Liquid Biopsy for Advanced NSCLC: A Consensus Statement From the International Association for the Study of Lung Cancer

Rolfo, Christian; Mack, Philip C.; Scagliotti, Giorgio Vittorio; Aggarwal, Charu; Arcila, Maria E.; Barlési, Fabrice; Bivona, Trever G.; Diehn, Maximilian; Dive, Caroline; Dziadziuszko, Rafał; Leighl, Natasha B.; Malapelle, Umberto; Mok, Tony; Peled, Nir; Raez, Luis E.; Sequist, Lecia V.; Sholl, Lynette M.; Swanton, Charles; Abbosh, Chris; Tan, Daniel; Wakelee, Heather A.; Wistuba, Ignacio I.; Bunn, Rebecca A.; Freeman-Daily, Janet; Wynes, Murry W.; Belani, Chandra P.; Mitsudomi, Tetsuya; Gandara, David R.

doi:10.1016/j.jtho.2021.06.017

Cited by 381 publications

(351 citation statements)

References 128 publications

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“…In our analysis, we used commercial list prices for this technology, resulting in routine ctDNA testing in all patients plus EGFR/ALK testing in tissue as the most expensive population-based testing strategy. Recent recommendations for plasma ctDNA testing include NGS-based platforms in treatment-naïve patients and in those who have developed drug resistance, now allowing a growing list of guideline-recommended targets to be assessed [49]. Although such platforms offer broad-based testing of known and unknown variants, non-NGS PCR-based ctDNA assays (either as a single gene or multiplexed), known to be highly sensitive for detecting a select few targetable alterations, may still offer a lower-cost alternative in resource-limited settings.…”

Section: Discussionmentioning

confidence: 99%

Reflex ROS1 IHC Screening with FISH Confirmation for Advanced Non-Small Cell Lung Cancer—A Cost-Efficient Strategy in a Public Healthcare System

et al. 2021

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ROS1 rearrangements are identified in 1–2% of lung adenocarcinoma cases, and reflex testing is guideline-recommended. We developed a decision model for population-based ROS1 testing from a Canadian public healthcare perspective to determine the strategy that optimized detection of true-positive (TP) cases while minimizing costs and turnaround time (TAT). Eight diagnostic strategies were compared, including reflex single gene testing via immunohistochemistry (IHC) screening, fluorescence in-situ hybridization (FISH), next-generation sequencing (NGS), and biomarker-informed (EGFR/ALK/KRAS wildtype) testing initiated by pathologists and clinician-initiated strategies. Reflex IHC screening with FISH confirmation of positive cases yielded the best results for TAT, TP detection rate, and cost. IHC screening saved CAD 1,000,000 versus reflex FISH testing. NGS was the costliest reflex strategy. Biomarker-informed testing was cost-efficient but delayed TAT. Clinician-initiated testing was the least costly but resulted in long TAT and missed TP cases, highlighting the importance of reflex testing. Thus, reflex IHC screening for ROS1 with FISH confirmation provides a cost-efficient strategy with short TAT and maximizes the number of TP cases detected.

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Section: Discussionmentioning

confidence: 99%

Reflex ROS1 IHC Screening with FISH Confirmation for Advanced Non-Small Cell Lung Cancer—A Cost-Efficient Strategy in a Public Healthcare System

et al. 2021

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“…Currently, the NCCN guidelines only endorse 1) a plasma-first approach for testing for EGFR T790M in patients who have developed resistance to first-or second-generation tyrosine kinase inhibitors (TKIs), with tissue biopsy being recommended in cases where plasma testing is negative 8 , and 2) liquid biopsy in specific clinical circumstances where the patient is medically unfit for invasive tissue sampling or when tumor tissue specimen is inadequate or unobtainable, following pathological confirmation of diagnosis, with a follow-up tissue-based analysis in cases where no oncogenic driver is identified in plasma cfDNA 8 . This is aligned with the latest recommendations from the International Association for the Study of Lung Cancer (IASLC) for liquid biopsy for NSCLC, where liquid biopsy is recommended for cases where tissue sample is unavailable ('plasma first' approach), or in cases where tissue biopsy is inadequate for conducting comprehensive tissue genotyping ('complementary' approach) 19 . Furthermore, according to the IASLC recommendations, for cases with oncogene-addicted NSCLC progressing after initial targeted therapy, a 'plasma first' approach should be considered standard of care 19 .…”

Section: Introductionmentioning

confidence: 72%

“…This is aligned with the latest recommendations from the International Association for the Study of Lung Cancer (IASLC) for liquid biopsy for NSCLC, where liquid biopsy is recommended for cases where tissue sample is unavailable ('plasma first' approach), or in cases where tissue biopsy is inadequate for conducting comprehensive tissue genotyping ('complementary' approach) 19 . Furthermore, according to the IASLC recommendations, for cases with oncogene-addicted NSCLC progressing after initial targeted therapy, a 'plasma first' approach should be considered standard of care 19 .…”

Section: Introductionmentioning

confidence: 72%

“…In this single-centre prospective study we assessed the clinical utility of adding plasma NGS testing to the diagnostic workflow for suspected lung cancer and molecular testing workflow for diagnosed NSCLC. This approach may be labelled as 'plasma-first' for cases with no tissue sample available for testing, or complementary where both tumor and plasma sample may be tested for comprehensive target coverage, or where there is uncertainty about adequacy of tissue sample for molecular testing 19 . Plasma NGS demonstrated significantly higher sample accessibility levels, lower average reporting time and matched specificity and accuracy when compared to standard tissue EGFR testing.…”

Section: Discussionmentioning

confidence: 99%

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Complementing Tissue Testing with Plasma mutation Profiling Improves Therapeutic Decision Making for Lung Cancer Patients

Choudhury¹,

Tan²,

Shi

et al. 2021

Preprint

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Background: Tissue biopsy is an integral part of the diagnostic approach to lung cancer. It is however invasive and associated with limitations of tissue heterogeneity. Liquid biopsies may complement tissue testing by providing additional molecular information and may be particularly helpful in patients from whom obtaining sufficient tissue for genomic profiling is challenging. Methods: Patients with suspected lung cancer (n=71) were prospectively recruited. Blood and diagnostic tissue samples were collected within 48 hrs of each other. Plasma cell-free DNA (cfDNA) testing was done using an ultrasensitive amplicon-based next-generation sequencing (NGS) panel (plasma NGS testing). For cases diagnosed as non-small cell lung carcinoma (NSCLC) via histology or cytology, targeted testing for epidermal growth factor receptor (EGFR) mutations was performed using tissue biopsy samples, where available (tissue EGFR testing). Concordance of clinically actionable mutations between methods and sample types were assessed. Results: For confirmed NSCLC cases (n = 54), tissue EGFR test results were available only for 70.3% (38/54) due to sample inadequacies, compared to blood samples for 98.1% (53/54) cases. Tissue EGFR testing identified sensitizing EGFR (L858R or exon 19 deletion) mutation in 31.6% (12/38) of cases. Plasma NGS identified clinically actionable mutations in 37.7% (20/53) of cases, including EGFR mutations in two cases with no tissue EGFR results, and mutations in KRAS, BRAF and MET. Overall sensitivity of EGFR sensitizing mutation detection by plasma NGS was 75% (9/12), and specificity was 100% (25/25) in patients tested in both tissue EGFR and plasma NGS (n=37). In this cohort of patients, tissue EGFR testing alone informed clinical decisions in 22.2% (12/54) of cases. Adding plasma NGS to tissue EGFR testing increased the detection rate of actionable mutations to 42.6% (23/54), representing a near doubling (1.9-fold increase) of clinically relevant findings. The average turnaround time (TAT) of plasma NGS was shorter than standard tissue testing (10 days vs. 29.9 days, p-value <0.05). Conclusions: In the first-line setting, plasma NGS was highly concordant with tissue EGFR testing. Plasma NGS increases the detection of actionable findings with shorter time to results. This study outlines the clinical utility of a complementary plasma mutation profiling in the routine management of lung cancer patients.

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“…Recently, a targeted therapy was approved for patients with lung cancer harbouring the KRAS G12C mutation, the first successful treatment for KRAS mutated lung cancers. This personalized approach is advancing even further with the ability now to genotype a patient's lung cancer using cell free DNA in patients' plasma or "liquid biopsies" [27], allowing multiple samples to be taken longitudinally on treatment to detect dynamic changes over time.…”

Section: Discussionmentioning

confidence: 99%

Tumour Genome Characterization of a Rare Case of Pulmonary Enteric Adenocarcinoma and Prior Colon Adenocarcinoma

Smyth

Thomas

Fay

et al. 2021

JPM

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Pulmonary enteric adenocarcinoma (PEAC) is a rare variant of lung adenocarcinoma first described in the early 1990s in a lung tumour with overlapping lung and small intestine features. It is a rare tumour with fewer than 300 cases described in the published literature and was only formally classified in 2011. Given these characteristics the diagnosis is challenging, but even more so in a patient with prior gastrointestinal malignancy. A 68-year-old Caucasian female presented with a cough and was found to have a right upper lobe mass. Her history was significant for a pT3N1 colon adenocarcinoma. The resected lung tumour showed invasive lung adenocarcinoma but also features of colorectal origin. Immuno-stains were strongly and diffusely positive for lung and enteric markers. Multi-region, whole-exome sequencing of the mass and archival tissue from the prior colorectal cancer showed distinct genomic signatures with higher mutational burden in the PEAC and very minimal overlap in mutations between the two tumours. This case highlights the challenge of diagnosing rare lung tumours, but more specifically PEAC in a patient with prior gastro-intestinal cancer. Our use of multi-region, next-generation sequencing revealed distinct genomic signatures between the two tumours further supporting our diagnosis, and evidence of PEAC intra-tumour heterogeneity.

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Liquid Biopsy for Advanced NSCLC: A Consensus Statement From the International Association for the Study of Lung Cancer

Cited by 381 publications

References 128 publications

Reflex ROS1 IHC Screening with FISH Confirmation for Advanced Non-Small Cell Lung Cancer—A Cost-Efficient Strategy in a Public Healthcare System

Reflex ROS1 IHC Screening with FISH Confirmation for Advanced Non-Small Cell Lung Cancer—A Cost-Efficient Strategy in a Public Healthcare System

Complementing Tissue Testing with Plasma mutation Profiling Improves Therapeutic Decision Making for Lung Cancer Patients

Tumour Genome Characterization of a Rare Case of Pulmonary Enteric Adenocarcinoma and Prior Colon Adenocarcinoma

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