Liquid Biopsy Approaches for Cancer Characterization, Residual Disease Detection, and Therapy Monitoring.

Liquid biopsy encompasses a variety of molecular approaches to detect circulating tumor DNA (ctDNA) and has become a powerful tool in the diagnosis and treatment of solid tumors. Current applications include comprehensive genomic profiling for identifying targetable mutations and therapeutic resistance mechanisms, with emerging applications in minimal residual disease detection and treatment response monitoring. Increasingly, the potential for liquid biopsy in guiding treatment decisions is under active investigation through prospective clinical trials using ctDNA-adaptive interventions in patients with early-stage and metastatic cancers.

Consolidation ALK Tyrosine Kinase Inhibitors Versus Durvalumab or Observation After Chemoradiation in Unresectable Stage III ALK-Positive NSCLC.

Introduction: Patients with advanced ALK-positive NSCLC typically have poor response to immunotherapy; the benefit of consolidation durvalumab in patients with unresectable stage III ALK-positive NSCLC remains unclear. Herein, we compare the efficacy and safety of consolidation ALK tyrosine kinase inhibitor (TKI) versus durvalumab or observation after concurrent chemoradiation.

Methods: We conducted a retrospective study using a multicenter study of 17 institutions globally.

Neoadjuvant Osimertinib for the Treatment of Stage I-IIIA Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer: A Phase II Multicenter Study.

Purpose: To assess the safety and efficacy of the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor osimertinib as neoadjuvant therapy in patients with surgically resectable stage I-IIIA -mutated non-small cell lung cancer (NSCLC).

Patients And Methods: This was a multi-institutional phase II trial of neoadjuvant osimertinib for patients with surgically resectable stage I-IIIA (American Joint Committee on Cancer [AJCC] V7) -mutated (L858R or exon 19 deletion) NSCLC (ClinicalTrials.gov identifier: NCT03433469).

Top advances of the year: Perioperative therapy for lung cancer.

Emerging data supporting the rise of perioperative immune checkpoint inhibitors (ICIs) as a standard of care in the treatment of early stage, surgically resectable non-small cell lung cancer (NSCLC) dominated the NSCLC news in 2023. Adjuvant pembrolizumab became the second adjuvant ICI to receive US Food and Drug Administration approval in early 2023 after the 2021 approval of adjuvant atezolizumab and the 2022 approval of neoadjuvant nivolumab with chemotherapy. Subsequently in 2023, multiple phase 3 trials examining perioperative ICIs were positive and demonstrated clinically meaningful outcomes by prolonging event-free survival, improving pathologic complete response rates, and trending toward improved overall survival in most.

Consolidation Osimertinib Versus Durvalumab Versus Observation After Concurrent Chemoradiation in Unresectable EGFR-Mutant NSCLC: A Multicenter Retrospective Cohort Study.

Introduction: Durvalumab improves survival when used as consolidation therapy after chemoradiation (CRT) in patients with stage III NSCLC. The optimal consolidation therapy for patients with EGFR-mutant (EGFRmut) stage III NSCLC remains unknown.

Methods: In this multi-institutional, international retrospective analysis across 24 institutions, we evaluated outcomes in patients with stage III EGFRmut NSCLC treated with concurrent CRT followed by consolidation therapy with osimertinib, durvalumab, or observation between 2015 and 2022.

Second Primary Lung Cancer Among Lung Cancer Survivors Who Never Smoked.

Importance: Lung cancer among never-smokers accounts for 25% of all lung cancers in the US; recent therapeutic advances have improved survival among patients with initial primary lung cancer (IPLC), who are now at high risk of developing second primary lung cancer (SPLC). As smoking rates continue to decline in the US, it is critical to examine more closely the epidemiology of lung cancer among patients who never smoked, including their risk for SPLC.

Objective: To estimate and compare the cumulative SPLC incidence among lung cancer survivors who have never smoked vs those who have ever smoked.

Risk Model-Based Lung Cancer Screening and Racial and Ethnic Disparities in the US.

Importance: The revised 2021 US Preventive Services Task Force (USPSTF) guidelines for lung cancer screening have been shown to reduce disparities in screening eligibility and performance between African American and White individuals vs the 2013 guidelines. However, potential disparities across other racial and ethnic groups in the US remain unknown. Risk model-based screening may reduce racial and ethnic disparities and improve screening performance, but neither validation of key risk prediction models nor their screening performance has been examined by race and ethnicity.

Risk model-based management for second primary lung cancer among lung cancer survivors through a validated risk prediction model.

Background: Recent therapeutic advances and screening technologies have improved survival among patients with lung cancer, who are now at high risk of developing second primary lung cancer (SPLC). Recently, an SPLC risk-prediction model (called SPLC-RAT) was developed and validated using data from population-based epidemiological cohorts and clinical trials, but real-world validation has been lacking. The predictive performance of SPLC-RAT was evaluated in a hospital-based cohort of lung cancer survivors.

Efficacy of Osimertinib in Patients with Lung Cancer Positive for Uncommon EGFR Exon 19 Deletion Mutations.

Purpose: The uncommon EGFR exon 19 deletion (ex19del), L747_A750>P, demonstrates reduced sensitivity to osimertinib compared with the common ex19del, E746_A750del in preclinical models. The clinical efficacy of osimertinib in patients with non-small cell lung cancer harboring L747_A750>P and other uncommon ex19dels is not known.

Experimental Design: The AACR GENIE database was interrogated to characterize the frequency of individual ex19dels relative to other variants, and a multicenter retrospective cohort was used to compare clinical outcomes for patients with tumors harboring E746_A750del, L747_A750>P, and other uncommon ex19dels who received osimertinib in the first line (1L) or in second or later lines of therapy and were T790M+ (≥2L).

Implementation and evaluation of an elective quality improvement curriculum for preclinical students: a prospective controlled study.

Background: Quality improvement (QI) is a systematic approach to improving healthcare delivery with applications across all fields of medicine. However, exposure to QI is minimal in early medical education. We evaluated the effectiveness of an elective QI curriculum in teaching preclinical health professional students foundational QI concepts.

Induction EGFR tyrosine kinase inhibitors prior to definitive chemoradiotherapy in unresectable stage III EGFR-mutated non-small cell lung cancer.

Introduction: Increasing evidence suggests that consolidation durvalumab confers limited benefits for patients with stage III EGFR-mutated NSCLC. Induction or maintenance EGFR tyrosine kinase inhibitors (TKIs) added to concurrent chemoradiotherapy (CRT) may optimize definitive treatment, but there are limited data supporting an induction TKI strategy.

Methods: We evaluated the efficacy and safety of induction EGFR TKIs administered before concurrent CRT in a retrospective series of patients with unresectable locally advanced EGFR-mutated NSCLC.

Racial and Ethnic Disparities in Lung Cancer Screening by the 2021 USPSTF Guidelines Versus Risk-Based Criteria: The Multiethnic Cohort Study.

Background: In 2021, the US Preventive Services Task Force (USPSTF) revised its lung cancer screening guidelines to expand screening eligibility. We evaluated screening sensitivities and racial and ethnic disparities under the 2021 USPSTF criteria vs alternative risk-based criteria in a racially and ethnically diverse population.

Methods: In the Multiethnic Cohort, we evaluated the proportion of ever-smoking lung cancer cases eligible for screening (ie, screening sensitivity) under the 2021 USPSTF criteria and under risk-based criteria through the PLCOm2012 model (6-year risk ≥1.

High-Dose Osimertinib for CNS Progression in EGFR+ NSCLC: A Multi-Institutional Experience.

Introduction: This multicenter review evaluated the efficacy and safety of osimertinib dose escalation for central nervous system (CNS) progression developing on osimertinib 80 mg in -mutant NSCLC.

Methods: Retrospective review identified 105 patients from eight institutions with advanced -mutant NSCLC treated with osimertinib 160 mg daily between October 2013 and January 2020. Radiographic responses were clinically assessed, and Kaplan-Meier analyses were used.

Afatinib After Progression on Osimertinib in EGFR-Mutated Non-Small Cell Lung Cancer.

Introduction: After the development of acquired resistance to osimertinib, the standard-of-care treatment for advanced EGFR-mutated NSCLC is chemotherapy. Whether afatinib, a pan-ErbB family tyrosine kinase inhibitor, is active after progression on osimertinib is unknown.

Methods: We conducted a single-institution retrospective analysis of patients with advanced EGFR-mutated NSCLC who received afatinib-containing therapy after progression on osimertinib.

The Survival Impact of Second Primary Lung Cancer in Patients With Lung Cancer.

Background: Lung cancer survivors have a high risk of developing second primary lung cancer (SPLC), but little is known about the survival impact of SPLC diagnosis.

Methods: We analyzed data from 138 969 patients in the Surveillance, Epidemiology, and End Results (SEER), who were surgically treated for initial primary lung cancer (IPLC) in 1988-2013. Each patient was followed from the date of IPLC diagnosis to SPLC diagnosis (for those with SPLC) and last vital status through 2016.

Smoking Cessation After Lung Cancer Diagnosis and the Risk of Second Primary Lung Cancer: The Multiethnic Cohort Study.

Background: Smoking cessation reduces lung cancer mortality. However, little is known about whether diagnosis of lung cancer impacts changes in smoking behaviors. Furthermore, the effects of smoking cessation on the risk of second primary lung cancer (SPLC) have not been established yet.

EGFR exon 20 Insertion NSCLC and Response to Platinum-Based Chemotherapy.

Introduction: In classical EGFR mutant non-small-cell lung cancer (NSCLC), EGFR tyrosine kinase inhibitor (TKI) therapy yields better outcomes than platinum-based chemotherapy. However, EGFR exon 20 insertion (ex20ins) NSCLC is relatively resistant to currently available EGFR TKIs. Though platinum-based chemotherapy is the frontline standard of care for EGFR ex20ins NSCLC, its efficacy is not fully described.