly depending from molecular subtypes with a better prognosis for HER2-positive versus luminal and TN MBC pts, median OS of 3.1 (95%CI 2.8-3.4), 3.0 (95%CI: 2.9-3.1) and 1.5 (95%CI: 1.3-1.7) years respectively (p-value2 years show a median OS of 3 years (95% CI: 2.9 – 3.2), while those with DFI CONCLUSIONS - Molecular subtype is crucial for prognosis: HER2-positive subtype has the best prognosis, while TN subtype has the shorter OS. Having a longer DFI from diagnosis (>2 years) correlate with a better prognosis. Our study confirm that sites of metastasis affects outcome: visceral involvement correlates with poor prognosis and, particularly, pts with brain metastasis represent the worst subgroup, while pts with solely bone disease have the best prognosis. The COSMO study provides a view on the Italian landscape of MBC between 2000 and 2008, adding new insights about pts prognosis. Citation Format: La Verde N, Collovà E, Blasi L, Pinotti G, Bernardo A, Bonotto M, Garrone O, Brunello A, Cavazzini MG, Bareggi C, Prochilo T, Porcu L, Moretti A, Barni S, On Behalf of COSMO Study Group. Overall survival in metastatic breast cancer patients in the third millennium: Results of an Italian study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-14-04.

Anaplastic lymphoma kinase (ALK) rearrangement confers sensitivity to ALK inhibitors (ALKis) in non-small-cell lung cancer (NSCLC). Although several drugs provided an impressive outcome benefit, the most effective sequential strategy is still unknown. We describe outcomes of real-life patients according to the treatment strategy received. We retrospectively collected 290 ALK rearranged advanced NSCLC diagnosed between 2011 and 2017 in 23 Italian institutions. After a median follow-up of 26 months, PFS for crizotinib and a new generation ALKis were 9.4 [CI 95% 7.9–11.2] and 11.1 months [CI 95% 9.2–13.8], respectively, while TTF were 10.2 [CI 95% 8.5–12.6] and 11.9 months [CI 95% 9.7–17.4], respectively, being consistent across the different settings. The composed outcomes (the sum of PFS or TTF) in patients treated with crizotinib followed by a new generation ALKis were 27.8 months [CI 95% 24.3–33.7] in PFS and 30.4 months [CI 95% 24.7–34.9] in TTF. The median OS from the diagnosis of advanced disease was 39 months [CI 95% 31.8–54.5]. Patients receiving crizotinib followed by a new generation ALKis showed a higher median OS [57 months (CI 95% 42.0–73.8)] compared to those that did not receive crizotinib [38 months (CI 95% 18.6–NR)] and those who performed only crizotinib as target agent [15 months (CI 95% 11.3–34.0)] (P

BackgroundConcomitant medications, such as steroids, proton pump inhibitors (PPI) and antibiotics, might affect clinical outcomes with immune checkpoint inhibitors.MethodsWe conducted a multicenter observational retrospective study aimed at evaluating the impact of concomitant medications on clinical outcomes, by weighing their associations with baseline clinical characteristics (including performance status, burden of disease and body mass index) and the underlying causes for their prescription. This analysis included consecutive stage IV patients with cancer, who underwent treatment with single agent antiprogrammed death-1/programmed death ligand-1 (PD-1/PD-L1) with standard doses and schedules at the medical oncology departments of 20 Italian institutions. Each medication taken at the immunotherapy initiation was screened and collected into key categories as follows: corticosteroids, antibiotics, gastric acid suppressants (including proton pump inhibitors - PPIs), statins and other lipid-lowering agents, aspirin, anticoagulants, non-steroidal anti-inflammatory drugs (NSAIDs), ACE inhibitors/Angiotensin II receptor blockers, calcium antagonists, β-blockers, metformin and other oral antidiabetics, opioids.ResultsFrom June 2014 to March 2020, 1012 patients were included in the analysis. Primary tumors were: non-small cell lung cancer (52.2%), melanoma (26%), renal cell carcinoma (18.3%) and others (3.6%). Baseline statins (HR 1.60 (95% CI 1.14 to 2.25), p=0.0064), aspirin (HR 1.47 (95% CI 1.04 to 2.08, p=0.0267) and β-blockers (HR 1.76 (95% CI 1.16 to 2.69), p=0.0080) were confirmed to be independently related to an increased objective response rate. Patients receiving cancer-related steroids (HR 1.72 (95% CI 1.43 to 2.07), pConclusionWe confirmed the association between baseline steroids administered for cancer-related indication, systemic antibiotics, PPIs and worse clinical outcomes with PD-1/PD-L1 checkpoint inhibitors, which can be assumed to have immune-modulating detrimental effects.

Highlights • There is limited data on the novel coronavirus respiratory illness (COVID-19) in patients with cancer. • COVID-19 diffusion in cancer patients is not prominent as expected, rather seems as contagious as for the general population. • There is no clear role for immune-suppression as an additional risk factor for coronavirus infection. • The pathogenicity of COVID-19 is exacerbated by the host’s immune system’s reaction. • Patients receiving immunotherapy may be more at risk for an aberrant response in case of infection., The novel coronavirus respiratory illness (COVID-19) is a public health emergency of global concern. Patients with cancer are at high risk of infections, due to an overall immunocompromised status. However, this connection is not straightforward for coronavirus (CoV) infection, in which the host immune response is the main driver of tissue damage. We performed a thorough review of data on CoV pathogenesis and morbidity rate in cancer patients, through the analysis of the previous CoV pandemics. Considering the interaction between CoV and the host immune system, cancer patients receiving immunotherapy might be more at risk for an aberrant immune response in case of infection, and might therefore deserve additional precautions. The limited available data do not allow us to provide practical indications for the management of cancer patients in this critical situation. Efforts should be made to prospectively collect data, to identify effective interventions to guide treatment decision.

Aim of special session To highlight examples and best practice in the area of occupational disease and modelling morbidity.

Introduction Lung cancer (LC) is the leading oncologic cause of death among males. The role of occupational history with exposure to well-established carcinogens is very important, but usually deeply underestimated. To undervalue the occupational origin of cancer can affect the efficacy of preventive measures and preclude patients to receive insurance benefits. We performed a systematic occupational medicine evaluation of a cases-series of lung cancer cases to properly quantify the proportion of LC cases with previous occupational exposure to carcinogens. Methods We systematically evaluated all consecutive LC cases hospitalised in a large university hospital, in Milan. An active systematic search was carried out for 24 months, by trained occupational physicians, using a standardised questionnaire. Results We collected 123 consecutive LC cases (66% males). Former and current smoking habit was found in 61% and 22%, respectively. A clear exposure to occupational carcinogens (in details: asbestos, polycyclic aromatic hydrocarbons, paintings, diesel exhaust) was recognised in 10% of males cases. Discussion Previous occupational exposure to carcinogens was frequent among males cases in Northern Italy. The observed prevalence was even lower than the one reported in a previous systematic search in Lombardy (Porru S , et al. Int Arch Occ Env Health 89:981–9). If we applied our observed proportion of occupational cases to the entire incident LC cases in Lombardy population, we should observe about 460 male occupational LC cases per year (AIRTUM-AIOM report 2016), actually more than the entire number of cancer (all sites, both gender) annually notified to National Institute for Insurance (INAIL Rapporto regionale 2015).

Introduction Malignant Pleural Mesothelioma (MPM) is an aggressive cancer mainly caused by asbestos exposure. Due to its long latency and insidious onset, MPM is often diagnosed in advanced stages with poor prognosis. In addition, asbestos is still used in many non-European countries and the incidence of MPM is expected to increase. In this context, the need of reliable diagnostic markers for early MPM diagnosis is of paramount importance. Along with the more frequently studied biological markers (mesothelin, fibulin-3), new emerging biomarkers include miRNA expression in peripheral blood. Methods We previously investigated 23 MPM patients and 19 subjects with past asbestos exposure (PAE) to examine if a specific miRNA signature in plasmatic extracellular vesicles (EV) might help to discriminate between MPM and PAE ( PLoS One, 2017 ). Criteria for enrollment, blood collection, miRNA extraction, screening and validation have been previously described. We found a two miRNA (miR-103a-3p and mir-30-3ep) diagnostic signature that discriminates the two groups with high accuracy (AUC 0.942), high sensitivity (95.5%) and good specificity (80.0%). We are currently expanding our study population to additionally include 25 MPM cases, 50 subjects with PAE, and 20 subjects with other respiratory diseases. Alongside miRNA expression, plasma mesothelin and fibulin-3 will be also measured. Results The diagnostic performance (AUC, Sensitivity and Specificity) of the best five miRNAs previously detected in our study will be examined in combination with plasma mesothelin and fibulin-3, taking into account major confounders (e.g. age, gender, BMI and smoking habit). Conclusions The combination of biological markers belonging to different molecular pathways might help in identifying a panel of biomarkers able to improve the overall diagnostic performance as suggested by Weber et al. ( PLoS One, 2014 ), who recently showed an improved AUC of 0.93 when combining mesothelin and miR-103a-3p.

Background Identification of predictive molecular alterations in lung adenocarcinoma is essential for accurate therapeutic decisions. Although several molecular approaches are available, a number of issues, including tumor heterogeneity, frequent material scarcity, and the large number of loci to be investigated, must be taken into account in selecting the most appropriate technique. MALDI-TOF mass spectrometry (MS), which allows multiplexed genotyping, has been adopted in routine diagnostics as a sensitive, reliable, fast, and cost-effective method. Our aim was to test the reliability of this approach in detecting targetable mutations in non-small cell lung cancer (NSCLC). In addition, we also analyzed low-quality samples, such as cytologic specimens, that often, are the unique source of starting material in lung cancer cases, to test the sensitivity of the system. Methods We designed a MS–based assay for testing 158 mutations in the EGFR, KRAS, BRAF, ALK, PIK3CA, ERBB2, DDR2, AKT, and MEK1 genes and applied it to 92 NSCLC specimens and 13 liquid biopsies from another subset of NSCLC patients. We also tested the sensitivity of the method to distinguish low represented mutations using serial dilutions of mutated DNA. Results Our panel is able to detect the most common NSCLC mutations and the frequency of the mutations observed in our cohort was comparable to literature data. The assay identifies mutated alleles at frequencies of 2.5–10%. In addition, we found that the amount of DNA template was irrelevant to efficiently uncover mutated alleles present at high frequency. However, when using less than 10 ng of DNA, the assay can detect mutations present in at least 10% of the alleles. Finally, using MS and a commercial kit for RT-PCR we tested liquid biopsy from 13 patients with identified mutations in cancers and detected the mutations in 4 (MS) and in 5 samples (RT-PCR). Conclusions MS is a powerful method for the routine predictive tests of lung cancer also using low quality and scant tissues. Finally, after appropriate validation and improvement, MS could represent a promising and cost-effective strategy for monitoring the presence and percentage of the mutations also in non-invasive sampling. Electronic supplementary material The online version of this article (10.1186/s13000-017-0683-7) contains supplementary material, which is available to authorized users.

Introduction: Lung cancer (LC) is the leading cause of neoplastic death among males. The role of occupational exposure to carcinogens is usually largely underestimated. To undervalue the occupational origin of cancer can affect the efficacy of preventive measures and preclude patients to receive insurance benefits. Aims: To properly quantify the proportion of LC cases with previous occupational exposure to carcinogens. Methods: We systematically evaluated all consecutive LC cases hospitalized in a large university hospital, in Milan. An active systematic search was carried in 2015-2016? by trained occupational physicians using a standardized questionnaire. Results: We collected 123 consecutive LC cases (66% males). Former and current smoking habit was found in 91.4% of men (71.6% and 19.8%, respectively) and 66.7% of women (40.5% and 26.2%, respectively). Definite exposure to occupational carcinogens (asbestos, polycyclic aromatic hydrocarbons, paintings, diesel exhaust) was recognized in 8 cases, all men (10%). Conclusions: Previous occupational exposure to carcinogens was frequent among male cases in Northern Italy. The prevalence we observed was lower than the one (26%) reported in a previous systematic search in Lombardy (Porru et al. Int Arch Occ Env Health 2016). If we applied our observed proportion of occupational cases to the entire incident LC cases in Lombardy population (AIRTUM-AIOM report 2016),, we should observe about 460 male occupational LC cases per year actually more than the entire number of cancer (all sites, both gender) annually notified to National Institute for Insurance (INAIL Rapporto regionale 2015).

Objectives Malignant Pleural Mesothelioma (MPM) is an aggressive cancer refractory to current therapies caused almost exclusively by asbestos. New specific diagnostic markers for early MPM diagnosis are needed. MiRNAs are single stranded noncoding that post-transcriptionally regulate gene expression by triggering mRNA cleavage or repressing translation. Changes in miRNA expression have been implicated in several diseases and cancers, including MPM. miRNAs are stable molecules that can be easily investigated in different specimens (e.g. blood), and used as a disease biomarker. We examined if a specific miRNA signature in plasma may help to discriminate between malignant pleural mesothelioma patients (MPM) and healthy subjects with a Past Asbestos Exposure (PAE). Methods We investigated 23 MPM patients and 19 healthy subjects with Past Asbestos Exposure (PAE). We screened 754 miRNAs in blood by TaqMan™ OpenArray® Human MiRNA Panel. The top-25 differential miRNAs were chosen for validation by Real time PCR. RNU48 was used as endogenous control. miRNA profiling between MPM and PAE subjects were compared using multiple linear and logistic regression models adjusted for age, sex, BMI, and smoking. Kaplan-Meier log rank test was used to evaluate the association between miRNA expression and survival in MPM patients. Results After miRNA screening, 57 differential miRNAs in plasma were detected. Among the top 25 differential miRNAs, 16 were validated and were able to discriminate between MPM and PEA subjects. In receiver operating characteristic (ROC) curve analysis, the three best miRNAs were miR-103 (area under curve, AUC = 0.86), miR-98 (AUC = 0.86) and miR-148 (AUC = 0.85), all characterised by high sensitivity (100%) and low specificity (66–73%). When we combined the two first miRNA (103 and 98) with miRNA 30e-3p (Se 64%, Sp 93%) we found the best discriminating signature ((AUC 0.94; Se 95.5%, Sp 86.7%). Subjects with miRNA 103 and 98 expression above the median had better survival (p

Purpose Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. We describe a case of MPM with an uncommon onset, characterized by pseudoachalasia as demonstrated with high-resolution manometry (HRM). Methods A 56-year-old man was referred to our hospital reporting worsening dysphagia. On the hypothesis of an esophageal motor disorder, the patient was referred for an HRM examination, which revealed features consistent with a diagnosis of type II achalasia. Results At the time of the first pneumatic dilation the endoscopist stopped the procedure in order to prevent perforation when he noticed only partial expansion of the pneumatic balloon. A CT scan and subsequent CT-guided excisional biopsy revealed an epithelioid pleural mesothelioma infiltrating the muscle wall. Given his good clinical condition, the patient was eligible for chemotherapy with cisplatin 75 mg/m2 and pemetrexed 500 mg/m2, resulting in a good response with partial remission of the disease and resolution of the dysphagia symptoms. Conclusions Pseudoachalasia as the first or only manifestation of mesothelioma is a rare occurrence that may expose patients to the risk of diagnostic delay. Close attention should be paid whenever a patient with symptoms and signs consistent with achalasia shows unusual features.

BACKGROUND: Patients with small-cell lung cancer (SCLC) that progress after first-line chemotherapy have a poor prognosis and the evidence of a benefit from second-line (SL) chemotherapy is limited. Patients relapsing or progressing more than 90 days after completion of first-line treatment are considered platinum sensitive and may be rechallenged with platinum-based chemotherapy. Topotecan is approved as SL treatment independent of time to progression. This retrospective analysis evaluates the clinical outcomes of SCLC patients who received SL chemotherapy after platinum-etoposide chemotherapy. PATIENTS AND METHODS: We retrospectively reviewed 161 patients who received SL chemotherapy for SCLC. Patients were divided into four subgroups by type of SL treatment: (1) platinum-based rechallenge; (2) anthracycline-based regimens; (3) topotecan; (4) other single agents. The endpoints were overall survival (OS), progression-free survival (PFS) and response rate (RR). Survival curves were plotted using the Kaplan-Meier method. The Cox proportional hazard model was used for multivariate analysis to investigate factors influencing survival. RESULTS: The median age was 63. There were 125 males and 36 females. Eastern Cooperative Oncology Group performance status (ECOG-PS) was 0, 1 and 2 in 12.5%, 62.5% and 25% of patients, respectively. Platinum sensitive/platinum resistant/platinum refractory/unknown=121/29/3/8 patients. Median time to SL chemotherapy was 6.9 months. The median PFS from starting second-line treatment was 4.3 months and median OS was 5.8 months. The overall RR was 22.9%. There was a trend toward higher RR (34.5% vs 17.5%, p for trend: 0.06) and OS (9.2 months vs 5.8 months, p=0.08) for patients with sensitive disease who were rechallenged with platinum-based chemotherapy. A multivariate analysis that adjusted for the time to SL treatment showed that a platinum-containing regimen achieves better RR, PFS and OS independently of the time to SL chemotherapy and that response to first-line treatment and PS at SL are the only independent prognostic factors. CONCLUSIONS: The outcome for second-line therapy for SCLC was poor and benefit appeared to be limited to those patients with good PS and rechallenged with platinum-based chemotherapy. Platinum-based rechallenge should be considered as a standard comparator in future randomized controlled trials of SL chemotherapy.

Among angiosarcomas, radiation-induced breast sarcomas (RIBS) represent a well-known entity generally characterized by a poor outcome, especially in patients with advanced disease. Despite the unfavorable prognosis, some chemotherapeutic agents have been used to treat these malignancies, occasionally with success. Treatments with demonstrated activity against sarcomas include ifosfamide-based regimens and, more recently, taxane derivatives. We report a case of a patient having a secondary breast angiosarcoma recurring early after surgery, who achieved complete remission following treatment with weekly paclitaxel. After 4 years of maintenance therapy, with an interval between consecutive administrations of no longer than 3 weeks, the patient is still in complete remission. A locoregional recurrence was documented twice during this period, the first as a consequence of a brief treatment interruption and the second because of a treatment delay. Nonetheless, in both instances a new complete remission was rapidly achieved with the resumption of the same treatment, without evidence of any significant adverse effects. We discuss the highly unusual behavior of this malignancy and the possible role of the two different mechanisms of action of paclitaxel-antiangiogenic versus cytotoxic-depending on the schedule of administration, with evidence of “false” drug-resistance.

Background: Screening of the oral cavity and dental care was suggested as mandatory preventive measures of osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates (BPs). We investigated the occurrence of ONJ before and after implementation of dental preventive measures when starting BP therapy. Patients and methods: Since April 2005, 154 consecutive patients treated with BPs (POST-Group) have undergone a baseline mouth assessment (dental visit 6 orthopantomography of the jaws) to detect potential dental conditions and dental care if required. A retrospective review was also conducted of all consecutive cancer patients with bone metastases (PRE-Group) and treated for the first time with BPs from January 1999 to April 2005 in our clinic without receiving any preventive measure. Incidence proportion and incidence rate (IR) were used to estimate the incidence of ONJ. Results: Among the study population (966 patients; male/female = 179/787), 73% had breast cancer. 25% of patients were given zoledronic acid (ZOL), 62% pamidronate (PAM), 8% PAM followed by ZOL and 5% clodronate. ONJ was observed in 28 patients (2.9%); we observed a reduction in the incidence of ONJ from 3.2% to 1.3%, when comparing—pre and post-implementation of preventive measures programme. Considering the patients exposed to ZOL, the performance of a dental examination and the application of preventive measures led to a sustained reduction in ONJ IR (7.8% in the PRE-Group versus 1.7% in the POST-Group; P = 0.016), with an IR ratio of 0.30 (95% confidence interval 0.03–1.26). Conclusions: ONJ is a manageable and preventable condition. Our data confirm that the application of preventive measures can significantly reduce the incidence of ONJ in cancer patients receiving BPs therapy. Dental exams combined to the identification of patients at risk in cooperation with the Dental Team can improve outcomes and increase the number of ONJ-free patients.

Osteonecrosis of the jaw (ONJ) is a severe complication of bisphosphonates treatment. Bisphosphonates reduce skeletal adverse events and give a clinical benefit to cancer patients. Therefore, it is necessary to identify appropriate procedures to reduce ONJ injures by using a successful monitoring program. In a retrospective study we analyzed the impact of a prevention program based on clinical oral cavity examination, dentists, and patients' education. The aim of the study was to evaluate if this approach might improve ONJ outcome in patients receiving pamidronate or zoledronate.We analyzed retrospectively two different groups of patients treated at our Institution: patients treated from October 2003 to June 2005 (group A) and patients treated from June 2005 to April 2007 (group B). In June 2005 the prevention program started for all our patients.One hundred and eighty-six cancer patients with bone involvement, treated with bisphosphonates, were considered. Sixteen of them developed ONJ: eight before and eight after June 2005. We observed a consistent difference in the evolution of the two groups. In the first group, four patients underwent a major surgery (one partial maxillectomy, complicated by septic shock and oronasal communication; two partial mandibulectomies; and one segmental mandibular resection), with an important impairment of their quality of life; while the eight new ONJ cases, diagnosed after June 2005, were successfully treated without aggressive dental interventions, and achieved a good control of symptoms.Bisphosphonates-related ONJ is a frequent adverse event (8.6%). The monitoring program proved very efficient to improve the clinical outcome of ONJ, avoiding an aggressive treatment and using a conservative approach and medical therapy.

MicroRNAs were described to target mRNA and regulate the transcription of genes involved in processes de-regulated in tumorigenesis, such as proliferation, differentiation and survival. In particular, the miRNA let-7 has been suggested to regulate the expression of the KRAS gene, a common mutated gene in non-small cell lung cancer (NSCLC), through a let-7 complementary site (LCS) in 3′UTR of KRAS mRNA. We have reported the analysis performed on the role of the polymorphism located in the KRAS-LCS (rs61764370) which is involved in the disruption of the let-7 complementary site in NSCLC patients enrolled within the TAILOR trial, a randomised trial comparing erlotinib versus docetaxel in second line treatment. In our cohort of patients, KRAS-LCS6 polymorphism did not have any impact on both overall survival (OS) and progression free survival (PFS) and was not associated with any patient’s baseline characteristics included in the study. Overall, patients had a better prognosis when treated with docetaxel instead of erlotinib for both OS and PFS. Considering KRAS-LCS6 status, the TG/GG patients had a benefit from docetaxel treatment (HR(docetaxel vs erlotinib) = 0.35, 95% CI 0.15–0.79, p = 0.011) compared with the TT patients (HR(docetaxel vs erlotinib) = 0.72, 95% CI 0.52–1.01, p = 0.056) in terms of PFS.

Hand-foot syndrome is a toxic effect of some chemotherapy agents such as 5-fluorouracil (5-FU), capecitabine and liposomal doxorubicin. The symptoms and signs are localized erythema and paresthesia. Floxuridine (FUDR) is an analogue of 5-FU, used for arterial hepatic infusion in patients affected by liver metastases from colorectal cancer. A patient who was treated for colorectal cancer with liver metastases underwent locoregional chemotherapy with FUDR and systemic chemotherapy with FOLFOX4. After three cycles he developed severe painful dermatitis of the right leg. Abdominal X-ray showed displacement of the catheter to the right common iliac artery. Treatment was discontinued and the patient had a rapid recovery.

To date, no predictive factors are recognized and applied in the therapeutic choice for metastatic renal cell carcinoma. Due to significant side-effects and costs, which are relevant issues in this setting, optimization of treatments has become a priority.We herein report a case of complete remission of metastatic renal cell carcinoma after 1 year of treatment with sunitinib. Since pancreatic metastases were detected by a 68Ga-DOTA-NOC positron emission tomography, it was decided to perform a histological revision of the specimens, with immunohistochemical staining for neuroendocrine markers on the primary tumor.On the basis of the detection of neuroendocrine markers on the primary neoplasm, together with pancreatic metastases positive on a 68Ga-DOTA-NOC positron emission tomography (PET), we hypothesize and discuss about a potential role of specific neuroendocrine markers as predictive indicators of response to sunitinib (and allegedly to other target therapies) in the treatment of this neoplasm.

Background The level of HER2/neu amplification may vary widely in breast cancers with HER2/neu alteration. The clinical significance of this phenomenon is still unclear. This study was aimed to explore the level of HER2/neu amplification in primary tumours and metastases in HER2-positive metastatic breast cancer (MBC) and its potential impact on survival after a trastuzumab-containing therapy. Methods We retrospectively identified MBC patients treated with a trastuzumab-containing therapy and performed dual-colour FISH on tumour samples from either primary tumour and/or metastasis in a central laboratory. Results We retrieved 110 tumour samples from 91 patients and included 79 tumour samples (primary = 56; metastasis = 23) from 63 patients in the final analysis. We found higher level of HER2/neu amplification in the metastases than in the primary tumours (median HER2/CEP17 ratio: 10.5 vs 7.0, respectively). In 69% of patients ( n = 16) with two tumour samples, the level of HER2/neu amplification was higher in the metastasis than in the paired primary tumour (median HER2/CEP17 ratio: 10.9 vs 8.3, respectively, p = 0.004). The incremental gain in level of HER2/neu amplification was associated with significantly shorter OS after trastuzumab-containing therapy ( p = 0.023, HR 1.014, CI95%: 1.002–1.025). Conclusions The level of HER2/neu amplification tends to increase from the primary tumour to the paired metastases in a significant proportion of patients with HER2-positive MBC. This phenomenon, although still not completely understood, could lead to a shorter OS after trastuzumab therapy.

Aims and background The purpose of the study was to evaluate the outcome of metastatic colorectal cancer patients treated, as first line, with 5-fluorouracil bolus/leucovorin + oxaliplatin, in terms of response, progression-free and overall survival. Materials and methods A retrospective cohort of consecutive metastatic colorectal cancer patients, treated from 2003 to 2006, was identified and analyzed. All patients, without a central venous device, were treated with oxaliplatin + 5-fluorouracil and leucovorin. Results Twenty-five metastatic colorectal cancer patients were treated. No 3–4 grade toxicity was observed. Five of 23 patients achieved a partial response: one of them resulted in a complete response after radiofrequency and another one after surgery. Fifteen of 23 patients had stable disease (one underwent radical surgery after chemotherapy, obtaining a complete remission) and 3 had progressive disease. Median progression-free survival was 7.2 months, and median overall survival was 30 months. Conclusions Based on this case-series study, the regimen seems to offer a good control of disease (86.9%) and can be considered as an alternative choice for patients who cannot receive continuous infusion.

To define the role of surgical management of lung metastases in ACC. Twenty ACC patients referred to lung metastasectomy were retrospectively reviewed. Twenty-six operations were performed; at the first metastasectomy, a resection with clear margins (R0) was achieved in 11 patients (55%), 3 are alive and well. Four out of 9 patients with residual disease (R2) are still alive. Median survival after metastasectomy was 78 and 52 months for R0 and R2 (p=0.4); median freedom from progression (FFP) in R0 and R2 groups was 30 and 15 months (p=0.2), respectively. A better outcome was obtained for patients with a disease-free interval 36 months and 6 metastases and bilateral involvement were critical in achieving a R0 intervention. Lung metastasectomy provided a prolonged FFP in a high selected subset of patients with ACC. However, if this could be translated into a survival benefit, it is still to be demonstrated.

Clozapine is a neuroleptic drug used in selected schizophrenic patients. Its use is limited because of unpredictable myelotoxicity. The potentially dangerous interaction between cancer treatment and clozapine is virtually unknown. A 37-year-old schizophrenic patient under treatment with clozapine, diagnosed with undifferentiated nasopharyngeal carcinoma, was treated with full-dose cisplatin and concomitant radiotherapy without reporting significant neutropenia. Clozapine may be cautiously administered when full-dose concomitant chemoradiation therapy is required.

e22174 Background: Uncommon breast tumors are often neglected by large clinical trials, even if their incidence is not so low. Methods: We investigated stage, treatment and outcome of 112 patients affected by uncommon breast cancer, out of 2,185 breast cancer patients diagnosed and followed in our Institution from January 1985 to October 2008. Results: Rare subtypes were represented as follows: tubular 2.7% (58 pts), mucinous 1.1% (25 pts), medullary 1% (21 pts), papillary 0.4% (8 pts). Median age at diagnosis was 56.5 years among patients with tubular histotype, 68.9 years for mucinous, 55 and 61.7 years for medullary and papillary, respectively. Stage I tumors were 87.7% among patients with tubular differentiation, 60% for mucinous, 26.3% for medullary and 50% for papillary, (compared to 45.7% in invasive ductal carcinoma: 1,626 pts). Stage II represented 12.3% among patients with tubular carcinoma, 32% for mucinous, 57.9% for medullary and 37.5% for papillary. Surgical option for stage I and stage II was usually conservative surgery (quadrantectomy, lumpectomy) plus local radiotherapy, followed by estrogenic blockade. In stage III radical mastectomy was often performed, followed by hormonal suppression. Median DFS for patients with tubular cancer was 4.1 years, for mucinous 3.7 years, 10.5 and 5.1 years for medullary and papillary, respectively. Median OS for patients with tubular cancer was 4.3 years, whereas for mucinous 4.2 years, for medullary 11 years and 5.3 years for papillary. Conclusions: In our retrospective analysis, uncommon breast tumors are often diagnosed at limited stages, resulting in good prognosis, with standard treatment. Further studies are warranted for a better management of these diseases. No significant financial relationships to disclose.