Risk Factor Analysis and Nomogram Development and Verification for Medullary Carcinoma of the Colon Using SEER Database

Overview

Journal Sci Rep

Specialty Science

Date 2024 May 19

PMID 38763982

Authors

Lu Yang

Lei Yu

Qiang Zhou

Li Liu

Na Shen

Na Li

Affiliations

Soon will be listed here.

Abstract

Medullary Carcinoma of the Colon (MCC) is a rare histological subtype of colon cancer, and there is currently no recognized optimal treatment plan for it, with its prognosis remaining unclear. The aim of this study is to analyze the independent prognostic factors for MCC patients and develop and validate nomograms to predict overall survival (OS). A total of 760 patients newly diagnosed with MCC from 2004 to 2020 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. All patients were randomly allocated to a training group and a validation group in a 7:3 ratio. Univariate and multivariable Cox regression analyses were conducted to identify prognostic factors and construct nomograms. The nomogram prediction model was evaluated and validated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). The study found that elderly women are more susceptible to MCC, and the ascending colon and cecum are the most common sites of involvement. MCC is poorly differentiated, with stages II and III being the most common. Surgery is the primary treatment for MCC. The prognosis for patients with stage IV MCC is poor, with a median survival time of only 10 months. Independent prognostic factors for MCC include age, N stage, M stage, surgery, chemotherapy, and tumor size. Among them, age < 75 years and completion of chemotherapy were protective factors for colon medullary carcinoma, while N2 (HR = 2.18, 95%CI 1.40-3.38), M1 (HR = 3.31, 95%CI 2.01-5.46), no surgery (HR = 27.94, 95%CI 3.69-211.75), and tumor diameter > 7 cm (HR = 1.66, 95%CI 1.20-2.30) were risk factors for colon medullary carcinoma. The results of ROC, AUC, calibration curves, and DCA demonstrate that the nomogram prediction model exhibits good predictive performance. We have updated the demographic characteristics of colon medullary carcinoma and identified age, N staging, M staging, surgery, chemotherapy and tumor size as independent prognostic factors for colon medullary carcinoma. Additionally, we have established nomograms for prognostic prediction. These nomograms can provide personalized predictions and serve as valuable references for clinical decision-making.

References

Arai T, Esaki Y, Sawabe M, Honma N, Nakamura K, Takubo K . Hypermethylation of the hMLH1 promoter with absent hMLH1 expression in medullary-type poorly differentiated colorectal adenocarcinoma in the elderly. Mod Pathol. 2003; 17(2):172-9. DOI: 10.1038/modpathol.3800018. View

Nagtegaal I, Odze R, Klimstra D, Paradis V, Rugge M, Schirmacher P . The 2019 WHO classification of tumours of the digestive system. Histopathology. 2019; 76(2):182-188. PMC: 7003895. DOI: 10.1111/his.13975. View

Gomez-Alvarez M, Lino-Silva L, Salcedo-Hernandez R, Padilla-Rosciano A, Ruiz-Garcia E, Lopez-Basave H . Medullary colonic carcinoma with microsatellite instability has lower survival compared with conventional colonic adenocarcinoma with microsatellite instability. Prz Gastroenterol. 2017; 12(3):208-214. PMC: 5672702. DOI: 10.5114/pg.2016.64740. View

Jessurun J, Manivel J . Medullary adenocarcinoma of the colon: clinicopathologic study of 11 cases. Hum Pathol. 1999; 30(7):843-8. DOI: 10.1016/s0046-8177(99)90146-6. View

Lanza G, Gafa R, Matteuzzi M, Santini A . Medullary-type poorly differentiated adenocarcinoma of the large bowel: a distinct clinicopathologic entity characterized by microsatellite instability and improved survival. J Clin Oncol. 1999; 17(8):2429-38. DOI: 10.1200/JCO.1999.17.8.2429. View

Gonzalez H, Sidhu S, Eisner T . A Rare Case of Medullary Carcinoma of the Ileum. Cureus. 2019; 10(12):e3721. PMC: 6428359. DOI: 10.7759/cureus.3721. View

Gupta A, Protyniak B, Dove J, Chu K, Erchinger T, Bannon J . A Comparison of Treatments and Outcomes for Medullary versus Nonmedullary Colon Cancer: A Single Institutional Experience Showing a Worse Prognosis for Stage 3 Disease. Surg Res Pract. 2020; 2020:5783729. PMC: 7142354. DOI: 10.1155/2020/5783729. View

Jabbal I, Nagarajan A, Rivera C, Yaghi M, Liang H, Nahleh Z . Medullary carcinoma of the colon: A comprehensive analysis of the National Cancer Database. Surg Oncol. 2022; 45:101856. DOI: 10.1016/j.suronc.2022.101856. View

Fane M, Weeraratna A . How the ageing microenvironment influences tumour progression. Nat Rev Cancer. 2019; 20(2):89-106. PMC: 7377404. DOI: 10.1038/s41568-019-0222-9. View

10.

Al-Ishaq F, Al-Dhaheri M, Toffaha A, Awad S, Rizvi S, Abunada M . Colonic medullary carcinoma: an exceedingly rare type of colorectal malignancy: a case report and review of the literature. J Med Case Rep. 2023; 17(1):434. PMC: 10583308. DOI: 10.1186/s13256-023-04160-0. View

11.

Hinoi T, Tani M, Lucas P, Caca K, Dunn R, Macri E . Loss of CDX2 expression and microsatellite instability are prominent features of large cell minimally differentiated carcinomas of the colon. Am J Pathol. 2001; 159(6):2239-48. PMC: 1850596. DOI: 10.1016/S0002-9440(10)63074-X. View

12.

Liu L, Kaur S, Dayyani F, Cho M, Ran-Castillo D, Chong E . Medullary carcinoma of the duodenum treated with pembrolizumab: a case report. J Gastrointest Oncol. 2023; 14(2):1149-1154. PMC: 10186505. DOI: 10.21037/jgo-22-755. View

13.

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View

14.

Friedman K, Brodsky A, Lu S, Wood S, Gill A, Lombardo K . Medullary carcinoma of the colon: a distinct morphology reveals a distinctive immunoregulatory microenvironment. Mod Pathol. 2016; 29(5):528-41. DOI: 10.1038/modpathol.2016.54. View

15.

DECOSSE J, Ngoi S, Jacobson J, Cennerazzo W . Gender and colorectal cancer. Eur J Cancer Prev. 1993; 2(2):105-15. DOI: 10.1097/00008469-199303000-00003. View

16.

Fiehn A, Grauslund M, Glenthoj A, Melchior L, Vainer B, Willemoe G . Medullary carcinoma of the colon: can the undifferentiated be differentiated?. Virchows Arch. 2014; 466(1):13-20. DOI: 10.1007/s00428-014-1675-6. View

17.

Thirunavukarasu P, Sathaiah M, Singla S, Sukumar S, Karunamurthy A, Pragatheeshwar K . Medullary carcinoma of the large intestine: a population based analysis. Int J Oncol. 2010; 37(4):901-7. PMC: 4127912. DOI: 10.3892/ijo_00000741. View

18.

Peycru T, Jarry J, Soubeyran I . Sporadic medullary carcinoma of the ileum. Clin Gastroenterol Hepatol. 2011; 9(8):A24. DOI: 10.1016/j.cgh.2011.03.006. View

19.

Cunningham J, Kantekure K, Saif M . Medullary carcinoma of the colon: a case series and review of the literature. In Vivo. 2014; 28(3):311-4. View

20.

Lee L, Yantiss R, Sadot E, Ren B, Calvacanti M, Hechtman J . Diagnosing colorectal medullary carcinoma: interobserver variability and clinicopathological implications. Hum Pathol. 2016; 62:74-82. PMC: 5392420. DOI: 10.1016/j.humpath.2016.12.013. View