scholarly journals Circulating Tumor DNA Is an Accurate Measurement of Determining Radiation-Induced Therapeutic Response and Tumor Burden Monitoring in a Prostate Cancer Bone Metastases Murine Model

2019 ◽  
Vol 105 (1) ◽  
pp. E665
Author(s):  
A. Mishra ◽  
K. Zennami ◽  
E. Velarde ◽  
J.B. Coulter ◽  
S. Yegnasubramanian ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Murine Model ◽  
Therapeutic Response ◽  
Circulating Tumor Dna ◽  
Tumor Burden ◽  
Radiation Induced ◽  
Tumor Dna

Assessing tumor heterogeneity using circulating tumor DNA to predict and monitor therapeutic response in metastatic breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11543-11543
Author(s):  
Fei Ma ◽  
Yanfang Guan ◽  
Zongbi Yi ◽  
Lianpeng Chang ◽  
Xuefeng Xia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Heterogeneity ◽  
Therapeutic Response ◽  
Metastatic Breast ◽  
Circulating Tumor Dna ◽  
Tumor Burden ◽  
Response To Treatment ◽  
Clonal Population ◽  
Tumor Dna

11543 Background: Within metastatic breast cancer (mBC), tumor heterogeneity limited efficacy and duration of response to treatment. In this study, circulating tumor DNA (ctDNA) was used to evaluate tumor heterogeneity as a prognostic factor and monitor therapeutic response in patients with mBC. Methods: We collected plasma samples from 37 HER2-positive mBC patients treated with pyrotinib. Target-capture deep sequencing was performed to detect somatic mutations in plasma ctDNA. Clonal population structures were identified based on variations from ctDNA using Bayesian cluster with PyClone. Molecular tumor burden index (mTBI) was calculated with the mean variant allele frequency of mutations in trunk clonal population. Results: Mutations in TP53 and genes of PI3K/Akt/mTOR pathway were associated with drug resistance for pyrotinib. The result showed that patients with resistant mutations occurring as a truncal event, who receiving monotherapy of pyrotinib, presented worse therapeutic effect (HR, 4.52; P = 0.03). The median PFS of patients with versus without resistant mutations in trunk clonal population was 7.8 weeks (95% CI 7.4 to 26.8 weeks) versus 31.6 weeks (95% CI 15.7 to 60 weeks), respectively. Patients with high heterogeneity (clonal population ≥3) had a significantly worse PFS (HR, 2.79; 95% CI 1.23 to 6.34; P = 0.014). The median PFS among patients with high versus low heterogeneity was 30.0 weeks (95% CI 13.9 to 53.5 weeks) versus 60.0 weeks (95% CI 31.4 to 84 weeks), respectively. Longitudinal monitoring of 21 patients during treatment showed positive correlation between mTBI in ctDNA and tumor size evaluated by CT imaging (P < 0.0001). Monitoring the mTBI in serial ctDNA increased sensitivity for prediction of progressive disease in 6 of 21 patients, with a mean time of 12.7 weeks earlier than using CT scan. ROC curve analysis showed an area under the curve value was 0.97 (p < 0.0001). Conclusions: Assessing tumor heterogeneity in ctDNA provides genetic predictors of treatment outcome. Molecular tumor burden in ctDNA is a potential indicator of therapeutic response. These observations might be supplements for the current therapeutic response evaluation.

Analysis of circulating tumor DNA to monitor metastatic breast cancer patients treated with first-line chemotherapy (CAMELLIA study).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14568-e14568
Author(s):  
Zongbi Yi ◽  
Fei Ma ◽  
Guohua Rong ◽  
Jin Li ◽  
Lianpeng Chang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Therapeutic Response ◽  
Metastatic Breast ◽  
Circulating Tumor Dna ◽  
Tumor Burden ◽  
Breast Cancer Patients ◽  
First Line ◽  
Tumor Dna ◽  
Line Chemotherapy

e14568 Background: Our precious study indicated that the dynamic changes in circulating tumor DNA (ctDNA) could reflect changes in tumor burden. We conduct this study to validate the role of ctDNA as a therapeutic response biomarker in a larger cohort prospective phase III randomized multicenter study. Methods: In this study, we collected 292 serial ctDNA samples from 125 metastatic breast cancer patients treated with first line chemotherapy. Target-capture deep sequencing of 1021 genes was performed to detect somatic variants in ctDNA. Results: 81.4% patients had detectable ctDNA at baseline. An undetectable ctDNA at baseline was associated with a lower disease volume (p < 0.05). The commonly mutated genes were PIK3CA (35.0%), TP53 (34.2%), MLL3 (9.4%) and ESR1 (9.4%). Kaplan–Meier analysis showed that TP53 gene mutations and remaining C2 (detected at base line and remaining at the second cycle of chemotherapy) were significantly associated with poor PFS. Longitudinal monitoring of 27 patients during treatment showed that the molecular tumor burden index ([mTBI] a measure of the percentage of ctDNA in samples) was positively correlated with tumor size as evaluated by computed tomography (P < 0.05). The evaluations based on mTBI values were consistent with those based on CT scans in 87.5% of cases at the endpoint of clinical observation. Conclusions: ctDNA could be used to predict treatment outcomes and the mTBI is a potential method to assess therapeutic response in metastatic breast cancer. Clinical trial information: NCT01917279.

scholarly journals Circulating tumor DNA as an early marker of therapeutic response in patients with metastatic colorectal cancer

2015 ◽  
Vol 26 (8) ◽  
pp. 1715-1722 ◽  
Author(s):  
J. Tie ◽  
I. Kinde ◽  
Y. Wang ◽  
H.L. Wong ◽  
J. Roebert ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Therapeutic Response ◽  
Circulating Tumor Dna ◽  
Early Marker ◽  
Tumor Dna

Genomic analysis of circulating tumor DNA in 3,334 patients with advanced prostate cancer to identify targetable BRCA alterations and AR resistance mechanisms.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 25-25
Author(s):  
Hanna Tukachinsky ◽  
Russell Madison ◽  
Jon Chung ◽  
Lucas Dennis ◽  
Bernard Fendler ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Advanced Prostate Cancer ◽  
Acquired Resistance ◽  
Genomic Analysis ◽  
Circulating Tumor Dna ◽  
Resistance Mechanisms ◽  
Cancer Tissue ◽  
Castration Resistant Prostate Cancer ◽  
High Level ◽  
Tumor Dna

25 Background: Comprehensive genomic profiling (CGP) by next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) from plasma provides a minimally invasive method to identify targetable genomic alterations (GAs) and resistance mechanisms in patients with metastatic castration-resistant prostate cancer (mCRPC). The circulating tumor fraction in patients with mCRPC and the clinical validity of GAs detected in plasma remain unknown. We evaluated the landscape of GAs using ctDNA-based CGP and assessed concordance with tissue-based CGP. Methods: Plasma from 3,334 patients with advanced prostate cancer (including 1,674 mCRPC screening samples from the TRITON2/3 trials and 1,660 samples from routine clinical CGP) was analyzed using hybrid-capture-based gene panel NGS assays. Results were compared with CGP of 2,006 metastatic prostate cancer tissue biopsies. Concordance was evaluated in 837 patients with both tissue (archival or contemporaneous) and plasma NGS results. Results: 3,127 patients [94%] had detectable ctDNA. BRCA1/2 were mutated in 295 patients [8.8%]. In concordance analysis, 72/837 [8.6%] patients had BRCA1/2 mutations detected in tissue, 67 [93%] of whom were also identified by ctDNA, and 20 patients were identified using ctDNA but not tissue [23% of all patients identified using ctDNA]. ctDNA detected subclonal BRCA1/2 reversions in 10 of 1,660 [0.6%] routine clinical CGP samples. AR alterations, including amplifications and hotspot mutations, which were detected in 940/2,213 patients [42%]. Rare AR compound mutations, rearrangements, and novel in-frame deletions were identified. Altered pathways included PI3K/AKT/mTOR [14%], WNT/β-catenin [17%], and RAS/RAF/MEK [5%]. Microsatellite instability was detected in 31/2,213 patients [1.4%]. Conclusions: In the largest study of mCRPC plasma samples conducted to date, CGP of ctDNA recapitulated the genomic landscape detected in tissue biopsies, with a high level of agreement in detection of BRCA1/2 alterations. It also identified patients who may have gained somatic BRCA1/2 alterations since archival tissue was collected. ctDNA detected more acquired resistance GAs than tissue, including novel AR-activating variants. The large percentage of patients with rich genomic signal from ctDNA, and the sensitive, specific detection of BRCA1/2 alterations position liquid biopsy as a compelling clinical complement to tissue CGP for patients with mCRPC.

scholarly journals Detection of Circulating Tumor DNA in Patients With Leiomyosarcoma With Progressive Disease

2019 ◽  
pp. 1-11 ◽  
Author(s):  
Matthew L. Hemming ◽  
Kelly Klega ◽  
Justin Rhoades ◽  
Gavin Ha ◽  
Kate E. Acker ◽  
...  
Keyword(s):  
Disease Progression ◽  
Tumor Size ◽  
Disease Burden ◽  
Progressive Disease ◽  
Circulating Tumor Dna ◽  
Tumor Burden ◽  
Blood Draw ◽  
Cell Free Dna ◽  
Free Dna ◽  
Tumor Dna

Purpose Leiomyosarcoma (LMS) is a soft-tissue sarcoma characterized by multiple copy number alterations (CNAs) and without common recurrent single-nucleotide variants. We evaluated the feasibility of detecting circulating tumor DNA (ctDNA) with next-generation sequencing in a cohort of patients with LMS whose tumor burden ranged from no evidence of disease to metastatic progressive disease. Patients and Methods We evaluated cell-free DNA in plasma samples and paired genomic DNA from resected tumors from patients with LMS by ultra-low passage whole-genome sequencing. Sequencing reads were aligned to the human genome and CNAs that were identified in cell-free DNA and tumor DNA by ichorCNA software to determine the presence of ctDNA. Clinical data were reviewed to assess disease burden and clinicopathologic features. Results We identified LMS ctDNA in 11 (69%) of 16 patients with disease progression and total tumor burden greater than 5 cm. Sixteen patients with stable disease or low disease burden at the time of blood draw were found to have no detectable ctDNA. Higher ctDNA fraction of total cell-free DNA was associated with increasing tumor size and disease progression. Conserved CNAs were found between primary tumors and ctDNA in each case, and recurrent CNAs were found across LMS samples. ctDNA levels declined after resection of progressive disease in one case and became detectable upon disease relapse in another individual patient. Conclusion These results suggest that ctDNA, assayed by a widely available sequencing approach, may be useful as a biomarker for a subset of patients with uterine and extrauterine LMS. Higher levels of ctDNA correlate with tumor size and disease progression. Liquid biopsies may assist in guiding treatment decisions, monitoring response to systemic therapy, surveying for disease recurrence, and differentiating benign and malignant smooth muscle tumors.

Dynamic analysis of circulating tumor DNA to predict prognosis and monitor therapeutic response in metastatic relapsed cervical cancer

2020 ◽  
Vol 148 (4) ◽  
pp. 921-931
Author(s):  
Xiaoyuan Tian ◽  
Dongcen Ge ◽  
Feng Zhang ◽  
Bocheng Zhang ◽  
Wanting Bai ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Dynamic Analysis ◽  
Therapeutic Response ◽  
Circulating Tumor Dna ◽  
Tumor Dna

scholarly journals Analysis of mutational and proteomic heterogeneity of gastric cancer suggests an effective pipeline to monitor post-treatment tumor burden using circulating tumor DNA

PLoS ONE ◽  
2020 ◽  
Vol 15 (10) ◽  
pp. e0239966
Author(s):  
Noriyuki Sasaki ◽  
Takeshi Iwaya ◽  
Takehiro Chiba ◽  
Masashi Fujita ◽  
Zhenlin Ju ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Circulating Tumor Dna ◽  
Tumor Burden ◽  
Post Treatment ◽  
Tumor Dna
Sign in / Sign up

Export Citation Format

Share Document