scholarly journals Detection of Tumor Recurrence via Circulating Tumor DNA Profiling in Patients with Localized Lung Cancer: Clinical Considerations and Challenges

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3759
Author(s):  
Bryan Ulrich ◽  
Anne Pradines ◽  
Julien Mazières ◽  
Nicolas Guibert
Keyword(s):  
Lung Cancer ◽  
Residual Disease ◽  
Lung Cancer Screening ◽  
Circulating Tumor Dna ◽  
Definitive Treatment ◽  
Curative Intent ◽  
Screening Programs ◽  
Adjuvant Therapies ◽  
Sequencing Platforms ◽  
Tumor Dna

Approximately 30% of patients with non-small-cell lung cancer (NSCLC) present with localized/non-metastatic disease and are eligible for surgical resection or other “treatment with curative intent”. Due to the high prevalence of recurrence after treatment, adjuvant therapy is standard care for most patients. The effect of adjuvant chemotherapy is, however, modest, and new tools are needed to identify candidates for adjuvant treatments (chemotherapy, immunotherapy, or targeted therapies), especially since expanded lung cancer screening programs will increase the rate of patients detected with localized NSCLC. Circulating tumor DNA (ctDNA) has shown strong potential to detect minimal residual disease (MRD) and to guide adjuvant therapies. In this manuscript, we review the technical aspects and performances of the main ctDNA sequencing platforms (TRACERx, CAPP-seq) investigated in this purpose, and discuss the potential of this approach to guide or spare adjuvant therapies after definitive treatment of NSCLC.

NSCLC: Früherkennung von Rezidiven mittels zirkulierender Tumor-DNA

2021 ◽  
pp. 1-2
Author(s):  
Khosro Hekmat
Keyword(s):  
Lung Cancer ◽  
Residual Disease ◽  
Lung Cancer Screening ◽  
Circulating Tumor Dna ◽  
Definitive Treatment ◽  
Curative Intent ◽  
Screening Programs ◽  
Adjuvant Therapies ◽  
Sequencing Platforms ◽  
Tumor Dna

Approximately 30% of patients with non-small-cell lung cancer (NSCLC) present with localized/non-metastatic disease and are eligible for surgical resection or other «treatment with curative intent». Due to the high prevalence of recurrence after treatment, adjuvant therapy is standard care for most patients. The effect of adjuvant chemotherapy is, however, modest, and new tools are needed to identify candidates for adjuvant treatments (chemotherapy, immunotherapy, or targeted therapies), especially since expanded lung cancer screening programs will increase the rate of patients detected with localized NSCLC. Circulating tumor DNA (ctDNA) has shown strong potential to detect minimal residual disease (MRD) and to guide adjuvant therapies. In this manuscript, we review the technical aspects and performances of the main ctDNA sequencing platforms (TRACERx, CAPP-seq) investigated in this purpose, and discuss the potential of this approach to guide or spare adjuvant therapies after definitive treatment of NSCLC.

Circulating Tumor DNA Minimal Residual Disease Detection of Non–Small-Cell Lung Cancer Treated With Curative Intent

2022 ◽  
Author(s):  
Bruna Pellini ◽  
Aadel A. Chaudhuri
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Residual Disease ◽  
Circulating Tumor Dna ◽  
Small Cell ◽  
Post Treatment ◽  
Small Cell Lung ◽  
Curative Intent ◽  
Tumor Dna ◽  
Minimal Residual

Circulating tumor DNA (ctDNA) minimal residual disease (MRD) is a powerful biomarker with the potential to improve survival outcomes for non–small-cell lung cancer (NSCLC). Multiple groups have shown the ability to detect MRD following curative-intent NSCLC treatment using next-generation sequencing–based assays of plasma cell-free DNA. These studies have been modest in size, largely retrospective, and without thorough prospective clinical validation. Still, when restricting measurement to the first post-treatment timepoint to assess the clinical performance of ctDNA MRD detection, they have demonstrated sensitivity for predicting disease relapse ranging between 36% and 100%, and specificity ranging between 71% and 100%. When considering all post-treatment follow-up timepoints (surveillance), including those beyond the initial post-treatment measurement, these assays' performances improve with sensitivity and specificity for identifying relapse ranging from 82% to 100% and 70% to 100%, respectively. In this manuscript, we review the evidence available to date regarding ctDNA MRD detection in patients with NSCLC undergoing curative-intent treatment and the ongoing prospective studies involving ctDNA MRD detection in this patient population.

scholarly journals Liquid biopsy in NSCLC: a new challenge in radiation therapy

2021 ◽  
Author(s):  
Annarita Perillo ◽  
Mohamed Vincenzo Agbaje Olufemi ◽  
Jacopo De Robbio ◽  
Rossella Margherita Mancuso ◽  
Anna Roscigno ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Liquid Biopsy ◽  
Residual Disease ◽  
Biological Fluids ◽  
Circulating Tumor Dna ◽  
Minimum Residual ◽  
Nsclc Patients ◽  
Choice Of Therapy ◽  
Tumor Dna

Lung cancer is the most common cancer and the leading cause of cancer mortality worldwide. To date, tissue biopsy has been the gold standard for the diagnosis and the identification of specific molecular mutations, to guide choice of therapy. However, this procedure has several limitations. Liquid biopsy could represent a solution to the intrinsic limits of traditional biopsy. It can detect cancer markers such as circulating tumor DNA or RNA (ctDNA, ctRNA), and circulating tumor cells, in plasma, serum or other biological fluids. This procedure is minimally invasive, reproducible and can be used repeatedly. The main clinical applications of liquid biopsy in non-small cell lung cancer (NSCLC) patients are the early diagnosis, stratification of the risk of relapse, identification of mutations to guide application of targeted therapy and the evaluation of the minimum residual disease. In this review, the current role of liquid biopsy and associated markers in the management of NSCLC patients was analyzed, with emphasis on ctDNA and CTCs, and radiotherapy.

scholarly journals MA17.07 Circulating Tumor DNA Detects Minimal Residual Disease and Predicts Outcome in Localized Lung Cancer

2017 ◽  
Vol 12 (1) ◽  
pp. S445
Author(s):  
Aadel Chaudhuri ◽  
Alexander Lovejoy ◽  
Jacob Chabon ◽  
Aaron Newman ◽  
Henning Stehr ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Circulating Tumor Dna ◽  
Tumor Dna ◽  
Minimal Residual

Analysis of circulating tumor DNA in localized lung cancer for detection of molecular residual disease and personalization of adjuvant strategies.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8519-8519 ◽  
Author(s):  
Aadel Chaudhuri ◽  
Jacob J. Chabon ◽  
Alexander F. Lovejoy ◽  
Aaron M. Newman ◽  
Henning Stehr ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adjuvant Treatment ◽  
Residual Disease ◽  
Primary Lung Cancer ◽  
Circulating Tumor Dna ◽  
Post Treatment ◽  
Egfr Mutations ◽  
Predictive Values ◽  
Synonymous Mutations ◽  
Tumor Dna

8519 Background: Identifying localized non-small cell lung cancer (NSCLC) patients with residual disease following curative intent therapy is difficult due to normal tissue changes caused by surgery or radiation and an inability to detect microscopic disease. Analysis of circulating tumor DNA (ctDNA) might enable identification of molecular residual disease (MRD) and personalization of adjuvant treatment approaches but has not been explored in lung cancer. Methods: We applied CAPP-Seq, an ultra-sensitive next-generation sequencing based ctDNA quantitation method, to pre- and post-treatment blood samples from a cohort of 41 patients treated with chemoradiation, radiotherapy or surgery for stage I-III primary lung cancer. Detection of ctDNA at a single MRD time-point within 4 months of treatment completion was compared with surveillance by cross-sectional imaging. Furthermore, we developed an approach for identification of tumor mutation burden based on mutations detected in plasma, leveraging whole exome sequencing data from 1,177 NSCLCs sequenced by TCGA. Results: Median follow-up time was 35 months. Pre-treatment ctDNA was detected in 38 (93%) patients and 19 (46%) had detectable post-treatment ctDNA MRD. MRD+ patients displayed significantly inferior 3-year freedom from progression (0% vs. 92%; HR 38; P < 0.0001) and 3-year overall survival (8% vs. 75%; HR 12; P < 0.0001) than MRD- patients. Detection of ctDNA MRD had positive and negative predictive values for disease progression of 100% and 93%, respectively. Furthermore, we non-invasively identified activating EGFR mutations or high mutational burden (≥5 CAPP-Seq non-synonymous mutations, corresponding to > 200 non-synonymous mutations per exome or > 4 single nucleotide variants per megabase of exome) in 47% of patients with detectable ctDNA MRD, suggesting potentially favorable responses to TKIs and immune checkpoint inhibitors, respectively. Conclusions: Our results indicate that ctDNA analysis accurately detects MRD in localized lung cancer patients and could facilitate personalized adjuvant treatment at early time-points when disease burden is minimal.

scholarly journals Early Detection of Circulating Tumor DNA Postoperatively Enables Discovery of Resectable Metastatic Disease in a Patient with Colon Cancer

2021 ◽  
pp. 1748-1753
Author(s):  
Benjamin A. Weinberg ◽  
Emily R. Winslow ◽  
Mohammed Bayasi ◽  
Michael R. Krainock ◽  
Perry M. Olshan ◽  
...  
Keyword(s):  
Early Detection ◽  
Residual Disease ◽  
Colon Adenocarcinoma ◽  
Circulating Tumor Dna ◽  
Close Monitoring ◽  
Curative Intent ◽  
Contrast Enhanced ◽  
Metastatic Relapse ◽  
Invasive Method ◽  
Tumor Dna

Currently, serum carcinoembryonic agent (CEA) along with contrast-enhanced imaging and colonoscopy are used for evaluation of recurrence of colorectal cancer. However, CEA is an unreliable and nonspecific biomarker that may fail to rise and signal relapse. Analysis of circulating tumor DNA (ctDNA) in patients offers a minimally invasive method to assess risk of relapse several months ahead of conventional clinical means. Here, we report the case of a colon adenocarcinoma with postoperative liver metastasis diagnosed early by ctDNA measurement, using a personalized NGS-mPCR assay. While ctDNA levels continued to rise, CEA levels tested negative. Metastatic relapse to the liver was promptly confirmed by PET/CT scan. The patient underwent a successful metastasectomy with curative intent. Following surgery, the patient exhibited no evidence of disease and ctDNA levels remained negative. Our case report suggests that the early detection of postoperative molecular residual disease by means of ctDNA measurement can accurately predict mCRC relapse in cases where CEA levels fail to increase. Close monitoring of ctDNA levels during the postoperative period can allow for earlier intervention and more favorable outcomes in relapsing mCRC patients.

Circulating Tumor DNA in Non–Small-Cell Lung Cancer: A Primer for the Clinician

2017 ◽  
pp. 1-13 ◽  
Author(s):  
Aditi P. Singh ◽  
Haiying Cheng ◽  
Xiaoling Guo ◽  
Benjamin Levy ◽  
Balazs Halmos
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Residual Disease ◽  
Circulating Tumor Dna ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Early Stage Disease ◽  
Tumor Dna

Circulating tumor DNA (ctDNA) consists of short, double-stranded DNA fragments that are released into the circulation by tumor cells. With the advent of newer molecular platforms, ctDNA can be detected with high sensitivity and specificity in plasma. The assay’s noninvasive nature, ability to reflect intratumoral heterogeneity, short turnaround time, and ability to obtain serial samples make it an attractive option compared with traditional tissue biopsy tumor sequencing. Currently, this technology is mostly being used for the detection of EGFR mutations in patients with advanced non–small-cell lung cancer where tissue is inadequate to detect EGFR mutations that drive acquired resistance, most notably EGFR T790M. Emerging uses include the incorporation of ctDNA testing into primary diagnosis, treatment monitoring, detection of minimal residual disease, and detection of early-stage disease in screening populations. This review summarizes both validated and evolving uses of ctDNA testing in non–small-cell lung cancer in the context of oncologists’ daily practice and some of its potential challenges in the era of targeted therapy and immunotherapy.

scholarly journals Personalized circulating tumor DNA analysis to detect residual disease after neoadjuvant therapy in breast cancer

2019 ◽  
Vol 11 (504) ◽  
pp. eaax7392 ◽  
Author(s):  
Bradon R. McDonald ◽  
Tania Contente-Cuomo ◽  
Stephen-John Sammut ◽  
Ahuva Odenheimer-Bergman ◽  
Brenda Ernst ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Therapy ◽  
Dna Analysis ◽  
Residual Disease ◽  
Circulating Tumor Dna ◽  
Patient Specific ◽  
Molecular Response ◽  
Curative Intent ◽  
Current Limit ◽  
Tumor Dna

Longitudinal analysis of circulating tumor DNA (ctDNA) has shown promise for monitoring treatment response. However, most current methods lack adequate sensitivity for residual disease detection during or after completion of treatment in patients with nonmetastatic cancer. To address this gap and to improve sensitivity for minute quantities of residual tumor DNA in plasma, we have developed targeted digital sequencing (TARDIS) for multiplexed analysis of patient-specific cancer mutations. In reference samples, by simultaneously analyzing 8 to 16 known mutations, TARDIS achieved 91 and 53% sensitivity at mutant allele fractions (AFs) of 3 in 104 and 3 in 105, respectively, with 96% specificity, using input DNA equivalent to a single tube of blood. We successfully analyzed up to 115 mutations per patient in 80 plasma samples from 33 women with stage I to III breast cancer. Before treatment, TARDIS detected ctDNA in all patients with 0.11% median AF. After completion of neoadjuvant therapy, ctDNA concentrations were lower in patients who achieved pathological complete response (pathCR) compared to patients with residual disease (median AFs, 0.003 and 0.017%, respectively, P = 0.0057, AUC = 0.83). In addition, patients with pathCR showed a larger decrease in ctDNA concentrations during neoadjuvant therapy. These results demonstrate high accuracy for assessment of molecular response and residual disease during neoadjuvant therapy using ctDNA analysis. TARDIS has achieved up to 100-fold improvement beyond the current limit of ctDNA detection using clinically relevant blood volumes, demonstrating that personalized ctDNA tracking could enable individualized clinical management of patients with cancer treated with curative intent.

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