BackgroundColorectal cancer represents the most common malignancy of the gastrointestinal tract. Owing to differences in dietary habits and lifestyle, this neoplasm is more common in industrialized countries than in developing ones. Evidence from a wide range of sources supports the assumption that the link between diet and colorectal cancer may be due to an imbalance of the intestinal microflora.DiscussionProbiotic bacteria are live microorganisms that, when administered in adequate amounts, confer a healthy benefit on the host, and they have been investigated for their protective anti-tumor effects. In vivo and molecular studies have displayed encouraging findings that support a role of probiotics in colorectal cancer prevention.SummarySeveral mechanisms could explain the preventive action of probiotics against colorectal cancer onset. They include: alteration of the intestinal microflora; inactivation of cancerogenic compounds; competition with putrefactive and pathogenic microbiota; improvement of the host’s immune response; anti-proliferative effects via regulation of apoptosis and cell differentiation; fermentation of undigested food; inhibition of tyrosine kinase signaling pathways.

Endometriosis is a benign gynecologic condition affecting up to one woman out of ten of reproductive age. It is defined by the presence of endometrial-like tissue in localizations outside of the uterine cavity. It often causes symptoms such as chronic pain, most frequently associated with the menstrual cycle, and infertility, but may also be oligo-or asymptomatic. There is evidence that some ovarian carcinoma (OC) histotypes, mainly the ovarian clear cell (OCCC) and endometrioid (EnOC) carcinoma, may arise from endometriosis. The most frequent genomic alterations in these carcinomas are mutations in the AT-rich interacting domain containing protein 1A (ARID1A) gene, a subunit of the SWI/SNF chromatin remodeling complex, and alterations in the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway, which frequently co-occur. In ARID1A deficient cancers preclinical experimental data suggest different targetable mechanisms including epigenetic regulation, cell cycle, genomic instability, the PI3K/AKT/mTOR pathway, inflammatory pathways, immune modulation, or metabolic alterations as potential precision oncology approaches. Most of these strategies are relying on the concept of synthetic lethality in which tumors deficient in ARID1A are more sensitive to the different compounds. Some of these approaches are currently being or have recently been investigated in early clinical trials. The remarkably frequent occurrence of these mutations in endometriosisassociated ovarian cancer, the occurrence in a relatively young population, and the high proportion of platinumresistant disease certainly warrants further investigation of precision oncology opportunities in this population. Furthermore, advanced knowledge about oncogenic mutations involved in endometriosis-associated ovarian carcinomas may be potentially useful for early cancer detection. However, this approach may be complicated by the frequent occurrence of somatic mutations in benign endometriotic tissue as recent studies suggest. In this narrative review of the current literature, we will discuss the data available on endometriosis-associated ovarian carcinoma, with special emphasis on epidemiology, diagnosis and molecular changes that could have therapeutic implications and clinical applicability in the future.

Introduction Baseline neutrophil-to-lymphocyte ratio (NLR) has been repeatedly reported as a significant prognostic factor in advanced cancer patients. We explored whether changes in NLR may predict outcome of advanced cancer patients enrolled into phase 1 trials and treated with PD-1/PD-L1 inhibitors. Patients and Methods Advanced cancer patients enrolled into phase 1 trials between September 2013 and May 2016 and treated with anti-PD-1/PD-L1 agents were included in this retrospective study. NLR was calculated at baseline and after 2 cycles of treatment. Royal Marsden Hospital (RMH) prognostic score and Eastern Cooperative Group (ECOG) performance status (PS) were determined at baseline. Kaplan-Meier estimation and Cox regression analyses were used to assess the impact of NLR dynamics on PFS. Results Among the 55 patients eligible, 26 (47%) were treated with anti-PD-L1 monotherapy, 22 (40%) received single agent anti-PD-1, and 7 (13%) were given a tyrosine kinase inhibitor (TKI) plus a PD-1 inhibitor. Neither ECOG PS nor RMH prognostic score was significantly associated with PFS in our cohort, whereas changes in NLR significantly impacted on PFS. Conclusion Changes in the NLR may be a useful predicting factor in advanced cancer patients treated with anti-PD-1/PD-L1 agents. Further prospective trials are needed to verify these findings.

Background Second‐line therapy has consistently demonstrated survival benefit if compared with best supportive care; however, there is limited evidence whether further lines of treatment may improve the prognosis of advanced gastric cancer (AGC) patients. Materials and Methods Starting from a real‐world cohort of 868 AGC patients, we retrospectively analyzed baseline parameters, tumor characteristics, and treatment data of those treated with at least three lines. Categorical features were described through cross‐tables and chi‐square test. We explored the impact of treatment intensity and progression‐free survival (PFS) experienced in previous lines on PFS and overall survival in third‐line by uni‐ and multivariate Cox regression models and described by Kaplan‐Meier estimator plot with log‐rank test. Results Overall, 300 patients were included in the analysis. The most common site of primary tumor was gastric body; 45.3% of cancers had an intestinal histotype, 14% were human epidermal growth receptor 2 positive. In third‐line, 45.7% of patients received a single‐agent chemotherapy, 49.7% a combination regimen. Patients who had experienced a first‐line PFS ≥6.9 months had a better prognosis compared with those who had achieved a shorter one. Consistently, a second‐line PFS ≥3.5 months positively influenced the prognosis. Patients receiving a third‐line combination regimen had better outcomes compared with those treated with a single‐agent chemotherapy. Conclusion Our real‐world study confirms that selected AGC patients may receive third‐line treatment. Longer PFS in previous lines or a more intense third‐line treatment positively influenced prognosis. Further efforts are warranted to define the best therapeutic sequences, and to identify the optimal candidate for treatment beyond second‐line. Implications for Practice The benefit of third‐line treatment to advanced gastric cancer patients is controversial. This study depicts a real scenario of the clinical practice in Italy, confirming that a non‐negligible proportion of patients receive a third‐line therapy. Longer progression‐free survival in previous treatment lines or higher third‐line treatment intensity positively influenced prognosis. Including a large number of real‐world patients, this study provides information on third‐line treatment from the daily clinical practice; moreover, its results help in defining the best therapeutic sequence and offer some hints to select the optimal candidate for treatment beyond second‐line.

Newly diagnosed high grade serous epithelial ovarian cancer (EOC) patients are treated with radical surgery followed by adjuvant platinum and taxane combination chemotherapy. In EOC patients where upfront surgery is contraindicated for medical reasons (e.g., comorbidities or poor performance status), or where complete cytoreduction cannot be achieved, neoadjuvant chemotherapy (NACT) prior to interval debulking surgery (IDS), and adjuvant chemotherapy is an alternative therapeutic option. There is currently a lack of consensus about who are the best candidates to receive NACT, and some authors have even suggested that this approach could be harmful in a subset of patients via promotion of early chemoresistance.Standard and novel imaging techniques together with a better molecular characterization of the disease have the potential to improve selection of patients, but ultimately well designed randomised clinical trials are needed to guide treatment decisions in this setting. The advent of new and effective treatment options (antiangiogenics and PARP inhibitors), now approved for use in the first line and relapse settings has opened the way to clinical trials aiming to investigate these agents as substitute or in addition to chemotherapy in the neoadjuvant setting in molecularly selected EOC patients. Here, we will review the evidence supporting the use of NACT in newly diagnosed EOCs, data highlighting the importance of its use in selected patients, new imaging methodologies and biomarkers that can guide patient selection.