Resected pN1 non-small cell lung cancer: recurrence patterns and nodal risk factors may suggest selection criteria for post-operative radiotherapy.

PURPOSE: To describe the pattern of recurrence in resected pN1 non-small cell lung cancer (NSCLC) and to identify factors predicting an increased risk of locoregional recurrence (LR) or distant metastasis (DM) to define a selected population who may benefit from postoperative radiotherapy (PORT). METHODS: 285 patients with resected pN1 NSCLC were identified. Patients with positive surgical margins, undergoing neoadjuvant treatment or PORT, were excluded. LR was defined as first event of recurrence at the surgical bed, ipsilateral hilum or mediastinum, and other sites were considered as DM. Kaplan-Meier actuarial estimates of overall survival (OS), progression-free survival (PFS), freedom from LR (FFLR) and freedom from DM (FFDM) in different subgroups were compared with the log-rank test. Multivariate analysis was calculated. RESULTS: 202 patients met the inclusion criteria, 24 % received adjuvant chemotherapy. The median follow-up was 39 months. The total number of recurrences was 118 (64.4 %): 44 (24 %) and 74 (40.4 %) for LR and DM, respectively. Five-year OS and PFS rates were 39.2 and 33.3 %, respectively. Extra capsular extension (ECE) (RR 2.10, p = 0.01) and lymph nodal ratio (LNR) >0:15 (RR 1.68, p = 0.015) were associated with a worse PFS. ECE and LNR >0.15 were significantly related to a worst FFLR (RR 3.04 and 4.42, respectively), and adenocarcinoma to an unfavorable FFDM (RR 1.97, p = 0.013). CONCLUSIONS: Nodal factors as high LNR and ECE can predict an increased risk of worse FFLR and PFS. Prospective data on selected patients, treated with modern radiotherapy techniques, need to be collected to re-evaluate the role of radiotherapy.

CT texture analysis as predictive factor in metastatic lung adenocarcinoma treated with tyrosine kinase inhibitors (TKIs).

PURPOSE: To assess the predictive and prognostic value of pre-treatment CT texture features in lung adenocarcinoma treated with tyrosine kinase inhibitors (TKI). MATERIALS AND METHODS: Texture analysis was performed using commercially available software (TexRAD Ltd, Cambridge, UK) on pre-treatment contrast-enhanced CT studies from 50 patients with metastatic lung adenocarcinoma treated by TKI. Texture features were quantified on a 5-mm-thick central slice of the primary tumor and were correlated with progression-free and overall survival (PFS and OS) using an internally cross-validated machine learning approach then validated on a bootstrapped sample. RESULTS: Median PFS and OS were 10.5 and 20.7 months, respectively. A noninvasive signature based on five texture parameters predicted 6-month progression with Area Under the Curve (AUC) of 0.8 (95% CI) and 1-year progression with AUC of 0.76. A high-risk group had hazard ratios for progression of 4.63 and 5.78 when divided by median and best cut-off points, respectively. Texture signature did not correlate with OS. Available clinical variables did not correlate with PFS or with OS. CONCLUSION: Texture features seem to be associated with PFS in lung adenocarcinoma treated with TKI.

Significance of neutrophil-to-lymphocyte ratio in Western advanced EGFR-mutated non-small cell lung cancer receiving a targeted therapy.

PURPOSE: Lung cancer is one of the leading causes of cancer-related death worldwide and, although targeted therapy with tyrosine kinase inhibitors has dramatically improved the rates of response and survival in advanced EGFR-mutated adenocarcinoma, the overall outcome remains unsatisfactory. Therefore, new prognostic factors, preferably simple, inexpensive, and easy to reproduce on a large scale, are needed. We performed a retrospective analysis of our database including 63 western Caucasian patients with advanced EGFR-mutated lung adenocarcinoma and receiving gefitinib, erlotinib, or afatinib as first- or second-line therapy. Several studies demonstrated a strong link between elevated neutrophil-to-lymphocyte ratio (NLR) and poor prognosis both in early and advanced stages of non-small-cell lung cancer (NSCLC). METHODS: From January 2011 to December 2015, 63 consecutive elegible patients with advanced EGFR-mutated NSCLC were included in this analysis from 5 institutions. The NLR was derived from the absolute neutrophil and the absolute lymphocyte counts of a full blood count and the cutoff value was determined according to the mean NLR level. RESULTS: Despite the small sample analyzed, we found that NLR has a prognostic role for progression-free survival (PFS) and overall survival (OS), reaching a statistically significant difference with a better PFS and OS in the lower NLR group. CONCLUSIONS: Pretreatment NLR seems to represent a reliable, simple, and easy to reproduce laboratory tool to predict outcome and response to cancer therapies in this setting of Western Caucasian patients with EGFR-mutated NSCLC.

Economic burden of patients affected by non-small cell lung cancer (NSCLC): the LIFE study.

PURPOSE: Non-small cell lung cancer (NSCLC) is a condition with significant clinical burden for patients and relevant economic impact. Limited evidence exists on the management costs of NSCLC patients, especially in the late phases of the disease. The main objective of this analysis was to evaluate the economic impact of clinical management of NSCLC patients in the Italian population. METHODS: This evaluation was an economic analysis of the observational and multicentre study LIFE, which described the therapeutic approach in routine clinical practice for NSCLC patients, progressing after first-line treatment. This study evaluated resource consumption in different Italian hospitals, including specialist visits, hospitalizations, accesses to first aid, pharmacological treatment, laboratory tests and palliative care. The National Healthcare Service perspective was adopted. RESULTS: In this study, N = 191 patients enrolled in the LIFE study were included. Patients were aged 64.2 years and were predominantly males (66%). In the different line of treatments, monthly costs of patients ranged between €1471 (first line) and €1788 (third line). The overall healthcare cost over the average period of observation (16.4 months) was €25,859 per patient. Overall, oncology therapy was the cost driver, although the composition of medical costs changed across the different lines of treatment, with costs for concomitant medication and palliative care being predominant in late phase of the disease. CONCLUSIONS: The economic burden of NSCLC is extremely high during the overall period of treatment, and a significant level of care is required in each stage of the disease.

Advanced non-small cell lung cancer management in patients progressing after first-line treatment: results of the cross-sectional phase of the Italian LIFE observational study.

PURPOSE: LIFE (non-small cell Lung cancer management In patients progressing after First-linE of treatment in the metastatic setting) is a multicentre Italian observational study, including a cross-sectional and a longitudinal phase, with the aim of describing the therapeutic approach in clinical practice for advanced non-small cell lung cancer (NSCLC) patients, progressing after first-line treatment. METHODS: In this paper, the cross-sectional phase is outlined, with the primary endpoint of describing the proportion of patients receiving second-line treatment among those progressed during or after first-line treatment according to clinical practice. RESULTS: From July 2011 to January 2012, 603 patients were enrolled and 541 (90 %) were evaluable. A total of 464 (86 %) patients received a second-line therapy outside clinical trials. Chemotherapy and targeted therapies were administered to 65 and 34 % of patients, respectively (1 % both). No tissue collection was required within the observational trial, and biomarkers analysis was performed at diagnosis or later in 314 patients (58 %). In details, activating epidermal growth factor receptor mutations were detected in 21 % of 311 evaluable patients, Kirsten rat sarcoma 2 viral oncogene homolog mutation in 22 % of the 77 evaluable patients and anaplastic lymphoma kinase translocations analysis was performed in 74 patients and resulted positive in 23 % of cases. These high proportions were probably due to enriched patient population tested. CONCLUSIONS: These results showed a pattern of care for NSCLC second-line therapy which reflects international guidelines recommendations and current expected clinical practice. Interestingly, biomarkers analyses were performed in a higher percentage than expected.

Medical treatment choices for patients affected by advanced NSCLC in routine clinical practice: results from the Italian observational "SUN" (Survey on the lUng cancer maNagement) study.

Lung cancer is the most common cancer in the world today, in terms of both incidence and mortality. Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers, and the majority of people diagnosed with NSCLC have locally advanced or metastatic disease. Treatment algorithms have rapidly changed in the last 10 years because of the introduction of new chemotherapeutic and targeted agents in clinical practice. SUN is a 1-year longitudinal observational multicenter study that has consecutively enrolled patients affected by stage IIIB or IV NSCLC with the aim to describe the pattern of care and evolving approaches in the treatment of advanced NSCLC. 987 consecutive NSCLC patients were enrolled between January 2007 and March 2008 at the 74 participating centers throughout Italy and a 12-month follow-up was performed. Cyto-histological diagnosis was performed mainly by broncoscopy with only 24% by CT-scan guided fine-needle aspiration biopsy. 91.4% of the patients received a first-line medical treatment and 8.6% supportive care only. Median age of patients receiving first-line treatment was 66 years. First-line chemotherapy consisted of a single agent in 20% of patients and combination chemotherapy in 80%. The most frequently used chemotherapy regimens were cisplatin plus gemcitabine and carboplatin plus gemcitabine. Median survival of patients receiving first-line chemotherapy was 9.1 months. 32% percent of patients received a second-line treatment that consisted of chemotherapy in 71% of cases and erlotinib in 29%. Overall third-line treatment was given to 7.3% of patients. These results showed a pattern of care for advanced NSCLC that reflects the current clinical practice in Italy at the study time with a high adherence to the International guidelines by the Italian Oncologists.