Plasma-first: accelerating lung cancer diagnosis and molecular profiling through liquid biopsy

Abstract

Introduction: Molecular profiling of tumor tissue is the gold standard for treatment decision-making in advanced non-small cell lung cancer (NSCLC). Results may be delayed or unavailable due to insufficient tissue, prolonged wait times for biopsy, pathology assessment and testing. We piloted the use of plasma testing in the initial diagnostic workup for patients with suspected advanced lung cancer. Methods: Patients with ⩽15 pack-year smoking history and suspected advanced lung cancer referred to the lung cancer rapid diagnostic program underwent plasma circulating-tumor DNA testing using a DNA-based mutation panel. Tissue testing was performed per standard of care, including comprehensive next-generation sequencing (NGS). The primary endpoint was time from diagnostic program referral to cancer treatment in stage IV NSCLC patients (Cohort A) compared to a contemporary cohort not enrolled in the study (Cohort B) and an historical pre-COVID cohort referred to the program between 2018 and 2019 (Cohort C). Results: From January to June 2021, 20 patients were enrolled in Cohort A; median age was 70.5 years (range 33–87), 70% were female, 55% Caucasian, 85% never smokers, and 75% were diagnosed with NSCLC. Seven had actionable alterations detected in plasma or tissue (4/7 concordant). Fusions, not tested in plasma, were identified by immunohistochemistry for three patients. Mean result turnaround time was 17.8 days for plasma NGS and 23.6 days for tissue ( p = 0.10). Mean time from referral to treatment initiation was significantly shorter in cohort A at 32.6 days (SD 13.1) versus 62.2 days (SD 31.2) in cohort B and 61.5 days (SD 29.1) in cohort C, both p < 0.0001. Conclusion: Liquid biopsy in the initial diagnostic workup of patients with suspected advanced NSCLC can lead to faster molecular results and shorten time to treatment even with smaller DNA panels. An expansion study using comprehensive NGS plasma testing with faster turnaround time is ongoing (NCT04862924).

Selinexor for the treatment of recurrent or metastatic salivary gland tumors: Results from the GEMS‐001 clinical trial

“…The advancements in noninvasive techniques for genomic analyses such as liquid biopsies may, in the near future, may help to inform in a timely manner treatment selection strategies. 29,30 Lastly, the small number of patients enrolled and the variety of SGT histologies included may have hindered the possibility to identify activity signals in specific subtypes of SGT or individuals with specific genomic alterations. Further multi-institutional efforts or master protocols will be required to fully elucidate the role of selinexor in biomarker enriched populations of SGT and its role with other molecularly-guided therapies.…”

“…Presumably given that only patients who had progressing tumors were eligible to enroll onto selinexor and thus had an inherent poor prognosis which could have impacted the outcomes and moderate signs of activity observed in this cohort. The advancements in non‐invasive techniques for genomic analyses such as liquid biopsies may, in the near future, may help to inform in a timely manner treatment selection strategies 29,30 . Lastly, the small number of patients enrolled and the variety of SGT histologies included may have hindered the possibility to identify activity signals in specific subtypes of SGT or individuals with specific genomic alterations.…”

The economic value of liquid biopsy for genomic profiling in advanced non-small cell lung cancer

“…Although our analysis looked at the concurrent approach of performing LB in patients who already had a tissue diagnosis, several studies are already examining the impact of a plasma-first strategy, 28,29 as well as its cost-effectiveness. 30 This may be preferred for patients in whom obtaining a tissue biopsy is too risky or difficult and may accelerate genomic testing and treatment initiation. However, it is important to recall that a plasma-first approach does not obviate the need for TT for pathologic diagnosis and studies such as PD-L1 expression.…”

Current and future applications of liquid biopsy in non-small-cell lung cancer—a narrative review

“…Supplementing the standard tissue evaluation with liquid biopsy was also shown to save system costs and increase the number of patients administered appropriate targeted therapies (13)(14)(15). Finally, a liquid biopsy may significantly shorten turnaround times at primary diagnosis and at progression (16)(17)(18).…”