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Background: Colorectal cancer is a worldwide leading cause of death accounting for high-rate mortality. Mutations in the epidermal growth factor receptor and RAS/MAPK pathways, as well as altered methylation genes profiles, have been described as molecular mechanisms promoting and sustaining tumour development and progression. Aberrant methylation is a well-known epigenetic mechanism involved in gene regulation; particularly several genes were reported as hypermethylated in CRC. Recently, it was shown that epigenetic alterations in genes such as neuropeptide y, proenkephalin and Wnt inhibitory factor 1 can be used as promising disease biomarkers. Almost all methods developed for the DNA methylation analysis combined next generation sequencing, conventional qRT-PCR or ddPCR with the prior DNA modification with sodium bisulfite., Methods and Results: We implemented a ddPCR method to assess the methylation status of Wnt inhibitory factor 1 and neuropeptide y using the methylation sensitive restriction enzyme approach that does not impact on DNA quality and guarantees the discrimination of DNA methylation independent of bisulfite conversion., Conclusions: We showed that this method is robust and sensitive also allowing the monitoring of CRC disease progression when applied to circulating free DNA samples from liquid biopsies, proving to be a fast and easy to implement assay to be used for the monitoring of the methylation pattern of clinically relevant target genes., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: About 90% of cholangiocarcinomas are adenocarcinomas with glandular or tubular structures lined by epithelial cells, with no bile production and with a variable degree of differentiation, arising in the background of desmoplastic stroma. The remaining 10% is represented by rarer histological variants of which there is little knowledge regarding the biological behavior, molecular characterization, and sensitivity to the various possible therapies, including molecular-based treatments. Such rare tumors are described only in case reports or small retrospective series because of their exclusion from clinical trials. This national initiative, here presented, aims to address the following knowledge gap: a) how much does histological diversity translate into clinical manifestation variety? b) are those chemotherapy regimens, recommended for conventional biliary tract cancers, potentially active in rare variants?Therefore, epidemiological, pathological, and clinical characterization of series of rare biliary histotypes/variants, for which therapeutic and follow-up data are available, will be collected., Methods: An Italian task force on rare tumors of the biliary tract (IRaBiCa) has been created, whose initiative is a multicenter retrospective study involving 34 Italian cancer centers.Clinical data from approximately 100 patients will be collected and analyzed. Continuous variables will be presented as median ± standard deviation, while categorical variables will be expressed in terms of frequency. Kaplan-Maier analyses will be used to compare disease free, progression free and overall survival, according to the different histotypes., Conclusions: We expect to gather novel data on rare histotypes of biliary tract cancer that will be useful to support their molecular and immunological characterization., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: LR reports consulting fees from AstraZeneca, Basilea, Bayer, BMS, Eisai, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Jazz Pharmaceuticals, Lilly, MSD, Nerviano Medical Sciences, Roche, Servier, Taiho Oncology, Zymeworks; lecture fees from AstraZeneca, Bayer, Eisai, Gilead, Incyte, Ipsen, Merck Serono, Roche, Sanofi, Servier; travel expenses from AstraZeneca; research grants (to Institution) from Agios, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, Ipsen, Lilly, MSD, Nerviano Medical Sciences, Roche, Zymeworks.NS reports consulting fees from MSD, Bristol Myers Squibb, GSK.MN:Travel expenses from AstraZeneca, speaker honorarium from Accademia della Medicina and Incyte; honoraria from Sandoz, Medpoint SRL, Incyte and Servier for editorial collaboration. Consultant honoraria from EMD Serono, Basilea Pharmaceutica, Incyte, MSD Italia, Servier, Astrazeneca and TaihoAll other authors have nothing to declare

The introduction of inhibitors of poly-(ADP-ribose) polymerase (PARP) for the treatment of women with epithelial ovarian cancers (EOC) has radically changed the treatment in maintenance setting after responding to first- and second-line chemotherapy. The aim of this paper was to assess the pharmacological costs of PARP inhibitors (olaparib, niraparib, rucaparib and veliparib) in maintenance treatment after responding to first-line chemotherapy in EOC. Incremental cost-effectiveness ratio (ICER) was calculated as the ratio between the difference of the costs in the intervention and in the control groups (pharmacy costs) and the difference between the effect in the intervention and in the control groups (progression-free survival (PFS)). We have considered the pivotal phase III randomized controlled trials (RCTs). Three different populations were considered: the overall population, patients with germline BRCA mutation (gBRCA) and homologous recombination deficiency (HRD) patients non-gBRCA mutation. Three thousand four hundred and twenty patients and 1209 patients were considered in maintenance treatment after responding to first- and second-line chemotherapy in EOC, respectively. At the actual price, the treatment with PARP inhibitors is not cost-effective in maintenance treatment after responding to first-line and second-line chemotherapy in EOC. A reduction in pharmacological costs is mandatory.

Background: According to the WHO, detainees attempt suicide ten times more than the general population., Aims: To investigate the impact of migration trauma on Suicidal and Self-Harm Behaviours (SSHB) of migrants in jail and to explore how substance use and other psychiatric features affect this relationship., Methods: Prospective cohort study, conducted at the 'Sant'Anna' jail in Modena (Italy) between February 2017 and September 2019. Socio-demographic, psychiatric features and records of previous SSHB were collected. Experience of migration-related trauma was assessed with the LiMEs (List of Migration Experiences) checklist. Participants were followed-up for the occurrence of further SSHB. Survival analysis was performed and Cox's Hazard Ratios (HR) were used as a measure of association of comparisons., Results: Amongst the 112 subjects (96% male, median age 33), the prevalence of any mental disorder was 26% and of substance abuse 59%. History of SSHB was present in 36% of the sample. Median follow-up time was 80 days. During follow-up, 11 events were observed (of which three were suicide attempts). Cumulative survival probability was 85%. Having experienced trauma related to war and violence was significantly associated with SSHB, HR: 7.05. No SSHB were recorded amongst subjects without substance abuse., Conclusions: Migrants in custody who experienced trauma in the post-migration period, attempt SSHB seven times more frequently than those without traumas at any time. War trauma and post-migration trauma due to exposure to violence seem to be more strongly associated with SSHB, also controlling for psychiatric diagnosis, ongoing psychopharmacological therapy and substance abuse. Further research and possible intervention programs should focus on addressing post-migration living-difficulties.

Background: Due to the relative rarity of small bowel adenocarcinoma (SBA), prospective trials, helping to guide therapeutic decisions, are lacking and the optimal therapy for advanced SBA is unknown. The role of targeted agents, such as anti-epidermal growth factor receptor (EGFR) and anti-vascular endothelial growth factor (VEGF), is unknown., Patients and Methods: This is a retrospective multicenter observational study that included patients with metastatic SBA treated with anti-EGFR antibodies (cetuximab or panitumumab) ± chemotherapy in the first (I) or second (II) line., Results: Thirteen patients with metastatic SBA, recruited from 5 Italian referral institutions, were included in the present retrospective analysis. All patients received anti-EGFR inhibitors as a single agent or in association with chemotherapy. More common G2 treatment-related side effects were skin reaction (8 patients, 53.8%), hypomagnesemia (6 patients, 46.2%), and diarrhea (8 patients, 61.5%). Grade 3 diarrhea was observed in only 1 patient. Conjunctivitis was not reported in any patients. Grade 4 toxicity was not reported. In the overall population, median progression-free survival was 5.526 months (95% confidence interval [CI]: 3.684-12.467). Median overall survival was 15.86 months (95% CI: 14.43-24.30). Complete response was observed in 15% of patients, partial response in 39% of patients, stable disease in 23% of patients, and progression disease in 15% of patients., Conclusions: In this retrospective analysis, anti-EGFR inhibitors showed to be a suitable addendum to chemotherapy in the I and II line, with an excellent tolerance and safety profile both in I and II line., Competing Interests: Declaration of Conflicting Interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Introduction: Exocrine pancreatic cancers include common type pancreatic ductal adenocarcinoma and cystic neoplasms, which account for 85% and 10% of cases, respectively. The remaining 5% are rare histotypes, comprising adenosquamous carcinoma, acinar cell carcinoma, signet ring cell carcinoma, medullary carcinoma, pancreatoblastoma, hepatoid carcinoma, undifferentiated carcinoma and its variant with osteoclast-like giant cells, solid pseudopapillary carcinoma, and carcinosarcoma. Due to their low incidence, little knowledge is available on their clinical and molecular features as well as on treatment choices. The national initiative presented here aims at the molecular characterization of series of rare histotypes for which therapeutic and follow-up data are available., Methods: A nationwide Italian Rare Pancreatic Cancer (IRaPaCa) task force whose first initiative is a multicentric retrospective study involving 21 Italian cancer centers to retrieve histologic material and clinical and treatment data of at least 100 patients with rare exocrine pancreatic cancers has been created. After histologic revision by a panel of expert pathologists, DNA and RNA from paraffin tissues will be investigated by next-generation sequencing using molecular pathway-oriented and immune-oriented mutational and expression profiling panels constructed availing of the information from the International Cancer Genome Consortium. Bioinformatic analysis of data will drive validation studies by immunohistochemistry and in situ hybridization, as well as nanostring assays., Conclusions: We expect to gather novel data on rare pancreatic cancer types that will be useful to inform the design of therapeutic choices.

Introduction: Although sorafenib is the upfront standard of care for advanced hepatocellular carcinoma (HCC), molecular predictors of efficacy have not been identified yet. In the ALICE-1 study, rs2010963 of VEGF-A and VEGF-C proved to be independent predictive factors for progression-free survival (PFS) and overall survival (OS) in multivariate analysis. The ALICE-1 study results were confirmed in the ALICE-2 study, in which VEGF and VEGFR SNPs were analyzed. In the ePHAS study we analyzed the SNPs of eNOS. In univariate analysis, patients homozygous for an eNOS haplotype (HT1: T-4b at eNOS-786/eNOS VNTR) had significantly shorter median PFS and OS than those with other haplotypes. These data were confirmed in the validation set., Methods: This nonpharmacological, interventional, prospective multicenter study aims to determine whether eNOS, HIF-1, VEGF, Ang2 and VEGFR polymorphisms play a role in predicting the objective response rate, PFS, and OS of advanced HCC patients treated with sorafenib. The study will involve 160 advanced HCC patients with Child-Pugh class A disease. The primary aim is to validate the prognostic or predictive roles of eNOS, Ang2, HIF-1, VEGF and VEGFR polymorphisms in relation to the clinical outcome (PFS) of HCC patients treated with sorafenib., Conclusions: Overall, our data may suggest that polymorphism analysis of the VEGF, VEGFR-2, HIF and eNOS genes can identify HCC patients who are more likely to benefit from sorafenib.

Cancer care involves many ethical issues. The need for more patient-centered healthcare together with the improved empowerment of every person diagnosed with cancer have been transposed by the Italian Association of Medical Oncology (AIOM) and eventually translated in the Ragusa statement. This position paper describes the philosophy that lies beneath this document and its fundamental principles.

The combination of erlotinib and gemcitabine is a recognized option for patients with metastatic pancreatic cancer whose common adverse events such as skin rash, diarrhea, or fatigue are usually easily manageable. Interstitial lung disease (ILD) is a life-threatening toxicity reported in patients with non-small-cell lung cancers treated with epidermal growth factor receptor-tyrosine kinase inhibitors or gemcitabine. This side effect is extremely rare in patients with pancreatic cancer. We report fatal treatment-related ILD that occurred in a 67-year-old patient with metastatic pancreatic cancer. Risk factors and pathophysiology of ILD need further investigation but caution is highly recommended for patients with an underlying pulmonary disease when using erlotinib in monotherapy or combination therapy.

The adoption and implementation of information technology are dramatically remodeling healthcare services all over the world, resulting in an unstoppable and sometimes overwhelming process. After the introduction of the main elements of electronic health records and a description of what every cancer-care professional should be familiar with, we present a narrative review focusing on the current use of computerized clinical information and decision systems in oncology practice. Following a detailed analysis of the many coveted goals that oncologists have reached while embracing informatics progress, the authors suggest how to overcome the main obstacles for a complete physicians' engagement and for a full information technology adoption, and try to forecast what the future holds.