Exploration of Targeted Anti-tumor Therapy

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Table 1

From: The promises and perils of circulating tumor DNA for monitoring immunotherapy response in non-small cell lung cancer

Table 1. Benefits and limitations of ctDNA-based technology for the assessment of immunotherapy response

Benefits	Limitations
Reduction in ctDNA levels associated with overall survival and progression-free survival	Comorbidities can affect ctDNA levels (smoking, pregnancy, heart disease, inflammation)
Detection of immunotherapy response after about 8 weeks	Clonal hematopoiesis
Allows for serial monitoring to detect developing resistance and genomic variants	Variable ctDNA fraction based on primary malignancy and stage
Non-invasive detection (blood test)	Multiple assays to choose from with no standardization
Comprehensive, patient-specific molecular profiling	Wide variability in cost
-	Concordance between aberrations detected in ctDNA and tumor tissue
-	Low concentration and fragmentation
-	Unable to detect genomic fusion events and copy number changes

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ctDNA: circulating tumor DNA; -: no data

Declarations

Author contributions

BJH and JB: Conceptualization, Writing—original draft, Writing—review & editing. Both authors read and approved the submitted version.

Conflicts of interest

Both authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

References

Borghaei H, Gettinger S, Vokes EE, Chow LQM, Burgio MA, Carpeno JdC, et al. Five-Year Outcomes From the Randomized, Phase III Trials CheckMate 017 and 057: Nivolumab Versus Docetaxel in Previously Treated Non-Small-Cell Lung Cancer. J Clin Oncol. 2021;39:723–33. Erratum in: J Clin Oncol. 2021;39:1190. [DOI] [PubMed] [PMC]

Wu Y, Yu G, Jin K, Qian J. Advancing non-small cell lung cancer treatment: the power of combination immunotherapies. Front Immunol. 2024;15:1349502. [DOI] [PubMed] [PMC]

Ayati N, Lee ST, Zakavi SR, Cheng M, Lau WFE, Parakh S, et al. Response Evaluation and Survival Prediction After PD-1 Immunotherapy in Patients with Non-Small Cell Lung Cancer: Comparison of Assessment Methods. J Nucl Med. 2021;62:926–33. [DOI] [PubMed]

Seegobin K, Majeed U, Wiest N, Manochakian R, Lou Y, Zhao Y. Immunotherapy in Non-Small Cell Lung Cancer With Actionable Mutations Other Than EGFR. Front Oncol. 2021;11:750657. [DOI] [PubMed] [PMC]

Cristescu R, Mogg R, Ayers M, Albright A, Murphy E, Yearley J, et al. Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy. Science. 2018;362:eaar3593. Erratum in: Science. 2019;363:eaax1384. [DOI] [PubMed] [PMC]

Green AK. Challenges in Assessing the Cost-effectiveness of Cancer Immunotherapy. JAMA Netw Open. 2021;4:e2034020. [DOI] [PubMed]

Tian Y, Li Q, Yang Z, Zhang S, Xu J, Wang Z, et al. Single-cell transcriptomic profiling reveals the tumor heterogeneity of small-cell lung cancer. Signal Transduct Target Ther. 2022;7:346. [DOI] [PubMed] [PMC]

Goldberg SB, Narayan A, Kole AJ, Decker RH, Teysir J, Carriero NJ, et al. Early Assessment of Lung Cancer Immunotherapy Response via Circulating Tumor DNA. Clin Cancer Res. 2018;24:1872–80. [DOI] [PubMed] [PMC]

Anagnostou V, Forde PM, White JR, Niknafs N, Hruban C, Naidoo J, et al. Dynamics of Tumor and Immune Responses during Immune Checkpoint Blockade in Non-Small Cell Lung Cancer. Cancer Res. 2019;79:1214–25. [DOI] [PubMed] [PMC]

10.

Raja R, Kuziora M, Brohawn PZ, Higgs BW, Gupta A, Dennis PA, et al. Early Reduction in ctDNA Predicts Survival in Patients with Lung and Bladder Cancer Treated with Durvalumab. Clin Cancer Res. 2018;24:6212–22. [DOI] [PubMed]

11.

Al-Showbaki L, Wilson B, Tamimi F, Molto C, Mittal A, Cescon DW, et al. Changes in circulating tumor DNA and outcomes in solid tumors treated with immune checkpoint inhibitors: a systematic review. J Immunother Cancer. 2023;11:e005854. [DOI] [PubMed] [PMC]

12.

Sun X, Abrahamson P, Ballew N, Kalilani L, Phiri K, Bell KF, et al. The Utility of ctDNA in Lung Cancer Clinical Research and Practice: A Systematic Review and Meta-Analysis of Clinical Studies. Cancer Invest. 2023;41:571–92. [DOI] [PubMed]

13.

Wang H, Zhou F, Qiao M, Li X, Zhao C, Cheng L, et al. The Role of Circulating Tumor DNA in Advanced Non-Small Cell Lung Cancer Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis. Front Oncol. 2021;11:671874. [DOI] [PubMed] [PMC]

14.

Vega DM, Nishimura KK, Zariffa N, Thompson JC, Hoering A, Cilento V, et al. Changes in Circulating Tumor DNA Reflect Clinical Benefit Across Multiple Studies of Patients With Non-Small-Cell Lung Cancer Treated With Immune Checkpoint Inhibitors. JCO Precis Oncol. 2022;6:e2100372. Erratum in: JCO Precis Oncol. 2023;7:e2300144. [DOI] [PubMed] [PMC]

15.

Anagnostou V, Ho C, Nicholas G, Juergens RA, Sacher A, Fung AS, et al. ctDNA response after pembrolizumab in non-small cell lung cancer: phase 2 adaptive trial results. Nat Med. 2023;29:2559–69. [DOI] [PubMed] [PMC]

16.

Hellmann MD, Nabet BY, Rizvi H, Chaudhuri AA, Wells DK, Dunphy MPS, et al. Circulating Tumor DNA Analysis to Assess Risk of Progression after Long-term Response to PD-(L)1 Blockade in NSCLC. Clin Cancer Res. 2020;26:2849–58. [DOI] [PubMed] [PMC]

17.

Dong S, Wang Z, Zhang J, Yan B, Zhang C, Gao X, et al. Circulating Tumor DNA-Guided De-Escalation Targeted Therapy for Advanced Non-Small Cell Lung Cancer: A Nonrandomized Controlled Trial. JAMA Oncol. 2024;10:932–40. [DOI] [PubMed]

18.

Remon J, Besse B, Aix SP, Callejo A, Al-Rabi K, Bernabe R, et al. Osimertinib treatment based on plasma T790M monitoring in patients with EGFR-mutant non-small-cell lung cancer (NSCLC): EORTC Lung Cancer Group 1613 APPLE phase II randomized clinical trial. Ann Oncol. 2023;34:468–76. [DOI] [PubMed]

19.

Bittla P, Kaur S, Sojitra V, Zahra A, Hutchinson J, Adefokun O, et al. Exploring Circulating Tumor DNA (CtDNA) and Its Role in Early Detection of Cancer: A Systematic Review. Cureus. 2023;15:e45784. [DOI] [PubMed] [PMC]

20.

Liu J, Chen X, Wang J, Zhou S, Wang CL, Ye MZ, et al. Biological background of the genomic variations of cf-DNA in healthy individuals. Ann Oncol. 2019;30:464–70. [DOI] [PubMed]

21.

Zheng J, Wang Y, Hu C, Zhu M, Ii J, Lin C, et al. Predictive value of early kinetics of ctDNA combined with cfDNA and serum CEA for EGFR-TKI treatment in advanced non-small cell lung cancer. Thorac Cancer. 2022;13:3162–73. [DOI] [PubMed] [PMC]

22.

Husain H, Pavlick DC, Fendler BJ, Madison RW, Decker B, Gjoerup O, et al. Tumor Fraction Correlates With Detection of Actionable Variants Across > 23,000 Circulating Tumor DNA Samples. JCO Precis Oncol. 2022;6:e2200261. Erratum in: JCO Precis Oncol. 2022;6:e2200622. [DOI] [PubMed] [PMC]

23.

Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014;6:224ra24. [DOI] [PubMed] [PMC]

24.

Singareddy A, Flanagan ME, Samson PP, Waqar SN, Devarakonda S, Ward JP, et al. Trends in Stage I Lung Cancer. Clin Lung Cancer. 2023;24:114–9. [DOI] [PubMed]

25.

Cohen JD, Li L, Wang Y, Thoburn C, Afsari B, Danilova L, et al. Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science. 2018;359:926–30. [DOI] [PubMed] [PMC]

26.

Kramer A, Schuuring E, Vessies DCL, Leest Pvd, Geerlings MJ, Rozendal P, et al. A Micro-Costing Framework for Circulating Tumor DNA Testing in Dutch Clinical Practice. J Mol Diagn. 2023;25:36–45. Erratum in: J Mol Diagn. 2024;26:739. [DOI] [PubMed]

27.

Fagery M, Khorshidi HA, Wong SQ, Vu M, IJzerman M. Health Economic Evidence and Modeling Challenges for Liquid Biopsy Assays in Cancer Management: A Systematic Literature Review. Pharmacoeconomics. 2023;41:1229–48. [DOI] [PubMed] [PMC]

28.

Tran MC, Strohbehn GW, Karrison TG, Rouhani SJ, Segal JP, Shergill A, et al. Brief Report: Discordance Between Liquid and Tissue Biopsy-Based Next-Generation Sequencing in Lung Adenocarcinoma at Disease Progression. Clin Lung Cancer. 2023;24:e117–21. [DOI] [PubMed]

29.

Murray JC, Sivapalan L, Hummelink K, Balan A, White JR, Niknafs N, et al. Elucidating the Heterogeneity of Immunotherapy Response and Immune-Related Toxicities by Longitudinal ctDNA and Immune Cell Compartment Tracking in Lung Cancer. Clin Cancer Res. 2024;30:389–403. [DOI] [PubMed] [PMC]

30.

Chaudhuri AA, Chabon JJ, Lovejoy AF, Newman AM, Stehr H, Azad TD, et al. Early Detection of Molecular Residual Disease in Localized Lung Cancer by Circulating Tumor DNA Profiling. Cancer Discov. 2017;7:1394–403. [DOI] [PubMed] [PMC]

31.

Riely GJ, Wood DE, Ettinger DS, Aisner DL, Akerley W, Bauman JR, et al. Non-Small Cell Lung Cancer, Version 4.2024, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2024;22:249–74. [DOI] [PubMed]