Opportunities and Challenges of Using Circulating Tumor DNA to Predict Lung Cancer Immunotherapy Efficacy

Overview

Journal J Cancer Res Clin Oncol

Specialty Oncology

Date 2024 Nov 15

PMID 39545998

Authors

Shanshan Li

Ting Yuan

Jing Yuan

Bo Zhu

Degao Chen

Affiliations

Soon will be listed here.

Abstract

Immune checkpoint inhibitors (ICIs), particularly anti-programmed death 1 (PD-1)/ programmed death ligand 1 (PD-L1) antibodies, have led to significant progress in lung cancer treatment. However, only a minority of patients have responses to these therapies. Detecting peripheral blood of circulating tumor DNA (ctDNA) allows minimally invasive diagnosis, characterization, and monitoring of lung cancer. ctDNA has potential to be a prognostic biomarker and a predictor of the response to ICI therapy since it can indicate the genomic status and tumor burden. Recent studies on lung cancer have shown that pretreatment ctDNA analysis can detect residual proliferative disease in the adjuvant immunotherapy setting and evaluate tumor burden in patients with metastatic disease. Early ctDNA dynamics can not only predict the clinical outcome of ICI therapy but also help distinguish between pseudoprogression and real progression. Furthermore, in addition to quantitative assessment, ctDNA can also detect genetic predictors of response to ICI therapy. However, barriers still exist in the application of ctDNA analysis in clinical lung cancer treatment. The predictive value of ctDNA in lung cancer immunotherapy requires further identification and resolution of these challenges. This review aims to summarize the existing data of ctDNA analysis in patients receiving immunotherapy for lung cancer, understand the limitations of clinical treatment, and discuss future research directions.

References

Abbosh C, Birkbak N, Wilson G, Jamal-Hanjani M, Constantin T, Salari R . Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature. 2017; 545(7655):446-451. PMC: 5812436. DOI: 10.1038/nature22364. View

Abbosh C, Birkbak N, Swanton C . Early stage NSCLC - challenges to implementing ctDNA-based screening and MRD detection. Nat Rev Clin Oncol. 2018; 15(9):577-586. DOI: 10.1038/s41571-018-0058-3. View

Aggarwal C, Thompson J, Chien A, Quinn K, Hwang W, Black T . Baseline Plasma Tumor Mutation Burden Predicts Response to Pembrolizumab-based Therapy in Patients with Metastatic Non-Small Cell Lung Cancer. Clin Cancer Res. 2020; 26(10):2354-2361. PMC: 7231655. DOI: 10.1158/1078-0432.CCR-19-3663. View

Anagnostou V, Forde P, White J, Niknafs N, Hruban C, Naidoo J . Dynamics of Tumor and Immune Responses during Immune Checkpoint Blockade in Non-Small Cell Lung Cancer. Cancer Res. 2018; 79(6):1214-1225. PMC: 6432636. DOI: 10.1158/0008-5472.CAN-18-1127. View

Anagnostou V, Niknafs N, Marrone K, Bruhm D, White J, Naidoo J . Multimodal genomic features predict outcome of immune checkpoint blockade in non-small-cell lung cancer. Nat Cancer. 2020; 1(1):99-111. PMC: 7514475. DOI: 10.1038/s43018-019-0008-8. View

Anagnostou V, Landon B, Medina J, Forde P, Velculescu V . Translating the evolving molecular landscape of tumors to biomarkers of response for cancer immunotherapy. Sci Transl Med. 2022; 14(670):eabo3958. PMC: 9844537. DOI: 10.1126/scitranslmed.abo3958. View

Assaf Z, Zou W, Fine A, Socinski M, Young A, Lipson D . A longitudinal circulating tumor DNA-based model associated with survival in metastatic non-small-cell lung cancer. Nat Med. 2023; 29(4):859-868. PMC: 10115641. DOI: 10.1038/s41591-023-02226-6. View

Avanzini S, Kurtz D, Chabon J, Moding E, Hori S, Gambhir S . A mathematical model of ctDNA shedding predicts tumor detection size. Sci Adv. 2020; 6(50). PMC: 7732186. DOI: 10.1126/sciadv.abc4308. View

Berti A, Bortolotti R, Dipasquale M, Kinspergher S, Prokop L, Grandi G . Meta-analysis of immune-related adverse events in phase 3 clinical trials assessing immune checkpoint inhibitors for lung cancer. Crit Rev Oncol Hematol. 2021; 162:103351. DOI: 10.1016/j.critrevonc.2021.103351. View

10.

Borghaei H, Paz-Ares L, Horn L, Spigel D, Steins M, Ready N . Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015; 373(17):1627-39. PMC: 5705936. DOI: 10.1056/NEJMoa1507643. View

11.

Bratman S, Yang S, Iafolla M, Liu Z, Hansen A, Bedard P . Personalized circulating tumor DNA analysis as a predictive biomarker in solid tumor patients treated with pembrolizumab. Nat Cancer. 2022; 1(9):873-881. DOI: 10.1038/s43018-020-0096-5. View

12.

Cabel L, Riva F, Servois V, Livartowski A, Daniel C, Rampanou A . Circulating tumor DNA changes for early monitoring of anti-PD1 immunotherapy: a proof-of-concept study. Ann Oncol. 2017; 28(8):1996-2001. DOI: 10.1093/annonc/mdx212. View

13.

Cabel L, Proudhon C, Romano E, Girard N, Lantz O, Stern M . Clinical potential of circulating tumour DNA in patients receiving anticancer immunotherapy. Nat Rev Clin Oncol. 2018; 15(10):639-650. DOI: 10.1038/s41571-018-0074-3. View

14.

Carbone D, Reck M, Paz-Ares L, Creelan B, Horn L, Steins M . First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer. N Engl J Med. 2017; 376(25):2415-2426. PMC: 6487310. DOI: 10.1056/NEJMoa1613493. View

15.

Chaffer C, Weinberg R . A perspective on cancer cell metastasis. Science. 2011; 331(6024):1559-64. DOI: 10.1126/science.1203543. View

16.

Chaudhuri A, Chabon J, Lovejoy A, Newman A, Stehr H, Azad T . Early Detection of Molecular Residual Disease in Localized Lung Cancer by Circulating Tumor DNA Profiling. Cancer Discov. 2017; 7(12):1394-1403. PMC: 5895851. DOI: 10.1158/2159-8290.CD-17-0716. View

17.

Chiou V, Burotto M . Pseudoprogression and Immune-Related Response in Solid Tumors. J Clin Oncol. 2015; 33(31):3541-3. PMC: 4622096. DOI: 10.1200/JCO.2015.61.6870. View

18.

Cristiano S, Leal A, Phallen J, Fiksel J, Adleff V, Bruhm D . Genome-wide cell-free DNA fragmentation in patients with cancer. Nature. 2019; 570(7761):385-389. PMC: 6774252. DOI: 10.1038/s41586-019-1272-6. View

19.

de Castro Jr G, Rizvi N, Schmid P, Syrigos K, Martin C, Yamamoto N . NEPTUNE: Phase 3 Study of First-Line Durvalumab Plus Tremelimumab in Patients With Metastatic NSCLC. J Thorac Oncol. 2022; 18(1):106-119. DOI: 10.1016/j.jtho.2022.09.223. View

20.

Diehl F, Schmidt K, Choti M, Romans K, Goodman S, Li M . Circulating mutant DNA to assess tumor dynamics. Nat Med. 2008; 14(9):985-90. PMC: 2820391. DOI: 10.1038/nm.1789. View