Natural History and Real-World Treatment Outcomes for Patients With NSCLC Having Exon 20 Insertion Mutation: An International Association for the Study of Lung Cancer-American Society of Clinical Oncology CancerLinQ Study.

Introduction: EGFR exon 20 insertion (ex20ins) mutations account for approximately 10% of EGFR mutations in lung adenocarcinoma. Patients with ex20ins mutation do not respond to standard EGFR tyrosine kinase inhibitor therapy. In this work, we analyzed the characteristics, treatment patterns, and outcomes in this subgroup of patients with NSCLC.

Characterization of effective, simple, and low-cost precipitation methods for depleting abundant plasma proteins to enhance the depth and breadth of plasma proteomics.

Plasma is an abundant source of proteins and potential biomarkers to aid in the detection, diagnosis, and prognosis of human diseases. These proteins are often present at low levels in the blood and difficult to identify and measure due to the large dynamic range of proteins. The goal of this work was to characterize and compare various protein precipitation methods related to how they affect the depth and breadth of plasma proteomic studies.

International Association for the Study of Lung Cancer Study of Reproducibility in Assessment of Pathologic Response in Resected Lung Cancers After Neoadjuvant Therapy.

Introduction: Pathologic response has been proposed as an early clinical trial end point of survival after neoadjuvant treatment in clinical trials of NSCLC. The International Association for the Study of Lung Cancer (IASLC) published recommendations for pathologic evaluation of resected lung cancers after neoadjuvant therapy. The aim of this study was to assess pathologic response interobserver reproducibility using IASLC criteria.

Design of experiments approach for systematic optimization of a single-shot diaPASEF plasma proteomics workflow applicable for high-throughput.

Purpose: Plasma is an abundant source of protein biomarkers. Mass spectrometry (MS) is an effective means to measure a large number of proteins in a single run. The recent development of data-independent acquisition with parallel accumulation and serial fragmentation (diaPASEF) on a trapped ion mobility spectrometer (TIMS) affords deep proteomic coverage with short liquid chromatography gradients.

The International Association for the Study of Lung Cancer Early Lung Imaging Confederation Open-Source Deep Learning and Quantitative Measurement Initiative.

Introduction: With global adoption of computed tomography (CT) lung cancer screening, there is increasing interest to use artificial intelligence (AI) deep learning methods to improve the clinical management process. To enable AI research using an open-source, cloud-based, globally distributed, screening CT imaging data set and computational environment that are compliant with the most stringent international privacy regulations that also protect the intellectual properties of researchers, the International Association for the Study of Lung Cancer sponsored development of the Early Lung Imaging Confederation (ELIC) resource in 2018. The objective of this report is to describe the updated capabilities of ELIC and illustrate how this resource can be used for clinically relevant AI research.

A phase 1 study of veliparib (ABT-888) plus weekly carboplatin and paclitaxel in advanced solid malignancies, with an expansion cohort in triple negative breast cancer (TNBC) (ETCTN 8620).

Background: Veliparib is a poly-ADP-ribose polymerase (PARP) inhibitor, and it has clinical activity with every 3 weeks carboplatin and paclitaxel. In breast cancer, weekly paclitaxel is associated with improved overall survival. We aimed to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of veliparib with weekly carboplatin and paclitaxel as well as safety, pharmacokinetics, and preliminary clinical activity in triple negative breast cancer (TNBC).

A Phase 1, Open-Label, Dose-Escalation Study of L-DOS47 in Combination With Pemetrexed Plus Carboplatin in Patients With Stage IV Recurrent or Metastatic Nonsquamous NSCLC.

Introduction: L-DOS47, a targeted urease-anti-CEACAM6 immunoconjugate, alters the acidity of the tumor microenvironment by increasing local ammonia production. In vitro, the cytotoxic effects of L-DOS47 were additive when combined with pemetrexed and carboplatin.

Methods: This phase I, open-label, dose-escalation study evaluated the safety and tolerability of up to four cycles of L-DOS47 (administered on days 1, 8, and 15 of each cycle at doses ranging from 0.

Optimizing data-independent acquisition (DIA) spectral library workflows for plasma proteomics studies.

Traditional data-independent acquisition (DIA) workflows employ off-column fractionation with data-dependent acquisition (DDA) to generate spectral libraries for data extraction. Recent advances have led to the establishment of library-independent approaches for DIA analyses. The selection of a DIA workflow may affect the outcome of plasma proteomics studies.

Utilization and costs of epidermal growth factor receptor mutation testing and targeted therapy in Medicare patients with metastatic lung adenocarcinoma.

Background: Guidelines in 2013 and 2014 recommended Epidermal Growth Factor Receptor (EGFR) testing for metastatic lung adenocarcinoma patients as the efficacy of targeted therapies depends on the mutations. However, adherence to these guidelines and the corresponding costs have not been well-studied.

Methods: We identified 2362 patients at least 65 years old newly diagnosed with metastatic lung adenocarcinoma from January 2013 to December 2015 using the SEER-Medicare database.

Diversity and heterogeneity of immune states in non-small cell lung cancer and small cell lung cancer.

Blood-based biomarkers including systemic inflammation (SI) indicators or circulating factors (cytokines, chemokines, or growth factors) are associated with a poor prognosis for lung cancer patients. Collectively these biomarkers can predict the immune state of a patient. We wanted to define and compare the immune states of small cell and non-small cell lung cancer patients, in the hopes that the information gained could lead to overall improvements in patient care and outcomes.

Guidance on the Clinical Management of Electronic Cigarette or Vaping-Associated Lung Injury.

In the summer of 2019, there was a rise in clusters of adolescents and young adults in the United States reporting to emergency departments with acute respiratory distress related to use of e-cigarette (electronic cigarette) or vaping. The number of patients with e-cigarette or vaping-associated lung injury continued to rise through the summer before peaking in September 2019. Through the efforts of state and federal public health agencies, officials were able to define the condition, identify the relationship of the respiratory injury to tetrahydrocannabinol-containing products, and stem the rise in new cases.

The International Association for the Study of Lung Cancer Global Survey on Molecular Testing in Lung Cancer.

Introduction: Access to targeted therapies for lung cancer depends on the accurate identification of patients' biomarkers through molecular testing. The International Association for the Study of Lung Cancer (IASLC) conducted an international survey to evaluate perceptions on current practice and barriers to implementation of molecular testing.

Methods: We distributed the survey to IASLC members and other health care professionals around the world.

Treatment Guidance for Patients With Lung Cancer During the Coronavirus 2019 Pandemic.

The global coronavirus disease 2019 pandemic continues to escalate at a rapid pace inundating medical facilities and creating substantial challenges globally. The risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with cancer seems to be higher, especially as they are more likely to present with an immunocompromised condition, either from cancer itself or from the treatments they receive. A major consideration in the delivery of cancer care during the pandemic is to balance the risk of patient exposure and infection with the need to provide effective cancer treatment.

Mutations in genes connected with the TCF7L2 transcription factor are associated with a poor prognosis in non-small cell lung cancer.

Objectives: Precision medicine with molecular profiling has revolutionized the management of lung cancer leading to improved outcomes. Patients with actionable mutations receive targeted therapy. As next-generation sequencing (NGS) becomes standard in lung cancer clinics, we sought to use molecular information to identify novel pathways to target in order to improve survival for non-small cell lung cancer (NSCLC) patients.

Trimodality Therapy in the Treatment of Stage III N2-Positive Non-Small Cell Lung Cancer: A National Cancer Database Analysis.

Background: Significant controversy remains regarding the care of patients with clinical stage III (N2-positive) NSCLC. Although multimodality therapy is effective, the roles of surgery, chemotherapy, and radiotherapy are not fully defined and the optimal treatment approach is not firmly established. We analyzed outcomes and predictors associated with trimodality therapy (TT) in the National Cancer Database.

A rewiring model of intratumoral interaction networks.

Intratumoral heterogeneity (ITH) has been regarded as a key cause of the failure and resistance of cancer therapy, but how it behaves and functions remains unclear. Advances in single-cell analysis have facilitated the collection of a massive amount of data about genetic and molecular states of individual cancer cells, providing a fuel to dissect the mechanistic organization of ITH at the molecular, metabolic and positional level. Taking advantage of these data, we propose a computational model to rewire up a topological network of cell-cell interdependences and interactions that operate within a tumor mass.

Randomized Phase II Study of Paclitaxel plus Alisertib versus Paclitaxel plus Placebo as Second-Line Therapy for SCLC: Primary and Correlative Biomarker Analyses.

Introduction: We assessed the Aurora A kinase inhibitor, alisertib, plus paclitaxel (henceforth referred to as alisertib/paclitaxel) as second-line treatment for SCLC.

Methods: In this double-blind study, patients with relapsed or refractory SCLC were stratified by relapse type (sensitive versus resistant or refractory) and brain metastases and randomized 1:1 to alisertib/paclitaxel or placebo plus paclitaxel (henceforth referred to as placebo/paclitaxel) in 28-day cycles. The primary end point was progression-free survival (PFS).

Phase 1 study of veliparib (ABT-888), a poly (ADP-ribose) polymerase inhibitor, with carboplatin and paclitaxel in advanced solid malignancies.

Purpose: Veliparib is an oral inhibitor of poly (ADP-ribose) polymerase (PARP)-1 and -2. PARP-1 expression may be increased in cancer, and this increase confers resistance to cytotoxic agents. We aimed to determine the recommended phase 2 dose (RP2D), maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacokinetics (PK) of veliparib combined with paclitaxel and carboplatin.

Pemetrexed, Bevacizumab, or the Combination As Maintenance Therapy for Advanced Nonsquamous Non-Small-Cell Lung Cancer: ECOG-ACRIN 5508.

Purpose: Pemetrexed or bevacizumab is used for maintenance therapy of advanced nonsquamous non-small-cell lung cancer (NSCLC). The combination of bevacizumab and pemetrexed has also demonstrated efficacy. We conducted a randomized study to determine the optimal maintenance therapy.

Survival Outcomes With Thoracic Radiotherapy in Extensive-Stage Small-Cell Lung Cancer: A Propensity Score-Matched Analysis of the National Cancer Database.

Background: The prognosis of patients with extensive-stage small-cell lung carcinoma (ES-SCLC) is poor. The benefit of consolidative thoracic radiation therapy (TRT) in ES-SCLC has been inconclusive, and its use inconsistent. The objective of this study was to evaluate overall survival (OS) of ES-SCLC patients treated with chemotherapy (CT) with or without TRT using an administrative database approach.

A phase I pharmacokinetic study of belinostat in patients with advanced cancers and varying degrees of liver dysfunction.

Aims: The histone deacetylase inhibitor belinostat has activity in various cancers. Because belinostat is metabolized by the liver, reduced hepatic clearance could lead to excessive drug accumulation and increased toxicity. Safety data in patients with liver dysfunction are needed for this drug to reach its full potential in the clinic.

EGFR mutations and AKT phosphorylation are markers for sensitivity to combined MCL-1 and BCL-2/xL inhibition in non-small cell lung cancer.

Lung cancer is among the common and deadly cancers. Although the treatment options for late-stage cancer patients have continued to increase in numbers, the overall survival rates for these patients have not shown significant improvement. This highlights the need for new targets and drugs to more effectively treat lung cancer patients.

Advanced NSCLC patients with high IL-6 levels have altered peripheral T cell population and signaling.

Objectives: High levels of circulating interleukin-6 (IL-6) are associated with a poor prognosis in many types of cancer including non-small cell lung cancer (NSCLC). While the inflammatory cytokine can stimulate the immune system and promote tumor growth, it remains unclear how circulating IL-6 can potentiate a poor prognosis. We hypothesized that a mechanism for IL-6-associated poor prognosis is that these patients would have altered T-cell populations and impaired T-cell signaling.

Phase II Trial of Cabozantinib Plus Erlotinib in Patients With Advanced Epidermal Growth Factor Receptor ()-Mutant Non-small Cell Lung Cancer With Progressive Disease on Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy: A California Cancer Consortium Phase II Trial (NCI 9303).

Mesenchymal epidermal transition and vascular endothelial growth factor pathways are important in mediating non-small cell lung cancer (NSCLC) tumorigenesis and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance. We hypothesized that treatment with cabozantinib plus erlotinib in mutation-positive NSCLC following progression on EGFR TKI therapy may allow tumors to overcome this resistance or restore sensitivity to therapy regardless of T790M status. Patients with advanced NSCLC, known mutation and progressive disease on an EGFR TKI immediately prior to enrollment without intervening therapy were enrolled.