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
5389 - Two-weekly accelerated BEP (aBEP) regimen as induction chemotherapy (CT) in intermediate and poor prognosis patients (pts) with nonseminomatous germ cell tumors (NSGCT): final results of phase II trial.
Presenter: Alexey Tryakin
Session: Poster Display session 3
Resources:
Abstract
2934 - Differential expression of circulating miR375 and miR371 to detect teratoma and viable germ cell malignancy
Presenter: Lucia Nappi
Session: Poster Display session 3
Resources:
Abstract
3585 - Prognosis of anaemia in disseminated testicular germ cell tumours. On behalf of the Spanish Germ Cell Cancer Group (SGCCG)
Presenter: Esmeralda Garcia Torralba
Session: Poster Display session 3
Resources:
Abstract
2254 - The Effects Of Primary Testicular Tumor Localization On Prognosis In Patients With Nonseminomatous Testis Cancer
Presenter: Birol Yildiz
Session: Poster Display session 3
Resources:
Abstract
4505 - Initial Results of a Phase II study of Nivolumab and Ipilimumab in Metastatic Adrenal Tumors.
Presenter: Matthew Campbell
Session: Poster Display session 3
Resources:
Abstract
3369 - NEMIO: a randomized phase II trial evaluating efficacy and safety of dose dense MVAC (ddMVAC) + durvalumab +/- tremelimumab as neoadjuvant treatment in patients with bladder muscle-invasive urothelial carcinoma
Presenter: Constance Thibault
Session: Poster Display session 3
Resources:
Abstract
2075 - KEYNOTE-866: Phase 3 Study of Perioperative Pembrolizumab (pembro) or Placebo (pbo) in Combination With Neoadjuvant Chemotherapy in Cisplatin (cis)-Eligible Patients (pts) With Muscle-Invasive Bladder Cancer (MIBC)
Presenter: Arlene Siefker-Radtke
Session: Poster Display session 3
Resources:
Abstract
4824 - KEYNOTE-905: A Phase 3 Study of Cystectomy Plus Perioperative Pembrolizumab Versus Cystectomy Alone in Cisplatin (cis)-Ineligible Patients (pts) With Muscle-Invasive Bladder Cancer (MIBC)
Presenter: Matthew Galsky
Session: Poster Display session 3
Resources:
Abstract
2253 - Phase 3 LEAP-011 trial: First-Line Pembrolizumab With Lenvatinib in Patients With Advanced Urothelial Carcinoma Ineligible to Receive Platinum-Based Chemotherapy
Presenter: Yohann Loriot
Session: Poster Display session 3
Resources:
Abstract
4310 - PULSE : A Single Arm Trial Assessing The Activity and Safety of Avelumab Immunotherapy Maintenance among Patients With Locally Advanced or Metastatic Squamous Cell Penile Carcinoma (mSCPC).
Presenter: Noemie Gassian
Session: Poster Display session 3
Resources:
Abstract