EGFR-Targeted Therapy for Non-Small Cell Lung Cancer: Focus on EGFR Oncogenic Mutation

The two essential requirements for pathologic specimens in the era of personalized therapies for non-small cell lung carcinoma (NSCLC) are accurate subtyping as adenocarcinoma (ADC) versus squamous cell carcinoma (SqCC) and suitability for EGFR molecular testing, as well as for testing of other oncogenes such as EML4-ALK and KRAS. Actually, the value of EGFR expressed in patients with NSCLC in predicting a benefit in terms of survival from treatment with an epidermal growth factor receptor targeted therapy is still in debate, while there is a convincing evidence on the predictive role of the EGFR mutational status with regard to the response to tyrosine kinase inhibitors (TKIs).This is a literature overview on the state-of-the-art of EGFR oncogenic mutation in NSCLC. It is designed to highlight the preclinical rationale driving the molecular footprint assessment, the progressive development of a specific pharmacological treatment and the best method to identify those NSCLC who would most likely benefit from treatment with EGFR-targeted therapy. This is supported by the belief that a rationale for the prioritization of specific regimens based on patient-tailored therapy could be closer than commonly expected.     

Quantitative evaluation of background parenchymal enhancement (BPE) on breast MRI. A feasibility study with a semi-automatic and automatic software compared to observer-based scores

Objective:

To evaluate quantitative measurements of background parenchymal enhancement (BPE) on breast MRI and compare them with observer-based scores.

Methods:

BPE of 48 patients (mean age: 48 years; age range: 36–66 years) referred to 3.0-T breast MRI between 2012 and 2014 was evaluated independently and blindly to each other by two radiologists. BPE was estimated qualitatively with the standard Breast Imaging Reporting and Data System (BI-RADS) scale and quantitatively with a semi-automatic and an automatic software interface. To assess intrareader agreement, MRIs were re-read after a 4-month interval by the same two readers. The Pearson correlation coefficient (r) and the Bland–Altman method were used to compare the methods used to estimate BPE. p-value <0.05 was considered significant.

Results:

The mean value of BPE with the semi-automatic software evaluated by each reader was 14% (range: 2–79%) for Reader 1 and 16% (range: 1–61%) for Reader 2 (p > 0.05). Mean values of BPE percentages for the automatic software were 17.5 ± 13.1 (p > 0.05 vs semi-automatic). The automatic software was unable to produce BPE values for 2 of 48 (4%) patients. With BI-RADS, interreader and intrareader values were κ = 0.70 [95% confidence interval (CI) 0.49–0.91] and κ = 0.69 (95% CI 0.46–0.93), respectively. With semi-automated software, interreader and intrareader values were κ = 0.81 (95% CI 0.59–0.99) and κ = 0.85 (95% CI 0.43–0.99), respectively. BI-RADS scores correlated with the automatic (r = 0.55, p < 0.001) and semi-automatic scores (r = 0.60, p < 0.001). Automatic scores correlated with the semi-automatic scores (r = 0.77, p < 0.001). The mean percentage difference between automatic and semi-automatic scores was 3.5% (95% CI 1.5–5.2).

Conclusion:

BPE quantitative evaluation is feasible with both semi-automatic and automatic software and correlates with radiologists'' estimation.

Advances in knowledge:

Computerized BPE quantitative evaluation is feasible with both semi-automatic and automatic software. Computerized BPE quantitative scores correlate with radiologists'' estimation.     

Impact of intensified chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC) in clinical routine in Europe

Background

Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis. Gemcitabine is the standard chemotherapy for patients with metastatic pancreatic adenocarcinoma (MPA). Randomized clinical trials evaluating intensified chemotherapies including FOLFIRINOX and nab-paclitaxel plus gemcitabine (NAB+GEM) have shown improvement in survival. Here, we have evaluated the efficacy of intensified chemotherapy versus gemcitabine monotherapy in real-life settings across Europe.

Anesthesia and the developing brain: a way forward for clinical research

It is now well established that many general anesthetics have a variety of effects on the developing brain in animal models. In contrast, human cohort studies show mixed evidence for any association between neurobehavioural outcome and anesthesia exposure in early childhood. In spite of large volumes of research, it remains very unclear if the animal studies have any clinical relevance; or indeed how, or if, clinical practice needs to be altered. Answering these questions is of great importance given the huge numbers of young children exposed to general anesthetics. A recent meeting in Genoa brought together researchers and clinicians to map a path forward for future clinical studies. This paper describes these discussions and conclusions. It was agreed that there is a need for large, detailed, prospective, observational studies, and for carefully designed trials. It may be impossible to design or conduct a single study to completely exclude the possibility that anesthetics can, under certain circumstances, produce long‐term neurobehavioural changes in humans; however , observational studies will improve our understanding of which children are at greatest risk, and may also suggest potential underlying etiologies, and clinical trials will provide the strongest evidence to test the effectiveness of different strategies or anesthetic regimens with respect to better neurobehavioral outcome.