Chitinase 3-like-1 (CHI3L1) in the pathogenesis of epidermal growth factor receptor mutant non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) accounts for 85 % of all lung cancers. In NSCLC, 10-20 % of Caucasian patients and 30-50 % of Asian patients have tumors with activating mutations in the Epidermal Growth Factor Receptor (EGFR). A high percentage of these patients exhibit favorable responses to treatment with tyrosine kinase inhibitors (TKI).

Preclinical Synergistic Combination Therapy of Lurbinectedin with Irinotecan and 5-Fluorouracil in Pancreatic Cancer.

Pancreatic cancer is a devastating disease with a poor prognosis. Novel chemotherapeutics in pancreatic cancer have shown limited success, illustrating the urgent need for new treatments. Lurbinectedin (PM01183; LY-01017) received FDA approval in 2020 for metastatic small cell lung cancer on or after platinum-based chemotherapy and is currently undergoing clinical trials in a variety of tumor types.

Predictors of Pneumonitis in Patients With Locally Advanced Non-Small Cell Lung Cancer Treated With Definitive Chemoradiation Followed by Consolidative Durvalumab.

Purpose: In patients with locally advanced, unresectable non-small cell lung cancer (NSCLC), the standard of care is concurrent chemoradiation (CRT) followed by consolidative immunotherapy with durvalumab. Pneumonitis is a known adverse event of both radiation therapy and immune checkpoint inhibitors such as durvalumab. We sought to characterize pneumonitis rates and dosimetric predictors of pneumonitis in a real-world population of patients with NSCLC treated with definitive CRT followed by consolidative durvalumab.

Retrospective Study to Examine Prognostic Value of C-Reactive Protein in Patients With Surgically Resectable Non-Small-Cell Lung Cancer.

Background: This study evaluated the association between elevated C-reactive protein (CRP) and clinical outcomes among adults treated with surgery for non-small cell lung cancer (NSCLC) in the US.

Materials And Methods: Adults with NSCLC who underwent lung cancer surgery and had ≥1 CRP measurement prior to, or >1 month following, index surgery were identified in the Optum Clinformatics claims database. The association between elevated CRP (>10 mg/L) and risk of NSCLC recurrence/death was assessed separately during the 6 months before surgery (pre surgery cohort) and 2 years following surgery (post-surgery cohort) using multivariate regressions and Kaplan-Meier analysis.

Prediction of lung malignancy progression and survival with machine learning based on pre-treatment FDG-PET/CT.

Background: Pre-treatment FDG-PET/CT scans were analyzed with machine learning to predict progression of lung malignancies and overall survival (OS).

Methods: A retrospective review across three institutions identified patients with a pre-procedure FDG-PET/CT and an associated malignancy diagnosis. Lesions were manually and automatically segmented, and convolutional neural networks (CNNs) were trained using FDG-PET/CT inputs to predict malignancy progression.

The effect that pathologic and radiologic interpretation of invasive and non-invasive areas in lung adenocarcinoma has on T-stage and treatment.

Lung adenocarcinoma is currently staged based on invasive tumor size, excluding areas of lepidic (in situ) growth. Invasive tumor size may be determined by pathologic assessment of a surgical specimen or radiographic assessment on computerized tomography (CT) scan. When invasive tumor size is the primary stage determinate, radiographic-pathologic discordance or discordant interpretation among pathologists may alter tumor stage and treatment.

Randomized Phase II Study of 3 Months or 2 Years of Adjuvant Afatinib in Patients With Surgically Resected Stage I-III -Mutant Non-Small-Cell Lung Cancer.

Unlabelled: For patients with surgically resected disease, multiple studies suggest a benefit of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in delaying cancer recurrence. The necessary duration of therapy for benefit is unknown.

Materials And Methods: This randomized phase II study enrolled patients with completely resected stage IA-IIIB -mutant non-small-cell lung cancer (American Joint Committee on Cancer 7th edition) after stage-appropriate standard-of-care adjuvant therapy.

Evolution of systemic therapy for stages I-III non-metastatic non-small-cell lung cancer.

The treatment goal for patients with early-stage lung cancer is cure. Multidisciplinary discussions of surgical resectability and medical operability determine the modality of definitive local treatment (surgery or radiotherapy) and the associated systemic therapies to further improve the likelihood of cure. Trial evidence supports cisplatin-based adjuvant therapy either after surgical resection or concurrently with radiotherapy.

Thoracic nuclear protein in testis (NUT) carcinoma: expanded pathological spectrum with expression of thyroid transcription factor-1 and neuroendocrine markers.

Aims: Nuclear protein in testis (NUT) carcinoma, an aggressive tumour driven by NUTM1 rearrangements, often involves the lung/mediastinum and shows squamous differentiation. We encountered an index patient with a thoracic NUT carcinoma diagnosed by molecular testing, showing extensive pleural involvement and diffuse thyroid transcription factor-1 (TTF-1) expression, initially suggestive of lung adenocarcinoma with pseudomesotheliomatous growth. We thus gathered an institutional series of thoracic NUT carcinomas to examine their pathological spectrum.

Revisiting MET: Clinical Characteristics and Treatment Outcomes of Patients with Locally Advanced or Metastatic, MET-Amplified Esophagogastric Cancers.

Background: Metastatic esophagogastric cancers (EGCs) have a poor prognosis with an approximately 5% 5-year survival. Additional treatment approaches are needed. c-MET gene-amplified tumors are an uncommon but potentially targetable subset of EGC.

Non-Small Cell Lung Cancer in the Era of Personalized Medicine: Molecular Tests that Matter.

The diagnosis and treatment of lung cancer is entering a new era. With increasingly advanced diagnostic tools, we are more able than ever to pinpoint genetic changes in tumor cells that allow us to treat with highly effective, targeted therapy. In a growing number of patients, we are able to avoid cytotoxic therapies altogether.

MET Alterations Are a Recurring and Actionable Resistance Mechanism in ALK-Positive Lung Cancer.

Purpose: Most -positive lung cancers will develop ALK-independent resistance after treatment with next-generation ALK inhibitors. amplification has been described in patients progressing on ALK inhibitors, but frequency of this event has not been comprehensively assessed.

Experimental Design: We performed FISH and/or next-generation sequencing on 207 posttreatment tissue ( = 101) or plasma ( = 106) specimens from patients with ALK-positive lung cancer to detect genetic alterations.

FOLFOX plus ziv-aflibercept or placebo in first-line metastatic esophagogastric adenocarcinoma: A double-blind, randomized, multicenter phase 2 trial.

Background: Antiangiogenic therapy is a proven therapeutic modality for refractory gastric and gastroesophageal junction adenocarcinoma. This trial assessed whether the addition of a high affinity angiogenesis inhibitor, ziv-aflibercept, could improve the efficacy of first-line mFOLFOX6 (oxaliplatin, leucovorin, and bolus plus infusional 5- fluorouracil) in metastatic esophagogastric adenocarcinoma.

Methods: Patients with treatment-naive metastatic esophagogastric adenocarcinoma were randomly assigned (in a 2:1 ratio) in a multicenter, placebo-controlled, double-blind trial to receive first-line mFOLFOX6 with or without ziv-aflibercept (4 mg/kg) every 2 weeks.

SELECT: A Phase II Trial of Adjuvant Erlotinib in Patients With Resected Epidermal Growth Factor Receptor-Mutant Non-Small-Cell Lung Cancer.

Purpose: Given the pivotal role of epidermal growth factor receptor (EGFR) inhibitors in advanced EGFR-mutant non-small-cell lung cancer (NSCLC), we tested adjuvant erlotinib in patients with EGFR-mutant early-stage NSCLC.

Materials And Methods: In this open-label phase II trial, patients with resected stage IA to IIIA (7 edition of the American Joint Committee on Cancer staging system) EGFR-mutant NSCLC were treated with erlotinib 150 mg per day for 2 years after standard adjuvant chemotherapy with or without radiotherapy. The study was designed for 100 patients and powered to demonstrate a primary end point of 2-year disease-free survival (DFS) greater than 85%, improving on historic data of 76%.

Exploiting MCL1 Dependency with Combination MEK + MCL1 Inhibitors Leads to Induction of Apoptosis and Tumor Regression in -Mutant Non-Small Cell Lung Cancer.

BH3 mimetic drugs, which inhibit prosurvival BCL2 family proteins, have limited single-agent activity in solid tumor models. The potential of BH3 mimetics for these cancers may depend on their ability to potentiate the apoptotic response to chemotherapy and targeted therapies. Using a novel class of potent and selective MCL1 inhibitors, we demonstrate that concurrent MEK + MCL1 inhibition induces apoptosis and tumor regression in -mutant non-small cell lung cancer (NSCLC) models, which respond poorly to MEK inhibition alone.

Tracking the Evolution of Resistance to ALK Tyrosine Kinase Inhibitors through Longitudinal Analysis of Circulating Tumor DNA.

Purpose: rearrangements predict for sensitivity to ALK tyrosine kinase inhibitors (TKIs). However, responses to ALK TKIs are generally short-lived. Serial molecular analysis is an informative strategy for identifying genetic mediators of resistance.

Beyond and and gene rearrangements in non-small cell lung cancer.

The discovery of gene rearrangements involving the receptor tyrosine kinase genes and has revolutionized management of the subset of non-small cell lung cancers characterized by these alterations. The oncogenic fusion proteins expressed in these tumors drive cancer cell growth and survival, and targeted inhibition of this signaling can lead to dramatic and durable responses in patients. While the best characterized gene fusions in non-small cell lung cancer (NSCLC) involve and , fusions involving other kinases including , , and are now established as additional targetable drivers.