A. Diana

Pancreatic neuroendocrine tumors: Nosography, management and treatment.

Pancreatic neuroendocrine tumors (pNETs) represent about 7% of all NETs, 8.7% of gastroenteropancreatic NETs (GEP-NETs) and 1-2% of all pancreatic neoplasms. In the last two decades, the increased diagnosis of pNETs has generated great interest and the development of different classifications, grading and staging systems. Recently, several trials were performed in order to improve the knowledge of biomarkers and imaging and to provide an early diagnosis, but their role is still under debate. Nowadays, surgery represents the only curative approach for pNETs. Approximately 90% of pNETs are silent and non-functional; therefore, most patients are diagnosed in late stage and present metastatic (60%) or locally unresectable advanced disease (21%) with a poor prognosis. Not many therapeutic options are available for pNETs, with different treatments for G1-G2 and G3 tumors, because these diseases are still rare and trials are made up of few series of patients. At present, medical treatments is controversial. On these bases, we believe that a multidisciplinary team composed of surgeons, oncologists, endocrinologists, radiation oncologists, radiologists, pathologists and medicals nuclear is required. This paper presents a review of present state-of-the-art in the field of pNETs.

Neutrophil to lymphocyte ratio (NLR) for prediction of distant metastasis-free survival (DMFS) in early breast cancer: a propensity score-matched analysis

Objective To assess the correlation between presurgery neutrophil to lymphocyte ratio (NLR) and distant metastasis-free survival (DMFS) in patients with early breast cancer. Design Retrospective analysis. Participants 300 Caucasian patients with early (T1–2, N0–1, non-metastatic) breast cancer who were followed from July 1999 to June 2015 at our Institution. Main outcome measures Distant metastasis-free survival (DMFS). Results Of whole populations (300 patients), 134 and 166 patients were grouped as low and high NLR, respectively, on the basis of NLR value of 1.97, as established by receiver operating characteristic (ROC) curve analysis (area under curve (AUC)=0.625, p=0.0160). The DMFS rates for 1, 3, 6, 9, 12 and 15 years were better in low NLR patients (100%, 98.9%, 91.7%, 82.7%, 82.7%, 82.7%, respectively), than in high NLR patients (99.4%, 94.3%, 84.5%, 69.2%, 66.0%, 51.4%, respectively), with a statistically significant association. On multivariate analysis, premenopausal status (HR=2.78, 95% CI 1.36 to 5.67, p=0.0049), N1 stage (HR=2.31, 95% CI 1.16 to 4.60, p=0.0167) and a high NLR value (HR=2.64, 95% CI 1.22 to 5.638, p=0.0133) were shown to be independent prognostic factors related to poor recurrence rate. To avoid risk of confounding bias, a propensity score-matched analysis was performed and multivariate analysis according to the Cox model confirmed premenopausal status (HR=2.94, 95% CI 1.25 to 6.93, p=0.0136), N1 stage (HR=2.77, 95% CI 1.25 to 6.12, p=0.0117) and high NLR values (HR=2.52, 95% CI 1.11 to 5.73, p=0.0271), as independent prognostic variables of worse outcome. Conclusions This is the first study, to our knowledge, to show a significant correlation between high NLR and worse prognosis in Caucasian patients with early breast cancer by means of propensity score-matched analysis. Further well designed prospective trials with a large sample size are needed to verify our findings and to justify introducing NLR assessment in clinical practice for prediction of cancer recurrence.

Comparison of the current AJCC-TNM numeric-based with a new anatomical location-based lymph node staging system for gastric cancer: A western experience.

Background In gastric cancer, the current AJCC numeric-based lymph node staging does not provide information on the anatomical extent of the disease and lymphadenectomy. A new anatomical location-based node staging, proposed by Choi, has shown better prognostic performance, thus soliciting Western world validation. Study design Data from 284 gastric cancers undergoing radical surgery at the Second University of Naples from 2000 to 2014 were reviewed. The lymph nodes were reclassified into three groups (lesser and greater curvature, and extraperigastric nodes); presence of any metastatic lymph node in a given group was considered positive, prompting a new N and TNM stage classification. Receiver-operating-characteristic (ROC) curves for censored survival data and bootstrap methods were used to compare the capability of the two models to predict tumor recurrence. Results More than one third of node positive patients were reclassified into different N and TNM stages by the new system. Compared to the current staging system, the new classification significantly correlated with tumor recurrence rates and displayed improved indices of prognostic performance, such as the Bayesian information criterion and the Harrell C-index. Higher values at survival ROC analysis demonstrated a significantly better stratification of patients by the new system, mostly in the early phase of the follow-up, with a worse prognosis in more advanced new N stages, despite the same current N stage. Conclusions This study suggests that the anatomical location-based classification of lymph node metastasis may be an important tool for gastric cancer prognosis and should be considered for future revision of the TNM staging system.

Eribulin for metastatic breast cancer (MBC) treatment: a retrospective, multicenter study based in Campania, south Italy (Eri-001 trial)

Background On the basis of the results of two pivotal phase III clinical trials, eribulin mesylate is currently approved in EU for the treatment of advanced breast cancer (aBC) in patients who have previously received an anthracycline and a taxane in either the adjuvant or the metastatic setting, and at least one chemotherapeutic regimen for metastatic disease. Methods In our study, we investigated the efficacy and tolerability of eribulin as second or further line chemotherapy in 137 women affected by aBC. Results Eribulin as monotherapy provided benefit in terms of progression-free survival (PFS), response rate (RR) and disease control rate (DCR) independently of its use as second or late-line therapy. The overall RR and DCR were 17.5% and 64%, respectively. In particular, DCR and overall RR were 50% and 13.6%, 65.4% and 21.1%, 70.4% and 14.8% and 66.7% and 16.7% in second, third, fourth and further lines of treatment, respectively. Median PFS (mPFS) according to the line of therapy was 5.7, 6.3, 4.5 and 4.0 months in patients treated with eribulin in second, third, fourth and over the fourth line, respectively. No significant difference in terms of mPFS was found between the various BC subtypes. Overall, eribulin resulted safe and most adverse events were of grade 1 or 2 and easily manageable. Grades 3–4 toxicities were neutropaenia and neurotoxicity. Conclusions With the limitations due to the observational nature of our findings, eribulin was shown to be an effective and safe therapeutic option in heavily pretreated patients with aBC.

Exemestane and Everolimus combination treatment of hormone receptor positive, HER2 negative metastatic breast cancer: A retrospective study of 9 cancer centers in the Campania Region (Southern Italy) focused on activity, efficacy and safety

Exemestane (Exe) in combination with Everolimus (Eve) represents an important treatment option for patients diagnosed with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer (MBC), which was previously treated with non-steroidal aromatase inhibitors (NSAI). Data from unselected populations may be useful for defining the optimal therapeutic algorithm within a clinical setting. Data from 264 HR+, HER2-MBC patients who received Exe-Eve treatment in combination, following the failure of NSAIs was retrospectively analyzed. Different lines of endocrine treatment (ET) were investigated to evaluate the efficacy and toxicity of the treatment within the ‘everyday clinical practice’ population. The disease control rate (DCR) was 73.1%, with no statistically significant difference among the different settings. At a median follow-up of 42 months, the median progression free survival (PFS) was 11.6, 9.7 and 7.5 months for patients treated with Exe-Eve as first, second or third line therapy, respectively. There was a statistically significant correlation with younger age, no previous adjuvant chemotherapy (CT), no previous adjuvant endocrine therapy (ET), HT duration ≥36 months, involvement of liver and/or lung, no prior CT for metastatic disease and PS=0 at the start of treatment. The median overall survival (OS) was 33.0 months; at a median follow-up of 67 months, the median OS was 43.1, 31.7 and 27.9 months in patients treated with Exe-Eve in first, second or third line therapy, respectively. On multivariate analysis, diabetes and previous CT for metastatic disease were revealed to correlate with a worse outcome. Conversely, the presence of mucositis was significantly associated with long-term survival. Overall, Exe-Eve was typically well tolerated and the majority toxicities were G1 or 2, while treatment discontinuation due to unacceptable toxicity was only required in 5.7% of patients. Despite the limitations due to the observational nature of this study, the findings suggest that treatment with Exe-Eve is an active and safe therapeutic option for endocrine-sensitive MBC patients in a real-world clinical setting, regardless of treatment lines.

Neutrophil to Lymphocyte Ratio as a Predictor of Poor Prognosis in Metastatic Pancreatic Cancer Patients Treated with Nab-Paclitaxel plus Gemcitabine: A Propensity Score Analysis

Background High neutrophil to lymphocyte ratio (NLR) has shown to be a predictor of poor outcomes in various malignancies, including pancreatic cancer. Methods We assessed 70 consecutive pts with histologically confirmed mPC who received chemotherapy with nab-paclitaxel/gemcitabine at two different European oncologic centers between January 2012 and November 2015. Variables assessed for prognostic correlations included age ≥ 66, sex, Karnofsky PS score, primary tumor site, baseline CA19.9 level ≥ 59xULN, 12-week decrease of the CA19.9 level ≥ 50% from baseline, basal bilirubin level, baseline NLR, biliary stent implantation, and liver metastasis. Survival analyses were generated according to the Kaplan-Meier method. Univariate and multivariate analyses were performed by a Cox proportional hazard model. Results According to NLR values, the patients were divided into two groups: high and low. Low group patients showed a better median PFS (7 months versus 5 months) and median OS (13 months versus 7 months) in respect to high group patients. At multivariate analysis, Karnofsky PS < 80% (HR = 0.4; CI 0.2–1.2), liver metastases (HR = 0.4; CI 0.18–0.82), and NLR ≥ 5 (HR = 2.7; 95% CI 1.4–5.2) were predictors of poorer OS. Based on the presence of one or more independent prognostic factors, three risk categories were identified: good-risk, intermediate-risk and poor-risk. The median OS was 22, 10, and 7 months, respectively. Conclusions Baseline NLR is an independent predictor of survival of patients with mPC receiving palliative chemotherapy and could be useful to develop a simple clinical score to identify a subgroup of patients with a low chance to benefit from chemotherapy.