Nataliya Khobta

Ipilimumab: its potential in non-small cell lung cancer

Ipilimumab is a fully human monoclonal antibody that enhances antitumor immunity by way of cytotoxic T-lymphocyte antigen 4 blockade. It has already been approved by the US Food and Drug Administration for the treatment of metastatic melanoma and is being investigated for treating other solid tumors such as renal cell, prostate and lung cancers. This review details the potential of ipilimumab in the management of non-small cell lung cancer (NSCLC). In particular, ipilimumab showed promising results in a first-line NSCLC phase II study combining carboplatin/paclitaxel chemotherapy with concurrent or phased ipilimumab. The median immune-related progression-free survival was 5.68 months for the phased ipilimumab arm versus 4.63 months for chemotherapy alone (hazard ratio [HR] = 0.68, p = 0.026) and 5.52 months for the concurrent ipilimumab arm versus 4.63 months for chemotherapy alone (HR = 0.77, p = 0.094). The main adverse events were immune related, such as hypophysitis, enterocolitis, and hyperthyroidism. These adverse events may be improved with high-dose glucocorticoids and may be correlated with tumor response. Phase III studies are ongoing. Future studies may investigate ipilimumab in the management of early stage lung cancer. Strategies for potential translational research studies are also discussed to identify prognostic and predictive biomarkers for the use of ipilimumab in the treatment of patients with NSCLC.

EGFR and KRAS Mutations Predict the Incidence and Outcome of Brain Metastases in Non-Small Cell Lung Cancer

Background: Lung cancer is the leading cause of brain metastases (BM). The identification of driver oncogenes and matched targeted therapies has improved outcome in non-small cell lung cancer (NSCLC) patients; however, a better understanding of BM molecular biology is needed to further drive the process in this field. Methods: In this observational study, stage IV NSCLC patients tested for EGFR and KRAS mutations were selected, and BM incidence, recurrence and patients’ outcome were assessed. Results: A total of 144 patients (142 Caucasian and two Asian) were selected, including 11.27% with EGFR-mutant and 33.10% with KRAS-mutant tumors, and 57.04% patients had developed BM. BM incidence was more frequent in patients with EGFR mutation according to multivariate analyses (MVA) (Odds ratio OR = 8.745 [1.743–43.881], p = 0.008). Among patients with treated BM, recurrence after local treatment was less frequent in patients with KRAS mutation (OR = 0.234 [0.078–0.699], p = 0.009). Among patients with untreated BM, overall survival (OS) was shorter for patients with KRAS mutation according to univariate analysis (OR = 7.130 [1.240–41.012], p = 0.028), but not MVA. Conclusions: EGFR and KRAS mutations have a predictive role on BM incidence, recurrence and outcome in Caucasian NSCLC patients. These results may impact the routine management of disease in these patients. Further studies are required to assess the influence of other biomarkers on NSCLC BM.

Solitary cystic mediastinal lymphangioma

To the Editor: Solitary cystic mediastinal lymphangioma (CML) is a very uncommon benign vascular tumour developed from lymphatic vessels. Cystic lymphangioma is a cyst caused by a congenital malformation of the lymphatic vessels and can affect any site in the body, but <1% of lymphangiomas are mediastinal [1] and pulmonary lesions are even less common. They are most often located in the anterior mediastinum. We report a case of anterior CML in a 16-yr-old male, with a short review of the literature. A 16-yr-old male was admitted to the Thoracic Oncology unit (Hopital Nord, Marseilles, France) for recurrent left pleural effusion. The patient reported a 6-month history of chest pain and dyspnoea with hyperthermia. An initial diagnosis of left empyema was suspected. It was managed by iterative thoracentesis with saline pleural lavages, antibiotics and physiotherapy. On admission, physical examination was unremarkable except for left-sided dullness on percussion. The patient was afebrile. Chest radiography revealed a large basal opacity of the left lung silhouetting out the heart and diaphragm. Initially, this opacity was thought to represent a recurrent pleural effusion (fig. 1a). Computed tomography scans revealed a cystic lesion in the left basithoracic and anterolateral pleura with smooth borders measuring 63×90 mm (fig. 1b). No other intra- or extrapulmonary cystic lesions were found. With a presumptive diagnosis of a pleuropericardial cyst, video-assisted thoracic surgery was performed. Cytology and bacteriology were performed. The cyst contained serous fluid and had no connection or adhesion to adjacent organs, and was vascularised by …

The place of pemetrexed in the management of non-small-cell lung cancer patients

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer death worldwide. Chemotherapy is included in the management of the majority of NSCLC patients either in addition to a local treatment (surgery/radiotherapy) or alone. In this setting, pemetrexed has become one of the most important partners of current chemotherapy regimens for nonsquamous NSCLC patients. Indeed, pemetrexed demonstrated a comparable efficacy to other previously available drugs in NSCLC, with however a better safety profile and an easier schedule of administration. In addition, pemetrexed demonstrated a greater efficacy in nonsquamous NSCLC that lead to an exploration of the underlying potential biological background. It is now suggested that the tumor thymidylate synthase level may act as a predictor of pemetrexed efficacy, therefore potentially providing clinicians in the future with a predictor of efficacy, which it is usually lacking with standard chemotherapies.