Multimodal treatment of oligometastatic non-small cell lung cancer.

The management of patients with oligometastatic non-small cell lung cancer has undergone significant improvement in recent years. The combination of increase in sensitivity of diagnostic tests, development in systemic therapies, surgical techniques and radiotherapy allowing radical ablative treatment of metastases have significantly influenced the treatment of advanced lung cancer, mainly in the patients in which these treatment modalities converge.We report a rare case of a young patient with an oligometastatic lung adenocarcinoma with a single synchronous brain metastasis, who underwent aggressive locoregional and systemic therapies and is still in annual follow-up with excellent quality of life and progression-free survival of 164 months.

Pharmacogenetics of advanced lung cancer: Predictive value of functional genetic polymorphism AGXT Pro11Leu in clinical outcome?

INTRODUCTION: AGXT gene codes for the enzyme alanine glyoxylate aminotransferase, which is involved in hepatic peroxisomal metabolism of platinum-based chemotherapeutic agents. The association of genetic variant AGXT rs34116584 on the clinical outcome and response to chemotherapy of patients with non-small cell lung cancer (NSCLC) remains to be established. Our aim was to evaluate the association of functional AGXT gene polymorphism in NSCLC progression, considering as primary and secondary endpoint, progression free survival (PFS) and overall survival (OS), respectively. METHODS: Genotyping of theAGXT rs34116584 genetic polymorphism was performed by mass spectrometry on 168 DNA samples from patients with NSCLC (stages IIIA-IVB). Univariate survival analysis included the study of Kaplan-Meier curves with the Log-Rank test, while Cox regression was used as a multivariate analysis. RESULTS: Multivariate analysis showed shorter PFS for T carriers [HR=2.0, 95% CI, 1.4-3.0, p<0.0001] and shorter OS [HR=1.8, 95% CI, 1.1-3.0, p=0.017] globally, as well as in a subgroup of patients (n=144) treated with first line platinum-based chemotherapy [HR=2.0, 95% CI, 1.3-3.1, p=0.001] and [HR=1.8, 95% CI, 1.1-3.1, p=0.026], respectively. CONCLUSION: This polymorphism seems to have an impact on NSCLC progression, opening new perspectives for its inclusion as a pharmacogenetic predictor of response to platinum-based chemotherapy.

Germline Genetic Variants of the Renin-Angiotensin System, Hypoxia and Angiogenesis in Non-Small Cell Lung Cancer Progression: Discovery and Validation Studies.

INTRODUCTION: The renin-angiotensin system (RAS) is involved in cell proliferation, immunoinflammatory response, hypoxia and angiogenesis, which are critical biological processes in lung cancer. Our aim was to study the association of putatively functional genetic polymorphisms in genes coding for proteins involved in RAS, hypoxia and angiogenesis with non-small cell lung cancer (NSCLC) prognosis. METHODS: Genotyping of 52 germline variants from genes of the RAS and hypoxic/angiogenic factors/receptors was performed using MassARRAY iPLEX Gold in a retrospective cohort (n = 167) of advanced NSCLC patients. Validation of the resulting genetic markers was conducted in an independent group (n = 190), matched by clinicopathological characteristics. RESULTS: Multivariate analysis on the discovery set revealed that MME rs701109 C carriers were protected from disease progression in comparison with homozygous T (hazard ratio (HR) = 0.5, 95% confidence interval (CI) = 0.2-0.8, p = 0.010). Homozygous A and T genotypes for KDR rs1870377 were at increased risk for disease progression and death compared to heterozygous (HR = 1.7, 95% CI = 1.2-2.5, p = 0.005 and HR = 2.1, 95% CI = 1.2-3.4, p = 0.006, respectively). Carriers of homozygous genotypes for ACE2 rs908004 presented increased risk for disease progression, only in the subgroup of patients without tumour actionable driver mutations (HR = 2.9, 95% CI = 1.3-6.3, p = 0.010). Importantly, the association of homozygous genotypes in MME rs701109 with risk for disease progression was confirmed after multivariate analysis in the validation set. CONCLUSION: This study provides evidence that MME polymorphism, which encodes neprilysin, may modulate progression-free survival in advanced NSCLC. Present genetic variation findings will foster basic, translational, and clinical research on their role in NSCLC.

Recurrence and Risk Factors for Relapse in Patients with Non-Small Cell Lung Cancer Treated by Surgery with Curative Intent.

INTRODUCTION: Surgery remains the potentially curative treatment for early-stage non-small cell lung cancer (NSCLC). Despite this, tumor recurrence is the most common cause of treatment failure after surgery. METHODS: Data were collected retrospectively from clinical files of patients who underwent lung surgery for NSCLC from January 2008 to December 2012 in a University Hospital. Demographic data, tumor characteristics, type of surgery and recurrence were recorded. A comparison of the distribution of variables using adjustment tests was made. RESULTS: The study included 102 patients, 68.6% were male with a mean age of 63.7 ± 9.3 years old. The majority of tumors had a peripheral location (72.5%) and consisted of adenocarcinomas (61.8%). The most frequently performed surgery was lobectomy. Recurrence was noted in 43.1% of cases. Mean disease-free survival was 57.9 ± 3.8 months. Multifactorial analyses showed that stage IIIA, tumor located in other lobes than the right lower lobe and pleural invasion were independent predictors of recurrence. CONCLUSION: Our recurrence rate was similar to those in the international literature. As in other studies, we found a positive relation between the lymphatic permeation and pleural invasion and the risk of lung cancer recurrence. We consider that some characteristics of the tumor should be assessed to define alternative modalities of treatment and follow-up in order to predict and rapidly recognize the recurrence.

[Epithelioid hemangioendothelioma of the pleura - A rare presentation of a clinical case]. / Hemangioendotelioma epitelióide da pleura - Uma apresentação rara a propósito de um caso clínico.

Epithelioid Hemangioendothelioma (EHE) is a vascular tumour with rare pleural presentation. As there are a small number of cases described in the literature the authors present the case of a 65 -year -old woman, who was admitted to the Emergency Department for a right -sided chest pain, which progressed over 7 months, after a thoracic trauma. The chest X -ray showed signs of a moderate right -sided pleural effusion. A pleural -pulmonary biopsy carried out by toracotomy established the histological diagnosis of EHE of the pleura. Due to the locally advanced stage of the tumour, chemotherapy with carboplatin and etoposide was prescribed and the patient died 6 months later. This case confirms that pleural EHE has an aggressive behaviour, similar to an angiossarcoma, with a median survival of only a few months after diagnosis.