scholarly journals Association of circulating tumor DNA (ctDNA) detection in metastatic renal cell carcinoma (mRCC) with tumor burden.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4582-4582 ◽  
Author(s):  
Manuel Caitano Maia ◽  
Paulo Gustavo Bergerot ◽  
Nazli Dizman ◽  
JoAnn Hsu ◽  
Jeremy Jones ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Clinical Care ◽  
Stage Iv ◽  
Circulating Tumor Dna ◽  
Continuous Variable ◽  
Tumor Burden ◽  
Variable Number ◽  
Clinical Annotation ◽  
Scan Data ◽  
Tumor Dna

4582 Background: In a series of 224 pts with advanced RCC, we have previously reported ctDNA detection in 79% of pts (Pal SK et al ASCO GU 2017). Clinical factors associated with detection are unknown. Methods: Data was obtained from pts with radiographically confirmed stage IV RCC who received ctDNA profiling as a part of routine clinical care using a CLIAA-certified platform evaluating 73 genes. Detailed clinical annotation was performed, including assessment of Heng risk score, previous and current treatments and calculation of tumor burden using scan data most proximal to ctDNA assessment. Tumor burden was equated to the sum of longest diameter (SLD) of all measurable lesions. Results: 32 pts were assessed (M:F 19:13) with a median age of 62 (range, 34-84). 25 pts, 4 pts and 3 pts had clear cell, sarcomatoid and papillary histology, respectively. Heng risk was good, intermediate and poor in 13, 18 and 1 pt, respectively. Pts received a median of 2 lines of prior tx. Specifically, 4 pts were not on active therapy (tx), 16 pts were receiving VEGF-directed tx, 6 pts were receiving checkpoint inhibitors (CPIs) and 6 pts were receiving combined VEGF/CPI tx. ctDNA was detected in 16 pts (50%) with a median of 2 genomic alterations (GAs) per pt. No associations were found between Heng risk, histology or tx type and presence/absence of ctDNA. However, pts with detectable ctDNA had a higher SLD compared to pts with no detectable ctDNA (99.6 vs 50.0 mm; P = 0.041). Furthermore, when evaluated as a continuous variable, number of GAs was correlated with SLD (P = 0.023). TP53 and VHL alterations were the most frequent GAs in this series, each occurring in 25% of the cohort. All 3 pts with brain metastases had ctDNA detected. Conclusions: With the caveat of a limited sample size, it appears that SLD (a surrogate for tumor burden) is higher in mRCC pts with detectable ctDNA, and increasing SLD may be associated with a higher number of GAs. Further validation of these findings may help identify appropriate pts for ctDNA assessment and maximize yield in clinical practice.

CAcTUS: A parallel arm, biomarker driven, phase II feasibility trial to determine the role of circulating tumor DNA in guiding a switch between targeted therapy and immune therapy in patients with advanced cutaneous melanoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS9587-TPS9587
Author(s):  
Rebecca Lee ◽  
Dominic G. Rothwell ◽  
Shien Chow ◽  
Heather May Shaw ◽  
Samra Turajlic ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
T Cell ◽  
Phase Ii ◽  
Immune Therapy ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Circulating Tumor Dna ◽  
Tumor Burden ◽  
Feasibility Trial ◽  
Tumor Dna

TPS9587 Background: Circulating tumor DNA (ctDNA; the tumour derived fraction of circulating free DNA in the blood) has been shown to be a biomarker of tumor burden/progression in many cancers. We recently accurately monitored treatment response and resistance in stage IV melanoma by ctDNA analysis in serial peripheral blood samples. Pre-clinical data has previously revealed that BRAF inhibition provokes a micro-environment with increased T cell infiltration, improved T cell recognition of melanoma associated antigens and reduced production of immunosuppressive cytokines that could enhance immune responses. We aimed to test the hypothesis that ctDNA could be implemented as a personalised, real-time liquid biopsy to identify when tumours are responding to targeted therapy in order optimise a switch to immunotherapy. Methods: We validated the ctDNA assays for BRAF mutation calling as a primary trial endpoint. We designed a phase II multicenter, parallel arm study across 6 UK sites, to assess primary objectives of i). Whether a ctDNA result can be turned around within 7 days and actioned in a clinically relevant timeframe ii). to assess whether a decrease in ctDNA levels of mutant BRAF by ≥80% from baseline on targeted therapy is an appropriate ‘cut off’ to instruct switching to immunotherapy. Secondary endpoints include Overall Response Rate (ORR) to immunotherapy, radiological/clinical and ctDNA determined progression free survival (PFS) on each treatment. Forty patients are planned based on inclusion criteria of stage IV or stage III unresectable cutaneous BRAF mutant melanoma, baseline ctDNA BRAF variant allele frequency (VAF) ≥1.5%, ECOG 0/1/2, no symptomatic brain metastases, no prior adjuvant nivolumab plus ipilimumab (N+I). Prior adjuvant dabrafinib + trametinib (D+T) is allowed as long as recurrence is >6 months from completion. Patients are randomised 1:1 to either standard Arm A; investigator choice of either D+T (150mg BD +2mg OD respectively) or N+I (1 mg/kg N +3 mg/kg I q3 wkly, then N 480mg q4 wkly) first line, then switch on progression to the other treatment. In the experimental Arm B; all patients start on D+T and have BRAF ctDNA monitored q2 wkly for 4 wks then q4 wkly. When ≥80% decrease vs. baseline in ctDNA BRAF VAF occurs, patients switch to N+I. If patients subsequently progress on N+I, they will resume D+T. The study is open with 9 patients enrolled at time of submission. Clinical trial information: NCT03808441.

INVESTIGATION KRAS MUTATION IN CIRCULATION TUMOR DNA IN DIFFERENT STAGES OF COLORECTAL CANCER

2019 ◽  
Vol 65 (5) ◽  
pp. 701-707
Author(s):  
Vitaliy Shubin ◽  
Yuriy Shelygin ◽  
Sergey Achkasov ◽  
Yevgeniy Rybakov ◽  
Aleksey Ponomarenko ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Plasma Volume ◽  
Kras Mutation ◽  
Stage Iv ◽  
Circulating Tumor Dna ◽  
Stage Ii ◽  
Kras Gene ◽  
Kras Mutations ◽  
Droplet Pcr ◽  
Tumor Dna

To determine mutations in the plasma KRAS gene in patients with colorectal cancer was the aim of this study. The material was obtained from 44 patients with colorectal cancer of different stages (T1-4N0-2bM0-1c). Plasma for the presence of KRAS gene mutation in circulating tumor DNA was investigated using digital droplet polymerase chain reaction (PCR). KRAS mutations in circulating tumor DNA isolated from 1 ml of plasma were detected in 13 (30%) patients with cancer of different stages. Of these, with stage II, there were 3 patients, with III - 5 and with IV - 5. Patients who did not have mutations in 1 ml of plasma were analyzed for mutations of KRAS in circulating tumor DNA isolated from 3 ml of plasma. Five more patients with KRAS mutations were found with II and III stages. The highest concentrations of circulating tumor DNA with KRAS mutation were found in patients with stage IV. The increase in plasma volume to 3 ml did not lead to the identification of mutations in I stage. This study showed that digital droplet PCR allows identification of circulating tumor DNA with the KRAS mutations in patients with stage II-IV of colon cancer. The results can be used to determine the degree of aggressiveness of the tumor at different stages of the disease, but not the 1st, and it is recommended to use a plasma volume of at least 3 ml.

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.

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

scholarly journals Accurate detection of circulating tumor DNA using nanopore consensus sequencing

2020 ◽  
Author(s):  
Alessio Marcozzi ◽  
Myrthe Jager ◽  
Martin Elferink ◽  
Roy Straver ◽  
Joost H. van Ginkel ◽  
...  
Keyword(s):  
Point Of Care ◽  
Circulating Tumor Dna ◽  
Tumor Burden ◽  
Liquid Biopsies ◽  
Genomic Locus ◽  
Base Calling ◽  
Accurate Detection ◽  
Tumor Diagnostics ◽  
A New Technique ◽  
Tumor Dna

ABSTRACTLevels of circulating tumor DNA (ctDNA) in liquid biopsies may serve as a sensitive biomarker for real-time, minimally-invasive tumor diagnostics and monitoring. However, detecting ctDNA is challenging, as much fewer than 5% of the cell-free DNA in the blood typically originates from the tumor. To detect lowly abundant ctDNA molecules based on somatic variants, extremely sensitive sequencing methods are required. Here, we describe a new technique, CyclomicsSeq, which is based on Oxford Nanopore sequencing of concatenated copies of a single DNA molecule. Consensus calling of the DNA copies increased the base-calling accuracy ∼60x, enabling accurate detection of TP53 mutations at frequencies down to 0.02%. We demonstrate that a TP53-specific CyclomicsSeq assay can be successfully used to monitor tumor burden during treatment for head-and-neck cancer patients. CyclomicsSeq can be applied to any genomic locus and offers an accurate diagnostic liquid biopsy approach that can be implemented in point-of-care clinical workflows.

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