Scite.AI: MRD Studies in Lung Cancer

 There seem to be many fewer studies for Minimal Residual Disease monitoring (MRD) in lung cancer, compared to colorectal cancer. What are the best studies of MRD in lung cancer (circulating tumor DNA) and if possible discuss why this field lags behind MRD studies in colorectal cancer.

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SCITE.AI

Minimal Residual Disease (MRD) monitoring in lung cancer, particularly through the analysis of circulating tumor DNA (ctDNA), has garnered attention, yet it remains significantly less explored compared to colorectal cancer. This disparity can be attributed to several factors, including the complexity of lung cancer biology, the historical focus on colorectal cancer in MRD studies, and the challenges associated with ctDNA detection in lung cancer.

 Recent studies have begun to elucidate the potential of ctDNA in monitoring MRD in lung cancer. For instance, demonstrated that longitudinally undetectable MRD in localized non-small cell lung cancer (NSCLC) patients correlates with a high likelihood of remaining disease-free, suggesting a potential for identifying a "cured" population within this cohort (Zhang et al., 2022). Furthermore, highlighted the efficacy of ctDNA profiling in early detection of MRD, emphasizing its role in guiding treatment decisions (Chaudhuri et al., 2017). These findings indicate that while the prognostic value of ctDNA in lung cancer is promising, the body of research is still developing.

 In contrast, colorectal cancer has seen a more robust integration of ctDNA in MRD monitoring. Studies such as those by have established ctDNA as a reliable biomarker for recurrence in resected colorectal cancer, demonstrating its superiority over traditional imaging methods in certain contexts (Fakih et al., 2022). The comparative abundance of studies in colorectal cancer can be attributed to its well-defined treatment pathways and the established role of biomarkers like carcinoembryonic antigen (CEA) in clinical practice (Fakih et al., 2022). This has facilitated a more extensive exploration of ctDNA applications, leading to a wealth of data supporting its use in MRD monitoring.

 The lag in lung cancer research can also be linked to the inherent biological complexities of lung tumors. noted that most studies have focused on single qualitative markers in ctDNA, such as specific mutations (e.g., EGFR and KRAS), rather than adopting a comprehensive multi-marker approach that has proven effective in colorectal cancer (Szpechcinski et al., 2015). This limitation in study design may hinder the broader applicability of ctDNA as a reliable MRD marker in lung cancer.

 Moreover, the technical challenges associated with ctDNA detection in lung cancer cannot be overlooked. The sensitivity of ctDNA assays can be affected by the tumor's heterogeneity and the low levels of ctDNA present in the bloodstream, particularly in early-stage disease (Yan & Liu, 2022). This contrasts with colorectal cancer, where ctDNA levels are often higher and more consistent, facilitating easier detection and monitoring.

 In summary, while there are promising studies indicating the potential of ctDNA for MRD monitoring in lung cancer, the field lags behind colorectal cancer due to a combination of historical focus, biological complexity, and technical challenges in ctDNA detection. Continued research and the development of more sensitive and comprehensive ctDNA assays may bridge this gap in the future.

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Could you focus on 2023 and 2024 studies of circulating tumor dna to detect minimal residual disease (MRD) or recurrence, in lung cancer.

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In recent years, the application of circulating tumor DNA (ctDNA) for monitoring minimal residual disease (MRD) and recurrence in lung cancer has gained traction, with several notable studies emerging in 2023 and 2024. These studies highlight the potential of ctDNA as a non-invasive biomarker for assessing disease status post-treatment and guiding clinical decisions.

 One significant study by Kang et al. (2023) introduced a dynamic methylation-based analysis of cell-free DNA for postoperative monitoring in lung cancer patients. The study found that patients with low MRD scores were unlikely to experience relapse within four months, suggesting that such a methylation-based approach could personalize postoperative management and reduce unnecessary imaging (Kang et al., 2023). This finding underscores the utility of ctDNA in providing timely insights into patient status, potentially leading to more tailored treatment strategies.

 Another important contribution is from (Franzi, 2023), who conducted a meta-analysis on the role of liquid biopsy in non-small cell lung cancer (NSCLC). The authors noted that dynamic changes in ctDNA levels correlated with therapeutic responses, indicating that ctDNA could be effectively used for early detection of MRD and recurrence in early-stage lung cancer (Franzi, 2023). This study reinforces the idea that ctDNA monitoring can enhance the management of lung cancer by identifying patients at risk for relapse.

 O'Sullivan et al. (2023) further explored the challenges and future directions of MRD monitoring in radically treated NSCLC. They emphasized that the variant allele frequency (VAF) of ctDNA is prognostic, particularly in early-stage patients. Those with detectable ctDNA prior to resection exhibited a higher risk of recurrence compared to those without detectable ctDNA, highlighting the potential of ctDNA as a predictive tool in clinical practice (O’Sullivan et al., 2023). This study illustrates the critical role of ctDNA in stratifying patients based on their risk of relapse, which could inform follow-up and treatment decisions.

 Desai (2024) also contributed to this field by discussing the integration of ctDNA into clinical practice for managing EGFR-mutant NSCLC. The study highlighted ctDNA's role in risk stratification and treatment decision-making, particularly for patients undergoing curative-intent treatment (Desai, 2024). This aligns with the growing recognition of ctDNA as a valuable tool for monitoring MRD and guiding therapeutic interventions.

 Moreover, Morgensztern (2024) emphasized the expanding role of ctDNA in resectable NSCLC, suggesting that its detection could facilitate personalized treatment approaches. By identifying patients at high risk for relapse, clinicians may opt for more aggressive therapies, while those at low risk could avoid overtreatment (Morgensztern, 2024). This personalized approach is crucial in improving outcomes for lung cancer patients.

 In summary, the studies from 2023 and 2024 collectively demonstrate the promising role of ctDNA in detecting MRD and predicting recurrence in lung cancer. The ability to provide real-time insights into disease status and risk stratification positions ctDNA as a vital component of modern oncological practice, particularly in the management of NSCLC.

 References:

Chaudhuri, A., Chabon, J., Lovejoy, A., Newman, A., Stehr, H., Azad, T., … & Diehn, M. (2017). Early detection of molecular residual disease in localized lung cancer by circulating tumor dna profiling. Cancer Discovery, 7(12), 1394-1403. https://doi.org/10.1158/2159-8290.cd-17-0716

Desai, A. (2024). Ctdna for the evaluation and management of egfr-mutant non-small cell lung cancer. Cancers, 16(5), 940. https://doi.org/10.3390/cancers16050940

Fakih, M., Sandhu, J., Wang, C., Kim, J., Chen, Y., Lai, L., … & Kaiser, A. (2022). Evaluation of comparative surveillance strategies of circulating tumor dna, imaging, and carcinoembryonic antigen levels in patients with resected colorectal cancer. Jama Network Open, 5(3), e221093. https://doi.org/10.1001/jamanetworkopen.2022.1093

Franzi, S. (2023). Liquid biopsy in non-small cell lung cancer: a meta-analysis of state-of-the-art and future perspectives. Frontiers in Genetics, 14. https://doi.org/10.3389/fgene.2023.1254839

Kang, G., Lizaso, A., Beck, S., Lyskjær, I., Chervova, O., Li, B., … & Wang, J. (2023). Individualized dynamic methylation-based analysis of cell-free dna in postoperative monitoring of lung cancer. BMC Medicine, 21(1). https://doi.org/10.1186/s12916-023-02954-z

Morgensztern, D. (2024). The expanding role of circulating tumor dna in resectable non–small cell lung cancer. Cancer, 130(10), 1730-1732. https://doi.org/10.1002/cncr.35268

O’Sullivan, H., Feber, A., & Popat, S. (2023). Minimal residual disease monitoring in radically treated non-small cell lung cancer: challenges and future directions. Oncotargets and Therapy, Volume 16, 249-259. https://doi.org/10.2147/ott.s322242

Szpechcinski, A., Chorostowska‐Wynimko, J., Struniawski, R., Kupis, W., Rudziński, P., Langfort, R., … & Orłowski, T. (2015). Cell-free dna levels in plasma of patients with non-small-cell lung cancer and inflammatory lung disease. British Journal of Cancer, 113(3), 476-483. https://doi.org/10.1038/bjc.2015.225

Yan, X. and Liu, C. (2022). Clinical application and prospect of mrd evaluation in lung cancer based on ctdna level: a review. Tumori Journal, 109(4), 356-362. https://doi.org/10.1177/03008916221101927

Zhang, J., Liu, S., Gao, W., Liu, S., Yan, H., Ji, L., … & Wu, Y. (2022). Longitudinal undetectable molecular residual disease defines potentially cured population in localized non–small cell lung cancer. Cancer Discovery, 12(7), 1690-1701. https://doi.org/10.1158/2159-8290.cd-21-1486