Background
Methods
Patient population
Preparation and quantification of plasma cell-free DNA
Analytic validation of the FoundationACT ctDNA assay
PET/CT data acquisition and image analysis
Statistical analysis
Results
Patient characteristics
Group A (N = 14) | Group B (N = 67) | Total (N = 81) | |
---|---|---|---|
Type of specimen | Frozen plasma | Fresh whole blood | All samples |
Age: median (range) | 68 (44–73) | 67 (45–93) | 67 (44–93) |
Gender: female N (%) | 9 (64%) | 46 (69%) | 55 (68%) |
Race/ethnicity: N (%) | |||
Caucasian | 8 (57%) | 43 (64%) | 51 (63%) |
Asian | 2 (14%) | 13 (19%) | 15 (19%) |
Hispanic | 2 (14%) | 6 (9%) | 8 (10%) |
African American | 2 (14%) | 5 (7%) | 7 (9%) |
Cancer type/histology: N (%) | |||
LUAD | 2 (14%) | 40 (60%) | 42 (52%) |
LUSC | 9 (64%) | 8 (12%) | 17 (21%) |
Breast | 3 (21%) | 13 (19%) | 16 (20%) |
Other cancer types* | 0 | 6 (9%) | 6 (7%) |
Detection of GAs in plasma ctDNA
FoundationACT | Group A (N = 14) | Group B (N = 67) | Total (N = 81) |
---|---|---|---|
Specimen type | Frozen plasma | Fresh whole blood | All samples |
Volume (mL) | ~ 3.0 | 8.5 (5.5–11.5) | 8.0 (3.0–11.5) |
cfDNA (ng/mL) | 2.5 ± 5.0 | 14.2 ± 32.2 | P = 0.023 |
GA ≥ 1 | 13 (93%) | 56 (84%) | 69 (85%) |
Total number of GAs (average/case, range) | 49 (3.5/case; 1–9) | 166 (2.5/case; 1–11) | 215 (2.7/case; 1–11) |
Base substitutions | 36 (73%) | 118 (71%) | 154 (72%) |
Insertions/deletions | 8 (16%) | 26 (16%) | 34 (16%) |
Amplifications | 1 (2%) | 13 (8%) | 14 (7%) |
Rearrangements/fusions | 4 (8%) | 9 (5%) | 13 (6%) |
cfDNA (mean ± SD) ng/mL; (GA ≥ 1 vs GA = 0) | 3.1 ± 5.9 vs 0.3 ± 0.1 (P = 0.5293) | 8.6 ± 18.1 vs 18.9 ± 51.6 (P = 0.2314) | 7.6 ± 16.7 vs 16.3 ± 47.3 (P = 0.2362) |
MSAF (mean ± SD); (GA ≥1 vs GA = 0) | 0.0648 ± 0.0823 vs 0.0005 ± 0.0007 (P = 0.3062) | 0.1219 ± 0.2031 vs 0.0003 ± 0.0009 (P = 0.0432) | 0.1117 ± 0.1880 vs 0.0003 ± 0.0009 (P = 0.0304) |
Tumor burden by RECIST V1.1 cm (GA ≥ 1 vs GA = 0) (mean ± SD) | 7.6 ± 6.4 vs 12.0 ± 12.0 (P = 0.4610) | 9.8 ± 5.8 vs 5.7 ± 3.4 (P = 0.0292) | 9.4 ± 5.9 vs 6.6 ± 5.3 (P = 0.1301) |
Tumor metabolic activity by SUVmax mg/dL (GA ≥1 vs GA = 0) (mean ± SD) | 51.1 ± 34.8 vs 31.2 ± 30.7 (P = 0.4772) | 48.1 ± 29.5 vs 14.3 ± 12.6 (P = 0.0006) | 48.6 ± 30.2 vs 16.9 ± 15.8 (P = 0.0006) |
Tumor types | Genomic alterations | No. concordance (N = 22) | No. unique to FoundationOne (N = 4) | % concordance (N = 26) | No. unique to FoundationACT (N = 8) |
---|---|---|---|---|---|
NSCLC (N = 33) | EGFR L858R and exon 19 deletions | 8 | 2 | 80% | 0 |
EGFR T790 M | 2 | 1 | 67% | 0 | |
ALK rearrangements | 4 | 0 | 100% | 0 | |
BRAF V600 mutation | 1 | 0 | 100% | 0 | |
MET exon 14 skip site alterations | 2 | 1 | 67% | 0 | |
ERBB2 mutations | 0 | 0 | 100% | 2 | |
Breast (N = 7) | ERBB2 amplification or mutation | 1 | 0 | 100% | 1 |
BRCA1/2 mutations | 2 | 0 | 100% | 4 | |
Ovarian (N = 2) | BRCA1/2 mutations | 2 | 0 | 100% | 0 |
Pt No. | Age (years old) | Gender | Race/ethnicity | Diagnosis | Cohort (A = frozen plasma; B=fresh blood) | cfDNA ng/mL | GA MAF (%) | MSAF | RECIST V1.1 (cm) | Total SUVmax | Clinical scenario |
---|---|---|---|---|---|---|---|---|---|---|---|
Pt 1 | 59 | F | Not Hispanic, White | Breast, IDC | B | 0.55 | No reportable GA | 0 | 1.8 | N/A | CR |
Pt 2 | 52 | F | Not Hispanic, Asian | LUAD | B | 4.20 | No reportable GA | 0 | 2.3 | 1.1 | CR |
Pt 3 | 68 | M | Not Hispanic, White | LUAD | B | 0.49 | No reportable GA | 0 | 2.5 | 2.6 | CR |
Pt 4 | 54 | M | Not Hispanic, Filipino | LUAD | B | 12.21 | No reportable GA | 0 | 6.2 | 5.8 | CR |
Pt 5 | 65 | F | Not Hispanic, White | LUAD | B | 0.75 | No reportable GA | 0 | 7.3 | 14.4 | CR |
Pt 6 | 68 | M | Not Hispanic, White | LUSC | A | 0.21 | No reportable GA | 0 | 20.5 | 52.9 | *CR (ongoing at 3 years), pneumonitis |
Pt 7 | 55 | F | Not Hispanic, Asian | LUAD | B | 2.94 | TP53 E358V (49.1%) | 0 | 2.3 | 4.3 | PR |
Pt 8 | 73 | F | Not Hispanic, White | LUAD | B | 7.25 | BRCA2 S1121* (44.6%) | 0 | 7.9 | 14.6 | PD vs inflammation |
Pt 9 | 68 | F | Not Hispanic, White | LUAD | B | 182.16 | No reportable GA | 0 | 5.8 | 34.1 | PD vs inflammation |
Pt 10 | 84 | M | Not Hispanic, White | LUAD | B | 9.04 | No reportable GA | 0 | 7.7 | 30.2 | Small volume, indolent disease |
Pt 11 | 67 | F | Not Hispanic, Iran | Breast, inflammatory | B | 5.93 | No reportable GA | 0 | 9.6 | 11.3 | Small volume, indolent disease vs pneumonia |
Pt 12 | 54 | M | Not Hispanic, Filipino | LUAD | B | 0.05 | No reportable GA | 0 | 10.8 | 32.0 | Small volume, indolent disease vs pneumonia |