Inflamed Tumor Phenotype as Predictor of Long-Term Response to Pembrolizumab in an EGFR-Mutated Non-Small Cell Lung Cancer (NSCLC) Patient with Acquired Resistance to Afatinib: a Case Report and Review of the Literature.

Treatment with immune checkpoint inhibitors (ICIs) that target the programmed cell death 1/programmed cell death ligand-1 (PD-1/PD-L1) axis is usually ineffective in patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC), either as first-line treatment or in later lines. By contrast, especially for patients with common EGFR mutations (exon 19 deletion/L858R point mutation), an orally bioavailable EGFR tyrosine kinase inhibitor (EGFR-TKI) is the best upfront therapy, being able to provide response rates well above 50% and a median progression-free survival ranging from 11 to 19 months, depending on whether a second-generation (e.g., afatinib) or a third-generation (i.e., osimertinib) EGFR-TKI is used. Unfortunately, treatment options for these patients at the time of acquired resistance are limited. As for afatinib-pretreated patients, those who develop a T790M mutation may benefit from osimertinib, whereas platinum-based chemotherapy is the preferable therapeutic strategy for T790M-negative patients as well as for patients who progress on osimertinib administered as first-line therapy. Here, we describe the case of an exon-19-deleted patient who experienced a complete response to the anti-PD-1 agent pembrolizumab upon the development of T790M-negative acquired resistance to afatinib. Furthermore, we discuss this case in the context of the existing literature, especially focusing on the importance of evaluating multiple markers of immune response post-EGFR-TKI and prior to ICI treatment in order to select the best treatment strategy in this clinical scenario.

CT-Guided Percutaneous Trans-scapular Lung Biopsy in the Diagnosis of Peripheral Pulmonary Lesion Nodules of the Superior Lobes Using Large Needles.

PURPOSE: CT-guided percutaneous transthoracic lung needle biopsy (PLB) is an effective procedure for obtaining cyto-histological diagnoses of peripheral lesions. However, upper postero-lateral lung nodules (UPLN) may be difficult to reach using a standard intercostal either anterior or lateral approach or when the nodule is just behind a rib or scapula. We evaluated the feasibility and effectiveness of trans-scapular approach (tPLB) in these patients using large-core needles. METHODS: We retrospectively collected the data of 11 consecutive patients (mean age 74.6 years, SD 5.9) among those scheduled to undergo CT-guided PLB over the period February 2015 to February 2017. In these patients, the presence of a UPLN required a tPLB using a co-axial technique and large full-core needles (15G for the scapular piercing and 18-19G for tissue sampling). All patients were assessed by telephone at 24 h, 78 h and at an office visit at 30 days after the procedure to evaluate post-procedural pain (VAS score) and shoulder mobility. RESULTS: Ten of the eleven samples were diagnostic. No major complications were encountered. Three patients developed a pneumothorax, but none required pleural drainage. All the patients confirmed the absence of pain at 24-72 h and 30 days, reporting a VAS score less than 1, without any shoulder mobility limitation. CONCLUSION: tPLB seems to be an effective and feasible procedure, accompanied by a low risk of pneumothorax in UPLN cases.

Bilateral Staged Computed Tomography-Guided Gluteal Artery Puncture for Internal Iliac Embolization in a Patient with Type II Endoleak.

Repair of isolated iliac aneurysm with stent-graft implantation and internal iliac coverage may induce significant type II endoleak from patent internal iliac refilling leading to ongoing aneurysm growth. Subsequent treatment of such complication can be challenging especially in case of bilateral iliac involvement. Open repair is technically demanding and often a high risk procedure, while embolization via transfemoral approach is unviable due to the stent-graft coverage precluding direct antegrade access between the common and the internal iliac lumen. Percutaneous retrograde embolization from superior gluteal artery is a feasible technique in case of impossible access through the origin of internal iliac artery.

Impact of specific mutant KRAS on clinical outcome of EGFR-TKI-treated advanced non-small cell lung cancer patients with an EGFR wild type genotype.

INTRODUCTION: This retrospective study was undertaken to investigate the impact of specific mutant KRAS on clinical outcome to either gefitinib or erlotinib (EGFR tyrosine kinase inhibitor, EGFR-TKI) in patients with EGFR wild type (WT) advanced non-small cell lung cancer (NSCLC). METHODS: Patients with an EGFR WT genotype who were treated with an EGFR-TKI for advanced disease at our Institution were identified. Simultaneous availability of KRAS mutation status was required for study inclusion. RESULTS: Sixty-seven patients were eligible. Median age was 60 years (39-84), and 10 patients (14.9%) had received an EGFR-TKI as upfront therapy. Overall, the median progression-free survival (PFS) and overall survival (OS) were 2.9 months and 18.0 months, respectively. KRAS mutant patients (n=18) experienced a significantly shorter PFS compared with those carrying a KRAS WT genotype (n=49) (1.6 months vs 3.0 months, respectively, P=0.04; HR=1.92). However, within the KRAS mutant group a great variability in terms of sensitivity to treatment was noted (PFS ranging from 0.7 months to 38.7 months). KRAS codon 13 mutant patients (n=4) experienced the worse outcome when compared with KRAS codon 12 mutants (n=14) and KRAS WT patients (P<0.0001 and P=0.01 for PFS and OS, respectively). CONCLUSIONS: Though we found that EGFR WT/KRAS mutant advanced NSCLC patients are associated with an increased resistance to treatment, specific mutant KRAS may account for differential sensitivity to an EGFR-TKI. KRAS codon 13 mutants are those who seem to experience the worse clinical outcome.