Patient And Tumor Characteristics
Clinical characteristics are shown in Table 1. A total of 60 patients with lmCRC had undergone 18F-FDG PET/CT imaging in Shanghai cancer center before treatment. Median age of these patients was 62 years (range 29–86). Of the 60 primary tumours, 47 (78.33%) were colon cancer and 13 (21.67%) were rectal cancer. 13 (21.67%) of the patients had ≥ 5 liver metastatic sites (group by colorectal liver oligometastases criteria(17)). 30 were KRAS/NRAS wild-type, 56 were BRAF wild-type, and 27 were KRAS/NRAS/BRAF wild-type.
Table 1
Patients and tumor characteristics.
Characteristic | Patients (n = 60) |
Age(y) | |
Median (range) | 62(29–86) |
Sex | |
Male | 33 |
Female | 27 |
Blood glucose | |
Mean ± SD | 5.48 ± 0.78 |
Range | 4.2–8.2 |
CEA | |
< 5.0 | 9 |
≥ 5.0 | 51 |
Location | |
colon | 47 |
rectum | 13 |
NO. of liver Metastatic sites | |
≤ 5 | 47 |
> 5 | 13 |
KRAS/NRAS | |
wild-type | 30 |
mutation | 30 |
BRAF | |
wild-type | 56 |
mutation | 4 |
KRAS/NRAS/BRAF | |
wild-type | 27 |
mutation | 33 |
Correlations Between Kras/nras/braf Mutation Status And Patient Characteristics
Two groups were divided among patients according to the mutation status of the KRAS/NRAS/BRAF. In the 60 patients with lmCRC, correlations between the KRAS/NRAS/BRAF mutation status and clinical characteristics were evaluated by univariate analysis. Because all patient have liver metastasis, the relationship between mutation of KRAS/NRAS/BRAF and TNM stage was not evaluated. There was no significant difference in age, gender, location, CEA between the KRAS/NRAS/BRAF mutation group and the wild-type group. However, the two groups were significantly different in terms of the number of liver metastatic sites (p = 0.02; Table 2).
Table 2
Univariate analysis of factors associated with KRAS/NRAS/BRAF mutation status.
Factor | KRAS/NRAS/BRAF mutation (n = 33) | KRAS/NRAS/BRAF wild-type (n = 27) | p value |
Mean age ± SD (y) | 58.18 ± 13.49 | 58.96 ± 10.24 | 0.98 |
Sex | | | |
Male | 16 | 17 | 0.26 |
Female | 17 | 10 | |
Location | | | 0.59 |
Colon | 25 | 22 | |
Rectum | 8 | 5 | |
CEA | | | 0.49 |
< 5.0 | 4 | 5 | |
≥ 5.0 | 29 | 22 | |
NO. of liver metastatic sites | | | 0.02a |
< 5 | 22 | 25 | |
≥ 5 | 11 | 2 | |
SUVmax - P | 18.65 ± 9.27 | 14.74 ± 5.88 | 0.13 |
MTV - P | 80.26 ± 165.55 | 49.12 ± 55.26 | 0.35 |
TLG - P | 564.04 ± 1135.22 | 279.49 ± 315.73 | 0.21 |
SUVmax - T | 18.35 ± 9.48 | 14.55 ± 6.04 | 0.12 |
MTV - T | 46.89 ± 40.98 | 33.54 ± 23.85 | 0.14 |
TLG - T | 358.67 ± 436.62 | 189.69 ± 130.60 | 0.18 |
SUVmax - L | 11.58 ± 4.82 | 9.67 ± 2.58 | 0.77 |
MTV - L | 77.81 ± 166.44 | 134.69 ± 169.22 | 0.14 |
TLG - L | 423.25 ± 1101.98 | 672.91 ± 859.16 | 0.06 |
HI - P | 18.35 ± 9.48 | 14.55 ± 6.04 | 0.12 |
HI - T | 2.64 ± 0.57 | 2.51 ± 0.64 | 0.25 |
HI - L | 2.48 ± 0.69 | 2.05 ± 0.31 | 0.01a |
ap < .05 is considered significant. |
Abbreviations: HI, heterogeneity index; -P, patient; -T, primary tumor; -L, Liver metastasis |
Correlation Between Pet Parameters And Kras/nras/braf Mutation Status
Only HI-L has significant correlation with KRAS/NRAS/BRAF mutation status, and SUVmax-P, MTV-P, TLG-P, SUVmax-T, MTV-T, TLG-T, SUVmax-L, MTV-L, TLG-L, HI-P and HI-T have no correlation with the status (Table 2). HI-L of KRAS/NRAS/BRAF mutation was significantly higher than KRAS/NRAS/BRAF wild-type (2.48 ± 0.69 and 2.05 ± 0.31, respectively, p = 0.01).
Then the optimal HI-L threshold was determined for predicting KRAS/NRAS/BRAF mutation. Receiver operating characteristic (ROC) curve analysis showed that when the HI-L cut-off value was 2.12, the prediction accuracy of KRAS / NRAS / BRAF mutation was the highest. The area under the ROC curve was 0.712 ± 0.067. The sensitivity and specificity were 72.7% and 70.4% to predict KRAS/NRAS/BRAF mutation (Fig. 1). These results show that 18F-FDG PET/CT may be used to predict the KRAS/NRAS/BRAF mutation status in patients with lmCRC. Representative PET/CT images are shown in Fig. 2.
In the multivariate analysis, only HI-L was still significantly associated with KRAS / NRAS / BRAF mutation status (Table 3; odds ratio, 6.78; 95% confidence interval, 1.63–28.08; p = 0.008).
Table 3
Multivariate analysis of KRAS/NRAS/BRAF mutation status.
Factor | Odds ratio | 95% confidence interval | p |
HI-L | 6.78 | 1.63–28.08 | 0.008 |
No. of liver metastatic sites | 0.49 | 0.49–7.08 | 0.358 |