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• Oligometastatic NSCLC represents a category without a standard therapeutic approach. • In selected oligometastatic NSCLC, radical surgery seems to offer a good prognosis. • Treatment of selected synchronous oligometastatic NSCLC could be conducted safely. Oligometastatic Non-Small Cell Lung Cancer (NSCLC) patients represent a category without a standard therapeutic approach. However, in selected oligometastatic NSCLC, radical surgery seems to offer a good prognosis. This retrospective study aimed to analyse the long-term outcomes of synchronous oligometastatic patients treated with curative intent and identify the factors associated with better results and the proposal of a risk stratification system for classifying the synchronous oligometastatic NSCLC. The medical records of patients from 18 centres with pathologically diagnosed synchronous oligometastatic NSCLC were retrospectively reviewed. The inclusion criteria were synchronous oligometastatic NSCLC, radical surgical treatment of the primary tumour with or without neoadjuvant/adjuvant therapy and radical treatment of all metastatic sites. The Kaplan – Meier method estimated survivals. A stratified backward stepwise Cox regression model was assessed for multivariable survival analyses. 281 patients were included. The most common site of metastasis was the brain, in 50.89 % patients. Median overall survival was 40 months (95 % CI: 29–53). Age ≤65 years (HR = 1.02, 95 % CI: 1.00–1.05; p = 0.019), single metastasis (HR = 0.71, 95 % CI: 0.45–1.13; p = 0.15) and presence of contralateral lung metastases (HR = 0.30, 95 % CI: 0.15 – 0.62; p = 0.001) were associated with a good prognosis. The presence of pathological N2 metastases negatively affected survival (HR = 2.00, 95 % CI: 1.21–3.32; p = 0.0065). These prognostic factors were used to build a simple risk classification scheme. Treatment of selected synchronous oligometastatic NSCLC with curative purpose could be conducted safely and at acceptable 5-year survival levels, especially in younger patients with pN0 disease. [ABSTRACT FROM AUTHOR]

Objectives Tumor angiogenesis is an essential and complex process necessary for the growth of all tumors which represents a potential therapeutic target. Angiogenesis inhibitors targeting vascular endothelial growth factor (VEGF) or their receptor tyrosine kinases have been approved by the FDA. In thymic epithelial tumors (TET), targeted therapies have been sporadically applied due to their rarity. To ascertain the presence of potential therapeutic targets, we analyzed by immunohistochemistry the expression of angiogenesis-related biomarkers in a large series of TET arranged in Tissue Micro Arrays (TMA). Materials and methods We assessed by immunohistochemistry the expression of the possible molecular target of anti-angiogenic therapy, i.e. VEGFA, VEGFC, VEGFD, VEGFR1, VEGFR2, VEGFR3, and PDGFRβ, in a TMA series of 200 TET collected in the framework of a multi-institutional collaborative project for Rare Diseases. Results When compared to the low-risk tumors, high-risk TET (B2, B3, carcinomas) contained higher proportion of cancer cells expressing VEGFA, VEGFC and VEGFD (P<0.001, P<0.001, and P<0.001) growth factors, and their receptors VEGFR1 (P=0.002), VEGFR2 (P=0.013), and VEGFR3 (P=0.041). No differences were observed in terms of PDGFRβ expression. Conclusions According to our data, it is possible to hypothesize the existence of multiple paracrine and/or autocrine loops in TET, particularly in the high-risk ones, involved in TET growth and progression. Anti-angiogenic agents, directed to inhibit these loops, are therefore to be considered as potential tools in advanced TET therapy. [ABSTRACT FROM AUTHOR]

Despite notable advances made in preoperative staging, unexpected nodal metastases after surgery are still significantly detected. Given the promising role of neoadjuvant targeted treatments, the definition of novel predictive factors of nodal metastases is an extremely important issue. In this study we aim to analyze the upstaging rate in patients with early stage NSCLC without evidence of nodal disease in the preoperative staging who underwent lobectomy and radical lymphadenectomy. Patients who underwent lobectomy and systematic lymphadenectomy for early stage LUAD without evidence of nodal disease at the preoperative staging using NGS analysis for actionable molecular targets evaluation after surgery were evaluated. Exclusion criteria included the neoadjuvant treatment, incomplete resection and no adherence to preoperative guidelines. A total of 359 patients were included in the study. 172 patients were female, and the median age was 68 (61–72). The variables that showed a significant correlation with the upstaging rate at the univariate analysis were the ALK rearrangement, the number of resected lymph nodes and the diameter of the tumor. This result was confirmed in the multivariate analysis, with an OR of 8.052 (CI95% 3.123–20.763, p = 0.00001) for ALK rearrangement, 1.087 (CI95% 1.048–1.127, p = 0.00001) for the number of resected nodes and 1.817 (CI95% 1.214–2.719, p = 0.004) for cT status. Our results showed that in a homogeneous cohort of patients with clinical node early stage LUAD the ALK rearrangement, the number of resected lymph nodes and the tumor diameter can significantly predict nodal metastasis. [ABSTRACT FROM AUTHOR]

Introduction So far no specific oncological strategies have been validated for locally-advanced epithelial thymic tumors (TETs). We herein report the long-term results of a large multicentric experience adopting a multimodal treatment. Methods From 01/1990 to 12/2010, the clinical data of 108 Masaoka Stage-III TETs patients surgically treated after induction therapy (IT) were retrospectively reviewed. Different IT-regimens were administered: ADOC (32 pts); PAC (38 pts); CEE (38 pts). Radiotherapy was concurrently used in 5 patients only. The end-points of the study were the evaluation of: (1) resectability; (2) overall long-term survival (LTS) and disease-free survival (DFS); and (3) independent prognostic factors. The Mann–Whitney and Fisher’s exact tests were applied to test the associations. Survival analysis was performed by the Kaplan–Meier method and log-rank test. Results Mean age and male/female ratio were 51 ± 13 years and 61/47, respectively. World Health Organization (WHO) histotype was: A in 6 pts (5.6%), AB in 18 (16.7%), B1 in 15 (13.9%), B2 in 26 (24.1%), B3 in 23 (21.3%), and thymic carcinoma in 20 (18.5%). Thirty-day mortality was 1.8%. A total of 81 (75%) had R0-resection, 11 (10.2%) R1 and 16 (14.8%) R2-resection. Adjuvant therapy was performed in 71 patients. During the follow-up a relapse of disease was observed in 38 pts(35.2%). Five-years DFS and LTS were 69.3% and 79.3%, respectively. At univariate analysis, WHO-type B3/C (“high-risk”) TETs ( p = 0.001) and recurrence of disease ( p = 0.02) were predictors of poor LTS while only a slight correlation was found for R-status and “CHT-regimen type” ( p = 0.097 and p = 0.067, respectively). At multivariate analysis WHO “high-risk” TETs (H.R.5.73;C.I.:1.77–18.57) and ADOC-regimen (H.R.2.84;C.I.:1.37–5.86) were independent predictors of poor survival. Conclusions A multimodal treatment for Stage-III thymic tumors may achieve a rewarding survival. WHO-Histology seems to be the most important prognostic factor. [ABSTRACT FROM AUTHOR]

Background Thymic epithelial tumors (TET) are the most frequent human primary mediastinal tumors in adults. A deep biological characterization of the processes at the basis of the transformed phenotype could strongly improve our understanding of the morphological and clinical heterogeneity of these diseases. MicroRNAs (miRNAs) are non-coding RNAs involved in post-transcriptional regulation and their altered expression accounts for the pathogenesis of several tumors. Objectives The aim of this study was to identify the miRNAs that are differentially expressed in tumor vs normal thymic tissues or among the different tumor histotypes and that could impact on the biology of TET. Materials and methods microRNAs expression profiling was performed by microarray analysis of formalin-fixed paraffin embedded (FFPE) tissue from 54 thymic tumor samples and 12 normal counterparts, derived from two patient cohorts. Results and conclusion We identified groups of miRNAs differentially expressed between: (i) TET and normal thymic tissues, (ii) thymomas and thymic carcinomas, (iii) histotype groups. Moreover, we identified putative molecular pathways targeted by these differentially expressed miRNAs that could be involved in thymic carcinogenesis and in the maintenance and spreading of this tumor. [ABSTRACT FROM AUTHOR]

Summary: Objective: Large cell neuroendocrine carcinoma of the lung are considered aggressive. However, reported prognoses are heterogeneous and the optimum treatment remains undefined. We retrospectively evaluated outcomes in a series of patients with a pathological diagnosis of large cell neuroendocrine lung carcinoma, who underwent lung resection. We also assessed the utility of chemotherapy in a small subgroup. Patients and methods: The clinical records of 144 consecutive patients were reviewed in a multicenter study. Survival times, assessed from the day of surgery until death or most recent follow-up, were estimated by the Kaplan–Meier method, and compared by the log rank test. Results: There were 117 men and 27 women of median age 63 years. Twelve wedge resections, 3 segmentectomies, 95 lobectomies, 7 bilobectomies and 24 pneumonectomies were performed. Induction chemotherapy was given in 21 and postoperative chemotherapy in 24. Pathologically, 73 (50%) were stage I, 29 (20%) stage II, 40 (28%) stage III and 2 stage IV. Postoperative mortality was 2.8% and morbidity 26%. Overall 5-year survival was 42.5%: 52% for stage I, 59% for stage II and 20% for stage III (p =0.001 log-rank test on Kaplan–Meier curves). A trend to better outcome was associated with preoperative or postoperative chemotherapy in stage I disease (p =0.077) compared to no chemotherapy. The response rate to induction chemotherapy was 80% in the 15 patients with data available. Conclusion: large cell neuroendocrine carcinoma of the lung are confirmed as aggressive but are also chemosensitive. Our experience suggests that chemotherapy may improve prognosis in stage I disease. [Copyright &y& Elsevier]