You are here
Circulating tumor DNA as a non-invasive tool to identify patients at risk for recurrence after chemoradiotherapy in stage III non-small cell lung cancer.
Background: Outcomes for curative-intent chemoradiotherapy of unresectable stage III non-small cell lung cancer (NSCLC) remains poor. Heterogeneity in tumors is correlated with therapeutic resistance and poor prognosis. We hypothesize that tumor-specific alterations (alts) in circulating tumor DNA (ctDNA) quantifies tumor heterogeneity and can serve as a non-invasive means to determine prognosis and recurrence. Methods: Between 2009-2013, 156 patients (pts) with unresectable NSCLC receiving definitive radiotherapy (XRT) or chemo-XRT were consented to have blood drawn pre-XRT, 1-2 times during XRT, and 1-2 times in follow up ( > 670 samples). We used a ctDNA NGS assay to detect SNVs in 70 genes, amplifications in 16, and select fusions and indels. Statistical analyses were performed for association between OS/PFS and ctDNA serial samples results. Here we report the initial interim analysis. Results: Of 44 pts, 32 (73%) recurred (PFS range 0-26.6 months) and 12(27%) had no evidence of recurrence as of last contact (1.9-43.5 months post-XRT). We found 4 main patterns of ctDNA changes: specific alts persistent throughout XRT (n = 9); no alts detected in the post-XRT sample (n = 14), increased levels from baseline (n = 10), or fluctuates throughout therapy (n = 11). Alleles which persisted throughout XRT were found in TP53, ARID1A, BRCA2, NF1, KRAS, APC, AR, ERRB2, PIK3CA, ATM, MET, BRAF, PDGFRA, CRCA1, NOTCH1, RAF1, GATA3, KIT. While the 4 patterns of cfDNA fluctuations were not found to be prognostic in this interim analysis, the presence of specific mutations appears to correlate with outcomes, with reappearance of the driver mutations post-tx associated with shorter PFS. Using FDR cutoff of 0.1, NF1 mutations were associated with shorter OS (p = 0.07), and APC/ARID1Amutations associated with shorter PFS (p = 0.09) after adjustment for tumor histology or stage. Conclusions: In this interim analysis, we found that specific mutant alleles in cfDNA are correlated with potentially treatment resistance and early metastatic recurrence. Final analysis of the larger cohort may be required to achieve significance for additional prognostic patterns.
Abstracts by Steven H. Lin:
Clinical outcomes of elderly patients with esophageal cancer treated with chemoradiotherapy in the modern era.Meeting: 2017 Gastrointestinal Cancers Symposium | Abstract No: 174
The impact of proton beam therapy on blood cell count nadir during neoadjuvant chemoradiation therapy for esophageal cancer.Meeting: 2017 Gastrointestinal Cancers Symposium | Abstract No: 137
Analysis of PD-L1 and RAD50 in circulating cells recovered from lung cancer patients before and after induction of radiotherapy.Meeting: 2016 ASCO Annual Meeting | Abstract No: e20537
Presentations by Steven H. Lin:
Meeting: 2017 Gastrointestinal Cancers Symposium
Session: Welcome and General Session 1: Advances in Local Management and Therapy for Esophageal Cancer (General Session)