Consistency and prognostic value of preoperative staging and postoperative pathological staging using 18 F-FDG PET/MRI in patients with non-small cell lung cancer

doi:10.21203/rs.3.rs-1617895/v1

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Consistency and prognostic value of preoperative staging and postoperative pathological staging using 18 F-FDG PET/MRI in patients with non-small cell lung cancer

https://doi.org/10.21203/rs.3.rs-1617895/v1

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Background

In recent years, PET/MRI has been used clinically as a method to diagnose non-small cell lung cancer (NSCLC). However, no study has shown the usefulness of PET/MRI for lung tumor staging or its consistency with pathological staging compared to CT. This study aimed to evaluate the concordance of staging and prognostic ability of NSCLC patients using thin-section CT and ¹⁸F-FDG PET/MRI.

Methods

This retrospective study was performed on consecutive NSCLC patients who underwent both diagnostic CT and ¹⁸F-FDG PET/MRI before surgery between November 2015 and May 2019. The cTNM staging yielded from PET/MRI was compared with CT and pathological staging, and concordance was investigated. To assess the prognostic value of disease-free survival (DFS) and overall survival (OS), we dichotomized the typical prognostic factors and TNM classification staging (Stage I vs. Stage II or higher). Kaplan-Meier curves derived by the log-rank test were generated, and univariate and multivariate analyses were performed to identify the factors associated with DFS and OS.

Results

A total of 82 subjects were included; PET/MRI staging was more consistent (59 of 82) with pathological staging than with CT staging. There were a total of 21 cases of CT and 11 cases of PET/MRI that were judged as cStage I but were actually pStage II or pStage III. CT tended to judge pN0 as cN1 or cN2 compared to PET/MRI. There was a significant difference between NSCLC patients with Stage I and Stage II or higher by PET/MRI staging as well as prognosis prediction of DFS by pathological staging (P < 0.001). In univariate analysis, PET/MRI, CT, and pathological staging (Stage I or lower vs. Stage II or higher) all showed significant differences. In multivariate analysis, pathological staging was the only independent factor for recurrence (P = 0.009), and preoperative PET/MRI staging was a predictor of patient survival (P = 0.013).

Conclusions

In NSCLC, pathologic staging was better at predicting recurrence, and preoperative PET/MRI staging was better at predicting the patients’ survival. Preoperative staging by PET/MRI was superior to CT in diagnosing hilar and mediastinal lymph node metastases, which contributed to the high concordance with pathologic staging.

non-small cell lung cancer

18F-FDG PET/MRI

TNM staging

prognosis

Lung cancer is the leading cause of cancer-related mortality in the world, and clinical imaging plays an important role in the diagnosis and management [1, 2], as the presence of the primary lung tumor and distant metastases influences therapy regimens and patient survival [3]. Computed tomography (CT) has been regarded as the standard examination for identification of pulmonary lesions [4]. For further scrutiny, ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT provides accurate data of lymph node metastases [5]. On the other hand, frequent CT and PET/CT scans are disadvantageous for patients with lung cancers due to repeated radiation exposure. This burden is increased at the time of preoperative examinations in particular, as both contrast-enhanced chest CT scan with breath-holding and whole-body CT scan without breath-holding accompanied by PET/CT are often performed. MRI does not involve radiation exposure and has also been reported as one of the important proven methods to evaluate malignancies in pulmonary nodular diseases [6-10].

A combined PET/MRI machine has been newly released, and it has been used to detect various malignancies in clinical practice. A previous study comparing ¹⁸F-FDG PET/MRI and ¹⁸F-FDG PET/CT showed equivalent, high diagnostic performance for T and N staging in patients with non-small cell lung cancer (NSCLC) [11]. Several studies have also compared the diagnostic value of MRI with that of ¹⁸F-FDG PET/CT in NSCLC patients and suggested PET/MRI provides almost identical diagnostic ability as PET/CT without radiation exposure [3, 12]. However, the literature on the usefulness of clinical tumor staging by ¹⁸F-FDG PET/MRI and its concordance with pathologic staging is currently unclear.

In this study, we retrospectively evaluated the concordance between clinical and pathologic staging and prognostic value of ¹⁸F-FDG PET/MRI in preoperative NSCLC patients.

Patients

Consecutive patients that were suspected to have lung cancer who received both CT and ¹⁸F-FDG PET/MRI before surgery from November 2015 to May 2019 at National Cancer Center Hospital were enrolled in this study. The inclusion criteria were as follows: 1) pathologically proven non-small cell lung cancer, 2) both CT and PET/MRI were performed before thoracic surgery, and 3) follow-up after the operation was performed at the same institute. The exclusion criteria were as follows: 1) preoperative distant metastatic disease, 2) advanced primary cancer other than NSCLC, 3) treatment with chemotherapy before surgery, 4) multiple primary tumors, 5) invasive mucinous adenocarcinoma, and 6) small nodular lesion less than 5 mm on the long axis by thin-section CT images and/or PET/MRI. Since this was a retrospective single-center study, the informed consent requirement was waived by the institutional review board (research proposal number 2018-048).

¹⁸F-FDG PET/MRI acquisition and data analysis

Before the injection of ¹⁸F-FDG, patients fasted for at least 4 h. If plasma glucose levels were less than 200 mg/dL, patients were injected intravenously with 3-4 MBq/kg of the radiotracer, depending on patient height and body weight. After injection, patients rested for 50–70 min before image acquisition. ¹⁸F-FDG PET/MRI imaging was performed using a 3T PET/MRI (SIGNA PET/MRI, GE Healthcare, Milwaukee, WI, USA). Patients were positioned in the supine headfirst position. The acquisition was started in the pelvic region and moved toward the head. A localizer MRI scan was performed to define the bed positions. The axial field of view contained the body volume from the head to the thigh.

The adaptive PET/MRI protocol for the lung after whole-body PET/MRI was performed using a dedicated coil. The standard pulse sequences consisted of multiplanar 2D T2-weighted fast spin-echo (transaxial and coronal) with a 5-mm slice thickness. To avoid respiratory motion-induced artifacts, all lung surveys were performed with breath-holding. Furthermore, the protocol included a transaxial 3D T1-weighted spoiled gradient-echo sequence, with and without contrast enhancement, with 5-mm slice thickness (axial and coronal) covering the primary site of the lung cancer. Intravenous contrast agents (meglumine gadoterate; Guerbet, Tokyo, Japan) were administered.

Both the whole-body MRI and the adaptive PET/MRI images were reconstructed according to the ordered-subsets expectation maximization using 2 iterations, 16 subsets, with a matrix size of 192 × 192, and 5.0 mm³ post-filter at a dedicated workstation with MRI-based attenuation correction, scatter, and decay corrections. The voxel size for PET was 3.125 × 3.125 × 2.780 mm³ and that of MR images was 2.0 × 1.6 × 2.0 mm³ for whole-body imaging and 0.58 × 0.58 × 2.5 mm³ for adaptive chest imaging. After correct positioning of the spatial acquisition windows had been ensured, the whole-body PET/MRI acquisition was initiated at a 2-min acquisition time per bed position. For attenuation correction of the PET data from the PET/MRI scanner, the reconstruction software provided by the manufacturer used attenuation maps generated based on the 2-point Dixon MRI sequences obtained for every bed position. This approach has recently been demonstrated to provide results comparable to those of conventional attenuation correction by low dose CT [13, 14]. The procedure was implemented in the post-processing software of the scanner and operated automatically. The Dixon fat- and water-weighted images were used to create an attenuation map with 4 distinct tissue-classes: background, lungs, fat, and soft tissue. The lungs were identified by connected component analysis of the air in the inner part of the body. By application of a morphologic closing filter, virtual air artifacts induced by the absence of an MRI signal in cortical bone, heart, and aorta (due to blood flow) were corrected. Attenuation of the PET signal caused by instrumentation such as the patient bed and the fixed MRI coils was automatically integrated into the attenuation maps [15] without contrast enhancement, at 5-mm slice thickness (axial and coronal).

CT imaging

All CT scans of the study were performed on a multi-detector CT scanner (Aquilion PRIME, Aquilion Precision, Aquilion 64; Canon Medical Systems Corporation). Scans were performed supine after full inspiration with caudocranial scan direction including the entire ribcage and upper abdomen with Tube-current modulation (range, 85-545 mA), and 120 kV. An intravenous contrast agent (iopamidol; FujiPharma, Toyama, Japan) was used in most patients. Contiguous 5-mm section images were obtained and reconstruction of 1-mm thin-slice section images of the lung around the tumor was added.

All CT images were viewed using standard lung windows (window level, -600 HU; window width, 1900 HU). All image data were stored in DICOM format on PACS.

Image analysis

TNM staging was determined according to the UICC TNM Classification of Malignant Tumors, Eighth Edition. Location of primary tumors, tumor size in the greatest dimension, density of tumors, atelectasis, separate tumor nodules, and tumor invasion into the other structures were registered for clinical T-factor. Considering the quality of PET/MRI images, the size criteria of T1 and T2 in the TNM classification were only defined as ≤3 cm and 3 cm to ≤5 cm, respectively, and no subdivisions were used. Density criteria were assessed by only thin-section CT alone and not by PET/MRI. Location of primary tumors, atelectasis, separate tumor nodules, and tumor invasion into other structures were assessed based on visual assessments of each modality.

One board-certified radiologist (HW) specialized in chest imaging with 25 years of experience reviewed all chest CT images. Tumor size was assessed based on linear measurement of the largest diameter in axial thin-section CT-lung window. The reader used the monitor (Eizo RadiForce RX440) to measure the tumor size. The diagnosis of T3 was based on the thin-section CT-mediastinal window. In cases where the tumor diameter was less than 5 cm, infiltration was considered positive if the contact between the tumor and the parietal pleura was more than 3 cm, if there was thickening of the pleura in contact with the tumor, or if the tumor clearly formed a mass on the chest wall. In addition, nodular lesions were considered as intrapulmonary metastases if they were found in the same lobe by the CT-lung field, except for nodules with no change over time, or in cases with obvious calcification. For the diagnosis of N-factor, lymph node metastasis was considered positive if the short diameter was 10 mm or more in thin-section CT-mediastinal window.

One nuclear medicine physician (KI), board-certified in diagnostic radiology with 16 years of experience, interpreted all PET/MRI images. An FDG–avid lesion was defined as focal, abnormally increased ¹⁸F-FDG uptake versus background, with or without a corresponding anatomic lesion on the MR scan and suggestive of lung lesion and metastasis. PET/MRI images were analyzed using PET VCAR software by visually examining all the images on a computer display at the workstation (Advantage Workstation; GE Healthcare). The maximum standardized uptake value (SUVmax) of each lesion was measured visually using a circular region-of-interest. Tumor size was assessed by measuring the maximum diameter on the axial section of the MRI T2-weighted image. For the evaluation of the N factor, lymph nodes with a short diameter of 10 mm or more on MRI T2-weighted images or high signal on diffusion-weighted images and visually higher abnormal accumulation than surrounding tissues coincident with the lymph nodes on PET/MRI fusion images were considered positive for lymph node metastasis.

Pathological evaluation

A board-certified pathologist reviewed hematoxylin-eosin stained, formalin-fixed paraffin-embedded specimens, histologically confirmed diagnosis, and evaluated histopathological findings of each case of lung cancer.

Statistical analysis

Statistical analyses were performed using R [16]. Data were presented as mean ± standard deviation [SD], and a P value of 0.05 or less was considered significant. κ statistics were performed to analyze the concordance of PET/MRI, CT, and pathological staging. Bland-Altman plots were used to examine the concordance of tumor size measurements performed based on PET/MRI, CT, and pathological specimens. For each type of measurement, the percentage of the relative difference between the tumor size measurements was plotted by using the average of the two measurements. The limits of agreement were then calculated by taking the mean of the percentage of relative differences between the two measurements and two standard deviations of these differences. The cutoff value of SUVmax was determined by the receiver operating characteristic curve.

Disease-free survival (DFS) was defined as the time from surgery until an occurrence of recurrence or metastasis or last follow-up visit. Overall survival (OS) was defined as the time from surgery to death from any cause or last follow-up. Surviving patients were censored at the last follow-up period. The last follow-up date for DFS and OS calculation was April 30, 2021. For DFS and OS analysis, the data were dichotomized by TNM staging (less than Stage I and higher than Stage II). DFS analysis of N-factor (N0 or higher than N1) was also performed. The log-rank (Mantel-Cox) test was used to evaluate the difference between Kaplan–Meier curves. To calculate the risk ratios and 95% confidence intervals (CIs), univariate analysis was used to identify factors associated with DFS and OS. Then, factors found to be significant by univariate analysis (P < 0.05) were entered into a Cox multivariate regression analysis model. For the univariate analysis, we used dummy variables of 1 for the following factors: age ≥ 75 y, male, ex-smoker or current smoker, and pathology other than squamous cell carcinoma. Then, forward stepwise multivariate regression analysis was performed to identify factors correlated with DFS and OS based on calculating hazard ratios (HRs) and 95% CIs.

Patient characteristics

Two hundred fifty-four patients that were suspected of pulmonary malignancies and underwent both CT and PET/MRI were identified, and 82 patients with pathologically confirmed NSCLC were enrolled. A flow diagram summarizing the selection of patients is shown in Figure 1. The majority of this cohort were men with adenocarcinoma who received lobectomy. Other clinical parameters are summarized in Table 1.

Characterization of imaging and pathological findings

The mean interval between PET/MRI and operation was 3.1 ± 1.7 weeks. The mean interval between thin-section CT and operation was 3.7 ± 2.2 weeks.

The median size of the lung tumors in the greatest dimension identified by thin-section CT was 29 mm (range: 10 to 101 mm). The density of the tumors was as follows; one pure ground-glass nodule (GGN), 21 part-solid nodules, and 60 solid nodules. Atelectasis of the peripheral lesion of the lung from the tumors was seen in one patient with a solid nodule. There was no patient with separate tumor nodules. Of the 82 cases, 21 were associated with withdrawn pleura, and 2 were suspected to have chest wall invasion.

The median sizes of lung tumors identified by PET/MRI and pathological specimens were 29 mm (range: 6 to 114 mm) and 32 mm (range: 5 to 110 mm), respectively. The smallest solid nodule had a maximum diameter of 10 mm on CT and a maximum MRI diameter of 6 mm. The only pure GGN was measured to have a maximum diameter of 16 mm on CT and a maximum diameter of 19 mm on MRI.

The median value of SUVmax in the primary tumor was 7.84 (range: 0.72 to 31.93). The cutoff value of SUVmax according to the ROC curve based on the presence or absence of metastatic recurrence was 7.140 (area under the curve: 0.729, P < 0.05, 95%CI 0.609-0.850). A reference image of a case is shown in Figure 2.

Correlation of imaging and pathology in tumor staging

Table 2 shows the number of cases with concordant tumor staging for each modality: PET/MRI and pathology staging was concordant in 59/82 (72%) cases; CT and pathology and PET/MRI and CT staging were concordant in 52/82 (63%) and 65/82 (79%) cases, respectively. Of the cases judged to be cStage I by CT, 11 were actually pStage II and 10 were pStage III by pathology. Of these 21 understaged cases, 11 cases judged pN0 were classified as cN1 or cN2. Of the cases judged to be Stage I by PET/MRI, 7 were actually pStage II and 4 were pStage III by pathology. Of the 11 cases that were understaged above, 3 cases judged pN0 were found to be cN1 or cN2.

The kappa for PET/MRI and pathology staging and CT and pathology staging were 0.54 (95% CI 0.39-0.68) and 0.36 (95% CI 0.21-0.51), respectively; the kappa for PET/MRI and CT TNM staging was 0.59 (95% CI 0.43-0.75).

Figure 3 shows the Bland Altmann plot of tumor size measurement. Tumor size measurements presented by PET/MRI and CT were generally consistent, with a discrepancy between PET/MRI and pathology tumor sizes of more than +2 SD in 3 patients and -2 SD in 3 patients. Tumor size on CT and pathology deviated by more than +2 SD in 1 patient and -2 SD in 4 patients. Two of the four patients with deviations of more than -2 SD on CT and pathology and one of the three patients with deviations of more than -2 SD on PET/MRI and pathology had severe emphysema. In the remaining two cases without associated emphysema, contractile changes with indrawn pleura were observed.

Patient outcome of survival

The mean follow-up term was 32.9 months (range: 5-62 months). Tumor recurrence and patient death were confirmed in 27 and 12 of 82 patients during the follow-up period, respectively. The Kaplan-Meier curve of DFS for each TNM stage is shown in Figure 4. The PET/MRI cStage I group showed a significantly better DFS rate than cStage II or higher groups (P < 0.001), and the median DFS for cStage II or higher groups were 17.54 months. Similarly, the groups of CT cStage I showed significantly better DFS rate than cStage II or higher groups (P < 0.001), and the median DFS for cStage II or higher groups were 17.54 months.

The median DFS for the group with pStage II or higher by pathological findings were 23.82 months, and the groups with p Stage I or less showed significantly better DFS rate than p Stage II or higher groups (P < 0.001). In terms of OS, the group with Stage I or less by PET/MRI, CT, and pathological findings had significantly longer OS than the group with Stage II or higher (P < 0.001, P = 0.03, and P = 0.01, respectively).

For the N factor, there was a significant difference in the Kaplan-Meier estimation of DFS for those judged to be cN0 vs. cN1 or higher by PET/MRI (P < 0.001).

Similarly, there was a significant difference in the Kaplan-Meier estimation of DFS for those judged to be cN0 vs. cN1 or higher by CT and pN0 vs. pN1 or higher by pathology (p=0.04 and p<0.001, respectively).

The results of univariate and multivariate analysis of DFS are shown in Table 3. In univariate analysis, ¹⁸F-FDG PET/MRI, CT, pathological staging, and SUVmax showed significant differences as factors. In multivariate analysis, only pathological staging remained as a predictor. For OS, PET/MRI staging showed a significant difference as a factor (P = 0.013), as shown in Table 4.

The findings of this study are twofold. First, preoperative staging by PET/MRI was more consistent with pathologic staging results than CT in NSCLC. Second, the prognosis of patients with NSCLC in Stage I and Stage II or higher categories was similar for PET/MRI and pathologic evaluation: only pathologic staging was a prognostic factor for DFS, whereas PET/MRI staging was a prognostic factor for OS.

Lung tumor staging is defined by TNM factors, and in issuing the UICC Cancer Staging Manual 8th edition, the tumor diameter that defines the T factor is subdivided compared to the 7^th edition, indicating that the 8th edition of the T classification shows the importance of tumor density to predict patient prognosis [17,18]. Thin-section CT is considered to be the best modality for this evaluation. On the other hand, ¹⁸F-FDG PET is generally not recommended for the evaluation of lung nodules smaller than 10 mm due to its spatial resolution. Pure GGNs can also result in a false-negative ¹⁸F-FDG PET scan due to their low glucose metabolism [19, 20]. Furthermore, on chest MRI, lung nodules smaller than 5 mm are undetectable on T1WI or T2WI sequences [21-23], and pure GGNs are also difficult to detect with routine MRI sequences. In this study, the smallest pulmonary nodule was calculated to be 10 mm in diameter by CT and 6 mm in diameter by MRI, although this was an incidental result, and there was only one case of pure GGN, which was 16 mm in diameter by CT and 19 mm in diameter by MRI. Therefore, small lung nodules and pure GGNs, which are difficult to detect by MRI as pointed out in previous studies, could not be evaluated. These may be due to selection bias by the clinicians who chose PET/MRI instead of PET/CT as part of the preoperative evaluation. In the past, literature comparing the size of preoperative CT and postoperative pathology of lung cancer reported that the size of CT was significantly smaller in patients with emphysema [23]. In the present study, advanced emphysema was confirmed in 2 of 4 patients with a deviation of -2 SD or more on Bland Altmann plot on CT and in 1 of 3 patients on PET/MRI. Furthermore, the remaining two cases without associated emphysema both showed contractile changes with indrawn pleura and had a common histological type of lung adenocarcinoma. Park et al. reported that the pathologic tumor size of lung adenocarcinoma with indrawn pleura was significantly larger than the tumor size measured by CT compared to cases without indrawn pleura [24]. These results suggest that the images may underestimate the actual tumor size due to the influence of background lung and indrawn pleura.

Therefore, although the results of the present study indicate that PET/MRI and CT measurements may have less error in determining tumor size for NSCLC with tumor diameters of 5 mm or greater, the actual tumor size may be affected by background conditions such as emphysema and pleural indentation. However, it is also clear that MRI with PET/MRI and low-dose CT with PET/CT are inferior to thin-section CT in terms of density, so T factor should still be evaluated with thin-section CT, and ¹⁸F-FDG PET/MRI should be used as a complement to thin-section CT.

While the superiority of CT over PET/MRI in the imaging evaluation of the T factor has been pointed out, this study showed that PET/MRI and pathological staging agreed in 72% of cases, which was more consistent with pathological staging results than CT (63%).The number of understaged cases was also lower with PET/MRI than with CT. When we checked the cases in which tumor was understaged in CT and PET/MRI examinations compared to pathology, CT had more cases in which pN0 was judged as cN1 or cN2 compared to PET/MRI. This may be due to the fact that CT could not detect hilar or mediastinal lymph node metastases, for which PET/MRI was capable. On the other hand, for the T-factor, there was little difference between CT and PET/MRI, and the discrepancy between the results and pathology was due to the fact that the pleural infiltration detected by pathology could not be identified on the images.

Therefore, PET/MRI was superior to CT in diagnosing hilar and mediastinal lymph node metastases, which may have contributed to the high concordance between PET/MRI and pathological staging. Meanwhile, the prognostic value of PET/MRI and pathology was similar in Stage I and II or higher categories. N-factor is one of the most important prognostic factors in determining patient survival from NSCLC [9]. Though there is a size-criteria of 10 mm in diagnosing lymph node involvement in conventional CT, this lower sensitivity than that of ¹⁸F-FDG PET for focal lymph node metastases can frequently occur in normal-sized nodes, and inflammation may also show irregular-sized nodes [25]. Therefore¹⁸F-FDG PET/MRI is useful in N staging due to its detection of neoplasm of normal-sized lymph nodes by glucose metabolism and various MRI sequences [26-28]. The previous papers on the pathological N-factor of NSCLC using the 8th edition of the TNM classification states that there was a significant difference in OS between pN0 and pN1-3 regardless of the T factor [29, 30]. Therefore, accurate determination of N-factor in operable patients is important from the viewpoint of prognosis between Stage I, which is based on N0M0, and Stage II and above, which involve factors N1-3. Furthermore, the DFS of N0 in this study was significantly longer than that of N1-3 classified by PET/MRI, and the results were similar to those of pathological N-factor classification. In addition, the prognostic value of NSCLC in the TNM Stage I group by PET/MRI, CT, and pathology showed significantly better prognosis than the Stage II group. Among them, pathological staging was an important predictor of recurrence in multivariate analysis, and only PET/MRI staging remained a factor when it came to predicting patient survival.

Previous studies have reported that PET/CT is more predictive of OS in NSCLC patients compared to conventional imaging [31, 32], and these previous studies above and our results, combined with the fact that PET/MRI staging is more similar to pathological staging than CT, suggest that the use of PET/MRI in addition to preoperative evaluation of NSCLC patients may have a significant impact on patient prognosis in the future.

There are several limitations to this study. First, this study is a comparison between CT and PET/MRI and not PET/CT. In this regard, since a direct comparison is not realistic considering radiation exposure, PET/MRI and CT are compared in this study. Other factors include the retrospective design and relatively small patient population due to the selection of postoperative NSCLC patients who underwent both CT and PET/MRI.

Furthermore, there is no protocol for choosing PET/MRI instead of PET/CT preoperatively, and the decision was left up to the clinician, which may have created selection bias. Therefore, further prospective studies with a large number of patients are warranted. In addition, because of the recent introduction of PET/MRI at our institution, the observation period was short, averaging less than 5 years. Longer observation periods are needed to obtain solid evidence.

In addition, although this study was conducted on patients with NSCLC who were eligible for surgery, the use of PET/MRI in patients who are not eligible for surgery or who have brain or bone metastases may help shorten the screening period, predict patient prognosis, and reduce patient radiation exposure.

Preoperative staging by ¹⁸F-FDG PET/MRI was superior to thin-section CT in diagnosing hilar and mediastinal lymph node metastases, which contributed to the high concordance with pathologic staging. Pathologic staging was a good predictor of recurrence in patients with NSCLC, and preoperative PET/MRI staging was a predictor of patient survival.

NSCLC

non-small cell lung cancer

SCC

squamous cell carcinoma

computed tomography

MRI

magnetic resonance imaging

¹⁸FDG

¹⁸F-fluorodeoxyglucose

PET

positron emission tomography

DFS

disease-free survival

overall survival

confidence intervals

HRs

hazard ratios

Ethics declarations

Ethics approval and consent to participate:

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of National Cancer Center Hospital (Research proposal number 2018-048). As this was a retrospective study, the need for an informed consent was waived.

Consent for publication: Not applicable.

Competing interests: The authors declare that they have no competing interests.

Funding: None declared.

Author’s contributions:

AK and KI analyzed and interpreted the patient data and were major contributors in writing the manuscript; HW reviewed all CT data; SM and SW performed the surgery and provided the clinical data; YY performed the histological examination of the lung; SM, TG, and MK confirmed the contents of the paper.

All authors read and approved the final manuscript.

Acknowledgements:

None.

Availability of data and material:

The data sets generated and/or analysed during the current study are not publicly available due patient confdentiality reasons but are available from the corresponding author on reasonable request and pending approval from the Ethics Committee of National Cancer Center Hospital.

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Consistency and prognostic value of preoperative staging and postoperative pathological staging using 18 F-FDG PET/MRI in patients with non-small cell lung cancer

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