Abstract 2400: Circulating tumor DNA as a non-invasive substitute to metastasis biopsy for targeted sequencing in a prospective randomized trial for personalized treatment in all tumor type: The SHIVA study

A rapid molecular diagnostic technique targeting circulating tumor DNA (ctDNA) has become one of the most clinically significant liquid biopsy methods for non-invasive and timely diagnosis of cancer.

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Non-Invasive Monitoring of Urinary KRAS Circulating Tumor DNA for Treatment Response and Minimal Residual Disease in Patients with Lung Adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.15_suppl.e19092 ◽

2015 ◽

Vol 33 (15_suppl) ◽

pp. e19092-e19092 ◽

Cited By ~ 1

Author(s):

James Michael Randall ◽

Mark G. Erlander ◽

Cecile Rose T. Vibat ◽

Saege Hancock ◽

Vlada Melnikova ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Treatment Response ◽

Minimal Residual Disease ◽

Residual Disease ◽

Circulating Tumor Dna ◽

Invasive Monitoring ◽

Non Invasive ◽

Tumor Dna ◽

Minimal Residual

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TECHNICAL ASPECTS OF LIQUID BIOPSY: INFLUENCE OF PREANALYTICAL PARAMETERS ON THE CONCENTRATION OF CIRCULATING TUMOR DNA IN PLASMA OF CANCER PATIENTS

Problems in oncology ◽

10.37469/0507-3758-2020-66-4-391-397 ◽

2020 ◽

Vol 66 (4) ◽

pp. 391-397

Author(s):

T. Sokolova ◽

T. Laidus ◽

R. Meerovich ◽

K. Zagorodnev ◽

Aleksandr Martyanov ◽

...

Keyword(s):

Liquid Biopsy ◽

Distant Metastases ◽

Circulating Tumor Dna ◽

Cancer Diagnostics ◽

Braf V600e ◽

Nucleotide Substitutions ◽

Non Invasive ◽

Intrapatient Variability ◽

Lung Adenocarcinomas ◽

Tumor Dna

«Liquid biopsy» is gradually becoming a mandatory procedure in cancer diagnostics. The aim of this procedure is to detect and monitor tumor-specific markers in various body fluids (blood, urine, pleural fluid, etc.). Significant efforts have been made to convert the most common mutational tests (EGFR, KRAS, BRAF) into non-invasive procedures. Despite some advantages, “liquid biopsy” is still not equivalent to traditional tissue analysis due to limited sensitivity and specificity; it cannot be routinely used in cancer medicine until the standardization of pre-analytical procedures is agreed. We intend to improve the performance of liquid biopsy for detection of a number of clinically relevant mutations (EGFR: ex19del and L858R; KRAS: 12, 13, 61, 146 codon nucleotide substitutions; BRAF: V600E). 417 plasma samples obtained from 88 patients (KRAS/NRAS/BRAF-mutated colorectal cancer (CRC): n= 57; EGFR-mutated lung adenocarcinomas (LC): n = 14; BRAF-mutated melanoma: n = 17) were analyzed by ddPCR for the presence of corresponding mutations in the circulating tumor DNA (ctDNA). Presence of tumor-specific mutations in plasma was confirmed in 32/57 (56%) CRC, 7/14 (50%) LC, and 4/17 (24%) melanoma cases. The proportion of mutation-positive plasma cases was tended to be higher in the group of patients with distant metastases compared to subjects with localized disease [34/56 (61%) vs. 5/15 (33%), р = 0.058]. 86 patients provided their blood at 9.00 (morning) and at 16.00 (afternoon). In addition, blood-takes were performed before and 15 minutes after usual breakfast as well as before and 15 minutes after moderate physical exercise. The detection rate of cancer-specific mutations in plasma was not significantly correlated with described above circumstances of blood-take. Meanwhile, the noticeable intrapatient variability of circulating mutation success rate has been detected. Thus, depending on clinical circumstances, at least negative ctDNA tests could be advised to be repeated in some patients, in order to ensure the reliability of results.

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Non-invasive diagnosis and tracking of tumor evolution by targeted sequencing of circulating tumor DNA in metastatic pancreatic cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e15769 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e15769-e15769

Author(s):

Thomas Seufferlein ◽

Andreas W. Berger ◽

Daniel Schwerdel ◽

Thomas Jens Ettrich ◽

Stefan A. Schmidt ◽

...

Keyword(s):

Tumor Tissue ◽

Early Stage ◽

Therapy Monitoring ◽

Circulating Tumor Dna ◽

Ductal Adenocarcinoma ◽

Tumor Evolution ◽

Imaging Data ◽

Non Invasive ◽

Outcome Monitoring ◽

Tumor Dna

e15769 Background: Treatment of stage IV pancreatic ductal adenocarcinoma (PDAC) has made substantial progress over the last years, therapy monitoring still is at an early stage. This could be substantially supported by tools that allow to establish and monitor the molecular setup of the tumor even during treatment. In particular, non-invasive approaches are desirable. Characterization of circulating tumor DNA (ctDNA) may help to achieve this goal. Methods: We analyzed a cohort of 20 patients with histologically confirmed metastatic PDAC (mPDAC) prior to and during palliative treatment including disease progression. ctDNA and corresponding tumor tissue were analyzed by targeted NGS and droplet digital PCR for the 7 most frequently mutated genes in PDAC ( TP53, SMAD4, CDKN2A, KRAS, APC, ATM, FBXW7). Findings were correlated with clinical and imaging data to establish its prognostic and predictive value. Results: ctDNA was analyzed at baseline prior to initiation of the respective line of treatment. Mutations in either of the genes examined were detectable in 15/20 patients (75%). Tissue-blood concordance was 80% in therapy naïve patients. 96% of mutations in ctDNA of therapy naïve patients were in KRAS and/or TP53. The combined mutated allele frequencies (CMAF) of theese 2 genes significantly decreased (p = 0.0173) during therapy and increased at progression (p = 0.0145) across all treatment lines. By sequential ctDNA analyses we detected a change in the mutational landscape compared to the respective baseline ctDNA status in 7/11 patients during 1st line, in 3/7 patients during 2nd line and 2/2 patients during 3rdline treatment. In therapy naïve patients, the decline of the CMAF during therapy significantly correlated with progression-free survival (p = 0.0013). Conclusions: Molecular genotyping of ctDNA in mPDAC patients proved to be feasible and there was a high concordance between tumor tissue and ctDNA. The molecular genotype changed significantly during treatment and changes correlated with outcome. Monitoring of ctDNA may enable to adapt therapeutic strategies to the specific molecular changes present at a certain time during treatment of mPDAC.

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Genomic profiling of circulating tumor DNA (ctDNA) from patients (pts) with advanced cancers of the GI tract and anus.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.618 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 618-618 ◽

Cited By ~ 1

Author(s):

Alexa Betzig Schrock ◽

Lauren Young ◽

Samuel Jacob Klempner ◽

Rodolfo Bordoni ◽

Jeffrey S. Ross ◽

...

Keyword(s):

Molecular Profiling ◽

Circulating Tumor Dna ◽

Genomic Profiling ◽

Tissue Sampling ◽

Gi Tract ◽

Hybrid Capture ◽

Non Invasive ◽

Clinical Support ◽

Average Maximum ◽

Tumor Dna

618 Background: The treatment of GI carcinomas (CA) is influenced by the presence or absence of prognostic and predictive genomic alterations (GA). Tissue sampling is the historical platform for genomic biomarker assessment, but non-invasive ctDNA assay provides an alternative when tissue is unavailable or cannot be safely obtained. Methods: Hybrid-capture based genomic profiling using a ctDNA assay (FoundationACT) was performed on blood samples from 82 consecutive pts with lower alimentary canal CA. Results: Median age was 62 (range 28-92) and 61% were male. Anatomic breakdown included CRC (n = 51), esophageal (n = 9), gastric (n = 8), gastroesophageal (n = 3) and small bowel adenoCA (SBA, n = 2), anus squamous cell CA (n = 5), and other GI CA (n = 4). At least one GA was reported in 72% of cases. In 23 cases with no GA reported, the average maximum somatic allele frequency was 0.17% (95% CI: 0-0.6%) vs. 16.7% (95% CI: 0-54.4%) for the 59 cases with GAs (P < 0.0001). For the 3 of 18 patients with both blood and tissue testing performed and samples collected within a 30-day interval, 8/9 (89%) GA detected in tissue were also detected in ctDNA. An average of 1.7 GA/sample were detected in ctDNA. The most commonly altered genes were TP53 (61%), KRAS (24%), BRAF (10%) and PIK3CA (10%). Comparative analysis using the tissue-based Foundation Core database showed a similar trend with overall slightly higher frequencies of GAs in individual genes . RAF and RAS short variants (SV) were exclusive to lower GI and anal CA. KRAS and RAF1 amplification (amp) occurred only in esophageal CA (4/11, 36%). FGFR SV or amp was identified in 3 cases across the cohort. Of CRC, 4 (8%) had ≥ 1 ERBB2 activating SV or amp, 2 (4%) had IDH1/2 hotspot SV, and 2 (4%) had BRCA2 inactivating alterations. ERBB2 activating SV and EGFR amp were found in a SBA and an esophagus CA, respectively. A kinase fusion was identified as the sole driver in 1 CRC ( STRN-ALK) and 1 SBA ( GOPC-ROS1). Outcomes to targeted therapies will be presented for the available subset of patients. Conclusions: Our results provide early clinical support and confirm that hybrid-capture based ctDNA testing can reliably detect all 4 classes of GA and provide a molecular profiling option for patients with GI CA.

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Circulating tumor DNA-targeted sequencing to reveal germline and somatic alterations that can guide decision-making in metastatic castration-resistant prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e17556 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e17556-e17556

Author(s):

Baijun Dong ◽

Liancheng Fan ◽

Bin Yang ◽

Wei Chen ◽

Yonghong Li ◽

...

Keyword(s):

Prostate Cancer ◽

Circulating Tumor Dna ◽

Targeted Sequencing ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Genomic Landscape ◽

Platinum Based Chemotherapy ◽

Somatic Alterations ◽

Multiple Treatments ◽

Tumor Dna

e17556 Background: The genomic landscape of metastatic castration-resistant prostate cancer (mCRPC) is dynamic with the application of multiple treatments. The circulating tumor DNA (ctDNA), which reveals germline and somatic alterations, provides a mini-invasive tool for monitoring tumor evolution. Methods: We performed an exploratory analysis of 299 ctDNA samples from 8 centers through application of multiple-gene deep targeted sequencing. Results: The most common recurrent genomic alterations were in AR(34.7%), TP53(18.9%), CDK12(15.4%), BRCA2(13.3%), and the majority of these clinically actionable gene alterations were identified in somatic level (CDK12 100% in somatic). The results showed the frequency of AR amplification and TP53 defect significantly increased in post-second and later line treatment group compared with treatment-naive group. AR amplification and TP53 or RB1 defect were associated with resistance to abiraterone or docetaxel. CDK12 was more frequently altered in our cohort than those in previous reports which mainly focused on Caucasian population. The patients with CDK12 defect showed rapid resistance to abiraterone and limited efficacy of Poly (ADP-ribose) polymerase inhibitors (PARPi). However, these patients seemed to benefit from chemotherapy, especially platinum-based chemotherapy. Conclusions: This multi-institutional real-world study explored the genomic landscape and captured the significant diversity of mCRPC at different treatment stages by liquid biopsy. These findings established genomic drivers associated with resistance to multiple treatments (including PARPi and platinum-based chemotherapy) in mCRPC. Hence, ctDNA targeted sequencing can help guide clinical decision making in mCRPC throughout the whole treatment process. CDK12 might be able to be a novel predictive biomarker to guide treatment selection in mCRPC.

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