Pembrolizumab With or Without Maintenance Olaparib for Metastatic Squamous NSCLC That Responded to First-Line Pembrolizumab Plus Chemotherapy.

Introduction: Poly (adenosine diphosphate-ribose) polymerase inhibitors can up-regulate programmed cell death-ligand 1 expression and promote immune-mediated responses and may improve efficacy of first-line anti‒programmed cell death protein 1‒based therapies in patients with metastatic squamous NSCLC.

Methods: In this randomized, double-blind, phase 3 trial (NCT03976362), adults with previously untreated stage IV squamous NSCLC received four cycles of induction therapy (pembrolizumab 200 mg every 3 weeks plus carboplatin and paclitaxel or nab-paclitaxel). Patients with disease control were randomized to 31 cycles of pembrolizumab 200 mg every 3 weeks plus olaparib 300 mg orally twice daily or placebo.

Gene Therapy for Lung Cancer.

Gene therapy was originally conceived to treat monogenic diseases. The replacement of a defective gene with a functional gene can theoretically cure the disease. In cancer, multiple genetic defects are present and the molecular profile changes during the course of the disease, making the replacement of all defective genes impossible.

A window of opportunity study of potential tumor and soluble biomarkers of response to preoperative erlotinib in early stage non-small cell lung cancer.

Background: Erlotinib is highly active in EGFR mutant NSCLC, but may benefit some with wild-type tumors. We examined pre-operative erlotinib in early stage NSCLC to assess response and correlation with potential biomarkers.

Results: Twenty-five patients were enrolled; 22 received erlotinib treatment and were evaluable (median follow-up 4.

The right drugs at the right time for the right patient: the MD Anderson precision oncology decision support platform.

The development of resources for clinical interpretation of cancer-associated genetic alterations has significantly lagged behind the technical developments enabling their detection in a time- and cost-efficient manner. The lack of scientific and informatics decision support for oncologists can lead to no action being taken or suboptimal therapeutic choices being made, which could affect the clinical outcome of a patient as well as convoluting research findings from clinical trials. In this article, we describe the precision oncology decision support (PODS) platform developed within The Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy (IPCT) at MD Anderson Cancer Center; the platform aims to bridge the gap between molecular alteration detection and identification of appropriate treatments.

Exogenous Restoration of TUSC2 Expression Induces Responsiveness to Erlotinib in Wildtype Epidermal Growth Factor Receptor (EGFR) Lung Cancer Cells through Context Specific Pathways Resulting in Enhanced Therapeutic Efficacy.

Expression of the tumor suppressor gene TUSC2 is reduced or absent in most lung cancers and is associated with worse overall survival. In this study, we restored TUSC2 gene expression in several wild type EGFR non-small cell lung cancer (NSCLC) cell lines resistant to the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib and analyzed their sensitivity to erlotinib in vitro and in vivo. A significant inhibition of cell growth and colony formation was observed with TUSC2 transient and stable expression.

Using Ontology Fingerprints to disambiguate gene name entities in the biomedical literature.

Ambiguous gene names in the biomedical literature are a barrier to accurate information extraction. To overcome this hurdle, we generated Ontology Fingerprints for selected genes that are relevant for personalized cancer therapy. These Ontology Fingerprints were used to evaluate the association between genes and biomedical literature to disambiguate gene names.

Lung adenocarcinoma with concurrent KRAS mutation and ALK rearrangement responding to crizotinib: case report.

Chromosomal translocation resulting in the fusion between the echinoderm microtubule-associated protein-like 4 (EML4) gene and the anaplastic lymphoma kinase (ALK) gene was recently identified as a novel genetic alteration in a subset of non-small cell lung cancer (NSCLC). EML4-ALK translocations are rare events associated with specific clinicopathological features, such as never or light smoking history, young age and adenocarcinoma with signet ring or acinar histology. Reports suggest ALK gene arrangements are mutually exclusive with EGFR and KRAS mutations.

Selected Reaction Monitoring (SRM) Analysis of Epidermal Growth Factor Receptor (EGFR) in Formalin Fixed Tumor Tissue.

Background: Analysis of key therapeutic targets such as epidermal growth factor receptor (EGFR) in clinical tissue samples is typically done by immunohistochemistry (IHC) and is only subjectively quantitative through a narrow dynamic range. The development of a standardized, highly-sensitive, linear, and quantitative assay for EGFR for use in patient tumor tissue carries high potential for identifying those patients most likely to benefit from EGFR-targeted therapies.

Methods: A mass spectrometry-based Selected Reaction Monitoring (SRM) assay for the EGFR protein (EGFR-SRM) was developed utilizing the Liquid Tissue®-SRM technology platform.

Histopathological and immunohistochemical features associated with clinical response to neoadjuvant gefitinib therapy in early stage non-small cell lung cancer.

To define the pathological features associated with response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in NSCLC, we have evaluated tumor histopathological features and immunohistochemical markers of proliferation (Ki-67) and epithelial mesenchymal transition (EMT) in 36 resected early stage NSCLC from patients treated preoperatively with gefitinib for 28 days. Tumors studied included 7 squamous cell carcinoma, 27 adenocarcinoma (ADC), one adenosquamous carcinoma, and one large cell carcinoma. Six of the ADC harboured an EGFR tyrosine kinase domain (TKD) mutation; five were the sensitizing type.

Phase II study of preoperative gefitinib in clinical stage I non-small-cell lung cancer.

Purpose: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have proven efficacy in advanced non-small-cell lung cancer (NSCLC). Their role in early-stage NSCLC has not been established. Our purpose was to explore the use of preoperative gefitinib in clinical stage I NSCLC to assess tumor response, toxicity, and clinical and molecular predictors of response.

The role of intrapulmonary de novo lymphoid tissue in obliterative bronchiolitis after lung transplantation.

Chronic rejection after lung transplantation is manifested as obliterative bronchiolitis (OB). The development of de novo lymphoid tissue (lymphoid neogenesis) may contribute to local immune responses in small airways. Compared with normal lungs, the lung tissue of 13 lung transplant recipients who developed OB demonstrated a significantly larger number of small, airway-associated, peripheral node addressin-positive (PNAd(+)) high endothelial venules (HEVs) unique to lymphoid tissue (p < 0.

Tissue heterogeneity of EGFR mutation in lung adenocarcinoma.

Tissue heterogeneity of EGFR gene mutation was studied in 10 formalin-fixed paraffin-embedded (FFPE) samples from four cases that demonstrated EGFR mutations in snap-frozen samples. EGFR mutations identical to those in frozen sample were demonstrated in 8 of 10 FFPE samples by direct sequencing and in 9 of 10 by fragment length analysis, but an exon-19 deletion mutation could not be identified in one FFPE sample analyzed by both techniques, despite multiple repeated assays. This suggests that some tumors may demonstrate intratumoral heterogeneity for the occurrence of EGFR mutation.

Tomographic comparison of ventilation techniques for CT-guided thoracoscopic staple excision of subcentimeter lung nodules.

This study was planned to compare the computed tomographic detectability of lung nodules in three ventilatory conditions: total lung capacity, high-frequency ventilation, and total lung deflation. In an ex vivo lung model, 44 nodules were simulated. Using computed tomography (CT) scans, nodules were detected and compared to the actual number and excised under CT guidance.

CT-Directed microcoil localization of small peripheral lung nodules: a feasibility study in pigs.

Platinum microcoils were placed in porcine lungs to determine the feasibility for use as a lung nodule marker. Using computed tomography (CT) guidance, the microcoils were successfully deployed in 17 out of 19 attempts. Coil deployment depth ranged from 7 mm to 34 mm below the pleural surface.

Peripheral lung nodules: fluoroscopically guided video-assisted thoracoscopic resection after computed tomography-guided localization using platinum microcoils.

Objectives: We sought to test the safety and efficacy of fluoroscopically guided, video-assisted, thoracoscopic resection after computed tomography (CT)-guided localization using platinum microcoils.

Summary Background Data: Video-assisted thoracoscopic (VATS) resection of small pulmonary nodules >5 mm deep to the visceral pleura fails to locate the nodule and requires conversion to open thoracotomy in two thirds of cases. Therefore, we developed a new technique for intraoperative localization of these nodules using CT-guided placement of platinum microcoils.

[Evaluation of the use of bovine pericardium in non-anatomical lung resections in dogs].

Unlabelled: In this study we assessed the usefulness, healing, as well as the integration to lung tissue of glutaraldehyde preserved at 0.5% bovine pericardium GPBP and lyophilized (GPBPL), after reinforced resection of lung tissue in dogs by thoracotomy or thoracoscopy.

Material And Methods: GPBP and GPBPL were prepared and used to reinforce the suture line of lung resection in 30 mongrel dogs: Group I (n = 6): The GPBP were fixed on the lung with 4-0 polypropylene by thoracotomy.