Original Article

Volumetric Evaluation of Staging 18F-FDG PET/CT Images in Patients with Esophageal Cancer


  • Nazlı Pınar Karahan Şen
  • Ayşegül Aksu
  • Gamze Çapa Kaya

Received Date: 03.11.2021 Accepted Date: 20.02.2022 Mol Imaging Radionucl Ther 2022;31(3):216-222 PMID: 36268888


The aim of this study was to evaluate the metastatic potential of primary tumor and survival in esophageal cancer (EC) patients by using metabolic tumor volume (MTV) and total lesion glycolysis (TLG) from the staging 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) images. Another aim is to determine a tumor volume-based cut-off value to predict long-term survival.


Medical records of EC patients were retrospectively evaluated. Sixty-two patients with staging 18F-FDG PET/CT and at least five years of follow-up were included in the study. The region of interest to the primary tumor and all metastatic sites was created and MTV and TLG values of the primary tumor (MTVp, TLGp) and total tumor volume (MTVt and TLGt) values were obtained. The relationship between the obtained MTV and TLG values and short-time (one-year) and long time (five-year) survival was investigated.


Significant factors on survival were determined as lymph node or distant metastasis (p=0.024, 0.008, respectively) at the staging PET/CT. A significant relationship between volumetric parameters of the primary tumor and total tumor burden (MTVp, TLGp, MTVwb and TLGwb) between survivors and non-survivors for one-year and five-year was detected. In receiver operating characteristics analysis, the most significant volumetric parameter was MTVwb, with area under curve 0.771 in estimated five-year survival. The best cut-off value was detected as 36.1 mL with 78% sensitivity and 75% specificity for MTVwb in determining long-term survivors.


Tumor burden in 18F-FDG PET/CT images at the time of staging of patients with EC will contribute to the prediction of long-term survivors.

Keywords: 18F-FDG PET/CT, metabolic tumor volume, esophageal cancer


Esophageal cancer (EC) ranks seventh cause in terms of incidence and the sixth most common cause of mortality across the world (1). Five-year survival rate is 19.9% (2). In distant metastatic (DM) disease, worse prognosis and lower five-year survival rates are declared (5.2%) (2).

18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is a standard diagnostic workup in EC. PET/CT provides essential information about the distribution of the lesions, size, and presence of metastases at the time of staging. As a quantitative parameter standard uptake value (SUV) provides information about the intensity of the uptake in the lesion and most commonly maximum standard uptake value (SUVmax) is used to determine the tumor metabolic activity (3). However, SUV do not represent the whole tumor (4). Metabolic tumor volume (MTV) and tumor lesion glycolysis (TLG) are the parameters that are increasingly being studied to define the combined volumetric and metabolic characteristics of the tumors (5,6).

This study evaluates the relationship between the volumetric characteristics of the primary tumor obtained from the staging 18F-FDG PET/CT images and the metastatic potential of the primary tumor at the time of diagnosis in EC patients. Another aim is, use volumetric parameters, to determine a volume-based cut-off value to predict long-term survival in EC patients.

Materials and Methods

Patients’ medical records, who had undergone 18F-FDG PET/CT at the time of initial staging with EC, between January 2008 and September 2019 at our department, were retrospectively analyzed. Patients whose follow-up was insufficient (less than five-years) were excluded. In total, 62 patients were included in this study. This study was approved by the Local Ethical Committee at Dokuz Eylul University Institution (decision no: 2019/23-09, date: 16.09.2019).


Patients with appropriate patient preparation (fasting for at least 4 h and adequate blood glucose levels) were enrolled in PET/CT. Approximately 1 h after the average injection of 4.1 MBq/kg 18F-FDG all scan was performed using a Phlips Gemini TOF PET/CT (Eindhoven, Netherlands). The emission scans were 10-12 beds per patient and for 1.5 minutes/bed position and the transmission scans were obtained from low-dose CT with 50 mAs and 120 kVp, 5 mm re-structured section thickness.

Determination of Region of Interest (ROI)

Conventional and volumetric data of the primary tumor and all metastatic sites were obtained by drawing the ROI of the primary tumors from PET/CT images via LIFEx software (http://www.lifexsoft.org) by a nuclear medicine physician (12 years of experience) (7,8). To prevent manual error, the area of interest was drawn in the tumor area with a minimum SUV of 2 and above (Figure 1). SUV (maximum and mean), MTV and TLG of the primary tumor (MTVp, TLGp) and total tumor volume in the whole body (MTVwb and TLGwb) values were obtained.

Statistical Analysis

Statistical Package for the Social Sciences software version 22.0 for Windows was used for statistical analysis. A statistically significant difference between the obtained SUV, MTV and TLG values and short-time (one-year), long time (five-year) survival; lymph node (LN) and DM in subgroups according to the localization and histopathology were investigated. Non-parametric tests (The Mann-Whitney U test and Kruskal-Wallis test) were used because of the heterogeneity of our data. A p value of <0.05 was set as significant. The receiver operating characteristics (ROC) analysis was performed for significant parameters (p<0.05) to determine a cut-off value to predict long and short-time survival. Median overall survival (OS) and cumulative survival were calculated using Kaplan-Meier analysis.

Patient Group and Treatment Procedure

Thirty-one patients were administered neoadjuvant chemo-radiotheraphy (NCRT) but only 13 of them had surgery after NCRT. One patient underwent surgery after only neoadjuvant chemotherapy. Four patients underwent surgery as first-line treatment. Thirteen patients with no chance of surgery or local treatment were administered only chemotherapy. After diagnosis, twelve patients had no chance to start a treatment procedure. One patient with only local disease had no chance to administer chemotherapy, only radiotherapy applied, resulted with progression.


Seventeen (27.4%) of 62 patients had DM and 42 (67.7%) had local lymph node metastasis (LNM). Twenty patients (32.3%) had only a local tumor with no metastasis (NM) (no LNM or DM). Twenty-five patients (40.3%) had primary tumor and local only lymph node metastasis (OLNM), and seventeen patients (27.4%) had both local LN and DM (lung, bone, liver or distant lymph node). Fifty patients (80.6%) had squamous cell cancer (SCC) and 12 patients (19.4%) had adeno cancer (AC). Primary tumors were located in the upper, middle and lower esophagus, in 10 (16.1%), 26 (41.9%), and 26 (41.9%) patients, respectively (Table 1).

LNM was detected in 62% of the SCC and 91.7% of the AC groups, and DM rates were 24% and 41.7%, respectively. According to metastasis rates, no significant difference was detected between pathological subgroups (p>0.05). It was observed that primary tumor volumetric parameters (MTVp, TLGp, SUVmax and SUVmean) were not significant indicators in predicting LN or DM at the time of staging.

Median OS was detected 13.3±2.0 months [95% confidence interval (CI): 9.35-17.26]. Median OS for NM, OLNM and DM was detected 20.9±16.4 months, 12.6±2.2 and 8.3±3.2, respectively (p=0.004) (Figure 2). LNM and DM at the staging PET/CT were detected as significant factors (p=0.024, 0.008, respectively) on OS in the Kaplan-Meier analysis. However, location of the tumor, gender, or histopathological subtype were not significant factors (p>0.05). One-year and five-year cumulative OS were determined as 56.5%±0.63% and 19.4%±0.50%, respectively.

When evaluated according to histopathological subtypes, MTVp, TLGp, and SUVmax and SUVmean of the primary tumor had no significant difference between SCC and AC patients (p>0.05). Similarly, MTVp TLGp, and SUVmax and SUVmean of the primary tumor were not related to the tumor’s localization (p>0.05). According to the localization of the primary tumor, a significant difference was detected between SCCs and AC (p<0.005). SCCs were detected mainly located in the middle esophagus, unlike AC located mainly in the lower esophagus.

A significant relationship between volumetric parameters of the primary tumor and total tumor burden (MTVp, TLGp, MTVwb and TLGwb) between survivors and non-survivors for one-year and five-year was detected. In ROC analysis, the most significant volumetric parameter was MTVwb, with area under curve (AUC) 0.771 in estimated five-year survival. The results are given in Table 2. According to the Youden index, the best cut-off value was detected as 36.1 mL with 78% sensitivity and 75% specificity for MTVwb in determining long-term survivors (Figure 3). When patients were divided into groups according to the cut-off value as low (<36.1 mL) and high (≥36.1 mL) MTVwb, Kaplan-Meier analysis demonstrated high and low MTVwb as a significant factor on OS (p<0.001). In the low MTVwb and high MTVwb groups, OS was detected as 10.1±1.94 and 35.9±19.34 months, respectively (Figure 4).


In this study, we investigated the metastatic potential of the primary tumor at the time of diagnosis and the role of metabolic parameters (MTV and TLG) in OS for both the primary tumor and metastasis obtained from 18F-FDG PET/CT images. We determined a cut-off value for tumor volume to predict long-time survivors. Among the volumetric parameters, MTVwb, which depicts whole-body tumor volume (tumor burden) in a patient, was determined to be the most significant parameter in detecting five-year survival in patients with EC.

An endpoint of our study was whether the primary tumor’s metabolic features obtained from staging PET/CT was associated with LN or DM. Studies investigate the relation between the metabolic parameters in EC patients and LN or DM or response to treatment. A study, which investigated LNM status at baseline PET/CT, determined in multivariate analysis that MTV of primary tumor with 40% threshold method [Odds ratio (OR): 1.127, p=0.04] and SURmax (maximum tumor-to-blood SUV ratio) (OR: 1.446, p=0.004) were independent predictors of LNM, with sensitivity and specificity were 51.2%, 83.7% vs. 53.7%, 79.1% respectively. In the detection of occult LNM, only MTV was detected significantly (p=0.024) (9). However, our study revealed that primary tumor metabolic parameters (MTVp, TLGp, SUVmax and SUVmean) were not significant indicators in predicting LN or DM at the time of staging. Also, the discrimination of histopathological subtypes of EC is impossible with current imaging modalities. One study suggested that SUVmax was not related to histopathological subtypes of EC but, MTV values of AC patients were significantly higher than those of SCC patients (10). However, there are also studies, which could not determine histopathological subtypes with SUVmax or MTV (11). Similarly, in our study, primary tumor’s volumetric parameters have no significant difference in discriminating histopathological subtypes or localization of the primary tumor (p>0.05). Two main histological subtypes, SCC and AC, account for 95% of all EC cases (12). SCC is the most commonly seen subtype and mainly located in the mid to upper part of the esophagus (13). However, AC is mainly located in the distal esophagus. In accordance with literature, according to the localization of primary tumors, a significant difference was detected between the two histopathological subtypes (p=0.005) in our study.

Comparison of primary tumor MTV and TLG calculated from initial PET/CT images in patients with EC and treatment response, OS and progression-free survival have been investigated in various studies (14,15,16,17,18,19). A study reported that MTV and TLG of the primary tumor were associated with survival after surgery (p≤0.05) (16). Another study, which included 151 EC patients, while MTV of the primary tumor was detected as an independent prognostic factor on OS (p=0.021), the SUVmax of the primary tumor was not significant (17). Similarly, in our study, among the metabolic features of the primary tumor (SUVmax, SUVmean, MTVp and TLGp) only MTVp was significantly related to one-year and five-year OS (p=0.048, 0.041, respectively).

There are studies have investigated the role of whole-body TLG and MTV on survival in EC patients. Kitajima et al. (20) stated that MTVwb and TLGwb are predictors of OS in univariate analysis (p<0.0001), but multivariate analysis pointed to a reduction rate of TLG [Hazard ratios (HR): 2.21, 95% CI, 1.04-4.68; p=0.040] as an independent predictor of OS. In a study in which pretreatment whole-body TLG, MTV and SUVmax were investigated in patients with EC, while SUVmax was not significant, whole-body TLG and MTV were determined as independent predictors of OS, local control, and progression-free survival. HR of TLG and MTV for OS were determined as HR: 2.15 and HR: 2.36, respectively (21). Similarly, our results demonstrate that MTVwb and TLGwb are significant predictors of OS. Apart from our study, Takahashi et al. (21) studied in a limited group and included in their study only patients with stage 2 and 3 thoracic esophageal SCC patients and created the groups for low and high MTV and TLG based on median values (15.57 mL for MTV and 103.68 for TLG). Additionally, in their study, they underline that whole-body TLG has a higher HR than MTV. However, our results determined MTVwb has a higher predictive value than TLGwb. In another study, the five-year survival rate was detected as 49.8%, and MTVp, TLGp and TLGwb were associated with OS. The only significant parameter was TLGwb in multivariate analysis. However, that study included only stage 1-3 SCC EC patients and did not calculate MTVwb values (22). Similar to our results, Zhang et al. (11) reported in their study, in which 36 patients evaluated for short (less than one-year) and long (higher than one-year) survival, higher MTV values were related to short OS in EC. In our study, LNM and DM at the staging PET/CT were detected as significant factors (p=0.024, 0.008, respectively) on OS in EC patients. Additionally, metastasis groups (NM, OLNM and DM) were significant factors in long-term survival (p=0.004). However, the determined MTVwb cut-off value was demonstrated as the most significant factor on OS (p<0.001).

Study Limitations

Limited sample size, heterogeneity in the number of patients in the pathological subgroups and the retrospective design of the study are the main limitations.

Our patient group is a heterogeneous group consisting of patients with a diagnosis of EC who underwent PET/CT at the time of staging, but in clinically different stages, with different treatment and management processes. In the treatment management, patients with EC are primarily evaluated in terms of operability, and even in locally advanced stages, the lesion size is reduced with neoadjuvant treatment methods. The surgery option is considered first because surgery is accepted as the most effective treatment strategy (23). In metastatic patients, chemotherapy regimens are the first choice. However, some patients may die before starting or completing treatment regimens, with complications such as bleeding due to the disease, fistula, aspiration, decreased oral intake due to mass effect, while still at the time of staging. Although heterogeneity may seem like a disadvantage in our study group, in general practice, we already encounter a heterogeneous patient group.

In our data, in predicting long-term survivors, AUC was calculated 0.771 for MTVwb. This value is acceptable for determine a cut-off value. The ROC curve is a plot of sensitivity versus 1-specificity at all possible cut-off values. Different cut-off values could be calculated from ROC plot. However, we determined our best cut-off value as 36.1 mL using Youden index. In it is also possible to determine different cut-off values for different patient groups. Including only local/or only metastatic patients could give different cut-off values. Heterogeneity of our data could be seen as an advantage in this regard. Conducting similar studies in different clinics will be beneficial for consolidating the results of our study.


This study suggests that, in addition to the role of metabolic volume of the primary tumor in initial 18F-FDG PET/CT, tumor burden (MTVwb) in 18F-FDG PET/CT images at the time of staging of patients with EC will contribute to the prediction of the long-term survivors. Patients with MTVwb <36.1 mL at the staging 18F-FDG PET/CT could demonstrate better OS results and this value could predict long-term survivors.


Ethics Committee Approval: This study was approved by the Local Ethical Committee at Dokuz Eylul University Institution (decision no: 2019/23-09, date: 16.09.2019).

Informed Consent: Retrospective cross sectional study.

Peer-review: Externally peer-reviewed.

Authorship Contributions

Surgical and Medical Practices: N.P.K.Ş., A.A., G.Ç.K., Concept: N.P.K.Ş., G.Ç.K., Design: N.P.K.Ş., G.Ç.K., Data Collection or Processing: N.P.K.Ş., Analysis or Interpretation: N.P.K.Ş., A.A., Literature Search: N.P.K.Ş., Writing: N.P.K.Ş.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

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