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.

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.

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 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.

scholarly journals Early Detection of Molecular Residual Disease in Localized Lung Cancer by Circulating Tumor DNA Profiling

2017 ◽  
Vol 7 (12) ◽  
pp. 1394-1403 ◽  
Author(s):  
Aadel A. Chaudhuri ◽  
Jacob J. Chabon ◽  
Alexander F. Lovejoy ◽  
Aaron M. Newman ◽  
Henning Stehr ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Early Detection ◽  
Residual Disease ◽  
Circulating Tumor Dna ◽  
Dna Profiling ◽  
Tumor Dna

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.

scholarly journals Circulating tumor DNA is detectable in canine histiocytic sarcoma, oral malignant melanoma, and multicentric lymphoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anaïs Prouteau ◽  
Jérôme Alexandre Denis ◽  
Pauline De Fornel ◽  
Edouard Cadieu ◽  
Thomas Derrien ◽  
...  
Keyword(s):  
Residual Disease ◽  
Specific Antigen ◽  
Point Mutations ◽  
Antigen Receptor ◽  
Digital Pcr ◽  
Circulating Tumor Dna ◽  
Histiocytic Sarcoma ◽  
Oncology Research ◽  
Tumor Dna

AbstractCirculating tumor DNA (ctDNA) has become an attractive biomarker in human oncology, and its use may be informative in canine cancer. Thus, we used droplet digital PCR or PCR for antigen receptor rearrangement, to explore tumor-specific point mutations, copy number alterations, and chromosomal rearrangements in the plasma of cancer-affected dogs. We detected ctDNA in 21/23 (91.3%) of histiocytic sarcoma (HS), 2/8 (25%) of oral melanoma, and 12/13 (92.3%) of lymphoma cases. The utility of ctDNA in diagnosing HS was explored in 133 dogs, including 49 with HS, and the screening of recurrent PTPN11 mutations in plasma had a specificity of 98.8% and a sensitivity between 42.8 and 77% according to the clinical presentation of HS. Sensitivity was greater in visceral forms and especially related to pulmonary location. Follow-up of four dogs by targeting lymphoma-specific antigen receptor rearrangement in plasma showed that minimal residual disease detection was concordant with clinical evaluation and treatment response. Thus, our study shows that ctDNA is detectable in the plasma of cancer-affected dogs and is a promising biomarker for diagnosis and clinical follow-up. ctDNA detection appears to be useful in comparative oncology research due to growing interest in the study of natural canine tumors and exploration of new therapies.

scholarly journals Patient-Specific Circulating Tumor DNA Detection during Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer

2017 ◽  
Vol 63 (3) ◽  
pp. 691-699 ◽  
Author(s):  
Francesca Riva ◽  
Francois-Clement Bidard ◽  
Alexandre Houy ◽  
Adrien Saliou ◽  
Jordan Madic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Minimal Residual Disease ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Residual Disease ◽  
Circulating Tumor Dna ◽  
Tp53 Mutations ◽  
Tumor Dna ◽  
Minimal Residual

Abstract BACKGROUND In nonmetastatic triple-negative breast cancer (TNBC) patients, we investigated whether circulating tumor DNA (ctDNA) detection can reflect the tumor response to neoadjuvant chemotherapy (NCT) and detect minimal residual disease after surgery. METHODS Ten milliliters of plasma were collected at 4 time points: before NCT; after 1 cycle; before surgery; after surgery. Customized droplet digital PCR (ddPCR) assays were used to track tumor protein p53 (TP53) mutations previously characterized in tumor tissue by massively parallel sequencing (MPS). RESULTS Forty-six patients with nonmetastatic TNBC were enrolled. TP53 mutations were identified in 40 of them. Customized ddPCR probes were validated for 38 patients, with excellent correlation with MPS (r = 0.99), specificity (≥2 droplets/assay), and sensitivity (at least 0.1%). At baseline, ctDNA was detected in 27/36 patients (75%). Its detection was associated with mitotic index (P = 0.003), tumor grade (P = 0.003), and stage (P = 0.03). During treatment, we observed a drop of ctDNA levels in all patients but 1. No patient had detectable ctDNA after surgery. The patient with rising ctDNA levels experienced tumor progression during NCT. Pathological complete response (16/38 patients) was not correlated with ctDNA detection at any time point. ctDNA positivity after 1 cycle of NCT was correlated with shorter disease-free (P < 0.001) and overall (P = 0.006) survival. CONCLUSIONS Customized ctDNA detection by ddPCR achieved a 75% detection rate at baseline. During NCT, ctDNA levels decreased quickly and minimal residual disease was not detected after surgery. However, a slow decrease of ctDNA level during NCT was strongly associated with shorter survival.

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