Development of a web-based calculator to predict three-month mortality among patients with bone metastases from cancer of unknown primary: An internally and externally validated study using machine-learning techniques.

Background: Individualized therapeutic strategies can be carried out under the guidance of expected lifespan, hence survival prediction is important. Nonetheless, reliable survival estimation in individuals with bone metastases from cancer of unknown primary (CUP) is still scarce. The objective of the study is to construct a model as well as a web-based calculator to predict three-month mortality among bone metastasis patients with CUP using machine learning-based techniques. Methods: This study enrolled 1010 patients from a large oncological database, the Surveillance, Epidemiology, and End Results (SEER) database, in the United States between 2010 and 2018. The entire patient population was classified into two cohorts at random: a training cohort (n=600, 60%) and a validation cohort (410, 40%). Patients from the validation cohort were used to validate models after they had been developed using the four machine learning approaches of random forest, gradient boosting machine, decision tree, and eXGBoosting machine on patients from the training cohort. In addition, 101 patients from two large teaching hospital were served as an external validation cohort. To evaluate each model's ability to predict the outcome, prediction measures such as area under the receiver operating characteristic (AUROC) curves, accuracy, and Youden index were generated. The study's risk stratification was done using the best cut-off value. The Streamlit software was used to establish a web-based calculator. Results: The three-month mortality was 72.38% (731/1010) in the entire cohort. The multivariate analysis revealed that older age (P=0.031), lung metastasis (P=0.012), and liver metastasis (P=0.008) were risk contributors for three-month mortality, while radiation (P=0.002) and chemotherapy (P<0.001) were protective factors. The random forest model showed the highest area under curve (AUC) value (0.796, 95% CI: 0.746-0.847), the second-highest precision (0.876) and accuracy (0.778), and the highest Youden index (1.486), in comparison to the other three machine learning approaches. The AUC value was 0.748 (95% CI: 0.653-0.843) and the accuracy was 0.745, according to the external validation cohort. Based on the random forest model, a web calculator was established: https://starxueshu-codeok-main-8jv2ws.streamlitapp.com/. When compared to patients in the low-risk groups, patients in the high-risk groups had a 1.99 times higher chance of dying within three months in the internal validation cohort and a 2.37 times higher chance in the external validation cohort (Both P<0.001). Conclusions: The random forest model has promising performance with favorable discrimination and calibration. This study suggests a web-based calculator based on the random forest model to estimate the three-month mortality among bone metastases from CUP, and it may be a helpful tool to direct clinical decision-making, inform patients about their prognosis, and facilitate therapeutic communication between patients and physicians.