Immunotherapy for Early-Stage Non-Small Cell Lung Cancer: A Practical Guide of Current Controversies
The role of immunotherapy as systemic therapy for nonmetastatic non-small cell lung cancer (NSCLC) has evolved rapidly over the last decade. There are several well-conducted phase 3 clinical trials evaluating immunotherapy in the neoadjuvant, perioperative, adjuvant and nonoperative setting. In this narrative review, we summarize the data from these studies and discuss ongoing controversies in applying these data to clinical practice. These controversies relate to the value of the adjuvant component of perioperative immunotherapy, treatment of patients with PDL1 negative tumors, defining resectability, optimal use of operative versus nonoperative management, the role of stereotactic radiation therapy for very early lung cancers, and management of tumors with an oncogenic driver.
Kirsten Rat Sarcoma Virus Mutations Effect On Tumor Doubling Time And Prognosis Of Solid Dominant Stage I Lung Adenocarcinoma
To analyze the impact of Kirsten-Rat-Sarcoma Virus (KRAS) mutations on tumor-growth as estimated by tumor-doubling-time (TDT) among solid-dominant clinical-stage I lung adenocarcinoma. Moreover, to evaluate the prognostic role of KRAS mutations, TDT and their combination in completely-resected pathologic-stage I adenocarcinomas.
Regimen Selection for Chemoimmunotherapy in Nonsquamous Non-Small Cell Lung Cancer with Low PD-L1 Expression: A Multicenter Retrospective Cohort Study
Although chemoimmunotherapy is recommended for advanced nonsquamous non-small cell lung cancer (NSCLC) with low programmed cell death ligand 1 (PD-L1) expression, no head-to-head comparisons of immune checkpoint inhibitors (ICIs) have been performed. Therefore, we compared the effect and safety of regimens in these patients to guide evidence-based treatment.
Imaging Findings Related to Lung Tract Sealant Use in Percutaneous CT-guided Lung Biopsy
This study examines the imaging findings and malignancy suspicion associated with hydrogel lung tract sealants (h-LTS) used after CT-guided lung biopsy (CTLB).
POLE Mutation Associated With Microsatellite Instability and High Tumor Mutational Burden Confers Exquisite Sensitivity to Immune Checkpoint Inhibitor Therapy in Non-Small Cell Lung Cancer: A Case Report and Genomic Database Analysis
Prognostic Analysis of Pathological Stage I Lung Adenocarcinoma Harboring Major EGFR Mutations
While Epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma (LUAD) has favorable outcomes with targeted therapy, early-stage prognosis remains influenced by pathological factors and central nervous system (CNS) recurrence. The study aimed to clarify prognostic factors in pathological stage (pStage) I EGFR mutation-positive LUAD.
Neratinib Efficacy in Patients With EGFR Exon 18-Mutant Non-Small-Cell Lung Cancer: Findings From the SUMMIT Basket Trial
Activating mutations in the epidermal growth factor receptor (EGFR) gene occur in 7% to 23% of patients with non-small-cell lung cancer (NSCLC). A small proportion of these (3-5%) are exon 18 mutations. Neratinib, an irreversible pan-HER tyrosine kinase inhibitor (TKI), had activity in the phase II SUMMIT basket study. We report efficacy and safety of neratinib in patients with EGFR exon 18-mutant NSCLC in SUMMIT, according to prior EGFR TKI treatment.
Phase I Clinical Trial of Autologous Hematopoietic Stem Cell Transplantation-Supported Dose-Intensified Chemotherapy With Adebrelimab as First-Line Treatment for Extensive-Stage Small Cell Lung Cancer
Small cell lung cancer (SCLC) is initially highly sensitive to chemotherapy, which often leads to significant tumor reduction. However, the majority of patients eventually develop resistance, and the disease is further complicated by its "cold" tumor microenvironment, characterized by low tumor immunogenicity and limited CD8+ T cell infiltration. These factors contribute to the poor response to immunotherapy in many cases of extensive-stage SCLC (ES-SCLC). High-dose chemotherapy has shown potential in enhancing tumor cytoreduction, but its use is often limited by severe hematologic toxicity. Combining chemotherapy with immune checkpoint inhibitors (ICIs) can create a synergistic effect by promoting immunogenic cell death and enhancing immune activation. Autologous hematopoietic stem cell transplantation (auto-HSCT) provides a means to support hematopoietic recovery, mitigate chemotherapy-induced myelosuppression, and contribute to immune reconstitution. In this context, the integration of auto-HSCT with dose-intensified chemotherapy and ICIs aims to both protect the bone marrow and enhance antitumor immune responses, potentially overcoming resistance to immunotherapy in ES-SCLC.
Association of Immune-Related Adverse Events With Efficacy in Consolidation Nivolumab Plus Ipilimumab or Nivolumab Alone After Chemoradiation in Patients With Unresectable Stage III Nonsmall Cell Lung Cancer: An Exploratory Analysis From the Big 10 Cancer Research Consortium Study BTCRC LUN 16-081
Immunotherapy has been widely incorporated into the treatment of patients with non-small-cell lung cancer (NSCLC). Many of these patients will experience immune-related adverse events (irAEs) without decreased efficacy. We report a retrospective analysis of the association between irAEs and efficacy outcomes from the BTCRC LUN 16-081 randomized phase 2 trial of consolidation nivolumab (N) plus ipilimumab (IPI) vs N alone following chemoradiotherapy in unresectable Stage IIIA/IIIB NSCLC.
Computer Assisted Nodule Analysis and Risk Yield is Associated With Occult Lymph Node Status in Clinical Stage I-IIA Lung Adenocarcinoma Undergoing Resection
Current staging work-up does not capture all occult lymph node (OLN) disease. We sought to determine if Computer Assisted Nodule Analysis and Risk Yield (CANARY) analysis could help distinguish OLN status in early-stage lung adenocarcinoma.
PEARL: A Multicenter Phase 2 Study of Lorlatinib in Patients with ALK-Rearranged NSCLC and Central Nervous System Disease
Patients with ALK-rearranged non-small cell lung cancer (ALK+ NSCLC) with symptomatic brain (BM) and leptomeningeal (LM) metastases are underrepresented in clinical trials due to poor performance status. Additionally, the need for improved and validated assessment criteria for evaluating central nervous system (CNS) response remains critical. Lorlatinib has demonstrated systemic activity in patients with ALK+ NSCLC. This ongoing phase II study aims to evaluate the efficacy and safety of lorlatinib in ALK+ NSCLC patients with progressive CNS metastases.
Comparison of Sublobar Resection and Proton Therapy for Early-Stage Non-small Cell Lung Cancer
For early-stage lung cancer, sublobar resection (SLR) is an alternative to lobectomy, which is the standard treatment. Recently, proton therapy (PT) is being increasingly used, even in patients with operable lung cancer, as an attractive alternative to conventional radiation therapy. Thus, we performed propensity score matching (PSM) to compare the outcomes of SLR and PT in patients with early-stage non-small cell lung cancer (NSCLC).
Brief Report: Osimertinib Plus Capmatinib for Patients With MET-Altered EGFR-Mutant NSCLC Following Progression on Front Line Therapy
A Phase II, Open Label, Single-Arm Study on the Efficacy of Cabozantinib in Patients With Advanced/Metastatic Nonsmall Cell Lung Cancer Harboring MET Exon 14 Alterations who Developed Acquired Resistance to Tepotinib or Capmatinib (CAPTURE Trial)
MET gene exon 14 skipping was identified as a potential driver mutation that occurs in approximately 3%-4% of patients with nonsmall cell lung cancer (NSCLC), typically in the absence of other driver mutations. Capmatinib and tepotinib were the first MET- tyrosine kinase inhibitors (MET-TKIs) approved by the FDA and PMDA, specifically for patients with metastatic NSCLC. Several studies have reported acquired resistance after MET-TKI treatment for MET mutation-positive NSCLC. Sequencing of the MET kinase region of resistant cell lines revealed secondary mutations at residues D1228 and Y1230 that were sensitive to type II MET-TKIs, such as cabozantinib. This suggested that sequential administration of other MET-TKIs may overcome the development of secondary mutations after acquired resistance in MET exon 14 mutation-positive NSCLC.
Tarlatamab Rechallenge After Grade 3 Cytokine Release Syndrome Leading to Tumor Regression in Two Weeks and Reopening of a Collapsed Lung: A Case Report
Phase II Parallel Arm Study of Sacituzumab Govitecan-Hziy in Patients With Advanced Thymoma or Thymic Carcinoma
Thymic epithelial tumors (TETs), including thymoma and thymic carcinoma, are rare thoracic tumors of the anterior mediastinum. For those with advanced disease, platinum-based chemotherapy is used as first-line treatment. However, there is no standard regimen established for TET at progression after initial therapy, and treatment options for advanced/recurrent TETs are limited. Trop-2, a transmembrane glycoprotein, is overexpressed in solid tumors including thymomas and thymic carcinomas. Sacituzumab govitecan-hziy, a Trop-2-directed antibody-drug conjugate, has shown efficacy and safety in several tumors including breast cancer. The overexpression of Trop-2 in TETs and the clinical efficacy in other malignancies provide rationale for exploring its use in thymoma and thymic carcinoma.
Adjuvant Chemotherapy Decisions in the Treatment of Lung Cancer Considering Nonrelapse Mortality: A Multicenter Study
Adjuvant chemotherapy (Adj) reduces recurrence and improves long-term survival in patients with surgically resected lung cancer. However, it has minimal impact on patients who die without relapsing. To optimize Adj indications, we aimed to identify factors associated with nonrelapse mortality (NRM).
Radiation Induced Unilateral Vocal Fold Paralysis Following Lung Stereotactic Ablative Radiation Therapy: A Case Report and Review of the Literature
Statin Use With Immune Checkpoint Inhibitors and Survival in Nonsmall Cell Lung Cancer
To determine the association between concurrent statin use with immune checkpoint inhibitors (ICIs) and lung cancer-specific and overall mortality in patients with nonsmall cell lung cancer (NSCLC).
Surgical and Pathological Results Following Neoadjuvant Nivolumab and Platinum-Based Chemotherapy for Locally Advanced Resectable NSCLC: A Multicentre Real-World Series From England
To evaluate the real-world surgical and pathological outcomes following neoadjuvant nivolumab in combination with chemotherapy in a multicentre national cohort of patients.
Conversion Surgery for Initially Unresectable Stage Ⅲ Nonsmall Cell Lung Cancer After Induction Treatment of Immunochemotherapy: A Multicenter Study
Immuno-chemotherapy has demonstrated significant anti-tumor effects in patients with resectable nonsmall cell lung cancer (NSCLC). Additionally, for patients initially diagnosed with unresectable stage III NSCLC, induction immuno-chemotherapy may achieve tumor downstaging, enabling conversion to resectable disease allowing for by R0 resection. This study aimed to assess the effectiveness and safety of induction immuno-chemotherapy followed by conversion surgery in unresectable stage III NSCLC.