Concurrent TP53 Mutations Facilitate Resistance Evolution in EGFR-Mutant Lung Adenocarcinoma.

Introduction: Patients with EGFR-mutant NSCLC experience variable duration of benefit on EGFR tyrosine kinase inhibitors. The effect of concurrent genomic alterations on outcome has been incompletely described.

Methods: In this retrospective study, targeted next-generation sequencing data were collected from patients with EGFR-mutant lung cancer treated at the Dana-Farber Cancer Institute.

Tumor volume dynamics and tumor growth rate in -rearranged advanced non-small-cell lung cancer treated with crizotinib.

Purpose: The purpose of the study is to investigate volumetric tumor burden dynamics and tumor growth rates in -rearranged advanced NSCLC patients during crizotinib monotherapy.

Methods: The study included 44 -rearranged advanced NSCLC patients treated with crizotinib monotherapy as their initial ALK-directed therapy, who had at least one measurable lung lesion and at least two follow-up CT scans, and experienced tumor volume increase while on crizotinib. The tumor volume (in mm) of the dominant lung lesion was measured on serial CT scans during therapy for analysis of tumor growth rates after the volume nadir.

The Impact of COVID-19 on Clinical Trial Execution at the Dana-Farber Cancer Institute.

Interventions designed to limit the spread of coronavirus disease 2019 (COVID-19) are having profound effects on the delivery of health care, but data showing the impact on oncology clinical trial enrollment, treatment, and monitoring are limited. We prospectively tracked relevant data from oncology clinical trials at Dana-Farber Cancer Institute from January 1, 2018, to June 30, 2020, including the number of open trials, new patient enrollments, in-person and virtual patient visits, dispensed investigational infusions, dispensed or shipped oral investigational agents, research biopsies, and blood samples. We ascertained why patients came off trials and determined on-site clinical research staffing levels.

Tumor Volume Analysis as a Predictive Marker for Prolonged Survival in Anaplastic Lymphoma Kinase-rearranged Advanced Non-Small Cell Lung Cancer Patients Treated With Crizotinib.

Purpose: Targeted inhibition of anaplastic lymphoma kinase (ALK) has been widely used for the treatment of advanced non-small cell lung cancer (NSCLC) with ALK rearrangements. We performed tumor volume analysis of ALK-rearranged advanced NSCLC treated with crizotinib to identify an early predictive marker for prolonged survival.

Materials And Methods: Cases of 42 patients with ALK-rearranged advanced NSCLC (16 men, 26 women; median age: 55.

Interstitial lung abnormality in stage IV non-small cell lung cancer: A validation study for the association with poor clinical outcome.

Purpose: The presence of interstitial lung abnormality (ILA) at diagnosis of stage IV non-small cell lung cancer (NSCLC) patients has previously shown to be associated with shorter overall survival (OS). The present study aimed to validate the association between ILA and shorter OS in a larger cohort of treatment-naïve stage IV NSCLC patients.

Materials And Methods: This study includes 484 patients (205 men and 279 women) with a pathological diagnosis of stage IV NSCLC with pretreatment baseline CT available for review.

M1b Disease in the 8th Edition of TNM Staging of Lung Cancer: Pattern of Single Extrathoracic Metastasis and Clinical Outcome.

Background: The 8th edition of TNM staging of non-small cell lung cancer (NSCLC) has revised M classification and defined M1b disease with single extrathoracic metastasis, which is distinguished from M1c with multiple extrathoracic metastases. We investigated the prevalence, characteristics, and overall survival (OS) of M1b disease in patients with stage IV NSCLC.

Methods: The study reviewed the medical records and imaging studies of 567 patients with stage IV NSCLC to determine M stage using the 8th edition of TNM staging.

Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses.

Mesenchymal tumor subpopulations secrete pro-tumorigenic cytokines and promote treatment resistance. This phenomenon has been implicated in chemorefractory small cell lung cancer and resistance to targeted therapies, but remains incompletely defined. Here, we identify a subclass of endogenous retroviruses (ERVs) that engages innate immune signaling in these cells.

Safety and Efficacy of PD-1 Inhibitors Among HIV-Positive Patients With Non-Small Cell Lung Cancer.

Introduction: 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.

Methods: Here, we describe seven patients with metastatic NSCLC and HIV infection who were treated with PD-1 inhibitors nivolumab (two cases) or pembrolizumab (five cases with three in the first-line setting).

Results: Partial responses to immune checkpoint inhibitors were observed in three of seven cases.

Epitope mapping of spontaneous autoantibodies to anaplastic lymphoma kinase (ALK) in non-small cell lung cancer.

The anaplastic lymphoma kinase (ALK) is recognized by the immune system as a tumor antigen, and preclinical evidence suggests that ALK-rearranged NSCLCs can also be successfully targeted immunologically using vaccine-based approaches. In contrast to ALK-rearranged lymphomas, the frequency and clinical significance of spontaneous ALK immune responses in patients with ALK-rearranged NSCLCs are largely unknown. We developed an enzyme-linked immunosorbent assay (ELISA) to measure anti-ALK antibody levels and mapped specific peptide epitope sequences within the ALK cytoplasmic domain in patients with non-small cell lung cancer.

Tumor Response Dynamics of Advanced Non-small Cell Lung Cancer Patients Treated with PD-1 Inhibitors: Imaging Markers for Treatment Outcome.

We evaluated tumor burden dynamics in patients with advanced non-small cell lung cancer (NSCLC) treated with commercial PD-1 inhibitors to identify imaging markers associated with improved overall survival (OS). The study included 160 patients with advanced NSCLC treated with commercial nivolumab or pembrolizumab monotherapy as a part of clinical care. Tumor burden dynamics were studied for the association with OS.

Cost and Survival Analysis Before and After Implementation of Dana-Farber Clinical Pathways for Patients With Stage IV Non-Small-Cell Lung Cancer.

Purpose: Increasing costs and medical complexity are significant challenges in modern oncology. We explored the use of clinical pathways to support clinical decision making and manage resources prospectively across our network.

Materials And Methods: We created customized lung cancer pathways and partnered with a commercial vendor to provide a Web-based platform for real-time decision support and post-treatment data aggregation.

Acquired METD1228V Mutation and Resistance to MET Inhibition in Lung Cancer.

Unlabelled: Amplified and/or mutated MET can act as both a primary oncogenic driver and as a promoter of tyrosine kinase inhibitor (TKI) resistance in non-small cell lung cancer (NSCLC). However, the landscape of MET-specific targeting agents remains underdeveloped, and understanding of mechanisms of resistance to MET TKIs is limited. Here, we present a case of a patient with lung adenocarcinoma harboring both a mutation in EGFR and an amplification of MET, who after progression on erlotinib responded dramatically to combined MET and EGFR inhibition with savolitinib and osimertinib.

Five-Year Survival in EGFR-Mutant Metastatic Lung Adenocarcinoma Treated with EGFR-TKIs.

Introduction: Activating mutations in the epidermal growth factor receptor gene (EGFR) predict for prolonged progression-free survival in patients with advanced non-small cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs) versus chemotherapy. Long-term survival outcomes, however, remain undefined. The objective of this study was to determine the 5-year survival in these patients and identify clinical factors associated with overall survival (OS).