(S036) Circulating Tumor DNA and Implications for Clinical Decision-Making in Stage I NSCLC

Publication
Article
OncologyOncology Vol 29 No 4_Suppl_1
Volume 29
Issue 4_Suppl_1

Our model suggests that ctDNA could improve clinical decision-making for stage I NSCLC. Prospectively identified high-risk patients could benefit from systemic therapy. We assumed that occult micrometastases and ctDNA had clinical significance, which is supported in published literature.

Julie Koenig, Ben Durkee, Erqi Pollom, Iris Gibbs, Max Diehn; Stanford University School of Medicine; Department of Radiation Oncology, Stanford University Medical Center; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University

BACKGROUND: A nontrivial fraction of stage I non–small-cell lung cancer (NSCLC) is occult metastatic disease [Rusch, JCO 2011]. These patients have worse disease-free survival and overall survival (OS) [Rusch, JCO 2011]. The phase III Cancer and Leukemia Group B (CALGB) 9633 trial found a small benefit for adjuvant chemotherapy in stage I patients with high-risk disease based on size criterion [Strauss, JCO 2008]. However, the authors could not reproducibly identify these high-risk patients [Strauss, JCO 2008].

Circulating tumor DNA (ctDNA) is highly predictive of residual disease after definitive therapy [Newman, Nat Med 2014]. We hypothesize that ctDNA could identify high-risk patients with stage I NSCLC who could benefit from early systemic therapy.

METHODS: We created a Bayesian model to simulate posterior probabilities after screening for occult metastatic disease by ctDNA. We used prevalence data from the American College of Surgeons Oncology Group (ACOSOG) Z0040 trial, and recently published receiver operating characteristics for ctDNA [Newman, Nat Med 2014].

Next, we built a two-state Markov model, with the assumption that occult micrometastases conferred worse survival (hazard ratio [HR] = 1.82), based on ACOSOG. Patients receiving chemotherapy were assigned a survival benefit (HR = 0.69, high risk) and detriment (HR = 1.12, low risk) by extrapolation from Cancer and Leukemia Group B (CALGB) trial 9633. The model was run with no patient receiving chemotherapy and rerun with patients who had detectable ctDNA receiving adjuvant chemotherapy.

RESULTS: The 3-year OS rate was 71% and 73% for high- and low-risk patients, respectively, with a total payoff of 2.56 life-years. These modeled estimates correlate well with CALGB data. The positive likelihood ratio for ctDNA was 10.0. After screening for ctDNA, the posterior probability of occult disease for a positive test improved to 67.0%, from a baseline prevalence of 16.9%. Treating high-risk patients with adjuvant chemotherapy improved survival to 79%. The number needed to treat was 12.5.

CONCLUSION: Our model suggests that ctDNA could improve clinical decision-making for stage I NSCLC. Prospectively identified high-risk patients could benefit from systemic therapy. There are limitations to this study: a model does not substitute for a clinical trial. We did not do a sensitivity analysis. Our time horizon (3 yr) is short. We assumed that our high-risk patients (defined by ctDNA) would derive the same benefit as high-risk patients in the CALGB trial (defined by size). To support this, the data show that ctDNA levels correlate with tumor volume [Newman, Nat Med 2014]. We assumed that occult micrometastases and ctDNA had clinical significance, which is supported in published literature.

Proceedings of the 97th Annual Meeting of the American Radium Society - americanradiumsociety.org

Articles in this issue

(P005) Ultrasensitive PSA Identifies Patients With Organ-Confined Prostate Cancer Requiring Postop Radiotherapy
(P001) Disparities in the Local Management of Breast Cancer in the United States According to Health Insurance Status
(P002) Predictors of CNS Disease in Metastatic Melanoma: Desmoplastic Subtype Associated With Higher Risk
(P003) Identification of Somatic Mutations Using Fine Needle Aspiration: Correlation With Clinical Outcomes in Patients With Locally Advanced Pancreatic Cancer
(P004) A Retrospective Study to Assess Disparities in the Utilization of Intensity-Modulated Radiotherapy (IMRT) and Proton Therapy (PT) in the Treatment of Prostate Cancer (PCa)
(S001) Tumor Control and Toxicity Outcomes for Head and Neck Cancer Patients Re-Treated With Intensity-Modulated Radiation Therapy (IMRT)-A Fifteen-Year Experience
(S003) Weekly IGRT Volumetric Response Analysis as a Predictive Tool for Locoregional Control in Head and Neck Cancer Radiotherapy 
(S004) Combination of Radiotherapy and Cetuximab for Aggressive, High-Risk Cutaneous Squamous Cell Cancer of the Head and Neck: A Propensity Score Analysis
(S005) Radiotherapy for Carcinoma of the Hypopharynx Over Five Decades: Experience at a Single Institution
(S002) Prognostic Value of Intraradiation Treatment FDG-PET Parameters in Locally Advanced Oropharyngeal Cancer
(P006) The Role of Sequential Imaging in Cervical Cancer Management
(P008) Pretreatment FDG Uptake of Nontarget Lung Tissue Correlates With Symptomatic Pneumonitis Following Stereotactic Ablative Radiotherapy (SABR)
(P009) Monte Carlo Dosimetry Evaluation of Lung Stereotactic Body Radiosurgery
(P010) Stereotactic Body Radiotherapy for Treatment of Adrenal Gland Metastasis: Toxicity, Outcomes, and Patterns of Failure
(P011) Stereotactic Radiosurgery and BRAF Inhibitor Therapy for Melanoma Brain Metastases Is Associated With Increased Risk for Radiation Necrosis
Related Videos
Barbara Smith, MD, PhD, spoke about the potential use of pegulicianine-guided breast cancer surgery based on reports from the phase 3 INSITE trial.
Patient-reported symptoms following surgery appear to improve with the use of perioperative telemonitoring, says Kelly M. Mahuron, MD.
Treatment options in the refractory setting must improve for patients with resected colorectal cancer peritoneal metastasis, says Muhammad Talha Waheed, MD.
Although immature, overall survival data from the KEYNOTE-868 trial may support the use of pembrolizumab plus chemotherapy in patients with endometrial cancer.
Dostarlimab plus chemotherapy appears to yield favorable overall survival in patients with mismatch repair proficient endometrial cancer.
Some patients with large B-cell lymphoma may have to travel a great distance for an initial evaluation for CAR T-cell therapy.
Brian Slomovitz, MD, MS, FACOG discusses the use of new antibody drug conjugates for treating patients with various gynecologic cancers.
Education is essential to referring oncologists manage toxicities associated with CAR T-cell therapy for patients with large B-cell lymphoma.
There is no absolute age cutoff where CAR T cells are contraindicated for those with large B-cell lymphoma, says David L. Porter, MD.
David L. Porter, MD, emphasizes referring patients with large B-cell lymphoma early for CAR T-cell therapy consultation.
Related Content