Impact of Tumor-intrinsic Molecular Features on Survival and Acquired Tyrosine Kinase Inhibitor Resistance in ALK-positive NSCLC.

Unlabelled: While tyrosine kinase inhibitors (TKI) have shown remarkable efficacy in anaplastic lymphoma kinase (ALK) fusion-positive advanced non-small cell lung cancer (NSCLC), clinical outcomes vary and acquired resistance remains a significant challenge. We conducted a retrospective study of patients with ALK-positive NSCLC who had clinico-genomic data independently collected from two academic institutions (n = 309). This was paired with a large-scale genomic cohort of patients with ALK-positive NSCLC who underwent liquid biopsies (n = 1,118).

Clinical and Genomic Characterization of Long-Term Responders Receiving Immune Checkpoint Blockade for Metastatic Non-Small-Cell Lung Cancer.

Objectives: Understand from a real-world cohort the unique clinical and genomic determinants of a durable response to immune checkpoint inhibitors (ICIs).

Materials And Methods: This is a retrospective study of patients with NSCLC who received any ICI-based regimen as first or second line therapy. Long-term responders (LTR) achieved an overall survival (OS) ≥ 3 years from time of treatment start, while nonresponders (NR) were patients who had an OS of 6 to 12 months from time of treatment start.

Elucidating the Heterogeneity of Immunotherapy Response and Immune-Related Toxicities by Longitudinal ctDNA and Immune Cell Compartment Tracking in Lung Cancer.

Purpose: Although immunotherapy is the mainstay of therapy for advanced non-small cell lung cancer (NSCLC), robust biomarkers of clinical response are lacking. The heterogeneity of clinical responses together with the limited value of radiographic response assessments to timely and accurately predict therapeutic effect-especially in the setting of stable disease-calls for the development of molecularly informed real-time minimally invasive approaches. In addition to capturing tumor regression, liquid biopsies may be informative in capturing immune-related adverse events (irAE).

Improved lung cancer clinical outcomes in patients with autoimmune rheumatic diseases.

Purpose: Concomitant autoimmune rheumatic diseases (ARD) can add morbidity and complicate treatment decisions for patients with lung cancer. We evaluated the tumour characteristics at diagnosis and clinical outcomes in lung cancer patients with or without ARD.

Methods: This retrospective cohort study included 10 963 patients with lung cancer, treated at Johns Hopkins.

Mesothelioma: Peritoneal, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.

Mesothelioma is a rare cancer originating in mesothelial surfaces of the peritoneum, pleura, and other sites. These NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) focus on peritoneal mesothelioma (PeM). The NCCN Guidelines for PeM provide recommendations for workup, diagnosis, and treatment of primary as well as previously treated PeM.

Pathologic Complete Response and Clinical Outcomes in Patients With Localized Soft Tissue Sarcoma Treated With Neoadjuvant Chemoradiotherapy or Radiotherapy: The NRG/RTOG 9514 and 0630 Nonrandomized Clinical Trials.

Importance: Pathologic complete response (pCR) may be associated with prognosis in patients with soft tissue sarcoma (STS).

Objective: We sought to determine the prognostic significance of pCR on survival outcomes in STS for patients receiving neoadjuvant chemoradiotherapy (CT-RT) (Radiation Therapy Oncology Group [RTOG] 9514) or preoperative image-guided radiotherapy alone (RT, RTOG 0630) and provide a long-term update of RTOG 0630.

Design, Setting, And Participants: RTOG has completed 2 multi-institutional, nonrandomized phase 2 clinical trials for patients with localized STS.

Lung Cancer Recurrence Risk Prediction through Integrated Deep Learning Evaluation.

Background: Prognostic risk factors for completely resected stage IA non-small-cell lung cancers (NSCLCs) have advanced minimally over recent decades. Although several biomarkers have been found to be associated with cancer recurrence, their added value to TNM staging and tumor grade are unclear. Methods: Features of preoperative low-dose CT image and histologic findings of hematoxylin- and eosin-stained tissue sections of resected lung tumor specimens were extracted from 182 stage IA NSCLC patients in the National Lung Screening Trial.

Definitive Chemoradiation and Durvalumab Consolidation for Locally Advanced, Unresectable KRAS-mutated Non-Small Cell Lung Cancer.

Background: Consolidation durvalumab immunotherapy following definitive chemoradiation (CRT) for unresectable stage III non-small cell lung cancer (NSCLC) improves overall survival. As therapeutic options for patients with KRAS-driven disease evolve, more understanding regarding genomic determinants of response and patterns of progression for durvalumab consolidation is needed to optimize outcomes.

Methods: We conducted a single-institutional retrospective analysis of real-world patients with locally advanced, unresectable NSCLC who completed CRT and received durvalumab consolidation.

Sex-specific differences in immunogenomic features of response to immune checkpoint blockade.

Introduction: The magnitude of response to immune checkpoint inhibitor (ICI) therapy may be sex-dependent, as females have lower response rates and decreased survival after ICI monotherapy. The mechanisms underlying this sex dimorphism in ICI response are unknown, and may be related to sex-driven differences in the immunogenomic landscape of tumors that shape anti-tumor immune responses in the context of therapy.

Methods: To investigate the association of immunogenic mutations with HLA haplotypes, we leveraged whole exome sequence data and HLA genotypes from 482 non-small cell lung cancer (NSCLC) tumors from The Cancer Genome Atlas (TCGA).

Clinical Features, Survival, and Burden of Toxicities in Survivors More Than One Year After Lung Cancer Immunotherapy.

Introduction: Anti-PD-(L)1 immune checkpoint inhibitors (ICI) improve survival in patients with advanced non-small cell lung cancer (aNSCLC). The clinical features, survival, and burden of toxicities of patients with aNSCLC alive >1 year from ICI initiation are poorly understood.

Materials And Methods: We defined ICI survivors as patients alive >1 year after ICI start and retrospectively reviewed demographics, treatment, and immune-related adverse events (irAEs).

NCCN Guidelines® Insights: Lung Cancer Screening, Version 1.2022.

The NCCN Guidelines for Lung Cancer Screening recommend criteria for selecting individuals for screening and provide recommendations for evaluation and follow-up of lung nodules found during initial and subsequent screening. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Lung Cancer Screening.

An Oncology Urgent Care Clinic for the Management of Immune-Related Adverse Events: A Descriptive Analysis.

Introduction: With the increasing use of immune checkpoint inhibitors (ICI) for cancer, there is a growing burden on the healthcare system to provide care for the toxicities associated with these agents. Herein, we aim to identify and describe the distribution of encounters seen in an urgent care setting for immune-related adverse events (irAEs) and the clinical outcomes from irAE management. Methods: Patient demographics, disease characteristics, and treatment data were collected retrospectively from encounters at an oncology Urgent Care Clinic (UCC) from a single tertiary center for upper aerodigestive malignancies from 1 July 2018 to 30 June 2019.

Non-Small Cell Lung Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) provide recommended management for patients with NSCLC, including diagnosis, primary treatment, surveillance for relapse, and subsequent treatment. Patients with metastatic lung cancer who are eligible for targeted therapies or immunotherapies are now surviving longer. This selection from the NCCN Guidelines for NSCLC focuses on targeted therapies for patients with metastatic NSCLC and actionable mutations.

Pretreatment Lung Function and Checkpoint Inhibitor Pneumonitis in NSCLC.

Introduction: Checkpoint inhibitor pneumonitis (CIP) is a serious toxicity of anti-programmed death-(ligand) 1 immunotherapy. Whether pretreatment differences in pulmonary function exist in patients who develop CIP is unknown. We analyzed the pulmonary function tests (PFTs) of patients with NSCLC treated with immune checkpoint inhibitors (ICIs) to evaluate whether pretreatment lung function was associated with CIP development.

An experiment on deception, reputation and trust.

An experiment is designed to shed light on how deception works. The experiment involves a twenty period sender/receiver game in which period 5 has more weight than other periods. In each period, the informed sender communicates about the realized state, the receiver then reports a belief about the state before being informed whether the sender lied.

Mutation status and postresection survival of patients with non-small cell lung cancer brain metastasis: implications of biomarker-driven therapy.

Objective: Non-small cell lung cancer (NSCLC) is the most common primary tumor to develop brain metastasis. Prognostic markers are needed to better determine survival after neurosurgical resection of intracranial disease. Given the importance of mutation subtyping in determining systemic therapy and overall prognosis of NSCLC, the authors examined the prognostic value of mutation status for postresection survival of patients with NSCLC brain metastasis.

Tethered spinal cord among individuals with myelomeningocele: an analysis of the National Spina Bifida Patient Registry.

Objective: The aims of this study were to review the National Spina Bifida Patient Registry (NSBPR) data set to study the rates of tethered spinal cord release (TCR) among patients with myelomeningocele and variability between centers, to compare TCR rates between males and females, and to study the relationships between TCR rates and other condition-specific characteristics.

Methods: The NSBPR registry was queried to identify all patients with myelomeningocele. TCR rates were calculated over time using survival analyses; rates between centers and between males and females were compared.

NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 2.2021.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines regarding targeted therapies, immunotherapies, and their respective biomarkers.

Multisystem Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors for Treatment of Non-Small Cell Lung Cancer.

Importance: The spectrum of individual immune-related adverse events (irAEs) from anti-programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) has been reported widely, and their development is associated with improved patient survival across tumor types. The spectrum and impact on survival for patients with non-small cell lung cancer (NSCLC) who develop multisystem irAEs from ICIs, has not been described.

Objective: To characterize multisystem irAEs, their association with survival, and risk factors for multisystem irAE development.

Multimodal genomic features predict outcome of immune checkpoint blockade in non-small-cell lung cancer.

Despite progress in immunotherapy, identifying patients that respond has remained a challenge. Through analysis of whole-exome and targeted sequence data from 5,449 tumors, we found a significant correlation between tumor mutation burden (TMB) and tumor purity, suggesting that low tumor purity tumors are likely to have inaccurate TMB estimates. We developed a new method to estimate a corrected TMB (cTMB) that was adjusted for tumor purity and more accurately predicted outcome to immune checkpoint blockade (ICB).

Radiologic response of chemotherapy alone versus radiation and chemotherapy in the treatment of locally-advanced or advanced thymic epithelial tumors.

Background: Here, we investigated radiological responses following chemotherapy alone as compared to both radiation/chemotherapy (chemoRT) in patients with thymic epithelial tumors (TETs) who did not receive upfront surgery.

Methods: TETs treated at a tertiary academic cancer center between January 2007 and July 2018 were identified. Patients received chemotherapy or chemoRT as initial therapy and pre- and post-treatment scans were available.