Significance of the Presence of Microscopic Vascular Invasion After Complete Resection of Stage I–II pT1-T2N0 Non-small Cell Lung Cancer and Its Relation with T-Size Categories: Did the 2009 7th Edition of the TNM Staging System Miss Something?

Introduction:The aim of this study was to assess the significance of microscopic vascular invasion (MVI) in a population of resected patients with early-stage non-small cell lung cancer (NSCLC), along with an analysis of the effect of the combination of MVI and tumor size for the T-size categories T1a-T2b according to the 2009 7th edition of the tumor, node, metastasis (TNM) classification.Methods:From January 1993 to August 2008, 746 patients with pT1-T2N0 NSCLC received resection at our institution. MVI was ascertained using histopathological and immunohistochemical techniques.Results:MVI was observed in 257 patients (34%). Prevalence was higher in adenocarcinoma (ADK) than in squamous cell carcinoma (p = 0.002). A significant correlation was found between MVI and ADK (p = 0.03), increased tumor dimension (p = 0.05), and the presence of tumor-infiltrating lymphocytes (p = 0.02). The presence of MVI was associated with a reduced 5-year survival overall (p = 0.003) and in ADK (p = 0.0002). In a multivariate survival analysis, MVI was an indicator of poor survival overall (p = 0.003) and in ADK (p = 0.0005). In each T category (T1a-T2b) of the 2009 TNM staging system, survival of MVI+ patients was significantly lower than the corresponding MVI− patients; T1a and T1b MVI+ patients had a survival similar to MVI− T2 patients.Conclusions:The finding of MVI in pT1-T2N0 NSCLC is frequent. MVI correlates with adenocarcinoma histotype, increased tumor dimensions, and tumor-infiltrating lymphocytes. The presence of MVI is an independent negative prognostic factor. In our experience, MVI was a stronger prognostic indicator than T size in T1a-T2b categories according to the 2009 TNM staging system

Valutazione economica in base allo studio NAVoTRIAL01 con riferimento al contesto sanitario italiano: Vinorelbine orale e Cisplatino o Pemetrexed e Cisplatino seguiti da mantenimento rispettivamente con Vinorelbine orale e Pemetrexed nel trattamento del Carcinoma Polmonare Non a Piccole Cellule Non Squamoso (NS-NSCLC) in stadio avanzato

Background Vinorelbine and Cisplatin is a standard treatment in non small cell lung cancer; oral Vinorelbine is registered in 45 countries. Pemetrexed and Cisplatin are recommended in front-line chemotherapy of non-squamous non small cell lung cancer (NS-NSCLC). An economic evaluation of oral Vinorelbine plus Cisplatin and Pemetrexed plus Cisplatin was implemented in NS-NSCLC patients, adopting specific costs and clinical settings reflecting the Italian practice

LIGHT as regulator of bone homeostasis during osteolytic bone metastasis formation in non-small cell lung cancer patients

Tumor necrosis factor superfamily member 14 (TNFSF14), LIGHT is one of the cytokines produced by tumor and immune cells, which promotes homeostasis of lymphoid organs, liver and bone. Nonsmall cell lung cancer (NSCLC) commonly metastasizes bone, altering bone homeostasis and causing osteolysis. Here we investigated the role of LIGHT in NSCLC-induced osteolytic bone disease. The LIGHT expression in monocytes was higher in patients with metastatic bone lesions than in non-bone metastatic ones (66.5 ± 24.5 vs 43.3 ± 25.2 mean ± SD, p = 0.001), in healthy donors (66.5 ± 24.5 vs 8.5 ± 4.6 p = 0.0002), and in non-bone metastatic patients than in healthy donors (43.3 ± 25.2 vs 8.5 ± 4.6, p = 0.0001). Serum LIGHT levels were also significantly higher in bone metastatic patients than in non-bone metastatic ones (186.8 ± 191.2 pg/ml vs 115.8 ± 73 pg/ml, p = 0.04) and in healthy donors (186.8 ± 191.2 pg/ml vs 85.7 ± 38.4 pg/ml, p = 0.04). A neutralizing mAb anti-LIGHT added to osteoclast (OC) cultures of both bone and non-bone metastases inhibited osteoclastogenesis, but the decrease was statistically significant only for bone metastatic patients (272 ± 98 vs 132 ± 74, p = 0.01). To investigate the role of LIGHT in NSCLC- induced bone lesion in vivo, we performed an intratibial injection of a mouse lung cancer cell line LLC-1, in wild-type (WT) and LIGHT KO mice. The WT-injected mice displayed a significant reduction of about 20% for BV/TV, Tb.N, Tb.Th, and Tb.Sp compared to the WT-vehicle mice (pb 0.01). These parameters did not show significant variation for KO-injected mice vs vehicle or for WT-injected mice vs KO-injected mice. These data indicate LIGHT as a regulator of bone homeostasis during NSCLC metastatic invasion, thus it may be a novel therapeutic target in osteolytic bone metastases

Novel therapeutic strategies for patients with NSCLC that do not respond to treatment with EGFR inhibitors

Introduction: Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) yields tumour responses in non-small cell lung cancer (NSCLC) patients harbouring activating EGFR mutations. However, even in long-lasting responses, resistance to EGFR TKIs invariably occurs. Areas covered: This review examines resistance mechanisms to EGFR TKI treatment, which mainly arise from secondary EGFR mutations. Other resistance-inducing processes include mesenchymal\u2013epithelial transition factor (MET) amplification, epithelial\u2013mesenchymal transformation, phenotypic change from NSCLC to small-cell lung carcinoma, and modifications in parallel signalling pathways. Current therapeutic strategies to overcome these EGFR TKI resistance mechanisms focus on the inhibition or blocking of multiple members of the ErbB family. Several molecules which target multiple ErbB receptors are being investigated in NSCLC and other indications including afatinib, an ErbB Family Blocker, as well as dacomitinib and lapatinib. Novel, non-quinazoline, EGFR inhibitors, that also target EGFR activating and resistance (T790M) mutations, are currently under clinical development. Other therapeutic strategies include inhibition of parallel and downstream pathways, using agents which target heat shock protein (HSP)90 orpoly (ADP-ribose) polymerase in addition to mammalian target of rapamycin (mTOR), monoclonal antibodies against the insulin-like growth factor-1 receptor, and fulvestrant-mediated oestrogen receptor regulation. Conclusion: Improved understanding of mechanisms underlying resistance to EGFR TKIs emphasises the importance of a genotype-guided approach to therapy. Elucidation of resistance mechanisms is indeed crucial to target innovative therapeutic approaches and to improve the efficacy of anticancer regimes in NSCLC