Abstract
Purpose
Oral cavity squamous cell carcinoma (OCC) can spread to the neck without apparent lymphadenopathy. Pretreatment detection or prediction of occult metastasis might contribute to proper management of clinically node-negative (cN0) OCC. We examined the role of tumour quantitative 18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) measurements for predicting OCC occult metastasis and survival.
Methods
This study included 130 cN0 OCC patients who underwent 18F-FDG PET/CT scanning and subsequent curative surgery and neck dissection. Maximum, peak, and mean standardized uptake value (SUVmax, SUVpeak, and SUVmean), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were measured on pretreatment 18F-FDG PET/CT. Binary logistic regression was used to identify factors predicting occult cervical metastasis. Univariate and multivariate Cox proportional hazard regression were used to find factors associated with overall survival (OS).
Results
Pathological cervical metastasis (pN +) was found in 29 (22.3%) patients. Age, tumour differentiation, lymphovascular invasion, and T classification were significantly associated with pN + (all P < 0.05). After adjustment for these factors, MTV and TLG independently predicted pN + (P < 0.05). Invasion depth, lymphovascular invasion, T and N classifications, and overall TNM stage were significantly associated with OS. After adjustment for these factors, SUVmax and TLG independently predicted OS (all P < 0.05). Patients with TLG > 9.3 g had a 5.7-fold increased risk of overall mortality.
Conclusions
Tumour 18F-FDG PET/CT parameters might predict occult metastasis and survival in cN0 OCC patients.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abd El-Hafez YG, Moustafa HM, Khalil HF, Liao CT, Yen TC (2013) Total lesion glycolysis: a possible new prognostic parameter in oral cavity squamous cell carcinoma. Oral Oncol 49(3):261–268. https://doi.org/10.1016/j.oraloncology.2012.09.005
Abgral R, Keromnes N, Robin P, Le Roux PY, Bourhis D, Palard X, Rousset J, Valette G, Marianowski R, Salaun PY (2014) Prognostic value of volumetric parameters measured by 18F-FDG PET/CT in patients with head and neck squamous cell carcinoma. Eur J Nucl Med Mol Imaging 41(4):659–667. https://doi.org/10.1007/s00259-013-2618-1
Boellaard R, O'Doherty MJ, Weber WA, Mottaghy FM, Lonsdale MN, Stroobants SG, Oyen WJ, Kotzerke J, Hoekstra OS, Pruim J, Marsden PK, Tatsch K, Hoekstra CJ, Visser EP, Arends B, Verzijlbergen FJ, Zijlstra JM, Comans EF, Lammertsma AA, Paans AM, Willemsen AT, Beyer T, Bockisch A, Schaefer-Prokop C, Delbeke D, Baum RP, Chiti A, Krause BJ (2010) FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0. Eur J Nucl Med Mol Imaging 37(1):181–200. https://doi.org/10.1007/s00259-009-1297-4
Chong A, Ha JM, Han YH, Kong E, Choi Y, Hong KH, Park JH, Kim SH, Park JM (2017) Preoperative lymph node staging by FDG PET/CT with contrast enhancement for thyroid cancer: a multicenter study and comparison with neck CT. Clin Exp Otorhinolaryngol 10(1):121–128. https://doi.org/10.21053/ceo.2015.01424
Chung MK, Jeong HS, Son YI, So YK, Park GY, Choi JY, Hyun SH, Kim HJ, Ko YH, Baek CH (2009) Metabolic tumor volumes by [18F]-fluorodeoxyglucose PET/CT correlate with occult metastasis in oral squamous cell carcinoma of the tongue. Ann Surg Oncol 16(11):3111–3117. https://doi.org/10.1245/s10434-009-0621-3
D'Cruz AK, Vaish R, Kapre N, Dandekar M, Gupta S, Hawaldar R, Agarwal JP, Pantvaidya G, Chaukar D, Deshmukh A, Kane S, Arya S, Ghosh-Laskar S, Chaturvedi P, Pai P, Nair S, Nair D, Badwe R (2015) Elective versus therapeutic neck dissection in node-negative oral cancer. N Engl J Med 373(6):521–529. https://doi.org/10.1056/NEJMoa1506007
Denaro N, Merlano MC, Russi EG (2016) Follow-up in head and neck cancer: do more does it mean do better? A systematic review and our proposal based on our experience. Clin Exp Otorhinolaryngol 9(4):287–297. https://doi.org/10.21053/ceo.2015.00976
Dibble EH, Alvarez AC, Truong MT, Mercier G, Cook EF, Subramaniam RM (2012) 18F-FDG metabolic tumor volume and total glycolytic activity of oral cavity and oropharyngeal squamous cell cancer: adding value to clinical staging. J Nucl Med 53(5):709–715. https://doi.org/10.2967/jnumed.111.099531
Dik EA, Willems SM, Ipenburg NA, Rosenberg AJ, Van Cann EM, van Es RJ (2016) Watchful waiting of the neck in early stage oral cancer is unfavourable for patients with occult nodal disease. Int J Oral Maxillofac Surg 45(8):945–950. https://doi.org/10.1016/j.ijom.2016.03.007
Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A (2010) Oral cavity cancer in AJCC cancer staging manual. Springer_Verlag, New York, pp 29–40
Evangelista L, Cervino AR, Chondrogiannis S, Marzola MC, Maffione AM, Colletti PM, Muzzio PC, Rubello D (2014) Comparison between anatomical cross-sectional imaging and 18F-FDG PET/CT in the staging, restaging, treatment response, and long-term surveillance of squamous cell head and neck cancer: a systematic literature overview. Nucl Med Commun 35(2):123–134. https://doi.org/10.1097/mnm.0000000000000022
Farmer RW, McCall L, Civantos FJ, Myers JN, Yarbrough WG, Murphy B, O'Leary M, Zitsch R, Siegel BA (2015) Lymphatic drainage patterns in oral squamous cell carcinoma: findings of the ACOSOG Z0360 (Alliance) study. Otolaryngol Head Neck Surg 152(4):673–677. https://doi.org/10.1177/0194599815572585
Fukano H, Matsuura H, Hasegawa Y, Nakamura S (1997) Depth of invasion as a predictive factor for cervical lymph node metastasis in tongue carcinoma. Head Neck 19(3):205–210
Goerkem M, Braun J, Stoeckli SJ (2010) Evaluation of clinical and histomorphological parameters as potential predictors of occult metastases in sentinel lymph nodes of early squamous cell carcinoma of the oral cavity. Ann Surg Oncol 17(2):527–535. https://doi.org/10.1245/s10434-009-0755-3
Hegde P, Roy S, Shetty T, Prasad BR, Shetty U (2017) Tumor infiltration depth as a prognostic parameter for nodal metastasis in oral squamous cell carcinoma. Int J Appl Basic Med Res 7(4):252–257. https://doi.org/10.4103/ijabmr.IJABMR_66_17
Ho AS, Kim S, Tighiouart M, Gudino C, Mita A, Scher KS, Laury A, Prasad R, Shiao SL, Van Eyk JE, Zumsteg ZS (2017) Metastatic lymph node burden and survival in oral cavity cancer. J Clin Oncol 35(31):3601–3609. https://doi.org/10.1200/jco.2016.71.1176
Hofele C, Freier K, Thiele OC, Haberkorn U, Buchmann I (2009) High 2-[18F]fluoro-2-deoxy-d-glucose (18FDG) uptake measured by positron emission tomography is associated with reduced overall survival in patients with oral squamous cell carcinoma. Oral Oncol 45(11):963–967. https://doi.org/10.1016/j.oraloncology.2009.06.008
Joo YH, Koo BS (2019) Evolving strategy for surgical management of oral cancer: present and future. Clin Exp Otorhinolaryngol 12(2):101–102. https://doi.org/10.21053/ceo.2019.00164
Joo YH, Cho JK, Koo BS, Kwon M, Kwon SK, Kwon SY, Kim MS, Kim JK, Kim H, Nam I, Roh JL, Park YM, Park IS, Park JJ, Shin SC, Ahn SH, Won S, Ryu CH, Yoon TM, Lee G, Lee DY, Lee MC, Lee JK, Lee JC, Lim JY, Chang JW, Jang JY, Chung MK, Jung YS, Cho JG, Choi YS, Choi JS, Lee GH, Chung PS (2019) Guidelines for the surgical management of oral cancer: Korean Society of Thyroid-Head and Neck Surgery. Clin Exp Otorhinolaryngol 12(2):107–144. https://doi.org/10.21053/ceo.2018.01816
Kim DH, Song BI, Hong CM, Jeong SY, Lee SW, Lee J, Ahn BC (2014) Metabolic parameters using (1)(8)F-FDG PET/CT correlate with occult lymph node metastasis in squamous cell lung carcinoma. Eur J Nucl Med Mol Imaging 41(11):2051–2057. https://doi.org/10.1007/s00259-014-2831-6
Kunkel M, Reichert TE, Benz P, Lehr HA, Jeong JH, Wieand S, Bartenstein P, Wagner W, Whiteside TL (2003) Overexpression of Glut-1 and increased glucose metabolism in tumors are associated with a poor prognosis in patients with oral squamous cell carcinoma. Cancer 97(4):1015–1024. https://doi.org/10.1002/cncr.11159
Lasnon C, Desmonts C, Quak E, Gervais R, Do P, Dubos-Arvis C, Aide N (2013) Harmonizing SUVs in multicentre trials when using different generation PET systems: prospective validation in non-small cell lung cancer patients. Eur J Nucl Med Mol Imaging 40(7):985–996. https://doi.org/10.1007/s00259-013-2391-1
Lee SJ, Choi JY, Lee HJ, Baek CH, Son YI, Hyun SH, Moon SH, Kim BT (2012) Prognostic value of volume-based (18)F-fluorodeoxyglucose PET/CT parameters in patients with clinically node-negative oral tongue squamous cell carcinoma. Korean J Radiol 13(6):752–759. https://doi.org/10.3348/kjr.2012.13.6.752
Liao CT, Chang JT, Wang HM, Ng SH, Hsueh C, Lee LY, Lin CH, Chen IH, Huang SF, Cheng AJ, See LC, Yen TC (2009) Pretreatment primary tumor SUVmax measured by FDG-PET and pathologic tumor depth predict for poor outcomes in patients with oral cavity squamous cell carcinoma and pathologically positive lymph nodes. Int J Radiat Oncol Biol Phys 73(3):764–771. https://doi.org/10.1016/j.ijrobp.2008.05.004
Manca G, Vanzi E, Rubello D, Giammarile F, Grassetto G, Wong KK, Perkins AC, Colletti PM, Volterrani D (2016) (18)F-FDG PET/CT quantification in head and neck squamous cell cancer: principles, technical issues and clinical applications. Eur J Nucl Med Mol Imaging 43(7):1360–1375. https://doi.org/10.1007/s00259-015-3294-0
Moon SH, Kim HS, Hyun SH, Choi YS, Zo JI, Shim YM, Lee KH, Kim BT, Choi JY (2014) Prediction of occult lymph node metastasis by metabolic parameters in patients with clinically N0 esophageal squamous cell carcinoma. J Nucl Med 55(5):743–748. https://doi.org/10.2967/jnumed.113.130716
Mucke T, Mitchell DA, Wagenpfeil S, Ritschl LM, Wolff KD, Kanatas A (2014) Incidence and outcome for patients with occult lymph node involvement in T1 and T2 oral squamous cell carcinoma: a prospective study. BMC Cancer 14:346. https://doi.org/10.1186/1471-2407-14-346
National Comprehensive Cancer Network (NCCN) (2018) NCCN Clinical Practice Guidelines in Oncology: head and neck cancers. NCCN, Fort Washington
Pak K, Cheon GJ, Nam HY, Kim SJ, Kang KW, Chung JK, Kim EE, Lee DS (2014) Prognostic value of metabolic tumor volume and total lesion glycolysis in head and neck cancer: a systematic review and meta-analysis. J Nucl Med 55(6):884–890. https://doi.org/10.2967/jnumed.113.133801
Pentenero M, Gandolfo S, Carrozzo M (2005) Importance of tumor thickness and depth of invasion in nodal involvement and prognosis of oral squamous cell carcinoma: a review of the literature. Head Neck 27(12):1080–1091. https://doi.org/10.1002/hed.20275
Ryu IS, Kim JS, Roh JL, Cho KJ, Choi SH, Nam SY, Kim SY (2014) Prognostic significance of preoperative metabolic tumour volume and total lesion glycolysis measured by (18)F-FDG PET/CT in squamous cell carcinoma of the oral cavity. Eur J Nucl Med Mol Imaging 41(3):452–461. https://doi.org/10.1007/s00259-013-2571-z
Schilling C, Stoeckli SJ, Haerle SK, Broglie MA, Huber GF, Sorensen JA, Bakholdt V, Krogdahl A, von Buchwald C, Bilde A, Sebbesen LR, Odell E, Gurney B, O'Doherty M, de Bree R, Bloemena E, Flach GB, Villarreal PM, Fresno Forcelledo MF, Junquera Gutierrez LM, Amezaga JA, Barbier L, Santamaria-Zuazua J, Moreira A, Jacome M, Vigili MG, Rahimi S, Tartaglione G, Lawson G, Nollevaux MC, Grandi C, Donner D, Bragantini E, Dequanter D, Lothaire P, Poli T, Silini EM, Sesenna E, Dolivet G, Mastronicola R, Leroux A, Sassoon I, Sloan P, McGurk M (2015) Sentinel European Node Trial (SENT): 3-year results of sentinel node biopsy in oral cancer. Eur J Cancer 51(18):2777–2784. https://doi.org/10.1016/j.ejca.2015.08.023
Schilling C, Shaw R, Schache A, McMahon J, Chegini S, Kerawala C, McGurk M (2017) Sentinel lymph node biopsy for oral squamous cell carcinoma. Where are we now? Br J Oral Maxillofac Surg 55(8):757–762. https://doi.org/10.1016/j.bjoms.2017.07.007
Shah JP, Candela FC, Poddar AK (1990) The patterns of cervical lymph node metastases from squamous carcinoma of the oral cavity. Cancer 66(1):109–113
Tian M, Zhang H, Nakasone Y, Mogi K, Endo K (2004) Expression of Glut-1 and Glut-3 in untreated oral squamous cell carcinoma compared with FDG accumulation in a PET study. Eur J Nucl Med Mol Imaging 31(1):5–12. https://doi.org/10.1007/s00259-003-1316-9
Wang L, Bai J, Duan P (2019) Prognostic value of 18F-FDG PET/CT functional parameters in patients with head and neck cancer: a meta-analysis. Nucl Med Commun 40(4):361–369. https://doi.org/10.1097/mnm.0000000000000974
Yang TL, Lou PJ, Chang YL, Wu CT, Wang CP, Ko JY (2011) Tumor satellite in predicting occult nodal metastasis of tongue cancer. Otolaryngol Head Neck Surg 145(4):599–605. https://doi.org/10.1177/0194599811411635
Funding
This study was supported by the National Research Foundation of Korea (NRF) grant, funded by the Ministry of Science and ICT (MSIT), the Government of Korea (No. 2019R1A2C2002259).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors have no conflict of interest to disclose.
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research board and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors. Informed consent from all individual participants was obtained.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Bae, M.R., Roh, JL., Kim, J.S. et al. Prediction of cervical metastasis and survival in cN0 oral cavity cancer using tumour 18F-FDG PET/CT functional parameters. J Cancer Res Clin Oncol 146, 3341–3348 (2020). https://doi.org/10.1007/s00432-020-03313-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00432-020-03313-8