Analysis of prognostic factors and construction of a nomogram for patients with brain metastases from cancer of unknown primary based on the SEER database

Discover Oncology https://doi.org/10.1007/s12672-026-05332-2 Article in Press Analysis of prognostic factors and construction of a nomogram for patients with brain metastases from cancer of unknown primary based on the SEER database Xiaolu Ma, Chuanxia Zhang, Xiaoxi Wan, Heng Lu, Mengyuan Kang, Qianhao Meng & Guangru Xu Received: 4 December 2025 Accepted: 27 May 2026 Cite this article as: Ma X., Zhang C., Wan X. et al. Analysis of prognostic factors and construction of a nomogram for patients with brain metastases from cancer of unknown primary based on the SEER database. Discov Onc (2026). https://doi.org/10.1007/ s12672-026-05332-2 A E R P S S We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply. 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To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. ACCEPTED ARTICLEMANUSCRIPT IN PRESS Analysis of Prognostic Factors and Construction of a Nomogram for Patients with Brain Metastases from Cancer of Unknown Primary Based on the SEER Database Xiaolu Ma1, Chuanxia Zhang1, Xiaoxi Wan1, Heng Lu1, Mengyuan Kang1, Qianhao Meng1, Guangru Xu1* 1 Department of Oncology, Shanghai Pudong New Area People's Hospital, Shanghai, China, 201299 *Corresponding author Dr. Guangru Xu, Department of Oncology, Shanghai Pudong New Area People's Hospital, Shanghai, China, 201299 E-mail: ORCID E L C I T R A IN S S E R P Xiaolu Ma https://orcid.org/0000-0001-9514-6042 E-mail Addresses: Xiaolu Ma: Chuanxia Zhang: Xiaoxi Wan: Heng Lu: Mengyuan Kang: Qianhao Meng: Guangru Xu: Author Contributions: M.X. and X.G. conceived and designed the study. M.X., K.M., M.Q., and W.X. ACCEPTED ARTICLEMANUSCRIPT IN PRESS collected the data. M.X., Z.C., and L.H. performed data analysis. M.X. drafted the initial manuscript. All authors (M.X., Z.C., W.X., L.H., K.M., M.Q., and X.G.) participated in critical revision of the manuscript, approved the final version, and are accountable for all aspects of the work. Declarations: Ethics Approval The study was conducted in accordance with the principles of the Declaration of Helsinki. Access was permitted by SEER to the database, which is available for public use. Therefore, individual consent was not required for this S S E R P retrospective analysis, and ethics approval was waived. Consent to participate IN The data was obtained from the SEER database. Informed consent was not E L C I T R A required as the data is de-identified and publicly available. Consent to publish Not applicable. This manuscript does not contain any individual person's data in any form. All data presented are aggregated and anonymized. Funding Information: This study was supported by the Setting Sail Program of Shanghai Pudong New Area People's Hospital (PRYQH202404). Acknowledgments: All the authors thank the support and assistance provided by Shanghai Pudong New Area People's Hospital. Disclosure: ACCEPTED ARTICLEMANUSCRIPT IN PRESS The authors report no conflicts of interest in this work. Data Availability Statement: Data supporting the findings of the study could be acquired from the corresponding author by reasonable request. Clinical Trial Number: Not applicable. Abbreviations: CUP-BM, cancer of unknown primary with brain metastases; SEER, the Surveillance, Epidemiology, and End Results; OS, overall survival; HR, hazard S S E R P ratio; CI, confidence interval; ACC, adenocarcinoma; SCC, squamous cell carcinoma; NEC, neuroendocrine carcinoma; NOS, carcinoma not otherwise IN specified; C-index, concordance index; ROC, receiver operating characteristic E L C I T R A curve; DCA, decision curve analysis; AUC, area under the ROC curve; WBRT, whole-brain radiotherapy; ctDNA, circulating tumor DNA; CTC, circulating tumor cell; TCR, T-cell receptor. Abstract: Objective: Cancer of unknown primary with brain metastases (CUP-BM) represents a distinct and challenging disease entity characterized by an extremely poor prognosis. Currently, there is a lack of systematic research on its prognostic factors. This study aimed to analyze the prognostic factors associated with CUP-BM. Methods: Patients diagnosed with CUP-BM between 2010 and 2022 were identified from the SEER database. Kaplan-Meier survival curves were utilized ACCEPTED ARTICLEMANUSCRIPT IN PRESS to analyze survival differences among various histological subtypes. Univariate and multivariate Cox proportional hazards regression analyses were employed to identify prognostic factors and construct a prognostic nomogram model. Subgroup analysis was conducted to assess the robustness of age as a prognostic factor and explore potential interaction effects with other variables. Results: A total of 700 eligible CUP-BM patients were included. The neuroendocrine subtype demonstrated the most favorable prognosis. Multivariate analysis revealed that histological type, chemotherapy, liver S S E R P metastasis, lung metastasis, bone metastasis, and age were independent prognostic factors for overall survival (OS). The constructed nomogram IN exhibited satisfactory predictive performance (bias-corrected C-index = E L C I T R A 0.663). Subgroup analysis showed that age remained a significant prognostic factor in most clinical strata, although its effect varied across subgroups defined by metastatic burden and histological subtype. Conclusion: Neuroendocrine histology and chemotherapy were associated with improved survival, while adenocarcinoma histology, age greater than 60 years, and the presence of liver, lung, or bone metastasis were identified as poor prognostic factors for CUP-BM. The nomogram exhibited good calibration and discrimination capability for prognostic prediction (...truncated)