The Impact of Lifestyle Interventions in High-Risk Early Breast Cancer Patients: A Modeling Approach from a Single Institution Experience.

A healthy lifestyle plays a strategic role in the prevention of BC. The aim of our prospective study is to evaluate the effects of a lifestyle interventions program based on special exercise and nutrition education on weight, psycho-physical well-being, blood lipid and hormonal profile among BC patients who underwent primary surgery. From January 2014 to March 2017, a multidisciplinary group of oncologists, dieticians, physiatrists and an exercise specialist evaluated 98 adult BC female patients at baseline and at different time points. The patients had at least one of the following risk factors: BMI ≥ 25 kg/m2, high testosterone levels, high serum insulin levels or diagnosis of MS. Statistically significant differences are shown in terms of BMI variation with the lifestyle interventions program, as well as in waist circumference and blood glucose, insulin and testosterone levels. Moreover, a statistically significant difference was reported in variations of total Hospital Anxiety and Depression Scale (HADS) score, in the anxiety HADS score and improvement in joint pain. Our results suggested that promoting a healthy lifestyle in clinical practice reduces risk factors involved in BC recurrence and ensures psycho-physical well-being.

Prognostic Impact of Ki-67 Change in Locally Advanced and Early Breast Cancer after Neoadjuvant Chemotherapy: A Single Institution Experience.

Systemic neoadjuvant chemotherapy (NCT) is a standard treatment for locally advanced breast cancer (LABC) and for selected early breast cancer (EBC). In these settings, the prognostic and predictive role of Ki-67 before and after NCT is unclear. The aim of our study was to investigate the prognostic role of Ki-67 change in patients not achieving pathological complete response (pCR). We retrospectively analyzed data of patients who did not achieve pCR assessing Ki-67 expression pre- and post-NCT. We stratified three groups: high reduction (>20%), low reduction (1-20%), and no reduction in Ki-67. These groups were correlated with clinical and pathological data by χ2 test. We estimated disease-free survival (DFS) and overall survival (OS) using Kaplan-Meier method, and we adopted univariate and multivariate Cox proportional hazard models. We selected 82 patients from a database of 143 patients, excluding those who were metastatic at diagnosis, achieved pCR, or lack data regarding Ki-67. Median age at diagnosis was 54 years (range 30-75); 51 patients were Luminal B, 10 human epidermal growth factor receptor 2 (HER-2) enriched, and 21 triple negative. A significant correlation between high Ki-67 reduction and luminal B HER-2-negative subtype was observed (p = 0,0035). The change in Ki-67 was significantly associated with DFS (p = 0,0596) and OS (p = 0,0120), also at multivariate analysis (p = 0,0256 for DFS; p = 0,0093 for OS). In particular, as compared to patients with low/no reduction of Ki-67, those with high Ki-67 reduction (>20%) after NCT showed better survival (60% vs. 56% vs. 83% after 5 years from diagnosis, respectively; p = 0.01). In conclusion, in our study, Ki-67 change showed a significant prognostic role in breast cancer patients treated with NCT who did not achieve pCR. Crucially, Ki-67 < 20% identifies a high-risk population that may be eligible for clinical trials with novel therapeutic interventions in adjuvant setting.

The role of angiogenetic single-nucleotide polymorphisms in thymic malignancies and thymic benign lesions.

BACKGROUND: We previously showed that selected single-nucleotide-polymorphisms (SNPs) of genes involved in angiogenesis influence the aggressiveness of thymic epithelial tumors (TETs). This study analyzes their role in TETs and in thymic benign lesions, in order to investigate potential correlation with risk and outcome. METHODS: Genomic DNA was extracted from paraffin-embedded tissue of 92 patients, undergoing surgery at our Institution. We investigated by Real-Time PCR the SNPs of the following genes: platelet-derived growth factor receptor-α (PDGFRα), hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor A (VEGF-A), vascular endothelial growth factor receptor-2 and 3 (VEGF-2, VEGFR-3), excision repair cross-complementation group-1 (ERCC1). RESULTS: Fifty-seven TETs and 35 thymic benign lesions were included into the study. Frequency of SNPs was as follows: rs2057482 C, rs11158358 C and rs11549465 C polymorphisms of HIF1-a: thymomas < general population (P=0.008, P=0.007, and P=0.044 respectively). HIF1-a alleles: general population > study groups, rs1951795C SNP (P=0.026 for benign lesions and P=0.0007 for thymomas), rs10873142T SNP (P=0.008 and P=0.001 respectively), rs12434438 A SNP (P=0.034 and P=0.0007) and rs2301113A SNP (P=0.027 and P=0.010). rs699947C polymorphism of VEGF-A: benign lesions > general population (P=0.012). CONCLUSIONS: This is the first study investigating the angiogenetic polymorphisms in thymic benign lesions and TETs. SNPs analysis may represent a further asset in identification of patients who could benefit from anti-angiogenetic therapy.

Body Mass Index and Hormone Receptor Status Influence Recurrence Risk in HER2-Positive Early Breast Cancer Patients.

INTRODUCTION: A reliable risk stratification on the basis of tumor biology and host factors of HER2-positive (HER2+) early breast cancer (eBC) patients is needed. The aim of our study was to assess the prognostic role of body mass index (BMI) and hormone receptor (HR) expression in this setting. PATIENTS AND METHODS: We retrospectively evaluated 238 women with stage I to III HER2+ breast cancer who completed adjuvant chemotherapy (CHT) and 1 year of treatment with trastuzumab. The end point was 3-year distant disease-free survival (3yDDFS). Survival analysis was evaluated using the Kaplan-Meier method. Multivariate analysis was performed using Cox proportional-hazards model adjusting for HR status, BMI, tumor staging, size, nodal status, and type of adjuvant CHT. Association among categorical variables was assessed using χ2 test. RESULTS: The early recurrence rate after 3 years resulted as 4.2% (40% HR+ patients and 60% HR- patients). Neither HR status nor BMI alone showed an association with 3yDDFS in multivariate analysis. However, the hazard ratios for patients with HR- tumors who had also BMI ≥25 (3yDDFS 86.9%; 95% confidence interval [CI], 75.0%-97.7%) were amplified compared with patients with HR+ tumors and with BMI <25 (3yDDFS 98%; 95% CI, 94.8%-100.0%) and other subgroups (P = .003). This observation was confirmed in multivariate analysis (hazard ratio, 1.79; 95% CI, 1.04-3.07; P = .03). CONCLUSION: Our real-life data highlight a different risk of eBC recurrence after grouping patients according to HR status and BMI. These results might help clinicians to identify correct treatment strategies. Patients who are HR- and have BMI ≥25 might benefit from escalation approaches, whereas those who are HR+ and have BMI <25 might be eligible for a shorter duration of adjuvant treatment with anti-HER2 agents.

Pre-treatment systemic immune-inflammation represents a prognostic factor in patients with advanced non-small cell lung cancer.

BACKGROUND: Inflammation plays an important role in pathogenesis, development and progression of lung cancer. The aim of the study is to assess the prognostic role of Systemic Immune-Inflammation Index (SII), obtained by analyzing the neutrophil, lymphocyte and platelet counts, and to design prognostic models for patients receiving first-line chemo- or targeted therapy for advanced non-small cell lung cancer (NSCLC). METHODS: We conducted an analysis on 311 patients with advanced NSCLC, treated with first line chemo- or targeted therapy till June 2015 at our Institution. Patients were stratified in two groups with SII ≥1,270 (Group A) vs. SII <1,270 (Group B). Progression free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier method. The best SII cutoff was identified by X-tiles program. A Cox regression model was carried out for univariate and multivariate analyses. RESULTS: At baseline, 179 patients had SII ≥1,270 (Group A), whilst 132 had lower SII (Group B). The median OS was 12.4 months in Group A and 21.7 months in Group B (P<0.001), whilst the median PFS was 3.3 and 5.2 months, respectively (P=0.029). At multivariate analysis, male gender, ECOG-PS ≥2 and SII >1,270 were predictors of worst OS, whilst IV tumor stage was only slightly significant (P=0.08). Otherwise, only wild-type EGFR status and SII ≥1,270 were independent prognostic factors for worst PFS. CONCLUSIONS: Pre-treatment SII is an independent prognostic factor for patients with advanced NSCLC treated with first-line therapies.

Impact of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR) single nucleotide polymorphisms on outcome in gastroenteropancreatic neuroendocrine neoplasms.

Angiogenesis represents a key event in cancer development, leading to local invasion e metastatization, and might be considered a basic feature in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) with a high expression of angiogenic molecules. We aimed to analyze the prognostic and predictive role of angiogenic factors in GEP-NENs through the analysis of single nucleotide polymorphisms (SNPs) of VEGF-A, VEGFR2 and VEGFR3. The genomic DNA of 58 consecutive patients with GEP-NENs treated at our Institution was extracted from peripheral blood. Two SNPs were identified respectively in VEGF-A (rs2010963G>C, rs699947A>C), VEGFR-2 (rs2305948C>T, rs1870377T>A), and VEGFR-3 (rs307821T>C, rs307826C>A) gene. Gene polymorphisms were determined by Real-Time PCR using TaqMan assays. Median age was 57 years (range 24-79 years); 32 patients were male and 77.5% of NENs were localized in the pancreas. The allele frequency of VEGFR-2 rs2305948T and of VEGF-A rs2010963C showed a trend of higher frequency than in general population (12.1% vs. 8.0% and 34.5% vs. 31.2%, respectively). Three out SNPs (VEGF-A rs699947C, VEGF-A rs2010963GC and VEGFR-3 rs307821C) showed a correlation with an increased risk of disease relapse. Moreover median PFS changes according to the presence of 0-1 SNPs (20.7% of cases; 61.9 months), 2 SNPs (25.9%; 49.2 months) and 3 SNPs (53.4%; 27.8 months) (p = 0.034). Results suggest, for the first time, that specific SNPs in VEGF-A and VEGFR-3 correlate with poor prognosis in GEP-NENs. The identification of this new prognostic factor might be helpful in order to optimize the management of these heterogeneous neoplasms.

Long-responders to anti-HER2 therapies: A case report and review of the literature.

Since the introduction of targeted therapies, prognosis in human epidermal growth factor receptor (HER) 2-positive metastatic breast cancer (MBC) has radically changed. The addition of Pertuzumab to Trastuzumab and standard chemotherapy has further increased patients' overall survival (OS). However, there is no agreement regarding the optimal duration of trastuzumab therapy in selected patients achieving long-term complete remission. In addition, no potential factors of long-term benefit have been identified yet. In the present study, we report the case of a MBC woman who was successfully treated with trastuzumab for over 10 years. At the time of diagnosis (February 2005), she revealed lung, nodal and bone metastases. Therefore, a first-line chemotherapy with Epirubicine and Docetaxel was administered for 6 cycles and then the patient started Trastuzumab plus hormonal therapy until reaching a sensible reduction of mammary lump and disappearance of distant metastases. Following a multidisciplinary evaluation, in November 2006, the patient underwent radical mastectomy and axillary dissection, achieving a complete remission. She continued Trastuzumab until September 2015 (for a total of 156 cycles) when a pleural diffusion was demonstrated. Long-term survival during anti-HER2 treatment remains a rare and optimal situation. Currently, no data exist to support trastuzumab interruption in this setting and collaborative efforts to better analyze the characteristics of long-responder patients are needed. Data regarding prognostic factors in this setting are relatively confusing. Our review reveals that hormonal receptor (HR)-positive disease is associated with a better prognosis, whereas the role of visceral spread differs by single or dual target anti HER2-inhibition. The introduction of Pertuzumab is raising concerns in terms of toxicity and its cost effectiveness. While waiting for novel molecular data and randomized trials, available evidence advocates continuous use of anti-HER2 therapies until disease progression or development of side effects.

Impact of phosphoinositide-3-kinase and vitamin D3 nuclear receptor single-nucleotide polymorphisms on the outcome of malignant melanoma patients.

BACKGROUND: Several studies associating single nucleotide polymorphisms (SNPs) frequencies with tumors outcome have been conducted, nevertheless malignant melanoma literature data are inconclusive.Therefore we evaluate the impact of different genotypes for phosphoinositide-3-kinase (PI3K) and vitamin D3 nuclear receptor (VDR) SNPs on melanoma patients' outcome. MATERIALS AND METHODS: Genomic DNA of 88 patients was extracted from blood and tumor samples. SNPs were determined by PCR using TaqMan assays. We selected polymorphisms of the regulatory and catalytic subunit of PI3K (PIK3R1 and PIK3CA genes, respectively), analyzing rs2699887C>T of PIK3CA and rs3730089G>A of PIK3R1 SNPs. Furthermore we considered the following VDR SNPs: rs2228570A>G (Fok1), rs731236A>G (Taq1) and rs1544410C>T (Bsm1).Progression free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method and with Mantel-Haenszel log-rank test. RESULTS: The statistical analysis for Fok1 of VDR showed a significant difference in PFS after the first line therapy (median PFS= 21.2 months in the homozygous recessive genotype group vs. 3.3 months of homozygous dominant and heterozygous ones, p= 0.03). In particular, in homozygous recessive patients for Fok1 SNPs of VDR a high rate of histological regression and BRAF (B- Rapidly Accelerated Fibrosarcoma gene) mutation were observed. Furthermore, more efficacy of BRAF +/- MEK (MAPK-ERK-Kinase) inhibitors therapies in homozygous recessive patients vs. homozygous dominant and heterozygous ones was shown. CONCLUSIONS: Our study showed a significant correlation between homozygous recessive genotype of Fok1 SNPs of VDR gene and an increased PFS in patients who underwent a first line therapy with BRAF inhibitors.

Managing hyponatremia in lung cancer: latest evidence and clinical implications.

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.

Hormonal receptors in lung adenocarcinoma: expression and difference in outcome by sex.

BACKGROUND: Lung cancer seems to have different epidemiological, biomolecular and clinical characteristics in females than in males, with a better prognosis for women. The aim of the study is to determine gender differences in lung adenocarcinoma in terms of androgen (AR), estrogen (ER)α and progesterone (PgR) receptors expression and their impact on outcome. RESULTS: Overall survival was significantly better in ERα and in PgR positive lung adenocarcinoma patients (median survival 45 vs. 19 months).Eight out of 62 patients showed positive expression of nuclear (n) AR and 18 of cytoplasmic (c) AR with a significantly better survival (49 vs. 19 and 45 vs. 19 months, respectively). There was a significant difference in survival between patients with vs. without c-AR expression (30 vs. 17 months). Finally, in the subgroup of women, median survival was greater in positive expression of c-AR than for women with negative c-AR (45 vs. 21 months). MATERIALS AND METHODS: We conducted an analysis on a cohort of 62 patients with advanced NSCLC treated at our institution. We investigated the immunohistochemical expression of n/c AR, ERα and PgR in 62 NSCLC and we correlated it with patients' clinic-pathologic characteristics and with prognosis. CONCLUSIONS: Our results showed that the positive expression of one hormonal receptor could represent a prognostic factor.Furthermore our study suggests that AR should become object of close examination in a larger series of lung adenocarcinoma patients, also for selection of the patients with best prognosis that can perform more chemotherapy lines.

Risk of Hyponatraemia in Cancer Patients Treated with Targeted Therapies: A Systematic Review and Meta-Analysis of Clinical Trials.

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.

Gastro-entero-pancreatic neuroendocrine tumors: Is now time for a new approach?

Gastro-entero-pancreatic tumors (GEP-NETs) are rare neoplasms often characterized by an overexpression of somatostatin receptors. Thus, radiolabeled somatostatin analogues have showed an increasing relevance both in diagnosis and treatment, especially in low- and intermediate-differentiated GEP-NETs. These evidences have led to a growing development of new functional imaging techniques as 68Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) proved useful in the management of these neoplasms. However these tumors have a heterogeneous behavior also modifying their aggressiveness through time. Therefore sometimes 18F-fluorodeoxyglucose PET/CT appears to be more appropriate to obtain a better assessment of the disease. According to these considerations, the combination of different functional imaging techniques should be considered in the management of GEP-NETs patients allowing clinicians to choose the tailored therapeutic approach among available options.

Medical treatment for gastro-entero-pancreatic neuroendocrine tumours.

Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) represents a various family of rare tumours. Surgery is the first choice in GEP-NENs patients with localized disease whilst in the metastatic setting many other treatment options are available. Somatostatin analogues are indicated for symptoms control in functioning tumours. Furthermore they may be effective to inhibit tumour progression. GEP-NENs pathogenesis has been extensively studied in the last years therefore several driver mutations pathway genes have been identified as crucial factors in their tumourigenesis. GEP-NENs can over-express vascular endothelial growth factor (VEGF), basic-fibroblastic growth factor, transforming growth factor (TGF-α and -ß), platelet derived growth factor (PDGF), insulin-like growth factor-1 (IGF-1) and their receptors PDGF receptor, IGF-1 receptor, epidermal growth factor receptor, VEGF receptor, and c-kit (stem cell factor receptor) that can be considered as potential targets. The availability of new targeted agents, such as everolimus and sunitinib that are effective in advanced and metastatic pancreatic neuroendocrine tumours, has provided new treatment opportunities. Many trials combing new drugs are ongoing.

Hyponatremia in cancer patients: Time for a new approach.

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.

Correlation of Stomatitis and Cutaneous Toxicity With Clinical Outcome in Patients With Metastatic Renal-Cell Carcinoma Treated With Everolimus.

BACKGROUND: In clinical practice, discontinuation or dose reduction of everolimus may be induced not only by grade 3 or 4 toxicities but also by prolonged grade 2 toxicities, such as stomatitis and/or cutaneous toxicity, which share some pathogenetic mechanisms. We assessed the correlation between either everolimus discontinuation or dose reduction induced by stomatitis-cutaneous toxicity events (SCTE) and clinical outcome of patients with metastatic renal-cell cancer (mRCC). PATIENTS AND METHODS: We retrospectively reviewed the clinical data of patients with mRCC treated with everolimus in 2 Italian centers. Clinical evidence of SCTE was evaluated, and corresponding clinical data were reviewed for response and clinical outcome. RESULTS: Seventy-nine mRCC patients treated with everolimus (57 male, 22 female; median age 66 years; range, 44-88 years) were evaluated. SCTE were observed in 20 (25%) of 79 patients at a median of 30.5 days of everolimus treatment (range, 10-270 days). Partial response or stable disease was achieved in 15 (79%) of 19 evaluable patients with SCTE compared to 28 (48%) of 58 with no SCTE (P = .03). At a median follow-up of 19 months, a significant difference was found in the median PFS equal to 7.8 months (95% confidence interval [CI], 2.8-24.4) in SCTE patients versus 4.3 months (95% CI, 2.7-7.5) in non-SCTE patients (P = .029), and in the median OS equal to 30.6 months (95% CI, 19.6-not reached) in SCTE patients versus 13.5 months (95% CI, 9.9-17.7) in non-SCTE patients (P = .0007). CONCLUSION: These data suggest that SCTE may be a predictive marker of favorable outcome in mRCC patients treated with everolimus.

Prognostic models to predict survival in patients with advanced non-small cell lung cancer treated with first-line chemo- or targeted therapy.

BACKGROUND: We aimed to assess the prognostic role of neutrophilia, lymphocytopenia and the neutrophil-to-lymphocyte ratio (NLR), and to design models to define the prognosis of patients receiving first-line chemo- or targeted therapy for advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We retrospectively analysed 401 consecutive patients with advanced NSCLC treated with first line chemo- or targeted therapy. Patients were stratified into two groups with pre-treatment NLR ≥ 3.7 (Group A) vs. < 3.7 (Group B). The best NLR cut-off was identified by ROC curve analysis. RESULTS: At baseline 264 patients had NLR≥3.7 (Group A), whilst 137 had lower NLR (Group B). Median OS was 10.8 months and 19.4 months in the two groups (p < 0.001), while median PFS was 3.6 months and 5.6 months, respectively (p = 0.012). At multivariate analysis, ECOG-PS≥2, stage IV cancer, non-adenocarcinoma histology, EGFR wild-type status and NLR were predictors of worse OS. Stage IV cancer, wild type EGFR status and NLR≥3.7 were independent prognostic factors for worse PFS. Patients were stratified according to the presence of 0-1 prognostic factors (8%), 2-3 factors (73%) and 4-5 factors (19%) and median OS in these groups was 33.7 months, 14.6 months and 6.6 months, respectively (p < 0.001). Similarly, patients were stratified for PFS based on the presence of 0-1 prognostic factor (15%), 2 factors (41%) and 3 factors (44%). The median PFS was 8.3 months, 4.6 months and 3.3 months respectively (p < 0.001). CONCLUSIONS: Pre-treatment NLR is an independent prognostic factor for patients with advanced NSCLC treated with first-line therapies.

Clinical and pathologic predictors of clinical outcome of malignant pleural mesothelioma.

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.

Impact of VEGF, VEGFR, PDGFR, HIF and ERCC1 gene polymorphisms on thymic malignancies outcome after thymectomy.

We aimed to analyze genotypes of VEGF-A, VEGFR2, Flt4, PDGFRα, HIF-1α and ERCC1 and their correlation with thymic tumor risk and patient outcome. DNA of 57 consecutive patients (43 thymomas and 14 thymic carcinomas) who underwent total thymectomy at our Institution was extracted from paraffin-embedded tissue. We selected polymorphisms in the following genes:HIF1-α (rs2057482T > C, rs1951795A > C, rs2301113C > A, rs10873142C > T, rs11158358G > C, rs12434438G > A, rs11549465C > T, rs11549467G > A), VEGF-A (rs2010963G > C, rs699947A > C), VEGFR-2 (rs2305948C > T, rs1870377T > A), VEGFR-3 (rs307826T > C, rs307821C > A), PDGFR-α (rs35597368C > T) and ERCC1 (rs11615A > G). Gene polymorphisms were determined by Real-Time PCR using TaqMan assays. As compared to the general population, the allele frequency of PDGFR-α rs35597368T was significantly higher (95% vs. 87%, p = 0.036), while the frequency of alleles HIF1-α rs2057482C (78% vs. 90%), rs1951795C (69% vs. 87%), rs2301113A (70% vs. 83%), rs10873142T (70% vs. 87%), rs11158358C (75% vs. 88%), rs12434438A (67% vs. 84%) were significantly lower. VEGFR-3 rs307821C frequency was significantly higher in thymomas vs. thymic carcinomas (79% vs. 72%, p = 0.0371). The following factors were significantly correlated with a longer overall survival: VEGFR-3 rs307826C, VEGFR-2 rs1870377A, PDGFR-α rs35597368T/C, HIF1-α rs2301113C, rs2057482C/T, rs1951795C, rs11158358G/C and rs10873142T/C, ERCC1 rs11615A (p < 0.05). Our results suggest, for the first time, that PDGFR-α, HIF-1α and VEGFR-3 SNPs are associated with thymic cancer risk and survival.

High neutrophil-to-lymphocyte ratio persistent during first-line chemotherapy predicts poor clinical outcome in patients with advanced urothelial cancer.

BACKGROUND: Increased neutrophil-to-lymphocyte ratio (NLR), an index of systemic inflammation, is associated with poor outcome for various types of cancers. We assessed the role on outcome prediction of NLR at baseline and persistent during first-line chemotherapy in patients with advanced urothelial cancer. METHODS: We retrospectively reviewed 292 patients with unresectable or metastatic urothelial cancer treated with first-line chemotherapy between January 2003 and December 2012. The cutoff values of NLR (>3 vs. <3) were evaluated before therapy and at day 1 of the second and third cycle (follow-up NLR). After univariate analysis, a multivariate analysis was carried out by Cox regression model and included the following variables: Eastern Cooperative Oncology Group (ECOG) performance status (≥ 2 vs. 0-1), visceral disease (present vs. absent), hemoglobin (<12 g/dL vs. >12 g/dL), pretherapy NLR (>3 vs. <3), and follow-up NLR (>3 vs. ≤ 3). RESULTS: Patients with pre- and follow-up NLR of >3 had a median progression-free survival of 3.2 months and a median overall survival of 5.7 months. In multivariate analysis, visceral metastases, pretherapy hemoglobin, and follow-up NLR were significant predictors of progression-free survival [hazard ratio (HR) 1.75, P = 0.0001; HR 1.57, P = 0.0015; HR 2.77, P < 0.0001, respectively], and of overall survival (HR 1.60, P = 0.0023; HR 1.59, P = 0.0024; HR 2.89, P < 0.0001, respectively); whereas pretherapy NLR remained as predictor of overall survival only (HR 1.53, P = 0.0101). CONCLUSIONS: An increased NLR persistent during first-line chemotherapy is an independent predictive factor for patients with advanced urothelial cancer.

Chromium exposure and germinal embryonal carcinoma: first two cases and review of the literature.

The aim of the study was to determine the potential role of occupational exposures to chromium (Cr) in the onset of extragonadal germinal embryonal carcinoma. The first two cases of workers in a company with Cr exposure are reported. The published scientific literature regarding the topic in peer-reviewed journals including MEDLINE and CancerLit databases was extensively reviewed. Two young patients who were coworkers in the same company, exposed to Cr, developed extragonadal germinal embryonal carcinomas. One of them also developed angiosarcoma of the mediastinum. To the best of our knowledge these are the first two cases of germinal embryonal carcinoma in patients with occupational exposure to Cr.