Novel radiogenomics approach to predict and characterize pneumonitis in stage III NSCLC.

Unresectable stage III NSCLC is now treated with chemoradiation (CRT) followed by immune checkpoint inhibitors (ICI). Pneumonitis, a common CRT complication, has heightened risk with ICI, potentially causing severe outcomes. Currently, there are no biomarkers to predict pneumonitis risk or differentiate between radiation-induced pneumonitis (RTP) and ICI-induced pneumonitis (IIP).

mutation testing, treatment and survival in stage I-III non-small cell lung cancer: CancerLinQ Discovery database retrospective analysis.

To describe real-world biomarker testing, treatment and survival in stage IA-IIIC non-small cell lung cancer (NSCLC). Electronic records of USA-based patients in the CancerLinQ Discovery database with stage IA-IIIC NSCLC (diagnosed between 2014 and 2018) were screened; a curated cohort of 14,452 records was identified for further analysis. Of 3121 (21.

Outcomes for pembrolizumab stratified by pemetrexed maintenance post pembrolizumab-platinum-pemetrexed induction in metastatic non-small-cell lung cancer.

We assessed treatment patterns and outcomes in patients with metastatic nonsquamous non-small-cell lung cancer (mNSCLC) who initiated first-line pembrolizumab-platinum-pemetrexed (induction) in US community oncology settings. Patients initiating induction were retrospectively identified. Patients continuing pembrolizumab afterward underwent chart review.

Clinical Nomogram Using Novel Computed Tomography-Based Radiomics Predicts Survival in Patients With Non-Small-Cell Lung Cancer Treated With Stereotactic Body Radiation Therapy.

Purpose: Improved survival prediction and risk stratification in non-small-cell lung cancer (NSCLC) would lead to better prognosis counseling, adjuvant therapy selection, and clinical trial design. We propose the persistent homology (PHOM) score, the radiomic quantification of solid tumor topology, as a solution.

Materials And Methods: Patients diagnosed with stage I or II NSCLC primarily treated with stereotactic body radiation therapy (SBRT) were selected (N = 554).

Clinical Outcomes With Pembrolizumab-Based Therapies in Recurrent/Refractory NSCLC After Chemoradiation and Consolidative Durvalumab.

Background: Often, patients with NSCLC experience recurrent/refractory (R/R) disease within 2 years of chemoradiation (CRT) and consolidative durvalumab. Despite prior immune checkpoint inhibitor exposure, immunotherapy with or without chemotherapy is typically initiated if a driver-oncogene is absent. However, there remains a paucity of data regarding the efficacy of immunotherapy in this patient population.

Genomic and transcriptomic analysis of checkpoint blockade response in advanced non-small cell lung cancer.

Anti-PD-1/PD-L1 agents have transformed the treatment landscape of advanced non-small cell lung cancer (NSCLC). To expand our understanding of the molecular features underlying response to checkpoint inhibitors in NSCLC, we describe here the first joint analysis of the Stand Up To Cancer-Mark Foundation cohort, a resource of whole exome and/or RNA sequencing from 393 patients with NSCLC treated with anti-PD-(L)1 therapy, along with matched clinical response annotation. We identify a number of associations between molecular features and outcome, including (1) favorable (for example, ATM altered) and unfavorable (for example, TERT amplified) genomic subgroups, (2) a prominent association between expression of inducible components of the immunoproteasome and response and (3) a dedifferentiated tumor-intrinsic subtype with enhanced response to checkpoint blockade.

TRUST-II: a global phase II study of taletrectinib in -positive non-small-cell lung cancer and other solid tumors.

Crizotinib and entrectinib have been approved to treat fusion-positive (ROS1) non-small-cell lung cancer. However, unmet needs remain, including treatment of patients with resistance mutations, efficacy in brain metastasis and avoidance of neurological side effects. Taletrectinib was designed to: improve efficacy; overcome resistance to first-generation ROS1 inhibitors; and address brain metastasis while conferring fewer neurological adverse events.

Modeling Costs and Life-Years Gained by Population-Wide Next-Generation Sequencing or Single-Gene Testing in Nonsquamous Non-Small-Cell Lung Cancer in the United States.

Purpose: Many patients with actionable driver oncogenes (ADOs) are never identified and thus never receive targeted treatment. This study evaluated the economic impact and the potential life-years gained (LYG) that can be attributed to the extent of next-generation sequencing (NGS) testing in the United States compared with single-gene testing (SGT) in patients with metastatic nonsquamous non-small-cell lung cancer in the United States.

Methods: A model was developed to evaluate incremental rates of SGT or NSG testing on the basis of LYG and cost per LYG.

Optimal predictive probability designs for randomized biomarker-guided oncology trials.

Introduction: Efforts to develop biomarker-targeted anti-cancer therapies have progressed rapidly in recent years. With efforts to expedite regulatory reviews of promising therapies, several targeted cancer therapies have been granted accelerated approval on the basis of evidence acquired in single-arm phase II clinical trials. And yet, in the absence of randomization, patient prognosis for progression-free survival and overall survival may not have been studied under standard of care chemotherapies for emerging biomarker subpopulations prior to the submission of an accelerated approval application.

Quantifying the Value of Multigene Testing in Resected Early Stage Lung Adenocarcinoma.

Introduction: Tyrosine kinase inhibitors and immune checkpoint inhibitors (ICIs), each requiring testing for precision biomarkers, have recently been approved in the adjuvant setting. We assessed the potential value of multigene testing in early lung adenocarcinoma (LUAD).

Methods: Using a real-world clinicogenomic database linking deidentified electronic health record-derived clinical data to genomic data, we selected patients with LUAD who underwent tissue comprehensive genomic profiling (CGP).

Perioperative Systemic Therapy for Resectable Non-Small Cell Lung Cancer.

Despite remarkable treatment advancements in patients with advanced non-small cell lung cancer (NSCLC), recurrence rates for those with resectable, early-stage disease remains high. Immune checkpoint inhibitors and targeted therapies are 2 promising treatment modalities that may improve survival outcomes for patients with resected NSCLC when moved from the advanced stage to the curable setting. There are many clinical studies that have evaluated or are currently evaluating immunotherapy or targeted therapy in the perioperative setting, and recent trials such as CheckMate 816, ADAURA, and IMpower010 have led to new approvals and demonstrated the promise of this approach.

A Review of Concurrent Chemo/Radiation, Immunotherapy, Radiation Planning, and Biomarkers for Locally Advanced Non-small Cell Lung Cancer and Their Role in the Development of ECOG-ACRIN EA5181.

ECOG-ACRIN EA5181 is a current prospective, randomized trial that is investigating whether the addition of concomitant durvalumab to standard chemo/radiation followed by 1 year of consolidative durvalumab results in an overall survival benefit over standard chemo/radiation alone followed by 1 year of consolidative durvalumab in patients with locally advanced, unresectable non-small cell lung cancer (NSCLC). Because multiple phase I/II trials have shown the relative safety of adding immunotherapy to chemo/radiation and due to the known synergism between chemotherapy and immunotherapy, it is hoped that concomitant durvalumab can reduce the relatively high incidence of local failure (38%-46%) as seen in recent prospective, randomized trials of standard chemo/radiation in this patient population. We will review the history of radiation for LA-NSCLC and discuss the role of induction, concurrent and consolidative chemotherapy as well as the concerns for late cardiac and pulmonary toxicities associated with treatment.

Impact of Socioeconomic Factors on Overall Survival in SCLC.

Objectives: To determine how the incidence and demographics of SCLC have changed over time and to evaluate whether patient demographics, disease presentation, and treatment characteristics affect patient outcomes.

Methods: We identified patients with SCLC in the National Cancer Database from 2004 to 2016. Differences in demographics, disease, and treatment characteristics were assessed by year of diagnosis using chi-square test.

A Phase 1 Study of Concurrent Neoadjuvant Pembrolizumab Plus Chemoradiation Followed by Consolidation Pembrolizumab in Patients With Resectable Stage IIIA NSCLC.

Introduction: Evidence supports the addition of immunotherapy to definitive chemoradiation for unresectable stage IIIA NSCLC. Adding pembrolizumab to neoadjuvant chemoradiation in patients with resectable stage IIIA NSCLC requires study for safety and feasibility.

Methods: Patients with resectable stage IIIA NSCLC received neoadjuvant cisplatin, etoposide, and pembrolizumab concurrently with thoracic radiotherapy of 45 Gy in 25 fractions.

Novel Radiomic Measurements of Tumor-Associated Vasculature Morphology on Clinical Imaging as a Biomarker of Treatment Response in Multiple Cancers.

Purpose: The tumor-associated vasculature (TAV) differs from healthy blood vessels by its convolutedness, leakiness, and chaotic architecture, and these attributes facilitate the creation of a treatment-resistant tumor microenvironment. Measurable differences in these attributes might also help stratify patients by likely benefit of systemic therapy (e.g.

Adagrasib in Non-Small-Cell Lung Cancer Harboring a Mutation.

Background: Adagrasib, a KRAS inhibitor, irreversibly and selectively binds KRAS, locking it in its inactive state. Adagrasib showed clinical activity and had an acceptable adverse-event profile in the phase 1-1b part of the KRYSTAL-1 phase 1-2 study.

Methods: In a registrational phase 2 cohort, we evaluated adagrasib (600 mg orally twice daily) in patients with -mutated non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy and anti-programmed death 1 or programmed death ligand 1 therapy.

Impact of Workforce Challenges and Funds Flow on Cancer Clinical Trial Development and Conduct.

The conduct of clinical cancer research has faced considerable challenges in recent years, and the situation has only been exacerbated by the global pandemic. The growing complexity of clinical trials and rising administrative burdens had been causing greater expense and difficulty in recruiting and retaining an appropriately trained workforce even before the well-publicized increase in turnover caused by the pandemic. Longstanding issues such as restrictive inclusion criteria and complicated trial designs have negatively affected already low clinical trial accrual rates, limited sites capable of opening studies and enrolling patients, and worsened disparities in trial participation.

The Rise of the Expert Patient in Cancer: From Backseat Passenger to Co-navigator.

Purpose: Patients who have cancer have leveraged the Internet to gain a better understanding of their disease and connect across geographic boundaries with others facing the same challenges. Online cancer communities have developed into resources that highlight new research and evolving care pathways. Combined with increasing health literacy and social media, they have enabled some patients to become experts in their cancer.

Modeling the Cost-Effectiveness of Adjuvant Osimertinib for Patients with Resected EGFR-mutant Non-Small Cell Lung Cancer.

Introduction: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor osimertinib was recently approved for resected EGFR-mutant stages IB-IIIA non-small cell lung cancer due to improved disease-free survival (DFS) in this population compared with placebo. This study aimed to evaluate the cost-effectiveness (CE) of this strategy.

Materials And Methods: We constructed a Markov model using post-resection health state transitions with digitized DFS data from the ADAURA trial to compare cost and quality-adjusted life years (QALYs) of 3 years of adjuvant osimertinib versus placebo over a 10-year time horizon.