Small-intestine adenocarcinoma is a rare tumor that has a very low incidence compared with colorectal cancer. The smallness of the available samples associated with this rarity restricts data analyses and the ability to draw generalized conclusions in studies of small-intestine adenocarcinoma, which means that the relevant prognosis factors are still controversial [16, 17]. Nomograms have been widely used in recent years for predicting individualized survival outcomes in cancer patients [18-22]. The rarity of small-intestine adenocarcinoma increases the practicality of using a brief nomogram to predict patient survival in clinical decision-making.
Prognostic factors closely associated with CSS in small-intestine adenocarcinoma were included in the construction of the present nomogram, which was used to predict the 1- and 3-year CSS for small-intestine adenocarcinoma. Compared with the AJCC staging system, the nomogram shows better predictive performance, with a C-index of 0.858. Furthermore, the ROC curve, NRI, and IDI also demonstrated that the nomogram showed better predictive ability than the AJCC staging system. Moreover, the calibration curves indicated that the predicted 3- and 5-year CSS rates for the training and validation cohorts were almost identical to the actual observations, especially for the 3-year CSS. Finally, the DCA curves showed that the nomogram exhibits better clinical usefulness for predicting survival compared to the AJCC staging system.
The proposed nomogram contains several independent prognostic factors—age at diagnosis, sex, marital status, insurance status, histology grade, AJCC TNM stage, surgery status, chemotherapy—that were selected by applying both forward and backward stepwise selection methods in a Cox regression model. We found that increasing age was associated with worse survival outcomes, which is consistent with previous findings [3]. Some studies have suggested that small-intestine adenocarcinoma is more prevalent in males than in females [23]. We similarly found that the proportion of male patients in our study cohort was higher than that of females (52.2% vs 47.7%), and that being female appeared to be a protective factor for the CSS of small-intestine adenocarcinoma. In addition, we included insurance status in our analysis, and found that Medicaid and uninsured patients had an increased risk of death compared to insured patients, this result is consistent with our previous findings[24]
Surgery remains the most commonly used treatment method for small-intestine adenocarcinoma [25, 26], and it has been shown that radiation can also play a role in improving survival outcomes in these patients [1, 27, 28]. However, our research did not find this association, the main reason being that the current data on radiotherapy in the SEER database have potential bias because many factors that influence the course of treatment are not captured in the registry data. In addition, our research showed that chemotherapy was associated with poor survival, which may be because chemotherapy is main treatment strategies for unresectable stage IV small bowel adenocarcinoma[29], and the worse survival is caused by advanced disease.
Our nomogram highlights the significant contribution of histology grade, which is consistent with previous studies showing that histology grade is an independent predictor of survival [7, 30, 31]. In addition, there was no definitive correlation between tumor differentiation and tumor size or lymph node metastasis, while the last one is an important component of the TNM staging system. Even two patients at the same TNM stage can exhibit different scores for CSS on our nomogram based on their degrees of tumor differentiation. This may also be the reason why the survival predictions of our nomogram are superior to using the AJCC staging system.
Besides the factors mentioned above, distant metastasis and increased tumor and lymph node metastasis are risk factors for survival in small-intestine adenocarcinoma, as found previously [7, 31-33]. Moreover, this study also showed that not being married is associated with a poor prognosis of small-intestine adenocarcinoma, which is consistent with the findings of our previous study[34].
This study was subject to several limitations. First, although 10 variables were involved, only 8 of them are included in the nomogram, and there are also many other variables such as comorbidities, chemotherapy drugs, and molecular factors not included in the SEER database that might affect patient survival. Second, although we randomly divided the patients into the training and validation cohorts (at a ratio of 7:3) to evaluate the nomogram both internally and externally, it remains necessary to assess the accuracy of the model based on external validation in other populations. Third, the SEER database is retrospective and we excluded patients with incomplete information, which may have led to selection bias. Finally, although the DCA demonstrated the superiority of our nomogram over the AJCC staging system with a greater net benefit, this analysis is not absolutely accurate and so should only be used as reference information in clinical decision-making.