ctDNA: An emerging neoadjuvant biomarker in resectable solid tumors

Abbosh, Christopher; Swanton, Charles

doi:10.1371/journal.pmed.1003771

Cited by 9 publications

(4 citation statements)

References 13 publications

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“…Recently, Gouda et al proposed the Liquid Biopsy Response Evaluation Criteria (LB-RE-CIST) to be used in the context of clinical trials [72]. The newer platforms have increased sensitivity and specificity [73]. The potential role of ctDNA in resectable NSCLC includes diagnosis, prognosis, predicting response (pCR or MPR) leading to treatment escalation/de-escalation, predicting need for adjuvant treatment, and predicting a recurrence after surgery (Figure 3).…”

Section: Predictive Biomarkers and Modelsmentioning

confidence: 99%

An Updated Review of Management of Resectable Stage III NSCLC in the Era of Neoadjuvant Immunotherapy

Verma,

Breadner,

Mittal

et al. 2024

Cancers

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Immune-checkpoint inhibitors (ICIs) have an established role in the treatment of locally advanced and metastatic non-small cell lung cancer (NSCLC). ICIs have now entered the paradigm of early-stage NSCLC. The recent evidence shows that the addition of ICI to neoadjuvant chemotherapy improves the pathological complete response (pCR) rate and survival rate in early-stage resectable NSCLC and is now a standard of care option in this setting. In this regard, stage III NSCLC merits special consideration, as it is heterogenous and requires a multidisciplinary approach to management. As the neoadjuvant approach is being adopted widely, new challenges have emerged and the boundaries for resectability are being re-examined. Consequently, it is ever more important to carefully individualize the treatment strategy for each patient with resectable stage III NSCLC. In this review, we discuss the recent literature in this field with particular focus on evolving definitions of resectability, T4 disease, N2 disease (single and multi-station), and nodal downstaging. We also highlight the controversy around adjuvant treatment in this setting and discuss the selection of patients for adjuvant treatment, options of salvage, and next line treatment in cases of progression on/after neoadjuvant treatment or after R2 resection. We will conclude with a brief discussion of predictive biomarkers, predictive models, ongoing studies, and directions for future research in this space.

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Section: Predictive Biomarkers and Modelsmentioning

confidence: 99%

An Updated Review of Management of Resectable Stage III NSCLC in the Era of Neoadjuvant Immunotherapy

Verma,

Breadner,

Mittal

et al. 2024

Cancers

View full text Add to dashboard Cite

show abstract

“…Second, monitoring the dynamics of ctDNA during treatment could serve as an early and reliable surrogate endpoint of treatment efficacy [117,118]. In neoadjuvant and palliative settings, ctDNA changes over treatment may offer advantages over conventional endpoints, such as response, by providing a greater dynamic range, higher sensitivity, and easier temporal monitoring [39].…”

Section: Application Of Plasma Ctdna Sequencing In the Clinical Trial...mentioning

confidence: 99%

Utilizing Plasma Circulating Tumor DNA Sequencing for Precision Medicine in the Management of Solid Cancers

Cha¹,

Kim²,

Han³

2023

Cancer Res Treat

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Plasma circulating tumor DNA (ctDNA) sequencing has demonstrated clinical utility for tumor molecular profiling at initial diagnosis or tumor progression in advanced solid cancers and is being rapidly incorporated into the clinical practice guidelines, including non–small cell lung and breast cancer. Despite relatively low sensitivity, plasma ctDNA sequencing has several advantages over tissue-based assays, including ease of sampling, rapid turnaround time, repeatability, and the ability to overcome spatial heterogeneity, which makes it ideal for investigating acquired resistance and monitoring tumor evolution and dynamics. With technological advancement and declining costs, the clinical application of plasma ctDNA is expanding, and numerous ongoing clinical trials are examining its potential to guide the management of advanced, localized, and even preclinical cancers of various tumor types. The ability of plasma ctDNA analysis to detect minimal residual disease following curative treatment in the absence of clinical disease is among its most promising attributes. Plasma ctDNA sequencing can also facilitate the conduct of clinical trials and drug development, particularly in immunotherapy. In order to incorporate plasma ctDNA sequencing for clinical decision-making, it is important to understand the preanalytical and analytical factors that may affect its sensitivity and reliability.

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“…Furthermore, recent data on resectable NSCLC support ctDNA as a response biomarker in neoadjuvant ICI treatment ( 49 ). In the CheckMate-816 study, a phase III study exploring the efficacy of neoadjuvant nivolumab in stage IB–IIIA NSCLC, ctDNA clearance on day 1 cycle 3 post-ICI treatment was associated with a pathological complete response ( 50 ).…”

Section: Emerging Applications Of Ctdna For Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Applications of Circulating Tumor DNA in Immune Checkpoint Inhibition: Emerging Roles and Future Perspectives

et al. 2022

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Immune checkpoint inhibitors (ICIs), especially anti-programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) antibodies, have made dramatic progress in the treatment of lung cancer, especially for patients with cancers not driven by oncogenes. However, responses are limited to a subset of patients, and which subset of patients will optimally benefit from ICI remains unknown. With the advantage of being minimally invasive and dynamic, noninvasive biomarkers are promising candidates to predict response, monitor resistance, and track the evolution of lung cancer during ICI treatment. In this review, we focus on the application of circulating tumor DNA (ctDNA) in plasma in immunotherapy. We examine the potential of pre- and on-treatment features of ctDNA as biomarkers, and following multiparameter analysis, we determine the potential clinical value of integrating predictive liquid biomarkers of ICIs to optimize patient management. We further discuss the role of ctDNA in monitoring treatment resistance, as well as challenges in clinical translation.

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ctDNA: An emerging neoadjuvant biomarker in resectable solid tumors

Abstract: Christopher Abbosh and Charles Swanton discuss circulating tumor DNA as a potential biomarker for neoadjuvant treatment response in solid tumors.

Cited by 9 publications

References 13 publications

An Updated Review of Management of Resectable Stage III NSCLC in the Era of Neoadjuvant Immunotherapy

An Updated Review of Management of Resectable Stage III NSCLC in the Era of Neoadjuvant Immunotherapy

Utilizing Plasma Circulating Tumor DNA Sequencing for Precision Medicine in the Management of Solid Cancers

Applications of Circulating Tumor DNA in Immune Checkpoint Inhibition: Emerging Roles and Future Perspectives

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