Publications by authors named "Christina J Falcon"

Article Synopsis
  • The study aims to understand how specific molecular changes, particularly the expression of a certain gene, influence the clinical outcomes of patients with pulmonary carcinoids, which can range from slow-growing to deadly tumors.
  • Researchers analyzed RNA sequencing data from two cohorts of pulmonary carcinoid patients (totaling 193) to determine the prognostic value of this gene expression and its relationship with telomerase activity, which is linked to tumor aggressiveness.
  • Results showed that high expression of the gene correlates with worse survival rates and is an independent predictor of poor clinical outcomes, suggesting that it could be a key factor in assessing the severity of pulmonary carcinoids.
View Article and Find Full Text PDF

Small cell lung carcinoma (SCLC) is a highly aggressive malignancy that is typically associated with tobacco exposure and inactivation of RB1 and TP53 genes. Here we performed detailed clinicopathologic, genomic and transcriptomic profiling of an atypical subset of SCLC that lacked RB1 and TP53 co-inactivation and arose in never/light smokers. We found that most cases were associated with chromothripsis - massive, localized chromosome shattering - recurrently involving chromosomes 11 or 12, and resulting in extrachromosomal (ecDNA) amplification of CCND1 or co-amplification of CCND2/CDK4/MDM2, respectively.

View Article and Find Full Text PDF

Introduction: Immune checkpoint inhibitors (ICIs) can yield remarkable clinical responses in subsets of patients with solid tumors but can also often lead to immune-related adverse events (irAEs). Predictive features of clinically severe irAEs leading to cessation of ICIs have yet to be established. Using data from 1,327 patients with lung cancer treated with ICIs between 2009 and 2022 at four academic medical centers, we evaluated the association of a germline polygenic risk score for autoimmune disease and discontinuation of ICIs due to irAEs.

View Article and Find Full Text PDF

Immune checkpoint inhibitor-mediated colitis (IMC) is a common adverse event of treatment with immune checkpoint inhibitors (ICI). We hypothesize that genetic susceptibility to Crohn's disease (CD) and ulcerative colitis (UC) predisposes to IMC. In this study, we first develop a polygenic risk scores for CD (PRS) and UC (PRS) in cancer-free individuals and then test these PRSs on IMC in a cohort of 1316 patients with ICI-treated non-small cell lung cancer and perform a replication in 873 ICI-treated pan-cancer patients.

View Article and Find Full Text PDF

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).

View Article and Find Full Text PDF
Article Synopsis
  • Immune checkpoint inhibitors (ICIs) have vastly improved cancer treatment but can lead to serious immune-related adverse events (irAEs), particularly immune checkpoint inhibitor-mediated colitis (IMC), which can mimic diseases like Crohn's and ulcerative colitis.
  • Researchers hypothesized that genetic predispositions related to these diseases might increase the risk of developing IMC in cancer patients receiving ICIs, and they developed polygenic risk scores (PRS) to test this in a study of 1,316 non-small cell lung cancer patients.
  • The study found that higher PRS scores were linked to an increased risk of all-grade and severe IMC, suggesting that genetic testing could help identify patients at higher risk and enable better monitoring and
View Article and Find Full Text PDF

Introduction: Central nervous system (CNS) metastases develop in nearly half of patients with RET fusion-positive NSCLCs and cause morbidity and mortality. The selective RET inhibitor selpercatinib treats existing intracranial disease, but no studies have investigated whether early initiation of selpercatinib is associated with decreased development of CNS metastases.

Methods: A total of 61 patients with RET fusion-positive advanced NSCLC with and without CNS metastases treated with selpercatinib on the LIBRETTO-001 trial (NCT03157128) or the LIBRETTO-201 expanded access program (NCT03906331) were identified.

View Article and Find Full Text PDF

Introduction: Preferred first-line treatment for patients with metastatic EGFR-mutant lung cancer is osimertinib, yet it is not known whether patient outcomes may be improved by identifying and intervening on molecular markers associated with therapeutic resistance.

Methods: All patients with metastatic EGFR-mutant lung cancer treated with first-line osimertinib at the Memorial Sloan Kettering Cancer Center (n = 327) were identified. Available pretreatment and postprogression tumor samples underwent targeted gene panel sequencing and mutational signature analysis using SigMA algorithm.

View Article and Find Full Text PDF

Purpose: Clinical relevance thresholds and laboratory methods are poorly defined for MET amplification, a targetable biomarker across malignancies.

Experimental Design: The utility of next-generation sequencing (NGS) in assessing MET copy number alterations was determined in >50,000 solid tumors. Using fluorescence in situ hybridization as reference, we validated and optimized NGS analysis.

View Article and Find Full Text PDF

Introduction: Spontaneous chylous effusions are rare; however, they have been observed by independent investigators in patients treated with RET tyrosine kinase inhibitors (TKIs).

Methods: This multicenter, retrospective study evaluated the frequency of chylous effusions in patients treated with RET TKIs. Clinicopathologic features and management of patients with chylous effusions were evaluated.

View Article and Find Full Text PDF

Residual cancer cells that survive drug treatments with targeted therapies act as a reservoir from which eventual resistant disease emerges. Although there is great interest in therapeutically targeting residual cells, efforts are hampered by our limited knowledge of the vulnerabilities existing in this cell state. Here, we report that diverse oncogene-targeted therapies, including inhibitors of epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), KRAS, and BRAF, induce DNA double-strand breaks and, consequently, ataxia-telangiectasia mutated (ATM)-dependent DNA repair in oncogene-matched residual tumor cells.

View Article and Find Full Text PDF

Introduction: fusions are oncogenic drivers in 1% to 3% of NSCLCs. The activity of immune checkpoint inhibitor (ICI) monotherapy or in combination with chemotherapy (chemotherapy with ICI [chemo-ICI]) in these tumors and their immunophenotype have not been systematically described.

Methods: In this multi-institutional retrospective study, tumor programmed death-ligand 1 (PD-L1) expression and tumor mutational burden (TMB) were evaluated in patients with rearranged NSCLC.

View Article and Find Full Text PDF

Purpose: Current standard initial therapy for advanced, ROS proto-oncogene 1, receptor tyrosine kinase fusion ()-positive (ROS1) non-small cell lung cancer (NSCLC) is crizotinib or entrectinib. Lorlatinib, a next-generation anaplastic lymphoma kinase/ROS1 inhibitor, recently demonstrated efficacy in ROS1 NSCLC, including in crizotinib-pretreated patients. However, mechanisms of lorlatinib resistance in ROS1 disease remain poorly understood.

View Article and Find Full Text PDF

Purpose: exon 20 insertions (ex20ins) are an uncommon genotype in non-small cell lung cancer (NSCLC) for which targeted therapies are under development. We sought to describe treatment outcomes and genomic and immunophenotypic characteristics of these tumors.

Experimental Design: We identified sequential patients with NSCLC with ex20ins and compared their clinical outcomes and pathologic features with other patients with NSCLC.

View Article and Find Full Text PDF

A PHP Error was encountered

Severity: Warning

Message: fopen(/var/lib/php/sessions/ci_session3mqqdtbko1uq0pr0hk38b3ifm8u0hpe7): Failed to open stream: No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 177

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)

Filename: Session/Session.php

Line Number: 137

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once