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S. Mortimer
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P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.02-011 - A Prospective Study of Serial Circulating Tumor DNA Assessment in Detecting Recurrence of Resected Early-stage Lung Cancer (ID 10062)
09:30 - 09:30 | Author(s): S. Mortimer
- Abstract
Background:
In advanced non-small cell lung cancer (NSCLC), circulating tumor DNA (ctDNA) can be used to identify clinically actionable mutations when tissue is insufficient or unobtainable for genotyping. In early-stage NSCLC, the persistence of ctDNA after complete resection may suggest the presence of minimal residual disease and predict an increased risk of recurrence; however, data on the longitudinal use of ctDNA is very limited. The aim of this study is to assess the clinical feasibility of ctDNA assessment for the prediction of lung cancer recurrence following surgical resection.
Method:
Patients undergoing curative-intent surgery for NSCLC were prospectively enrolled. Peripheral blood samples were collected at pre-specified time points immediately prior to surgery and 2-3 weeks after surgery. Plasma cell-free DNA samples were analyzed with a novel 21-gene Digital Sequencing NGS panel (Guardant Health, Inc.) with a theoretical genomic sensitivity of > 90% for NSCLC. For each patient, the identities and quantities of somatic alterations identified in ctDNA were correlated to clinical outcomes.
Result:
Of the 55 pair-matched patients, 33 were evaluable at the time of abstract submission. The median age was 61 (18 men). The histologic type was adenocarcinoma in 19 (58%), squamous cell carcinoma in 14 (42%), and small cell lung cancer in 2 (6%). The pathologic stage was I in 20 (61%), II in 3 (9%), and IIIA in 10 (30%). Median clinical follow up was 13 months. Of the 4 patients with detectable post-operative ctDNA, 3 recurred within the follow-up period. Of the 8 total recurrences observed, the most common site was the brain (4) and lung (3). One of 4 adenocarcinoma recurrences, 1 of 2 squamous cell carcinoma recurrences, and 1 of 2 small cell recurrences were associated with detectable post-operative ctDNA. By stage, post-operative ctDNA was detected in 1 of 1 stage II and 3 of 7 stage IIIA patients. Recurrences not associated with detectable post-operative ctDNA were enriched in oligometastatic recurrence (4 of 5 unpredicted recurrences were in isolated lymph nodes or the brain).
Conclusion:
In this small pilot cohort, ctDNA detected at 2 weeks post resection was associated with recurrence (RR 9.38, p=0.038), while the absence of detectable ctDNA was not significantly associated with lack of recurrence (RR 0.65, p=0.12). Oligometastatic disease, especially in the brain, was a primary risk factor for ctDNA-negative recurrence. These findings establish proof of concept for the use of ctDNA diagnostics as a risk stratification tool in resected lung cancer.
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P3.05 - Early Stage NSCLC (ID 721)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.05-012 - Clinicopathological Determinants of Circulating Tumor DNA Detection in Early-Stage Non-Small Cell Lung Cancer (ID 10329)
09:30 - 09:30 | Author(s): S. Mortimer
- Abstract
Background:
Circulating tumor DNA (ctDNA)-based liquid biopsies have recently demonstrated substantial promise in the diagnosis and monitoring of advanced non-small cell lung cancer (NSCLC); however, data regarding utility in early-stage (operable) disease are very limited. The aim of this study is to define the clinical feasibility of ctDNA assessment in operable NSCLC.
Method:
We prospectively recruited 80 patients with clinical stage I-IIIa NSCLC undergoing cruative intent tumor resection. Pre-surgical plasma cell-free DNA (cfDNA) and matched tumor genomic DNA were collected and analyzed with a novel 21-gene Digital Sequencing NGS panel (Guardant Health, Inc.) with a theoretical genomic sensitivity of > 90% for NSCLC. Genomic results, including cfDNA yields, technical sequencing information, and identity and quantity of somatic variants, were correlated with various clinicopathological characteristics, including age, sex, smoking history, clinical and pathologic stage, histological tumor type, and preoperative treatment status.
Result:
[Cohort enrollment and sample collection is complete. Sequencing and analysis have been completed for the first 20 patients. The remaining patients will be completed within 1-2 months. Results from the complete cohort will be updated as directed by the Core Program Committee and will include the data elements described in the methods above. A preliminary review of the data is included below.] Of the 18 patients with somatic variants detected in tumor tissue (18/20, 90%), pre-operative ctDNA was detected in 12 (67%). Pre-operative ctDNA detection was high in squamous cell carcinoma (8/8), small cell lung cancer (1/1) and mixed histology (1/1) relative to adenocarcinoma (2/10, 20%). Clinical stage did not influence detection of small cell or squamous cell carcinoma; however, no ctDNA was detected in stage I or II adenocarcinoma samples (0/5). Detailed data from the complete cohort will be submitted as a late-breaking abstract.
Conclusion:
[Conclusion to be updated pending full cohort data.] ctDNA demonstrates sufficient pre-operative clinical sensitivity to be a feasible recurrence monitoring tool but appears to be influenced by tumor type.
