Development of a Machine Learning Model for Nasopharyngeal Carcinoma Screening Based on Tongue Imaging

Nasopharyngeal Carcinoma Clinical Trial

Official title:

Development of a Machine Learning Model for Nasopharyngeal Carcinoma Screening Based on Tongue Imaging: a Prospective Multicenter Cross-sectional Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06129201
• Other study ID #: ZDWY.ZYZLK.006
• Status: Not yet recruiting
• Start date: November 15, 2023
• Est. completion date: December 1, 2025

Study information

• Verified date: November 2023
• Source: Fifth Affiliated Hospital, Sun Yat-Sen University
• Contact: Yulong Zhang, Doctor
• Phone: 18810550602
• Email: zhongxiyi1101[@]163.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Nasopharyngeal cancer is common in China, Southeast Asia, and North Africa, and is usually associated with Epstein-Barr virus (EBV) infection. Using EBV specific antibodies or EBV DNA screening can increase the proportion of patients diagnosed with early nasopharyngeal carcinoma from approximately 20% to over 70%. However, the application of nasopharyngeal carcinoma screening in clinical practice is hindered by low positive predictive values, even in areas where the EB virus is prevalent in China, the positive predictive value is only 4.8%. Therefore, there is an urgent need to identify new biomarkers or strategies with high sensitivity and positive predictive value for nasopharyngeal carcinoma screening. A study published in the Lancet sub journal 《eClinicalMedicine》 in 2023 showed that a tongue image model based on machine learning can serve as a stable diagnostic method for gastric cancer (AUC=0.89), and has been clinically validated in multiple centers. This study inspires researchers to introduce artificial intelligence machine learning technology into the diagnosis and treatment of nasopharyngeal cancer. In summary, this plan explores the establishment of tongue image machine learning models in nasopharyngeal carcinoma patients to help improve the positive predictive value of nasopharyngeal carcinoma screening.

Description:

Nasopharyngeal cancer is common in China, Southeast Asia, and North Africa, and is generally associated with Epstein-Barr virus (EBV) infection. Using EBV specific antibodies or EBV DNA screening can increase the proportion of patients diagnosed with early nasopharyngeal carcinoma from approximately 20% to over 70%. In previous studies, researchers found that participants who underwent screening were more likely to achieve long-term survival after being diagnosed with nasopharyngeal carcinoma compared to the control group, and the risk of nasopharyngeal carcinoma specific death was lower among screened patients (relative risk 0.22). However, the application of nasopharyngeal carcinoma screening in clinical practice is hindered by low positive predictive values, even in areas where the EB virus is prevalent in China, the positive predictive value is only 4.8%. More than 95% of high-risk participants identified through primary serological screening underwent unnecessary and time-consuming clinical examinations and follow-up. The combination of various biomarkers, multi-step screening, and identification of new biomarkers are used to improve the performance of nasopharyngeal cancer screening strategies. However, the progress achieved so far is still unsatisfactory, characterized by low sensitivity, complex operation, or high cost. Therefore, there is an urgent need to identify new biomarkers or strategies with high sensitivity and positive predictive value for nasopharyngeal carcinoma screening. In 《The New England Journal of Medicine》 in 2023, Professor Xia Ningshao's team reported on the identification and validation of anti BNLF2 total antibody (P85Ab) as a new serological biomarker for nasopharyngeal cancer screening.The sensitivity of P85-Ab nasopharyngeal carcinoma is 97.9%, with a positive predictive value of 10.0%. Furthermore, on the basis of P85-Ab positivity, if further detection of EB double antibodies (EBV nuclear antigen 1 [EBNA1]-IgA and EBV-specific viral capsid antigen [VCA]-IgA) is carried out, intermediate or medium high risk individuals with EB double antibodies can undergo nasopharyngoscopy examination, which can increase the positive predictive value of nasopharyngeal carcinoma screening to 29.6% -44.6%, that is, for every 2-3 nasopharyngoscopes performed, one case of nasopharyngeal carcinoma can be diagnosed. The sensitivity of this study is very high, but the positive predictive value is only 10%. Even when combined with traditional EB dual antibody monitoring and nasal endoscopy, one-third to one-half of non nasopharyngeal carcinoma patients still undergo unnecessary and time-consuming clinical examinations. Therefore, it is still necessary to explore simple and cost-effective methods to improve the strategy of positive predictive value for nasopharyngeal carcinoma screening. A study published in the Lancet sub journal 《eClinicalMedicine》 in 2023 showed that a tongue image model based on machine learning can serve as a stable diagnostic method for gastric cancer (AUC=0.89), and has been clinically validated in multiple centers. This study inspires researchers to introduce artificial intelligence machine learning technology into the diagnosis and treatment of nasopharyngeal cancer. In summary, this plan explores the establishment of tongue image machine learning models in nasopharyngeal carcinoma patients to help improve the positive predictive value of nasopharyngeal carcinoma screening.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 5000
• Est. completion date: December 1, 2025
• Est. primary completion date: November 15, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Cancer patients confirmed by histology/cytology
• Patients with nasopharyngeal carcinoma in the training group are initially diagnosed
• Subjects voluntarily participate in the study

Exclusion Criteria:

• Subjects taking medication or diet may affect their tongue image (such as aluminum magnesium carbonate, traditional Chinese medicine rhubarb, etc.)
• The researchers determined that the subjects had other factors that could force them to terminate the study.

Related Conditions & MeSH terms

• Carcinoma
• Nasopharyngeal Carcinoma

Intervention

Other:
• Tongue image
Using intelligent imaging devices to collect subject tongue images

Locations

Country	Name	City	State
China	The Fifth Affiliated Hospital of Sun Yat sen University	Zhuhai

Sponsors (1)

Lead Sponsor	Collaborator
Fifth Affiliated Hospital, Sun Yat-Sen University

Country where clinical trial is conducted

China, 

References & Publications (16)

Chan KCA, Woo JKS, King A, Zee BCY, Lam WKJ, Chan SL, Chu SWI, Mak C, Tse IOL, Leung SYM, Chan G, Hui EP, Ma BBY, Chiu RWK, Leung SF, van Hasselt AC, Chan ATC, Lo YMD. Analysis of Plasma Epstein-Barr Virus DNA to Screen for Nasopharyngeal Cancer. N Engl J Med. 2017 Aug 10;377(6):513-522. doi: 10.1056/NEJMoa1701717. Erratum In: N Engl J Med. 2018 Mar 8;378(10 ):973. — View Citation

Chen GH, Liu Z, Yu KJ, Coghill AE, Chen XX, Xie SH, Lin DF, Huang QH, Lu YQ, Ling W, Lin CY, Lu ZJ, Fan YY, Tang LQ, Sampson JN, Li H, King AD, Middeldorp JM, Hildesheim A, Cao SM. Utility of Epstein-Barr Virus DNA in Nasopharynx Swabs as a Reflex Test to Triage Seropositive Individuals in Nasopharyngeal Carcinoma Screening Programs. Clin Chem. 2022 Jul 3;68(7):953-962. doi: 10.1093/clinchem/hvac032. — View Citation

Chen YP, Chan ATC, Le QT, Blanchard P, Sun Y, Ma J. Nasopharyngeal carcinoma. Lancet. 2019 Jul 6;394(10192):64-80. doi: 10.1016/S0140-6736(19)30956-0. Epub 2019 Jun 6. — View Citation

Coghill AE, Pfeiffer RM, Proietti C, Hsu WL, Chien YC, Lekieffre L, Krause L, Teng A, Pablo J, Yu KJ, Lou PJ, Wang CP, Liu Z, Chen CJ, Middeldorp J, Mulvenna J, Bethony J, Hildesheim A, Doolan DL. Identification of a Novel, EBV-Based Antibody Risk Stratification Signature for Early Detection of Nasopharyngeal Carcinoma in Taiwan. Clin Cancer Res. 2018 Mar 15;24(6):1305-1314. doi: 10.1158/1078-0432.CCR-17-1929. Epub 2018 Jan 4. Erratum In: Clin Cancer Res. 2020 Jul 1;26(13):3496. — View Citation

He YQ, Wang TM, Ji M, Mai ZM, Tang M, Wang R, Zhou Y, Zheng Y, Xiao R, Yang D, Wu Z, Deng C, Zhang J, Xue W, Dong S, Zhan J, Cai Y, Li F, Wu B, Liao Y, Zhou T, Zheng M, Jia Y, Li D, Cao L, Yuan L, Zhang W, Luo L, Tong X, Wu Y, Li X, Zhang P, Zheng X, Zhang S, Hu Y, Qin W, Deng B, Liang X, Fan P, Feng Y, Song J, Xie SH, Chang ET, Zhang Z, Huang G, Xu M, Feng L, Jin G, Bei J, Cao S, Liu Q, Kozlakidis Z, Mai H, Sun Y, Ma J, Hu Z, Liu J, Lung ML, Adami HO, Shen H, Ye W, Lam TH, Zeng YX, Jia WH. A polygenic risk score for nasopharyngeal carcinoma shows potential for risk stratification and personalized screening. Nat Commun. 2022 Apr 12;13(1):1966. doi: 10.1038/s41467-022-29570-4. — View Citation

Ji MF, Sheng W, Cheng WM, Ng MH, Wu BH, Yu X, Wei KR, Li FG, Lian SF, Wang PP, Quan W, Deng L, Li XH, Liu XD, Xie YL, Huang SJ, Ge SX, Huang SL, Liang XJ, He SM, Huang HW, Xia SL, Ng PS, Chen HL, Xie SH, Liu Q, Hong MH, Ma J, Yuan Y, Xia NS, Zhang J, Cao SM. Incidence and mortality of nasopharyngeal carcinoma: interim analysis of a cluster randomized controlled screening trial (PRO-NPC-001) in southern China. Ann Oncol. 2019 Oct 1;30(10):1630-1637. doi: 10.1093/annonc/mdz231. — View Citation

Lam WKJ, Jiang P, Chan KCA, Cheng SH, Zhang H, Peng W, Tse OYO, Tong YK, Gai W, Zee BCY, Ma BBY, Hui EP, Chan ATC, Woo JKS, Chiu RWK, Lo YMD. Sequencing-based counting and size profiling of plasma Epstein-Barr virus DNA enhance population screening of nasopharyngeal carcinoma. Proc Natl Acad Sci U S A. 2018 May 29;115(22):E5115-E5124. doi: 10.1073/pnas.1804184115. Epub 2018 May 14. — View Citation

Lam WKJ, Jiang P, Chan KCA, Peng W, Shang H, Heung MMS, Cheng SH, Zhang H, Tse OYO, Raghupathy R, Ma BBY, Hui EP, Chan ATC, Woo JKS, Chiu RWK, Lo YMD. Methylation analysis of plasma DNA informs etiologies of Epstein-Barr virus-associated diseases. Nat Commun. 2019 Jul 22;10(1):3256. doi: 10.1038/s41467-019-11226-5. — View Citation

Li T, Li F, Guo X, Hong C, Yu X, Wu B, Lian S, Song L, Tang J, Wen S, Gao K, Hao M, Cheng W, Su Y, Zhang S, Huang S, Fang M, Wang Y, Ng MH, Chen H, Luo W, Ge S, Zhang J, Xia N, Ji M. Anti-Epstein-Barr Virus BNLF2b for Mass Screening for Nasopharyngeal Cancer. N Engl J Med. 2023 Aug 31;389(9):808-819. doi: 10.1056/NEJMoa2301496. — View Citation

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Miller JA, Le QT, Pinsky BA, Wang H. Cost-Effectiveness of Nasopharyngeal Carcinoma Screening With Epstein-Barr Virus Polymerase Chain Reaction or Serology in High-Incidence Populations Worldwide. J Natl Cancer Inst. 2021 Jul 1;113(7):852-862. doi: 10.1093/jnci/djaa198. — View Citation

Simon J, Liu Z, Brenner N, Yu KJ, Hsu WL, Wang CP, Chien YC, Coghill AE, Chen CJ, Butt J, Proietti C, Doolan DL, Hildesheim A, Waterboer T. Validation of an Epstein-Barr Virus Antibody Risk Stratification Signature for Nasopharyngeal Carcinoma by Use of Multiplex Serology. J Clin Microbiol. 2020 Apr 23;58(5):e00077-20. doi: 10.1128/JCM.00077-20. Print 2020 Apr 23. — View Citation

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Yuan L, Yang L, Zhang S, Xu Z, Qin J, Shi Y, Yu P, Wang Y, Bao Z, Xia Y, Sun J, He W, Chen T, Chen X, Hu C, Zhang Y, Dong C, Zhao P, Wang Y, Jiang N, Lv B, Xue Y, Jiao B, Gao H, Chai K, Li J, Wang H, Wang X, Guan X, Liu X, Zhao G, Zheng Z, Yan J, Yu H, Chen L, Ye Z, You H, Bao Y, Cheng X, Zhao P, Wang L, Zeng W, Tian Y, Chen M, You Y, Yuan G, Ruan H, Gao X, Xu J, Xu H, Du L, Zhang S, Fu H, Cheng X. Development of a tongue image-based machine learning tool for the diagnosis of gastric cancer: a prospective multicentre clinical cohort study. EClinicalMedicine. 2023 Feb 6;57:101834. doi: 10.1016/j.eclinm.2023.101834. eCollection 2023 Mar. — View Citation

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* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under Curve (AUC) of Diagnostic Model	Determine the screening effectiveness of the nasopharyngeal carcinoma tongue image model	12 months