Prognostic significance of the harmonized maximum standardized uptake value of 18F-FDG-PET/CT in patients with resectable oral tongue squamous cell carcinoma: a multicenter study

Abstract

Objectives: To investigate the usefulness of harmonized ¹⁸F-FDG-PET/CT parameters for predicting the postoperative recurrence and prognosis of oral tongue squamous cell carcinoma (OTSCC).

Methods: We retrospectively analyzed the cases of 107 OTSCC patients who underwent surgical resection at four institutions in Japan in 2010-2016 and evaluated the harmonized PET parameters of the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for the primary tumor as the pSUVmax, pMTV, and pTLG. For lymph node metastasis, we used harmonized PET parameters of nodal-SUVmax, nodal-total MTV (tMTV), and nodal-total TLG (tTLG). The associations between the harmonized PET parameters and the patients' relapse-free survival (RFS) and overall survival (OS) were evaluated by the Kaplan-Meier method and Cox proportional hazard regression analysis for model 1 (preoperative stage) and model 2 (preoperative + postoperative stages).

Results: The harmonized SUVmax values were significantly lower than those before harmonization (p=0.012). The pSUVmax was revealed as a significant preoperative risk factor for RFS and OS. Nodal-SUVmax, nodal-tMTV, and nodal-tTLG were significant preoperative risk factors for OS. The combination of pSUVmax + nodal-SUVmax significantly stratified the patients into a low-risk group (pSUVmax <3.97 + nodal-SUVmax <2.85 or ≥2.85) and a high-risk group (pSUVmax ≥3.97 + nodal-SUVmax <2.85 or pSUVmax ≥3.97 + nodal-SUVmax ≥2.85) for recurrence and prognosis (RFS: p=0.001; OS: p<0.001).

Conclusions: The harmonized pSUVmax is a significant prognostic factor for the survival of OTSCC patients. The combination of pSUVmax and nodal-SUVmax identified OTSCC patients at high risk for recurrence and poor prognosis at the preoperative stage.

Keywords: F18 Fluorodeoxyglucose; Oral Tongue Squamous Cell Carcinoma; Positron Emission Tomography Computed Tomography; Standardized uptake value.

Figure 1.

Recovery coefficient (RC)-based five different institution’s PET instruments obtained from 30 min/bed PET imaging on phantom study. (a) (b) The resultant data of pre-harmonization RC regarding SUVmax and (c) (d) the resultant data of RC about harmonized SUVmax. Coefficient of variation (CV) shows the reduction of interinstitutional difference in SUVmax by harmonization, and was calculated from following formula: CV = standard deviation (SD)/ average x 100 (%).

Figure 2.

Bland-Altman plots comparing SUVmax before and after harmonization. Centerline: the average measured values before and after harmonization. Upper dotted line: the upper limit of the 95%CI for the average difference. Lower dotted line: the lower limit of the 95%CI for the average difference.

Figure 3.

The case of a 70-year-old man with OTSCC (cStage I) with a reduction of PET parameters of the primary tumor after harmonization (white arrow). He underwent ¹⁸F-FDG-PET/CT (GEMINI TF64 scanner) (FWHM: 5.8 mm) for a staging evaluation. (a) Before and (b) after harmonization.

Figure 4.

(a:) The AUC obtained from the time-dependent ROC curve analysis for the prediction of RFS for all of the harmonized PET parameters. (b:) The time-dependent ROC curve of all of the harmonized PET parameters for predicting 120 month RFS.

Figure 5.

(a) Kaplan-Meier estimates of survival functions for RFS in a patient in the pSUVmax group. (b) Patients with the combination of pSUVmax <3.97  +  nodal-SUVmax (<2.85  or ≥2.85) (Group A), pSUVmax ≥3.97 + nodal-SUVmax <2.85 (Group B), and pSUVmax ≥3.97 + nodal-SUVmax ≥2.85 (Group C) among the 107 OTSCC patients. P-values were determined by the log-rank test.

Figure 6.

(a:) Kaplan-Meier estimates of survival functions for OS in the pSUVmax group and (b) the combination of pSUVmax <3.97 + nodal-SUVmax (<2.85 or  ≥2.85) (Group A), pSUVmax ≥3.97 + nodal-SUVmax <2.85 (Group B), and pSUVmax ≥3.97 + nodal-SUVmax ≥2.85 (Group C). P-values were determined by the log-rank test.

Figure 7.

A 38-year-old woman with OTSCC (cStage I). (a:) On the ¹⁸F-FDG-PET/CT image used for staging, the pSUVmax was 4.04, the pMTV was 1.26, and the pTLG was 3.75 (white arrow). She underwent only a partial glossectomy and followed up based on the WW concept. (b,c:) ¹⁸F-FDG-PET/CT showed high uptake in right-submandibular and superior deep cervical lymph nodes at 9 months after surgery, and this was diagnosed as late cervical lymph node metastasis (white arrows).