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Background Malignant pleural mesothelioma (MPM) is an aggressive disease, with few available treatment options. Identification of novel prognostic and predictive biomarkers is a priority. In MPM patients, BRCA-associated protein 1 (BAP1) alterations are detected in about 60% of cases and miR-31 seems to be involved in BAP1 regulation at post-transcriptional level. The aim of this study was to evaluate the interaction between BAP1 and miR-31 in MPM and their prognostic role in MPM. Methods The expression of BAP1 and miR-31 was analyzed in tissues of 55 MPM patients treated with first-line chemotherapy. Overall survival (OS) and progression-free survival (PFS) were assessed by Kaplan-Meier method and Log-rank test was used to investigate differences among subgroups. Multivariate Cox regression analysis was used to evaluate independent predictors of survival. Results In the whole cohort, loss of BAP1 was associated with a significant improvement in OS, but not in PFS. Lower miR-31 levels were detected in epithelioid MPM (e-MPM) compared to the non-epithelioid subtypes and resulted associated with BAP1 loss. By looking at the e-MPM subgroup, loss of BAP1 was not able to predict clinical outcome. Conversely, miR-31 levels were significantly associated with PFS (P=0.028), but not with OS (P=0.059). By combining the two biomarkers, e-MPM patients with BAP1 loss/low miR-31 levels showed a better prognosis compared to the ones with BAP1 retained/high miR-31 levels (median OS 22.6 vs. 17.0 months, P=0.017 and median PFS 8.7 vs. 5.1 months, P=0.020). The BAP1 and miR-31 combination was confirmed at multivariate analysis as an independent prognostic factor for e-MPM patients. Conclusions In this preliminary study, we found that the prognostic stratification of e-MPM patients may be improved by simultaneously assessing of BAP1 status and miR-31 levels. The two-biomarker score is useful to identify a subgroup of e-MPM tumors characterized by BAP1 retained and high miR-31 levels with worse clinical outcome.

Background: In preclinical models, statins showed vaccine adjuvant activities and synergized with PD-1 inhibitors. We analyzed the impact of statin treatment on clinical outcome in thoracic cancer patients treated with PD-1 inhibitors. Methods: A total of 82 malignant pleural mesothelioma (MPM) and 179 advanced non-small cell lung cancer (aNSCLC) patients treated with PD-1 inhibitors as second or further line treatment were examined. Seventy-seven MPM patients treated with standard chemotherapy were analyzed as control cohort. Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were calculated. Results: Among 253 patients with available data, statin use was associated with increased ORR (32% versus 18%, P =.02), PFS (median 6.7 versus 2.9 months, hazard ratio [HR] 0.57, 95% CI 0.39–0.83, P

Introduction The prognostic role of BRCA1 associated protein-1 (BAP1) expression in malignant pleural mesothelioma (MPM) is a matter of debate. We aimed to clarify whether MPM patients with loss of BAP1 expression have better overall survival (OS) compared to BAP1 positive patients. Methods BAP1 immunohistochemical staining of tumor samples from 60 MPM patients treated at our institution with first-line chemotherapy was evaluated. A systematic literature search was also performed. Only cohort studies that investigated BAP1 by immunohistochemistry (IHC) and reported hazard ratio (HR) values for OS obtained through multivariate analysis (or adjusted for histotype) were considered. A dataset comprising 638 MPM patients was added to our cohort and included in the meta-analysis. Results In our cohort, 23 samples (38 %) were BAP1 positive/retained (≥1 %) and 37 samples (62 %) were BAP1 negative/loss. BAP1 loss was associated with epithelioid histotype (p 0.01). Median OS times were 14.8 months (95 % CI: 10.7–29.3) and 18.1 months (95 % CI: 11.2–25.8) for negative and positive BAP1 expression, respectively (p 0.2). At multivariate analysis, again no differences were observed among the two groups (p 0.81). Similarly, the meta-analysis consisting of 698 patients showed no difference in terms of OS according to BAP1 status (HR 1.11; 95 % CI, 0·76-1·61; p 0.60). Conclusions BAP1 expression is not an independent prognostic factor for MPM patients and it should not be considered without taking into account tumor histotype. Future studies should investigate its predictive role in patients treated with new emerging therapies such as immunotherapy.

Objectives In the most of cases, for non-small cell lung cancer (NSCLC) patients who progressed to previous immune checkpoint inhibitors (CKI) administered as first- or as second-line therapy, chemotherapy (CT) remains the only viable options in the absence of “druggable” mutations. We aimed to explore the efficacy of salvage chemotherapy after immunotherapy (SCAI) in advanced NSCLC patients. Materials and Methods We designed a retrospective, multicenter study, involving 20 Italian centers, with the primary objective of describing the clinical outcome of advanced NSCLC patients treated with SCAI at the participating institutions from November 2013 to July 2019. The primary endpoint of the study was represented by overall survival (OS), defined as the time from CT initiation to death. Secondary outcome endpoints of the SCAI (progression free survival, PFS, objective response rate, ORR and toxicity) and explorative biomarkers (lactate dehydrogenase, LDH, and neutrophil-to-lymphocyte ratio, NLR during immunotherapy) were also analyzed. Results In our study population of 342 NSCLC patients, SCAI obtained a median OS of 6.8 months (95 % confidence interval, CI 5.5–8.1), median PFS of 4.1 months (95 % CI 3.4−4.8) and ORR of 22.8 %. A “Post-CKI score” was constructed by combining significant predictors of OS at the multivariate analyses (sex, ECOG PS, disease control with prior immunotherapy), Harrell’C was 0.65, (95 % CI:0.59−0.71). Conclusions Despite the late-line settings, our findings support the hypothesis that previous immunotherapy might increase the sensitivity of the tumor to the subsequent chemotherapy. The “Post-CKI score” was clinically effective in successfully discriminating three distinct prognostic subgroups of patients after the failure of CKI, representing a possibly useful tool for the tailored decision-making process of advanced treatment-line settings in NSCLC.

Lartruvo® (olaratumab) is a fully human immunoglobulin G subclass 1 (IgG1) monoclonal antibody that inhibits platelet-derived growth factor receptor alpha (PDGFRα). The antitumor activity of olaratumab has been tested in vitro and in vivo, and inhibition of tumor growth has been observed in cancer cell lines, including glioblastoma and leiomyosarcoma cells. It represents the first-in-class antibody to be approved by regulatory authorities for the treatment of advanced soft-tissue sarcomas (STSs) in combination with doxorubicin, based on the results of the Phase Ib/II trial by Tap et al. The median progression-free survival (PFS), which was the primary end point of the study, was improved for patients treated with olaratumab plus doxorubicin compared to those treated with doxorubicin monotherapy (6.6 vs 4.1 months, respectively; HR 0.672, 95% CI 0.442–1.021, p=0.0615). Moreover, final analysis of overall survival (OS) showed a median OS of 26.5 months with olaratumab plus doxorubicin vs 14.7 months with doxorubicin, with a gain of 11.8 months (HR 0.46, 95% CI 0.30–0.71, p=0.0003). In October 2016, olaratumab was admitted in the Accelerated Approval Program by the US Food and Drug Administration (FDA) for use in combination with doxorubicin for the treatment of adult patients with STSs. In November 2016, the European Medicines Agency (EMA) granted conditional approval for olaratumab in the same indication under its Accelerated Assessment Program. A double-blind, placebo-controlled, randomized Phase III study (ANNOUNCE trial, NCT02451943) is being performed in order to confirm the survival advantage of olaratumab and to provide definitive drug confirmation by regulators. The study is ongoing, but enrollment is closed. The purpose of this review was to evaluate the rationale of olaratumab in the treatment of advanced STSs and its emerging role in clinical practice.

Hyponatremia is the most common electrolyte disorder in lung cancer patients. This condition may be related to many causes including incidental medications, concurrent diseases and side effects of antineoplastic treatments or the disease itself. Although not frequently life-threatening, it is usually associated with prolonged hospitalization, delays in scheduled chemotherapy, worsening of patient performance status and quality of life and may also negatively affect treatment response and survival. Most of the available data focus on thoracic tumors, especially small-cell lung cancer (SCLC), where hyponatremia is frequently related to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Few studies specifically focus on non-small cell lung cancer (NSCLC) patients. Hyponatremia treatment needs to be personalized based on severity and duration of sodium serum reduction, extracellular fluid volume and etiology. However, literature data highlight the importance of early correction of the serum concentration levels. To achieve this the main options are fluid restriction, hypertonic saline, loop diuretics, isotonic saline, tolvaptan and urea. The aim of this review is to analyze the role of hyponatremia in lung cancer patients, evaluating causes, diagnosis, management and clinical implications.

Introduction Biliary tract cancers (BTC) include both gallbladder cancer and cholangiocarcinoma, both of which have a poor prognosis. The aim of our study was to evaluate the main clinical prognostic factors in this setting and to assess their impact on overall survival (OS). Methods We retrospectively analyzed data collected on 64 patients with BTC who underwent surgery with radical intent at our institution. OS was estimated using the Kaplan–Meier method. The Cox regression model was used to perform univariate and multivariate analyses. Results Preoperative hyponatremia was found to be an independent prognostic factor that correlated negatively with prognosis, with hyponatremic patients having a poor OS compared to the group of patients with normal serum sodium levels (9.44 vs. 15.47 months; p = 0.0215). In addition, high preoperative values for carbohydrate antigen 19-9 (Ca19.9), a tumor marker for some gastrointestinal cancers, and lactate dehydrogenase (LDH) were found to be prognostic factors for a significant reduction in OS (Ca19-9: 7.14 vs. 24.22 months, p = 0.0088; LDH: 1.70 vs. 15.47 months, p = 0.0384). Conclusion Identification of these prognostic factors may support strategies to identify, in clinical practice, those subgroups of patients with a favorable or unfavorable prognosis before surgical treatment and, therefore, to guide therapeutic choices. In particular, to our knowledge, this is the first report of the prognostic role of serum sodium level in BTC. Early detection and careful monitoring of hyponatremia and supportive therapy can help to improve the treatment and prognosis of BTC.

Previous works linked low sodium concentration with mortality risk in cancer. We aimed at weighing the prognostic impact of hyponatremia in all consecutive patients with metastatic solid tumors admitted in a two-years period at our medical oncology department. Patients were included in two cohorts based on serum sodium concentration on admission. A total of 1025 patients were included, of whom 279 (27.2%) were found to be hyponatremic. The highest prevalence of hyponatremia was observed in biliary tract (51%), prostate (45%) and small-cell lung cancer (38.9%). With a median follow-up of 26.9 months, median OS was 2 months and 13.2 months for the hyponatremia versus control cohort, respectively (HR, 2.65; P P

Hyponatremia and bone metastasis (BMs) are known as negative prognostic factors in patients affected by metastatic non-small cell lung cancer (NSCLC). Hyponatremia is associated with higher risk of osteoporosis and bone fracture, but no data are available about the relationship between hyponatremia and bone metastasis. This study aims to analyze the prognostic impact of hyponatremia in NSCLC patients with bone metastases. We retrospectively collected data about advanced NSCLC patients. Survival curves were estimated using Kaplan–Meier method, and comparisons were made using chi-square test. Six hundred forty-seven patients were enrolled into the study. BMs were present in 264 patients (41%) at diagnosis, while hyponatremia appeared in 237 (37%) patients during the first-line treatment. Patients without BMs had a median overall survival (mOS) of 15.9 months (95% CI 14.1–17.9) versus 11.4 months (95% CI 9.4–13.4) for patients with BMs (p = 0.001). Eunatremic patients had a better outcome (mOS 16.3 months, 95% CI 14.6–18.0 vs 10.3 months, 95% I 7.6–12.8, p = 0.003). Considering the two variables, patients with BMs and hyponatremia had a mOS of 10.1 months (95% CI 4.3–15.9), patients with hyponatremia without BMs 11.9 months (95% CI 11.4–12.4), while mOS was 13.1 months (95% CI 12.0–14.2) for eunatremic patients with BMs versus 17.1 months (95% CI 15.2–19.1) in eunatremic patients without BMs (p = 0.0020). Hyponatremic patients developed metachronous BMs significantly earlier (3.73 vs 5.76 months, p = 0.0187). Our study showed that hyponatremia is an important prognostic factor and it should be necessarily considered to enhance the management of NSCLC patients with BMs.

Introduction: Since December 2019, coronavirus disease 2019 (COVID-19) has spread to every country, taking on pandemic proportions in few months. Physicians were asked to redefine ordinary hospital organization, reprogramming clinically differentiable activities. Materials and Methods: During the COVID pandemic our Institution was supported by a call center (CC, named TOPS s.r.l.) to make a triage for cancer patients (pts) scheduled for follow-up in our outpatient clinics: C1 (dedicated to female tumors), C2 (for gastrointestinal, urogenital,and thoracic tumors) and D1 (for tumors in over 5 years’ follow-up). We report preliminary data referred to the period 7th April-24th May, 2020. The activity was divided into two phases (F): April (F1) and May (F2). In F2 pts were interviewed about their preferred visit modality. Physical examination was not postponed in case of clinical needs and first visits. Moreover, CC asked about programmed radiologic examinations and collected patients’ feedback about the service. Results: A total of 587 pts have been contacted: 341 during F1 and 246 in F2. 317/341 (93%) of the contacts in F1 were successful. A gender-stratified analysis showed a majority of patients were female (72.4%). The CC was able to get in touch with 42.8% C1 pts, 34.6% C2 pts, and 22.6% D1 pts. During F2 246 pts (96.5%) of 255 planned were efficiently contacted; female maintained the predominance (74.5%). 170 pts (69.1%) were scheduled in C1, 53 pts (21.5%) in C2, and 23 pts (9.4%) in D1. During F2, among the options provided 97 pts (39.4%) selected the phone call, 142 pts (57.7%) decided for video chat (whatsapp), and 2 (0.8%) for video conference with a dedicated platform (google.meet). Only 5 pts (2.1%) expressed their intention to come to the hospital for examination. In 69.1% of cases (170 pts) the programmed radiologic examinations were confirmed during the pandemic. According to some favorable reports, the service was helpful in preserving continuum of care and preventing cancer pts from being left aside in the emergency. Conclusions: This study show that cancer patients do appreciate technology-mediated follow-up visits, mainly including video chat (whatsapp), and therefore we should take this into consideration. Furthermore, a dedicated CC may be helpful to organize follow-up activities during COVID-19 and to strengthen the doctor-patient relationship in such a critical moment. Citation Format: Mariangela Torniai, Giulia Marcantognini, Ilaria Fiordoliva, Giulia Mentrasti, Veronica Agostinelli, Alessandra Pagliacci, Rossana Berardi, Michele Caporossi. Technology-mediated communication with patients is a challenge for oncologists in the digital and pandemic era… and the winner is WhatsApp! [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-039.

Background: The coronavirus disease 2019 (COVID-19) outbreak has been declared a global pandemic, and Italy is one of the first and most heavily affected countries. Cancer patients are a population at higher risk from COVID-19 both for intrinsic fragility bound to their underlying disease and oncologic treatment delay. The aim of our survey was to investigate how cancer patients perceived their health condition, their clinical management, and information communication by their medical oncologists during the pandemic. Methods: Between 15th April and 1st May, 2020, a survey was submitted to cancer patients under treatment at hospitals of Marche Region that had been invested by the pandemic. It consisted of questions regarding the perception of personal safety, continuity of cancer care, and information quality provided by the Oncology Department and individual psychological distress. Results: A total of 661 patients participated in the survey; 60.2% were female and 40.4% were aged between 46 and 65. Almost all of the attendees (97.7%) stated that the Oncologic Department complied with the appropriate safety standards, and 78% were reassured about their concerns during the medical interview, but 41% were worried of being at higher risk of infection upon entry into the Oncology Department and 53.3% felt at greater risk of infection because of chemotherapy treatment in general. The majority of the participants (62.2%) felt that postponing cancer treatment could reduce its efficacy; however, 80% declared they did not feel abandoned at the time of treatment delay. 79.4% of the attendees felt more worried for their underlying disease in this emergency situation, but the mood worsened for only 34.2% of the participants. Conclusions: Our survey reveals that Oncology Departments have been considered worthy of the emergency in terms of safety standards and care management by cancer patients. However, the majority of attendees perceived the mutual negative influence between their underlying oncologic disease and risk of Sars-CoV-2 infection and manifested concerns about their health condition, highlighting the need for special measures to ensure safe continuity of care. Citation Format: Filippo Merloni, Nicoletta Ranallo, Lucia Bastianelli, Francesca Vitarelli, Luca Cantini, Zelmira Ballatore, Giulia Ricci, Ilaria Fiordoliva, Laura Tassone, Benedetta Ferretti, Paolo Alessandroni, Michela Del Prete, Silvia Chiorrini, Safi Mobin, Rita Ficarelli, Giovanni Benedetti, Luca Faloppi, Rosa Stoico, Rossana Berardi. COVID-19 pandemic: Patients’ perspective during cancer treatment [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-052.

Background: The coronavirus disease 2019 (COVID-19) outbreak has been declared global pandemic and Italy is one of the first and heavily affected countries Cancer patients are a population at higher risk from COVID-19 both for intrinsic fragility bound to their underlying disease and oncologic treatment delay Aim of our survey was to investigate how cancer patients perceived their health condition, their clinical management and information communication by their medical oncologists during the pandemic Methods: Between 15th April and 1st May 2020 a survey was submitted to cancer patients under treatment at hospitals of Marche Region which had been invested by the pandemic It consisted of questions regarding the perception of personal safety, continuity of cancer care and information quality provided by the Oncology Department and individual psychological distress Results: A total of 661 patients participated in the survey;60 2% was female and 40 4% was aged between 46 and 65 Almost all of the attendees (97 7%) stated that the Oncologic Department complied with the appropriate safety standards and 78% was reassured about their concerns during the medical interview, but 41% was worried of being at higher risk of infection upon entry into the Oncology Department and 53 3% felt being at greater risk of infection because of chemotherapy treatment in general The majority of the participants (62 2%) felt that postponing cancer treatment could reduce its efficacy, however 80% declared they did not feel abandoned at the time of treatment delay 79 4% of the attendees felt more worried for their underlying disease in this emergency situation, but the mood worsened only for 34 2% of the participants Conclusions: Our survey reveals that Oncology Departments have been considered worthy of the emergency in terms of safety standards and care management by cancer patients However, the majority of attendees perceived the mutual negative influence between their underlying oncologic disease and risk of Sars-CoV-2 infection and manifested concerns about their health condition highlighting the need for special measures to ensure safe continuity of care Legal entity responsible for the study: Universita Politecnica delle Marche- AOU Ospedali Riuniti di Ancona Funding: Has not received any funding Disclosure: All authors have declared no conflicts of interest

Background Aim of this meta-analysis was to determine the relative risk (RR) of electrolyte disorders (EDs) in advanced non-small cell lung cancer (aNSCLC) patients treated with immune check-point inhibitors (ICIs). Methods We searched for phase II/III randomized controlled trials (RCTs) comparing ICIs (alone or combined with chemotherapy) with standard chemotherapy in aNSCLC. Summary incidence and RR were calculated. Results Six RCTs with data on all-grade hyponatremia were identified (n = 3257). The incidence was 8.7 % in the study group and 4.9 % in the control group (RR 1.78, 95 %CI 1.12–2.80). Looking at all-grade hypokalemia, 7 RCTs were included (n = 4119). Incidence was 10.4 % in ICIs-treated patients and 5.9 % in the control arms (RR 1.62, 95 % CI 1.30–2.02). Conclusions Treatment with ICIs in aNSCLC is associated with a significant increased risk of hyponatremia and hypokalemia compared to chemotherapy. Monitoring of electrolyte levels should be emphasized in this setting.

3074 Background: After progression to standard chemotherapy, only a small proportion of malignant pleural mesothelioma (MPM) and non-small cell lung cancer (NSCLC) patients (pts) benefit from anti-programmed cell death (PD-1) treatment. Combination strategies might improve response. In pre-clinical models, statins showed vaccine adjuvant activities and synergized with anti-PD1 agents. In this multi-center study, we evaluated the impact of baseline statin treatment in MPM and NSCLC pts. Methods: We separately examined MPM and NSCLC pts treated with anti-PD1 monotherapy after progression to standard chemotherapy at two European academic institutions. As control cohort, MPM pts treated with first-line chemotherapy were also examined. Pts receiving statins at start of treatment were compared with those who did not. Objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were analyzed. Results: A total of 287 patients were examined. Twenty-seven out of 80 (34%) MPM and 36 out of 130 (20%) NSCLC pts received statins at start of anti-PD1 treatment. The most common statins were simvastatin, atorvastatin and rosuvastatin. In MPM pts, statin use was associated with improved ORR (22% versus 5%, P = 0.05), longer PFS (median 6.7 versus 2.4 months, hazard ratio (HR) 0.42, 95% confidence interval (CI) 0.23–0.77, P < 0.01), and longer OS (median not reached versus 6.0 months, HR 0.43, 95% CI 0.21–0.85, P = 0.01). In NSCLC pts, statin use was associated with improved ORR (40% versus 22%, P = 0.04), longer PFS (median 7.8 versus 3.6 months, HR 0.59, 95% CI 0.37–0.97.2, P = 0.03) but similar OS (median 13.1 versus 10.1 months, HR 0.79, 95% CI 0.49–1.28, P = 0.30). At multivariate analyses, after adjusting for ECOG performance status (PS) and histological subtype, the impact of statins remained significant for ORR, PFS and OS in MPM and for PFS in NSCLC. Conversely, no association between statin use and outcomes was found in 77 MPM pts treated with first-line chemotherapy. Conclusions: This study shows that statin use at start of anti-PD1 treatment improves response to anti-PD1 agents in MPM and NSCLC pts who progressed to standard chemotherapy in routine clinical practice. This association could not be found in MPM pts treated with first-line chemotherapy, thus suggesting a synergy between statins and anti-PD1 agents. Prospective studies are needed to confirm whether the combination of statin and anti-PD1 therapy could improve outcome in pts with poorly immunogenic thoracic malignancies.

Purpose: Hyponatremia is the most common electrolyte disorder in hospitalized patients, and it might be an indicator of poor prognosis and might have negative effects on hospitalization length and quality of life in non-malignant as well as in malignant diseases. The aim of this study is to determine the impact of hyponatremia on the length and on the cost of hospitalization as well as on outcome in cancer patients. Methods: The present study includes 105 consecutive cancer patients hospitalized at our institution from June 2013 to December 2013. Data regarding age, sex, staging, histology, chemotherapy, and serum sodium levels at admission, during hospitalization, and at discharge were recorded and statistically analyzed. Impact of hyponatremia on length and cost of hospitalization and on outcome was evaluated. Results: A significant difference in overall survival since the date of admission was observed between eunatremic and hyponatremic patients (p = 0.0255). A statistically significant correlation was also found between the length of stay and the detection of hyponatremia. At multivariate analysis, hyponatremia at admission, severity of hyponatremia, and stage of disease resulted independent prognostic factors. Furthermore, a patient with moderate or severe hyponatremia cost, in rate terms, 128 and 299% more than a normonatremic patient, respectively. Conclusions: The occurrence of hyponatremia at the admission or during the hospitalization may represent a significant factor influencing the outcome and the length of hospitalization. Acting effective and timely on the normalization of sodium levels might have a positive effect on prognosis in this setting of patients, as well as on the length of stay in hospital, thus potentially resulting in savings.

Hyponatremia is a common electrolyte disorder in cancer patients. It may be related to cancer, to anti-cancer therapy or to other concomitant treatments. In this setting hyponatremia is often caused by the syndrome of inappropriate anti-diuretic hormone secretion, which is due to the ectopic production of antidiuretic hormone (vasopressin), to extracellular fluid depletion, to renal toxicity caused by chemotherapy or to other underlying conditions. Recent studies suggested that hyponatremia might be considered a negative prognostic factor for cancer patients therefore its early detection, monitoring and management might improve the patient's outcome. Treatment of hyponatremia depends on patient's symptoms severity, onset timing and extracellular volume status. In this review we summarize the main causes of hyponatremia in cancer patients and its management, including the available treatment options.

Background Hyponatraemia has been reported with targeted therapies in cancer patients. Aim of the study was to perform an up-to-date meta-analysis in order to determine the incidence and relative risk (RR) in cancer patients treated with these agents. Materials and Methods The scientific literature regarding hyponatraemia was extensively reviewed using MEDLINE, PubMed, Embase and Cochrane databases. Eligible studies were selected according to PRISMA statement. Summary incidence, RR, and 95% Confidence Intervals were calculated using random-effects or fixed-effects models based on the heterogeneity of selected studies. Results 4803 potentially relevant trials were identified: of them, 13 randomized phase III studies were included in this meta-analysis. 6670 patients treated with 8 targeted agents were included: 2574 patients had hepatocellular carcinoma, whilst 4096 had other malignancies. The highest incidences of all-grade hyponatraemia were observed with the combination of brivanib and cetuximab (63.4) and pazopanib (31.7), while the lowest incidence was reported by afatinib (1.7). The highest incidence of high-grade hyponatraemia was reported by cetuximab (34.8), while the lowest incidences were reported by gefitinib (1.0). Summary RR of developing all-grade and high-grade hyponatraemia with targeted agents was 1.36 and 1.52, respectively. The highest RRs of all-grade and high-grade hyponatraemia were associated with brivanib (6.5 and 5.2, respectively). Grouping by drug category, the RR of high-grade hyponatraemia with angiogenesis inhibitors was 2.69 compared to anti-Epidermal Growth Factor Receptors agents (1.12). Conclusion Treatment with biological therapy in cancer patients is associated with a significant increased risk of hyponatraemia, therefore frequent clinical monitoring should be emphasized when managing targeted agents.

Aims and background Although worldwide use of asbestos has decreased, the incidence of malignant pleural mesothelioma (MPM) is expected to increase over the next few decades. A number of scoring systems has been proposed to assess clinicopathologic features and to predict the prognosis. We assessed the relationship between patients’ features and disease evolution in order to choose the best treatment able to prolong overall survival (OS) and progression-free survival (PFS). Methods We retrospectively analyzed patients with locally advanced or metastatic MPM, treated at the Department of Medical Oncology, Università Politecnica Marche, Italy, from January 2003 to September 2013. Data on age, sex, smoking history, asbestos exposure, performance status, tumor stage, histology, type of treatment, and routine laboratory tests including complete blood count panel, date of death, or censored status were collected. The OS and PFS were estimated using Kaplan-Meier method and Cox analysis was performed to analyze the prognostic relevance of clinical parameters. Results We enrolled a total of 62 patients. Univariate analysis showed that histologic type, performance status, response to first-line therapy, pretreatment hemoglobin levels, and plasmatic Ca125 were significant prognostic factors. Conversely, no significant correlation was found between age, sex, smoking history, reported exposure to asbestos, stages at diagnosis, treatments, and OS and PFS. Conclusions Our results showed that anemia and increased Ca125 might be considered negative prognostic parameters in MPM patients and confirmed the prognostic role of histotype, performance status, and response to first-line chemotherapy.

Purpose: Hyponatraemia is one of the most common tumour-related electrolyte disorders. Several clinical, histological and serum factors have been found to influence prognosis, but, to date, there are no studies focusing on the prognostic role of hyponatraemia in mesothelioma. The aim of this study was to assess the prognostic role of hyponatraemia in malignant pleural mesothelioma.Methods: We analysed 62 consecutive patients with histologically or cytologically proven advanced malignant pleural mesothelioma undergoing chemotherapy at our institution between January 2003 and September 2013. Results: All patients received a first-line pemetrexed-based chemotherapy. A second-line chemotherapy was administered to 29 patients.The onset of hyponatraemia (serum sodium