Table 2.
Association of liquid biopsy results and radiological response, progression free survival and overall survival.
| (a) Association of KRAS mutation status and RR | |||||||
|---|---|---|---|---|---|---|---|
| PD/N | OR (PD) | 95% CI | p Value | Adjusted ORa | 95% CI | p Value | |
| T1 | |||||||
| KRAS positive | 16/35 | 2.0 | 0.8–5.3 | 0.1534 | 1.8 | 0.6–5.5 | 0.3062 |
| KRAS negative | 11/37 | 1 | 1 | ||||
| T2 | |||||||
| KRAS positive | 15/28 | 5.3 | 2.0–13.9 | 0.0008 | 7.3 | 2.1–25.0 | 0.0016 |
| KRAS negative | 7/38 | 1 | 1 | ||||
| T3 | |||||||
| KRAS positive | 12/21 | 7.8 | 2.1–29.2 | 0.0023 | 9.8 | 2.4–40.3 | 0.0015 |
| KRAS negative | 4/40 | 1 | 1 | ||||
| Δ (T1–T2) | |||||||
| MAFA increase | 9/17 | 3.5 | 1.1–10.9 | 0.0279 | 8.0 | 1.5–42.8 | 0.0145 |
| MAFA stable/decrease | 13/49 | 1 | 1 | ||||
| Δ (T1–T3) | |||||||
| MAFA increase | 10/16 | 10.8 | 2.5–47.2 | 0.0015 | 14.2 | 3.0–68.7 | 0.0009 |
| MAFA stable/decrease | 6/45 | 1 | 1 | ||||
| (b) Association of KRAS mutation status and PFS | ||||||||
|---|---|---|---|---|---|---|---|---|
| PD/N | Median PFS (95% CI) | HR | 95% CI | p Value | Adjusted HRb | 95% CI | p Value | |
| T1 | ||||||||
| KRAS positive | 28/35 | 5.6 (3.0–10.4) | 1.0 | 0.6–1.7 | 0.9483 | 0.9 | 0.5–1.6 | 0.7302 |
| KRAS negative | 33/38 | 7.2 (5.4–9.2) | 1 | 1 | ||||
| T2 | ||||||||
| KRAS positive | 24/28 | 4.7 (2.8–8.6) | 1.4 | 0.8–2.3 | 0.2483 | 1.4 | 0.8–2.4 | 0.1891 |
| KRAS negative | 31/39 | 8.1 (5.8–10.3) | 1 | 1 | ||||
| T3 | ||||||||
| KRAS positive | 20/21 | 3.8 (2.1–6.7) | 2.9 | 1.5–5.9 | 0.0025 | 2.3 | 1.1–4.6 | 0.0198 |
| KRAS negative | 30/40 | 9.9 (7.9–13.1) | 1 | 1 | ||||
| Δ (T1–T2) | ||||||||
| MAFA increase | 16/17 | 5.2 (2.1–9.2) | 1.6 | 0.9–2.9 | 0.0925 | 2.1 | 1.2–3.8 | 0.0142 |
| MAFA stable/decrease | 39/50 | 8.0 (5.6–9.9) | 1 | 1 | ||||
| Δ (T1–T3) | ||||||||
| MAFA increase | 15/16 | 2.8 (1.8–5.7) | 3.3 | 1.4–7.5 | 0.0055 | 2.8 | 1.3–6.3 | 0.0119 |
| MAFA stable/decrease | 35/45 | 9.9 (7.9–11.0) | 1 | 1 | ||||
| (c) Association of KRAS mutation status and OS | ||||||||
|---|---|---|---|---|---|---|---|---|
| Death/N | Median OS (95% CI) | HR | 95% CI | p Value | Adjusted HRc | 95% CI | p Value | |
| T1 | ||||||||
| KRAS positive | 19/35 | 11.2 (4.8–22.1) | 2.4 | 1.1–5.1 | 0.0231 | 2.1 | 0.9–4.7 | 0.0746 |
| KRAS negative | 11/38 | – | 1 | |||||
| T2 | ||||||||
| KRAS positive | 16/28 | 10.8 (4.5–22.1) | 3.0 | 1.4–6.6 | 0.0066 | 3.1 | 1.4–7.0 | 0.0063 |
| KRAS negative | 11/41 | – | 1 | |||||
| T3 | ||||||||
| KRAS positive | 13/21 | 10.7 (5.6–12.9) | 6.6 | 2.4–18.2 | 0.0002 | 5.0 | 1.6–15.0 | 0.0044 |
| KRAS negative | 6/40 | – | 1 | |||||
| Δ (T1–T2) | ||||||||
| MAFA increase | 10/17 | 10.7 (3.4–) | 2.4 | 1.1–5.4 | 0.0313 | 3.2 | 1.2–8.4 | 0.0168 |
| MAFA stable/decrease | 15/50 | 22.1 (11.9-) | 1 | |||||
| Δ (T1–T3) | ||||||||
| MAFA increase | 10/16 | 8.3 (4.4–11.2) | 4.5 | 1.7–11.8 | 0.0027 | 3.9 | 1.5–10.6 | 0.0067 |
| MAFA stable/decrease | 9/45 | 22.1 (21.5-) | 1 | |||||
PFS progression-free survival, OS overall survival, RR radiological response, MAFA mutated allele fractional abundance, PD progressive disease, N number of treatments, AUC area under the curve, CI confidence interval, OR odds ratio, HR hazard ratio.
Bold values indicate statistical significance p < 0.05.
aOR adjusted for clinical prognostic factors (see Supplementary Table 3).
bHR adjusted for clinical significant factors (see Supplementary Table 4).
cHR adjusted for clinical significant factors (see Supplementary Table 5).