Abstract 2833
Background
Circulating tumor DNA (ctDNA) is a promising, non-invasive biomarker for preclinical detection and monitoring of various cancers. The utility of ctDNA assessment in renal cell carcinoma (RCC) in not well established. Here, we evaluate the potential of a bespoke, multiplex PCR, whole exome sequencing (WES)-based approach for ctDNA detection.
Methods
The cohort consisted of 42 patients with stage Ib-IV RCC who underwent complete surgical resection. ctDNA was measured in plasma samples drawn pre-surgery (n = 34; baseline) and at post-operative time points (n = 41) using the bespoke assay targeting patient-specific tumor variants.
Results
A median of 11.7 ng (1.4-175 ng) of cfDNA was extracted from a median plasma volume of 3.2 mL (1.2-3.8 mL). ctDNA was detected with a mean mutant molecules/mL of 5.3 (0.22-62). Baseline ctDNA was detected in 41% (14/34) of patients. Presence of ctDNA was significantly associated with increased tumor size (mean 9.7 vs 7.1cm, p < 0.05), advanced tumor stage (stage III-IV vs I-II, p < 0.05) and poorly differentiated tumors (grade III-IV vs II, p < 0.0001). In the postoperative setting, 8/8 ctDNA-positive patients relapsed (positive predictive value (PPV=100%), while 16/33 ctDNA-negative patients relapsed (NPV=52%). Positive ctDNA status was associated with reduced relapse-free survival at post-surgical timepoints (HR: 2.8; 95% CI:1.2-6.6). None of the post-surgical samples from a control cohort of 17 non-relapsing patients were ctDNA-positive (specificity of 100%; median follow up of 64 months).
Conclusions
Presence of presurgical ctDNA strongly correlates with advanced stage RCC. Despite low plasma volumes, the bespoke assay detected ctDNA in 41% of baseline samples. Postoperative ctDNA presence is correlated with clinical relapse. However, absence of ctDNA does not preclude recurrence as RCC is known to shed limited amounts of ctDNA. Higher sample volumes and multiregion tumor biopsies could enhance detection rates. This personalized approach has the potential to be used for ctDNA-based detection of relapse in patients with advanced stage RCC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Natera, Inc.; Fox Chase Cancer Center.
Funding
Natera, Inc.; Fox Chase Cancer Center.
Disclosure
M. Balcioglu: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. H. Wu: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. S. Dashner: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. S. Shchegrova: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. E. Kalashnikova: Full / Part-time employment: Natera, Inc. H. Pawar: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. R.G. Uzzo: Advisory / Consultancy: Janssen; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis; Advisory / Consultancy: Argos. A. Aleshin: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. H. Sethi: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. R. Salari: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. M. Louie: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. B. Zimmermann: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. P. Abbosh: Advisory / Consultancy, Advisory: Janssen; Advisory / Consultancy, Advisory: AstraZeneca. All other authors have declared no conflicts of interest.
Resources from the same session
2142 - Low NK Cell Abundance Correlates with High Expression of PD-1 in CD8+ T Cells
Presenter: Moon Hee Lee
Session: Poster Display session 3
Resources:
Abstract
5501 - Tobacco smoking is associated with the immune suppressive microenvironment in head and neck squamous cell carcinoma (HNSCC)
Presenter: Christine Chung
Session: Poster Display session 3
Resources:
Abstract
5726 - Evaluation of Antibody-Dependent Cell Cytotoxicity (ADCC) in lung cancer cell lines treated with combined anti-EGFR and anti-PD-L1 therapy.
Presenter: Francesca Sparano
Session: Poster Display session 3
Resources:
Abstract
2534 - Radiomic Signatures for Identification of Tumors Sensitive to Nivolumab or Docetaxel in Squamous Non-Small Cell Lung Cancer (sqNSCLC)
Presenter: Laurent Dercle
Session: Poster Display session 3
Resources:
Abstract
3366 - Analysis of gut microbiota in advanced non-small cell lung cancer (NSCLC) patients treated with immune-checkpoints blockers
Presenter: FEIYU ZHANG
Session: Poster Display session 3
Resources:
Abstract
2089 - Pathogenesis of Myocarditis Following Treatment with Immune Checkpoint Inhibitors in a Cynomolgus Monkey Model
Presenter: Changhua Ji
Session: Poster Display session 3
Resources:
Abstract
4463 - Effects of dietary restriction in cancer patients receiving irinotecan
Presenter: Ruben Van Eerden
Session: Poster Display session 3
Resources:
Abstract
4841 - Investigating the Link between Burn Injury and Tumorigenesis
Presenter: Lucy Barrett
Session: Poster Display session 3
Resources:
Abstract
4619 - Prognostic value of the neutrophil-lymphocyte, platelet-lymphocyte and monocyte-lymphocyte ratio in male breast cancer patients
Presenter: Joanna Huszno
Session: Poster Display session 3
Resources:
Abstract
1122 - Platelets from metastatic cancer patients have increased aggregation and activation
Presenter: Meera Chauhan
Session: Poster Display session 3
Resources:
Abstract