The possibility of complete recovery for a lung cancer patient depends on very early diagnosis, as it allows total surgical resection. Screening for this cancer in a high-risk population can be ...performed using a radiological approach, but this holds a certain number of limitations. Liquid biopsy could become an alternative and complementary screening approach to chest imaging for early diagnosis of lung cancer.
Several circulating biomarkers indicative of lung cancer can be investigated in blood, such as circulating tumor cells, circulating free nucleic acids (RNA and DNA) and proteins. However, none of these biomarkers have yet been adopted in routine clinical practice and studies are ongoing to confirm or not the usefulness and practical interest in routine early diagnosis and screening for lung cancers.
Several potential circulating biomarkers for the early detection of lung cancer exist. When coupled to thoracic imaging, these biomarkers must give diagnosis of a totally resectable lung cancer and potentially provide new recommendations for surveillance by imagery of high-risk populations without a detectable nodule. Optimization of the specificity and sensitivity of the detection methods as well as standardization of the techniques is essential before considering for daily practice a liquid biopsy as an early diagnostic tool, or possibly as a predictive test, of lung cancer.
Recently, the liquid biopsy (LB), a non-invasive and easy to repeat approach, has started to compete with the tissue biopsy (TB) for detection of targets for administration of therapeutic strategies ...for patients with advanced stages of lung cancer at tumor progression. A LB at diagnosis of late stage non-small cell lung carcinoma (NSCLC) is also being performed. It may be asked if a LB can be complementary (according to the clinical presentation or systematics) or even an alternative to a TB for treatment-naïve advanced NSCLC patients. Nucleic acid analysis with a TB by next-generation sequencing (NGS) is gradually replacing targeted sequencing methods for assessment of genomic alterations in lung cancer patients with tumor progression, but also at baseline. However, LB is still not often used in daily practice for NGS. This review addresses different aspects relating to the use of LB for NGS at diagnosis in advanced NSCLC, including its advantages and limitations.
•Next generation sequencing from matched tissue and liquid biopsies can have an add value at diagnosis and at progression in advanced non-small cell lung patients in order.•To allow the detection of ...additional genomic alteration.•To identified clonal hematopoiesis of indeterminate potential.•To reduce the turnaround time to obtain the results.•To have an alternative in case of insufficient tissue material.•To develop translational and clinical research programs in prospective clinical trials.
The introduction of liquid biopsies (LB) has brought forth a number of therapeutic opportunities into the domain of thoracic oncology. Many of which have been adopted for care of patients presenting with advanced non-squamous non-small cell lung cancer (aNS-NSCLC). For example, one of the most frequent indications to perform a LB in these patients, at least in Europe, is for patients treated with tyrosine kinase inhibitors (TKIs) targeting EGFR and ALK genomic alterations when the tumor progresses. A tissue biopsy (TB) must then be taken, ideally from a site of a tumor that progresses, in particular if the LB does not permit detection of a mechanism of resistance to TKI. A LB from a patient with aNS-NSCLC is recommended before first-line therapy if no tissue and/or cytological material is accessible or if the extracted nucleic acid is insufficient in amount and/or of poor quality. At present a LB and a TB are rarely performed simultaneously before treatment and/or on tumor progression. This complementary/matched testing approach is still controversial but needs to be better evaluated to determine the true benefit to care of patients. This review provides an update on the complementarity of the LB and TB method for care of patients presenting with aNS-NSCLC.
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Patients with advanced-stage non-small cell lung carcinoma (NSCLC) harboring an ALK rearrangement, detected from a tissue sample, can benefit from targeted ALK inhibitor treatment. Several ...increasingly effective ALK inhibitors are now available for treatment of patients. However, despite an initial favorable response to treatment, in most cases relapse or progression occurs due to resistance mechanisms mainly caused by mutations in the tyrosine kinase domain of ALK. The detection of an ALK rearrangement is pivotal and can be done using different methods, which have variable sensitivity and specificity depending, in particular, on the quality and quantity of the patient's sample. This review will first highlight briefly some information regarding the pathobiology of an ALK rearrangement and the epidemiology of patients harboring this genomic alteration. The different methods used to detect an ALK rearrangement as well as their advantages and disadvantages will then be examined and algorithms proposed for detection in daily routine practice.
The survival of most patients with advanced stage non-small cell lung cancer is prolonged by several months when they are treated with first- and next-generation inhibitors targeting
rearrangements, ...but resistance inevitably emerges. Some of the mechanisms of resistance are sensitive to novel ALK inhibitors but after an initial tumor response, more or less long-term resistance sets in. Therefore, to adapt treatment it is necessary to repeat biological sampling over time to look for different mechanisms of resistance. To this aim it is essential to obtain liquid and/or tissue biopsies to detect therapeutic targets, in particular for the analysis of different genomic alterations. This review discusses the mechanisms of resistance to therapeutics targeting genomic alterations in
as well as the advantages and the limitations of liquid biopsies for their identification.
The practice of liquid biopsy (LB) has revolutionized the care of patients with metastatic lung cancer. Many oncologists now use this approach in daily practice, applying precise procedures for the ...detection of activating or resistance mutations in
. These tests are performed with plasma DNA and have been approved as companion diagnostic test for patients treated with tyrosine kinase inhibitors.
is another important target in lung cancer since it leads to treatment of patients who are positive for a rearrangement in
identified with tumor tissue. By analogy with
, LB for detection of genomic alterations in
(rearrangements or mutations) has been rapidly adopted in the clinic. However, this promising approach has some limitations and has not yet been disseminated as much as the blood test targeting
. In addition to these two therapeutic targets LB can be used for evaluation of the genomic status of other genes of interest of patients with lung cancer (
,
,
,
,
, etc.). LB can be performed to evaluate a specific target or for a more or less complex panel of genes. Considering the number of potential targets for clinical trials, techniques of next-generation sequencing of circulating DNA are on the rise. This review will provide an update on the contribution of LB to care of patients with metastatic lung cancer, including the present limits of this approach, and will consider certain perspectives.
Immunotherapy targeting the PD-L1/PD-1 axis has recently shown spectacular efficacy and promise for the future of patients with metastatic lung cancer. In the setting of second-line treatment of ...metastatic disease, this therapy has increased overall survival of patients by several months when compared to chemotherapy, both for squamous cell carcinoma (SCC) and adenocarcinoma (ADC) of the lung. Clinical trials targeting the PD-1/PD-L1 axis have shown a tendency towards higher efficacy if expression of PD-L1 is relatively high, as evaluated by immunohistochemistry (IHC) of tumour samples. Targeting the PD-1/PD-L1 axis is of crucial importance not only for metastatic non-small cell lung cancer (NSCLC) but probably also for patients with small cell lung cancer. Nivolumab, an antibody targeting PD-1, has recently received FDA and EMA approval for NSCLC, regardless of the PDL1 expression status (for both tumour types in the USA and for only SCC in EU). However, the need for a biomarker that allows better selection of patients is essential, to improve treatment efficacy and to manage cost of these therapies. Assessment of PD-L1 expression through immunohistochemical staining is advocated by many as one such potential biomarker. This prospect raises several questions, in particular how to define a threshold for positive PD-L1 labelling on biopsy tissue samples, taking into account that certain patients respond to treatment targeting PD-L1/PD-1, despite low or absent immunoreactivity of this biomarker. This review discusses major challenges related to detection of PD-L1 by immunohistochemistry as a companion diagnostic test, along with immune checkpoint blockade treatment of lung cancer.
Purpose To investigate whether the blood-brain barrier (BBB) leaks blood-circulating substances in patients with early forms of Alzheimer disease (AD), and if so, to examine the extent and pattern of ...leakage. Materials and Methods This study was approved by the local medical ethical committees of the Maastricht University Medical Center and Leiden University Medical Center, and written informed consent was obtained from all subjects. For this pilot study, 16 patients with early AD and 17 healthy age-matched control subjects underwent dynamic contrast material-enhanced magnetic resonance (MR) imaging sequence with dual time resolution for 25 minutes. The Patlak graphical approach was used to quantify the BBB leakage rate and local blood plasma volume. Subsequent histogram analysis was used to determine the volume fraction of the leaking brain tissue. Differences were assessed with linear regression analysis, adjusted for confounding variables. Results The BBB leakage rate was significantly higher in patients compared with that in control subjects in the total gray matter (P < .05) and cortex (P = .03). Patients had a significantly higher volume fraction of the leaking brain tissue in the gray matter (P = .004), normal-appearing white matter (P < .04), deep gray matter (P = .01), and cortex (P = .004). When all subjects were considered, scores on the Mini-Mental State Examination decreased significantly with increasing leakage in the deep gray matter (P = .007) and cortex (P < .05). Conclusion The results of this study showed global BBB leakage in patients with early AD that is associated with cognitive decline. A compromised BBB may be part of a cascade of pathologic events that eventually lead to cognitive decline and dementia.
RSNA, 2016 Online supplemental material is available for this article.
Patients with advanced stage non-small cell lung carcinoma (NSCLC) harboring an anaplastic lymphoma kinase
gene rearrangement, detected from a tissue sample, can benefit from targeted ALK inhibitor ...treatment. However, while treatment is initially effective in most cases, relapse or progression occurs due to different resistance mechanisms including mutations in the tyrosine kinase domain of echinoderm microtubule-associated protein-like 4 (EML44)-ALK. The liquid biopsy concept has recently radically changed the clinical care of NSCLC patients, in particular for those harboring an epidermal growth factor receptor (
) gene mutation. Therefore, liquid biopsy is an alternative or complementary method to tissue biopsy for the detection of some resistance mutations in
arising during tyrosine kinase inhibitor treatment. Moreover, in some frail patients, or if the tumor lesion is not accessible to a tissue biopsy, a liquid biopsy can also detect some activating mutations in
on initial assessment. Recent studies have evaluated the possibility of also using a liquid biopsy approach to detect an
rearrangement and/or the emergence during inhibitor treatment of some resistance mutations in
. These assessments can be performed by studying circulating tumor cells by fluorescent in situ hybridization and by immunocytochemistry and/or after the isolation of RNA from plasma samples, free or associated with platelets. Thus, the liquid biopsy may be a complementary or sometimes alternative method for the assessment of the
status in certain NSCLC patients, as well as a non-invasive approach for early detection of
mutations. In this review, we highlight the current data concerning the role of the liquid biopsy for the
status assessment for NSCLC patients, and we compare the different approaches for this evaluation from blood samples.
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