Molecular testing strategies in non-small cell lung cancer: optimizing the diagnostic journey

Abstract

Molecular testing identifies patients with advanced non-small cell lung cancer (NSCLC) who may benefit from targeted therapy or immunotherapy (i.e., immune checkpoint inhibitor treatment for patients with high tumor mutational burden (TMB), microsatellite instability-high or mismatch repairdeficient tumors). Current guidelines state that molecular testing should be conducted at the time of initial diagnosis and tumor progression on targeted therapy. In real-world clinical practice in the United States (US), molecular testing is often not conducted or happens late in the diagnostic journey, resulting in delayed or inappropriate treatment. Herein, we review the rationale for molecular testing in advanced NSCLC, along with best-practice guidelines based on published recommendations and our own clinical experience, including a case study. We propose three strategies to optimize molecular testing in newly diagnosed patients with advanced NSCLC: (I) pulmonologists, interventional radiologists, or thoracic surgeons order molecular tests as soon as advanced NSCLC with an adenocarcinoma component is suspected; (II) liquid biopsies conducted early in the diagnostic pathway; and (III) pathologist-directed reflex testing, as conducted in other areas of oncology. To help facilitate these strategies, we outline our recommendations for optimal sample collection techniques and stewardship. In summary, we believe that implementation of these individual strategies will allow clinicians to effectively leverage available treatment options for advanced NSCLC, reducing the time to optimal treatment and improving patient outcomes.

Polo‐like kinase 4 correlates with greater tumor size, lymph node metastasis and confers poor survival in non‐small cell lung cancer

“…As the leading cause of cancer‐related deaths worldwide, lung cancer is categorized into non‐small cell lung cancer (NSCLC) and small cell lung cancer with the former occupying 85% of all lung cancer cases . Since the initial presentation, NSCLC patients undergo multiple clinical and molecular examinations before implementation of treatment including clinical work‐up, biopsy, and molecular testing, and apart from surgery, platinum‐based chemotherapy, target therapy, and the novel immune therapy are administered accordingly . Although NSCLC is no longer incurable after decades of efforts, it is still premature to say that its prognosis is satisfying.…”

Inconsistent Intersample ALK FISH Results in Patients with Lung Cancer: Analysis of Potential Causes

“…These subclones can have distinct morphological and genetic features, including a different ALK status, and may further evolve, independent of or in response to therapies such as ALK inhibition. This phenomenon has an important practical implication, i.e., that tumor specimens collected from different anatomic sites or even the same anatomic site but at different time points in a lung cancer patient may need to be tested for ALK status [ 9 , 12 , 13 ].…”

“…Multiple assays that have been developed and applied for the assessment of ALK status, including fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), polymerase chain reaction (PCR) and reverse-transcription PCR (RT-PCR) assays, and next generation sequencing (NGS)-based DNA sequencing (DNA-seq) and RNA sequencing (RNA-seq) technologies. In numerous studies, improvements and optimization of these assays, rational diagnostic algorithms utilizing some or all these assays, and potential causes and solutions for the discrepant results obtained by different assays [ 9 , 10 , 11 , 12 ] have been reported.…”

Exosomal PD-L1: New Insights Into Tumor Immune Escape Mechanisms and Therapeutic Strategies

“…It is important to provide individualized precise treatment and to predict tumor response to immunotherapy ( Madore et al, 2015 ; Kaunitz et al, 2017 ; Sui et al, 2018 ; Liu and Wu, 2019 ). To fulfill the need for real-time monitoring, the analysis of liquid biopsy-based circulating biomarkers is preferred ( Nishino et al, 2013 ; Ando et al, 2019 ; Gregg et al, 2019 ; Kloten et al, 2019 ; Tang et al, 2020 ). Recent studies demonstrated that melanoma patients who were less responsive to anti-PD-1 blockade had a significantly higher level of circulating ExoPD-L1 prior to treatment as compared with responders ( Chen G. et al, 2018 ).…”