Method to risk-stratify oligometastatic non-small cell lung cancer patients using cell-free DNA liquid biopsies
Among the various aspects of the present disclosure is the provision of a method to risk-stratify cancer patients using circulating DNA assays. In other aspects, a method of selecting treatment for an early-stage non-small cell lung cancer for a patient in need that includes subjecting a blood sample from a patient to a liquid biopsy assay to identify at least one circulating tumor DNA (ctDNA) variant indicative of oligometastatic disease, and selecting a systemic therapy as a treatment if the liquid biopsy assay identifies the at least one ctDNA variant, or selecting a radiation therapy if the liquid biopsy assay identifies essentially zero ctDNA variants.
1 . A method of selecting a treatment for an early-stage non-small cell lung cancer (NSCLS) for a patient in need, the method comprising:
a. providing a blood sample from the patient in need prior to radiation therapy (RT);
b. subjecting the blood sample to a liquid biopsy assay configured to detect at least one circulating tumor DNA (ctDNA) variant indicative of oligometastatic (NSCLS) disease; and
c. selecting and administering a systemic therapy as a treatment if the liquid biopsy assay identifies the at least one ctDNA variant and otherwise selecting and administering a radiation therapy as the treatment.
2 . The method of claim 1 , wherein the at least one circulating tumor DNA (ctDNA) variant indicative of oligometastatic (NSCLS) disease is selected from an oncogenic mutation variant, a resistance mutation variant, and any combination thereof.
3 . The method of claim 2 , wherein the at least one oncogenic mutation variant, resistance mutation variant, and any combination thereof is selected from a single nucleotide variant (SNVs), an insertion/deletion (indel), a rearrangement, a copy number variation (CNV), and a microsatellite instability (MSI).
4 . The method of claim 1 , wherein the at least one circulating tumor DNA (ctDNA) variant is identified within at least one gene selected from EGFR, ALK, ROS1, MET, RET, BRAF, KRAS, ERBB2, and any combination thereof.
5 . The method of claim 1 , the method further comprising quantifying the maximum variant allele frequency (VAF) in the patient based on the at least one circulating tumor DNA (ctDNA) variant detected by the liquid biopsy assay.
6 . A method of selecting a treatment for an early-stage non-small cell lung cancer (NSCLS) for a patient in need, the method comprising:
a. providing a blood sample from the patient in need prior to radiation therapy (RT);
b. subjecting the blood sample to a liquid biopsy assay configured to detect at least one circulating tumor DNA (ctDNA) variant indicative of oligometastatic (NSCLS) disease;
c. quantifying a maximum variant allele frequency (VAF) in the patient based on the at least one circulating tumor DNA (ctDNA) variant detected by the liquid biopsy assay based on the at least one circulating tumor DNA (ctDNA) variant identified by the liquid biopsy assay; and
d. selecting and administering a systemic therapy as a treatment if the maximum VAF value falls above a threshold VAF value and otherwise selecting and administering a radiation therapy as the treatment.
7 . The method of claim 6 , wherein the threshold maximum VAF value is zero.
8 . The method of claim 7 , wherein the threshold maximum VAF value is 0.1.
9 . The method of claim 6 , wherein the at least one circulating tumor DNA (ctDNA) variant indicative of oligometastatic (NSCLS) disease is selected from an oncogenic mutation variant, a resistance mutation variant, and any combination thereof.
10 . The method of claim 9 , wherein the at least one oncogenic mutation variant, resistance mutation variant, and any combination thereof is selected from a single nucleotide variant (SNVs), an insertion/deletion (indel), a rearrangement, a copy number variation (CNV), and a microsatellite instability (MSI).
11 . The method of claim 10 , wherein the at least one variant is identified within a gene selected from EGFR, ALK, ROS1, MET, RET, BRAF, KRAS, ERBB2, and any combination thereof.