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.

Use of tyrosine kinase inhibitors in patients with metastatic kidney cancer receiving haemodialysis: a retrospective Italian survey.

UNLABELLED: What's known on the subject? and What does the study add? Sunitinib and sorafenib are orally administered multikinase inhibitors approved for the treatment of advanced RCC. The limited pharmacokinetics data on sunitinib and sorafenib suggest that haemodialysis does not significantly alter plasma concentrations. In this retrospective study we define the safety and efficacy of tyrosine kinase inhibitors in patients with metastatic RCC (mRCC) and end-stage renal disease requiring haemodialysis. Even though the retrospective nature of this survey and the relatively small sample size represent major limitations, these data indicate that treatment with sunitinib and sorafenib in this cohort of patients is feasible with no unexpected toxicity and good efficacy, results similar to those in the general population of patients with mRCC. OBJECTIVE: To investigate the safety and efficacy of tyrosine kinase inhibitors (TKIs) in patients with metastatic renal cell carcinoma (mRCC) and end-stage renal disease requiring haemodialysis (HD). PATIENTS AND METHODS: Between July 2006 and December 2010, 24 patients undergoing HD were treated with sunitinib and/or sorafenib for mRCC in 14 Italian institutions. We retrospectively reviewed the medical records of these patients to evaluate the administered doses of TKIs, treatment-related toxicities and the clinical response to therapy. RESULTS: Sunitinib was administered at 50 mg daily for 4-6 weeks in six patients, 37.5 mg daily for 4-6 weeks in seven patients (one patient subsequently increased the dose to 50 mg daily), 25 mg daily for 4-6 weeks in two patients and 12.5 mg daily for 4-6 weeks in one patient. Among the eight patients treated with sorafenib, four patients received 800 mg daily (400 mg every 12 h), three patients 400 mg daily and one patient 200 mg daily with a continuous schedule. The estimated median progression-free and overall survival periods of this cohort of patients were 10.3 months and 22.6 months, respectively. With regard to tolerability and safety, no unexpected adverse events were registered and no grade 4 haematological or non-haematological toxicities were reported. CONCLUSIONS: Sunitinib and sorafenib treatment is not contraindicated in patients with mRCC undergoing HD. The outcome of this patient population is similar to that observed in patients with normal renal function treated with TKIs. These results merit further confirmation by a larger prospective trial.

Gender Differences and Outcomes in Melanoma Patients.

INTRODUCTION: Melanoma is one of the most common cancers in younger people. The incidence of cutaneous melanoma is increasing in patients of both sexes, with female patients generally living longer than their male counterparts. The aim of this retrospective study was to evaluate and confirm the sex-based difference in survival of melanoma patients and the relationship of this difference with pathological features. METHODS: A total of 1023 patients who had been treated at the Department of Medical Oncology, Università Politecnica Marche (Ancona, Italy) and the INRCA-IRCCS Department of Dermatology (Ancona, Italy) between 1987 and 2014 were enrolled in the study. RESULTS: In terms of stage of disease at onset, there was a significant difference in disease-free survival (DFS) and overall survival (OS) in favor of female patients in disease stage I (P = 0.001 and P = 0.01, respectively) and II (P = 0.02 and P = 0.009, respectively). Female patients also showed a significant improvement in 12-year DFS and 12-year OS adjusted for pathological features (Breslow thickness, ulceration, "absent" tumor-infiltrating lymphocyte (TIL) melanomas, "non-brisk" TIL pattern). Globally, female patients had an advantage over with male patients in both DFS and OS (P < 0.001). CONCLUSIONS: Our results show that women have a survival benefit over with men after adjustment for many variables that can reduce mortality risk in female melanoma patients. In a future investigation we wish to examine possible biological sex differences in tumor-host interactions.

Prognostic relevance of programmed cell death protein 1/programmed death-ligand 1 pathway in thymic malignancies with combined immunohistochemical and biomolecular approach.

BACKGROUND: The aim of the study was to investigate Programmed cell Death protein 1 (PD-1) and Programmed Death-Ligand 1 (PD-L1) and their mRNA expression in thymic epithelial tumors (TETs). RESEARCH DESIGN AND METHODS: We analyzed 68 samples of formalin-fixed paraffin-embedded tissue (63 thymomas and 5 thymic carcinomas). PD-1 and PD-L1 protein expression were evaluated by immunohistochemistry, and mRNA expression was evaluated by real-time PCR. RESULTS: M/F ratio was 33/35, and median age was 60.5 years. Twenty patients had Myasthenia Gravis (MG). In the subgroup with large tumors (>5 cm), PD-L1 mRNA overexpression was significantly associated with worse prognosis vs. patients with no mRNA overexpression (p = 0.0083) and simultaneous PD-L1 immunostaining (>1%); PD-L1 mRNA overexpression was significantly associated with worse prognosis, respect to patient with PD-L1 negative immunostaining, and no PD-L1 mRNA overexpression (p = 0.0178). The elderly patients (>60 years) with large tumors showed worse prognosis (p = 0.0395). PD-L1 immunostaining (>50%) resulted to be significantly associated with MG. CONCLUSIONS: Our data suggest the potential involvement of the PD-1 and PD-L1 pathway in TETs' progression. According to our results, it may be helpful to design future trials with anti-PD-1 drugs to establish high-risk patients after surgery.

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.

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.

Hyponatremia normalization as an independent prognostic factor in patients with advanced non-small cell lung cancer treated with first-line therapy.

The aim of the study was to assess, for the first time, the prognostic role of hyponatremia and sodium normalization in patients receiving first-line chemo- or targeted therapy for advanced non-small cell lung cancer.Four hundred thirty-three patients with advanced non small cell lung cancer were treated with first line chemo- or targeted therapy between 2006 and 2015 at our institutions. Patients were stratified in two groups, with or without hyponatremia (group A and B, respectively). Progression free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier method. A Cox regression model was carried out for univariate and multivariate analyses.Sixty-nine patients (16%) presented with hyponatremia at the start of first-line therapy. The median OS was 8.78 months in Group A and 15.5 months in Group B (p < 0.001), while the median PFS was 4.1 months and 6.3 months respectively (p = 0.24). In Group A, median OS was significantly higher in patients who normalized their sodium levels (11.6 vs. 4.7 months, p = 0.0435). Similarly, the median PFS was significantly higher in patients who normalized their sodium levels (6.7 vs. 3.3 months, p = 0.011). At multivariate analysis, sodium normalization was an independent prognostic factor for both OS and PFS.Sodium normalization during first-line therapy is an independent prognostic factor for OS and PFS in patients with advanced lung cancer treated with first-line therapies. Frequent clinical monitoring and prompt treatment of hyponatremia should be emphasized to optimize the outcome of these patients.

Economic sustainability of anti-PD-1 agents nivolumab and pembrolizumab in cancer patients: Recent insights and future challenges.

Anti-programmed death (PD)-1 agents pembrolizumab and nivolumab have recently obtained enthusiastic results in terms of progression-free survival (PFS), overall survival (OS) and tolerability in cancer patients. Despite these promising data, the high cost of these agents needs careful consideration. Indeed, the evaluation of cost-effectiveness analysis (CEA) and quality-adjusted life year (QALY), as well as different drug reimbursement modalities, will represent fundamental tools in order to guarantee the economic sustainability of health system and the access to care for all cancer patients. In this review, we discussed the recent results obtained by immunotherapy in cancer patients and we evaluated the economic impact of recently approved nivolumab and pembrolizumab in patients with advanced melanoma, non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC).

Gastrointestinal neuroendocrine tumors: Searching the optimal treatment strategy--A literature review.

Neuroendocrine tumors of the gastro-entero-pancreatic system (GEP-NETs) are a heterogeneous group of neoplasms, with different malignant potential and behavior. Many treatment options are available. Surgery should be considered for localized tumors and in some selected cases of metastatic disease. Somatostatin analogs, useful for symptoms control in functioning tumors, are also effective to inhibit tumor progression in specific settings. The multi-TKI sunitinib and of the mTOR-inhibitor everolimus are efficacy for metastatic pancreatic NET (P-NET) treatment. Chemotherapy is generally used in symptomatic and progressive NETs. Peptide receptor radionuclide therapy (PRRT) should be recommended after failure of medical therapy. For tumors confined to the liver ablative techniques should be considered. Nevertheless a shared therapeutic sequence for GEP-NET treatment still does not exist. In this review, we analyzed available data trying to identify the better treatment strategy and to suggest potential therapeutic algorithms distinguishing P-NETs from gastrointestinal NETs (GI-NETs).

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.

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.

Elderly patients with advanced colorectal cancer: tolerability and activity of chemotherapy.

AIMS AND BACKGROUND: Colorectal cancer is the most common gastrointestinal tumor in Western countries and is increasing in elderly patients. In recent years, new treatments based on the use of 5-fluorouracil associated with oxaliplatin or CPT-11 have shown promising activity. The aim of the present study was to analyze the tolerability and activity of chemotherapy with 5-fluorouracil plus oxaliplatin or CPT-11 in elderly patients with advanced colorectal cancer. METHODS: Patients aged 70 years or older with advanced colorectal cancer were treated with 5-fluorouracil (400 mg/m2 in bolus and 600 mg/m2 in a 22-hr continuous infusion on days 1-2) plus folinic acid (100 mg/m2) associated to oxaliplatin (85 mg/m2 on day 1, FOLFOX regimen) or CPT-11 (180 mg/m2 on day 1, FOLFIRI regimen), every 14 days. RESULTS: Twenty-nine patients with a median age of 76 years (range, 70-82) were treated with FOLFOX or FOLFIRI as first-line chemotherapy for metastatic disease. We observed a partial response in 8/29 (27.6%), stable disease in 11/29 (37.9%) and progressive disease in 10/29 (34.5%). Median survival was 21 months; 1-year survival probability was 89.8%. Grade III leukopenia was observed in 2/29 (7%) patients and grade III diarrhea in 1/29 patients. No other grade III-IV toxicity was observed. CONCLUSIONS: FOLFOX and FOLFIRI appear to be active and well tolerated regimens for elderly patients with advanced colorectal cancer.

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.

Locally advanced rectal cancer: the importance of a multidisciplinary approach.

Rectal cancer accounts for a relevant part of colorectal cancer cases, with a mortality of 4-10/100000 per year. The development of locoregional recurrences and the occurrence of distant metastases both influences the prognosis of these patients. In the last two decades, new multimodality strategies have improved the prognosis of locally advanced rectal cancer with a significant reduction of local relapse and an increase in terms of overall survival. Radical surgery still remains the principal curative treatment and the introduction of total mesorectal excision has significantly achieved a reduction in terms of local recurrence rates. The employment of neoadjuvant treatment, delivered before surgery, also achieved an improved local control and an increased sphincter preservation rate in low-lying tumors, with an acceptable acute and late toxicity. This review describes the multidisciplinary management of rectal cancer, focusing on the effectiveness of neoadjuvant chemoradiotherapy and of post-operative adjuvant chemotherapy both in the standard combined modality treatment programs and in the ongoing research to improve these regimens.

Thymic neoplasms: an update on the use of chemotherapy and new targeted therapies. A literature review.

Thymic malignancies represent a wide range of clinical, histological and molecular entities, with probably considerable heterogeneity even among tumors of the same histotype. Systemic chemotherapy with cisplatin-based regimens continues to represent the standard of care in metastatic or inoperable refractory/recurrent diseases and ADOC regimen (including cisplatin, doxorubicin, vincristine and cyclophosphamide) demonstrated the longer overall response rate and median survival in the first line setting, although no randomized trial is available; and there is still a lack of standard treatment after first-line failure. To date research efforts are focused on translational studies on molecular pathways involved in thymic tumors carcinogenesis, aimed to better understand and predict the efficacy of chemotherapy and targeted therapy. Recent molecular characterization includes identification of a number of oncogenes, tumor suppressor genes, chromosomal aberrations, angiogenic factors, and tumor invasion factors involved in cellular survival and proliferation and in tumor growth. The use of biologic drugs is currently not recommended in a routine practice because there are limited data on their therapeutic role in thymic epitelial tumors. Because of the lack of data from adequate-sized, prospective trials are required for validation and the enrolment of patients with advanced disease into available clinical trials has to be encouraged.

Preoperative quality of life predicts survival following pulmonary resection in stage I non-small-cell lung cancer.

OBJECTIVES: The objective of this study was to assess the prognostic role of preoperative quality of life (QoL) in patients operated on for early-stage non-small-cell lung cancer (NSCLC). METHODS: This is an observational analysis of 131 consecutive patients (2003-08) submitted to pulmonary lobectomy and systematic nodal dissection for pathological pT1N0 or pT2N0 stages NSCLC with a complete follow-up (median 40 months). QoL was measured by the Short Form 36v2, a multidimensional survey assessing eight domains and two composite scales (physical component score [PCS] and mental component score [MCS]). Survival was calculated by the Kaplan-Meier method. The log-rank test was used to assess differences between groups. The relationships between survival and QoL composite scales were determined by Cox proportional hazards regression analysis adjusting for the effect of several baseline and clinical variables. PCS and MCS were categorized according to their values greater or lower than 50 percentiles (general population norms). RESULTS: Fifty-three (40%) patients had PCS <50 and 71 (54%) had MCS <50. Results from physical functioning (P = 0.03) and general health (P = 0.03) scales were directly associated with survival. Multivariable regression showed that significant factors associated with overall survival were age >70 (hazard ratio [HR] 2.4, 95% confidence interval [95% CI] 1.2-4.8, P = 0.01) and PCS <50 (HR 2.3, 95% CI 1.4-4.4, P = 0.01). MCS, pT stage, histology, forced expiratory volume in 1 s, DLCO were not associated with prognosis. Patients with PCS >50 lived longer than those with PCS <50 (5-year overall survival 79 vs 49%, P = 0.01), in both pT1 (5-year overall survival 80 vs 49%) and pT2 stages (5-year overall survival 78 vs 48%). Cancer-specific 5-year survival was better in patients with a preoperative PCS >50 compared with those with PCS <50 (89 vs 73%, P = 0.05). Deaths due to cancer recurrence were similar in patients with PCS <50 and >50 (55 vs 53%, P = 0.9). CONCLUSIONS: The physical component of QoL was associated with overall and cancer-specific survivals in patients operated on for early-stage NSCLC. Supportive interventions aimed at improving the perception of physical well-being should be tested to verify whether they can improve long-term prognosis after lung cancer surgery.

Resected biliary tract cancers: a novel clinical-pathological score correlates with global outcome.

BACKGROUND: Biliary tract cancer presents a poor prognosis. AIMS: The objective of this study is to find clinical-laboratory parameters like prognostic factors to select patients who can benefit from surgery and post-operative treatments. METHODS: Between 2005 and 2010, 41 patients underwent radical surgery at our Institution. A novel score was retrospectively calculated assigning a grade to the clinical-laboratory findings at diagnosis. 0 and 1 point were respectively assigned to the normal or abnormal parameter. Two groups were identified: SCORE 0 and SCORE 1. RESULTS: Patients with cholangiocarcinoma or Klatskin tumours or asymptomatic at diagnosis presented a significantly better overall survival (OS) than patients with different primary sites or who presented pain, jaundice or cholangitis. At univariate analysis, high levels of aspartate aminotransferase, alanine aminotransferase and CA19-9 before surgery, hyperbilirubinemia before and after surgery had a negative correlation with OS. A worse OS was observed in patients with a higher score (median OS in the "score 0" group=30.79 months vs. median OS in the "score 1"=17.98 months). CONCLUSION: Our results suggest that pre and post-surgery clinical-laboratory parameters and the novel score, could be useful, especially for intrahepatic tumours, in predicting the outcome in patients undergoing surgery and in selecting patients to receive adjuvant therapy.

State of the art for cardiotoxicity due to chemotherapy and to targeted therapies: a literature review.

Cardiotoxicity is a common complication of many anti-cancer agents and it remains a major limitation, strongly impacting the quality of life and the overall survival, regardless of the oncologic prognosis. Cardiotoxicity may occur during or shortly after treatment (within days or weeks), or it may become evident months, and sometimes years, after completion of chemotherapy. Cardiotoxicity associated with cancer therapies can range from asymptomatic subclinical abnormalities, including electrocardiographic changes and temporary left ventricular ejection fraction decline, to life-threatening events such as congestive heart failure or acute coronary syndromes. The aim of this review is to summarize potential cancer chemotherapeutics-related cardiovascular toxicities in adult cancer-patients and to suggest monitoring and treatment options for each agent, that can serve as a tool in the clinical practice.

Role of maspin in cancer.

Maspin (mammary serine protease inhibitor), is a member of the serine protease inhibitor/non-inhibitor superfamily. Its expression is down-regulated in breast, prostate, gastric and melanoma cancers but over-expressed in pancreatic, gallbladder, colorectal, and thyroid cancers suggesting that maspin may play different activities in different cell types. However, maspin expression seems to be correlated with better prognosis in prostate, bladder, lung, gastric, colorectal, head and neck, thyroid and melanoma cancer. In breast and ovarian cancer maspin significance is associated with its subcellular localization: nucleus maspin expression correlates with a good prognosis, whilst in pancreatic cancer it predicts a poor prognosis. Since tumor metastasis requires the detachment and invasion of tumor cells through the basement membrane and stroma, a selectively increased adhesion by the presence of maspin may contribute to the inhibition of tumor metastasis. Furthermore the different position of maspin inside the cell or its epigenetic modifications may explain the different behavior of the expression of maspin between tumors. The expression of maspin might be useful as a prognostic and possibly predictive factor for patients with particular types of cancer and data can guide physicians in selecting therapy. Its expression in circulating tumor cells especially in breast cancer, could be also useful in clinical practice along with other factors, such as age, comorbidities, blood examinations in order to select the best therapy to be carried out. Focusing on the malignancies in which maspin showed a positive prognostic value, therapeutic approaches studied so far aimed to re-activate a dormant tumor suppressor gene by designed transcription factors, to hit the system that inhibits the expression of maspin, to identify natural substances that can determine the activation and the expression of maspin or possible "molecules binds" to introduce maspin in cancer cell and gene therapy capable of up-regulating the maspin in an attempt to reduce primarily the risk of metastasis.Further studies in these directions are necessary to better define the therapeutic implication of maspin.