BACKGROUND: Detection of genetic alterations in the EGFR tyrosine kinase domain is a major concern in the management of non-small cell lung cancer because it conditions access to tyrosine kinase inhibitors. In practice, it is possible to characterize only well-documented mutations or to sequence all relevant EGFR exons and also other targets of theranostic interest. This prospective study compares the targeted EGFR characterization on Idylla platform (Biocartis) and a more extensive one by next generation sequencing using Ion Torrent technology.
METHODS: A total of 100 formalin-fixed paraffin-embedded tumour samples were tested simultaneously by both techniques under the conditions recommended by the suppliers. The comparison covered all technical and practical aspects of the laboratory.
RESULTS: At least one EGFR mutation of interest for tyrosine kinase inhibitors for 9 and 7 samples was detected respectively by sequencing and by the Idylla system. For three samples, EGFR sensitive mutations to tyrosine kinase inhibitors were detected only by next-generation sequencing. In addition, for 37 samples, mutations of clinical interest outside EGFR were characterized by sequencing and communicated to the prescriber.
CONCLUSIONS: Idylla technology allows the rapid characterization of a majority of EGFR variants. The result can be optimized by careful analysis of the amplification curves with the Idylla Explore tool or by increasing the amount of initial material. A complementary new generation sequencing analysis for non-contributory results by Idylla should also be recommended.

Stereotactic radiotherapy (or Stereotactic body radiotherapy [SBRT]) is a technique currently well established in the therapeutic arsenal for the management of bronchial cancers. It represents the standard treatment for inoperable patients or who refuses surgery. It is well tolerated, especially in elderly and frail patients, and the current issue is to define its indications in operated patients, based on retrospective and randomized trials comparing stereotactic radiotherapy and surgery, with results equivalents. This work analyzes in detail the different aspects of pulmonary stereotactic radiotherapy and suggests arguments that help in the therapeutic choice between surgery and stereotaxic irradiation. In all cases, the therapeutic decision must be discussed in a multidisciplinary consultation meeting, while informing the patient of the possible therapeutic options.

In cases of advanced EGFR mutation-positive non-small cell lung cancer, first or second generation EGFR-tyrosine kinase inhibitors (TKI-EGFR 1G or TKI-EGFR 2G) are recommended as first line treatment. Inexorably, progressive disease occurs and, in 50-60% of the cases, is secondary to a T790M resistant mutation. The prescription of osimertinib (TKI-EGFR3G) in second line is dependent on identification of the T790M mutation. We report 7 cases in which the identification of the T790M mutation required repeated analyses of cell free DNA and/or biopsies over a period of time. In some cases, a positive result was obtained a long time after progressive disease had been diagnosed during treatment with first or second generation EGFR-TKI. We discuss here the different modalities of screening for the T790M mutation and we encourage persevering in this search when no alternative mechanism of resistance has been identified.

BACKGROUND: Primary lung cancer is the leading cause of cancer death in men in the world. Although the introduction of new drugs, new therapeutic strategies and despite therapeutic advances, the prognosis is relatively improved during the last years.
OBJECTIVE: To evaluate the prognosis of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) and to identify prognostic factors at these stages.
METHODS: A retrospective study, including 140 cases of locally advanced or metastatic NSCLC diagnosed in our department between 2003 and 2013.
RESULTS: The average age was 61±10 years (35 to 90 years). Sex ratio was 18. The delays management were 80±25 days for presentation, 45±20 days for the diagnostic, while the treatment delay was 8±2.33 days. The cancer was at stage IIIA in 14%, IIIB in 27% and IV in 59%. Six months and one-year survival was between 50 and 74% and between 9 and 25%, respectively. Better survival was observed in patients with NSCLC on stage III, having better performance status, having comorbid conditions, with prolonged delays management, a short therapeutic delay and patients who received specific antitumor treatment.
CONCLUSIONS: The prognostic factors in locally advanced and metastatic NSCLC in our patients were: stage of cancer, performance status, comorbid conditions, delay of management and specific antitumoral treatment. These factors should be considered in the management of patients with advanced NSCLC.

Cabozantinib is an oral multiple tyrosine kinase receptor inhibitor (ITK): VEGFR2, c-MET and RET. Inhibition of VEGFR and c-MET decrease resistance of VEGFR inhibitor via c-MET axis. Cabozantinib improve progression-free survival (PFS) in progressive metastatic medullary thyroid cancer (MTC): 4 months in the placebo group and 11.2 months in the cabozantinib group (P<0.001) in all patient subgroups including those with or without prior ITK and RET mutation status. Cabozantinib increased overall survival (OS) compared with everolimus in patients with advanced renal cell carcinoma who progressed after previous VEGFR ITK treatment: 21.4 months in cabozantinib group and 16.5 months in everolimus group (P<0.0003). Cabozantinib obtained the AMM for the treatment of progressive metastatic MTC and advanced renal cell carcinoma. Cabozantinib is a new option in the treatment of MTC by inclusion in therapeutic trials (no payment in this indication) and advanced renal cell carcinoma (hospital delivery). Its tolerance is similar to anti-angiogenic therapies and justifies an optimal management of the secondary effect.

BACKGROUND: Ground-glass opacities nodules are frequently detected with the advances of radiological imaging. These can be preinvasive lesions such as atypical adenomatous hyperplasia but also invasive lesions. It leads to question in patients with lung cancer about treatment strategy and follow up.
METHODS: We report the case of a 72 years-old woman followed for a lung adenocarcinoma with an EGFR mutation of the right upper lobe stage IIb. The CT scan shows multiple pure ground-glass opacities in the same lobe of the primitive tumor but also in the other lobe. On the piece of lobectomy, histopathology of two ground-glass opacities showed atypical adenomatous hyperplasia.
CONCLUSIONS: Ground-glass opacities nodules could be found in patients with an operable lung cancer. These can be multiple and match with atypical adenomatous hyperplasia but also carcinomas lesions. The radiological surveillance is still the standard. The strategy for surgical resection has to be defined especially in case of multiple lesions which can require repeated surgical resection.

Platinum-based perioperative chemotherapy is actually the standard of care in stage II-IIIa non-small cell lung cancer (NSCLC). A benefit may also be seen in stage IB NSCLC with tumors of more than 4cm of diameter. Perioperative chemotherapy improves 5-year survival of 4 to 15%. This benefit is mainly proved by postoperative chemotherapy trials. Nevertheless, preoperative chemotherapy has advantages: a better tolerance, an estimation of tumor chemosensibility, without an increased postoperative morbimortality. However, pTNM and pathological tumor analyses are modified. Indications of postoperative radiotherapy are limited. In early stage NSCLC (stage I-II), radiotherapy worsens survival. Radiotherapy is routinely achieved in NSCLC with parietal tumor invasion and incomplete tumor resection. Indications of immunotherapy and targeted therapies in case of oncogenic addiction remain to be established in resected NSCLC. Several biomarkers are studied to better describe the indications of perioperative chemotherapy: recognize groups of patients with a worse prognosis and distinguish chemosensibility of the tumor.

BACKGROUND: Among patients with non-small-cell lung cancer, coexistence of EGFR mutation and ALK rearrangement is rare. We describe the clinical features of two patients with this double anomaly.
METHODS: A 62-year-old Caucasian non-smoking woman was diagnosed with cT4N0M0 lung adenocarcinoma. Initial biopsy showed EGFR mutation and ALK rearrangement. She received cisplatin-gemcitabine, followed by 17 months of gemcitabine. Owing to progression, she received erlotinib for 14 months, then paclitaxel for 6 months and finally crizotinib. A partial response was achieved and maintained for 24 months. A 45-year-old Caucasian woman, light smoker, was diagnosed with cT2N3M0 lung adenocarcinoma. Only EGFR mutation was found on initial analysis. She underwent treatment with cisplatin-gemcitabine and thoracic radiotherapy. Progression occurred after 8 months and afatinbib was started. Eight months later, progression was observed with a neoplasic pleural effusion in which tumor cells expressing ALK rearrangement were found. A new FISH analysis was performed on the initial tumor but did not find this rearrangement. Despite a third line of crizotinib, the patient died one month later.
CONCLUSIONS: The literature shows 45 other cases of these two abnormalities, observed either from the start or during follow-up. EGFR\'s TKI were almost always given before ALK\'s TKI.
CONCLUSIONS: Therapeutic strategy needs to be clarified in cases of double alteration. With regard to the second patient, appearance of ALK rearrangement may constitute a resistance mechanism to EGFR\'s TKI.

The acquisition of a resistance EGFR mutation in exon 20 (T790M) occurs in half of the cases of secondary resistance to EGFR tyrosine kinase inhibitors (TKI), given in first-line treatment in advanced EGFR-mutated non-small cell lung cancers (NSCLC). Osimertinib (AZD9291, Tagrisso®) is a third-generation, irreversible EGFR TKI, active in case of T790M mutation. A large phase I trial showed the efficacy of osimertinib after failure of first-generation EGFR TKI (erlotinib, gefitinib), with response rate at 51% and up to 61% in case of T790M mutation. Progression-free survival was 9.6 months in case of T790M. Toxicity profile was acceptable, with mainly digestive (diarrhea) and skin (rash) side effects. Preliminary data from a phase II trial confirmed these efficacy and safety data. Screening of T790M mutation at the time of progression with TKI can be performed in circulating tumor DNA in plasma, with good diagnostic performances.

Erlotinib can be prescribed in the treatment of locally advanced or metastatic non-small lung cancer cell (NSCLC) after failure of at least one prior chemotherapy regimen on the basis of the BR-21 study. Several publications have recently questioned these results. The metabolic imaging of solid tumours by positron emission tomography is a research field that could help customize the treatment of NSCLC and so complement the treatment approaches allowed by genetic analyses. This strategy is part of an innovative \"early metabolic look\" approach. The primary objective of this study is to determine if metabolic progression observed between the 7th and 14th day after initiation of treatment with erlotinib by 3\'-Deoxy-3\'-[18F]-Fluorothymidine PET in patients with EGFR naive NSCLC is predictive for morphological progression after 6 to 8 weeks of treatment. A health economic analysis will be conducted. This study is particularly innovative because it begins the exploration of the era of metabolic evaluation of therapeutic response in NSCLC.