Editors Choice
KEAP1-Mutant NSCLC: The Catastrophic Failure of a Cell-Protecting Hub
Mutations in the KEAP1-NRF2 pathway are common in NSCLC, albeit with a prevalence of KEAP1 mutations in lung adenocarcinoma and an equal representation of KEAP1 and NFE2L2 (the gene encoding for NRF2) alterations in lung squamous cell carcinoma. The KEAP1-NRF2 axis is a crucial modulator of cellular homeostasis, enabling cells to tolerate oxidative and metabolic stresses, and xenobiotics. The complex cytoprotective response orchestrated by NRF2-mediated gene transcription embraces detoxification mechanisms, ferroptosis protection, and metabolic reprogramming.Axillary Lymphadenopathy After Coronavirus Disease 2019 Vaccinations in Patients With Thoracic Malignancy: Incidence, Predisposing Factors, and Imaging Characteristics
Axillary lymphadenopathy from coronavirus disease 2019 (COVID-19) vaccine is an emerging phenomenon during unprecedented mass vaccinations, which can be incidentally found on computed tomography (CT) scans. This study investigated the incidence, predisposing factors, and imaging characteristics of vaccine-related axillary lymphadenopathy in patients with thoracic malignancy who underwent CT scans before and after COVID-19 vaccinations.An Alert to Possible False Positives With a Commercial Assay for MET Exon 14 Skipping
Because molecular-targeted drugs against MET exon 14 (METex14) skipping have been approved, molecular testing of the alteration has added to clinical guidelines. There are several such assays, but methodological issues have been reported.A Phase 1 Study Evaluating Rovalpituzumab Tesirine in Frontline Treatment of Patients With Extensive-Stage SCLC
Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate targeting DLL3, a Notch pathway ligand highly expressed on SCLC cells. Rova-T was evaluated alone or in combination with platinum-based chemotherapy (cisplatin or carboplatin combined with etoposide [CE]) in frontline treatment of extensive-stage SCLC.Role of Consolidation Durvalumab in Patients With EGFR- and HER2-Mutant Unresectable Stage III NSCLC
Despite the recent advance of consolidation durvalumab in the treatment of unresectable stage III NSCLC, not every patient benefits from durvalumab and the predictive markers of response have been difficult to identify.Four-Year Survival With Durvalumab After Chemoradiotherapy in Stage III NSCLC—an Update From the PACIFIC Trial
In the Phase 3, placebo-controlled PACIFIC trial of patients with unresectable, stage III NSCLC without disease progression after concurrent chemoradiotherapy, consolidative durvalumab was associated with significant improvements in the primary end points of overall survival (OS) (hazard ratio [HR] = 0.68; 95% confidence interval [CI]: 0.53–0.87; p = 0.00251; data cutoff, March 22, 2018) and progression-free survival (PFS) (blinded independent central review; Response Evaluation Criteria in Solid Tumors version 1.1) (HR = 0.52; 95% CI: 0.42–65; p < 0.0001; February 13, 2017) with manageable safety.A 10-Year Cross-Sectional Analysis of Public, Oncologist, and Patient Attitudes About Lung Cancer and Associated Stigma
Lung cancer stigma negatively impacts the clinical care and outcomes of those diagnosed, resulting in enduring disparities. The objective of this study was to determine whether attitudes toward lung cancer and the stigmatization of people diagnosed have changed over a decade.The Rare YAP1 Subtype of SCLC Revisited in a Biobank of 39 Circulating Tumor Cell Patient Derived Explant Models: A Brief Report
Recent consensus defines four SCLC subtypes on the basis of transcription factor expression: ASCL1, NEUROD1, POU2F3, and YAP1. The rare YAP1 subtype is associated with “neuroendocrine (NE)-low” cells among SCLC cell lines and patient samples. We evaluated YAP1 in 39 patients with phenotypically diverse circulating tumor cell–derived explant (CDX) models and revisited YAP1 in terms of prevalence, cell phenotype, and intertumor and intratumor heterogeneity.Programmed Cell Death Ligand 1 Expression in Untreated EGFR Mutated Advanced NSCLC and Response to Osimertinib Versus Comparator in FLAURA
EGFR mutated (EGFRm) NSCLC tumors occasionally express programmed cell death ligand 1 (PD-L1), although frequency and clinical relevance are not fully characterized. We report PD-L1 expression in patients with EGFRm advanced NSCLC and association with clinical outcomes following treatment with osimertinib or comparator EGFR tyrosine kinase inhibitors in the FLAURA trial (phase III, NCT02296125).A Brief Report on Survival After Robotic Lobectomy for Early-Stage Lung Cancer
Robotic-assisted surgery has become the first choice for several conditions since its introduction in clinical practice in 2000. However, the U.S. Food and Drug Administration has recently raised a warning against the use of robotic surgical approaches for the cure and prevention of cancer following the publication of two studies focused on endometrial cancer. We conducted an internal audit to retrospectively analyze our experience to assess the safety and feasibility of robotic-assisted surgery compared to open surgery.SWOG S1400C (NCT02154490)—A Phase II Study of Palbociclib for Previously Treated Cell Cycle Gene Alteration–Positive Patients with Stage IV Squamous Cell Lung Cancer (Lung-MAP Substudy)
Lung-MAP (SWOG S1400) is a master platform trial assessing targeted therapies in squamous NSCLC. The objective of study C (S1400C) was to evaluate the response rate to palbociclib, a cyclin-dependent kinase 4 and cyclin-dependent kinase 6 inhibitor, in patients with cell cycle gene abnormalities.A Novel Acquired Exon 20 EGFR M766Q Mutation in Lung Adenocarcinoma Mediates Osimertinib Resistance but is Sensitive to Neratinib and Poziotinib
Osimertinib is an effective third-generation tyrosine kinase inhibitor (TKI) for EGFR-mutant lung cancers. However, treatment for patients with acquired resistance to osimertinib remains challenging. We characterized a novel EGFR mutation in exon 20 that was acquired while on osimertinib.SWOG S1400D (NCT02965378), a Phase II Study of the Fibroblast Growth Factor Receptor Inhibitor AZD4547 in Previously Treated Patients With Fibroblast Growth Factor Pathway–Activated Stage IV Squamous Cell Lung Cancer (Lung-MAP Substudy)
S1400D is a biomarker-driven therapeutic substudy of Lung-MAP evaluating the fibroblast growth factor (FGF) receptor (FGFR) inhibitor AZD4547 in patients with FGF pathway-activated squamous cell. This is the first phase II trial to evaluate AZD4547 as a targeted approach in patients with previously treated FGFR-altered squamous cell NSCLC and is the first demonstration of successful implementation and conduct of a national umbrella protocol in this disease setting.SWOG S1400B (NCT02785913), a Phase II Study of GDC-0032 (Taselisib) for Previously Treated PI3K-Positive Patients with Stage IV Squamous Cell Lung Cancer (Lung-MAP Sub-Study)
S1400B is a biomarker-driven Lung-MAP substudy evaluating the phosphatidylinositol 3-kinase (PI3K) inhibitor taselisib (GDC-0032) in patients with PI3K pathway-activated squamous NSCLC (sqNSCLC).Efficacy of Immune Checkpoint Inhibitors in KRAS-Mutant Non-Small Cell Lung Cancer (NSCLC)
KRAS mutation is the most frequent molecular alteration found in advanced NSCLC; it is associated with a poor prognosis without available targeted therapy. Treatment options for NSCLC have been recently enriched by the development of immune checkpoint inhibitors (ICIs), and data about its efficacy in patients with KRAS-mutant NSCLC are discordant. This study assessed the routine efficacy of ICIs in advanced KRAS-mutant NSCLC.Prophylactic Cranial Irradiation for Limited-Stage Small-Cell Lung Cancer Patients: Secondary Findings From the Prospective Randomized Phase 3 CONVERT Trial
The impact of the dose and fractionation of thoracic radiotherapy on the risk of developing brain metastasis (BM) has not been evaluated prospectively in limited stage SCLC patients receiving prophylactic cerebral irradiation (PCI).A Brief Report of Transformation From NSCLC to SCLC: Molecular and Therapeutic Characteristics
Histologic transformation from NSCLC to SCLC is a mechanism of resistance in EGFR-mutant tumors but is also occasionally observed in nonmutated NSCLC.Increased Hepatotoxicity Associated with Sequential Immune Checkpoint Inhibitor and Crizotinib Therapy in Patients with Non–Small Cell Lung Cancer
Immune checkpoint inhibitors (ICIs) are standard therapies in advanced NSCLC. Although genotype-directed tyrosine kinase inhibitors represent the standard of care for subsets of oncogene-driven NSCLC, patients may receive ICIs during their disease course. The impact of sequential ICI and tyrosine kinase inhibitor therapy on the risk of hepatotoxicity has not been described.Survival Patterns for Patients with Resected N2 Non–Small Cell Lung Cancer and Postoperative Radiotherapy: A Prognostic Scoring Model and Heat Map Approach
The positive-to-resected lymph node ratio (LNR) predicts survival in many cancers, but little information is available on its value for patients with N2 NSCLC who receive postoperative radiotherapy (PORT) after resection. We tested the applicability of prognostic scoring models and heat mapping to predict overall survival (OS) and cancer-specific survival (CSS) in patients with resected N2 NSCLC and PORT.c-MET Overexpression as a Poor Predictor of MET Amplifications or Exon 14 Mutations in Lung Sarcomatoid Carcinomas
MNNG HOS transforming gene (MET) abnormalities such as amplification and exon 14 mutations may be responsive to targeted therapies. They are prevalent in lung sarcomatoid carcinomas (LSCs) and must be diagnosed as efficiently as possible. Hypothetically, c-MET overexpression by immunohistochemistry (IHC) may prove effective as a screening test for MET abnormalities.Early Use of Systemic Corticosteroids in Patients with Advanced NSCLC Treated with Nivolumab
Checkpoint inhibitors augment the immune system’s natural surveillance mechanisms and have increasing applications in NSCLC. Immunosuppressive corticosteroids are also frequently used in this population to treat unwanted inflammation. In view of this mechanistic opposition, we investigated the interaction between nivolumab and corticosteroids in patients with advanced NSCLC.Safety and Efficacy of PD-1 Inhibitors Among HIV-Positive Patients With Non–Small Cell Lung Cancer
Despite widespread administration of programmed death receptor 1 (PD-1) pathway inhibitors among individuals with NSCLC, little is known about the safety and activity of these agents among human immunodeficiency virus (HIV) – infected patients since this population has largely been excluded from immunotherapy clinical trials.Brief Report on Radiological Changes following Stereotactic Ablative Radiotherapy (SABR) for Early-Stage Lung Tumors: A Pictorial Essay
Distinctive patterns of early and late benign fibrosis are commonly observed after stereotactic ablative radiotherapy for lung malignancies. These changes on computed tomography scans need to be distinguished from so-called high-risk radiological features, which can be associated with a higher risk for tumor recurrence. This pictorial report illustrates the different radiological changes seen after stereotactic ablative radiotherapy delivered by using volumetric modulated radiotherapy, a technique that is being increasingly used in clinical care.A Phase II Study of Trastuzumab Emtansine in HER2-Positive Non–Small Cell Lung Cancer
Trastuzumab emtansine (T-DM1), an anti–erb-b2 receptor tyrosine kinase 2 (HER2) antibody-drug conjugate, has been shown to significantly improve survival in HER2-positive breast cancer. We report a phase II trial of T-DM1 monotherapy in relapsed NSCLC with documented HER2 positivity (an immunohistochemistry [IHC] score of 3+, both an IHC score of 2+ and fluorescence in situ hybridization positivity, or exon 20 mutation). This study was terminated early because of limited efficacy. The demographic characteristics in the 15 assessable patients were as follows: median age, 67 years; male sex, 47%; performance status of 0 to 1, 80%; HER2 status IHC 3+, 33%; HER status IHC 2+/fluorescence in situ hybridization–positive, 20%; and exon 20 mutation, 47%.Somatic Mutations and Ancestry Markers in Hispanic Lung Cancer Patients
To address the lack of genomic data from Hispanic/Latino (H/L) patients with lung cancer, the Latino Lung Cancer Registry was established to collect patient data and biospecimens from H/L patients.
