In this study, we examined the implications of the RI of the primary tumor as a predictor of lymph node metastasis in patients NSCLC. Several studies have examinde the role of tumor SUVmax as a risk marker for nodal metastasis [1–4]. The RI of the lymph node is also a predictor of lymph node metastasis in NSCLC, while higher RI of primary tumor is known to predict risk for distant metastasis and poor recurrence-free survival [5–7, 10, 11]. However, the role of the RI of the primary tumor as a predictor of lymph node metastasis in NSCLC remains unclear. To the best of our knowledge, no studies have been conducted in an attempt to compare the of primary tumor RI as a predictor of lymph node metastasis between different histological subtypes of NSCLC.
We found that the RI of the primary tumor predicted lymph node metastasis in patients with NSCLC across all histological subtypes. Furethermore, we demonstrated that, in patients with adenocarcinoma, the RI of the primary tumor was a significant predictor of lymph node metastasis; however, in patients with squamous cell carcinoma, and those with other NSCLC types, the RI of the primary tumor was not a significant predictor of lymph node metastasis.
RI values were higher in patients with squamous cell carcinoma than in those with adenocarcinoma. However, the RI was a reliable predictor of lymph node metastasis only in the adenocarcinoma group. We also demonstrated a correlation between the RI value and tumor size across all NSCLC types. Multivariable analysis demonstrated that, based on histology, the RI of the primary tumor was an independent risk factor for lymph node metastasis, but only in the adenocarcinoma group. The RI of the primary tumor was therefore a reliable predictor of lymph node metastasis in patients with adenocarcinoma.
Similar histo-pathological tendencies of the FDG-PET/CT SUVmax have been reported in other studies. The single-time-point FDG-PET/CT SUVmax of the primary tumor was significantly higher in squamous cell carcinoma than in adenocarcinoma. However, the significance of the SUVmax as a prognostic factor was stronger in adenocarcinoma and weaker in squamous epithelial carcinoma [12, 13]. Glucose metabolism abnormalities might explain the differences in the role of the SUVmax between adenocarcinoma and squamous cell carcinoma [12, 13]. Tumor glucose transporter (GLUT)-1 overexpression is associated with high FDG uptake. GLUT-1 is fully (100%) expressed in squamous cell carcinoma, but only partially (58%) expressed in adenocarcinoma [12, 13]. GLUT-1 expression could explain the variable significance of SUVs as a predictor of lymph node metastasis in different histological subtypes evident in our study. This biological difference likely modified the effect of the RI as a risk factor among different histo-pathological subtypes.
We investigated the DTP SUVmax, SUVmaxe at 50 min, and SUVmaxd at 120 min. In accordance with previous reports, both the SUVmaxe and SUVmaxd were higher in squamous cell carcinoma and other NSCLC subtypes than in adenocarcinoma. The RI is calculated using both the SUVmaxe and SUVmaxd. Therefore, we believe that there is a close histological link between the SUVmax and RI for different NSCLC subtypes.
The SUVmax and related indices (including the RI) are sensitive indicators of malignant potential in patients with adenocarcinoma. To the best of our knowledge, no prior studies have comprehensively investigated the clinical features and SUVmax or RI in detail in other patient samples with NSCLC. Furthermore,since number of the patients with other NSCLC subtypes was small, we could not determine the clinical behavior of those subgroups.
Numerous studies have mentioned that a high SUVmax of the primary tumor is a risk factor for lymph node metastasis, and the cut-off SUVmax of the primary tumor ranges from 2.5 to 4.0 [1, 3, 4, 14–18]. SUVmax data at the 60-min time-point following F18-FDG administration in many studies of single-time-point 18F-PET-CT examination are similar to the SUVmaxe demonstrated in this study, showing that an SUVmaxe cut-off of 2.8 was a predictor of nodal metastasis.
SUVmax values vary between facilities, and variations of up to 30% across three institutions have been reported . We consider the RI using DTP PET-CT a reliable assessment tool that does not require standardization, since it is the ratio of the two SUVmax values. The RI is a simple value that can be widely used in many facilities with DTP PET-CT scanning data. Additionary, in the real world, the SUVmax of hilum and mediastinum lymph nodes is often not calculated. We used our simple parameter for predicting metastasis in the real world. Therefore the primary tumor’s RI could help nodal metastasis widely in the real world.
This study had some limitations, including a retrospective, single-center design. Excluding the AIS, MIA, and old BAC categories from pathologic diagnoses constituted another limitation. This decision was motivated by our focus on targeting clear invasive adenocarcinoma. We thus did not formally consider the differences between the Union for International Cancer Control TNM 7th and 8th edition guidelines on adenocarcinoma in our study. Furthermore, the number of cases of other NSCLC types was small, which may have affected our results.