Evaluation of capability of ultrasound with elastometry and elastography for diagnosis of subclinical regional metastases of cancer of the oral mucosa

Objective. Evaluation of ultrasound capabilities for diagnosis of subclinical regional metastases of squamous cell carcinoma of the oral mucosa.

Introduction. Incidence of oral cancer in Russia is 3.86 per 100,000 population, and it’s increasing with the mean annual rate of 1.88 %. Head and neck cancer is characterized by high risk of metastases in regional lymph nodes which varies from 40 to 80 %. Lymph nodes status affects the treatment plan and appears to be the main predictive factor. Therefore, evaluation of the pathways of regional lymphatic outflow in oral mucosa cancer is of prime importance for disease prognosis and treatment selection. Ultrasound investigation (USI) is one of the main instrumental methods of regional lymph node investigation in oral mucosa cancer patients. Nevertheless, effectiveness of B-mode USI, elastometry and elastography for diagnosis of occult metastases of squamous cell carcinoma of the oral mucosa has not been investigated. There is no consensus on the threshold values of S-wave velocity and elastographic parameters in diagnosis of occult metastases.

Materials and methods. Patients with oral mucosa squamous cell carcinoma (stage cT1–3N0M0) were included in the study. All patients had morphologically verified diagnosis. At the first stage (outpatient) before inclusion into the study, all patients were evaluated by palpation and B-mode USI. If during USI metastases were suspected, FNAB was performed. Patients with cytologically confirmed metastases were not eligible for the study. During the clinical trial, 102 (82.3 %) patients underwent B-mode USI, and 22 (17.7 %) patients underwent USI with elastometry and elastography. USI results were compared with results of histological examination of cervical lymph nodes. Statistical evaluation of USI in different modes was performed.

Results. B-mode USI was characterized by 88.2 % specificity, 0 % sensitivity, 80.4 % accuracy, and 44.1 % efficacy. Positive predictive value (PPV) was estimated as 0 %, and negative predictive value (NPV) as 90.1 %. USI with elastography was characterized by 100 % specificity, 83.3 % sensitivity, 95.5 % accuracy, and 91.7 % efficacy. PPV was estimated as 100 %, and NPV as 94.1 %. Threshold value of elastometry for diagnosis of occult metastases was 2.42 m/s with 83.3 sensitivity, and 87.5 % specificity. Method was characterized by 86.4 % accuracy, 85.4 efficacy, 71.4 % PPV and 93.3 % NPV.

Conclusion. B-mode USI is characterized by low capability for diagnosis of subclinical regional metastases of squamous cell carcinoma of the oral mucosa. Elastometry and elastography offer a possibility to increase USI accuracy for diagnosis of subclinical regional metastases from 80 % to 86-95.5 % and efficacy from 44 % to 85–92 %.

1. Каприн А.Д., Старинский В.В., Петрова Г.В. Злокачественные новообразования в России в 2015 году (заболеваемость и смертность). М.: МНИОИ им. П.А. Герцена – филиал ФГБУ «НМИРЦ» Минздрава России, 2017. C. 17. [State of oncological care in Russia in 2015 (morbidity and mortality). Editors: A.D. Kaprin, V.V. Starinskiy, G.V. Petrova. Moscow: MNIOI imeni P.A. Hertzena – filial FGBU “NMIRC” Minzdrava Rossii, 2017. P. 17. (In Russ.)].

2. Матякин Е.Г., Подвязников С.О. Онкология: Справочник практического врача. Под ред. И.В. Поддубной. М.: МЕДпресс-информ, 2009. C. 162, 163. [Matyakin E.G., Podvyaznikov S.O. Oncology: Guidelines for practicing physicians. Ed. I.V. Poddubnaya. Moscow: MEDpress-inform, 2009. P. 162, 163. (In Russ.)].

3. Snow G.В., Patel P., Leemans C.R., Tiwari R. Management of cervical lymph nodes in patients with head and neck cancer. Eur Arch Otorhinolaryngol 1992;249(4):187–94. PMID: 1642874

4. Абузарова Г.Р., Алексеев Б.Я., Антипов В.А. и др. Онкология: клинические рекомендации. Под ред. В.И. Чиссова, С.Л. Дарьяловой. 2009. С. 154. [Abuzarova G.R., Alekseev B.Ya., Antipov V.A. et al. Oncology: Clinical guidelines. Eds. V.I. Chissov, S.L. Daryalova. 2009. P. 154. (In Russ.)].

5. Woolgar J.A., Triantafyllou A., Lewis J.S. Jr. et al. Prognostic biological features in neck dissection specimens. Eur Arch Otorhinolaryngol 2013;270:1581–92. DOI: 0.1007/s00405- 012-2170-9. PMID: 22983222

6. Jank S., Robatscher P., Emshoff R. et al. Norer: The diagnostic value of ultrasonography to detect occult lymph node involvement at different levels in patients with squamous cell carcinoma in the maxillofacial region. Int J Oral Maxillofac Surg 2003;32:39–42. DOI: 10.1054/ijom.2002.0326. PMID: 12653231

7. Eichhorn T., Schwerk W., Schroeder H.G. Hochauflosende Real-Time-Sonographie von Tumoren der Halsweichteile. Laryng Rhinol Otol 1985:64:506–12. [Article in German]. PMID: 3906321

8. Gritzmann N., Czembrik H., Hajek P. et al. Sonographie bei cervicalen Lymphknotenmetastasen. Radiologe 1987: 27:118–22. PMID: 3295982

9. Heppt W., Haels J., Lenarz T. et al. Detection and assessment of cervical lymph node metastases in head-neck tumors. A comparison of methods. Laringorhinootologie 1989: 68:327–32. DOI: 10.1055/s-2007-998346. PMID: 2662991

10. Alam F., Naito K., Horiguchi J., et al. Accuracy of sonographic elastography in the differential diagnosis of enlarged cervical lymph nodes: comparison with conventional B- mode sonography. AJR 2008; 191:604–10. DOI: 10.2214/AJR.07.3401. PMID: 18647939

11. Tan R., Xiao Y., He Q. Ultrasound elastography: Its potential role in assessment of cervical lymphadenopathy. Acad Radiol 2010;17:849–55. DOI: 10.1016/j.acra.2010.03.014. PMID: 20540909

12. Bhatia K.S., Cho C.C., Yuen Y.H. et al. Realtime qualitative ultrasound elastography of cervical lymph nodes in routine clinical practice: Interobserver agreement and correlation with malignancy. Ultrasound Med Biol 2010;36:1990–7. DOI: 10.14366/usg.15007.

13. Ishibashi N., Yamagata K., Sasaki H. et al. Real-time tissue elastography for the diagnosis of lymph node metastasis in oral squamous cell carcinoma. Ultrasound in Med & Biol 2012;38(3):389–95. DOI: 10.1016/j.ultrasmedbio.2011.12.004

14. Аллахвердиева Г.Ф., Синюкова Г.Т., Шолохов В.Н., Романов И.С. Возможности комплексного ультразвукового исследования в диагностике метастатического поражения лимфатических узлов шеи. Ультразвуковая и функциональная диагностика 2005;1:18–22. [Allakhverdieva G.F., Sinukova G.T., Sholokhov V.N., Romanov I.S. Complex ultrasound investigation opportunities in diagnostics of metastatic lesion of the neck lymph nodes. Ultrazvukovaya i funktsionalnaya diagnostika = Ultrasound and Functional Diagnostics 2005;1:18–22. (In Russ.)].

15. Friedrich-Rust M., Wunder K., Kriener S. et al. Liver fibrosis in viral hepatitis: Noninvasive assessment with acoustic radiation force impulse imaging versus transient elastography. Radiology 2009;252:595– 604. DOI: 10.1148/radiol.2523081928.

16. Shuang-Ming T., Ping Z., Ying Q. et al. Usefulness of acoustic radiation force impulse imaging in the differential diagnosis of benign and malignant liver lesions. Acad Radiol 2011;18:810–5. DOI: 10.1016/j.acra.2011.01.026. PMID: 21419668

17. Бердников С.Н., Шолохов В.Н., Патютко Ю.И., и др. Эластометрия и эластография в дифференциальной диагностике гиперэхогенных образований печени. Анналы хирургической гепатологии 2014;3:63–9. [Berdnikov S.N., Sholokhov V.N., Patutko Yu.I. et al. Elastometry and elastography in differential diagnosis of hyperechoic liver masses. Annaly khirurgicheskoy gepatologii = Annals of Surgical Hepatology 2014;3:63–9. (In Russ.)].

18. Tozaki M., Isobe S., Fukuma E. Preliminary study of ultrasonographic tissue quantification of the breast using the acoustic radiation force impulse (ARFI) technology. Eur J Radiol 2011;80:p182–7. DOI: 10.1016/j.ejrad.2011.05.020. PMID: 21788111

19. Zhai L., Polascik T.J., Foo W.C. et al. Acoustic radiation force impulse imaging of human prostates: Initial in vivo demonstration. Ultrasound Med Biol 2012;38:50–61. DOI: 10.1016/j.ultrasmedbio.2011.10.002. PMID: 22104533

20. Lyshchik A., Higashi T., Asato R. et al. Cervical lymph node metastases: diagnosis at sonoelastography: initial experience. Radiology 2007;243:258–67. DOI: 10.1148/radiol.2431052032. PMID: 17293571

21. Sumi M., Ohki M., Nakamura T. Comparison of sonography and CT for differentiating benign from malignant cervical lymph nodes in patients with squamous cell carcinoma of the head and neck. AJR Am J Roentgenol 2001;176(4):1019–24. DOI: 10.2214/ajr.176.4.1761019. PMID: 11264102

22. Teng D.K., Wang H., Lin Y.Q. et al. Value of ultrasound elastography in assessment of enlarged cervical lymph nodes. Asian Pac J Cancer Prev 2012;13:2081–5. PMID: 22901174

23. Choi Y.J., Lee J.H., Lim H.K. et al. Quantitative shear wave elastography in the evaluation of metastatic cervical lymph nodes. Ultrasound Med Biol 2013;39: 935–40.

24. DOI: 10.1016/j.ultrasmedbio.2012.12.009. PMID: 23453381

25. Fujiwara T., Tomokuni J., Iwanaga K. et al. Acoustic radiation force impulse imaging for reactive and malignant/metastatic cervical lymph nodes. Ultrasound in Med & Biol 2013;39(7):1178–83. DOI: 10.1016/j.ultrasmedbio.2013.02.001. PMID: 23562011

26. Gu J., Du L., Bai M., et al. Preliminary study on the diagnostic value of acoustic radiation force impulse technology for differentiating between benign and malignant thyroid nodules. J Ultrasound Med 2012;31:763–71. PMID: 22535724

27. Kishimoto R., Tachibana Y., Obata T. et al. Diagnostic potential of shear wave velocity measurement using acoustic radiation force impulse imaging for cervical lymph node metastasis. Poster # C-0368 Congress: ECR 2014. Available: http://posterng.netkey.at/esr/viewing/index.php?module=viewing_poster&doi=10.1594/ecr2014/C-0368. DOI: 10.1594/ecr2014/C-0368

28. Zhang Y.F., Xu H.X., He Y. et al. Virtual touch tissue quantification of acoustic radiation force impulse: a new ultrasound elastic imaging in the diagnosis of thyroid nodules. PLoS One 2012; 7: e49094. DOI: 10.1371/journal.pone.0049094. PMID: 23152855

29. Cheng K.L., Choi Y.J., Shim W.H. et al. Virtual touch tissue imaging quantification shear wave elastography: prospective assessment of cervical lymph nodes. Ultrasound Med Biol 2016;42:378–86. DOI: 10.1016/j.ultrasmedbio.2015.10.003. PMID: 26553206