Preoperative accurate evaluation of PNI in patients with PDAC affects the choice of appropriate treatment. Our retrospective study constructed a nomogram to preoperatively predict PNI based on the rad-score from the arterial and portal venous phases of CECT, CTLN and CTPNI. The nomogram could effectively predict the occurrence of PNI in both the training and testing groups. This study demonstrated that the nomogram was superior to the Rad-score and CTPNI for evaluating the occurrence of PNI.
The prevalence of PNI in PDAC patients is fairly high, varying from 42.3%-100% in previous reports[3], with an incidence of 54.4% in this study. Additionally, we found an interesting association between PNI status and LN status, and the PNI-positive group was more prone to LN metastasis. Previous studies have indicated that cancer cells grow along nerves in contact with LNs, indicating a complex link between LN metastasis and PNI[28, 29]. There was also a statistically significant difference in the CTLNs. In addition, patients with PNI were more likely to have poor pathological differentiation. Poorly differentiated PDAC has more aggressive behavior, which is related to poor prognosis, PNI and poor differentiation and reflects the malignant biological behavior of PDAC. We did not find significant differences in tumor size; dilation status of the CBD or MPD; CEA or CA19-9 levels; or resection margin status between the PNI-positive and PNI-negative groups. The relationship between PNI and tumor size is controversial. Crippa et al. reported that the incidence of PNI increased with tumor size[30]. However, Patel et al. suggested that no evidence was found between tumor size and PNI[31]. PNI occurs early in PDAC, and even tumors less than 2 cm may develop PNI[32]. This may be related to the greater probability of PNI due to tumor growth beyond the pancreas, while tumors within the pancreas generally do not develop PNI even if the tumor is large, based on the anatomical structure[33]. These controversial results suggest that the relationship between tumor size and PNI needs further investigation. CBD and MPD dilatation caused by obstruction may not be associated with PNI. CEA and CA19-9 are nonspecific in PDAC and may be abnormal in a variety of diseases, which may account for the lack of differences in CEA and CA19-9 between the PNI-positive and PNI-negative groups.
Eight radiomics features related to PNI were selected for this study. Kulkarni et al.[34] extracted CT texture features to analyze their association with PNI and did not find any texture features related to PNI. The possible reason is that the texture features were only extracted from the maximum level of the tumor, which included incomplete features. In addition, in this study, poorly vascularized tumors located in the head of the pancreas were selected. In our study, the radiomics features of the whole lesion were extracted at the three-dimensional level, which could help to discover more biological characteristics of tumors. These selected features were integrated into a Rad-score and exhibited moderate performance in preoperatively predicting the PNI status of PDAC in both the training and testing cohorts. Radiomics can improve the prediction performance of medical images by improving analysis and using computer algorithms to extract thousands of quantitative features, and it can mine a large amount of information that is invisible to the naked eye. According to the radiologists’ evaluation, the CTPNI achieved inferior performance, which may be attributed to perivascular inflammation or fibrosis easily mimicking PNI on CT. In addition, PDAC is characterized by lymphatic growth and PNI, which are easily confused with microvessels, LN or fibrosis on CT. This may have caused the unsatisfactory agreement between the two reviewers in assessing the CTPNI and CTLN in our study.
A nomogram combining the Rad-score, CTLN and CTPNI achieved the best performance (the AUC in the testing cohort was 0.778) for the preoperative assessment of PNI in patients with PDAC. Several possible reasons may contribute to the good performance of the nomogram. One is that the Rad-score combined with arterial and portal venous phases can provide valuable information. In addition, different CT scan parameters may lead to unsatisfactory reproducibility of radiomics features, which can be maximally alleviated by using resampling as a preprocessing method, which optimizes gray dispersion to maintain the stability of features[35]. Z score standardization eliminates the effect of different data dimensions. Moreover, the good performance of the nomogram was attributed to feature selection and modeling. Univariate analysis and LASSO regression confirmed that important features were selected for modeling. Tenfold validation was applied to guarantee the robustness of the model. Finally, the nomogram integrates selected radiomics features, the presence of PDAC on CT images and the experience of radiologists and combines the performance of different dimensions to better reflect the characteristics of PDAC. This result suggested that the nomogram has the potential to preoperatively predict PNI status in PDAC patients. The calibration curve revealed that the predicted PNI was in good agreement with the actual PNI probability. The decision curve indicated that the nomogram outperformed radiologists at any threshold probability.
This study has several limitations. First, this was a single-center study with a limited sample size and no external validation group. However, the number included in our study was relatively larger than that in previous studies. Therefore, the retrospective nature of the study may have led to biased results. Large sample, multicenter and prospective studies should be conducted to further verify the results. Moreover, although several studies have reported that PNI is associated with PDAC patient prognosis, the relationship between PNI and prognosis was not clarified in this study. Subsequently, the corresponding patients should be followed up on the basis of this study to explore the ability of the nomogram to predict survival. Ultimately, there was not a consistent one-to-one match between CT evaluation and pathology.
In conclusion, a nomogram based on the rad-score derived from both the arterial and portal venous phases of CECT combined with the CTLN and CTPNI may serve as a valuable noninvasive tool for the preoperative assessment of PNI in patients with PDAC. This approach offers a practical means to classify PDAC patients before surgery and enhance patient management.