Overall survival with circulating tumor DNA-guided therapy in advanced non-small-cell lung cancer

Jee, Justin; Lebow, Emily S.; Yeh, Randy; Das, Jeeban Paul; Namakydoust, Azadeh; Paik, Paul K.; Chaft, Jamie E.; Jayakumaran, Gowtham; Brannon, A. Rose; Benayed, Ryma; Zehir, Ahmet; Donoghue, Mark T.A.; Schultz, Nikolaus; Chakravarty, Debyani; Kundra, Ritika; Madupuri, Ramyasree; Murciano‐Goroff, Yonina R.; Tu, Hai‐Yan; Xu, Chong-Rui; Martinez, Andrés; Wilhelm, Clare; Galle, Jesse; Daly, Bobby; Yu, Helena A.; Offin, Michael; Hellmann, Matthew D.; Lito, Piro; Arbour, Kathryn C.; Zauderer, Marjorie G.; Kris, Mark G.; Ng, Kenneth K.; Eng, Juliana; Preeshagul, Isabel R.; Lai, W. Victoria; Fiore, John J.; Iqbal, Afsheen; Molena, Daniela; Rocco, Gaetano; Park, Bernard J.; Lim, Lee P.; Li, Mark; Tong-Li, Candace; Silva, Madhawa De; Chan, David; Diakos, Connie I.; Itchins, Malinda; Clarke, Stephen; Pavlakis, Nick; Lee, Adrian V.; Rekhtman, Natasha; Chang, Jason C.; Travis, William D.; Riely, Gregory J.; Solit, David B.; Gönen, Mithat; Rusch, Valerie W.; Rimner, Andreas; Gomez, Daniel R.; Drilon, Alexander; Scher, Howard I.; Shah, Sohrab P.; Berger, Michael F.; Arcila, Maria E.; Ladanyi, Marc; Levine, Ross L.; Shen, Ronglai; Razavi, Pedram; Reis‐Filho, Jorge S.; Jones, David R.; Rudin, Charles M.; Isbell, James M.; Li, Bob T.

doi:10.1038/s41591-022-02047-z

Cited by 72 publications

(41 citation statements)

References 76 publications

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“…These ctDNA variants not identified in tissue sequencing are largely due to spatial tumor heterogeneity, tumor evolution, or acquired resistance to drug, which could not be captured by patient‐specific panels detecting tissue‐derived mutations or standardized panels referring tissue mutations only. Indeed, Jee et al [ 32 ] reported that advanced NSCLC patients with ctDNA‐private mutations had worse OS than those with tissue‐matched ctDNA mutations, and these ctDNA‐private mutations featured subclonal drivers of resistance to targeted therapy. Ours and Jee's studies highlight the prognostic value of ctDNA mutations not matched in its tissue sample.…”

Section: Discussionmentioning

confidence: 99%

Postoperative circulating tumor DNA can refine risk stratification in resectable lung cancer: results from a multicenter study

Huang

Tian

et al. 2023

Molecular Oncology

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Circulating tumor DNA (ctDNA) has potential as a promising biomarker for molecular residual disease (MRD) detection in lung cancer. As the next‐generation sequencing standardized panel for ctDNA detection emerges, its clinical utility needs to be validated. We prospectively recruited 184 resectable lung cancer patients from four medical centers. Serial postoperative ctDNAs were analyzed by a standardized panel. A total of 427 postoperative plasma samples from 177 eligible patients were enrolled. ctDNA positivity after surgery was an independent predictor for disease recurrence and preceded radiological recurrence by a median of 6.6 months (range, 0.7–27.0 months). ctDNA‐positive or ‐negative patients with tumors of any stage had similar disease‐free survival (DFS). Patients who received targeted therapy had significantly improved DFS than those not receiving adjuvant therapy or receiving chemotherapy, regardless of baseline/preadjuvant ctDNA status. According to whether the ctDNA variants were detected in its matched tissue, they were classified into tissue derived and non‐tissue derived. Patients with detectable postoperative ctDNA with tissue‐derived mutations had comparable DFS with those with non‐tissue‐derived mutations. Collectively, we demonstrated that postoperative ctDNA has the potential to stratify prognosis and optimize tumor stage in resectable lung cancer. ctDNA variants not identified in tissue samples should be considered in MRD test.

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Section: Discussionmentioning

confidence: 99%

Postoperative circulating tumor DNA can refine risk stratification in resectable lung cancer: results from a multicenter study

Huang

Tian

et al. 2023

Molecular Oncology

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“…Circulating tumor DNA (ctDNA) proved to be a useful predictive biomarker of recurrence and outcome in the advanced NSCLC ( 45 ). In trials, researchers found that early clearance of ctDNA was predictive of a better response to treatment and a longer survival time in metastatic non-small cell lung cancer.…”

Section: Potential Predictive Factors Of Neoadjuvant Immunotherapymentioning

confidence: 99%

Progress on neoadjuvant immunotherapy in resectable non-small cell lung cancer and potential biomarkers

Chau

Bai

et al. 2023

Front. Oncol.

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Immune checkpoint inhibitors (ICIs) are highly concerned in the treatment of non-small cell lung cancer (NSCLC), represented by inhibitors of programmed death protein 1 (PD-1) and its ligand (PD-L1), and inhibitors of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4). The introduction of immunotherapy in the treatment of perioperative NSCLC has improved the prognosis to a great extent, as demonstrated by several phase II and III clinical trials. The target population for immunotherapy in early-stage NSCLC is still under discussion, and the biomarkers for neoadjuvant immunotherapy population selection are the next pending problem. The predictive efficacy of many potential makers is still being explored, including PD-L1 expression levels, tumor mutation burden, circulating tumor DNA, components of the tumor microenvironment, and several clinical factors. We summarize key findings on the utility of ICIs in clinical trials of preoperative NSCLC patients and conclude analyses of relevant biomarkers to provide a better understanding of potentially predictive biomarkers in neoadjuvant immunotherapy.

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“…Furthermore, together with known oncogenic drivers, co-occurring mutations can significantly modify cellular processes and clinical outcomes [ 14 , 15 , 16 ]. A recent study with over 1100 patients with NSCLC demonstrated that, overall, the presence of cfDNA has the potential to be used as an independent overall survival predictor, with hazard ratios (HRs) reaching 2.05 and 95% confidence intervals (CIs) 1.74–2.42 ( p < 0.001) [ 17 ]. Furthermore, increasing interest has been shown in the cfDNA dynamics during disease course, with a higher cfDNA amount detected after surgery for locally advanced NSCLC indicating shorter progression-free survival [ 18 ] or disease recurrence [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Surveillance of cfDNA Hot Spot Mutations in NSCLC Patients during Disease Progression

Sestokaite

Gedvilaite

Cicėnas

et al. 2023

IJMS

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Non-small cell cancer (NSCLC) has been identified with a great variation of mutations that can be surveyed during disease progression. The aim of the study was to identify and monitor lung cancer-specific mutations incidence in cell-free DNA as well as overall plasma cell-free DNA load by means of targeted next-generation sequencing. Sequencing libraries were prepared from cell-free DNA (cfDNA) isolated from 72 plasma samples of 41 patients using the Oncomine Lung cfDNA panel covering hot spot regions of 11 genes. Sequencing was performed with the Ion Torrent™ Ion S5™ system. Four genes were detected with highest mutation incidence: KRAS (43.9% of all cases), followed by ALK (36.6%), TP53 (31.7%), and PIK3CA (29.3%). Seven patients had co-occurring KRAS + TP53 (6/41, 14.6%) or KRAS + PIK3CA (7/41, 17.1%) mutations. Moreover, the mutational status of TP53 as well an overall cell-free DNA load were confirmed to be predictors of poor progression-free survival (HR = 2.5 [0.8–7.7]; p = 0.029 and HR = 2.3 [0.9–5.5]; p = 0.029, respectively) in NSCLC patients. In addition, TP53 mutation status significantly predicts shorter overall survival (HR = 3.4 [1.2–9.7]; p < 0.001). We demonstrated that TP53 mutation incidence as well as a cell-free DNA load can be used as biomarkers for NSCLC monitoring and can help to detect the disease progression prior to radiological confirmation of the status.

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Overall survival with circulating tumor DNA-guided therapy in advanced non-small-cell lung cancer

Cited by 72 publications

References 76 publications

Postoperative circulating tumor DNA can refine risk stratification in resectable lung cancer: results from a multicenter study

Postoperative circulating tumor DNA can refine risk stratification in resectable lung cancer: results from a multicenter study

Progress on neoadjuvant immunotherapy in resectable non-small cell lung cancer and potential biomarkers

Surveillance of cfDNA Hot Spot Mutations in NSCLC Patients during Disease Progression

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